Effectiveness of Fluoroquinolone De-escalation in Community-Acquired Pneumonia: Impact on Hospital Stay and Mortality

Effectiveness of Fluoroquinolone De-escalation in Community-Acquired Pneumonia: Impact on Hospital Stay and Mortality | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effectiveness of Fluoroquinolone De-escalation in Community-Acquired Pneumonia: Impact on Hospital Stay and Mortality Aseel Abu Awad, Khawla Abu Hammour, Alaa Abuawad, Mohammed Zawiah, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5784150/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: This study aimed to evaluate the effectiveness of fluoroquinolone de-escalation in adult patients with community-acquired pneumonia (CAP), examining its impact on hospital length of stay (LOS), mortality, and association with microbial culture results. Methods: A retrospective cohort study was conducted on adult patients diagnosed with CAP at a tertiary hospital in Jordan. The study analyzed fluoroquinolone de-escalation outcomes, including hospital LOS and mortality, as well as the relationship between microbial culture results and de-escalation success. Results: The study sample consisted of 125 patients, with a median age of 73 years (IQR = 24). Of these, 64.8% (n=81) were male, and 35.2% (n=44) were female. Fluoroquinolone therapy was predominantly levofloxacin (99.2%, n=124). Fluoroquinolone de-escalation was successfully achieved in 33.6% (n=42) of patients. Positive culture results significantly increased de-escalation success, as 61.5% (n=16) of patients with positive cultures successfully de-escalating compared to 26.0% (n=25) of those with negative cultures (p = 0.002). Among patients with negative cultures (n=96), 43.8% (n=42) underwent inappropriate de-escalation, and 30.2% (n=29) had failed de-escalation. Patients in the successfully de-escalated group had a significantly shorter median hospital stay of 12 days (IQR = 8) compared to 18 days (IQR = 11) in the failed/inappropriate group (p = 0.004). There was no significant difference in mortality between the two groups, with 70.1% (n=29) surviving in the successfully de-escalated group versus 76.5% (n=62) in the other group (p = 0.514). Conclusion: Fluoroquinolone de-escalation in CAP patients is linked to shorter hospital stays without affecting mortality. Positive culture results significantly increase de-escalation success, supporting the need for improved de-escalation protocols. Community-acquired pneumonia Fluoroquinolone de-escalation Antimicrobial resistance Hospital length of stay Mortality Figures Figure 1 Introduction Community-acquired pneumonia (CAP), a common and serious lung infection, is one of the leading causes of morbidity and mortality worldwide. In the United States alone, CAP results in approximately 1.5 million hospitalizations annually (File Jr and Ramirez 2023), while globally, it accounts for approximately three million deaths each year (World Health Organization 2018). CAP is caused by a variety of infectious agents, including bacteria, viruses, and fungi, with bacterial infections being the most prevalent (Jain et al. , 2015). Antimicrobial resistance has emerged as a significant global health threat, complicating the treatment of infections, and contributing to higher morbidity, mortality, and healthcare costs. The overuse and misuse of antibiotics, both in clinical settings and agriculture, are major contributors to this crisis (Dadgostar 2019a; Founou et al. , 2017; Prestinaci et al. , 2015; Shrestha et al. , 2018). Moreover, the evolution of bacterial resistance through mutations and horizontal gene transfer exacerbates the challenge (Dadgostar 2019b). In response to the rising threat of antimicrobial resistance, antibiotic stewardship strategies such as antibiotic de-escalation have become critical in clinical decision-making (Daniel Markley et al. , 2017). De-escalation typically involves the initial use of broad-spectrum antibiotics, followed by a transition to more targeted therapies once pathogen susceptibility is known (Kollef 2008; Trupka et al. , 2017). This approach aims to minimize unnecessary antibiotic exposure, thereby reducing the potential for resistance, while improving patient outcomes (Daniel Markley et al. , 2017; Kollef 2008; Trupka et al. , 2017). The effectiveness of de-escalation strategies has been primarily evaluated based on hospital Length of Stay (LOS) and mortality rates (Tabah et al., 2016). Fluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin, are broad-spectrum antibiotics widely used to treat pneumonia due to their potent activity against a variety of bacterial pathogens (Mancuso et al. , 2021; Nadeem et al. , 2020; Pitiriga et al. , 2017). However, the increasing resistance to fluoroquinolones, especially in pathogens like Escherichia coli and Pseudomonas aeruginosa , poses a significant challenge to the treatment of pneumonia (Mancuso et al. , 2021; Nadeem et al. , 2020; Pitiriga et al. , 2017). This growing resistance highlights the importance of effective antibiotic management strategies, such as de-escalation, to mitigate the risks of further resistance development. Despite the proven benefits of antibiotic de-escalation in reducing antimicrobial resistance and improving patient outcomes in certain settings, there is limited evidence regarding its application to fluoroquinolone therapy in pneumonia patients. Thus, this study aims to evaluate the rate and outcomes of antibiotic de-escalation among CAP patients treated with fluoroquinolones within 48 hours of culture and sensitivity results. Specifically, we focus on comparing the clinical outcomes of successful versus inappropriate de-escalation, including length of hospital stay, and all-cause mortality. Methods Study Design This retrospective cohort observational study was conducted at Jordan University Hospital (JUH) to investigate the prevalence and outcomes of fluoroquinolone de-escalation in patients diagnosed with CAP from December 2022 to March 2024. The study targeted adults aged 18 years and older who were suspected of having CAP, had blood and sputum cultures requested, received fluoroquinolone therapy as empiric treatment, and were hospitalized until culture and sensitivity results obtained. Individuals who were pregnant, had uncertain diagnoses, or whose data were incomplete were excluded from the study. Ethical Considerations The study was conducted in accordance with the principles outlined in the World Medical Association Declaration of Helsinki. It received approval from the JUH Institutional Review Board (approval number 10/2024/1389). To ensure patient confidentiality, all data were de-identified and anonymized. Given the retrospective, observational design of the study, the ethical committee decide that patient consent was not required. Data Collection Data collection involved extracting comprehensive information from the medical records of eligible patients using a pre-prepared data collection form. The collected data included demographic information such as age, gender, admission and discharge dates, and duration of hospital stay. Clinical information such as diagnoses, empiric antibiotic therapy (including names, routes of administration, and duration of treatment), and details of targeted antibiotics following culture results were also gathered. Laboratory data, including blood and sputum cultures and their sensitivity results, were collected to analyze the susceptibility patterns of the microbiological pathogens responsible for CAP. Fluoroquinolone De-escalation Antibiotic de-escalation refers to the process of transitioning from broad-spectrum to narrower-spectrum antibiotics based on final culture and sensitivity findings. Possible alternatives include cephalosporins, penicillins, trimethoprim/sulfamethoxazole, vancomycin, and linezolid. This strategy aims to reduce antibiotic use, and may also involve discontinuing treatment altogether if no infection is detected, ideally within 48 hours of receiving culture results. Patients were categorized into two primary groups: those requiring de-escalation and those who did not. The decision for de-escalation was based on final culture and sensitivity results. Patients with positive cultures for atypical bacteria or methicillin-resistant Staphylococcus aureus (MRSA) were not considered candidates for fluoroquinolone de-escalation. Those requiring de-escalation were further subdivided into three categories: successful de-escalation, failed de-escalation, and inappropriate de-escalation. Failed de-escalation refers to cases where empiric antibiotics were continued despite negative culture results or when broad-spectrum antibiotics were maintained in the presence of an identified pathogen for which a narrower-spectrum antibiotic would have been more appropriate. Inappropriate de-escalation refers to errors that compromise patient care. For instance, if culture results were negative, inappropriate de-escalation might involve switching from broad-spectrum to narrower-spectrum antibiotics when discontinuation of antibiotics would have been more appropriate. Conversely, if culture results were positive, inappropriate de-escalation might involve discontinuing antibiotics rather than switching to more targeted therapies. Secondary Outcomes The secondary objectives of the study involved examining various factors among patients who experienced successful de-escalation compared to those who had failed or incorrectly de-escalated treatment, after excluding cases where de-escalation was improperly performed. Specifically, these included instances where antibiotics were discontinued instead of being transitioned to a narrower spectrum following positive culture results. The evaluated secondary outcomes included the length of hospital stay and mortality upon discharge. Additionally, the study conducted a comparative analysis of the success rates of fluoroquinolone de-escalation between patients with positive culture results and those with negative results. Statistical Analysis The data were analyzed using IBM SPSS software version 26. Descriptive statistics were used to present frequencies and percentages for categorical variables, while continuous variables were summarized using medians and interquartile ranges (IQR). Normality of the data was assessed using the Shapiro-Wilk test. To compare all-cause mortality upon discharge between patients who were successfully de-escalated and those who failed or were inappropriately de-escalated, Fisher's exact test was used. The LOS was compared using the Mann-Whitney U test. Furthermore, to assess the association between microbial culture results and de-escalation practice, the Chi-square test was applied. All statistical tests were two-tailed, with a significance level set at p ≤ 0.05. Results Demographic and medical characteristics of the study sample During the study period, 125 patients were eligible after screening for inclusion criteria. The median age of participants was 73 years (IQR= 24), with the majority of patients (n = 80, 64%) being aged 65 years or older. In terms of gender distribution, there were 44 female patients (35.2%) , and 81 male patients (64.8%). The median LOS for patients was 13 days (IQR= 11). Regarding mortality upon discharge, 93 patients (74.4%) survived, while 32 patients (25.6%) died. Additionally, 20 patients (16%) were transferred to the ICU, 100 patients (80%) remained in the general ward, and 5 patients (4%) were already in the ICU at the time of hospital admission. The demographic and medical characteristics of the study sample are summarized in Table 1 . Antibiotic Prescription Patterns Among the Study Sample All patients in the study received fluoroquinolone therapy, with the vast majority being treated with levofloxacin (n = 124, 99.2%). A small proportion of patients were treated with fluoroquinolone monotherapy (n = 12, 9.6%), while the majority received multiple antibiotics in conjunction with fluoroquinolones. Specifically, 42 patients (33.6%) received two antibiotics, 49 patients (39.2%) received three antibiotics, and 22 patients (17.6%) received four antibiotics. Vancomycin was the most frequently prescribed adjunct antibiotic, administered to 72 patients (57.6%). The median number of prescribed empiric antibiotics was 3 (IQR = 1.0), resulting in a total of 331 empiric antibacterial agents, including fluoroquinolones, being prescribed. Blood or Sputum Culture and Susceptibility Testing The results of microbial cultures showed that 96 patients (76.8%) tested negative, while 29 patients (23.2%) had positive culture results. Susceptibility testing was conducted for the majority of the positive samples (n = 28/29, 96.6%), with only one positive sample (3.4%) not undergoing susceptibility testing. Most of the isolated pathogens exhibited resistance to fluoroquinolones (n = 23/28, 82.2%), while a smaller proportion were sensitive to fluoroquinolones (n = 3/28, 10.7%). Furthermore, two samples (7.1%) did not undergo fluoroquinolone susceptibility testing but were tested for other antibiotics. Among the positive culture specimens, the majority showed only one microorganism (n = 28/29, 96.6%), while one specimen (3.4%) exhibited two pathogens. The most frequently reported pathogens were Staphylococcus hominis (20.0%), Klebsiella pneumoniae (16.7%), Staphylococcus aureus (13.3%), and Staphylococcus epidermidis (10.0%). Assessing the Appropriateness of Fluoroquinolone De-escalation The study revealed that 76.8% of patients suspected of having CAP had negative blood and/or sputum cultures. These patients were subsequently categorized into three groups based on the appropriateness of fluoroquinolone de-escalation: those who inappropriately de-escalated (42/96, 43.8%), those with failed de-escalation (29/96, 30.2%), and those who successfully de-escalated (25/96, 26.0%). These findings are illustrated in Figure 1 . Table 2 contains examples illustrating the decision-making process related to the de-escalation for patients with both positive and negative culture results. Assessing the association between de-escalation and length of stay and mortality The study found that patients who were successfully de-escalated had a significantly shorter median hospital stay of 12 days (IQR= 8 days) compared to those who failed or were inappropriately de-escalated, with a median stay of 18 days (IQR = 11 days), with a p-value of 0.004 using the Mann-Whitney U test. In terms of mortality at discharge, the results showed no significant difference between the two groups. Among the successfully de-escalated patients, 29 (70.1%) survived, while 12 (29.9%) died. In contrast, among those who failed or were inappropriately de-escalated, 62 (76.5%) survived, and 19 (23.5%) died. Statistical analysis using Fisher's exact test resulted in a p-value of 0.514, indicating no significant difference in mortality upon discharge between the two groups. Further details are presented in Table 3 . Assessing the Association Between Culture Results and De-escalation Practice Among the patients with positive culture results, 16 patients (61.5%) were successfully de-escalated. However, 26.0% of patients (n= 25) with negative culture results were successfully de-escalated. The Chi-square test revealed a significantly higher success rate of de-escalation among individuals with positive culture results compared to those with negative culture results (p = 0.002). The details are presented in Table 4 . Discussion This study assessed the prevalence and effectiveness of fluoroquinolone de-escalation in 125 adult patients diagnosed with CAP at a tertiary teaching hospital in Jordan. Levofloxacin, a broad-spectrum respiratory fluoroquinolone, was the most commonly used antibiotic (99.2%) in our cohort. Its widespread use is due to its efficacy against both typical pathogens like Streptococcus pneumoniae and atypical pathogens such as Mycoplasma pneumoniae and Chlamydophila pneumonia . However, the study also revealed a concerning levofloxacin resistance rate of 82.2% across various bacterial strains, highlighting the increasing issue of antimicrobial resistance and the urgent need to reassess antibiotic treatment strategies (Khan et al. , 2023; Lynch III et al. , 2006). Our findings indicate a fluoroquinolone de-escalation success rate of 33.6%, which is consistent with previous studies. For example, Deshpande et al. reported de-escalation rates ranging from 2–35% in a multicenter study of 14,170 patients (Deshpande et al. , 2021), while Joung et al. observed a de-escalation rate of 32.1% (Joung et al. , 2011). A significant difference was found in de-escalation success rates between patients with negative cultures (26%) and those with positive cultures (61%) (P = 0.002). This difference can be attributed to that positive cultures allow clinicians to identify the pathogen, enabling them to switch from broad-spectrum to narrower-spectrum antibiotics. Conversely, negative cultures often leave clinicians uncertain about the causative pathogen, resulting in continued use of broad-spectrum antibiotics, which reduces the likelihood of de-escalation. An important observation in our study was that three patients with positive culture results stopped all antibiotics rather than transitioning to narrower-spectrum alternatives. This practice is concerning, as it may lead to inadequate treatment, prolonged hospital stays, treatment failure, and increased risk of complications, including the emergence of antibiotic-resistant bacteria. These findings highlight the importance of clear de-escalation protocols to ensure that appropriate antibiotic therapy is maintained throughout treatment. The study also found a significant difference in hospital LOS between the successfully de-escalated group (median 12 days) and the failed or inappropriate de-escalated group (median 18 days), highlighting the potential benefits of de-escalation in reducing hospital stays and improving hospital resource utilization (Arnold et al. , 2011). This is consistent with other studies, such as Giantsou et al., which showed a reduction in LOS among patients who underwent successful de-escalation (Giantsou et al., 2007). However, our results contrast with those of Knaak et al., who reported no significant difference in length of stay between de-escalated and non-de-escalated patients (Knaak et al. , 2013). These discrepancies suggest that factors like disease severity, comorbidities, and hospital protocols may influence outcomes, emphasizing the need for individualized treatment plans and tailored antibiotic management strategies. Although our study found no significant difference in mortality between the successfully de-escalated and failed de-escalation groups, this may reflect the influence of comorbidities or the severity of illness. Similar results were reported by López-Cortés et al., who found no significant differences in mortality between patients who underwent de-escalation and those who did not (López-Cortés et al. , 2024). In contrast, Joung et al. observed lower mortality rates in the de-escalated group, suggesting that de-escalation may be more beneficial for certain patient populations (Joung et al. , 2011). However, the absence of significant differences in mortality in our study suggests that de-escalation can be a safe and effective strategy, as it does not show an increase in the risk of adverse outcomes such as higher mortality or ICU transfers. Despite these valuable insights, the study's retrospective design, single-center nature, and relatively small sample size are important limitations. These factors may introduce biases, such as incomplete or inaccurate medical records, and limit the generalizability of the findings. Furthermore, the study could not control all potential confounding factors, such as disease severity and comorbidities, which may have influenced the outcomes. Future prospective, multicenter studies with larger sample sizes are needed to validate these findings and explore the long-term effects of de-escalation on patient outcomes. Conclusion In conclusion, this study demonstrates that fluoroquinolone de-escalation in the management of CAP is a safe and effective strategy that leads to shorter hospital stays without compromising patient survival. While no significant differences were found in mortality, de-escalation has the potential to optimize hospital resource use and reduce unnecessary antibiotic exposure. These findings highlight the importance of antibiotic stewardship programs in improving patient outcomes and reducing the global threat of antimicrobial resistance. Declarations Author Contribution A.A.A. and A.A. contributed to the conceptualization and design of the study, data collection, and drafting of the manuscript. K.A.H. provided critical input on the study methodology, reviewed data accuracy, and contributed to manuscript revisions. R.K.A.-F. supervised the project, contributed to the interpretation of findings, and assisted with manuscript editing. M.Z. contributed to the study design, and manuscript preparation, and coordinated the submission process as the corresponding author. All authors reviewed and approved the final version of the manuscript. Acknowledgments None Clinical trial Not applicable. Funding None Data availability Due to data privacy regulations regarding individual data, raw data cannot be publicly shared. Ethics approval and consent to participate The study was conducted in accordance with the principles outlined in the World Medical Association Declaration of Helsinki. It received approval from the JUH Institutional Review Board (approval number 10/2024/1389). To ensure patient confidentiality, all data were de-identified and anonymized. Given the retrospective, observational design of the study, the ethical committee decide that patient consent was not required. This study complied with the principles of the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Arnold, H.M. Micek, S.T. Skrupky, L.P. and Kollef, M.H. Antibiotic stewardship in the intensive care unit. In: Seminars in respiratory and critical care medicine, 2011. vol 02. © Thieme Medical Publishers, pp 215-227 Dadgostar, P. (2019a), Antimicrobial Resistance: Implications and Costs. Infection and Drug Resistance , 12,3903-3910. Dadgostar, P. (2019b), Antimicrobial resistance: implications and costs. Infection and Drug Resistance ,3903-3910. Daniel Markley, J. Bernard, S. Bearman, G. and Stevens, M.P. (2017), De-escalating antibiotic use in the inpatient setting: strategies, controversies, and challenges. Current infectious disease reports , 19,1-7. Deshpande, A. Richter, S.S. Haessler, S. Lindenauer, P.K. Yu, P.-C. Zilberberg, M.D. Imrey, P.B. Higgins, T. and Rothberg, M.B. (2021), De-escalation of empiric antibiotics following negative cultures in hospitalized patients with pneumonia: rates and outcomes. 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Timsit, J.-F. Leone, M. and Zahar, J.R. (2016), A systematic review of the definitions, determinants, and clinical outcomes of antimicrobial de-escalation in the intensive care unit. Clinical Infectious Diseases , 62,1009-1017. Trupka, T. Fisher, K. Micek, S.T. Juang, P. and Kollef, M.H. (2017), Enhanced antimicrobial de-escalation for pneumonia in mechanically ventilated patients: a cross-over study. Critical Care , 21,1-8. World Health Organization, S. (2018), Global health estimates 2016: deaths by cause, age, sex, by country and by region, 2000–2016. Geneva: World Health Organization ,1242-1247. Tables Table 1. Demographic and medical characteristics of the study sample (n= 125) Table 2. Examples illustrating the decision related to the de-escalation process for patients with positive and negative culture Decision Example Incorrectly de-escalated (De-escalation from broad to narrow spectrum despite negative culture result) An 88-year-old female was admitted to JUH. The patient received intravenous Levofloxacin before the results of the blood culture were available. Within 48 hours of admission, the culture result showed no bacterial growth. Subsequently, the patient's treatment was de-escalated to Ceftriaxone sodium injection 1gm on the following day, coinciding with the availability of the culture results. Incorrectly de-escalated ( Transition from multiple antibiotics to a single antibiotic despite negative culture result) An 81-year-old male was admitted to JUH. The patient received intravenous levofloxacin and piperacillin/tazobactam injections before the results of the blood culture were available. After more than 72 hours of admission, the culture result showed no bacterial growth. Levofloxacin was discontinued, and the patient continued with piperacillin/tazobactam on the same day that the culture results became available . Failed de-escalation (Continued all antibiotics despite negative culture result) A 100-year-old male was admitted to JUH. The patient received intravenous levofloxacin, intravenous vancomycin, and intravenous imipenem before the culture results were available. After more than 72 hours of admission, both blood and sputum cultures showed no bacterial growth. The patient's treatment was maintained with intravenous levofloxacin, intravenous vancomycin, and intravenous imipenem after the culture results became available. Failed de-escalation (Increased number of antibiotics despite negative culture result) A 63-year-old female was admitted to JUH. The patient received intravenous levofloxacin before the results of the blood culture were available. Within 72 hours of admission, the blood culture showed no bacterial growth. The patient's treatment regimen was adjusted, and she began receiving intravenous piperacillin/tazobactam injection in addition to levofloxacin on the same day as the culture results became available. Successfully de-escalated (Discontinuation of antibiotic for negative culture result) A 71-year-old male was admitted to JUH. The patient received intravenous levofloxacin, intravenous piperacillin/tazobactam, and oral amoxicillin/clavulanic Acid tablets before the results of the blood culture were available. After more than 72 hours of admission, the blood culture showed no bacterial growth. Consequently, the patient's treatment was de-escalated, and all antibiotics were discontinued on the same day as the culture results became available. Failed de-escalation (Continued the same antibiotics use despite suitability for narrower-spectrum antibiotics) A 60-year-old male was admitted to JUH. The patient received intravenous levofloxacin and pipracillin/tazobactam before the culture results were available. Within 48 hours of admission, the culture results showed the presence of Staphylococcus hominis . Despite the suitability of narrower-spectrum antibiotics, the same antibiotics were continued for the patient. Failed de-escalated (increase the number of antibiotics used despite suitability for narrower-spectrum antibiotics) A 76-year-old female was admitted to JUH. The patient received intravenous levofloxacin, vancomycin, and meropenem before the availability of culture results. After more than 72 hours of admission, a culture result was received, revealing the presence of Acinetobacter baumannii . Despite suitability of narrower antibiotics, gentamycin was initiated in addition to the ongoing antibiotics levofloxacin, vancomycin, and meropenem. Incorrectly de-escalated (Stopping antibiotics instead of converting to a narrow spectrum in culture result) A 55-year-old female was admitted to JUH. The patient received intravenous levofloxacin in addition to imipenem/cilastatin before the results of the culture were available. After more than 72 hours of admission, the culture result showed the presence of Staphylococcus aureus . Subsequently, the patient's treatment was discontinued, and all antibiotics were stopped, leaving the patient untreated. Successfully de-escalated (Transitioned to narrower spectrum antibiotics for positive culture results) An 88-year-old male was admitted to JUH. The patient received intravenous levofloxacin and imipenem/cilastatin before the culture results were available. After more than 72 hours of admission, the culture results showed the presence of Escherichia coli . Subsequently, the patient's treatment was transitioned from the broad-spectrum levofloxacin to the narrower-spectrum vancomycin in addition to imipenem/cilastatin. Successfully de-escalated (Transition from multiple antibiotics to a single antibiotic for positive culture results) A 65-year-old female was admitted to JUH. The patient received intravenous levofloxacin, meropenem, gentamycin, and ceftazidime/avibactam. Within 72 hours of admission, the culture result showed the presence of Klebsiella pneumoniae . Levofloxacin was discontinued, and the patient's treatment was continued with intravenous meropenem, gentamycin, and ceftazidime/avibactam without levofloxacin. Table 3. Assessing the association between de-escalation and length of stay and mortality Outcome Successfully de-escalated (n= 41) Failed/ inappropriate de-escalated (n= 81) P-value Length of hospital stay (days), Median (IQR) 12 (8.0) 18 (11.0) 0.004*^ Mortality upon discharge, n (%) Survived Died 29 (70.1%) 12 (29.9)% 62 (76.5%) 19 (23.5%) 0.514# *Significant at 0.05 significance level. ^ Using Mann Whitney U test. # Using Fisher Exact test Table 4. Assessing the association between cultural results and de-escalation practice Microbial culture result Positive culture result (n= 26) Negative culture result (n= 96) P-value Successfully de-escalated Failed/ inappropriate de-escalated 16 (61.5) 10 (38.5) 25 (26.0) 71 (74.0) 0.002*# *Significant at 0.05 significance level. # Using Chi-square test Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5784150","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":400467944,"identity":"9be1f0fc-2f70-4e65-9862-4c1fe7a642bf","order_by":0,"name":"Aseel Abu Awad","email":"","orcid":"","institution":"Applied Science Private University","correspondingAuthor":false,"prefix":"","firstName":"Aseel","middleName":"Abu","lastName":"Awad","suffix":""},{"id":400467945,"identity":"5b3dda10-094c-49cf-a6cf-87ff55481ed5","order_by":1,"name":"Khawla Abu Hammour","email":"","orcid":"","institution":"The University of Jordan","correspondingAuthor":false,"prefix":"","firstName":"Khawla","middleName":"Abu","lastName":"Hammour","suffix":""},{"id":400467947,"identity":"50a5d390-6489-407d-ab9b-080cc072fbf6","order_by":2,"name":"Alaa Abuawad","email":"","orcid":"","institution":"Applied Science Private University","correspondingAuthor":false,"prefix":"","firstName":"Alaa","middleName":"","lastName":"Abuawad","suffix":""},{"id":400467949,"identity":"2d199a0d-4fe7-46d2-bebe-b06b877ef92f","order_by":3,"name":"Mohammed Zawiah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYDACCRBhwJDAD6ITCkjRItkA0mJAtBaQ4gMQvYSB7uz2h595CuzyjM+vTvzwwIBBnl/sAH4tZncOJEvzGCQXm914u1kC6DDDmbMTCGi5kXBAOseAOXHbjbMbQFoSDG4T1JLY/DvHoD5x84yzm38QqSWZDWjL4cQN/L3biLUljc36j8HxxBk3eLdZJBhIEOOX9Mc3Z/ypTuzvP7v55o8KG3l+aQJaEEACrFKCWOUgwH+AFNWjYBSMglEwkgAAPgdHjfaf3CkAAAAASUVORK5CYII=","orcid":"","institution":"Hodeidah University","correspondingAuthor":true,"prefix":"","firstName":"Mohammed","middleName":"","lastName":"Zawiah","suffix":""},{"id":400467951,"identity":"abd740ef-b408-46c2-ab7a-305b0ad6b59d","order_by":4,"name":"Rana K. Abu-Farha","email":"","orcid":"","institution":"Applied Science Private University","correspondingAuthor":false,"prefix":"","firstName":"Rana","middleName":"K.","lastName":"Abu-Farha","suffix":""}],"badges":[],"createdAt":"2025-01-07 20:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5784150/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5784150/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73676277,"identity":"b47e09d9-3b02-4cf2-bd3d-0b76b463398b","added_by":"auto","created_at":"2025-01-13 13:09:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":208989,"visible":true,"origin":"","legend":"\u003cp\u003eDecision-making Scheme for De-escalation Process\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5784150/v1/ab00a320b74ad768932c2bc5.png"},{"id":91899985,"identity":"4f6fa642-8bde-4c99-b526-3b57ba4e259b","added_by":"auto","created_at":"2025-09-22 20:16:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1212610,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5784150/v1/5cb56910-61d1-4c57-b199-95560b32b0bb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effectiveness of Fluoroquinolone De-escalation in Community-Acquired Pneumonia: Impact on Hospital Stay and Mortality","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCommunity-acquired pneumonia (CAP), a common and serious lung infection, is one of the leading causes of morbidity and mortality worldwide. In the United States alone, CAP results in approximately 1.5\u0026nbsp;million hospitalizations annually (File Jr and Ramirez 2023), while globally, it accounts for approximately three million deaths each year (World Health Organization 2018). CAP is caused by a variety of infectious agents, including bacteria, viruses, and fungi, with bacterial infections being the most prevalent (Jain \u003cem\u003eet al.\u003c/em\u003e, 2015).\u003c/p\u003e \u003cp\u003eAntimicrobial resistance has emerged as a significant global health threat, complicating the treatment of infections, and contributing to higher morbidity, mortality, and healthcare costs. The overuse and misuse of antibiotics, both in clinical settings and agriculture, are major contributors to this crisis (Dadgostar 2019a; Founou \u003cem\u003eet al.\u003c/em\u003e, 2017; Prestinaci \u003cem\u003eet al.\u003c/em\u003e, 2015; Shrestha \u003cem\u003eet al.\u003c/em\u003e, 2018). Moreover, the evolution of bacterial resistance through mutations and horizontal gene transfer exacerbates the challenge (Dadgostar 2019b).\u003c/p\u003e \u003cp\u003eIn response to the rising threat of antimicrobial resistance, antibiotic stewardship strategies such as antibiotic de-escalation have become critical in clinical decision-making (Daniel Markley \u003cem\u003eet al.\u003c/em\u003e, 2017). De-escalation typically involves the initial use of broad-spectrum antibiotics, followed by a transition to more targeted therapies once pathogen susceptibility is known (Kollef 2008; Trupka \u003cem\u003eet al.\u003c/em\u003e, 2017). This approach aims to minimize unnecessary antibiotic exposure, thereby reducing the potential for resistance, while improving patient outcomes (Daniel Markley \u003cem\u003eet al.\u003c/em\u003e, 2017; Kollef 2008; Trupka \u003cem\u003eet al.\u003c/em\u003e, 2017). The effectiveness of de-escalation strategies has been primarily evaluated based on hospital Length of Stay (LOS) and mortality rates (Tabah et al., 2016).\u003c/p\u003e \u003cp\u003eFluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin, are broad-spectrum antibiotics widely used to treat pneumonia due to their potent activity against a variety of bacterial pathogens (Mancuso \u003cem\u003eet al.\u003c/em\u003e, 2021; Nadeem \u003cem\u003eet al.\u003c/em\u003e, 2020; Pitiriga \u003cem\u003eet al.\u003c/em\u003e, 2017). However, the increasing resistance to fluoroquinolones, especially in pathogens like \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, poses a significant challenge to the treatment of pneumonia (Mancuso \u003cem\u003eet al.\u003c/em\u003e, 2021; Nadeem \u003cem\u003eet al.\u003c/em\u003e, 2020; Pitiriga \u003cem\u003eet al.\u003c/em\u003e, 2017). This growing resistance highlights the importance of effective antibiotic management strategies, such as de-escalation, to mitigate the risks of further resistance development.\u003c/p\u003e \u003cp\u003eDespite the proven benefits of antibiotic de-escalation in reducing antimicrobial resistance and improving patient outcomes in certain settings, there is limited evidence regarding its application to fluoroquinolone therapy in pneumonia patients. Thus, this study aims to evaluate the rate and outcomes of antibiotic de-escalation among CAP patients treated with fluoroquinolones within 48 hours of culture and sensitivity results. Specifically, we focus on comparing the clinical outcomes of successful versus inappropriate de-escalation, including length of hospital stay, and all-cause mortality.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective cohort observational study was conducted at Jordan University Hospital (JUH) to investigate the prevalence and outcomes of fluoroquinolone de-escalation in patients diagnosed with CAP from December 2022 to March 2024. The study targeted adults aged 18 years and older who were suspected of having CAP, had blood and sputum cultures requested, received fluoroquinolone therapy as empiric treatment, and were hospitalized until culture and sensitivity results obtained. Individuals who were pregnant, had uncertain diagnoses, or whose data were incomplete were excluded from the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the principles outlined in the World Medical Association Declaration of Helsinki. It received approval from the JUH Institutional Review Board (approval number 10/2024/1389). To ensure patient confidentiality, all data were de-identified and anonymized. Given the retrospective, observational design of the study, the ethical committee decide that patient consent was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collection involved extracting comprehensive information from the medical records of eligible patients using a pre-prepared data collection form. The collected data included demographic information such as age, gender, admission and discharge dates, and duration of hospital stay. Clinical information such as diagnoses, empiric antibiotic therapy (including names, routes of administration, and duration of treatment), and details of targeted antibiotics following culture results were also gathered. Laboratory data, including blood and sputum cultures and their sensitivity results, were collected to analyze the susceptibility patterns of the microbiological pathogens responsible for CAP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFluoroquinolone De-escalation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAntibiotic de-escalation refers to the process of transitioning from broad-spectrum to narrower-spectrum antibiotics based on final culture and sensitivity findings. Possible alternatives include cephalosporins, penicillins, trimethoprim/sulfamethoxazole, vancomycin, and linezolid. This strategy aims to reduce antibiotic use, and may also involve discontinuing treatment altogether if no infection is detected, ideally within 48 hours of receiving culture results. Patients were categorized into two primary groups: those requiring de-escalation and those who did not. The decision for de-escalation was based on final culture and sensitivity results. Patients with positive cultures for atypical bacteria or methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA) were not considered candidates for fluoroquinolone de-escalation. Those requiring de-escalation were further subdivided into three categories: successful de-escalation, failed de-escalation, and inappropriate de-escalation. Failed de-escalation refers to cases where empiric antibiotics were continued despite negative culture results or when broad-spectrum antibiotics were maintained in the presence of an identified pathogen for which a narrower-spectrum antibiotic would have been more appropriate. Inappropriate de-escalation refers to errors that compromise patient care. For instance, if culture results were negative, inappropriate de-escalation might involve switching from broad-spectrum to narrower-spectrum antibiotics when discontinuation of antibiotics would have been more appropriate. Conversely, if culture results were positive, inappropriate de-escalation might involve discontinuing antibiotics rather than switching to more targeted therapies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe secondary objectives of the study involved examining various factors among patients who experienced successful de-escalation compared to those who had failed or incorrectly de-escalated treatment, after excluding cases where de-escalation was improperly performed. Specifically, these included instances where antibiotics were discontinued instead of being transitioned to a narrower spectrum following positive culture results. The evaluated secondary outcomes included the length of hospital stay and mortality upon discharge. Additionally, the study conducted a comparative analysis of the success rates of fluoroquinolone de-escalation between patients with positive culture results and those with negative results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data were analyzed using IBM SPSS software version 26. Descriptive statistics were used to present frequencies and percentages for categorical variables, while continuous variables were summarized using medians and interquartile ranges (IQR). Normality of the data was assessed using the Shapiro-Wilk test. To compare all-cause mortality upon discharge between patients who were successfully de-escalated and those who failed or were inappropriately de-escalated, Fisher\u0026apos;s exact test was used. The LOS was compared using the Mann-Whitney U test. Furthermore, to assess the association between microbial culture results and de-escalation practice, the Chi-square test was applied. All statistical tests were two-tailed, with a significance level set at p \u0026le; 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eDemographic and medical characteristics of the study sample\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the study period, 125 patients were eligible after screening for inclusion criteria. The median age of participants was 73 years (IQR= 24), with the majority of patients (n = 80, 64%) being aged 65 years or older. In terms of gender distribution, there were 44 female patients (35.2%) , and 81 male patients (64.8%). The median LOS for patients was 13 days (IQR= 11). Regarding mortality upon discharge, 93 patients (74.4%) survived, while 32 patients (25.6%) died. Additionally, 20 patients (16%) were transferred to the ICU, 100 patients (80%) remained in the general ward, and 5 patients (4%) were already in the ICU at the time of hospital admission. The demographic and medical characteristics of the study sample are summarized in \u003cstrong\u003eTable 1\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAntibiotic Prescription Patterns Among the Study Sample\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients in the study received fluoroquinolone therapy, with the vast majority being treated with levofloxacin (n = 124, 99.2%). A small proportion of patients were treated with fluoroquinolone monotherapy (n = 12, 9.6%), while the majority received multiple antibiotics in conjunction with fluoroquinolones. Specifically, 42 patients (33.6%) received two antibiotics, 49 patients (39.2%) received three antibiotics, and 22 patients (17.6%) received four antibiotics. Vancomycin was the most frequently prescribed adjunct antibiotic, administered to 72 patients (57.6%). The median number of prescribed empiric antibiotics was 3 (IQR = 1.0), resulting in a total of 331 empiric antibacterial agents, including fluoroquinolones, being prescribed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlood or Sputum Culture and Susceptibility Testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of microbial cultures showed that 96 patients (76.8%) tested negative, while 29 patients (23.2%) had positive culture results. Susceptibility testing was conducted for the majority of the positive samples (n = 28/29, 96.6%), with only one positive sample (3.4%) not undergoing susceptibility testing. Most of the isolated pathogens exhibited resistance to fluoroquinolones (n = 23/28, 82.2%), while a smaller proportion were sensitive to fluoroquinolones (n = 3/28, 10.7%). Furthermore, two samples (7.1%) did not undergo fluoroquinolone susceptibility testing but were tested for other antibiotics.\u003c/p\u003e\n\u003cp\u003eAmong the positive culture specimens, the majority showed only one microorganism (n = 28/29, 96.6%), while one specimen (3.4%) exhibited two pathogens. The most frequently reported pathogens were \u003cem\u003eStaphylococcus hominis\u003c/em\u003e (20.0%), \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (16.7%), \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (13.3%), and \u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e (10.0%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessing the Appropriateness of Fluoroquinolone De-escalation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study revealed that 76.8% of patients suspected of having CAP had negative blood and/or sputum cultures. These patients were subsequently categorized into three groups based on the appropriateness of fluoroquinolone de-escalation: those who inappropriately de-escalated (42/96, 43.8%), those with failed de-escalation (29/96, 30.2%), and those who successfully de-escalated (25/96, 26.0%). These findings are illustrated in \u003cstrong\u003eFigure 1\u003c/strong\u003e. \u003cstrong\u003eTable 2\u003c/strong\u003e contains examples illustrating the decision-making process related to the de-escalation for patients with both positive and negative culture results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessing the association between de-escalation and length of stay and mortality\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study found that patients who were successfully de-escalated had a significantly shorter median hospital stay of 12 days (IQR= 8 days) compared to those who failed or were inappropriately de-escalated, with a median stay of 18 days (IQR = 11 days), with a p-value of 0.004 using the Mann-Whitney U test.\u003c/p\u003e\n\u003cp\u003eIn terms of mortality at discharge, the results showed no significant difference between the two groups. Among the successfully de-escalated patients, 29 (70.1%) survived, while 12 (29.9%) died. In contrast, among those who failed or were inappropriately de-escalated, 62 (76.5%) survived, and 19 (23.5%) died. Statistical analysis using Fisher\u0026apos;s exact test resulted in a p-value of 0.514, indicating no significant difference in mortality upon discharge between the two groups. Further details are presented in \u003cstrong\u003eTable 3\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessing the Association Between Culture Results and De-escalation Practice\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the patients with positive culture results, 16 patients (61.5%) were successfully de-escalated. However, 26.0% of patients (n= 25) with negative culture results were successfully de-escalated. The Chi-square test revealed a significantly higher success rate of de-escalation among individuals with positive culture results compared to those with negative culture results (p = 0.002). The details are presented in \u003cstrong\u003eTable 4\u003c/strong\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study assessed the prevalence and effectiveness of fluoroquinolone de-escalation in 125 adult patients diagnosed with CAP at a tertiary teaching hospital in Jordan. Levofloxacin, a broad-spectrum respiratory fluoroquinolone, was the most commonly used antibiotic (99.2%) in our cohort. Its widespread use is due to its efficacy against both typical pathogens like \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e and atypical pathogens such as \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e and \u003cem\u003eChlamydophila pneumonia\u003c/em\u003e. However, the study also revealed a concerning levofloxacin resistance rate of 82.2% across various bacterial strains, highlighting the increasing issue of antimicrobial resistance and the urgent need to reassess antibiotic treatment strategies (Khan \u003cem\u003eet al.\u003c/em\u003e, 2023; Lynch III \u003cem\u003eet al.\u003c/em\u003e, 2006).\u003c/p\u003e \u003cp\u003eOur findings indicate a fluoroquinolone de-escalation success rate of 33.6%, which is consistent with previous studies. For example, Deshpande et al. reported de-escalation rates ranging from 2\u0026ndash;35% in a multicenter study of 14,170 patients (Deshpande \u003cem\u003eet al.\u003c/em\u003e, 2021), while Joung et al. observed a de-escalation rate of 32.1% (Joung \u003cem\u003eet al.\u003c/em\u003e, 2011). A significant difference was found in de-escalation success rates between patients with negative cultures (26%) and those with positive cultures (61%) (P\u0026thinsp;=\u0026thinsp;0.002). This difference can be attributed to that positive cultures allow clinicians to identify the pathogen, enabling them to switch from broad-spectrum to narrower-spectrum antibiotics. Conversely, negative cultures often leave clinicians uncertain about the causative pathogen, resulting in continued use of broad-spectrum antibiotics, which reduces the likelihood of de-escalation.\u003c/p\u003e \u003cp\u003eAn important observation in our study was that three patients with positive culture results stopped all antibiotics rather than transitioning to narrower-spectrum alternatives. This practice is concerning, as it may lead to inadequate treatment, prolonged hospital stays, treatment failure, and increased risk of complications, including the emergence of antibiotic-resistant bacteria. These findings highlight the importance of clear de-escalation protocols to ensure that appropriate antibiotic therapy is maintained throughout treatment.\u003c/p\u003e \u003cp\u003eThe study also found a significant difference in hospital LOS between the successfully de-escalated group (median 12 days) and the failed or inappropriate de-escalated group (median 18 days), highlighting the potential benefits of de-escalation in reducing hospital stays and improving hospital resource utilization (Arnold \u003cem\u003eet al.\u003c/em\u003e, 2011). This is consistent with other studies, such as Giantsou et al., which showed a reduction in LOS among patients who underwent successful de-escalation (Giantsou et al., 2007). However, our results contrast with those of Knaak et al., who reported no significant difference in length of stay between de-escalated and non-de-escalated patients (Knaak \u003cem\u003eet al.\u003c/em\u003e, 2013). These discrepancies suggest that factors like disease severity, comorbidities, and hospital protocols may influence outcomes, emphasizing the need for individualized treatment plans and tailored antibiotic management strategies.\u003c/p\u003e \u003cp\u003eAlthough our study found no significant difference in mortality between the successfully de-escalated and failed de-escalation groups, this may reflect the influence of comorbidities or the severity of illness. Similar results were reported by L\u0026oacute;pez-Cort\u0026eacute;s et al., who found no significant differences in mortality between patients who underwent de-escalation and those who did not (L\u0026oacute;pez-Cort\u0026eacute;s \u003cem\u003eet al.\u003c/em\u003e, 2024). In contrast, Joung et al. observed lower mortality rates in the de-escalated group, suggesting that de-escalation may be more beneficial for certain patient populations (Joung \u003cem\u003eet al.\u003c/em\u003e, 2011). However, the absence of significant differences in mortality in our study suggests that de-escalation can be a safe and effective strategy, as it does not show an increase in the risk of adverse outcomes such as higher mortality or ICU transfers.\u003c/p\u003e \u003cp\u003eDespite these valuable insights, the study's retrospective design, single-center nature, and relatively small sample size are important limitations. These factors may introduce biases, such as incomplete or inaccurate medical records, and limit the generalizability of the findings. Furthermore, the study could not control all potential confounding factors, such as disease severity and comorbidities, which may have influenced the outcomes. Future prospective, multicenter studies with larger sample sizes are needed to validate these findings and explore the long-term effects of de-escalation on patient outcomes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this study demonstrates that fluoroquinolone de-escalation in the management of CAP is a safe and effective strategy that leads to shorter hospital stays without compromising patient survival. While no significant differences were found in mortality, de-escalation has the potential to optimize hospital resource use and reduce unnecessary antibiotic exposure. These findings highlight the importance of antibiotic stewardship programs in improving patient outcomes and reducing the global threat of antimicrobial resistance.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.A.A. and A.A. contributed to the conceptualization and design of the study, data collection, and drafting of the manuscript. K.A.H. provided critical input on the study methodology, reviewed data accuracy, and contributed to manuscript revisions. R.K.A.-F. supervised the project, contributed to the interpretation of findings, and assisted with manuscript editing. M.Z. contributed to the study design, and manuscript preparation, and coordinated the submission process as the corresponding author. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to data privacy regulations regarding individual data, raw data cannot be publicly shared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the principles outlined in the World Medical Association Declaration of Helsinki. It received approval from the JUH Institutional Review Board (approval number 10/2024/1389). To ensure patient confidentiality, all data were de-identified and anonymized. Given the retrospective, observational design of the study, the ethical committee decide that patient consent was not required. This study complied with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eArnold, H.M. Micek, S.T. Skrupky, L.P. and Kollef, M.H. Antibiotic stewardship in the intensive care unit. 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(2007), De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate. \u003cstrong\u003eIntensive Care Medicine\u003c/strong\u003e, 33,1533-1540.\u003c/li\u003e\n \u003cli\u003eJain, S. Self, W.H. Wunderink, R.G. Fakhran, S. Balk, R. Bramley, A.M. Reed, C. Grijalva, C.G. Anderson, E.J. Courtney, D.M. Chappell, J.D. Qi, C. Hart, E.M. Carroll, F. Trabue, C. Donnelly, H.K. Williams, D.J. Zhu, Y. Arnold, S.R. Ampofo, K. Waterer, G.W. Levine, M. Lindstrom, S. Winchell, J.M. Katz, J.M. Erdman, D. Schneider, E. Hicks, L.A. McCullers, J.A. Pavia, A.T. Edwards, K.M. Finelli, L. and Team, C.E.S. (2015), Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. \u003cstrong\u003eThe New England journal of medicine\u003c/strong\u003e, 373,415-427.\u003c/li\u003e\n \u003cli\u003eJoung, K.M. Lee, J.-a. Moon, S.-y. Cheong, H.S. Joo, E.-J. Ha, Y.-E. Sohn, K.M. Chung, S.M. Suh, G.Y. and Chung, D.R. 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(2006), Levofloxacin for the treatment of community-acquired pneumonia. \u003cstrong\u003eExpert review of anti-infective therapy\u003c/strong\u003e, 4,725-742.\u003c/li\u003e\n \u003cli\u003eMancuso, G. Midiri, A. Gerace, E. and Biondo, C. (2021), Bacterial antibiotic resistance: The most critical pathogens. \u003cstrong\u003ePathogens\u003c/strong\u003e, 10,1310.\u003c/li\u003e\n \u003cli\u003eNadeem, S.F. Gohar, U.F. Tahir, S.F. Mukhtar, H. Pornpukdeewattana, S. Nukthamna, P. Moula Ali, A.M. Bavisetty, S.C.B. and Massa, S. (2020), Antimicrobial resistance: more than 70 years of war between humans and bacteria. \u003cstrong\u003eCritical Reviews in Microbiology\u003c/strong\u003e, 46,578-599.\u003c/li\u003e\n \u003cli\u003ePitiriga, V. Vrioni, G. Saroglou, G. and Tsakris, A. (2017), The impact of antibiotic stewardship programs in combating quinolone resistance: a systematic review and recommendations for more efficient interventions. \u003cstrong\u003eAdvances in therapy\u003c/strong\u003e, 34,854-865.\u003c/li\u003e\n \u003cli\u003ePrestinaci, F. Pezzotti, P. and Pantosti, A. (2015), Antimicrobial resistance: a global multifaceted phenomenon. \u003cstrong\u003ePathogens and Global Health\u003c/strong\u003e, 109,309-318.\u003c/li\u003e\n \u003cli\u003eShrestha, P. Cooper, B.S. Coast, J. Oppong, R. Do Thi Thuy, N. Phodha, T. Celhay, O. Guerin, P.J. Wertheim, H. and Lubell, Y. (2018), Enumerating the economic cost of antimicrobial resistance per antibiotic consumed to inform the evaluation of interventions affecting their use. \u003cstrong\u003eAntimicrobial Resistance \u0026amp; Infection Control\u003c/strong\u003e, 7,1-9.\u003c/li\u003e\n \u003cli\u003eTabah, A. Cotta, M.O. Garnacho-Montero, J. Schouten, J. Roberts, J.A. Lipman, J. Tacey, M. Timsit, J.-F. Leone, M. and Zahar, J.R. (2016), A systematic review of the definitions, determinants, and clinical outcomes of antimicrobial de-escalation in the intensive care unit. \u003cstrong\u003eClinical Infectious Diseases\u003c/strong\u003e, 62,1009-1017.\u003c/li\u003e\n \u003cli\u003eTrupka, T. Fisher, K. Micek, S.T. Juang, P. and Kollef, M.H. (2017), Enhanced antimicrobial de-escalation for pneumonia in mechanically ventilated patients: a cross-over study. \u003cstrong\u003eCritical Care\u003c/strong\u003e, 21,1-8.\u003c/li\u003e\n \u003cli\u003eWorld Health Organization, S. (2018), Global health estimates 2016: deaths by cause, age, sex, by country and by region, 2000\u0026ndash;2016. \u003cstrong\u003eGeneva: World Health Organization\u003c/strong\u003e,1242-1247.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style=\"text-align: left;\"\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eDemographic and medical characteristics of the study sample (n= 125)\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cimg 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cuRImJoO+iF++umn3XENHz48TB3YdIH65JNPUvdZA0Al07Xw1ltvDWpqanpcb86fP99tLAoA5P777w++++67YP/+/W6+paXF3aTKx4oVK4J9+/YFn376qXuNAoVNmzYFX375ZXDfffeFa2WXdJ3UdhctWtT1fo4ePerSq6qqcm5f2xw/frybjsuO6L3rfa9evTpMAVCxFLSUSlNTk36R3NDW1hamll97e3tHdXW1O76bTW1tbcfmzZvDOQBAuTU2NiZeb+rq6joaGhrCuc7rZnRd/abrOlpfXx+mZJcJbtz60e3oupcJNMK57LJdJ5WufRhd37Vd7VPvJxtdo/R6rRtH+80EP922D6AylbR62Lp169ydGHn77bfdOA1U1H3lypWuu1k3k8WLFwdr1qzJu5geAFB8cdcblcCoFOXxxx8PU4Jg5syZPdZdsmSJG+u6lY8NGza4sbblW7p0aXD27Nm8qpolXSdV3fv999/vVuIzatSortIgG8dRac9jjz3mqqwlUcmN9qlrGYDKVrKgRT+K+mHavXu3m1dxcq72Flru1+ONDvrBM1pXxd9+nd982s7odSoinzVrVpjSyerY+oO/PdUHtnT/OPx6vToWHX/0fWo7ft3fuGPV56N9aNsqPtdnp+1pWlT1y3+v+lGPe7+qiie64AAAyk/tNeIcP348qK6u7ladKq66stp6yLx589w4G11/VF1LVbWi25o8ebIbf/bZZ26cJOk6KQpW4qqoKXAR7TeOrmUHDhxI/Cx806ZNC9ra2nrVjgfAzaNkQcu2bdvcnRL9GNfW1gZXr14NDh48GC6N99RTT7m7NLoT1N7eHtTX17t0/ah3dHR01XHVD6oy+CNHjnR3glpbW932p06d2pXJT6KLhNZVnVmftt3Y2BjOBW6b/g+z6vSq1Ejr2HEo0HjllVdcYKbj0/G+8cYbwTPPPOOWi45Hx6VAQ+tou/oxfuSRR7qCG/0wHzp0yF1orl275kpKFLToOE+dOuWWv/XWW+5z0TZeeOGFxLtZduHIdrcLAFB++t2vq6sL55K9+eabbr240pqoH3/80Y3tBlacM2fOhFPxkq6T+Ug6RrWNsZuYudx5551unCu4AnCTy2R6iy6TMXd1Vo3qxGrXflpUc3OzW0d1f43VbVW63yZG9XtVL9Znr89Vn1Z1h7We1o+j7Wq53oPPjsUk1bu1er32equL7K9nx+CnaVpp2qa2bWkSrfMsmo/u2yS9BwBAeuj3PtvvtJbp9z/Xej675kSvkWLXGQ3Z5LpOxtE1Wq+Juy7pmDQYu0Zlo+X+NRdA5SlJSYuqMq1atSqc67zzotKSbMW9586dc+OxY8e6saho2+4W/frrr24sKrZWvVjfHXfc4ca5Shi+/fZbNx48eLAbR6kdjug9+FRKZCU/YqVG0WJyvU+x3lRGjBjhistvv/12Ny9DhgwJp3p66aWXuor0bduqFrZz585upUh+Hegk169fD6cAAGmia6F+25N62lJVYfWypWuaSj2mT5/uSvdLIdd1Mo7arWaCnR7XRKsW1pvewPS+AVSuogctagCuH9YFCxaEKZ0siFG1sWys7m7ULbfc4sbavn7Ili9f3tVGRIN1oSh9aYSuH9za2loXJPjbUfUsP1DQD7GOwz8GDRY0/fLLL26sgE1V2FRtS9tTOxwFXYWwOsB6j3q9tqMLXfTiEHXy5MlwCgCQJqr6lK1qmDL5HR0dQXNzc1cVa/3+R9tMpoGuh6py9vzzz4cpNxRSLSxOPm1VAdycih60qARCP67qk97PzCvIEJVA+CUGRj/KcuLECTc2+oFW6YXdjbISF/2Q6wc9brB2Hb1lvZZYj2f60VRpiX9HTIGD2rjE7V/Djh07wjU711UbHDVqVANDv8QmH9qv2rNYMKXPw+8MAAAwsOjmXj4l5rNnz3ZtKi1wUXuTbKyxfTZ2ve0PukarHaYCk2jDf12nFi5cmFiaBADZFDVo0Y+XShFUDSwuI28/lNGqV6IfNWXmlSm3KmT6UVdm3S+dsRKXr7/+2o2LwaqzWWnLRx995Bq/+4YOHeqOLdddLwVoCm4USOnhYdp2tuphSfR6XbhaWlrc9nSRyPXk4HwuXgCA0spVNSzOypUr3VidtWRjVZHjrk1Wk6GvN/Z8//znP4PNmzfHvhddpzT4NzA1WPVpm88mV40CADevogYtugOkNihJP4jWXkTBQNwP6uuvv+6Ky/XjrB+yrVu3uhIV3Wky+mFUqYeqYcVtI1ed3wceeMCNk6qhGevnXqUtOt5of/eqXyxJPaLZccyfP9+N/ZKXvtAPuIIXBVXqqSwbC/AAAOmhqmFx3QlnY+1LJk2a5MZJdP3Vja24m2r//e9/3Xju3LlunCTf66RunKm0KCn4UjATN1jbT5tPoms9gArWUUSZH6LEHq2M9a6V+aEKUzqpxywt83sJS1JfX++2EV3felrJRr2hxO0/jnou0braX5T1lKLB7/FMtL59Dlqu7fiy9R4W7SVMtD3rUczo+LV+HO0vuk8AQDro97mQnrlE15namB7BdN2L9ixm17nePhE/n+ukrktx70HXqrjrmE/vI+n6JXo/Wp7reg7g5laUoEU/UhZIZAtaLDDRehr8HzzrFlk/UvqhtEHbi24zuh39AGpeF4J8uoXUevn8GFpgkPSe7Jg16GKg49C2/SDHfpwtkNHYjl0/7HZRsH1pO9HAzd6fvTct13pxFwZ9NrZtAEC66LqX7aaSrk1armuCfs9FAYuuAdFrg3/zLLpM1xq7Jto12ubzoXWTrpO2LV2booOOJS6Y8dl6SSxoyrUdADe3ogQt9gNkg+bj+OtE19UPrn4E49bRoB9s+wEX+xG25fpxzffHWBcD7SsXbU/BQTb6UdU6OgaNLQgxtg0t13vVvIIXm9f7jn5+GvxASe/NX0fHHt2PsUAqegEDAJSfrlsakug33L8W6trnBzA+pWl59Ppo7Fqn7eg6Ush1Iek6qRtidmxxQz7XVrueJdHnk+vaC+DmN0h/Mj8WqaTuHJ988kk37XfXq4aHasOibpOt+9++UD3fBx980LVbSXp6r6jDAO27N/3Ll4t6KZsxY8aAOmYAQLrke53sb9rvmDFjgk8//ZRG+ECFS23QooBFjQP9Rvc+9bbyv//9r1+CFlGvXuo/Xo3ao900mtGjRwfHjh3r155WikldM+sCo/cEAEBf5HOd7G/WnT833gCU5In4hdIPo3royka9rUQfWNkX6u1E/co/9dRT3XpYURfHogBAvbsMlIBFn+H27duDvXv3hikAAPRe0nWyWNTr5kCr3QCgeFJZ0mIPatSDs+rr690P5dixY90yVRM7cOCA++FM6laxL7RvdVusH0kVgasamh3LQCllUcBy6tSpfiuFAgDA+NfJYrHnsyXVtgBQeVJbPUw/inomigKFtrY2l1ZdXe2e2/L888+XpGhaxdJ6EFZtba3rO74YQRIAAACA7FLdEB8AAAAAUtmmBQAAAAAMQQsAAACAVCNoAQAAAJBqBC0AAAAAUo2gBQAAAECqEbQAAAAASDWCFgAAAACpRtACAAAAINUIWgAAAACkGkELAAAAgFQjaAEAAACQagQtAAAAAFKNoAUAAABAqhG0AAAAAEg1ghYAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaAFAAAAQKoRtAAAAABINYIWAAAAAKlG0AIAAAAg1QhaAAAAAKQaQQsAAACAVCNoAQAAAJBqBC0AAAAAUo2gBQAAAECqEbTAeeKJJ4Jhw4YFFy5cCFNKb9euXcFXX30Vzg1Ma9euLetnCAAAcDMqedCyZcuWAZ8xRf9TZn/SpEnBlClTwpSBaePGjcGePXuCffv2hSkAAADoq0EdGeF00V2+fDkYM2ZMMHHixODIkSNh6s3HgrKBngEvlRUrVgT33XdfsGzZsjBlYNN5/uCDDwbvv/8+5wAAAEA/KGlJy/Hjx4OrV68GR48evamr0GzYsCGcQi6qEnbs2LGbJmCR4cOHu4DlkUcecQEMAAAA+qakQcu6deuCmpoaN/3222+78c1GpQYKypCbMvQvv/xysGrVqjDl5qESFrURWr9+fZgCAACA3ipZ0HL48OFg9OjRwe7du9286vznugut5WrroMzfoEGDegxqH2O0rgIGW3fChAkFtZ3R8eg1eq22oW1Fj0+lAnoPtn81XvdLjB5++OFg586dbnrq1Kk9jvH77793r0l6vdFx27HEDb64bUbft/Zhn6NoWuvqPUp0uS+fz1Wv13vXcq2nY7BtZ6O2Hyp5U1sWn23LH3x+un8s+qzt/6Ox/l9Ruf6Her+2jrat80LvSe9byzTY56dBx6ohzqxZs9z5ED2PAAAAUCC1aSmF2trajqampq5p7bqxsdHNJ9F61dXVHW1tbR3t7e0d9fX17nVK82lZTU1Nx+bNm918a2urW0frajoXbVev135Ex6XXKs1Ymr0HjTWvY/TpGJTe0tISpnSyY2pubnbzGms9pen4jV6ndHsvmq+qquq2b2PbsM9Rx69j9tfVtrUt24am9X41ryG63Jfv5+qvo2PQZxL9XOLYtqK0X/9/7X8+ovnoMWj9uro6t0xD3DmWz/9Q69hnqPekbfrvuaGhodt+NK9lcfR6f38AAADonZIELZbZNZZZ9NOiohlyUSbRMtcWYIgyh9FMsr1eGcxsLEjwgwzbj398lgn2WebWZxnVaNCi11vG3liG13+P2qb27bNtKmNu7Bj9NNHnonW1TOsYO347Bq3nf4Zx7y+fz1X/W837+9J09HVRWkev0/uNY+8v+lmIjsH/v1pgFz0Gbd9/fdx7zPY/tPegbVmApO1p/76k92DnVq5zEAAAANmVpHqYqtv47RZUJScTEASZTLOrNhbn3Llzbjx27Fg3FjVwVs9j8uuvv7qxbNq0KXjsscfCuU533HGHG+/fv9+Nk2zfvt0di9/Lk/Zz5cqV4Pz582FKEIwaNaqrPY7RevlQFS61c8lkgsOUTiNGjHDjTz75xI3l7NmzXe/RTJ482Y39akzWqcHcuXPDlE46zkwg45YdPHgwTL1h9erVbqz1NGSTz+d6yy23uLHfdkOfS/R1UT/++KMbJ32GSn/ppZfc+4h2H/zBBx8Ef/vb38K5zv+hqmL529J0JsBwr7cqZIX+D9UGS7SOejeTYcOGBa+88kq3Kl9PP/10OBXvjz/+CKcAAADQG0UPWpTRVqZzwYIFYUonC2K2bdvmxkkuXboUTnVnmWVtXxnT5cuXd7Uz0DB+/Hi3XPzMfpQy32q/kMuOHTuCM2fOuGllghV45dvg3jLoOib/GHXM4gdHEp03Q4cODaeC4NChQ248ePBgN/ZZBtsPhgqV7+dqQZLabuhztACjP3oDW7JkiQs8LHgQ7VO9jc2ePTtM6Qz09H/0j1ODjl/sHOrL/9CoZzjtT113qw2Ngpdc75WOGQAAAPqm6EGL7vYr83jrrbd2y1Bahl0ZOpVERFmpxIkTJ9zYKJOokhHLmFuJS3Nzs+r4xA65ShTypYyuMubKuOpOf7TkJMnFixfduL29Pfb4/CClrq7OlUD5gdaff/7pxvPmzXNjyXb33i+d6q1CPlcFA42Nja50atGiRa7Retz/tFAq4VBgoc/DgiGdTwqSfFre0NAQe4watA3T2/+h0bZaWlpcicuaNWtc8JJUWggAAID+UdSgRQGGqhgpUxmXmbQMY1wvTwpK7A6+ZQqVcdVdbr90xkpcvv76azfujXzuhGvf6hFMmV09GNO/05/LkCFD3Pj06dNunI26AFbpgvVepkHVkVStyc98mx9++CGc6qkvwVqhn6tKG37++edg8+bN7n80ffr0rCVc+XrxxRfd2Epb3n33XVcC49PnpdKXXPryP/SpKqECzaamJjc/Z86crIFLoYERAAAAuitq0KJ2F2qfkZR5toxoUrewr7/+uit5WLlypSud2bp1q7vz72c2Fdwo06rqQXHbsDv0SSxDGbee7sqrxECZb5Ug6FjiAodcrEtftcWI4+9b7+fNN990VcFUOqU7+Sq5UCbbZ21GvvzySzf2WcnMtGnT3Lg3evO5qmREbWZU6qLStbg2Neaee+5x46SqcMaqnynwVSCnY4qeT2rPokAprnRH/zv9H/v6P4yj7djnn62ao1+tDwAAAIUratCioMRvjxClO9bWMFrP7PApo6znX7zxxhsuY6uSGbVHiLs7rsyjMrVa37+7r0ystf1IsnjxYjdWhtjP9Gr673//u8u8+43+fXGZ+Sgdj7ahKm0KAKwExSjzb9XHRPPat8Z6z6pypepX0QbjaiNkQYX/nuWzzz5z+4vLnOdzzCafz1UBQbSkLJ/2LHo/+t9r+7nY9hTcvvDCC27aZ9XmVLqj4zF6r/q8FSD15n9owZ8v+pnqf5tUkmKlYDouAAAA9EEmY9zv1EVsfficjWjXvz6tl8m4uvU0+F3JWrfI6i5WXdDaoO1FtxndTiYT6eYzmfpuz/JIovWzvVbb17yWq3tiHaeOKxMYuDQdq3Vb7B+31tMxi7Zl29BY+9HrtS9t3yhNy/33rG3qPWcy+OFanWxf2oYt03Ho9f5npGV2rHY8Pu3ffy8mn89V+9Ey7dfeh/ahdaLHG6XX6LX5/o+0Tf+z8tn5pkHHaP9Tez96nV5vx5r0P9R6SleaxtH9KV37svdm798/d411aZ10zAAAAMhPUYIWyzDaoPk4/jrRdZUptExm3BDN7Gvaz7gqw5lPZlj0WmUwbX86huhrlam15dqPXqPMueb1Wv9Y7P3bekbbtGXaVnS5WEY3afCDClFm2Q8sou/bMtX+4P8/4pb7gY2OL9vnqtdr/5b51xD3+cXRtvU5KFjIRevoOLKxYEnHoGOKBhL5/A/tPfiDT+/T/7w1HxewiJblOmYAAADkNkh/MpmvVFLVnieffNJNnzx50o3l2rVrrlqUuk3uj65100TVm/Re9WwWddXrVx377rvvXINzVRm7Wahq2VtvvZWzbYuqZT377LPdnqeTZvo/PvLII65zgmjVPgAAABQmtUGLAhY9ODGphyf11vS///3vpgpa1FZE3ehGG9371L4k2/KBSP9rtQ1J+l+qPY0a2+cKbNJE/ye15xooQRYAAECaFf05Lb2hzLsaXWejxubRB1YOdOo1LFvDcH0uM2bMCOduHupowDofMPoc7LNQL2TqpnigWLt2revggYAFAACgf6SypEV31mtqaly3ufX19e4uvD0wUVWnDhw4EOzevdul30yU2VVvadXV1cHSpUuDcePGuSfeq5qYPWRTGfyblYKWO++802X29fBG/f9ra2td8GJPsk87VXdTF9c327kJAABQTqmtHqbA5e2333ZtONrCbnGVma+rqwuef/75m7adgDLu77//frcHXuo96+ntvX0Y4kCk6lX6DBS06nk9tAsBAACoXKluiA8AAAAAqWzTAgAAAACGoAUAAABAqhG0AAAAAEg1ghYAAAAAqUbQAgAAAJTIV1995R6RUGrl2m9/IWgpIz1Q8YknnggGDRrkhgkTJrgTKomWaR2tO3r06ODw4cPhkvzpmSd6Ar2eg2LbyfcE1mv1ui1btoQpuanrav89qitjvW8AAICBRPkg5YGUF+otPdpCz99btmxZmNJJ29bz+ix/prya0vIVzd9pHN2GnoOnZ8kpX1bIttOCoKVMlHGfPn16cPbsWfcAxaqqKjc9derUbk+GN0rTsqeffjpQL9V6lsucOXNi102iE1RBg14zceJE99wbPQNn+fLl7sTO5ZlnnnEPfMyX3qMeEqovTnt7uxtGjRoVjB8/PmtwBgAAkCa6UfzUU08Fa9asKSgv5FP+69ChQy5o8Fn+TM8mVF5Q+aUrV664tHyDC62rB3Hr9conaqx5pfv08GvlP/VeBhw9pwWlV1dX19HY2BjOdXRkTtCO+vp6PTOnIxPAhKmdtExpWu7TvNIzgUeYkp32p9doe0Zp2qeG1tbWMLWn5ubmjkwA4tbbvHlzmJpdJhhzr4nKBEvuuP3jAAAASDvlYXqTfVYeS6+Ly7MpXxVdpmmlNTQ0hCnJmpqaYrfd0tLi0pWHi1IeLd/8XFpQ0lIm999/f7eiQT3xfceOHa70QxG8XxKxZ88elzZ37twwpdOTTz7p0rU8H9euXXP78J8ur2PQU+fFfwq/T1H+K6+8Erz66qthSm4qZdH2Fi5cGKbcsHTpUnfcx48fD1MAAADST9Xqe0MlNHV1da7GiU95rE2bNrmaKf4yTasmzhtvvJGztOXixYvhVHe33367G//5559u7Fu8eLE7JlXjHygIWspk9erV4VR39mW45ZZb3FgOHDjgxnfccYcbG9VNlP3797txLkn7HDlypBsPGTLEjaNULUwBy+DBg8OU3K5fvx5O9TR58mQ3VhEpAADAzUw3onUjV9Wyok6fPu1u5OqmddSMGTPcONdN3nHjxrlxQ0ODG5tvvvnGNT+YOXNmmHKDmglIvje+06Digpbff//dNXQaMWJEV+NwlWCoHmFa6MRVnUOjeonip/na2tryrvOYTdxJbY39Z8+e7caF+u6778Kpnv74449wCgAA4Ob00UcfufHYsWPd2Hfu3Dk3Vg2cJP/973/DqXjKo6mkRjexrR2MarysW7cu+PLLL7vVsDFWqpPvje80qKigRQHL/Pnzg6FDh7qitI6ODjds3bo1eO2114Ldu3eHa5bP+fPnXfUpk2+D9R9//DGcKtwvv/ziiiDjiixXrlwZvPPOO2FK/qxIUsFgfwRUAAAAA5EaxMs999zjxr4vvvginEr27bffhlPJjhw54gIXleiMGTMmePPNN10pTtINb1HeTze+B0qvrhUVtChgefTRR4NVq1aFKZ3uvvvu4OOPP3aBSzlLXNSrhIrxkqpxFYPqMmq/ausSpWph27Zti43Qc1EApGJKFXkq6rc6kyq5+fvf/+6mFTwCAADczKzGTG/yU/nStq3URHkvTefbdjhblf40qZigRdGmiuCiAYu57bbbgueee85l0stBpREq8Sl1aY8CCwUs0VKWvlYLk40bNwabN292UbyqvOkZM35jsLi6nQAAACiMSktmzZoVtLa2Bo2NjS5t0aJFeT0a4+TJk+FUulVM0HLixImuhkpJVIRWrueHrF+/PnjhhRd6FONZY/tcbD1rp+MPSQ+D1ImsZ6jE9Rfe22phUSo1Ul/jqoan4lE1/LI7DnFtaAAAACqFNbbPJtc6yrfpRvCGDRtcPlI9wzY3N7vaOwpcbpZn41VcQ/w0UvAwbdq0HsGDsR4lom1DrMqV3+OE6idGB3U6EKWIXA274qqFqScJlY7ceuut3YIfPdxS1EVetmAoG+vZQuNo6Q4AAEAlsTyaHksRpTbHEpeP8x08eNBVCfPzkaop8+GHH7pp6wggifXqmnYVE7QoKLAeGpIoI59vyUZ/sWK7pIBF1K+3qIqb76effnJjWy5qiBUdotvW+/x//+//uepbcXTyqlpXdLDnuSgQ0nyhJ7neq+pYqqHY888/H6YCAADcvJTvkbhnolitk7g21daAP1fNlE8++SSc6s56Fcv1LBb/MRuppidMVoqHHnqoY8uWLeFcd7/99lvHXXfd1XH06NEwpfj0BNOGhCed+k+/1xNO9QR5P000r3Qtz5eeyJoJOsK57vR0/GxPxbcnq2YCljDlBr0u22v1NFa9trq6Out6AAAAaaU8VKHZZ+X19Brlo+LYcj8/p2mlRfOJSo9uR/m3pO0r3xWXbxPlITUMFBUVtCgwuffee90JoGmjQEXp7733XphSfApYdILp5I8OOoGiJ6mtr7HYCWrz+VCwoG1nou4e+9RJrfRskoIW+2JpiAZQeo2CKy3Tftrb28MlAAAAA4fyOMpHKU+TFIDEUf5Lr1HeLY7yRsqDadC09uPP+5Rf07b8/J+9Xsdmx6VtKP8Vtw1RmrYTzW+mWUUFLaJgRf8glaron6Vhzpw5JS1hsVKHbENcaYReZyerTsJCvjD+Fy1pSPoymaSgxb4s0S+G1tU+6+rqCgquAAAA0kQ3Xv08kwal5UvrKj+URPknu8mrvJPyqnHBhtWyieYT7fWW19NY83HbELsZHr3ZnGaD9Cdz0AAAAACKQO2Jx48f7zo6SkNHRHqGnnolK+WzAfuK3sMAAACAIlJXxE1NTV29qJaTdYE8kAIWIWgBAAAAiky9uc6bNy9YsWJFmFJ6KvHZvn17sHfv3jBl4KB6GAAAAFAiKum4dOlS1sddFIMCllOnTrmHTw5EBC0AAAAAUo3qYQAAAABSjaAFAAAAQKoRtAAAAABINYIWAAAAAKlG0AIAAACUiHoP27VrVzhXOuXab38haCkjdT2n7u4GDRrkhgkTJnQ98CfJ6NGju9a34fDhw+HS/KxduzYYNmxY1z7zff3ly5fd67Zs2RKm5HbhwoVu71FPYNX7BgAAGAiU0bd8TNxQSCCwb98+191xXLfDWhbdtvJphVJ+TcekPJe2obFMmTIlmDRpksuXaZ2Bhi6Py0QZ9+nTp7sgQIHIN998E1y9etUt0xNT4/ru1sm8devWYPjw4WFKEAwdOtSl58u2e//99wffffddsH//fjff0tLiTuZs9Fqtv3nz5ryeomrvUa97/fXXXdr69euDnTt35rU/AACAclPgoDya8ms+ZfzPnj0btLW1BaNGjQpTkym/dujQocR8m/bj5/Fk5cqVwezZs8O53JT3mj9/vjsmPX3/L3/5S4/8lgKaTz75JDhy5EiYMkAoaEHp1dXVdTQ2NoZzHR3t7e0d9fX1CiA7qqqqwtTuampq3Hq9lQmG3ODLBCBun9p3Ns3NzW7/WlevyUdtba17TVR1dbV7j315LwAAAMXW2tqamEdSPi4unxNH21EeKhNMhCndKX+Wb/4qSUtLi8tfadD+slEera/7KzWqh5WJSjr8okFF1jt27AgyGXoXzUeriSkqj4vACzFz5sweJThLlixx4ytXrrhxHN1JeOWVV4JXX301TMlNkf7Ro0eDhQsXhik3LF261L3H48ePhykAAADpoyfIK38WZ/fu3cHTTz8dzmW3Zs2aoK6uLrFEZt26dcGCBQvCucIp3/XII4+46S+//DK477773HSSxYsXu2NSNf6BgqClTJKqV1nR4y233OLGRiezqlWpXqKK9XpTFzEu4FG9Spk3b54bx3nmmWdcwDJ48OAwJbfr16+HUz1NnjzZjVVECgAAkFZxbU9EmX1VDdMN4Vx0I1o3clVlPo5uTKs616xZs4IVK1bkbN8cR8GTbggrwMoVsMjEiRPdeM+ePW48EFRc0PL777+7hugjRozoauQ0d+7c4NixY+Ea5afSFv+E08lrwYxO+uXLlwdjxozp1Ukd9eabb7rIP64NjVgj/ULqU/rUbibJH3/8EU4BAAAMHKotUlNTk1dblo8++siNx44d68ZRJ06ccHk/BS66QT116lQXvOR7g1p5NQVQ2kZSfi7KjtvaNg8EFRW0KGBR4yQ1Xr948aLa87hBjdtfe+01V8xXbufPn3fVp3xqQKXGUjpWNWCvra110bRO6t4GLipG1ImtYO3ll18OU7vTl0UNwN55550wJX+33367G2v7vSkVAgAASCtVwcq3atiZM2fc+J577nHjKJWOKP/X3t7uOjuqqqpywctTTz0VrpHdBx984MYqqdGNeetpVuNsPcQqP6lASXnCAUENWyrFQw891LFly5Zwrrvffvut46677uo4evRomFJ6aoSVb4MuNf7Sv0+N2gtlje9tUIOtaAN9UWcBaoBv1MBL6+fbcKuhocGtr/dkDc/8Bv3aPgAAwECijoSUj0lqVB+ldTXkS9u1vFJc/ixK+TjLV1kDfGuUr3Q/L+dTY3wt17oDQcWUtJw+fTo4d+5csGrVqjClu9tuuy147rnngm3btoUppaXSCJX45FvaozqWqtbVmwhZ7Wky//sgcxJ3ldpEiyH7Wi1MNm7c6O4Y6BhVZKmOBP78889waZBYtxMAACCtCqka1hvaruUH82n/q3ycqGaMNS9QLR3rQEC1ZrI5efJkOJVuFRO0qL7guHHjwrl4+kf3RzuR3tDzS1544YW8Gk+ZZ5991o39Ru/WTscfkh4GqYBE1c4scLHevPpSLSxKAZJ6JlOQpOJRNfxSvUvJp/EaAABAmiiQyLdqWG8pP6j8WSHtf6MdLqkZgKqa6ebxQOolLAm9h6WAeo2YNm1a3o2nTNzDGXWCRwd1OpCNReDXrl1zY/UkoRP81ltv7Rb8qA2NqIu8bMFQNnrQkY2LdYcCAACgGHRjV43XS3HjdcaMGeFUdgpMklgvYfn06pp2FRO0KChQ9bBsVM2q1E9pt6eiFhqwiI5X1a78Y1bJSXTItW3rynjSpElurJNX1bqiQ319vVuuQEjzhZ7keq/6oqtI9fnnnw9TAQAABgbVSlHeq5Abr8r3SKGlHeqBVc9TycXyeUm1hRTUZKvJE33MRmq5li0VIm0N8dW4So3V4+R6Qr1EG8r3lhr1ZwKRcC5Ztob4aviV7emrOk69Vh0H5HpKKwAAQBop75WUd0tiHRMV0uBdeSU1xo9SI/3odix/Fu3gyDoMiMu3iRrqaxgoKqp62Mcffxz85z//cd3Bqftjo255Vcz3j3/8w3UXVwoqdVi0aFHw7bffugdG+sOwYcO6FfVpXoOVyihSV8N5PRCykIbyisS1HVXrskb3elClGnslPe01Hzqe8ePHuyF6F0FRv451zpw5roRGHSIU0m4HAAAgDaxq2OOPPx6m5MfW/+GHH9zYp3yYqtwrj2Z5KHWGpKr4qi0TpXyqqutbnlBU40Y1YHRs2p5oW8pTqpRnyZIlLs2n96L2zFaLZkAIg5eKoRIVRbwqVdHb15DJUJe0hMVKHbINfmmESmQUCStdY5XC9Ka0wt+OBkXwir4ViecjqaRFr9e2NPjbsuNV5J9Pl30AAABppbxMbx41IarREi0JEeWbtMzPm6kGTBLlAZW3issH6nU6Pst/Kb+blMfTe9F6KrkZKAbpT+agAQAAABSB2iGrRoo6OkpDR0QqhVFDf/XyOlDQexgAAABQRKoa39TU1NWLajlZg/2BFLAIQQsAAABQZGq3ovbIautbLirx2b59e7B3794wZeCgehgAAABQIirpuHTpUs5HUvQ3BSynTp0Kli1bFqYMLAQtAAAAAFKN6mEAAAAAUo2gBQAAAECqEbQAAAAASDWCFgAAAACpRtACAAAAlIh6D9u1a1c4Vzrl2m9/IWgpo8uXL7vu7gYNGuQGTas7umxGjx7dtb4Nhw8fDpcWTscwbNiwYMuWLWFKskLWNRcuXOj2HvUE1lzvEQAAIC2U0ffzXdGhkEBg3759rrvjuG6HtSy67QkTJoRL86f8mo5JeS5tQ2OZMmVKMGnSJJcv0zoDDUFLmehk0UmkIGDz5s1BTU1NsH///mD69OmJJ5JO5qqqqqC2trZrqKurC2bPnh2uUbhnnnkmuHr1ajiXXSHrioITvS+9x/b2djeMGjUqGD9+fNfTWAEAANJs9+7dQXV1dbf8lwblcWTmzJlunIvycYcOHUp8PsvWrVt77OPVV18Nl+ZHea8HH3wwWL58efDAAw8ELS0twZEjR8KlnU/mV17zqaeeClMGED2nBaXX0NDQ0draGs51ypycemZOR1NTU5jSXebL0ZHJ+Idzfdfc3Oy2qX1mAqcwNV4h6xq9H70mKvPF78gEX/36XgAAAPqb8mr19fXhXHeNjY2x+Zw42o7yUG1tbWFKd8r75Zu/SpIJUFz+SkM0jxmlPFpf91dqlLSUyfPPP++iXd/KlSvd+Nq1a27sU3SuIsLhw4eHKX2j0pxXXnklrwi+kHWNIv2jR48GCxcuDFNuWLp0qSuxOX78eJgCAACQPnqC/I4dO8K57lQC8/TTT4dz2a1Zs8bVjlGNkzjr1q0LFixYEM4VTvmuRx55xE1/+eWXPfKYUYsXL3bHpGr8AwVBS5nEBR//+9//3DiumFEn886dO12VMtVT7GtdRFX1UhAyePDgMCVZIeua69evh1M9TZ482Y1VRAoAAJBWcW1PRJn9s2fP5lU1TFXidSNX1bLi6MZ0W1tbMGvWrGDFihW9qkKv4Ek3hBVg5QpYZOLEiW68Z88eNx4IKi5o+f3334O1a9cGI0aM6GrkNHfu3ODYsWPhGuWhIOStt94KGhsbe0ThOnnVAF900que4pgxY3rdLsQa7ufTFqaQdeN899134VRPf/zxRzgFAAAwcKi2SE1NTWLJie+jjz5y47Fjx7px1IkTJ1ybGQUuukE9depUF7zke4NaeTUFUNpGUnuZKDtutaceKCoqaFHAMn/+/GDo0KHBxYsX1Z7HDWr49Nprr7livnLQyaYSFDWyjysaVG8PakSlY1WDKjXMUjStk7rQwEVfAFVDe+edd8KUZIWsG3X77be7sYLBvpYKAQAApImqYOVbNezMmTNufM8997hxlEpHzp8/7zosUudMyg8qeMm3sfwHH3zgxiqp0Y1562lW42w9zCo/qUBpoPTqWlFBiwKWRx99NFi1alWY0unuu+8OPv74Yxe4lLrERcHKnDlzXISsQT0+ZDt5LIBRiYyoTmIhVNVr27ZtebWNKWTdKEXwDQ0NLrjSe7Q6k/ry/P3vf3fTCh4BAAAGEt2MVQlFvr2GKX8nufJTWr569Wq3vkpxVLtGVcdysbzrlStXgscff9wFQLrJrXnlMbMFLpKtSn+aVEzQcvr06eDcuXM9AhZz2223Bc8995zLpJeSAhBF1k1NTV1Fg2oYlYvqWKpBVyERsp20pagWJhs3bnR3DHSMem/qSODPP/8MlwaJdTsBAADSqpCqYb2h7Vrtn3za/9rjKFQzxtqz6Ca3dSBgHT0lOXnyZDiVbhUTtKi+4Lhx48K5ePpH97adSF8oslYdRAVWKhJUZJ1Pbw7PPvusG/sRsrXT8Qc9DLJU1cKidMdAkb6qtql4VA2/7I5DvncoAAAA0kKBRL5Vw3pLeVJV3yqk/W+0JEd5S+UrdfN4IPUSlqTiGuKnmU62+vp6N51PUZ2i6Cid4NFBnQ6odwidtLfeemu3gEbtYkSlOxbgFLJuoVRlzMbFukMBAABQDIVWDeuLGTNmhFPZKTBJYr2E5dOra9oN6tAt8AqgUgxl4LNFrOq96//+7/+Czz77LEwpPQUCmzZtcqUTuahamNrpqO5iLipBiiv+++WXX1xjL302+nLYiZvvunGBUxLVy1y0aJErUlW1uFx1OwEAANJEeRk9hiKfvJdR9XjVMtEN4UJu2KqkZN68eTl7BFNPY8qfqR1LNF+mdsXffPNNbL5Sy1S7p7W1Na9ukstOQUuleOihhzoyQUE4191vv/3Wcdddd3Vk/nlhSnnU1dXl/YRSrasn1feFnp6q0yCffWZbV09ezfb0VR2nXqun4ed6SisAAEAaKe/V0NAQzuVH6ysPpHxUvpRXinvafibw6bEdy5/p2Hzt7e1Z83hV4dPzB4qKqh6mHsL+85//uO7g1P2xUa8LKub7xz/+4bqLK4Vhw4a5ruisVwgVNypSFrUD8WldDbau6iVqXUXffWko3190POPHj3dDtM6kSnh0rOq9QiU0KvEaENE8AACAx6qGqYeuQtj6P/zwgxv79MBwVblXaYrlodQZkqriq1ZKlPKpqq7v9yqm0hV1fKRj0/ZE21JJimq3LFmyxKX59F7UgN+aJQwEFRW0qIcw9fggKqqzthrqMeztt98ueqMqn04SFROqupSOQX1xT5s2rdtJaKz3B62r4EXHqt7DchUXlsqQIUPcl0KDpo3e1yOPPOKKJNU7GlXCAADAQKU8pHpDLfTmqzWq17NdovR8Pi1TwGE9rf7vf/9LzDMpaFEblugzX3TDW4/DUFMH5b+UJ9O6Sdux/HBcQJNWFdOmBQAAACgHtUNWjZRC27UUi0ph1D45Wrsnzeg9DAAAACgilbao1on1olpO9niPgRSwCEELAAAAUGTWG5i1YS4Hlfhs37492Lt3b5gycFA9DAAAACgRlXRcunSp5G2TFbCcOnXKtYseiAhaAAAAAKQa1cMAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaAFAAAAKKPLly8HW7ZsCS5cuBCmlM7atWvLst9CEbSkiLrAGzRoUNdDf+KMHj3areMPhw8fDpfmT32ER7ejkzYbfaGGDRvmvlT50pdAXfrZPvQEVnW5BwAAkFbKiynPki3Po/yMn8eZMGFC1jxcEuWv1q9fHyxZsqTb0/KVrryZ8l7avvKAvcnzGR2b8n+Wl7Rj3bhxY7Bnz55g3759bj6tCFpSQifm4sWLw7l4OpmqqqqC2trarqGuri6YPXt2uEZ+FEgcO3as23Y06MuSzTPPPBNcvXo1nMtNX+aamhr3ZWtvb3eDvozjx4/v1ZcaAACgmJRHUqDyyCOPBEePHg1Te1IeZ/r06cHZs2ddHkr5M01PnTq1oMy/8n8KjvTslOHDh4epN9KVX9N29YSSVatWBXPmzCno5rFR8KNjO3PmTLBhw4agra0tmDJlSrg0CJ5//vlg3bp16c6f6TktKL+GhoaOTAZfz8zpaGlpCVO70/JMxj+c6736+vrEfSRpbm7uOr7NmzeHqdllvsTuNVHV1dUdmS93v7wXAACA/tbU1JQ1z1NXV9fR2NgYznW4PI3yV3qN8jj50nb0uijtV9uK5pVsH4Xk47QPvSZuPz5tM835M0paUkBRrSLehQsXhik9KWpXsaMfhfeGlbL40XUuivZfeeWV4NVXXw1TctMdCN2hiHtPS5cudSU2x48fD1MAAADS48477wyn4t1///3dniyv/NmOHTuC6upql8fJp8RC6+zfvz/2CfWbNm1yJTjRfN+TTz7pxh999JEb56LqYNpHJmBxx5eN8oaqHaOqamlE0FJmCgj+/ve/B2+88UaYEk9Fdjt37nRFhbt27XKv6423337bBUgKgPJteKVqYQpYBg8eHKbkdv369XCqp8mTJ7vxoUOH3BgAAGAgWb16dTjVndqLyC233OLG2aialqqV3XfffWHKDUnV8e2mcz5V0NT+RXlHBVK5AhYza9Ys95re5jOLqeKClt9//91l1keMGNHVcGru3Lmu9KEc/vnPfwZPP/10t4ZXUYrE7Uug0ovly5cHY8aMKbjeoU5ABSlW71KBkk5kBUFJrMFXoe1mzHfffRdO9fTHH3+EUwAAADcH5a3iAhGf8mPK002cODFM6embb74Jp3rKp42xasmIgqN8jRw50o3TWBumooIWBSzz588Phg4dGly8eNE1atKwdevW4LXXXgt2794drlkaCjq+/fbb2GJBn6LqI0eOuGNtaWlxxYU6WdWgqpDARUWM2s6VK1dcaYuKCkVBUFyjLgU5K1euDN55550wJX+33367GysYTGO0DgAA0N/Onz/vqsHn8tNPP7nxAw884MZRhVQzi6Nq+rpBbfxezlRlLClvlubaMBUVtChgefTRR13vC7677747+Pjjj13gUqoSF50sqhaWb3GdsQCmsbHRzefqcSyJSna0bwVBKnlZs2ZNj6piqha2bdu2XrWj0fYbGhrcF05V2mzbKrnR+xYFjwAAADcD6+U1qeqY79y5c248ZMgQN45S/kvUi5kFLtbFsmg/2Zw6dcqNbT3dgG5vb3c3rK25QTZprA1TMUHL6dOn3QkSDVjMbbfdFjz33HNdJ0mx5VMtLBuVzqi7Y5WY6CTuLQVBb775ppv2iwL7Wi1M1O/35s2b3THqjoHa0fz555/h0sB1FQgAADDQ6Wa0au70V60d5b+am5tdw3jVrFEzAVUn07yo7Uk2165dc2MFKQp0dAPa7yxApTDZ2sVk6+65XComaDlx4kQwbty4cC6e6h/2thiuEPlWC8vl2WefdWO/0bsV/flDrv687TjsBO9LtbAo3W1QdTRVbVPf4Kq7acWVM2fOdGMAAICBTD1uvfDCCznbshRCgYuqmykPpbHyVFYjaN68eW6cS1xJjt3AV954IKm4hvhpoAZRimCjwYWqaIkias3nCqCsBwmf2rtEB3U6kIvWM3oqqkpHbr311m7Hp+MSHafme/NwI1UZs3FvS5kAAADSQiUW06ZN66q6VSzqOEn5Mz24O9e+kqqdydixY91YN5WT+PnCtBiUid70wJmbnqqH6R+QrY7eW2+9Ffzf//1f8Nlnn4UpxaGTWx0BRH3xxRcumFFRnnpvWLBgQdaMvaqFqZ2Oou++UnGjSkC0PwVLJ0+eDJfc8Msvv7h6kPocZ8yY4RprxQVOSfS+Fy1a5L5sapfTm7YyAAAAxaa8kG7Wqpp7tjYqVsWq0IBF1fD1dPt8np8iyvNZtfovv/wyr97JVA1MeTbluXz23tQ+Olrrx5apCUK26mNloaClUjz00EMdW7ZsCee6++233zruuuuujkzQEKaUnj39NN+nnOoJp3pSfV/pia56In8uOi4dX9zTYVtbW92QRMep12a+QFnXAwAAKLdseR6jp+Yn5Z8ywUg4FU9Pndf2M0FFmJJM+Sbln6qqqtw+4+h429rawrlO2rb2Ec136Zi1rbgn3ytPqNf4T/tPi4qqHqYewv7zn/+457So+2Oj+oFqX/GPf/wjZ8OmclApiAaLeBU9q7s61WcspKG87gJYtS61W9GgokZF72o031s6nvHjx7sh2gOZInYdq+4mKNpXiVd/1vcEAADob59//rkb63lzyi9FWe0RtVFWT1z+oDxbrt69VNtEpRnZnsWi/JnybH4JS1yJjo5FpSPRPOzevXvdcajjJ8ufKd+n5/SpdCeuxovVBFJtn9QJg5eKoRIVRZgqVdHb15DJUJe1hMUklbQoqlZErGUaK3rvTWmFRer2vgstqUm666BIvaamxg1+1G7Hq/0k3RkAAABIC8vrRAc/b2a1R7IN+eTTbF9x61opicYq9YgrFTF6veUPo1T6onyYHZfyatF8pk/5xFylROVSMW1aAAAAgDRRyYlKZgp9bl8xqHaMngvz888/p7LdMb2HAQAAAGWgx0vokRB9eeZef1Hvtp9++mlqO0qipAUAAAAoE7WZeeqpp1xPZeVq96v23vfee2/BvaCVEkELAAAAUEYKXA4ePOg6hir1c+zUOH/SpEmp7yiJoAUAAABAqtGmBQAAAECqEbQAAAAASDWCFgAAAACpRtACAAAAINUIWgAAAACkGkELAAAAUCJ68ry6GU6zNB4jQUsKjB49Ohg0aFC34fDhw+HS7gpZNx/79u1zDxIaNmyY21Y26kNc623ZsiVMye3ChQtu+3asDz/8cCqe+goAAKC8jfI1yt9ko7zWhAkTuvIzmu5N/kv5rkuXLgXLli0LU27I91iilLfS0FsKUPSeNDZTpkxxz25RHk7HlQYELWWmk7eqqiqora3tGurq6oLZs2eHa9xQyLq56ATUCb5o0SI3/+GHHwbt7e1uOskzzzwTXL16NZzLTcFJTU2N+/Jp2xr0wKTx48d3+2IAAACUmoIOPYl+zZo1WfM3Wm/OnDnB008/Hejxhho0rbRCAhfl4w4dOhT71Pl8jyVKpSFHjx4N5wqn/ODixYvDue70sMnp06e740oFPVwS5ZPJ1HdkMvPhXHaFrJtNW1ub25b+/U1NTWFqds3NzV2v2bx5c5iaXSaocq+Jqq6u7sgEX/3yXgAAAPpC+ZJsWWItr6+vD+duSMrnxGltbXX7UB4sm1zH4tO2dAxaX+PeaGho6MrftbS0hKndadv55v2KiZKWMlLEreLF4cOHhynJClk3G0XUKp05e/ZskAlYYqP9KL3mlVdeCV599dUwJTeVsijyX7hwYZhyw9KlS91dhOPHj4cpAAAA5aGq99lkgoNwqjvVHsm3VEQlKMp/6TXZ5DoW34oVK4JMMBHOFU61XvTe4vJqPpXE6PhV5b+cCFrKaN26dcHOnTtdNS0V72WrM1jIutn885//dAFLfX19XgGLqFqYApbBgweHKbldv349nOpp8uTJbqwiUgAAgDSrqalxebBom9xjx465G7G5KDjQjVxVteovygs+8MADrgpXbygf+fe//z144403wpRkEydOdOM9e/a4cblUXNDy+++/B2vXrg1GjBjR1Zhq7ty57sQrJZ3AFk3rRF6+fHkwZsyY2LYehaybjU5QOzlffPFFN87F6mr2pt2MfPfdd+FUT3/88Uc4BQAAkE5W00RBh2q+iEo5Zs2aFaxevdrNZ/PRRx+58dixY924r1TisXv37uD5558PUwqnm9hql5Or5Edsnf3797txuVRU0KKAZf78+cHQoUODixcvdjWm2rp1a/Daa6+5E6BU1CvDkSNH3P5bWlpco3oVMU6dOrVHMFLIutkcPHjQjXXHQFWzrBeMpB7BFOSsXLkyeOedd8KU/N1+++1urGCwt6VCAAAA5aYbt6pSr7yXOjDSjWTd8N6xY0e4RnZnzpxx43vuuceN+0oB07/+9a9eNxlQ3vHbb7+N7cEsifKeqkpWzh5gKypoUcDy6KOPBqtWrQpTOt19993Bxx9/7AKXUpe4iAUljY2Nbj6pFwcpZN2oL7/8MpwKgrvuust9iXQCVldXu7qKKoHyqVrYtm3bevWlUFTe0NDgvuCq0mb1IFVyo+JIUfAIAACQdqpSr6r1oryT2vrme1NW1fKlr+2SxaqFKT/YG1YtLN+AKypb9f9iq5ig5fTp08G5c+d6BCzmtttuC5577jmXSS8XRbxqpJVPJFvIusaqY6mY06p7Kbiw4j5VHfODC+lttTDZuHGjayBmgZFKdv78889waWcxKwAAQNqpdEOUp1GNFQUiuilbytokpa4WFufkyZPhVOlVTNBy4sSJYNy4ceFcPDVmKrSdSH979tln3TifSDZuXWun4w/Rql/RBvU6cRUAyTfffNOnamFRqut55coVV7VNJTtqzGV3HGbOnOnGAAAAaaV8lGriqHRCeSbVeLGeWEv5DJNyVAtLk4priJ92hRT3xa2rOofRQZ0OSLbqWPfff78bX7t2zfUOoTsJt956a7fgR21oRFXJ4oKhfKjKmI17G+UDAACUyqZNm7r1EqagQQ3yVeKiDpJK0RWwAg7tS3kxP2+mQbRM0yr9SbJhw4au9fxB+TqxbWe7gW89wJbDoA7dAq8Aqh6mDHy2Hqveeuut4P/+7/+Czz77LEwpPVX1Utub8+fPhynJCllX9AVTAzJV2Yr2dqEARCdta2urK7mJK/775ZdfXJd/+hxnzJjhTtxCgizbv77kukvRH3U7AQAA+kIZfWXm47LEysArMx+Xd1JVej0VX50kZcsPqXq8SmV0QzjXDdukY1FgZB0qRSn/pmr4Cqx0ozrpkRbKh6kjqqgvvvjC7VNtdkaOHBksWLCgx3HacSmf2NtulvtMQUuleOihhzoymfNwrrvffvut46677urI/EPClPKoq6tzT5/PRyHrip5AryfR62mr0afRZwKJnE9T1ZNSdcrEPRVVT3rVkETHqddq39nWAwAAKCXlf7JliZV3issjNTU1uWXRPFWUnjqv7Sc9cd6X61jiaP2448sESXntU/m6XMen96mhnCqqeph6CPvPf/7jeslS98dG9RTVvuIf//iH63O7FNTNsAbr71sRtOoqzps3r0fj90LWzUYlG59++qmL9NevX+/armjQtpSmuwi9oeMZP368G6JFpLpDoe3rTkTmC+VKvMoWoQMAAHiUb1F7XkmqFqW2LCplUH7GGt6rlEXzWpar5sjjjz/uxj/88IMbJ8nnWAqhPK1KiSz/2Ft6z+oN1npPK5eKClrUQ5ieTyL2jBIN6jHs7bffdr0plIp1NafqUgpItH81jIor0itk3VxUfKliTDWKV5sVDWoor2LL3gYTQ4YMcVW+NGja6LN95JFH3PbVvzlVwgAAQFqoypOqVSlDLsrgx7UJUX6rubm5K++k/I26PP7www/zyospf6Ubt/6jJ6LyPZZCKGipqqrq8/NhLO+8ZMkSNy6XimnTAgAAAJSD2iGrRko+7VrSRsGT2jLn8/T/YqL3MAAAAKCIVNqiWifWi+pAYdXUyh2wCEELAAAAUGSqSqb2yGoLMxCodGj79u3B3r17w5TyonoYAAAAUCIqvbh06VKv2iaXigKWU6dOpepBlAQtAAAAAFKN6mEAAAAAUo2gBQAAAECqEbQAAAAASDWCFgAAAACpRtACAAAApMSFCxeCtWvXhnPFsWvXrq5nsAwUBC0D1OXLl90Jp6eUDho0yI3jjB492i33h8OHD4dLAQAAEEfd/qpbYss/KU+1ZcuWcGlPypdZvkv5Mr2+UHrNnj17go0bN4YpPVlQM2HCBLevbMckWq71fOrKWN0uFzs46k8ELQOQTugHH3wwWL58efDAAw8ELS0twZEjR8KlN+zbty+oqqoKamtru4a6urpg9uzZ4RoAAACIUmAwffr0YNiwYUF7e3ugJ4S8//77waZNm2Iz+npg5Msvv+zW0bozZsxwry8kcNG6Tz/9dPD888+HKT0pb1dTUxPs3LnTrdva2pr1afXa5po1a8K57hSQtbW15Qx60oLntJSBTuz77rsvWLBgQTB8+PAwNT8qynvkkUfc9Jdffum2k0QRuIKZQvcBAABQyZRXO3bsWHD+/PkwpZMy+AoCFMhY/kp5s6lTpwZNTU3dHhipUhfdPD5z5kyYkkw1aHRDesOGDYkPnVRJjm5YK2jJN3+nEh+9BwUncVl+7XfMmDHBp59+GkyZMiVMTSdKWsrgySefdJGvThJ9KRTN50OvyTdgUSSuoIWABQAAoDBJebMRI0a48bVr19xYFGjIzJkz3dgsXbo0OHv2bF7V8lUl7MqVK4kBi/J1hQYsCrAee+wxFzwl0Xa0z8WLF4cp6UXQUgaKZHfs2OFO5JEjR7oTUCdMrgZRKga8evWqe222gEXWrVvnig4VYSsyVyQNAACA3FT9XqUTykP5Tpw44arbjxo1ys0rf3X06FFXohINJCZPnuzGn332mRsn0TZU7WzWrFlhSncKoHSTW/bv359XwKIb3QcOHHBtV3KZNm2ae69pb/NccUHL77//7uoiKlK2hlVz5851RYClphNe9RAVWc+bNy/4+9//7qJhRdNROpEU5FRXVydG4UbBj0XV+iIpMlepzkDrJQIAAKAclixZ4gIR5aGsDYvyZ6rqtXfvXjcvP/74oxtPnDjRjePkqh52/Phxd1P6/vvvD1O6UymMltfX13cFS7noRvfu3bvDuezuvPNON84VXJVbRQUtCljmz58fDB06NLh48aKr26dh69atwWuvvZb3P7cYFIjopFYDLkXxavilYj0rnvzggw/cWFG4vjzWO4XG0chYJTkqOtR7UyN93RHQya76lgQuAAAA2Sk4UFV8BS5vvPGGy2/997//dXk1v6Tj5MmT4VQy3XTORtuVcePGuXGUas6IaueoxEV5ROUBk3ooU/5x4cKFOWvlGGvLEnfTPE0qKmhRwPLoo48Gq1atClM63X333cHHH3/sApdylLj4rOqYvijvvvtuV3GgHZdKZR5//HHXqEoBiebnzJmTWKRnAUxjY6ObHwh1FgEAAMpNmX7lyUTVpxQ8xAUJffXtt9+68eDBg93Yp/3pxrN58cUXXd5P+TrVplEPZX77G6sWlq1HsST+ftKoYoKW06dPB+fOnesRsJjbbrsteO6554Jt27aFKeWhkhAFKjoJ1YDLvix2Ir3zzjtdkbMFOLJy5Uo3TqI6jeruWF+6YnzhAAAAbiYqeVBtHOWdVDVLebFCuzHuq+vXr7ux2j8rELHqYcrX2TG9/fbbLk0KqRYWJ801ciomaFGVq6RiN6NgoFz/LH0x1NuXSkLUIOrnn3/udnKaaOMrVStT0aW+ULl6IXv22Wfd2L4AAAAA6En5wUWLFrmG78qL6Sbx5s2buwIX6+DIGttno2r6fRXX+N4a2VttnEKrhQ00FdcQP00UZOgEU91EtWX517/+5ap9KRCJnpwKTJJY469cwYjVWQQAAECy7du3d+slTHQzuaGhwQUuajwvt99+uxvH9dKqJ85L9AZ0IW655ZZwqicLTlRdTPT8GA3W0ZQNqkYmNp9NmvOKFRO0qPRC1cOyUXFfKf5ZVgVMRX2//PKLa6CldifZ9m09hiWVBCmoyRVZ6/2p9zGCFwAAgGQqYYljT6tXh06igET5OeXlooGLNbBXL7XZqHtlsSDHp7yd8m4WeMSxrpJVEhQ36PX+8iTZbpCnQkcFeeihhzq2bNkSznX322+/ddx1110dmZMiTCme+vr6jsxJ09He3h6m5NbS0qLHmHbU1dWFKZ20DaVre7notc3NzeEcAAAA4ijPlMnE98irtbW1uXyX8mVGeSulNTU1hSmdMsFCRyagCeeS2euT8nJK1/LGxsYwpZO9zj+WOLW1tW69JK2trW55NI+ZNhUVtCgwuffeezsaGhrctFGgovT33nsvTEmn6EmrL46+DBr8L5W+ZBrsy6P1FChFv0wAAADoSRl55aWUx1I+ytI0rzxVlNK0vtZRnsyfz4fWzRY0KPDQOhagaKz5uGOJyhW0WPCT9hvbFRW0iIIVBS0qVdE/SMOcOXNKUsLSHxSwKHLXcetk1XuJ3gVQcKJlto5O6Hy/NAAAAOgMUhRIWH5R+a9sNVu0zPJfep0FO/mw1yZRXk95Ptu+jiVa8pIkV9CifKK2l3aD9CfzRgAAAACUgdrDPPjgg8GGDRu62jGXgvY7ZsyY4NNPP019m2d6DysDPcHU79Uh26B1AQAAcPNSr7F60LmeCxPXE1mx7NmzJ3jppZcGRCdNlLQAAAAAKaCeXtVt8d69e2OfzdKf9IxA9XC2cePGMCXdCFoAAACAlNBz/A4ePOieC1Mshw8fduPZs2e78UBA0AIAAAAg1WjTAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaAFAAAAQKoRtAAAAABINYIWAAAAAKlG0AIAAAAg1QhaAAAAAKQaQQsAAACAVCNoAQAAAJBqBC0AAAAAUo2gBQAAAECqEbQAAAAASDWCFgAAAACpRtACAAAAINUIWgAAAACkGkELAAAAgFQjaAEAAACQagQtAAAAAFKNoAUAAABAqhG0AAAAAEg1ghYAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSreKDlgsXLgRr164Nhg0bFnz11VdhKgAAAIC0KEnQcvny5WDXrl3Bww8/HAwaNMgNChKeeOKJYN++fW75li1bwrVLRwHLwYMHg/379wdXr14NUwEAAACkSdGDlu+//z4YM2ZM8PLLLweLFy8O2trago6OjuDKlSvB3/72t2Dr1q3BrbfeGly7di18RemMGjUqWL16dVBTUxOmAAAAAEibogYtClimT58eVFdXBz///LMrWVGgYGbPnh0cOXLEBQ3ffvttmFp6999/fzgFAAAAIG2KFrSoytf8+fNdtavdu3cHw4cPD5d0p3RVzwIAAACAOEULWvbs2eOqgtXV1QX33XdfmBpPpS+PPfZYOHeDAp8VK1a49i9qBzNhwoRujeWtrczo0aNdukp2rN2M0jQfFd2m1v/uu+/Cpd3p9SodsnY4mlY7GOM34hdNaz1tHwAAAED/KFrQ8u6777qxqoflY9myZeFUJwUXCihGjhzp2r+0tra6UpupU6d2BSNqRK9SHAVHP/zwgwtg1q1bFzQ2Nrq0NWvWuPWMbfPMmTPB2bNng/b2dhcwxZX0aB8qKVK7G7XBaW5uduvNmjXLbUeD9r9z5053XOpIQOOqqirXuQAAAACA/lGUoEUlEAoaZOzYsW5cKJXUqOqYGsqLSmu2bdvmpt988003VqCzcOFCN33x4sVgx44dwZQpU1x6bW1tcPToUbfMrF+/3h2X2tEoWNH29Rq1uYlSwLN06VLX7kY0bmhocK9XsGLHNnHiRLdctC0FQxoAAAAA9I+iBC2//vprOJWdVbvyB+v6eNOmTT2qjN1xxx1uHFcy8pe//CWc6s6qk6lkRKUiquIVbV+j0hOfSlkU8Cjw8Y0YMcKNP/nkEzf2WXClYMjvbAAAAABA3xStepj5888/w6meVO1q8+bN4VzgqoAp86+SGlW1Wr58ebeAZvz48eGanaU5hTh+/Lgbq7pZVDTtxx9/dGPtz9+/jkfOnz/vxgAAAACKryhBi6poma+//jqcijd58uRwqrMKmFhJjdqRKLCJGwotzVD1sXzZumrzErdvghYAAACgdIpW0qJew6Q33Rnfcsstbpwr4CmWIUOGuPHp06fdGAAAAED5FC1o0RPwRQ3X1atXIVTiol64FPCoLUpUb3rnGjdunBsfOHDAjbOZNGmSG3/wwQduHEXvYAAAAEDpFC1oUeDR1NTkphXAxD0zJRs1mFfAoy6K/fYr2s6hQ4fCufw9+OCDLhBSz17RoOPatWvhVCcdu3oUU9CkZ674gZNeG1fVLC64AgAAANB3RW2Ir8DDAhc1alcA4Acvmv7oo4/Cue5ef/31oKamxgUZCiAUvOjhknrui5XiiD0Y8vPPP3djUQBh7U70/Bax7o1l0aJFrpcy9Sym8bFjx1z69u3bg8OHD7vpjz/+2AU56nFszJgxbv96YOXWrVuDJUuWuHUUTNl+1EUzAAAAgP43qEMty4tMQYSebaKugv1npygo0HNO1LXxggULenRFrNfp2SoKHETtZBSwWIN99egV1dLS4h5A6VPXxXo2iygoWblypSvFUTCkZ7+cO3cu+OKLL1y6PZdFFFTpeS06Zh2rgjAFUzpOBTzZ9gMAAACgf5QkaAEAAACA3ipq9TAAAAAA6CuCFgAAAACpRtACAAAAINUIWgAAAACkGkELAAAAgFQjaAEAAACQagQtAAAAAFKNoAUAAABAqhG0AAAAAEg1ghb02oULF4K1a9cGw4YNC1MAAACQzVdffRXs2rUrnEunNB4jQUsZPPzww8GgQYPyGnTSpNHly5eDgwcPBjt37gyuXr0apgIAAAxMyp9pyEch6/r27dsXXLp0KVi2bFmY0knpo0ePdnk/jbds2RIuiaf1o3nGCRMmhEuz+/7774Mnnnii2+ui+c0pU6YEkyZNcuspz5cGBC1lcOTIkaCtrS2orq5285s3bw46Ojq6DS0tLUFNTY1bnkbDhw8PVq9eHUycODFMAQAAGJhUqnD06NFwLrtC1vUp0Dh06JALBHza3tatW4OlS5cG9fX1wZUrV4I1a9ZkDVy0fm1tbbfh1VdfDZcmU8Ayffr04OzZs+41VVVVbnrq1Knu+Hz33XefW/epp54KU8qLoKVMRo0a5U7OJIpw//Wvf4VzAAAAKAZVd//kk0/CuewKWdenYGHRokXBG2+8EaZ00va07MyZM+5m8I4dO4JPP/3ULXv33XfdOErBxcKFC91NcH+YPXt2uEayN9980w3nz593r/n5559doCQrVqxwY5+VCOUq+SkFgpYUU+CiAQAAAMWhzLpqveSjkHV9Kjmpq6tzN619Q4YMcYGKT3k/1bZRiUucdevWBQsWLAjnCnP//fd3q5qmmjPav2r/qLp/XLOExYsXu+NXgFVOBC0DjCJdv85jtJHU4cOHXR1Lrac6iNZQXoOmRen60mkbSo8WB4q2a/vRoKLMQk5W24e2n1RfEgAAoJyU33nggQdcVahcClnXp/yPqpOpqlWUgoY4akYQrUYmyrNp2axZs1w+q9C8lUpz4ijPJ7fccosb+6wpwJ49e9y4XCouaPn9999d5n3EiBFdGfK5c+cGx44dC9dIh7hiOJ2c3333XXD69Omgvb3dnWDLly/vClwUsHzwwQfui3Ht2rXgmWeeCe69997gww8/dBG0iiR1sit92rRpQXNzs0tXcaWKJo22p+1u2LDBta9pamoK9u/f7/afDwUsCpxGjhzp7hK0tra66F31Jf39AAAAlItuxu7evTt4/vnnw5Rkhawb9dFHH7nx2LFj3TgX5cN00/f1118PU244ceKEy7spcFFnSMpbKX/WH43ltd24gMxKh5QXLKtMprRi/Pbbbx0PPfRQRyYgCFM6/fTTTy79vffeC1NKY/PmzR36F2js03w0raWlpaOqqqojE6yEKR1uWq9XutF6Squpqem2biZAiU3PBCQ9jqG2ttal+fS6aJrErattKd1n+6+rqwtTAAAAykd5FeWbjPIp0fyLKWTdKMtD+fmvOJlAxOWhtK7yZ9loW1pXecBCjiVJJmDpkff0afvaT2tra5hSehVV0jJ//vzg0UcfDVatWhWmdLr77ruDjz/+OHjttdfKUuKieoJW6qNB81Hbt293RYF+MaKm1etDXB1ENdDy1x08eLAbR9PvvPPOcOoGRdSqS+lLKr6Ms2nTpuCxxx4L5zrdcccdblz2KB0AAFQ8q+qVT9vhQtaNo965JFteSvk4lXRYHlC1YKxafxxtS1W9tG3l2VTLJq66fz70OuUnk6qO+a5fvx5OlV7FBC2qUnXu3LkeAYu57bbbgueeey7Ytm1bmFI6mcjWVcOyobGxMVxyg05KZfj94EaDPSNFfX73FzXIUi8Woi+R6lTm27Wfik91TKpe5h/n+PHjwzU61wEAACiHUlULK4QCIuUBVaXeevNStf5cbVZ0o1nHJ+pOuVCqVqbuk20buZw8eTKcKr2KCVpUB3DcuHHhXDzV4yu0QVMxRB84JKq72NDQ0C248Ye4xlp9oc9BbWbUruVvf/ub68s7H7/++qsbq71M3HFqiPacAQAAUCpqA6LHSuRTi6SQdfuD8qK6eawb2mLtYbLRa5RP++OPP8KU/K1fvz544YUXCu5coBzoPSylokV0KrYrVdU1FROqYZcClnz7/TbW68TXX3/txgAAAGmhm7KqPaJ8jl8jRINomabVoVAh6/a3JUuWuHFSt8dRM2bMCKfyp/yeOmYq5Mb35MmTw6nSq5igRf8UVQ/LRj1bpfW5KGrPoipicb1vqeiyv0qItC3Vo1Rf4r0pvVGkrgBLVdnierLobX1LAACAvrr99ttdKUbcIGpXomk9m6SQdbOxdsKFVI+3kp24bpLjqHfZXMfhs/xYoXm9uC6RS6ajgsT1HGbUs9hdd93VkYmaw5Tiy5zoricGjXOxXr7US4Tfe4V6j1CPDtYjhfUe1tDQ4OaNpUf3FU23+WgvX4X0HlZfX+/S9Br1hGHU4wS9hwEAgDRS3kX5mnwUsq7yZFrfz7/lojyT8ny5ehwTras8V5TyYHH7VJ4ymk80ysPF0bFoKKeKqh6mHsL+85//uN4Y9LwWo2pXM2fODP7xj3+4Eo1SUCnEu+++66a/+OKLnP1rKxJWwyx73oke1qjiyFtvvdVF1haR//DDD26s9+Rv09IPHDjQLd0aVNkx3HPPPV0lJeotQ89+0b6twb8ic6WL1j9//ryb9ktQ1K+47iqoZEh3IXScOl7dLXj55ZfDtQAAAG5+jz/+uBtbXsynPJWqmKntjJXEqPaMerz99NNPu7WlsXWVL7N1lU9Tj2Oqzh+lPK3yjH4eTdOqUfPtt9+6/Jk/6NkwygNGKb+nfKB1EFA2YfBSMVSiouhSpSp6+xrmzJlT0hIWK52IDvmUuGgdRbpaX1G1nn9i4rarCLuQdFEEbvtQxG19gWten53mrUTGH/w7DlrHSlw0qISlnH17AwAAZBPNy2RTyLqideNqmyhvpGekWH5J08o/+TVVjPJWft5N+cDGxsZwaU/ajvJzlv+yZ+ZlG+LyalbbJ+6YSmmQ/mQOBAAAAEARqE2yHv+g3mAHWi+qKoVRQ/98nuNSTPQeBgAAABSROipqampyj68YSKyjp3IHLELQAgAAABSZ2qLMmzfPtV8ZCFQ6tH379mDv3r1hSnlRPQwAAAAoEZVeXLp0qeDuhktJAcupU6diH3heLgQtAAAAAFKN6mEAAAAAUo2gBQAAAECqEbQAAAAASDWCFgAAAACpRtBSQS5fvhzs2rUrGD16dFe/2wAAACgd5cGUH0uzNB4jQUsZ7Nu3L1i7dm0waNAgN+hJo/nQCWSvsaEQBw8eDHbv3u2exgoAAFDJDh8+HEyYMKErT6VppSXRzd8tW7YEw4YNC1MKpzygujvO1pWw8nt6lotuMuu4ct1oVj4y37yk6H1o+3of2r7Gmle6mTJlSjBp0iTXLbOfXk4ELWWgE2Djxo1BXV2dmz969Ghw4cIFN52NHvBjGhsbg0J7q9YXZOHCheEcAABAZVJwMmfOnODpp592+SkNmlZaXOCitKeeeipYs2ZNcPXq1TC1MApYDh06lPX5LLqpPXXq1ODMmTPBhg0b3I1mBRBJVBqifGQhFOBo+2fPnnXvW2PNRwMfPcV/+vTp7n2nQuZgUSabN29W1OGG+vr6MDVe5qTtqK6u7lq/t2yfLS0tYQoAAEBlUZ4qLu9VW1vbUVNTE871ZHmxQrW2trrXKT+XpK6uzq2TK09otC0dr16jcT6amppij0P5QqU3NzeHKTdo28o/lhslLWWWOTHdeOfOnVmL395+++1g6dKl4RwAAAB6SyUYcUaNGpW1JEVVtnpDJTSqYaPtx1H1rP3797t84Y4dO8LU7PSaTDARzuXn4sWL4VR3t99+uxv/+eefbuxbvHixO/58agUVE0FLmY0cObIrcNmzZ48bRymYOXbsWLBkyZIwpSedSCputHqZ+lIV2oDKr9up+o0qokxLPUYAAID+UlNT424Yf//992FKJ+W3+vsmsdqkqAqXqlrFUf5Lx1JdXZ13wKI83gMPPOCqcBVi3LhxbtzQ0ODG5ptvvgmqqqqCmTNnhik3TJw40Y2T8qmlUnFBy++//+4y4yNGjOjK4M+dO9edpOXy5JNPuvGmTZtigwSdJLNmzQqGDx8epnSn12i57hq0t7e7QSfe8uXLczbeMqpn+corr7iG+h0dHS6QeuONN4JnnnkmXAMAAODm8Oqrr7qxAgnlgUQlF8pPrV692s33l48++siNx44d68ZRyn+J2rDkQzeqlV97/vnnw5T8zZ492wVsKtVRGxblIRW4rVu3Lvjyyy9j85pWOqTXlFNFBS0KWObPnx8MHTrUFY8pc65h69atwWuvveZOgHJQA6va2lpXHHn8+PEw9YZ33303ePHFF8O5nn788UcXsKiRvU42DfZlPHnypBtnoxNWX9R//etfXRG7Ogqwkzp6FwIAAGAgU+a9qanJ5b0WLVrkaqjoJna+JR2FUCN3ueeee9zYpzyWGsIbv9ZMtEcvY3m2pJvZuRw5csTl8VT6M2bMmODNN98MTp8+nbXURvlU5TXLmSesqKBFAcujjz4arFq1KkzpdPfddwcff/yxC1zKVeKi+oKiSNen6F8nVlIdSLnllltcyYoV+cngwYPDqdzUFbJEe6dQMaUU2isFAABA2ilAsCr6ypCrxCMuSOgrC0rigoxTp065sfJx8s4777gaMzouVRmL9uhl1cKy9SiWi47DSk0UtGk67qZ5nOvXr4dTpVcxQYsiyHPnzvUIWMxtt90WPPfcc8G2bdvClNLSF0dBgr40Vkwp77//fvDss8+Gc/EUGV+5csXdNdCXTX2IWxCUD0XNOmktsrfBTuhffvnFjQEAAG4WKrEQ5b10g1jBhVWZKpVr1665sYIU5QWtxoxKfJQv1DFZvrAv1cJ8yvepGlxra6t7hIaotMnPfybJpwZPsVRM0HLixIluJRFxlPnPtw1IMVhApUBFdCz64uQTTWs9tdVRMZ/kWy9S9CXQl9Wqy0WHYhSVAgAAlItu8Kp2jfI4qs2iKlPq3UtBQjmeSzJkyJBw6gbLFyoPK32tFibKL6odj/KJyvfqGX7Nzc2upEeBSznzwblUXEP8NFuwYIE7aVQdSyeNGm698MIL4dJkOgF1Z0Bfvp9//tk1ILvzzjvDpbmpjY++pKW8swAAAFAu6vzI7yVMgYBVyVc+rFTd+8YFK8Ya7qs2jfKFOi49eDJaM0a0TNPR6mRRahKg2jUq1TGqqfPhhx+6aes0IMnkyZPDqdKrmKBl2rRprnpYNiou60sdwb7SF8bqVioCVhDin1RJ1q9f74IOFRn2Jvq2LvisbUtUPsWFAAAAA4ECAGXc41hHRr/++qsb9wcFQhIXCFkXw1988YUbx1E+Tc9R0TNZ4gZRVTJN52oe8Mknn4RT3VmvYrmCNbWjLpeKCVoefPBBVz3srbfeClO6U89i//73v4OVK1eGKcVn9Rh99iwWRcz59hMed4LFPRwoiX1h1EVy9NkuKoospNQGAAAgzXSDWjVb4gIF5Z+0LK6nr95S+xGJC4RUNU09cynfF+2Z6/PPP3fHopo4Wk81aeIGUe9nmvZvdit/GK3u9dhjj7lxXDUwBXIzZswI57qz57hk62Gs6DoqyG+//dZx7733djQ0NLhpkzlRXPp7770XphRfe3t7RyYq7qirq3PTvvr6+o7MidEjvbGxsUP/Mg2aNpnI2qVlIuSOlpYWN5/5Arg0jbVuW1ubW1f7U7r24Wtqaurato5Lr9MxRNcDAAAY6Czfo3yO5beam5td3kfL4igvpeV6nfJb+WptbXWv8fNuPu1f21U+zvJrludLOhaf1lO+LUr5ueg2tC/tR/uz96B96nNQejTvKUrTdpR/LqeKClpEwYo+9Lvuusv9AzTMmTPHBS6lYgGFPyjQMDqJosFCdH0bRCeTbVMnqL509gXQvJ2U0ddq8Ol1doJr7B8TAADAzUT5HmXULU+kaaXFicu7xQUKSbSubhwnUeBgN5Y16FjyDYySjkV5SeUFFTT5lEe0ZXqtxn7wFmUBngVU5TJIfzIHAgAAAKAIVPVr/PjxrnvlbM/eSyM17le1MauKVi70HgYAAAAUkdqCNDU1BQ0NDWHKwGBtX8odsAhBCwAAAFBkaiQ/b968rodapp1Kh7Zv3x7s3bs3TCkvqocBAAAAJaLSi0uXLuX1WItyUcBy6tQp9/DJtCBoAQAAAJBqVA8DAAAAkGoELQAAAABSjaAFAAAAQKoRtAAAAABINYIWAAAAAKlG0AIAAAAg1QhaAAAAAKQaQQsAAACAVCNoAQAAAJBqBC0AAAAAUo2gBQAAAECqEbQAAAAASDWCFgAAAACpRtACAAAAINUIWgAAAACkGkELAAAAgFQjaAEAAACQagQtAAAAAFKNoAUAAABAqhG0AAAAAEg1ghYAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaAFAAAAQKoRtAAAAABINYIWAAAAAKlG0JKHr776KlixYkXw8MMPhymls2XLlmD06NHBoEGDgmHDhrl5AADK5cKFC8HatWvDueLYtWuXu/YCgClK0KKMtTLZccNAox/Nzz//PNi5c2eYUjoKlL777rvg/PnzQVtbWzBr1qxgzZo1wffffx+u0Z0uJHqNght91gp29L+4fPkywQ4ApJD9bue6KaYgwX7bJ0yYEBw+fDhckj8FAnYTTPtLupZko9fs2bMn2LhxY5jS3b59+9w+8gk4sq27bNmy4NKlS0UPjgAMIB1F0t7e3lFbW9uhXVRXV3e0tLSES9Jv8+bN4dQNeh96P6XS2trq9tnc3BymZJcJajqqqqo66urq3LSl1dfXJx67/keNjY3hHACglPT7q+tjruuLftc16NqksdbXUMh1VdcCXSPsNdqW5nWtyZfWrampcdeOKC2z602uYytkXXvfAFC06mHDhw8PZsyY4aZVQjBlyhQ3nXa64/PFF1+Ec+Vz6tQpNx48eLAb5/L222+78TvvvBOMGjXKTWu8Y8eOIHNhdPNRult27dq1cA4AUEoqTTh27Fg4F0+lEfPmzXPj1atXu3EmE++WffTRR26ci65rqi2g64Fdi7Utldw8/fTTbj4XldjPnz8/eOGFF9z1Peq+++5z288EI2FKskLW1TVt06ZNeZXcALi5laRNy8iRI8OpdFOx9yOPPBLOlVehwYSqGOgCFHcx0YXRAhmjC5+qmgEAyif62xw1c+bM4IknngjnOi1ZssSNr1y54sa5bNiwwY21Ld/SpUuDs2fP5lXVTDe5tL/osUQVcr3PZ11d07TPxYsXhykAKlUqG+LrB1R1dlXvVhlx1WnVXR6jOy5+HWC117C6vkn1X/26vNFB29E+p0+fHly9ejU4evRo17I4+ewvjt6D3+ZE71HBg8/aA1lAMXXqVDefTycAavcS3Z6ZNm1aONW5j0WLFrlp7Se6/ehnpQuGgiLRZ2/pNvjtZez4NeRzzACAZHE3otTWQ1QCk4uuO7qmVVVV9djW5MmT3fizzz5z4yTahko7VGuiHHT90vWtN+14ANxEwmpiRaF6qNpFIfVRm5qaXJ1Zq2fb0NDgtqF6raJ0S1MdYE3rNaoTq9cpPVo/1o7D0lWPWPMarP2Hse1GWXo++4uj/aj+sOrxqj6wBqvTq3FU9JhzUdsXra9Bn1X0fUVpu1o3+r+xz0bvUTTWvP+Z6LV6L0qPaxOjz8j+XwCA7KK/sbno9zXf31j7rY/bvi3TtSwbuw7kcy0v5NqV77p2nHHXSgCVI1VBizLyfkNBY8GBBTKiea3rZ87th83fn7aptOgPvH7AlW6Zc6O0uB93259/DHH7S6JtqsFllDXCjL7nfH/MffYaO1bNxzWYlKRjt8/FZ5+/z/YVF7Roff9zAgAk029p3HUnSr+rupZFr0XZ2G913PbtOhD9fY+yG4X5dAxj+8vn2lXIulpP7xtA5UpV9bCDBw+6cbTRfiZj78Yq4vZNnDgxtj6w35D+xx9/dOP777/fjY11EnDx4kU3zof2pwaEUeqWOBtVrdKxZy42YcoNVtd4+/btbtwXaliZuZAFmYuTq+amql9jxoxx1b3ypc8zE3SEc53iqieoTnXmAhK89dZbYUon60Iz7nMCAPSOqt6OHz8+2L9/v/t9V3XmpOrA/e3bb79143w7hikWvW8AlStVQYsyvPpR8ttLaNCPtPzyyy9u3BtJrx0yZEg41Xt//PFHOBXv+PHjbhy3r3vuuceN7T32lYKFI0eOBE1NTS7Y0+e5fPly15YmH+rR5cyZM25a7VfUniUaLIoCmZdeeqlHOxoFSPn2RgMAyI9uSnV0dATNzc1dN6b0u+6396wE9CIGVK5UBS0qkdBdfv0wxw3KUBdKpTYqEYh2K2m9c0V7UymGbD2BFatEQsHG6dOnu7rGVHeX+d6V00VBDfFVCvS3v/3NXSDjLFiwwI3XrVvnxrp4ah+WDgDoX7Nnz3Y3pixwsZtiSayxfTZJv/EAkCapClqGDh3qul/s7ztHCnZUImA9falER5n4hoaGnN1N9qds1cisClxv+T14GZWG6O6cBS7vv/++G2ejoEM9lilg0YVRF8gk+uzUz76VtujiqWAprjoZAKD/rFy50o1zdY9/++23u3HcddV6ISvldbCvBsoz3wD0v1QELdbmQnV0xdq2ROVbUhCljLQy16qXq+pmekCWqjZt3LgxXKO47C5W3EPE7ELS164k1Y4nKdjLt+RDJV3qClltb/SZ5ePFF190461bt7ph7ty5bh4AUDzWvmTSpElunMTaKcbdEPzvf//rxrl+tx944AE3tiCnXFRrAkDlKnvQolIPawxvVbXUBiPaeFx1d++8885wrjB6rfp5V8mBqpmdP3/elUDkw55P0heqAmZF+dHAy4r2LfPfF+vXrw+nuvvpp5/c2DofiKOLmXVaEJUUDIkuiApydEHU+8tWMgMA6B8//PCDu65EqxjrmmodophXX33VjaNVydSWUgFNrt/thx56yI0L6bimP9n7KddzYgCkRCYTXxTqajfzg+q6KVQXuFFaru6Go103Wn/wGtQdsLahdfz+2bW+livd7/LYnjGi11lXv1pux6DuFW1Q143qZjHaJbBeq/W1XN086vWF7C+JtqHXa7DuHTXWfLTbYG1Lx6ttR7tqTmKftcZ+95F6H9qHtucfo30uOnatr89Xy7Wu0nVMeq32b5+J/jdxXRzr9VquzxUAkD/9ztpvsX99MfoN1u+yfl/tN1y/w/pNj65vv+saosv0G6/t6Fqk7fjz+dC6ua5H2q5di3JdDwpZ1z4jjQFUrqIELfoBsh/OXIN+qKP0w2QZZY39H7S4bSvNfvz8wTLvFgDEDdEfbe1badqvpgvZXy7aj370bX0dV/RH2AKA6OB/BnEUYOkioMDC34d9fnax89l703uxz8ACSaVbIGPr2T7i6DVxF1wAQDz7nfaH6G+9/5usQdeNpN90pWm5hqTffNuWrhOF/Gbba5PYdSI6xClkXdG1KC6vAKCyDNKfzI/FTU2N1MeNG+fqAKtI3W+4eODAAdcIvrftZdBZdK9nwqj6HQDg5qNqwg8++KDrpCXfNo/9QfvV88Y+/fRTGuEDFe6mD1oUjKixYVKje/0gPvPMMwQtfWBthkp5IQMAlJZuUOk5XLpBVapeIq1nzHzboQK4eaWqy+NiyPVQRfVU9uyzz4ZzyJd1UKCgTw+jJGABgJubGv3v3r07eOqpp7J20NJfdDNRNSMIWADITV/SMmHCBNezVW1tres9yx60pWpin3zySbB48WIy3AVSz27q4U3V6mTbtm30GgYAFUI3rXTDr5jBxOHDh92YawsAc9MHLbobtGfPHtd2RcGLVFVVuUBl2bJlRXsi/c1MF5O//vWvwbBhwwhYAAAAUHQV0RAfAAAAwMB107dpAQAAADCwEbQAAAAASDWCFgAAAACpRtACAAAAINUIWgAAAACkGkELAAAAgFQjaAEAAACQagQtAAAAAFKNoAUAAABAqhG0AAAAAEg1ghYAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaClQF999VWwYsWK4OGHHw5TbnjiiSeCYcOGBRcuXAhT0BuXL18Odu3aFYwePTrYsmVLmNqpmJ+xtrl27Vq3fQAAAKRHUYKWffv2uczfoEGD3BCXwY+jgMBeY0OafP/998Hnn38e7Ny5M0xBMezZsyf45JNPgra2tjCl+BSwHDx40P1vr169GqYCAAAgDYoStOhu+MaNG4O6ujo3f/To0bzujG/fvj2cCoLGxsago6MjnOtfdie/UPfdd597X0kUrF25ciUYNWpUmNKpt/urVKtXrw4ee+yxcK67pM+4r7Q97XfixIlhCgAAANKiqNXD7r///nAqCN5+++1wKp6CmrNnz4ZzQbBs2bJwqv/pTv61a9fCueIr9f5uBmPHjg2nAAAAUOmK3qalvr7ejVXtRiUOSRTULF26NJwrHt2pX7NmTThXfKXeHwAAAHCzKXrQMnLkyK7ARSUOcRTMHDt2LFiyZEmYEk9tSlT1zNq7aFrtYHzRxtTWtkaN59Woe9GiRS5dgYTS/fY21vjb334+1dokul9J2p9t3wb/GKLteuJou3Hr+On+NqPHpvU0rfX0ucQFk735rA8fPtz1+Wn/2YLUKB2TvVZjtR2KivuMjf539p4mTJiQeLx6v/56OuYkud6Ptud/Rlo3Wg1Qx2AdN+j1GmtdBbMmup3o4L+PuP+LXg8AAHBT6yiizZs3u6GlpUWNUzqqqqo62tvbw6U3aJ1MYOOmtV7cYTU3N7v0xsZGN9/W1tZRU1Pj0pqamlyatq1taT9Kt+1qXoPYsWiZT9v1t6Wx5mtra928L5oe3a8vbn/+sdfV1YWpN+i9VldXx35WRtuI219ra2u349P+GxoaXJoGTesz8Y83+h5781krXfPan7avNP89Z2P/I71W7H/hbyPbZ2yfl45T7H9n2xN9LnqtvSdtT6/Renq90WehtFzvx16vz0XTGuwzsv1qn/bZa7v6X9u27P+u1+m4NK9p/7PWuj5tT/u047X/U65zBQAAYKArSdAifmYwys9wah0NPsvYRTNxeo3W1TI/02b7sn1rPdu+MpT+MmOv8VnmMUppWj8qbhtJ+7P0uKBFGV3LXGcTtz+JOz7LoPufvz4TCwIso93bz9rP+EvcMcSJCzAkLlCQuPesz1CfmU/z/jb1uujxaNvalv+Z2Paj56nS/NfH/V8tiIges9I02PEo+LDP0IIapRnbtv5nPu0/um17fT7nCwAAwEBV9OphZvHixW68bt06NzaqJpMJDrL2BnX8+HHXDe3cuXPDlE56TSZz65apu9oo9QYlWi9Xb1NaruPwDR8+PJzqf1OmTAkymdBg//79Par3qP3PggULwrn+oapLoupExj4/sepYvf2sZ8+eHU7doF7jctm6dWuQyZy7z8M3bdq0cCo3VffSZ6aqU+bxxx8PpzqrVOlY7Bw0Oj8y34Fun4mJS/vmm2/CqSC45ZZbgkwAF4wbNy5MCYLBgweHUz3pf23vUb3Q2bn17bffurHSjK2XCRTdWOw9aDu+ESNGuLG6iAYAALhZlSxoUSZQmVNlxPz6/O+//37w7LPPhnPxDh065MZxmULL7PU107Zjx47gzJkzblptCHS8+WS6+8ICOL9nNX02s2bNKmrA5PvLX/7ixpZ5LsVnbRSsqcc4C6h8d955ZziVm/U0N378eNd+RNvVsVrm3/6PhWwzjv/8Fm1fXS8rWFNbFbXJiQZFhYhrl6KgyPz4449urPfot3dZvny5Sz9//rwbAwAA3IxKFrTIqlWr3FiBiig4UIYvepc96o8//gineurPrnF1PMpAb9iwIfjb3/7W4652f9P7ViCnUgLLtOqz0b7LpVSftfz666/hVN8ogFDwo/+XPkt9pgoiik3nrjoGGDNmjJvXeVMoex6NX4pjDf790p6LFy+6cXt7uysdig4ELQAA4GZW0qBFVZ5091h3vhUgfPTRR8ELL7wQLs3thx9+CKd6ylX9KxeVcEydOtVlPI8cORJb3akYLKOr0hYFLsp8lmrfvujnV8zPuhh0TPq/tbS0uGp+6q1NAYXv5MmT4VTfWU9g6vXu559/dlXNelOSo++Ejlelbla9bf369e578uKLL7p5GTJkiBufPn3ajQEAACpJSYMWVXmyNhTKrCvDF9d2IMruRn/55Zdu7Pvzzz/duJA2EFEKFtQ1cV1dXV7H05+s2pxKCBS46BhKKfr5Ffuz9t1zzz1urCDWShf6SqVXCl70mb7xxhsubfLkyW787rvvunFUtJvifCiwUOnO7t27+1SVT6/VNlTCN336dFflS9XO9Pn7weGkSZPc+IMPPnDjKL/KJQAAwM2mqEFL3FPg7Vksyqjm+zBJK6GJa7T+2WefuQxqXLCRT0ZY61h7gaj+ykj7tM3odq3anAKXXM+qieNvz+7WJ1UXiu5bn58+25kzZ7r53n7WvaEMu1XBUxDgswApH9FnzWi7/rll1fDUnkrr+jRvpRiFiH42ku2Yo5+70f/r6aefdoGWghVV9VIAYu2HjOb1HvR/ib5frW/VxwAAAG5KmUxSUahL10wmq+v5Ez51Z5vJGPdI95/PEe3C1brGVTfE6n5XtI6243dtq2Xar9aNdg8rWq5lWkev07HoOLQd26+6rtVx23a0bzsedU2rNA12HGLv19Y3cfuLsv1nMvBhSn7s89Kxatt6v9btrgZ1h2td6Wrbtq7/+Skt2l1xvp+1/579bfifkd+Vbxwtt8/e3of2b8erY7DPPukz1rpaz/alY9Z6fjfI2q4dk5bpNdqv//8o5P3os9a89mufvR2zxjpmHYe/X/+zM9q/lulYtQ0Neq3WjX52/mdl54uOV8egYwcAALhZFSVoscybPygzZpQhi2beo+vb4FNGUhk0W6ZMrp+x8zOINuhYoizDqWX2emWCLUNogYytpwylP+8PSovbr/9+4/YXpffiZ8TzZZleZV7t9XofOmYLOMT+J0q396nPMhqwmN5+1kmfUTbarh2fjs0+U3tP+uyzfcY6Nnu9BttGlLZh7ym6TiHvR+vqmGyfOk59XkrTdjWvdeJeGz0uvS66jj9EvyfRz8rOVQAAgJvZIP3JZIBQZmrToEbWfWkfkY0ajatKHv/udFE1L1WNe/LJJ131snPnzoVLguCXX35xVb/UviVaXQwAAKCSELSkgDKmJ06ccM+KKRaClvRRwKL/i9qzJAWr6gFND8okaAEAAJWspL2H4Qa/IbeezeJ3b1sMSQ3BUT4HDx50PZAl0f9MD7QkYAEAAJWOkpYyUI9RerJ5VVWV6xFKT8DfuHFjuLT/2f6ktbWVTHBKHD58OJgzZ447D+rr64N7773XPetF1cS+/vrr4Ntvvw327t1btCqDAAAAAwUlLWVwyy23uGBFFi5cWNSARU+Gt4BFNF2Kp8UjNz1EtKWlxQWt6u5azwrSA05feeWVYMSIEVmrjQEAAFQSSloAAAAApBolLQAAAABSjaAFAAAAQKoRtAAAAABINYIWAAAAAKlG0IKsvvrqq2DYsGHuIYfFpods6mGL9G4GAABuVspb7dq1K5xLpzQeI0FLGenhgcqgjx49Ohg0aJALDlasWOEePFlpGXc9s+TQoUPuqf0AAADFpoz5hAkTXB5Mg/JgSQ/j1o1Vy69p3Nt8mrZz6dKlYNmyZWFK4IIDO4a4IVfwoBu+GnpLn4P2o7GZMmVKMGnSpOCJJ55IzQPKCVrKSCfYgQMH3BPx1fP0zz//HIwcOTKoqakJ1qxZE65VXjppr1y5UtRnyYieWfLss8+GcwAAAMWj4EHPRnv66addHqytrS04c+ZMMGbMmB6ZdAUNW7duDZYuXeoeBq18kfJphQYu2qdu0CoQ8O3evds9v6+2trbboPygzJw5043j6Nj6csNX73Xx4sXhXHd6GPn06dODp556KkwpMz2nBaXX1NSk5+N0tLS0hCk3tLa2umWVRp+F3vfmzZvDFAAAgP7V3t7eUVVV1dHQ0BCmdMoELi4fkgkYwpTOtEygEs51svxKJtAIU3KzvJ2251N6dPumsbGxIxO4hHM9aVs61ugxF0KfgfahbcTlSUXbTkPejJKWMrl48aIb33777W7sU2SrSB4AAAD96+DBg8HVq1eDv/zlL2FKp1GjRrkSDpVcqKq+DBkyJNixY4ebNqqFolIQlbjkSyUzdXV1bh++U6dO9di+UQmMSoKSqDpbJpgI5wqn6mAqYVq4cGGYEk8lMTp++0zKhaClzN5+++1wqrtp06aFU53VyKxeo19n0U/3iyh1EupE1nIV+9l6SrP1bfDrL8alxzWO99fT4C+LOyYdgxryq82O0q1hf1rqSAIAgMpx7dq1cKqnGTNmuPHx48fdePjw4W4cpcx+tJpXEuWpFAipqlWU37bFpwDh7NmziVXDVC3sgQcecDe6e0N5sL///e/BG2+8EaYkmzhxohvv2bPHjcul4oKW33//3WWYR4wY0ZW5njt3bnDs2LFwjdJYsGBBUFVVFezcudM1AvODB/G/CEeOHAmam5vDuRuU3tjYGM51+v7774PPP//cbVeeeeaZrqhedwRaWlrcfkXb1N0C09HR4e4cNDU1ufSkxvH6olo9y4aGhmD16tVuWnRMSlNJkaXrGHQ8X375pduH3pu+JOU++QEAQOX64YcfwqmesgU2Chh0A/b1118PU7L76KOP3Hjs2LFunA8FTcprRUtmRAGNSmGef/75MKVw//znP10pTtz2o2yd/fv3u3G5VFTQooBl/vz5wdChQ131LGWgNahx1WuvveZOgFLRCfDhhx+6AEKRtBqDWc9hcdRQPU70C6CI2xrNK9hQ43YVO7a2tgbvvPOOC0aS7gwo6tYdBVue1Dhex/7CCy+Ecz19++233b7IOskVpdvdAFv2xRdfuDEAAECp6Ma1fPLJJ26cL+XRVItk+fLlwYYNGxJLYaLUwF/uueceN86HbvQmVQ1TfvFf//pX3vuP0o1y5dWSSnniqNqcblrr5ni5VFTQooDl0UcfDVatWhWmdLr77ruDjz/+2AUupSxxUVCgHsOs/YpKI9R7RH9VndIJZiUpChjs5H7xxRfdeNu2bW5sVMczqQeJKAU2OlYds3+sOpkV1PhfJK2nIkzT2y8ZAABAXykPo1IM3dxVAKB8jAZVid+0aZNbR21ZfMroKz9jvbsuWrQo72fY6ea05Jv/0bHohm9c1TCrFubXlCmEtq1qYUntaHK5fv16OFV6FRO0nD59Ojh37lyPgMXcdtttwXPPPdcjI19sOoF14qjaloIMUdUpa49SDAoqog3NRCVNSaUwcdT1nxqyWb1P0ZcpGrmfP3++q/RHPwiqDgcAAFAuqs6um8a6+Xrrrbe6quyDBw92+RrRM0p8ChJUO0c1V+xms/Jr0er9/SGpalipq4XFOXnyZDhVehUTtJw4cSIYN25cOBdPpRHFOPnyoS+DvkBqT2JVxtavXx8u7X9WomIdAeh9z5o1y03nS+1yZN26dW6sIEtfqLhGYVb/U/+HUlbDAwAAiLKbxtZUQDdV//zzT7dMJSpxeRlRul5nvXZZe5X+pPbEcVXDylEtLE0qriF+Wvg9bvlU0vHpp5+6aWtMXwzaj4IjfUkVbOhLt2TJknBpfhSlq/s+1XHUF0F3BuKql+lL9vLLL7v6mfqiJ/0QAAAAlIPyQnYTNp9aN5ZnKqTb43zoOOKqhimfpRoyagNtHUnZIFqmadXUSaJ2OLaeP1iVN9t2thv4kydPDqdKr2KCFnUhrOph2ag9Rm/rCPaGeueKo2NQlF9sL730kisGVS9eKiHpTVGhNdRX0KMODaJfMgVFCr7efPNNghUAAJBKqt2im7Cq+pXU+ZHPSjviujGOsh5X/Sr5SXQDWHnAaJ5Mz/VT6U7cIHqNprO1Tday6Gs1WPMEvXfNxz1D0Nxyyy3hVBl0VJCHHnqoY8uWLeFcd7/99lvHXXfd1ZGJQMOU4sqcFO4JpHoqa5TS9K/JnERhSiel6TU+PS1V6ZkTLUzpFLduVObL6dbToCf0x8nnKfWZL0rsMYhep2U6TpP0/vLZFwAAQH/SU+EtXxKXL4ujJ9lXVVXltb5tP+mJ8766uroeT+rPJS5PJcrn5bNPy6tlW1fvVUM5VVT1MPUQ9p///Mf19qDuj416DFMJwT/+8Y+C23X0hdqtPPjgg67ExRrdq7RHRXuqupU5iVyaUVUsvUZVy1R05/daoRINpWs7VqyndbMV8Vn1Lu0rqQG+9WF+4MCBrmOMss4N4upIWjGiqofpfeo41dhNvvnmG5dmJU757AsAAKCvlM9Q/kN5LjWo1zPm1LY42l5EbXJVZcp/LIXyVuqRVtX582lf8vjjj7txtufCiI5JVcNs/b5SnlZVvpT36gsdl2rmWAcEZRMGLxVDJSqKYFWqorevYc6cOSUrYTGKahWdNzc3uxIKRa86Fo01r+g4SmmKpLWeSlEU5SsqVkmHSjK0PYuW/SFbyYX2nxTR2778IY72m61Ux+4w6L3ZsWjbmrcSmLh95XN3AAAAoBDKXyifofyT8lzZ8hvKa1mNEv81cfm0bJTPUSlKNqr1ou0XSsel7UdZ/lLvIRvLOyZ9DjouLS/0Pfe3QfqTORAAAAAARaCaNOPHj3ftZnrb3XC5qDRqxowZwerVq8OU8qD3MAAAAKCI1BmRHmuhamgDiTUzKHfAIgQtAAAAQJGp/fC8efNc+5iBQKVD27dvD/bu3RumlBfVwwAAAIASUenFpUuXEjtBSgMFLKdOnUrVgygJWgAAAACkGtXDAAAAAKQaQQsAAACAVCNoAQAAAJBqBC0AAAAAUo2gZQBTrxPDhg0LLly4EKb0jbazdu1at03rlxsAAAD9R3msXbt2hXPplMZjJGgpAz1ZdNCgQYmDggats2XLln4LSHLRfg4ePBjs378/uHr1apgKAABwc9q3b18wevRol/fSWPmuJFpm6yqfppu8ly9fDpfmT/tUd8fRroQL3b62Y/lGGyZMmBAuzZ/2oeDE8qYay5QpU4JJkya5G+S9eZ9FoS6PUXrt7e0d1dXV6m66o76+3s2blpYWl6ZlGjZv3hwuKb66ujq3Tx0DAADAzaixsbGjpqbG5bGU56qqqkrMc1merLa21r3G8mea9vNvuTQ1Nbl8VlRvtq9lWt8fmpubw6X5aW1t7cqLNjQ0xOb99Dlp22lA0FJG+mLoREkKSnRy24mrk6YU7JgIWgAAwM2ora3NBQo+5XuU/1Em3qeMvQIEvcZoXQty8s2faTta39+O9Gb7yh8m5R3zZfvQoGPIRkFLX/fXH6gelmIqksucrG56+fLlJasqBgAAcLMaMmRIsGPHjnCuk6pDZYKH4MqVK2FKJz0V/siRI8GoUaPClM517fWffPKJG+eyZs2aoK6urtt2pDfbX7duXbBgwYJwrnB62v0jjzzipr/88svgvvvuc9NJFi9e7I6/3PlQgpaUU53HTBTspvfs2ePG4jeaj1LdwxUrVrhlVscxrmF9dD3VY/zuu+/CpQAAADef4cOHh1PdtbW1uRvGPuXD4ta/88473Xjo0KFunI3yYEePHg2mT58eptxQ6PbVlkXHOWvWLJeH603HSU8//bRrv6zAKFfAIhMnTnRjPx9aDhUXtPz+++8usz9ixIiuhktz584Njh07Fq6RPvYFUiN5UbChRvM7d+7s0WheyxR8jBw50t0taG1tdetMnTrVRdbG1jtz5kxw9uzZoL293UX5tg8AAIBKocbouon7+uuvhyn5mTdvXjiV7KOPPnLjsWPHunEhots/ceJEUF1d7QIX5QOVv1PwonxdPg4fPuzyfdpGNEBLYqVA5c4jVlTQooBl/vz5Lmq9ePGi2vO4YevWrcFrr70W7N69O1wzXRSAiE5QUUS+evXqrsjXpyjYlosi6G3btrnpN998041l/fr1bntWJKnXKOLWSQwAAFAJVHNFPXepGv6GDRtiSz3iqAcw1YSZOXNmmJJMN4jlnnvuceN8JG1febXz58+7m82bN2926yh4eeqpp8I1svvggw/cWCU1uonv956mgCZJbW2tyzf6N8BLraKCFgUsjz76aLBq1aowpdPdd98dfPzxxy5wSXOJSz42bdoUPPbYY+FcpzvuuMON/ZIaneCKsKNfTp3EAAAANztVrdLNWrXXkEWLFrmMfD7UruTDDz/MK8hRyYbkGxBJru0rXTeotW21xVH1M1Udy8XyuaqN8/jjj7sAqKWlxc3PmTMna+Ai169fD6dKr2KCltOnTwfnzp3rEbCY2267LXjuuee6SiUGIt0tUFUw3S2wqm8axo8fH67Ruc7x48fdtJXg+OLSAAAAbjZq8K4aN6pKX19f79LeeOONnO1EVJVMN3lnz54dpvSvQrav2jJWU+jQoUNunI01K3jnnXe62rP4Df9XrlzpxklOnjwZTpVexQQtqgM4bty4cC6e/nm9adBUbL/88osbK5LO5tdff3Xj5ubmrqpv0UEnt6rGAQAAoDP/p0y7qluJtUGJo+pR6tGr0LYv+erN9nX8qr71xx9/hCm5RUtwVPtGVc1UBazcvYQlqbiG+AORFfctXLjQjZPccsstbvz111+7MQAAAPKzZMkSN452e2xUvV6lIHv37i2oqle++rL9GTNmhFPZWY+0caytdLYqYJMnTw6nSq9igpZp06a56mHZKLpVEVmaqHGYivJ0ktmXKYkiba2ntitxvUhY8GMlTgcOHHBjAACASmeBQlzXxMpXqRMjlYAUGlBYTZlsJRh92b7okRV6nkou1mNYUs0i5SOt2lgcu0FeDhUTtDz44IMus/7WW2+FKd2pZ7F///vfOevylZKCDGscpmLLfE5inYwq2lN3xv6XQwGZ1XXUZ6GTUo23oo22rl27Fk4BAABUDuWVlD+KPrhRAYV653rxxRd75MX0GpWOZGOdHFk1/qi+bl/rKO8X7cJY+cBocPLkk0+68fbt293Y6BjUmP+ll14KU7r75ptvcgY0RddRQX777beOe++9t6OhocFNm8w/yaW/9957YUrxtbe3d1RXV3foX7B58+YwtVNLS0tHfX29W5Y5QTqam5vDJTf4r29qagpTO9MzEb1L11BbW+vmtZ3W1tZwrQ73GltH+9c+NbbX1tXVxe4XAABgIGtsbHR5HeW1Mpl9l6Z8kPJVGvssX6VlylP5g+WZtE42yn9pPe03qpDt23Erj2bHrbya1o07hrh8oii/5x+PtqV9aYjbjtK0vvLP5VRRQYsoWNGHftddd7l/gIY5c+a4wKVUdHLZvuMGBRhaRydT3MmjL1T0NX7go9dY0KNBJ7cfsBid6HZCa6x5bUf7JmABAAA3I+WJLP9jeSA/gPFZ4JA0KI+VD+Wt4tYtZPvK3/l5SL02LhAyek/Rm9ZGr7PPQOsobxyX5xS70R33+ZTSIP3JHAgAAACAIlAVLj2CIpPx73rC/EChJgdq6G8PLi8Xeg8DAAAAikhtQZqamoKGhoYwZWCwNjHlDliEoAUAAAAoMjWUnzdvXrBixYowJd1UOqQG++qCOQ2oHgYAAACUiEovLl261KO3rzRRwHLq1Klg2bJlYUr5EbQAAAAASDWqhwEAAABINYIWAAAAAKlG0AIAAAAg1QhaAAAAAKQaQQsAAACAVCNoAQAAAJBqBC0AAAAAUo2gBQAAAECqEbQAAAAASDWCFgAAAACpRtACAAAAINUIWgAAAACkGkELAAAAgFQjaAEAAACQagQtAAAAAFKNoAUAAABAqhG0AAAAAEg1ghYAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaAFAAAAQKoRtAAAAABINYIWAAAAAKlG0AIAAAAg1QhaAAAAAKQaQQsAAACAVCNoKcDhw4eDCRMmBIMGDXLDihUrgsuXL4dLAQAAABRDUYKWr776qitjn8/w8MMPh69Mr3379gUrV64Mjhw5ErS3twebN28Odu7cGRw8eDBcY2CI+/w16H8WpYBsy5Yt3QK10aNHu2DtwoULwa5du9zrtI6/LX+Iilsnbt8AAACAKVpJS1VVVdDS0hJ0dHS4QdNSW1vblabMf319vUtPO2XU6+rqguHDh7th9erV7j0sW7YsXKP/KWhQYNCf/P+FNDQ0uLQpU6aEKZ0UpI0ZMyZ49913gxdeeMH9r7TesWPHgpEjRwY1NTXB8uXL3br2WejzMa2trS4tyt+/Ar+4fQMAAAC+ogUtO3bsyJkZVeZf640aNSpMSafvv/8+uHr1ajBkyJAwpTT27NkTXLt2LZzrP/7/5S9/+Us4dYMClkWLFgXV1dXB6dOngyeeeML9r0T/KwUpX375pQtMT5486dLl2WefdWMFpvfdd5+bjmP7X7JkiRsDAAAA2RQtaJk4cWI4lVu2DG4aXL9+PZwqHQUOa9asCedKR9W+VKok+/fv7wpWovQ/U8DZF0nbBgAAAHxFCVp0J72Q0hOrYqUM89q1a4Nhw4a5eU2rzYNlolVdypYrXWPN+43ho9tQ43m1w9D6ajsTbTiv9hS23NprqI2GLVP61KlT3byCCM1r8PkN9OOOSdvRdm3/GmtdBSZxtH+VdIjtM9ruR+v4x6356HvrDZXuqFRJVb1y/Q9VAlPq0icAAABUnqKVtBRKGW41alfjdmWalQnXWFWQLHP/zDPPuOWqmqS2EMo0v/HGGy6jLdFt6HXnzp0L3n//fdd25ujRo13rigKcRx55xC3X9jRWmw2j4CuuDYYGo3288sorwe7du1269qNj0rGKqpZ9/vnn7phE6RYMHDp0yI2jVP0quk91AGAUIB04cMAdq5atWrXKBTdxQVmh7Djvv/9+N86lmG16AAAAACeT6S2JTCZcOf2O2traMCWelmu9TGbdzbe1tblBoq9vb2+P3aZto7m5OUzpFF23sbGxo6amJpzrpNfYvo0dezRd+88EVW65T9vU+q2trWFK57412LpaptcnSdqn5pVun4nJBEux6yeJHo9om3Hp+bJjjv4/4mg9AAAAIB+pKWmJUmmDqFTCSibUMPyBBx5w05KrTcTs2bPDqRtU2mJUtens2bPdqmnpNflWebLujqMdDug4xd+XZDLzXeuqTUhv2nSoNy/13BWtuvXiiy+68aZNm9y4N3799ddwCgAAAEiP1AYtcc6fPx9s3LjRTSvQUDWpvpg5c6YLANR+RFWr7Hkh+VZ5sl7F1K7EH9SAXX755Rc37i/aX1tbW2ywoyBGVel0PDz3BAAAADeTARW0iJ5bosbuJ06ccO1I+kKZf7UV0bNKVCqiBvdqJ5NvuxC1iVHQ09HR2c4lOvS1d62oXL2YFdJjWxy/xOjSpUvhFAAAAFBeAypoUQ9cL7/8smuIr4CgP7pKVuCi0huVYKjHLJWSRHvqSjJ06FBXvaw/eu0qxDfffBNOxbv99tvDqcLZAyIVFPaWSsQAAACA/jJgghZVB1PPVm+++WZRnuui6lXahzLtCkTyqWI1ffp0N7a2LVF+W5n+oJIQqwKmqmJRCp7Uniba3qUQ9oBIfdYqScrFuoeWe+65x40VAGYL5HTsKqECAAAA8pHaoCWa6b148WI4dUNfSziU4Y5m/i3Tng+1iZHly5e7ams+lQrdeeed4VynvhyvXqvhpZdecvPR/SnAULC1YcOGMKV3FBip22ZRAJftmPU8mgULFoRznaVW6mxAkgI5UeC5cOHCcA4AAADIoaNEMhlg182tugj2uwL2qcvd6upqt15St8N6vbolbmpq6rZNpWlQN8K2Db/LY+1TaRps/9qHvVb0Wm1TXRb7rDthbTfaTbGOw7ar5eruV9vUa4wdu4Z8uxK27oe1Tb3Gtqf96/i0TF02i9ZVmo49H/7xJHWR7L9nvUftw+jz0vuM+z9G/4f2Oh23Xqfj9D8bAAAAIJeiBy1+Btkfos/yiFsvuk5DQ4NLV1BgmW0LEpSBT9qG1o2mK02Dvd7SlaH2AxP/NTZEj0uZccuoa2zHJkn7zoe9VvvzAwQdn47Tjju6z2z84/AHfXZRStN+7L1pUNChfUWDN5+WaR0LrmzQ+1AABAAAABRikP5kMpQAAAAAkEoDrstjAAAAAJWFoAUAAABAqhG0AAAAAEg1ghYAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaAFAAAAKJGvvvoq2LVrVziXTmk8RoKWMnj44YeDQYMG9Ri2bNkSrtFJ87nWAQAAQOGUpxo9erTLXw0bNixYu3ZtcPny5XBpd0rXcq2n9VesWJG4bjb79u0LLl26FCxbtixMuUHb0zFpH/lScKFjsfeh+XxovQkTJrjX6LWHDx8Ol3SaMmVKMGnSpOCJJ57o1fssig6URWNjY4c+fg3V1dUdbW1t4ZLuWlpa3Do1NTVuGgAAAH1TX1/v8le1tbUuj2V5Mk23t7eHa3XSvNI1KL+m+bq6uth1s2lqanKvi9Pc3OyOxY4jHw0NDV3HrG0n5SWjtK5ep7yoWF5T6VFaR8eVBgQtZbR582Z3klRVVSWe9K2trVmXAwAAIH/KW1kAYpRxV37Lz8wby6/562taaQoc8qF9RrcRRzeytV4uCn60noKvQig/qfcZfZ3mlR53fApa9BmUG9XDymj16tVB5ksTXL16NfjnP/8Zpna3Zs2a4NNPPw2GDx8epgAAAKC3Tp06FRw5ciQYNWpUmNJZHWrHjh1u+pNPPnFjUdWoTZs2ufyav76mM5n54I033sir+pTyc5lAo9s24qiqVi6qDrZ///4gE2h0HXO+9uzZ4/Kdc+fODVM6Pfnkky5dy6MWL17sjv/ChQthSnkQtJSZTrpMZOtO+mh9QjWAeuCBB9wXKY6+JDpxrX6l6iZG6zLqBLM2NFpPdRP1GgAAgEqk9iRxN4PvvPNONx46dKgby+nTp11mvrq6Oky5YcaMGW58/PhxN06ivNnRo0eD6dOnhym9p7zizp073fEUGrDIgQMH3PiOO+5wY2N5TeVLoyZOnOjGcQFNKVVc0PL777+7hlQjRoxwGXkNijaPHTsWrlFairjffPNNN/3Xv/61K1pXsLF79+7g+eefd/NRWk/ByMiRI4MrV64Era2t7ks1derU4Pvvvw/XClxUry9VR0dHcPbs2eCPP/4oe6QMAACQVvPmzQunguDcuXNufP/997txnP/+97/hVLyPPvrIjceOHevGffHKK6+48YYNG9y4UMoLyn333efGUW1tbT1Kjqx0KC6gKaWKCloUsMyfP99F0BcvXnQZeQ1bt24NXnvtNRcklIMifhUxKuh45plnXJpKQ/71r38lVgtTtKtlqmImOvm2bdvmpi0IUvCik3PJkiVuXifd3r173TQAAABuUK9eqv0yc+bMMCUIvvjii3Aq2bfffhtOxTtz5owb33PPPW7cW5avM6o9YzfglW/MVU0t357Ffvzxx3DqBuVTFdD4N8ZLraKCFgUsjz76aLBq1aowpdPdd98dfPzxxy5wKVeJi4IJfVEUxeokzFYtTFS/8rHHHgvnOllRn0XCt9xyixuvX7/ejUWBTvR1AAAAlW7dunXBhx9+2O/tiC3Q6Ot21RZHlF+Ud955J2hvb3dtW1RlTDVwiu369evhVOlVTNCiOokq4osGLOa2224Lnnvuua7SilLTiWx1ExV0JFULE1XvUqnM8uXLuyJsDePHjw/X6FxHJSt2Iqthl/oGl7i+wQEAACqV2hHPmjUrmD17dpiSPteuXXNj5e10g1t5R8s/qo2LgiPL6xXLyZMnw6nSq5ig5cSJE8G4cePCuXiqYpVv0VkxWAMwyRaN//rrr27c3NzcVcUtOlj9Q53IjY2Nrt3LokWLXGP9chbtAQAApInyReox7PXXXw9TbrDG9tnks05/GjJkSDh1g92UV343SbYaPL581yu1imuIfzOwal9ff/21G+eikpWff/452Lx5s4vC1XsFjfEBAEClUzsQlbKomn7cDWN13CRWyuH75Zdf3NjWKba4YMVYI3/dpM7GekGLtn+xfGFcL2m+yZMnh1OlVzFBy7Rp07p6gEiiSDut0aVPJULW/iWu0VVc0aC+iGq0r1IXVS07ePBguAQAAKDyKA+ldr8qYUmq4WKN8uPaPFsDe7/hfhw940X6esPY9pOtc4Bc3SqrV1lRswnfTz/95Ma2PIndOC+HiglaHnzwQVc97K233gpTulPPYv/+97+DlStXhinpprqM6sVBja78L4ECr0OHDrlpVXXT3QMf7VkAAEClU8Dy1FNPBS+++GKPgEV5Kcs/aVlDQ4OrqeLntzStNC1LCniM2sqIVe/vLVX9Vy9eeuZLtKr/559/7m5oL1iwIEzpPMZoswf1KKv1PvvsszClk+aVbj3ORn3zzTdueVJXySXRUUF+++23jnvvvbcjc4K5aZP557v09957L0wpj82bN3foX6KhpaUlTI3X3t7ekYncu9bPnMRuPnNCdbS2trp1tA0ta2xsdOuL9qF1MgGPmwcAAKgkloeqrq52+Sd/sLyV5ZvE1tegaeWh/PlclC+z/Fg22q7yaFo3KR+o/Wkd7dvyctquXtPU1OTmjd5fXLrm/fSk1xvtU8uVfy6nigpaRMGKPvS77rrL/QM0zJkzxwUu5WLBRdyQjU6i+vr6rnXr6uq6AhbRdnVS20mrQV9Ifx0AAIBKoryR5YviBuWnovw8l4IG5SXzCViM8l9x2zVaHj0OpcVRsKJt2Xp6P3FBjo7Xv5nta25u7sofJr3eWJBT7hveg/QncyAAAAAAikDVufRoikzGv6uH14FCTRHUQ5o90Lxc6D0MAAAAKCK1BWlqanJtYAYSaxNT7oBFCFoAAACAIlMnSvPmzQtWrFgRpqSbSoe2b9/uuoNOA6qHAQAAACWi0otLly65ICatFLCcOnUqVb3OErQAAAAASDWqhwEAAABINYIWAAAAAKlG0AIAAAAg1QhaAAAAAKQaQQsAAABQRpcvXw62bNkSXLhwIUxJp7Vr15btGAlaSkzd3A0aNKhrGDZsWOI/Xyevv64GpQEAAKAwyoPp6e658lJab8KECS7fNXr06ODw4cPhkp4KWTeJApb169cHS5Ys6fa0fKXrmS7KK2r7Gmte6XH6eizaroIS21/cvjZu3Bjs2bMn2LdvX5hSQuryGKXV3t7e0djYqK6m3VBTU+PS4ii9rq4u6zoAAACI19bW1rF58+aOqqoql+/SdJKmpia3jvJp0tLS4uaVHlXIukmUt1Mer7W1NUy5QekadPyisaVF9fVY7Dhsf9nyn5qvrq52+yglgpYyamhocCeUhvr6+jC1J325sn3BAAAAkJ1l7JPyVMqMK7CJ5sk0r3QLHqSQdbNRYBCXB7RjjW7HgpHm5uYwpX+ORZ9JdH+aVpryq1E6Dm07GtAUE9XDymjIkCFB5mR10zt37gx27drlpgEAANC/7rzzznAqnqo9Xb16NZg7d26Y0unJJ5906VpuClk3iapz7d+/P/ap8xcvXgynurv99tvd+M8//3Rj6euxqArYpk2bgpqamm7V0zRdW1sbvPHGGz2qiU2ZMsVVI1O1tlIhaCmz+++/P8hE0256+fLlwffff++m86V6maq3aPUXNZ9U1xEAAADxDhw44MZ33HGHGxtl0EUBhilk3SQbNmwIqqqqgvvuuy9MuWHcuHFu3NDQ4Mbmm2++ca+ZOXNmmNL3Yzl9+rQLbqqrq8OUG2bMmOHGx48fd2PfrFmz3E33UuU7Ky5o+f33310joxEjRriMvgZFpseOHQvXKL0nnnii66ScPn163v98NbbSiapj7+joCFatWhWsWbPGNTIjcAEAAMjf2bNn3TguiJC2trau/FUh68ZRJ0xHjx4NJk6cGKZ0N3v2bFfyoYDD8nW6sb1u3brgyy+/DIYPHx6u2fdjOXfunBvrRnqS//73v+HUDSNHjnTjuICmGCoqaFHAMn/+/GDo0KGu2E0ZfQ1bt24NXnvttWD37t3hmqWn3hhUBKdIVydnLipR0Umqk9mK8lS8WF9f79LzKZYEAABAZ1WtfPz4448FrZvkp59+cuMHHnjAjeMcOXLEBS4KbsaMGRO8+eabrlTED07641i++OKLcCrZt99+G07dMHnyZDc+dOiQGxdbRQUtClgeffRRVyLhu/vuu4OPP/7YBS7lLHHZu3evK5pT0KFu5rJ59913e9Q9lBdffNGNVTcRAAAA6WOlG2rfnESlKVa1Sze1NV2qUo1C/PHHH+FUcVVM0KLIVCdINGAxt912W/Dcc88F27ZtC1NKTyengifVVVQdwaQ+sFU8qKI+v2jQKIjR63Vy5xt9AwAAIF2U31O7kdbW1qCxsdGlLVq0qDzPSMlCJUGlUDFBy4kTJ7oaNSVRcVu5M/o6hh07drhpnZhxDfOvX78eTsVLqh8JAACAnqzRei5ar5B1e0ttUNTOWY31lTdUE4Dm5mZ3Y1r5Q8uv9sexWGP7bPJZp9gqriH+QKCG+Zs3b3bTqtJ27do1Nx2lHiSysW7xAAAAkJ31nhVttK5G8+L3rlXIur1x8OBBV2tGeUKjxvkffvihm/7oo4/cWPp6LOqcSuLym7/88osb2zpx1Ca7FComaJk2bVpX/cEkKtXoS1Tcn1avXu2e4aJqYOof26djtCpgcSUxOml1gkbbuwAAACCePTtPTQp81mjelksh68ax2j8WFER98skn4VR31quYBSTS12Ox7pPj2nWfOXPGjf0ulqPUwVUpVEzQ8uCDD7oT5K233gpTulPPYv/+97+DlStXhinl984777gTM85LL73kxtEHUuokVkN+FScCAAAgP0uWLHE3hT/77LMwpZPmla7lppB14yhfKn7w4XvsscfcOK7Zgm5a+9W1Cj0WbdPfr9pI69Ebyj/66Zan1LK4dtQ//PCDG6saW0nosfiV4rfffuu49957OzIfvps2R48edenvvfdemFJ87e3tHZnIt6O6utpNJ2ltbe3InHAdmzdvDlM66TWZgKZD/8LGxkaX1tbW5tK0XQAAANyg/J/yTconJeW9mpqa3Doai/JY/ryvkHXj6DiUx4tj+Twtb2lpcWnK59XX17v06PHneyy2nvKfPtufbdvylHH7MvZ5Ji3vbxUVtIiCFX3Id911l/ugNcyZM8cFLqWiAMT2bUM0KPE1NzfHLtdJopNXJ7S2oRMw23YAAAAqjTL90XyXBgsGopTvUp5K6yjTnrSeFLJulB2XblDHiebzNNZ8UpCQz7HYzXBtJ8r2Z/tSfjlbQKJ9xW2nWAbpT+bgAAAAAJSQGtoPGzasq+fYgUJVzB555JHg559/jq06Vgz0HgYAAACUgdovq7F7XMdKaaa2059++mnJAhahpAUAAAAoE/X6+tRTT7nHXeiZLGm3du3a4N577+3WHXMpELQAAAAAZaTARc9mUdfCaX5khXqtnTRpUlmCK4IWAAAAAKlGmxYAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gZoC5cuOC6nNMDidLEPy49eCgN1COHersYPXp0sGXLljC1/2jbgwYNCg4fPhymlN6+ffuChx9+2A0AAGBgUB6iHPmlcu23LwhaUkaZ6lwnkXWLt3PnzuDq1athavkpYNFx7d+/P1XHtWfPnuCTTz4J2trawpSbiwKWEydOBEePHg1TykOBW9wQdz7rXFmxYoULJG29CRMmuPNf57f1/a55f1v+EBW3zkD7QQYApIuuV3HXF12r+ko3edV98JQpU8KUnrQf3Qgu9Kar3azVseqGZvThlcuWLQsuXbrkjmGgIGhJEZ2YmzZtck8ZzUZPH129enUwceLEMCUd1K+4jqumpiZMSQcd02OPPRbO9T998dVz+OzZs8OUG5J+ZAr98clGGXwdQyGUme/vDL0+g5aWlnAuCBoaGlxa9MdYP5DV1dXuQrBt2za3jobdu3cHv/zyS3Drrbe6wFf0v9Oyuro6Ny+tra0uLUpptn89oEvz2S4EAADk8vbbbwe1tbXdBl1j+vokeN24GzFiRM7nnTzzzDMF3wjWtl9++eXg/fffd9fCGTNmBNOnT+8RuCj/oBu6/ZknKarMm0FKNDU1KSfmhsxJFKYmy3xx3Lppk/kyu+PKZCDDlPLTseiYdGylon3qfxTV3t7eUVVVFc71H72/uP3F0XrF+v/oOJL+//X19W6Zxknse+C/3v5/+bw/rafPGACAvlBeLN/raiEaGxs7qqurw7lkzc3NHTU1Ne66lm/+xa6Xupb6tD9tK8ryJMXKE/QnSlpSZN26dV2lFIrsMXDpbsYjjzwSzt2g0jQV05az+pzuwJSjKpna/KhKo0pZduzYEab2pDs/maAmnOudvt4BAwBAebHFixeHc/1D+QCVgqxatSpMiaf1XnnlleDVV18NU/JjtXX0ZH3f0qVLg7Nnz/Zof6vrpa67/f0+i4GgJSV0EqnuoarIiNop6IQtlDXIVlGfMs7apupC+kWCWmb1HDVWvccovy6kBp3Qqs4TpWNUJlj7sHqT3333Xbi0sxqSbcMGvxhS05aeqxG5tqV2D7a+ppOqOEXf4+effx4uuUGfuX1Weh/WgYAGq+Np70/bUbo+X5+W22dlx6LtqhhWgYmCAztefX4PPvig+9EQS/ffg15r79GOI+48iK7nf6bZ6P0qcJCpU6e610dfG/3s7PPpK/34Sq4faim0uhsAAP1J12xdL5UHUB4oev3vLbWzVf5AbVmyUbUwBSyDBw8OU3LTtVr5jqqqqh437yZPnuzGn332mRv7pk2b5qqJKW+RamGJS8X47bffOhoaGjruuusuV3ymYc6cOR2Zf3K4Rnmo+NGK8jSt41LxYTa2nlExYl1dnUvTe9Ty6LZULUfrqDhQQ9y+NK00Ox6rrqN1fXq9iho1qAhV81b9R4MVNWqsosfofoyOVceUTWtrq3u9VSvSvLapQfv1aR2/qNPejwYrXo1+VprW+/SLYjUfl659G23b0qNFq0qLfmZin3mU9qNt2fZ1XFov+tnY/8M+S//zjdtfVLbqe9q/BqueaJ+d0qKfcxKtH92+/f+S9puLXqPX5vP+tB4AAH3hX99t8K+PvaVqWrmuU5ZHEbv+5VM9LNu10pbpPUTZMstjpVVFXd0VsDz00EMdW7ZsCVM6/fTTTy79vffeC1NKSxk6v26jZUpz1XeMy/zaiedn5pVm42gmX9O2vonbrn1xfRYcRDOz9oW0/YpllC2j7dO2/UAgTlxG2zL1fpp9dn6aWDDlf+m1jtK0f/896MciLt22Hf3hiDs2UVrcD0fc56v96LOMbsM+d/t89GMZdwx2bHH7i0o6XkuP/iDHfXbZaN3o9u34NPSG/a/yeX+93QcAAHF0DbO8TVy+J196nbaha3sSraN92T7s+pfPNdiu43HXStuOhjhK9/OCaVRR1cPmz58fPProoz2qp9x9993Bxx9/HLz22mvBsWPHwtTSUfUi/5hUDJk5YftUVPfSSy91FQ1aD0rbt28PZs2a1a3IUNOZk9QVVVo1JfUClvlCuWkTLWZUEaSKTXWs0WXaR9SSJUvcft56660wpZNVW8vVe4Z62NDrb7/99jAlCIYMGRJO3bB161b32UV7jVLRZ5KFCxd2ew9WFBtNv/POO8Op/qeuoiV63HovYm1QVKwsCxYscGPTHz3Jvfvuu+7/rv+/78UXX3Rj9WzXWxcvXgynAAAYWJTXOX36tGtvqfzS+vXrwyWF+fHHH904mm/yqVqYetbMtk6xlLO9bT4qJmjRyXbu3LnE+vS33XZb8Nxzz7kTpZRUZ1L1JKOZUDvO/jwetaVQV7Jqq+APdpKqv25RI+kzZ864aQUy+rJGG24fP37cjUeOHOnGvrg0ffkUSCkQ8+uFKmB7+umnw7lkOoYrV664DLU+M9UxjWaila73qHYYUcUMOPqDgjf9H6L/G+v6V10Bi81HA4vofKG0f/1v4n4kte1oYAsAQCXR9fH11193NxP7q31LlN2ojnuEQqmk+TpfMUGLHr43bty4cC6e7vaX+p+lO+zKDOrZFH5mdfny5W65ggW/EX1fKFPaED47I25QYGD0OSjzr14o/va3v7l+yX29uXNugZl6SROV1sQFbEkUlKghuUpyVHKiOx6+X3/9NZwaePTeVMoR93/RYL1t6X9YDNevXw+n4vW1JMcaAIreKwAAA40CF/XCVYwSCeWJVq5cGbzzzjthSuH8a22SaH5uIKH3sDLSCarSAmVE4zKqdmLF9e7VG7pbnk/1NwUS6llKAcuRI0f6LeLXHXsFGlbaotKauOplcRS4WdWl8+fPu9fFVQ8bqIYOHepKiXROlNM333wTTsXzq+cVQtXedP5Jrn1ko/89AADlkk9g0Buq/q38UfQmtvJjsmbNGjefrbdQu0bH5SWsNk2umhlpfihzxQQtujOv6mHZKGNcyn+WMu26g510AlmJhNqO9EdmViUUyhjHldzo7rdKVzRetGiRewK5X/ISZaVWBw4ccON8WfsItT3RMHfuXDefi9ojSbbne9xzzz1urNKpcmf+C6UuksXatkRZUbS1NervbgktqNDdo7jzQ5+nisRz/dhlo+qBYud1NjoP/eJ3+9/qBz3b/9aCWwAAiuGHH37o9bPE7FoWdwNOwdDmzZt7DLYv3cjWfLagSddoXQPjboL+97//deNs+S67uZhWFRO06PkYymhHG4Kb33//Pfj3v//tiuZKRZm3bBk4ZSQtA2YNsPN17dq1cOqGefPmubEyyH41OJ3YaiOiL1NSFavoya/PUye3vhh+5lLi9m30hVJApNcpg5xvKU5ctajoflRiY6VT0UZyf/75ZzjVU7bj7U9J1aKUbg+BUrXAaMma/jfWJkedA4ieeeL/T7Jl5HOx47KgIrp/Ldf/yx5Y1VvqjEHns/6Xek9J9F70QC8/aPb/t0mBnbz55ptdnxEAAP1J1yc9T89uwBZK1zK7DkYpz7d69eoew5NPPumWz5gxw837N9d1oy56o9EeRmltj43axGrfcfku20ZcR0qp0lFB1OXxvffe67rK1bTRM1qUXqouj9WNXSZydt3LRbud9Wm9zAnW1UWduuI11iWe0tUVn8lE4S5NyzJfijD1BtuvBm07kxHstg1tNxOMuDR1T2x9hfv7sm6L/W5stV+9F43tmPU6/5hNId33GTtOHb9er7HtR/9P25a6Brbj1/61ro7TXq/X2PFrbGnWtaAkpdtnq2356dqP0nVMPvvM9BnoGO3/Yf8DbU/HZp+9/3nqtdqP3ou/Xe3X3rfG2rYG26bW13b944uy/dj/xz47f9v2GemYlaZ182H/Ww22XZ+/D70/7d+OVWP7X8Udv47FPlNt2z5PravtaLvR/wEAAIWyZ4vpuqLrmqXp+pTrEQ25WB4j3+0k5Zl0DVS6BrseGl0LlR/QPnSN9Ofj6Bqq7WicZhUVtEgaHi6pk972rUHzcfx1/HX9jKGfHt2uBvuy+XTiW8ZeX8joSaqMoy3Xia4TXq/RvD47P0Op11pGUmPNa10dS7aTX9uPfsmy0RfN9qNta94+B83729Iy+yy0Hx2P1tXr9d50/EmfVSHpEk3TekbvX/u3z8XoWJVmx+aLfp7R5WI/QLZP+x/Z9vL5XO392GuNbVvbynYMcex4okPcOaj/gwIh248GHZPSs9Hx6Xgs8CnktQAA5Ev5HbvG6FoYzf/0ll2v7eZgLpbXiV6LtR1dCzXEHZfWt2usrrfZ8ga67us9pt0g/cm8IaBkVAypBmVq5A8AAFBJVA1bzRXS0LmMqryNGTMm+PTTT0varrs3CFpQcmrPoI4RsjX0BwAAuFkpL6RHbSxbtixMKQ/rjUztZdKOLo9REtbYWxG9HlxJwAIAACqVekNVzZNoZ0alpH2rM6KBELAIQQuKTsWg1dXV7mGV6nXMerYAAACoVPYYh3I8hV6PThg8eHCwcePGMCX9qB6GotMX469//WswbNiwYNu2bf32sEoAAABUBoIWAAAAAKlG9TAAAAAAqUbQAgAAACDVCFoAAAAApBpBCwAAAIBUI2gBAAAAkGoELQAAAABSjaAFAAAAQKoRtAAAAPz/27VjGwBhIAiC/v6LBgLHyBFsMBNdCysdkCZaAACANNECAACkiRYAACBNtAAAAGmiBQAASBMtAABAmmgBAADSRAsAAJAmWgAAgDTRAgAApIkWAAAgTbQAAABpogUAAEgTLQAAQJpoAQAA0kQLAACQJloAAIC0uR57v5qZvQAAAL5zHC0AAAB/cA8DAADSRAsAAJAmWgAAgDTRAgAAhK11A/EmN92tvqR+AAAAAElFTkSuQmCC\" style=\"width: 813px;\" width=\"813\" height=\"673\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Examples illustrating the decision related to the de-escalation process for patients with positive and negative culture\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"636\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eDecision\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eExample\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eIncorrectly de-escalated (De-escalation from broad to narrow spectrum despite negative culture result)\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eAn 88-year-old female was admitted to JUH. The patient received intravenous Levofloxacin before the results of the blood culture were available. Within 48 hours of admission, the culture result showed no bacterial growth. Subsequently, the patient\u0026apos;s treatment was de-escalated to Ceftriaxone sodium injection 1gm on the following day, coinciding with the availability of the culture results.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eIncorrectly de-escalated (\u003c/span\u003e\u003cspan dir=\"LTR\"\u003eTransition from multiple antibiotics to a single antibiotic\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\"\u003edespite negative culture result)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eAn 81-year-old male was admitted to JUH. The patient received intravenous levofloxacin and piperacillin/tazobactam injections before the results of the blood culture were available. After more than 72 hours of admission, the culture result showed no bacterial growth. Levofloxacin was discontinued, and the patient continued with piperacillin/tazobactam on the same day that the culture results became available\u003c/span\u003e\u003cspan dir=\"LTR\"\u003e.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eFailed de-escalation (Continued all antibiotics despite negative culture result)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp style=\"text-align: left;\"\u003eA 100-year-old male was admitted to JUH. The patient received intravenous levofloxacin, intravenous vancomycin, and intravenous imipenem before the culture results were available. After more than 72 hours of admission, both blood and sputum cultures showed no bacterial growth. The patient\u0026apos;s treatment was maintained with intravenous levofloxacin, intravenous vancomycin, and intravenous imipenem after the culture results became available.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eFailed de-escalation (Increased number of antibiotics despite negative culture result)\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eA 63-year-old female was admitted to JUH. The patient received intravenous levofloxacin before the results of the blood culture were available. Within 72 hours of admission, the blood culture showed no bacterial growth. The patient\u0026apos;s treatment regimen was adjusted, and she began receiving intravenous piperacillin/tazobactam injection in addition to levofloxacin on the same day as the culture results became available.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eSuccessfully de-escalated (Discontinuation of antibiotic for negative culture result)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp style=\"text-align: left;\"\u003eA 71-year-old male was admitted to JUH. The patient received intravenous levofloxacin, intravenous piperacillin/tazobactam, and oral amoxicillin/clavulanic Acid tablets before the results of the blood culture were available. After more than 72 hours of admission, the blood culture showed no bacterial growth. Consequently, the patient\u0026apos;s treatment was de-escalated, and all antibiotics were discontinued on the same day as the culture results became available.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eFailed de-escalation\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e(Continued the same antibiotics use despite suitability for narrower-spectrum antibiotics)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp style=\"text-align: left;\"\u003eA 60-year-old male was admitted to JUH. The patient received intravenous levofloxacin and pipracillin/tazobactam before the culture results were available. Within 48 hours of admission, the culture results showed the presence of \u003cem\u003eStaphylococcus hominis\u003c/em\u003e. Despite the suitability of narrower-spectrum antibiotics, the same antibiotics were continued for the patient.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eFailed de-escalated (increase the number of antibiotics used despite suitability for narrower-spectrum antibiotics)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp style=\"text-align: left;\"\u003eA 76-year-old female was admitted to JUH. The patient received intravenous levofloxacin, vancomycin, and meropenem before the availability of culture results. After more than 72 hours of admission, a culture result was received, revealing the presence of \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e. Despite\u0026nbsp;suitability of\u0026nbsp;narrower antibiotics, gentamycin was initiated in addition to the ongoing antibiotics levofloxacin, vancomycin, and meropenem.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eIncorrectly de-escalated\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e(Stopping antibiotics instead of converting to a narrow spectrum in culture result)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eA 55-year-old female was admitted to JUH. The patient received intravenous levofloxacin in addition to imipenem/cilastatin before the results of the culture were available. After more than 72 hours of admission, the culture result showed the presence of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e. Subsequently, the patient\u0026apos;s treatment was discontinued, and all antibiotics were stopped, leaving the patient untreated.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eSuccessfully de-escalated (Transitioned to narrower spectrum antibiotics for positive culture results)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eAn 88-year-old male was admitted to JUH. The patient received intravenous levofloxacin and imipenem/cilastatin before the culture results were available. After more than 72 hours of admission, the culture results showed the presence of \u003cem\u003eEscherichia coli\u003c/em\u003e. Subsequently, the patient\u0026apos;s treatment was transitioned from the broad-spectrum levofloxacin to the narrower-spectrum vancomycin in addition to imipenem/cilastatin.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.9623%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eSuccessfully de-escalated\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e(Transition from multiple antibiotics to a single antibiotic for positive culture results)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66.0377%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eA 65-year-old female was admitted to JUH. The patient received intravenous levofloxacin, meropenem, gentamycin, and ceftazidime/avibactam. Within 72 hours of admission, the culture result showed the presence of \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e. Levofloxacin was discontinued, and the patient\u0026apos;s treatment was continued with intravenous meropenem, gentamycin, and ceftazidime/avibactam without levofloxacin.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eAssessing the association between de-escalation and length of stay and mortality\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"615\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 49.7561%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eOutcome\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.6098%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eSuccessfully de-escalated\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e(n= 41)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.439%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eFailed/ inappropriate de-escalated\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e(n= 81)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1951%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eP-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 49.7561%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eLength of hospital stay (days), Median (IQR)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.6098%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e12 (8.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.439%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e18 (11.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1951%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e0.004*^\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 49.7561%;\"\u003e\n \u003cp style=\"text-align: left;\"\u003eMortality upon discharge, n (%)\u003c/p\u003e\n \u003col\u003e\n \u003cli style=\"text-align: left;\"\u003eSurvived\u003c/li\u003e\n \u003cli style=\"text-align: left;\"\u003eDied\u003c/li\u003e\n \u003c/ol\u003e\n \u003cp style=\"text-align: left;\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.6098%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e29 (70.1%)\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e12 (29.9)%\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.439%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e62 (76.5%)\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e19 (23.5%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1951%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e0.514#\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"text-align: left;\"\u003e*Significant at 0.05 significance level. ^ Using Mann Whitney U test. # Using Fisher Exact test\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAssessing the association between cultural results and de-escalation practice\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"615\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45.8537%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eMicrobial culture result\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5122%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003ePositive culture result\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e(n= 26)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.439%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eNegative culture result\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e(n= 96)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1951%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eP-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45.8537%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eSuccessfully de-escalated\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003eFailed/ inappropriate de-escalated\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5122%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e16 (61.5)\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e10 (38.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.439%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e25 (26.0)\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e71 (74.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1951%;\"\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u003cspan dir=\"LTR\"\u003e0.002*#\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style=\"text-align: left;\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"text-align: left;\"\u003e*Significant at 0.05 significance level. # Using Chi-square test\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Community-acquired pneumonia, Fluoroquinolone de-escalation, Antimicrobial resistance, Hospital length of stay, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-5784150/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5784150/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThis study aimed to evaluate the effectiveness of fluoroquinolone de-escalation in adult patients with community-acquired pneumonia (CAP), examining its impact on hospital length of stay (LOS), mortality, and association with microbial culture results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA retrospective cohort study was conducted on adult patients diagnosed with CAP at a tertiary hospital in Jordan. The study analyzed fluoroquinolone de-escalation outcomes, including hospital LOS and mortality, as well as the relationship between microbial culture results and de-escalation success.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe study sample consisted of 125 patients, with a median age of 73 years (IQR = 24). Of these, 64.8% (n=81) were male, and 35.2% (n=44) were female. Fluoroquinolone therapy was predominantly levofloxacin (99.2%, n=124). Fluoroquinolone de-escalation was successfully achieved in 33.6% (n=42) of patients. Positive culture results significantly increased de-escalation success, as 61.5% (n=16) of patients with positive cultures successfully de-escalating compared to 26.0% (n=25) of those with negative cultures (p = 0.002). Among patients with negative cultures (n=96), 43.8% (n=42) underwent inappropriate de-escalation, and 30.2% (n=29) had failed de-escalation. Patients in the successfully de-escalated group had a significantly shorter median hospital stay of 12 days (IQR = 8) compared to 18 days (IQR = 11) in the failed/inappropriate group (p = 0.004). There was no significant difference in mortality between the two groups, with 70.1% (n=29) surviving in the successfully de-escalated group versus 76.5% (n=62) in the other group (p = 0.514).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eFluoroquinolone de-escalation in CAP patients is linked to shorter hospital stays without affecting mortality. Positive culture results significantly increase de-escalation success, supporting the need for improved de-escalation protocols.\u003c/p\u003e","manuscriptTitle":"Effectiveness of Fluoroquinolone De-escalation in Community-Acquired Pneumonia: Impact on Hospital Stay and Mortality","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-13 13:08:19","doi":"10.21203/rs.3.rs-5784150/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"38684acc-d26c-4749-a1e7-a98256a77684","owner":[],"postedDate":"January 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-22T20:08:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-13 13:08:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5784150","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5784150","identity":"rs-5784150","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}