Clinical Experience with Ceftazidime/Avibactam for the Treatment of Extensively Drug-Resistant or Pandrug-Resistant Klebsiella  pneumoniae in Neonates and Children

Clinical Experience with Ceftazidime/Avibactam for the Treatment of Extensively Drug-Resistant or Pandrug-Resistant Klebsiella pneumoniae in Neonates and Children | 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 Clinical Experience with Ceftazidime/Avibactam for the Treatment of Extensively Drug-Resistant or Pandrug-Resistant Klebsiella pneumoniae in Neonates and Children Ozlem Ozgur Gundeslioglu, Zeliha Haytoglu, Hatice Hale Gumuş, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4605917/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Oct, 2024 Read the published version in European Journal of Clinical Microbiology & Infectious Diseases → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose: Klebsiella pneumoniae is a significant cause of healthcare-associated infections, resulting in high morbidity and mortality rates due to limited treatment options. In this study, we aimed to evaluate the treatment outcomes and the safety of Ceftazidime-avibactam in infections caused by extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae in pediatric patients. Methods: This study included pediatric patients who received ceftazidime-avibactam treatment due to extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae infections, monitored in the pediatric intensive care, neonatal intensive care, and pediatric wards of Cukurova University Faculty of Medicine between 2022 and 2023. Patients' microbiological responses, clinical responses, medication side effects, and 30-day survival rates were evaluated. Results: Eleven pediatric patients were included in the study, of whom nine were male (81.8%). The median age of the patients was 15 months (min: 1 day - max: 183 months). Sepsis was diagnosed in 9 patients (81.8%). Two premature infants (27 and 35 weeks) were admitted to the neonatal ICU. Regarding the Klebsiella pneumoniae strains, 10 (91%) were extensively drug-resistant (XDR), and 1 (9%) was pandrug-resistant (PDR). Eight strains (72.7%) were carbapenem-resistant, and 9 (81.8%) were colistin-resistant. Microbiological response was noted in 8 patients (72.7%), clinical response was evident in 6 patients (54.5%). The 30-day survival rate was 54.5%, with six patients surviving. Conclusion: In our study, ceftazidime-avibactam has been identified as a significant treatment option for resistant Klebsiella pneumoniae infection in critically ill children and premature infants with sepsis and organ failure, and it has been found to be well tolerated. Ceftazidim-avibactam Children Carbapenem resistant Klebsiella pneumoniae Extensively drug-resistant Klebsiella pneumoniae Pandrug resistant Klebsiella pneumoniae Introduction The increase in antimicrobial resistance (AMR) continues to be a global health issue. In 2019, the number of deaths associated with AMR was reported as 1.2 million, and if sufficient measures are not taken, it is estimated that there will be 10 million deaths per year by 2050 [ 1 ]. The World Health Organization has defined extended-spectrum beta-lactamase (ESBL) positive and carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii , and carbapenem-resistant Pseudomonas aeruginosa as priority pathogens for new antibiotic research and development [ 2 ]. Healthcare-associated infections caused by Klebsiella pneumoniae ( K. pneumoniae ) account for one-third of gram-negative infections and are globally associated with carbapenem resistance [ 3 , 4 ]. In K. pneumoniae , carbapenem resistance primarily relies on the production of carbapenemases and the plasmid-mediated transfer of genes encoding these enzymes. These carbapenemases vary geographically. In pediatric patients with carbapenem-resistant K. pneumoniae infections, colistin is the most commonly used and defined as the last resort antibiotic. In recent years, the limited treatment options for gram-negative infections caused by pandrug-resistant strains resistant to colistin are concerning in children [ 5 ]. Ceftazidime-avibactam, a recently developed beta-lactam-beta-lactamase inhibitor, holds promise for treating resistant K. pneumoniae infections in children. First-generation beta-lactamase inhibitors (such as clavulanic acid, tazobactam, and sulbactam) exhibit low activity against many classes of beta-lactamase enzymes and are ineffective against multi-drug-resistant pathogens. Ceftazidime-avibactam possesses broad carbapenemase activity and demonstrates activity against Ambler class A, C, and certain class D enzymes. The combination ceftazidime-avibactam (CAZavi) was approved in the USA in 2015 and in Europe in 2016. In March 2019, FDA granted approval for use in children ≥ 3 months old. Data regarding the clinical use of CAZavi in children is still limited [ 6 – 9 ]. In our study, we aimed to assess the treatment outcomes and safety profile of CAZavi in pediatric patients with infections resulting from extensively drug-resistant or pandrug-resistant K. pneumoniae. Methods Study Design, Setting, Definitions This study included pediatric patients who received ceftazidime-avibactam treatment due to infections caused by extensively drug-resistant or pandrug-resistant K. pneumoniae monitored in the pediatric intensive care unit, neonatal intensive care unit, and pediatric wards at Çukurova University Faculty of Medicine between 2022 and 2023. From the medical records of the patients, information including age, gender, presence of underlying diseases, history of previous hospitalizations and antibiotic use, application of mechanical ventilation, central venous catheterization, urinary catheterization, characteristics and site of infection, culture results, antibiogram results, antibiotics administered, and patient prognosis were recorded. The definitions of Multi-Drug Resistance (MDR), eXtensive Drug Resistance (XDR), and Pan Drug Resistance (PDR) strains for Enterobacteriaceae were made according to the terminology recommended by the Centers for Disease Control and Prevention (CDC) and the European Centre for Disease Prevention and Control (ECDC) [10]. MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories). PDR was defined as non-susceptibility to all agents in all antimicrobial categories. Difficult-to-Treat Resistance (DTR) was defined as resistance to all of the typical first-line, lower toxicity agents as the beta-lactams (including carbapenems and beta-lactamase inhibitor combinations) and the fluoroquinolones [10,11]. The absence of growth in repeated cultures of the site of infection 48 hours after the initiation of ceftazidime-avibactam was considered a microbiological response. The clinical response was defined as the improvement/disappearance of major signs and symptoms. The lack of improvement, worsening of symptoms, or death while on antibiotic treatment was considered treatment failure. We utilized the Pediatric Organ Dysfunction Information Update Mandate (PODIUM), a scoring system introduced in 2022, to quantify organ dysfunction. This system provides detailed criteria and assessments for various organ systems, including the neurological, respiratory, cardiovascular, gastrointestinal, hepatic, renal, hematological, coagulation, endocrine, and immune systems [12]. By applying these criteria, we aimed to identify and categorize the number and types of organ failures present in our study cohort. Ethical approval for the study was obtained from the Cukurova University Faculty of Medicine Ethics Committee (05.04.2024-143/20). Microbiology Identification and antimicrobial susceptibility testing procedures were conducted as follows: Strains of K. pneumoniae were isolated from various specimens, including blood, catheter blood, urine, tracheal aspirate, and peritoneal fluid, using standard microbiology laboratory protocols. Identification was performed utilizing the VITEK 2 compact system (bioMerieux, Marcy-l’Étoile, France). Antimicrobial susceptibility testing was carried out using the VITEK 2 AST-N325 card (bioMerieux, Marcy-l’Étoile, France), the Kirby-Bauer disk diffusion susceptibility test for CAZavi (Oxoid, United Kingdom), and the gradient diffusion method for colistin (E-Test, Liofilchem, Italy) (Table 2). The antibiotics tested with the AST-N325 card included ampicillin/sulbactam, amoxicillin/clavulanate, piperacillin/tazobactam, cefazolin, cefoxitin, ceftazidime, ceftriaxone, cefepime, ertapenem, meropenem, gentamicin, amikacin, ciprofloxacin, colistin, tigecycline, and trimethoprim-sulfamethoxazole. Clinical breakpoint interpretation was based on guidelines provided by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) [13]. Statistical Analysis Statistical analysis was performed using IBM SPSS Statistics software version 23. Descriptive statistics were calculated for demographic and clinical characteristics, including measures mean, median, standard deviation, and range for continuous variables, while frequencies and percentages were reported for categorical variables. Results In this study, a total of 11 pediatric patients who underwent CAZavi therapy between 2022 and 2023 were enrolled. Of these, 9 were male (81.8%). The median age upon hospital admission was 15 months (range: 1 day - 183 months). Seven patients (63.6%) were younger than 2 years old, with 4 patients (36.3%) being under 3 months old. The youngest patient to receive CAZavi was admitted to the neonatal intensive care unit at 27 weeks gestation, weighing 640 grams due to prematurity, and commenced CAZavi treatment for sepsis and necrotizing enterocolitis (NEC) at 14 days of age. Eight patients (72.7%), including 3 in the neonatal intensive care unit, were admitted to the intensive care unit for monitoring. Sepsis was diagnosed in 9 patients (81.8%). Organ failure was present in 9 patients (81.8%), with only two (18.2%) showing no signs of organ failure. The demographic and clinical characteristics of the patients are detailed in Table 1 . The indications for CAZavi administration and the occurrence of organ failures among the patients are provided in Table 2 . K. pneumoniae was detected in blood cultures of 5 patients (45.5%), in urine cultures of 4 patients (36.4%), in tracheal aspirate cultures of 5 patients (45.5%), in catheter cultures of 3 patients (27.3%), and in peritoneal fluid cultures of 1 patient (9.1%). Among the K. pneumoniae strains obtained from patient cultures, 10 (91%) were XDR, and 1 (9%) was PDR. Eight (72.7%) of the K. pneumoniae strains were carbapenem-resistant, with only 3 (27.2%) being carbapenem-sensitive. Isolates obtained from 9 patients (81.8%) showed resistance to colistin. In one patient with pan-drug resistant strains, resistance to CAZavi was present. The antibiotic susceptibilities of K. pneumoniae isolates were presented in Table 2. Patients received a median of 14 days (min: 5 - max: 22 days) of CAZavi. In infants <3 months old, the dose of ceftazidime was 30 mg/kg/dose every 8 hours, in infants aged ≥3-6 months, the dose was 40 mg/kg/dose every 8 hours, and in children and adolescents aged ≥6 months to 18 years, the dose was 50 mg/kg/dose every 8 hours (maximum: 2 grams/dose). Ceftazidime-avibactam was administered post-hemodialysis in patients undergoing hemodialysis, and doses were adjusted based on estimated glomerular filtration rate (GFR). Two patients received CAZavi as monotherapy. One of the patients receiving monotherapy (Table 2, Patient 3) was initially treated for a urinary tract infection and was transferred to another hospital on the 5th day of treatment to continue antibiotic therapy. The other patient who received monotherapy was a 27-week premature infant (640 grams) diagnosed with sepsis and NEC at 14 days of age, receiving 12 days of CAZavi therapy. Both patients who received monotherapy showed clinical and microbiological responses. In 9 patients, at least two antibiotics (81.9%) were administered as combination therapy. Meropenem and CAZavi were administered together to 8 patients (72.7%). It was observed that there were no adverse effects during the use of CAZavi in patients, and treatment was not discontinued due to adverse effects. Microbiological response was observed in 8 patients (72.7%), and clinical response was observed in 6 patients (54.5%). Treatment failure was detected in 5 patients (36.4%). Among the 5 patients with treatment failure, 4 patients died. One patient was transferred to another hospital, and the outcome of this patient's treatment could not be determined. The 30-day survival rate was 54.5%. The clinical, diagnostic, treatment characteristics, and treatment outcomes of the patients are presented in Table 3 . Discussion Carbapenem-resistant and pan-drug resistant Enterobacteriaceae, particularly carbapenem-resistant Klebsiella pneumoniae, are widely reported worldwide. Globally, rates of CRE vary significantly, with the highest rates reported in countries such as Russia, the Eastern Mediterranean region, India, and Southeast Asia [14,15]. In our study, among the K. pneumoniae strains isolated from cultures of pediatric patients treated with CAZavi, 10 (91%) were XDR, and 1 (9%) was PDR. Eight (72.7%) of the K. pneumoniae strains were carbapenem-resistant, with only 3 (27.3%) being carbapenem-sensitive. In previous studies and case series, CRE infections have been reported more frequently in patients with underlying diseases, those undergoing intensive care, and those undergoing invasive procedures and broad-spectrum antibiotic therapy. Factors such as prior colonization or infection with resistant pathogens, trauma, recent surgical procedures, mechanical ventilation, urinary catheterization, and the presence of venous catheters are other risk factors associated with the development of colonization or infection with resistant gram-negative pathogens [16- 19]. In our study, 8 patients (72.7 %), including 3 (27.3%) in the neonatal intensive care unit, were admitted to intensive care. Sepsis was present in 9 patients (81.8%). Underlying diseases were present in 10 patients (91%). A history of broad-spectrum antibiotic use within the past 3 months was reported in 10 patients (91%). Eight patients (72.7%) had received carbapenems in the last 3 months. Central venous catheters were placed in 8 patients (72.7%) as invasive procedures, urinary catheters in 10 patients (91%), hemodialysis in 3 patients (27.3%), and mechanical ventilation in 9 patients (81.8%). Resistance genes in carbapenem-resistant Klebsiella and Enterobacter strains spread rapidly among strains. Conducting regular surveillance studies and implementing infection prevention measures in clinics where patients at risk for infection with resistant pathogens are admitted are extremely important in preventing the spread of infection [20]. In pediatric patients, colistin is used as a last resort drug for the treatment of carbapenem-resistant K. pneumoniae infections. Colistin resistance in K. pneumoniae is a growing concern, with studies reporting varying levels of resistance. Previous studies have reported colistin resistance rates ranging from 2.8% to 36.1% in carbapenem-resistant K. İsolates [21-23]. In our study, colistin susceptibility testing revealed colistin sensitivity in only 2 patients (18.2%), while colistin resistance was detected in 9 patients (81.8%). Both the EUCAST and the American Clinical and Laboratory Standards Institute (CLSI) recommend broth microdilution testing for evaluating colistin susceptibility [24,25]. However, in our study, broth microdilution testing could not be performed for colistin susceptibility assessment, and instead, E-test and VITEK-2 methods were utilized. Therefore, we cannot provide a definitive interpretation regarding colistin resistance based on our data. In recent years, newly developed β-lactam-β-lactamase inhibitors (βL-βLI) (such as ceftazidime-avibactam, meropenem-vaborbactam, and imipenem/silastatin-relebactam) have shown promise in the treatment of gram-negative resistant infections. However, clear recommendations for the treatment of children with MDR, XDR, or pandrug-resistant K. pneumoniae are lacking [26,27]. Avibactam is a novel broad-spectrum beta-lactamase inhibitor without antibacterial activity. Addition of avibactam to ceftazidime expands its antibacterial activity and spectrum. Ceftazidime-avibactam exhibits activity against most Enterobacteriaceae, including those producing AmpC beta-lactamase, ESBL, and some K. pneumoniae and OXA-type carbapenemases. Ceftazidime-avibactam received approval for use in children in 2019. However, studies regarding its use in the treatment of resistant gram-negative infections in children are limited. Lower mortality rates have been reported with the use of ceftazidime-avibactam in adults; however, these studies involve small patient cohorts [28- 32]. In a randomized, controlled, double-blind phase 2 study involving 95 pediatric patients aged ≥3 months to <18 years with urinary tract infections, CAZavi was reported to be effective and safe against gram-negative pathogens [33]. In a phase 2 randomized controlled double-blind study involving 83 pediatric patients aged ≥3 months to <18 years with intra-abdominal infections caused by pan-drug resistant strains, one group received meropenem while the other group received CAZavi in combination with metronidazole. The efficacy of CAZavi combined with metronidazole against gram-negative pathogens was found to be comparable to meropenem, with similar side effects observed [34]. In a case series evaluating newborns and children under 5 years of age who received ceftazidime-avibactam treatment for bloodstream infections, central nervous system infections, and urinary tract infections caused by carbapenem-resistant K. pneumoniae, all patients achieved clinical and microbiological response, and no adverse effects necessitating treatment discontinuation were reported. However, these patients were also receiving treatment with at least two other antibiotics in addition to CAZavi [4]. In a recent retrospective study evaluating 38 pediatric patients, including 20 (52.6%) with hematologic malignancies, who had carbapenem-resistant pathogens, 25 patients received targeted CAZavi treatment, and 13 received empirical treatment. The clinical response rate was reported as 84% (21/25), and the 30-day mortality rate was 20% (5/25). Among these patients, 21 received combination antibiotic therapy. One patient developed diarrhea, and no other adverse effects were reported [35]. In our study, we evaluated 11 critically ill patients who received CAZavi treatment, including 3 admitted in the neonatal intensive care unit and 8 (72.7%) in the intensive care unit. Sepsis was diagnosed in 9 patients, and organ failure was present in 9 patients (81.8%). We observed a clinical response in 6 patients (54.5%) and a microbiological response in 8 patients (72.7%), with a 30-day survival rate of 54.5%. Similar to case series presented in the literature, 9 patients (81.8%) in our study received combination therapy, while only 2 patients received ceftazidime-avibactam as monotherapy. One of the patients who received monotherapy was a 27-week-old (640 grams) premature infant diagnosed with sepsis/NEC at 14 days of age. This patient showed clinical and microbiological responses and survived for 30 days. In our study, no adverse effects were observed during the use of CAZavi. The most commonly reported side effects in the literature are gastrointestinal adverse effects such as nausea, vomiting, and diarrhea [33-35]. In our study, 4 cases (36.3%) were under 3 months of age, with 3 of these being neonatal cases. Among them, two premature babies, one born at 27 weeks gestation and the other at 35 weeks gestation, received CAZavi due to sepsis. The 640-gram, 27-week premature baby received CAZavi as monotherapy and achieved both clinical and microbiological response. There are few case reports in the literature demonstrating the successful use of CAZavi in rescuing therapy for resistant gram-negative infections in premature infants [36,37]. In this study, the limitation lies in the small number of patients and the retrospective nature of the study. Additionally, in our study, the broth microdilution test could not be used to evaluate antibiotic susceptibility for colistin, hence colistin resistance could not be definitively determined. In our study, sepsis was diagnosed in 81.8% of patients, with organ failure present in all patients except for two. In our study, which predominantly comprised children under the age of 2 (63.6%), including premature infants, CAZavi emerged as a significant treatment option for resistant K. pneumoniae infections in pediatric and premature patients, demonstrating good tolerability. Abbreviations ICU: Intensive Care Unit MDR: Multi-Drug Resistance XDR: Extensively Drug-Resistant PDR: Pan Drug-Resistant AMR: Antimicrobial Resistance ESBL: Extended-Spectrum Beta-Lactamase CRE: Carbapenem-Resistant Enterobacteriaceae CAZavi: Ceftazidime-Avibactam USA: The United States of America FDA: Food and Drug Administration CDC: Centers for Disease Control and Prevention ECDC: European Centre for Disease Prevention and Control DTR: Difficult-to-Treat Resistance PODIUM: Pediatric Organ Dysfunction Information Update Mandate EUCAST: European Committee on Antimicrobial Susceptibility Testing NEC: Necrotizing Enterocolitis Declarations Funding: None Data availability : All data relevant to the study are included in the article and are available from the corresponding author upon request Author contributions: Dr Ozlem Ozgur Gundeslioğlu, Dr.Zeliha Haytoglu, Dr. Hatice Hale Gumus, Dr. Faruk Ekinci conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Ozlem Ozgur Gundeslioglu, Dr. Ozden Ozgur Horoz, Dr. Filiz Kibar, Dr. Hatice Hale Gumus, Dr. Ummuhan Cay, designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Dr.Ozlem Ozgur Gundeslioglu, Dr. Derya Alabaz, Dr. Ummuhan Cay, conceptualized and Ferda Ozlu, Dr. Rıza Yıldızdas, Dr. Ozden Ozgur Horoz designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Ethical considerations Ethical approval for the study was obtained from the Cukurova University Faculty of Medicine Ethics Committee (05.04.2024-143/20). This study was conducted in compliance with the principles of the Declaration of Helsinki, Good Clinical Practice guidelines and local regulatory requirements. 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Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections. Open Forum Infect Dis. 2019 ;6(12):ofz522. Tumbarello M, Trecarichi EM, Corona A, De Rosa FG, Bassetti M, Mussini C, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis. 2019 ;68(3):355-364. Tsolaki V, Mantzarlis K, Mpakalis A, Malli E, Tsimpoukas F, Tsirogianni A, et al. Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients. Antimicrob Agents Chemother. 2020 ;64(3):e02320-19. Bradley JS, Roilides E, Broadhurst H, Cheng K, Huang LM, MasCasullo V, et al. Safety and Efficacy of Ceftazidime-Avibactam in the Treatment of Children ≥3 Months to <18 Years With Complicated Urinary Tract Infection: Results from a Phase 2 Randomized, Controlled Trial. Pediatr Infect Dis J. 2019 ;38(9):920-928. Bradley JS, Broadhurst H, Cheng K, Mendez M, Newell P, Prchlik M, et al. Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial. Pediatr Infect Dis J. 2019;38(8):816-824. Meng H, Zhao Y, An Q, Zhu B, Cao Z, Lu J. Use of Ceftazidime-Avibactam for Suspected or Confirmed Carbapenem-Resistant Organisms in Children: A Retrospective Study. Infect Drug Resist. 2023 ;16:5815-5824. Coskun Y, Atici S. Successful Treatment of Pandrug-resistant Klebsiella pneumoniae Infection With Ceftazidime-avibactam in a Preterm Infant: A Case Report. Pediatr Infect Dis J. 2020 ;39(9):854-856. Asfour SS, Alaklobi FA, Abdelrahim A, Taha MY, Asfour RS, Khalil TM, et al. Intravenous Ceftazidime-Avibactam in Extremely Premature Neonates With Carbapenem-Resistant Enterobacteriaceae: Two Case Reports. J Pediatr Pharmacol Ther. 2022;27(2):192-197. Tables Table 1. Demographic and Clinical Characteristics of the Patients Characteristics Age (months), median (min-max) 15 (min:2 days max:183 months) Gender, n (%) Male Female 9 (81.8) 2 (18.2) Presence of underlying disease, n (%) 10 (91) History of Hospitalization, n (%) 8 (72.7) History of Intensive Care Unit Admission, n (%) 5 (45.5) Antibiotic Use in the Last 3 Months, n (%) Carbapenem use Colistin use Glycopeptide use 10 (91) 8 (72.7) 4 (36.3) 9 (81.8) Presence of Invasive Procedures, n (%) Central venous catheter Urinary catheter Dialysis application Mechanical ventilation 8 (72.7) 10 (91) 3 (27.3) 9 (81.8) Table 2. Diagnoses, Treatment Characteristics, and Treatment Outcomes of Patients Patient Age month Diagnosis (Diagnosis for Ceftazidime-avibactam Administration) Underlying Disease Organ Dsyfunction Cr-Cl Treatment Ceftazidim Avibactam administration duration Clinic Response Microbiological Response 30-day survival 1 183 Sepsis, Intraabdominal infection, Pneumonia None Respiratory, Hematological, Immune system 206 Combined 14 Yes Yes Yes 2 59 *CRBI Sepsis Pneumonia İntracranial mass Cardiovascular, Neurological, Hematological 153 Combined 22 no Yes No 3 14 **UTI Nephrolithiasis None 108 Mono therapy 5 Yes Yes Yes 4 15 ***VIP, Sepsis, *CRBI ****HİE, Epilepsy, Laryngomalacia Cardiovascular, Neurological, Hematological Endocrin 106 Combined 22 No No No 5 44 gün ***VIP *****CHD Syndromic Infant Neurological 79 Combined 11 No No No 6 14 gün Sepsis, ******NEC Prematurity (27 weeks) Trisomy, *******DMI Respiratory, Gastrointestinal, Hematological 39 Mono theraphy 12 Yes Yes Yes 7 37 gün Sepsis *****CHD Prematurity (35 weeks) Cardiovascular, Neurological Renal, Hematological, Respiratory 16 Combined 14 No No No 8 15 **UTI Sepsis HİE, Epilepsy Laryngomalacia Immunological Respiratory 322 Combined 14 Yes Yes Yes 9 65 Sepsis ********ALL Tuberculosis Gastrointestinal, Hematological, Immunological Respiratory 168 Combined 6 No Yes No 10 127 Sepsis *CRBI *********SMA Immunological 283 Combined 14 Yes Yes Yes 11 2 **UTI Sepsis Posterior Üretral valv, Hydronephrosis None 60 Combined 10 Yes Yes Yes *CRBI: Catheter-related bloodstream infection, ** UTI: Urinary tract infection, *** VAP: Ventilator-associated pneumonia, **** HIE: Hypoxic ischemic encephalopathy, ***** CHD: Congenital heart disease, ****** NEC: Necrotizing enterocolitis, ******* IDM:Infant of diabetic mother, ******** ALL:Acute lymphoblastic leukemia, *********SMA: Spinal muscular atrophy Table 3. Antimicrobial susceptibility of Klebsiella pneumoniae isolates Patient Department Specimen Antimicrobial Susceptibility Test (VITEK 2) CST (VITEK 2/E-test) CAZavi (VITEK 2/Disc Diffusion Test) AMR Profile 1 ICU Peritoneal fluid R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT S (≤0.5 μg/mL) S (20mm) XDR 2 ICU Blood, Tracheal aspirate Catheter blood R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, CIP, TGC, CST, SXT R (≥16 μg/mL) S (17mm) XDR 3 Non-ICU Urine R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT R (≥16 μg/mL) R (12 mm) PDR 4 ICU Blood, Catheter blood, Tracheal aspirate R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT R (≥8 μg/mL) S (≤0.5 μg/mL) XDR 5 ICU Tracheal aspirate R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, AMK, GEN, CIP, TGC, CST, SXT R (≥8 μg/mL) S (≤0.5 μg/mL) XDR 6 ICU Blood R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT R (≥8 μg/mL) S (≤0.5 μg/mL) XDR 7 ICU Tracheal aspirate R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT R (≥16 μg/mL) S (≤0.5 μg/mL) XDR 8 ICU Urine R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT R (≥8 μg/mL) S (≤0.5 μg/mL) XDR 9 Non-ICU Blood, Urine R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT S (2 μg/mL) S (8 μg/mL) XDR 10 ICU Catheter Blood Tracheal aspirate R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, AMK, GEN, CIP, TGC, CST, SXT R (≥8 μg/mL) S (15 mm) XDR 11 Non-ICU Blood, Urine R to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, AMK, GEN, CIP, TGC, CST, SXT R (≥8 μg/mL) S (≤0.5 μg/mL) XDR ICU, intensive care unit; CST, colistin; CAZavi, ceftazidime-avibactam; S, sensitive; R, resistance; SAM, ampicillin-sulbactam; AMC, Amoxicillin-clavulanic acid; TZP, piperacillin-tazobactam; CFZ, cefazolin; FOX, cefoxitin; ; CAZ, ceftazidime; CRO, ceftriaxone; FEP, cefepime; ETP, ertapenem; MEM, meropenem; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; TGC, tigecycline; SXT, trimethoprim-sulfamethoxazole Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 01 Oct, 2024 Read the published version in European Journal of Clinical Microbiology & Infectious Diseases → Version 1 posted Reviewers agreed at journal 28 Jun, 2024 Reviewers agreed at journal 27 Jun, 2024 Reviewers agreed at journal 27 Jun, 2024 Reviewers invited by journal 27 Jun, 2024 Editor assigned by journal 26 Jun, 2024 Submission checks completed at journal 19 Jun, 2024 First submitted to journal 19 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-4605917","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":323282462,"identity":"51594ab3-4d19-464c-a5fa-3c89a618a212","order_by":0,"name":"Ozlem Ozgur Gundeslioglu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIie3PsUrEMBzH8YSCt5zXNeXwHQIFcSg9fA6XhECnds9wHImBv4vgKgj6CvUNDIVO4VwLdTi9FxAcddATO0kvuDnkO/2G/2f4IxQK/csi9TOw3n7IDCHiJXggkaFTV/yJTIAcQuMncWz1SydXed1bIMQ98qsbYzdomZ2NkURZk5buQNRrbk6o7Pn1UysoaotKjRBqNcwrmArqsO6Y67nqymOCVTNOGnzxXgHZEUUsrPmdl7QYogpo/kXOEw0PvPaR5BKbeekYSxw2KXIive8KQdmeX+K4sW+lXC1mbvK8RTI/uu2E3bwus1EyxIeD0+/BPOe7Fr9GKBQKhYY+AZ/+YuEfCEZ8AAAAAElFTkSuQmCC","orcid":"","institution":"Cukurova University","correspondingAuthor":true,"prefix":"","firstName":"Ozlem","middleName":"Ozgur","lastName":"Gundeslioglu","suffix":""},{"id":323282463,"identity":"092deeb7-3997-4cbf-b478-37b4e2477147","order_by":1,"name":"Zeliha Haytoglu","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Zeliha","middleName":"","lastName":"Haytoglu","suffix":""},{"id":323282466,"identity":"d1235aeb-9dfe-402d-84cc-955ab10ae36e","order_by":2,"name":"Hatice Hale Gumuş","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Hatice","middleName":"Hale","lastName":"Gumuş","suffix":""},{"id":323282468,"identity":"1f641101-2d11-433e-80ae-06632f8934ec","order_by":3,"name":"Faruk Ekinci","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Faruk","middleName":"","lastName":"Ekinci","suffix":""},{"id":323282469,"identity":"09167dc4-faa9-4b49-867a-ed0c04c03d1f","order_by":4,"name":"Filiz Kibar","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Filiz","middleName":"","lastName":"Kibar","suffix":""},{"id":323282470,"identity":"b61688a3-0ced-4470-a182-94c8df32e29f","order_by":5,"name":"Ummuhan Cay","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Ummuhan","middleName":"","lastName":"Cay","suffix":""},{"id":323282473,"identity":"dddcf470-b313-4315-a465-d79ebc6793ac","order_by":6,"name":"Ferda Ozlu","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Ferda","middleName":"","lastName":"Ozlu","suffix":""},{"id":323282475,"identity":"68e71123-d07a-434d-867f-b0c8f1b03b8d","order_by":7,"name":"Ozden Ozgur Horoz","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Ozden","middleName":"Ozgur","lastName":"Horoz","suffix":""},{"id":323282476,"identity":"df50faa2-dafc-43dd-913b-a858e06ae9f9","order_by":8,"name":"Derya Alabaz","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Derya","middleName":"","lastName":"Alabaz","suffix":""},{"id":323282478,"identity":"bc300bb3-4854-4af7-a409-55ff579cd46b","order_by":9,"name":"Rıza Dincer Yıldızdas","email":"","orcid":"","institution":"Cukurova University","correspondingAuthor":false,"prefix":"","firstName":"Rıza","middleName":"Dincer","lastName":"Yıldızdas","suffix":""}],"badges":[],"createdAt":"2024-06-19 12:33:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4605917/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4605917/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10096-024-04948-y","type":"published","date":"2024-10-01T15:58:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66096983,"identity":"f563f766-c09e-4c30-8109-913440381d8f","added_by":"auto","created_at":"2024-10-07 16:12:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":824235,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4605917/v1/93d5c39e-f51b-44ac-abef-f50f0fd665ba.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Experience with Ceftazidime/Avibactam for the Treatment of Extensively Drug-Resistant or Pandrug-Resistant Klebsiella pneumoniae in Neonates and Children","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe increase in antimicrobial resistance (AMR) continues to be a global health issue. In 2019, the number of deaths associated with AMR was reported as 1.2\u0026nbsp;million, and if sufficient measures are not taken, it is estimated that there will be 10\u0026nbsp;million deaths per year by 2050 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The World Health Organization has defined extended-spectrum beta-lactamase (ESBL) positive and carbapenem-resistant \u003cem\u003eEnterobacteriaceae\u003c/em\u003e (CRE), carbapenem-resistant \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e, and carbapenem-resistant \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e as priority pathogens for new antibiotic research and development [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Healthcare-associated infections caused by \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (\u003cem\u003eK. pneumoniae\u003c/em\u003e) account for one-third of gram-negative infections and are globally associated with carbapenem resistance [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn \u003cem\u003eK. pneumoniae\u003c/em\u003e, carbapenem resistance primarily relies on the production of carbapenemases and the plasmid-mediated transfer of genes encoding these enzymes. These carbapenemases vary geographically. In pediatric patients with carbapenem-resistant \u003cem\u003eK. pneumoniae\u003c/em\u003e infections, colistin is the most commonly used and defined as the last resort antibiotic. In recent years, the limited treatment options for gram-negative infections caused by pandrug-resistant strains resistant to colistin are concerning in children [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCeftazidime-avibactam, a recently developed beta-lactam-beta-lactamase inhibitor, holds promise for treating resistant \u003cem\u003eK. pneumoniae\u003c/em\u003e infections in children. First-generation beta-lactamase inhibitors (such as clavulanic acid, tazobactam, and sulbactam) exhibit low activity against many classes of beta-lactamase enzymes and are ineffective against multi-drug-resistant pathogens. Ceftazidime-avibactam possesses broad carbapenemase activity and demonstrates activity against Ambler class A, C, and certain class D enzymes. The combination ceftazidime-avibactam (CAZavi) was approved in the USA in 2015 and in Europe in 2016. In March 2019, FDA granted approval for use in children\u0026thinsp;\u0026ge;\u0026thinsp;3 months old. Data regarding the clinical use of CAZavi in children is still limited [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, we aimed to assess the treatment outcomes and safety profile of CAZavi in pediatric patients with infections resulting from extensively drug-resistant or pandrug-resistant \u003cem\u003eK. pneumoniae.\u003c/em\u003e\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design, Setting, Definitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study included pediatric patients who received ceftazidime-avibactam treatment due to infections caused by extensively drug-resistant or pandrug-resistant \u003cem\u003eK. pneumoniae\u003c/em\u003e monitored in the pediatric intensive care unit, neonatal intensive care unit, and pediatric wards at \u0026Ccedil;ukurova University Faculty of Medicine between 2022 and 2023. From the medical records of the patients, information including age, gender, presence of underlying diseases, history of previous hospitalizations and antibiotic use, application of mechanical ventilation, central venous catheterization, urinary catheterization, characteristics and site of infection, culture results, antibiogram results, antibiotics administered, and patient prognosis were recorded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe definitions of\u0026nbsp;Multi-Drug Resistance\u0026nbsp;(MDR),\u0026nbsp;eXtensive Drug Resistance\u0026nbsp;(XDR), and\u0026nbsp;Pan Drug Resistance\u0026nbsp;(PDR) strains for \u003cem\u003eEnterobacteriaceae\u003c/em\u003e were made according to the terminology recommended by the Centers for Disease Control and Prevention (CDC) and the European Centre for Disease Prevention and Control (ECDC) [10]. \u0026nbsp;MDR\u0026nbsp;was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories.\u0026nbsp;XDR\u0026nbsp;was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories). PDR\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewas defined as non-susceptibility to all agents in all antimicrobial categories.\u0026nbsp;\u003cstrong\u003eDifficult-to-Treat Resistance\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(DTR)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewas defined as\u0026nbsp;\u003cstrong\u003eresistance to all of the typical first-line, lower toxicity agents\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eas the beta-lactams (including carbapenems and beta-lactamase inhibitor combinations) and the fluoroquinolones [10,11]. The absence of growth in repeated cultures of the site of infection 48 hours after the initiation \u0026nbsp;of ceftazidime-avibactam was considered a microbiological response.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe clinical response\u0026nbsp;was defined as the improvement/disappearance of major signs and symptoms. The lack of improvement, worsening of symptoms, or death while on antibiotic treatment was considered treatment failure. We utilized the Pediatric Organ Dysfunction Information Update Mandate (PODIUM), a scoring system introduced in 2022, to quantify organ dysfunction. This system provides detailed criteria and assessments for various organ systems, including the neurological, respiratory, cardiovascular, gastrointestinal, hepatic, renal, hematological, coagulation, endocrine, and immune systems [12]. By applying these criteria, we aimed to identify and categorize the number and types of organ failures present in our study cohort.\u003c/p\u003e\n\u003cp\u003eEthical approval for the study was obtained from the \u003cem\u003eCukurova University Faculty of Medicine Ethics Committee\u003c/em\u003e (05.04.2024-143/20). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMicrobiology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIdentification and antimicrobial susceptibility testing procedures were conducted as follows: Strains of \u003cem\u003eK. pneumoniae\u003c/em\u003e were isolated from various specimens, including blood, catheter blood, urine, tracheal aspirate, and peritoneal fluid, using standard microbiology laboratory protocols. Identification was performed utilizing the VITEK 2 compact system (bioMerieux, Marcy-l\u0026rsquo;\u0026Eacute;toile, France). Antimicrobial susceptibility testing was carried out using the VITEK 2 AST-N325 card (bioMerieux, Marcy-l\u0026rsquo;\u0026Eacute;toile, France), the Kirby-Bauer disk diffusion susceptibility test for CAZavi (Oxoid, United Kingdom), and the gradient diffusion method for colistin (E-Test, Liofilchem, Italy) (Table 2). The antibiotics tested with the AST-N325 card included ampicillin/sulbactam, amoxicillin/clavulanate, piperacillin/tazobactam, cefazolin, cefoxitin, ceftazidime, ceftriaxone, cefepime, ertapenem, meropenem, gentamicin, amikacin, ciprofloxacin, colistin, tigecycline, and trimethoprim-sulfamethoxazole. Clinical breakpoint interpretation was based on guidelines provided by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) [13].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using IBM SPSS Statistics software version 23. Descriptive statistics were calculated for demographic and clinical characteristics, including measures mean, median, standard deviation, and range for continuous variables, while frequencies and percentages were reported for categorical variables.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, a total of 11 pediatric patients who underwent CAZavi therapy between 2022 and 2023 were enrolled. Of these, 9 were male (81.8%). The median age upon hospital admission was 15 months (range: 1 day - 183 months). Seven patients (63.6%) were younger than 2 years old, with 4 patients (36.3%) being under 3 months old. The youngest patient to receive CAZavi was admitted to the neonatal intensive care unit at 27 weeks gestation, weighing 640 grams due to prematurity, and commenced CAZavi treatment for sepsis and necrotizing enterocolitis (NEC) at 14 days of age.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEight patients (72.7%), including 3 in the neonatal intensive care unit, were admitted to the intensive care unit for monitoring. Sepsis was diagnosed in 9 patients (81.8%). Organ failure was present in 9 patients (81.8%), with only two (18.2%) showing no signs of organ failure. The demographic and clinical characteristics of the patients are detailed in \u003cstrong\u003eTable 1\u003c/strong\u003e. The indications for CAZavi administration and the occurrence of organ failures among the patients are provided in \u003cstrong\u003eTable 2\u003c/strong\u003e. K. \u0026nbsp;pneumoniae was detected in blood cultures of 5 patients (45.5%), in urine cultures of 4 patients (36.4%), in tracheal aspirate cultures of 5 patients (45.5%), in catheter cultures of 3 patients (27.3%), and in peritoneal fluid cultures of 1 patient (9.1%). Among the\u0026nbsp;K. pneumoniae strains obtained from patient cultures, 10 (91%) were XDR, and 1 (9%) was PDR. Eight (72.7%) of the K. pneumoniae strains were carbapenem-resistant, with only 3 (27.2%) being carbapenem-sensitive. Isolates obtained from 9 patients (81.8%) showed resistance to colistin. In one patient with pan-drug resistant strains, resistance to CAZavi was present.\u003c/p\u003e\n\u003cp\u003eThe antibiotic susceptibilities of K. \u0026nbsp;pneumoniae isolates were presented in \u003cstrong\u003eTable 2.\u003c/strong\u003e Patients received a median of 14 days (min: 5 - max: 22 days) of CAZavi. In infants \u0026lt;3 months old, the dose of ceftazidime was 30 mg/kg/dose every 8 hours, in infants aged ≥3-6 months, the dose was 40 mg/kg/dose every 8 hours, and in children and adolescents aged ≥6 months to 18 years, the dose was 50 mg/kg/dose every 8 hours (maximum: 2 grams/dose). Ceftazidime-avibactam was administered post-hemodialysis in patients undergoing hemodialysis, and doses were adjusted based on estimated glomerular filtration rate (GFR). Two patients received CAZavi as monotherapy. One of the patients receiving monotherapy (Table 2, Patient 3) was initially treated for a urinary tract infection and was transferred to another hospital on the 5th day of treatment to continue antibiotic therapy. The other patient who received monotherapy was a 27-week premature infant (640 grams) diagnosed with sepsis and NEC at 14 days of age, receiving 12 days of CAZavi therapy. Both patients who received monotherapy showed clinical and microbiological responses. In 9 patients, at least two antibiotics (81.9%) were administered as combination therapy. Meropenem and CAZavi were administered together to 8 patients (72.7%).\u003c/p\u003e\n\u003cp\u003eIt was observed that there were no adverse effects during the use of CAZavi in patients, and treatment was not discontinued due to adverse effects. Microbiological response was observed in 8 patients (72.7%), and clinical response was observed in 6 patients (54.5%). Treatment failure was detected in 5 patients (36.4%). Among the 5 patients with treatment failure, 4 patients died. One patient was transferred to another hospital, and the outcome of this patient's treatment could not be determined. The 30-day survival rate was 54.5%. The clinical, diagnostic, treatment characteristics, and treatment outcomes of the patients are presented in \u003cstrong\u003eTable 3\u003c/strong\u003e.\u003c/p\u003e\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n"},{"header":"Discussion","content":"\u003cp\u003eCarbapenem-resistant and pan-drug resistant Enterobacteriaceae, particularly carbapenem-resistant Klebsiella pneumoniae, are widely reported worldwide. Globally, rates of CRE vary significantly, with the highest rates reported in countries such as Russia, the Eastern Mediterranean region, India, and Southeast Asia\u0026nbsp;[14,15]. In our study, among the\u0026nbsp;K.\u0026nbsp;pneumoniae strains isolated from cultures of pediatric patients treated with\u0026nbsp;CAZavi, 10 (91%) were XDR, and 1 (9%) was PDR. Eight (72.7%) of the\u0026nbsp;K.\u0026nbsp;pneumoniae strains were carbapenem-resistant, with only 3 (27.3%) being carbapenem-sensitive.\u003c/p\u003e\u003cp\u003eIn previous studies and case series, CRE infections have been reported more frequently in patients with underlying diseases, those undergoing intensive care, and those undergoing invasive procedures and broad-spectrum antibiotic therapy. Factors such as prior colonization or infection with resistant pathogens, trauma, recent surgical procedures, mechanical ventilation, urinary catheterization, and the presence of venous catheters are other risk factors associated with the development of colonization or infection with resistant gram-negative pathogens\u0026nbsp;[16- 19].\u003c/p\u003e\u003cp\u003eIn our study, 8 patients (72.7 %), including 3 (27.3%) in the neonatal intensive care unit, were admitted to intensive care. Sepsis was present in 9 patients (81.8%). Underlying diseases were present in 10 patients (91%). A history of broad-spectrum antibiotic use within the past 3 months was reported in 10 patients (91%). Eight patients (72.7%) had received carbapenems in the last 3 months. Central venous catheters were placed in 8 patients (72.7%) as invasive procedures, urinary catheters in 10 patients (91%), hemodialysis in 3 patients (27.3%), and mechanical ventilation in 9 patients (81.8%). Resistance genes in carbapenem-resistant Klebsiella and Enterobacter strains spread rapidly among strains. Conducting regular surveillance studies and implementing infection prevention measures in clinics where patients at risk for infection with resistant pathogens are admitted are extremely important in preventing the spread of infection\u0026nbsp;[20].\u0026nbsp;\u003c/p\u003e\u003cp\u003eIn pediatric patients, colistin is used as a last resort drug for the treatment of carbapenem-resistant\u0026nbsp;K.\u0026nbsp;pneumoniae infections. Colistin resistance in\u0026nbsp;K.\u0026nbsp;pneumoniae is a growing concern, with studies reporting varying levels of resistance. Previous studies have reported colistin resistance rates ranging from 2.8% to 36.1% in carbapenem-resistant\u0026nbsp;K.\u0026nbsp;İsolates\u0026nbsp;[21-23]. \u0026nbsp;In our study, colistin susceptibility testing revealed colistin sensitivity in only 2 patients (18.2%), while colistin resistance was detected in 9 patients (81.8%). Both the EUCAST and the American Clinical and Laboratory Standards Institute (CLSI) recommend broth microdilution testing for evaluating colistin susceptibility\u0026nbsp;[24,25]. However, in our study, broth microdilution testing could not be performed for colistin susceptibility assessment, and instead, E-test and VITEK-2 methods were utilized. Therefore, we cannot provide a definitive interpretation regarding colistin resistance based on our data.\u003c/p\u003e\u003cp\u003eIn recent years, newly developed β-lactam-β-lactamase inhibitors (βL-βLI) (such as ceftazidime-avibactam, meropenem-vaborbactam, and imipenem/silastatin-relebactam) have shown promise in the treatment of gram-negative resistant infections. However, clear recommendations for the treatment of children with MDR, XDR, or pandrug-resistant\u0026nbsp;K.\u0026nbsp;pneumoniae are lacking [26,27].\u0026nbsp;\u003c/p\u003e\u003cp\u003eAvibactam is a novel broad-spectrum beta-lactamase inhibitor without antibacterial activity. Addition of avibactam to ceftazidime expands its antibacterial activity and spectrum. Ceftazidime-avibactam exhibits activity against most Enterobacteriaceae, including those producing AmpC beta-lactamase, ESBL, and some K. pneumoniae and OXA-type carbapenemases. Ceftazidime-avibactam received approval for use in children in 2019. However, studies regarding its use in the treatment of resistant gram-negative infections in children are limited. Lower mortality rates have been reported with the use of ceftazidime-avibactam in adults; however, these studies involve small patient cohorts [28- 32].\u0026nbsp;\u003c/p\u003e\u003cp\u003eIn a randomized, controlled, double-blind phase 2 study involving 95 pediatric patients aged ≥3 months to \u0026lt;18 years with urinary tract infections, CAZavi\u0026nbsp;was reported to be effective and safe against gram-negative pathogens [33].\u003c/p\u003e\u003cp\u003eIn a phase 2 randomized controlled double-blind study involving 83 pediatric patients aged ≥3 months to \u0026lt;18 years with intra-abdominal infections caused by pan-drug resistant strains, one group received meropenem while the other group received\u0026nbsp;CAZavi\u0026nbsp;in combination with metronidazole. The efficacy of\u0026nbsp;CAZavi\u0026nbsp;combined with metronidazole against gram-negative pathogens was found to be comparable to meropenem, with similar side effects observed\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e[34].\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIn a case series evaluating newborns and children under 5 years of age who received ceftazidime-avibactam treatment for bloodstream infections, central nervous system infections, and urinary tract infections caused by carbapenem-resistant K. pneumoniae, all patients achieved clinical and microbiological response, and no adverse effects necessitating treatment discontinuation were reported. However, these patients were also receiving treatment with at least two other antibiotics in addition to\u0026nbsp;CAZavi\u0026nbsp;[4].\u003c/p\u003e\u003cp\u003e\u0026nbsp;In a recent retrospective study evaluating 38 pediatric patients, including 20 (52.6%) with hematologic malignancies, who had carbapenem-resistant pathogens, 25 patients received targeted\u0026nbsp;CAZavi\u0026nbsp;treatment, and 13 received empirical treatment. The clinical response rate was reported as 84% (21/25), and the 30-day mortality rate was 20% (5/25). Among these patients, 21 received combination antibiotic therapy. One patient developed diarrhea, and no other adverse effects were reported [35].\u0026nbsp;\u003c/p\u003e\u003cp\u003eIn our study, we evaluated 11 critically ill patients who received\u0026nbsp;CAZavi\u0026nbsp;treatment, including 3 admitted in the neonatal intensive care unit and 8 (72.7%) in the intensive care unit. Sepsis was diagnosed in 9 patients, and organ failure was present in 9 patients (81.8%). We observed a clinical response in 6 patients (54.5%) and a microbiological response in 8 patients (72.7%), with a 30-day survival rate of 54.5%. Similar to case series presented in the literature, 9 patients (81.8%) in our study received combination therapy, while only 2 patients received ceftazidime-avibactam as monotherapy. One of the patients who received monotherapy was a 27-week-old (640 grams) premature infant diagnosed with sepsis/NEC at 14 days of age. This patient showed clinical and microbiological responses and survived for 30 days.\u003c/p\u003e\u003cp\u003eIn our study, no adverse effects were observed during the use of\u0026nbsp;CAZavi. The most commonly reported side effects in the literature are gastrointestinal adverse effects such as nausea, vomiting, and diarrhea [33-35].\u0026nbsp;\u003c/p\u003e\u003cp\u003eIn our study, 4 cases (36.3%) were under 3 months of age, with 3 of these being neonatal cases. Among them, two premature babies, one born at 27 weeks gestation and the other at 35 weeks gestation, received\u0026nbsp;CAZavi\u0026nbsp;due to sepsis. The 640-gram, 27-week premature baby received\u0026nbsp;CAZavi\u0026nbsp;as monotherapy and achieved both clinical and microbiological response. There are few case reports in the literature demonstrating the successful use of\u0026nbsp;CAZavi\u0026nbsp;in rescuing therapy for resistant gram-negative infections in premature infants [36,37].\u0026nbsp;\u003c/p\u003e\u003cp\u003eIn this study, the limitation lies in the small number of patients and the retrospective nature of the study. Additionally, in our study, the broth microdilution test could not be used to evaluate antibiotic susceptibility for colistin, hence colistin resistance could not be definitively determined.\u003c/p\u003e\u003cp\u003eIn our study, sepsis was diagnosed in 81.8% of patients, with organ failure present in all patients except for two. In our study, which predominantly comprised children under the age of 2 (63.6%), including premature infants, CAZavi emerged as a significant treatment option for resistant K. pneumoniae infections in pediatric and premature patients, demonstrating good tolerability.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eICU: Intensive Care Unit\u003c/p\u003e\n\u003cp\u003eMDR: Multi-Drug Resistance\u003c/p\u003e\n\u003cp\u003eXDR: Extensively Drug-Resistant\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePDR: Pan Drug-Resistant\u003c/p\u003e\n\u003cp\u003eAMR: Antimicrobial Resistance\u003c/p\u003e\n\u003cp\u003eESBL: Extended-Spectrum Beta-Lactamase\u003c/p\u003e\n\u003cp\u003eCRE: Carbapenem-Resistant \u003cem\u003eEnterobacteriaceae\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CAZavi: Ceftazidime-Avibactam\u003c/p\u003e\n\u003cp\u003eUSA: The\u0026nbsp;United States of America\u003c/p\u003e\n\u003cp\u003eFDA: Food and Drug Administration\u003c/p\u003e\n\u003cp\u003eCDC: Centers for Disease Control and Prevention\u003c/p\u003e\n\u003cp\u003eECDC: European Centre for Disease Prevention and Control\u003c/p\u003e\n\u003cp\u003eDTR:\u0026nbsp;\u003cstrong\u003eDifficult-to-Treat Resistance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePODIUM: Pediatric Organ Dysfunction Information Update Mandate\u003c/p\u003e\n\u003cp\u003eEUCAST: European Committee on Antimicrobial Susceptibility Testing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNEC: Necrotizing Enterocolitis\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eNone\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e: All data relevant to the study are included in the article and are available from the corresponding author upon request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Dr Ozlem Ozgur Gundeslioğlu, Dr.Zeliha Haytoglu, Dr. Hatice Hale Gumus, Dr. Faruk Ekinci conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Ozlem Ozgur Gundeslioglu, Dr. Ozden Ozgur Horoz, Dr. Filiz Kibar, Dr. Hatice Hale Gumus, Dr. Ummuhan Cay, designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Dr.Ozlem Ozgur Gundeslioglu, Dr. Derya Alabaz, Dr. Ummuhan Cay, conceptualized and Ferda Ozlu, Dr. Rıza Yıldızdas, Dr. Ozden Ozgur Horoz designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for the study was obtained from the \u003cem\u003eCukurova University Faculty of Medicine Ethics Committee\u003c/em\u003e (05.04.2024-143/20). \u0026nbsp;This study was conducted in compliance with the principles of the Declaration of Helsinki, Good Clinical Practice guidelines and local regulatory requirements. Due to the retrospective nature of the present research, no personal informed consent was required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eThe authors have indicated they have no conflicts of intereset relevant to this article to disclose.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eO\u0026rsquo;Neill J. 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Clin Microbiol Rev. 2020 ;34(1):e00115-20. \u003c/li\u003e\n\u003cli\u003eBassetti M, Giacobbe DR, Giamarellou H, Viscoli C, Daikos GL, Dimopoulos G, et al. Management of KPC-producing Klebsiella pneumoniae infections. Clin Microbiol Infect. 2018 ;24(2):133-144. \u003c/li\u003e\n\u003cli\u003eShields RK, Nguyen MH, Chen L, Press EG, Potoski BA, Marini RV, et al. Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia. Antimicrob Agents Chemother. 2017;61(8):e00883-17.\u003c/li\u003e\n\u003cli\u003evan Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, et al. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018 ;66(2):163-171. \u003c/li\u003e\n\u003cli\u003eJorgensen SCJ, Trinh TD, Zasowski EJ, Lagnf AM, Bhatia S, Melvin SM, et al. Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections. Open Forum Infect Dis. 2019 ;6(12):ofz522. \u003c/li\u003e\n\u003cli\u003eTumbarello M, Trecarichi EM, Corona A, De Rosa FG, Bassetti M, Mussini C, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis. 2019 ;68(3):355-364. \u003c/li\u003e\n\u003cli\u003eTsolaki V, Mantzarlis K, Mpakalis A, Malli E, Tsimpoukas F, Tsirogianni A, et al. Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients. Antimicrob Agents Chemother. 2020 ;64(3):e02320-19. \u003c/li\u003e\n\u003cli\u003eBradley JS, Roilides E, Broadhurst H, Cheng K, Huang LM, MasCasullo V, et al. Safety and Efficacy of Ceftazidime-Avibactam in the Treatment of Children \u0026ge;3 Months to \u0026lt;18 Years With Complicated Urinary Tract Infection: Results from a Phase 2 Randomized, Controlled Trial. Pediatr Infect Dis J. 2019 ;38(9):920-928. \u003c/li\u003e\n\u003cli\u003eBradley JS, Broadhurst H, Cheng K, Mendez M, Newell P, Prchlik M, et al. Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children \u0026ge;3 Months to \u0026lt;18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial. Pediatr Infect Dis J. 2019;38(8):816-824. \u003c/li\u003e\n\u003cli\u003eMeng H, Zhao Y, An Q, Zhu B, Cao Z, Lu J. Use of Ceftazidime-Avibactam for Suspected or Confirmed Carbapenem-Resistant Organisms in Children: A Retrospective Study. Infect Drug Resist. 2023 ;16:5815-5824. \u003c/li\u003e\n\u003cli\u003eCoskun Y, Atici S. Successful Treatment of Pandrug-resistant Klebsiella pneumoniae Infection With Ceftazidime-avibactam in a Preterm Infant: A Case Report. Pediatr Infect Dis J. 2020 ;39(9):854-856.\u003c/li\u003e\n\u003cli\u003eAsfour SS, Alaklobi FA, Abdelrahim A, Taha MY, Asfour RS, Khalil TM, et al. Intravenous Ceftazidime-Avibactam in Extremely Premature Neonates With Carbapenem-Resistant Enterobacteriaceae: Two Case Reports. J Pediatr Pharmacol Ther. 2022;27(2):192-197.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Demographic and Clinical Characteristics of the Patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (months), median (min-max)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e15 (min:2 days max:183 months)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (81.8)\u003c/p\u003e\n \u003cp\u003e2 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresence of underlying disease, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e10 (91)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistory of Hospitalization, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e8 (72.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistory of Intensive Care Unit Admission, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e5 (45.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntibiotic Use in the Last 3 Months, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCarbapenem use\u003c/p\u003e\n \u003cp\u003eColistin use\u003c/p\u003e\n \u003cp\u003eGlycopeptide use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e10 (91)\u003c/p\u003e\n \u003cp\u003e8 (72.7)\u003c/p\u003e\n \u003cp\u003e4 (36.3)\u003c/p\u003e\n \u003cp\u003e9 (81.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"62.25165562913907%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresence of Invasive Procedures, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCentral venous catheter\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eUrinary catheter\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDialysis application\u003c/p\u003e\n \u003cp\u003eMechanical ventilation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.74834437086093%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e8 (72.7)\u003c/p\u003e\n \u003cp\u003e10 (91)\u003c/p\u003e\n \u003cp\u003e3 (27.3)\u003c/p\u003e\n \u003cp\u003e9 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Diagnoses, Treatment Characteristics, and Treatment Outcomes of Patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"905\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003emonth\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Diagnosis for Ceftazidime-avibactam Administration)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnderlying Disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOrgan Dsyfunction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCr-Cl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCeftazidim\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAvibactam\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eadministration duration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinic Response\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMicrobiological\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eResponse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e30-day\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;survival\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis,\u003c/p\u003e\n \u003cp\u003eIntraabdominal infection,\u003c/p\u003e\n \u003cp\u003ePneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eRespiratory,\u003c/p\u003e\n \u003cp\u003eHematological,\u003c/p\u003e\n \u003cp\u003eImmune system\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003e*CRBI\u003c/p\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003cp\u003ePneumonia\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eİntracranial mass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eCardiovascular,\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNeurological,\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHematological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003e**UTI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eNephrolithiasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eMono\u003c/p\u003e\n \u003cp\u003etherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003e***VIP,\u003c/p\u003e\n \u003cp\u003eSepsis,\u003c/p\u003e\n \u003cp\u003e*CRBI\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003e****HİE,\u003c/p\u003e\n \u003cp\u003eEpilepsy,\u003c/p\u003e\n \u003cp\u003eLaryngomalacia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eCardiovascular,\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNeurological,\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHematological\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eEndocrin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e44 g\u0026uuml;n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003e***VIP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003e*****CHD\u003c/p\u003e\n \u003cp\u003eSyndromic\u003c/p\u003e\n \u003cp\u003eInfant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNeurological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e14 g\u0026uuml;n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis,\u003c/p\u003e\n \u003cp\u003e******NEC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003ePrematurity (27 weeks)\u003c/p\u003e\n \u003cp\u003eTrisomy,\u003c/p\u003e\n \u003cp\u003e*******DMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRespiratory,\u003c/p\u003e\n \u003cp\u003eGastrointestinal,\u003c/p\u003e\n \u003cp\u003eHematological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eMono\u003c/p\u003e\n \u003cp\u003etheraphy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e37 g\u0026uuml;n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e*****CHD\u003c/p\u003e\n \u003cp\u003ePrematurity (35 weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eCardiovascular,\u003c/p\u003e\n \u003cp\u003eNeurological\u003c/p\u003e\n \u003cp\u003eRenal,\u003c/p\u003e\n \u003cp\u003eHematological,\u003c/p\u003e\n \u003cp\u003eRespiratory\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003e**UTI\u003c/p\u003e\n \u003cp\u003eSepsis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eHİE,\u003c/p\u003e\n \u003cp\u003eEpilepsy\u003c/p\u003e\n \u003cp\u003eLaryngomalacia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eImmunological\u003c/p\u003e\n \u003cp\u003eRespiratory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003e********ALL\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eGastrointestinal,\u003c/p\u003e\n \u003cp\u003eHematological,\u003c/p\u003e\n \u003cp\u003eImmunological\u003c/p\u003e\n \u003cp\u003eRespiratory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003cp\u003e*CRBI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003e*********SMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eImmunological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.181015452538631%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.518763796909492%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.037527593818984%\" valign=\"top\"\u003e\n \u003cp\u003e**UTI\u003c/p\u003e\n \u003cp\u003eSepsis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003ePosterior\u003c/p\u003e\n \u003cp\u003e\u0026Uuml;retral valv,\u003c/p\u003e\n \u003cp\u003eHydronephrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.485651214128035%\" valign=\"top\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.28476821192053%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.388520971302428%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.381898454746137%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.479028697571744%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.375275938189846%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*CRBI: Catheter-related bloodstream infection, ** UTI: Urinary tract infection, *** VAP: Ventilator-associated pneumonia, **** HIE: Hypoxic ischemic encephalopathy, ***** CHD: Congenital heart disease, ****** NEC: Necrotizing enterocolitis, ******* IDM:Infant of diabetic mother, ******** ALL:Acute lymphoblastic leukemia, *********SMA: Spinal muscular atrophy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Antimicrobial susceptibility of \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e isolates\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDepartment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecimen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntimicrobial Susceptibility Test \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (VITEK 2) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCST\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(VITEK 2/E-test)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAZavi\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(VITEK 2/Disc Diffusion Test) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAMR Profile\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003ePeritoneal fluid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eS (\u0026le;0.5 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (20mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eBlood,\u003c/p\u003e\n \u003cp\u003eTracheal aspirate\u003c/p\u003e\n \u003cp\u003eCatheter blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;16 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (17mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eNon-ICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;16 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eR (12 mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003ePDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eBlood,\u003c/p\u003e\n \u003cp\u003eCatheter blood,\u003c/p\u003e\n \u003cp\u003eTracheal aspirate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;8 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (\u0026le;0.5 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eTracheal aspirate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;8 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (\u0026le;0.5 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eBlood\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;8 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (\u0026le;0.5 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eTracheal aspirate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;16 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (\u0026le;0.5 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;8 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (\u0026le;0.5 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eNon-ICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eBlood,\u003c/p\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, MEM, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eS (2 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (8 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eCatheter Blood\u003c/p\u003e\n \u003cp\u003eTracheal aspirate\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;8 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (15 mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.9742489270386265%\" valign=\"top\"\u003e\n \u003cp\u003e11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.085836909871245%\" valign=\"top\"\u003e\n \u003cp\u003eNon-ICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.017167381974248%\" valign=\"top\"\u003e\n \u003cp\u003eBlood,\u003c/p\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.44206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR to SAM, AMC, TZP, CFZ, FOX, CAZ, CRO; FEP; ETP, AMK, GEN, CIP, TGC, CST, SXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944206008583691%\" valign=\"top\"\u003e\n \u003cp\u003eR (\u0026ge;8 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.875536480686696%\" valign=\"top\"\u003e\n \u003cp\u003eS (\u0026le;0.5 \u0026mu;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.660944206008583%\" valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eICU, intensive care unit; CST, colistin; CAZavi, ceftazidime-avibactam; S, sensitive; R, resistance; SAM, ampicillin-sulbactam; AMC, Amoxicillin-clavulanic acid; TZP, piperacillin-tazobactam; CFZ, cefazolin; FOX, cefoxitin; \u003cem\u003e;\u003c/em\u003e CAZ, ceftazidime; CRO, ceftriaxone; FEP, cefepime; ETP, ertapenem; MEM, meropenem; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; TGC, tigecycline; SXT, trimethoprim-sulfamethoxazole\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-microbiology-and-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcm","sideBox":"Learn more about [European Journal of Clinical Microbiology \u0026 Infectious Diseases](https://www.springer.com/journal/10096)","snPcode":"10096","submissionUrl":"https://submission.nature.com/new-submission/10096/3","title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Ceftazidim-avibactam, Children, Carbapenem resistant Klebsiella pneumoniae, Extensively drug-resistant Klebsiella pneumoniae, Pandrug resistant Klebsiella pneumoniae","lastPublishedDoi":"10.21203/rs.3.rs-4605917/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4605917/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e is a significant cause of healthcare-associated infections, resulting in high morbidity and mortality rates due to limited treatment options. In this study, we aimed to evaluate the treatment outcomes and the safety of Ceftazidime-avibactam in infections caused by extensively drug-resistant or pandrug-resistant \u003cem\u003eKlebsiella pneumoniae \u003c/em\u003ein pediatric patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis study included pediatric patients who received ceftazidime-avibactam treatment due to extensively drug-resistant or pandrug-resistant \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e infections, monitored in the pediatric intensive care, neonatal intensive care, and pediatric wards of Cukurova University Faculty of Medicine between 2022 and 2023. Patients' microbiological responses, clinical responses, medication side effects, and 30-day survival rates were evaluated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Eleven pediatric patients were included in the study, of whom nine were male (81.8%). \u0026nbsp;The median age of the patients was 15 months (min: 1 day - max: 183 months). Sepsis was diagnosed in 9 patients (81.8%). Two premature infants (27 and 35 weeks) were admitted to the neonatal ICU. Regarding the \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e strains, 10 (91%) were extensively drug-resistant (XDR), and 1 (9%) was pandrug-resistant (PDR). Eight strains (72.7%) were carbapenem-resistant, and 9 (81.8%) were colistin-resistant. Microbiological response was noted in 8 patients (72.7%), clinical response was evident in 6 patients (54.5%). The 30-day survival rate was 54.5%, with six patients surviving.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eIn our study, ceftazidime-avibactam has been identified as a significant treatment option for resistant \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e infection in critically ill children and premature infants with sepsis and organ failure, and it has been found to be well tolerated.\u003c/p\u003e","manuscriptTitle":"Clinical Experience with Ceftazidime/Avibactam for the Treatment of Extensively Drug-Resistant or Pandrug-Resistant Klebsiella pneumoniae in Neonates and Children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-08 16:07:13","doi":"10.21203/rs.3.rs-4605917/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"276795941676437066389083563713348826513","date":"2024-06-28T17:40:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"47216839539728405771344449174780631708","date":"2024-06-27T13:30:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174388310732301234929228341798073913822","date":"2024-06-27T09:42:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-27T08:10:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-26T07:16:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-19T16:45:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","date":"2024-06-19T12:30:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-microbiology-and-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcm","sideBox":"Learn more about [European Journal of Clinical Microbiology \u0026 Infectious Diseases](https://www.springer.com/journal/10096)","snPcode":"10096","submissionUrl":"https://submission.nature.com/new-submission/10096/3","title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7903924f-048f-4d42-8c39-b0161b188a83","owner":[],"postedDate":"July 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-07T16:05:02+00:00","versionOfRecord":{"articleIdentity":"rs-4605917","link":"https://doi.org/10.1007/s10096-024-04948-y","journal":{"identity":"european-journal-of-clinical-microbiology-and-infectious-diseases","isVorOnly":false,"title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases"},"publishedOn":"2024-10-01 15:58:15","publishedOnDateReadable":"October 1st, 2024"},"versionCreatedAt":"2024-07-08 16:07:13","video":"","vorDoi":"10.1007/s10096-024-04948-y","vorDoiUrl":"https://doi.org/10.1007/s10096-024-04948-y","workflowStages":[]},"version":"v1","identity":"rs-4605917","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4605917","identity":"rs-4605917","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}