Ceftazidime-Avibactam for the Treatment of Febrile Neutropenia in HSCT Recipients and Acute Leukemia Patients Post Induction Chemotherapy

Ceftazidime-Avibactam for the Treatment of Febrile Neutropenia in HSCT Recipients and Acute Leukemia Patients Post Induction Chemotherapy | 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 Ceftazidime-Avibactam for the Treatment of Febrile Neutropenia in HSCT Recipients and Acute Leukemia Patients Post Induction Chemotherapy Jim Abi Frem, Alicia Khazzeka, Fatima Allaw, Caren Doueiry, Racha Ghoussaini, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4574482/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Febrile neutropenia is a common and major complication in patients with acute leukemia or those undergoing hematopoietic stem cell transplantation (HSCT). Understanding patient characteristics and patterns of susceptibility in febrile neutropenia is essential to provide the appropriate antimicrobial therapy. First-line agents should have Pseudomonas coverage, but with the increase in multi-drug resistant organisms, ceftazidime-avibactam has emerged as a new therapy in febrile neutropenia. Methods This is a retrospective case-control study of a total of 300 admissions (143 patients) between January 2009 and December 2017. Patients with hematologic neoplasms and patients that underwent HSCT who satisfied the definition of febrile neutropenia and treated with ceftazidime-avibactam (CAZAVI) were included in the study. A bivariate regression model to explore independent predictors of septic shock and mortality was constructed. Results Patients who received ceftazidime-avibactam (CAZAVI) were more likely to have a microbiologically documented infection (59.0% vs. 28.3%). Almost all complications were significantly more frequent in the CAZAVI group, with sepsis being the most common, occurring in 59.0% of patients in the CAZAVI arm. Our multivariable logistic regression analysis showed that receiving CAZAVI was an independent risk factor for both sepsis and mortality (aOR 6.33 [95% CI 2.81–14.30] and 7.82 [2.63–23.26], respectively). Conclusion Knowing the most common organisms isolated during a neutropenic fever episode as well as the patterns of resistance, compounded with an understanding of the risk factors for morbidity and mortality in such a vulnerable population, is key to providing them with appropriate prophylactic and therapeutic management. In addition, more studies should be done on the effectiveness of ceftazidime-avibactam in treating febrile neutropenia in the population at hand. Febrile neutropenia acute leukemia hematopoietic stem cell transplant ceftazidime-avibactam mortality morbidity INTRODUCTION Patients with hematological malignancies are at an increased risk of developing serious infections, which significantly affect both their survival and quality of life. More than 80% of patients with hematological malignancies will present with fever during a chemotherapy cycle that has caused neutropenia ( 1 ). Deficits in components of the innate immune system, as a result of the underlying malignancy, may predispose to the development of invasive bacterial and fungal infections ( 2 ). The treatment itself, more commonly, can lead to neutropenia, which is a major predisposing factor for infections ( 3 ). Cytotoxic antineoplastic therapy for hematological malignancies as well as stem cell transplantation are common causes of treatment-induced neutropenia due to a decrease in white blood cell production ( 4 ). Fever is often the only sign of infection, since the intensity of the neutrophil-mediated inflammatory response may be blunted ( 4 ). As such, a high index of suspicion followed by an extensive diagnostic work-up and prompt initiation of antimicrobial therapy are crucial ( 5 ). The epidemiology of microorganisms isolated from the blood of patients with neutropenic fever has changed over time. While Gram-negative pathogens predominated in the 1960s, the increased use of indwelling catheters in the 1980s and 1990s led to a higher incidence of Gram-positive organisms ( 6 ). Currently, the most common blood isolates in most centers are coagulase-negative staphylococci ( 6 ), although in some cases a trend reversal is being witnessed with the emergence of drug-resistant Gram-negative pathogens ( 7 , 8 ). In our country, however, this variation has not been observed. Over the years, several studies from Lebanon have shown a consistently higher prevalence of Gram-negative infections in febrile neutropenic patients ( 9 – 11 ). In addition, antimicrobial resistance among Gram-negative pathogens in Lebanon is substantial. The proportions of extended-spectrum beta-lactamase (ESBL) producing Enterobacterales exceed 30% ( 12 ), while proportions of carbapenem-resistant Enterobacterales range from 3–6% ( 13 ). Empiric therapy for febrile neutropenia, while guided by international guidelines ( 6 ), must also take into account the local epidemiology. Ceftazidime-avibactam (CAZAVI), a broad-spectrum beta-lactam/beta-lactamase inhibitor combination, has been increasingly used in patients with febrile neutropenia, whether empirically in patients who fail to respond to first-line therapy, or as directed therapy when a resistant Gram-negative pathogen is recovered from clinical cultures ( 14 , 15 ). The aim of our study is to characterize febrile neutropenia episodes in patients with acute leukemias and those undergoing hematopoietic stem cell transplantation (HSCT), and to compare the outcomes of patients who received traditional antimicrobial therapy to those who received CAZAVI. METHODS Study design and population: This is a retrospective case-control study conducted at the American University of Beirut Medical Center (AUBMC), a tertiary care center in Lebanon. Our sample included all adult patients presenting with febrile neutropenia following induction therapy for acute leukemia or during HSCT. The medical records of febrile neutropenic patients admitted to AUBMC between 2009 and 2022 were reviewed. Patients were included more than once if they developed another febrile neutropenia episode at least 14 days after the initial one. Study subjects were classified into cases who received CAZAVI for the treatment of febrile neutropenia, and controls who were treated with the best available therapy (BAT). Definitions and severity scores: We adopted the definitions of fever and neutropenia as set forth by the guidelines of the Infectious Diseases Society of America (IDSA): an oral temperature record of 38.3°C (101°F) or a temperature of ≥ 38.0°C (100.4°F) lasting for at least one hour, and a neutrophil count below 1500/mm 3 (16). Several indices were used to estimate baseline functioning and illness severity and were calculated based on published literature: the Charlson Comorbidity Index predicts the 10-year mortality for patients with a number of comorbidities (17); the Multinational Association for Supportive Care in Cancer (MASCC) score index measures the risk of complications in patients with febrile neutropenia, where a score of < 21 indicates high risk of having a serious infection (18); the Quick Sepsis Related Organ Failure Assessment (qSOFA) is a bedside tool used to screen for sepsis in patients with a suspected infection (19); the Eastern Cooperative Oncology Group (ECOG) performance status is a scale used to determine the disease progression and its effect on daily living habits of cancer patients, with a score ranging from 0 (fully active) to 5 (dead) (20). Statistical analysis: Data were entered into SPSS. Bivariable analysis was performed to detect statistical associations using the Chi-square test for categorical variables and the independent samples t-test for continuous variables. Backward stepwise binary logistic regression was performed to test for independent associations, including effect of treatment with CAZAVI on sepsis and mortality, controlling for potential confounders. Variables with a p-value of 0.2 or less on bivariable analysis were included in the regression model. Ethical considerations: The Institutional Review Board at the American University of Beirut approved the study. Informed consent was waived because of the retrospective nature of the analysis. RESULTS During the study period, we recorded 339 episodes of neutropenic fever, 39 of which were treated with CAZAVI and 300 with BAT. The baseline characteristics of patients are displayed in Table 1 . Age and sex distribution were similar in both study arms. Compared to the BAT group, there was a higher proportion of patients in the CAZAVI group who were undergoing HSCT (33.3% allo-HSCT and 15.4% auto-HSCT), whereas most patients in the BAT group were receiving induction therapy for acute myeloid leukemia (62.0%; p < 0.001). As far as baseline severity scores, there was no difference in the mean Charlson and ECOG scores between the two study groups. However, the MASCC score, which is calculated upon developing the episode of febrile neutropenia, was significantly lower in the CAZAVI group (19.5 ± 4.1 vs. 21.9 ± 4.1; p = 0.001), indicating a high risk for developing complications from neutropenic fever. More patients who received CAZAVI treatment had an established source of infection compared to those who received BAT (89.7% vs. 57.0%; p < 0.001). Table 1 Characteristics of patients and the febrile neutropenia episodes by treatment group Characteristic CAZAVI arm (N = 39) BAT arm (N = 300) p-value Age, years 48.9 ± 13.8 45.5 ± 16.4 0.23 Male sex 21 (53.8) 177 (59.0) 0.43 Chronic renal insufficiency 4 (10.3) 19 (6.3) 0.32 Diabetes mellitus 4 (10.3) 48 (16.0) 0.35 Chronic pulmonary disease 1 (2.6) 9 (3.0) 1.00 Underlying disease < 0.001 Acute myeloid leukemia 12 (30.8) 186 (62.0) Acute lymphocytic leukemia 8 (20.5) 61 (20.3) Auto-HSCT 6 (15.4) 6 (2.0) Allo-HSCT 13 (33.3) 47 (15.7) Hospital stay* 16 (41.0) 218 (72.7) < 0.001 ICU stay* 7 (17.9) 6 (2.0) < 0.001 Mechanical ventilation* 1 (2.6) 4 (1.3) 0.46 Central line* 3 (7.7) 123 (41.0) < 0.001 Urinary catheter* 1 (2.6) 9 (3.0) 1.00 Steroid therapy* 20 (51.3) 97 (32.3) 0.02 Surgery within 30 days 4 (10.3) 10 (3.3) 0.06 Charlson score 3.3 ± 1.8 3.0 ± 0.1 0.32 ECOG score 0.3 ± 0.6 0.4 ± 1.0 0.33 MASCC score 19.5 ± 4.1 21.9 ± 4.1 0.001 qSOFA score 0.6 ± 0.6 0.3 ± 0.7 Established source of infection 35 (89.7) 171 (57.0) < 0.001 Clinically/radiologically determined 17 (43.6) 149 (49.6) 0.47 Microbiologically determined 23 (59.0) 85 (28.3) < 0.001 Intravascular device 13 (33.3) 21 (7.0) Respiratory 11 (28.2) 44 (14.7) Gastrointestinal 4 (10.3) 45 (15.0) Urinary 4 (10.3) 36 (12.0) Skin and soft tissue 0 22 (7.3) Nasopharyngeal/oropharyngeal 0 16 (5.3) Musculoskeletal 0 1 (0.3) Central nervous system 0 1 (0.3) Numbers indicate n (%) for categorical variables and mean ± standard deviation for continuous variables *More than 48 hours within the past 30 days CAZAVI = ceftazidime-avibactam; BAT = best available therapy; Auto-HSCT = autologous hematopoietic stem cell transplantation; Allo-HSCT = allogeneic hematopoietic stem cell transplantation; ECOG = Eastern Cooperative Oncology Group; ICU = intensive care unit; MASCC = Multinational Association for Supportive Care in Cancer Patients in the CAZAVI arm were more likely to have a microbiologically documented infection (59.0% vs. 28.3%). The distribution of isolated organisms is shown in Table 2 . Gram-negative organisms predominated in both CAZAVI and BAT arms (74.4% and 38.3%, respectively), whereas Gram-positive organisms trailed by a considerable margin (28.2% and 15.7%, respectively). As expected, a larger number of patients who received CAZAVI had antimicrobial-resistant Gram-negative organisms, including ESBL-producing and carbapenem-resistant E. coli . Table 2 Isolated microorganisms in 339 febrile neutropenia episodes Organism CAZAVI arm (N = 39) BAT arm (N = 300) Gram-negatives 29 (74.4) 115 (38.3) Escherichia coli 21/39 (53.8) 79/300 (26.3) ESBL-producing E. coli 17/21 (80.9) 43/79 (54.4) Carbapenem-resistant E. coli 4/21 (19.0) 1/79 (1.3) Klebsiella spp. 3/39 (7.7) 11/300 (3.7) ESBL-producing Klebsiella spp. 0 5/11 (45.4) Pseudomonas aeruginosa 2/39 (5.1) 15/300 (5.0) Other Enterobacterales 1/39 (2.6) 6/300 (2.0) Acinetobacter spp. 1/39 (2.6) 2/300 (0.7) Stenotrophomonas maltophilia 1/39 (2.6) 1/300 (0.3) Salmonella non-typhi 0 1/300 (0.3) Gram-positives 11 (28.2) 47 (15.7) Coagulase-negative staphylococci 6/39 (15.4) 22/300 (7.3) Enterococcus spp. 4/39 (10.3) 12/300 (4.0) viridans streptococci 0 10/300 (3.3) Staphylococcus aureus 1/39 (2.6) 2/300 (0.7) Streptococcus pneumoniae 0 1/300 (0.3) Others Listeria monocytogenes 0 2/300 (0.7) Bacillus spp. 0 1/300 (0.3) Clostridium difficile 1/39 (2.6) 1/300 (0.3) Numbers indicate n (%) CAZAVI = ceftazidime-avibactam; BAT = best available therapy Up to 18.5% of study subjects had received carbapenem therapy for more than 48 hours in the 30 days preceding the febrile neutropenia episode. In addition, 85% of the overall population had received antibacterial and antiviral prophylaxis, and 89% had received antifungal prophylaxis. In the BAT arm, carbapenems were the most commonly used antibiotics for empiric as well as for directed therapy, followed by cefepime, piperacillin-tazobactam, and glycopeptides. The febrile neutropenia episodes in our study were associated with various complications, and almost all were significantly more frequent in the CAZAVI group (Table 3 ). The most commonly observed complication was sepsis, which occurred in 59.0% of patients in the CAZAVI arm and in 15.0% of patients in the BAT arm (p < 0.001). Other important complications included intensive care unit (ICU) admission, respiratory failure, and persistent bacteremia. Patients who received CAZAVI-based regimens were more likely to have a fatal outcome compared to patients who received BAT (23.1% vs. 3.0%). We conducted a multivariable logistic regression analysis to determine independent risk factors for sepsis and mortality, and we were particularly interested in evaluating whether the type of antibiotic treatment had an effect on patient outcome. The results of the multivariable models are shown in Table 4 . Receiving CAZAVI was an independent risk factor for both sepsis and mortality, with a large effect size for both outcomes (aOR 6.33 [95% CI 2.81–14.30] and 7.82 [2.63–23.26], respectively). Recent receipt of steroids was a significant risk factor for sepsis (aOR 2.12 [95% CI 1.08–4.15]) but not for mortality. On the other hand, MASCC score was negatively correlated with both sepsis and mortality. Table 3 Complications of febrile neutropenia episodes by treatment group Complication CAZAVI arm (N = 39) BAT arm (N = 300) p-value Sepsis 23 (59.0) 45 (15.0) < 0.001 ICU admission 12 (30.8) 14 (4.7) < 0.001 Respiratory failure 11 (28.2) 7 (2.3) < 0.001 Persistent bacteremia 8 (20.5) 12 (4.0) 0.001 Acute kidney injury 4 (10.3) 8 (2.7) 0.04 ARDS 3 (7.7) 13 (4.3) 0.41 Death 9 (23.1) 9 (3.0) < 0.001 Numbers indicate n (%) CAZAVI = ceftazidime-avibactam; BAT = best available therapy; ARDS = acute respiratory distress syndrome; ICU = intensive care unit Table 4 Logistic regression models showing independent associations with sepsis and mortality in patients with febrile neutropenia Variable Sepsis Mortality aOR (95% CI) p-value aOR (95% CI) p-value CAZAVI therapy 6.33 (2.81–14.30) < 0.001 7.82 (2.63–23.26) < 0.001 Steroid therapy* 2.12 (1.08–4.15) 0.03 — NS MASCC score 0.75 (0.69–0.81) < 0.001 0.77 (0.69–0.86) < 0.001 * More than 48 hours within the past 30 days aOR = adjusted odds ratio; CI = confidence interval; CAZAVI = ceftazidime-avibactam; MASCC = Multinational Association for Supportive Care in Cancer DISCUSSION This is a retrospective case-control study evaluating the effect of CAZAVI on patient outcomes with neutropenic fever compared to other treatment regimens. With the ever-increasing antimicrobial resistance rates among Gram-negative pathogens, broad-spectrum agents are more likely to be prescribed, despite not being traditional treatment options based on IDSA guidelines. This is particularly true for high-risk patients with hematological malignancies or HSCT recipients who experience more profound and prolonged neutropenia. As such, evaluating the prevalence of potentially causative organisms in patients with neutropenic fever is crucial, as it facilitates prompt initiation of antimicrobial treatment, preventing rapid progression to sepsis and shock ( 21 ). E. coli was the most common isolated organism among patients with febrile neutropenia in our study, consistent with the trend observed in Lebanon for the past 25 years ( 9 – 11 ). Few studies have been published from the Arab region regarding the epidemiology of febrile neutropenia in cancer patients, yielding variable results. Data from Saudi Arabia indicated a predominance of Gram-negative bloodstream infections in neutropenic patients, with E. coli being the most common isolated pathogen ( 22 ). A retrospective study from Qatar, which included more than 1000 episodes of febrile neutropenia, showed a prevalence of 41% of ESBL-producing organisms ( 23 ). The findings were different in Kuwait and the UAE, where there was a predominance of Gram-positive infections among febrile neutropenic patients ( 24 ). The emergence of multi-drug resistant Gram-negative pathogens can be attributed to the use of quinolones as prophylaxis, which in itself is a risk factor for colonization by such organisms ( 25 ). This correlates with our findings, given that levofloxacin was the most commonly used drug for prophylaxis, as it reduces the incidence of bloodstream infections with no effect on mortality ( 26 ). Patients with acute leukemia usually acquire resistant bacteria due to their immunocompromised state ( 27 ). They thus receive broad-spectrum antibiotics, eventually tailored to culture results. Initial empiric treatment in febrile neutropenia includes a beta-lactam with Pseudomonas coverage ( 28 – 30 ). In our center, carbapenems were most commonly used as empiric treatment, correlating with the rising number of Gram negative ESBL organisms. Vancomycin and cefepime were equally used due to the rising number of central venous catheters reflecting an increase in the incidence of Staphylococcus coagulase negative bacteremia. This is consistent with clinical practice guidelines ( 18 , 31 ). As expected, a larger number of patients who received ceftazidime-avibactam had antimicrobial resistant organisms. In fact, the increasing incidence of resistant pathogens remains a challenge in the management of febrile neutropenia and preliminary data have shown that CAZAVI can play a role as empiric therapy for those who had carbapenem-resistant Klebsiella bloodstream infections ( 32 ). Furthermore, patients who received CAZAVI-based regimens were more likely to have complications compared to the BAT group. Bacteremia represents 11.7% of all sources of infection, concordant with a study conducted in Saudi Arabia ( 24 ). A previous study done in Lebanon showed that bacteremia was the source in 18% of all patients with febrile neutropenia ( 11 ), while another study on patients with HSCT showed that the incidence of bacteremia was 41.2% ( 33 ), a value much higher than what we currently observed. Septic shock, cardiovascular complications and persistent infection were all significantly associated with increased mortality. A retrospective cohort study conducted in 2021 showed that septic shock is one of the two main independent predictors of mortality in febrile neutropenia ( 34 , 35 ). Our multivariable logistic regression analysis also revealed that CAZAVI was an independent risk factor for both sepsis and mortality, with a large effect size for both outcomes. This raises concerns about the role of CAZAVI in treating febrile neutropenia in this population. Some studies have reported similar outcomes with CAZAVI. For instance, a large retrospective study by Jorgensen et al. (2019) reported a 30-day mortality of 17% in patients treated with CAZAVI ( 36 ). However, these results should be interpreted with caution and may be biased due to several limitations. First, a smaller number of patients received CAZAVI compared to BAT. This may have been influenced by the fact that CAZAVI was not always available at our institution during the study period and was provided based on patient need and financial capacity. Additionally, many patients received CAZAVI empirically and may have died from complications or infections unrelated to the administered drug. Nevertheless, CAZAVI has proven effective in several recent studies for febrile neutropenia, particularly in patients with Klebsiella pneumoniae carbapenemase (KPC) ( 37 ) and has shown higher clinical cure rates ( 38 ). Limitations Limitations of this study include the retrospective nature of its design, the relatively small sample size, and its reliance on data generated from a single tertiary care center. CONCLUSION Awareness of the local patterns of infections and susceptibilities, as well as understanding the predictors for septic shock and mortality in patients with febrile neutropenia pave the way to successful treatment and prevention of neutropenic fever. Reducing the morbidity and mortality risk relies on the above in order to successfully initiate proper empiric treatment. More studies are needed to investigate adverse events related to the introduction of ceftazidime-avibactam and to establish a benefit to risk ratio, as there is still no consensus on appropriate CAZAVI dosage in such scenarios and its efficiency in resolving the febrile neutropenia. Declarations FUNDING None CONFLICTS OF INTEREST None to declare Author Contribution J.A., F.A., and R.M prepared protocol write-up; J.A., F.A., C.D.,R.G.,R.M., and A.K. collected the data; J.A., R.G., and A.K. wrote the main manuscript text and prepared the tables; F.A. edited the manuscript; Z.K. conceptualized the study, designed the study, analyzed the data, revised, and edited the main manuscript text. References Lyman GH, Kuderer NM . Epidemiology of febrile neutropenia. Support Cancer Ther. 2003;1(1):23-35. Logan C, Koura D, Taplitz R . Updates in infection risk and management in acute leukemia. Hematology Am Soc Hematol Educ Program. 2020;2020(1):135-9. Baden LR, Swaminathan S, Angarone M, Blouin G, Camins BC, Casper C, et al.Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2016;14(7):882-913. Stern A, Carrara E, Bitterman R, Yahav D, Leibovici L, Paul M . Early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution in people with cancer. Cochrane Database Syst Rev. 2019;1(1):CD012184. Satyanarayana G . Work-up for Fever During Neutropenia for Both the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient. Infect Dis Clin North Am. 2019;33(2):381-97. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al.Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4):e56-93. Cattaneo C, Quaresmini G, Casari S, Capucci MA, Micheletti M, Borlenghi E, et al.Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution. J Antimicrob Chemother. 2008;61(3):721-8. Oliveira AL, de Souza M, Carvalho-Dias VM, Ruiz MA, Silla L, Tanaka PY, et al.Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2007;39(12):775-81. Ghosn M, Dagher E, Nasr F, Chahine G, Taleb N, Nasnas R, et al.[Infections in cancer patients with granulocytopenia. Retrospective studies of 59 febrile episodes with hospitalization]. J Med Liban. 1994;42(3):117-22. Hamzeh F, Kanj SS, Uwaydah M . Febrile neutropenia in cancer patients in a tertiary care medical center in Lebanon: microbial spectrum and outcome. J Med Liban. 2000;48(3):136-42. Kanafani ZA, Dakdouki GK, El-Chammas KI, Eid S, Araj GF, Kanj SS . Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: a view of the past decade. Int J Infect Dis. 2007;11(5):450-3. Moghnieh RA, Kanafani ZA, Tabaja HZ, Sharara SL, Awad LS, Kanj SS . Epidemiology of common resistant bacterial pathogens in the countries of the Arab League. Lancet Infect Dis. 2018;18(12):e379-e94. Moussally M, Zahreddine N, Kazma J, Ahmadieh R, Kan SS, Kanafan ZA . Prevalence of antibiotic-resistant organisms among hospitalized patients at a tertiary care center in Lebanon, 2010-2018. J Infect Public Health. 2021;14(1):12-6. Clerici D, Oltolini C, Greco R, Ripa M, Giglio F, Mastaglio S, et al.The place of ceftazidime/avibactam and ceftolozane/tazobactam for therapy of haematological patients with febrile neutropenia. Int J Antimicrob Agents. 2021;57(6):106335. Soriano A, Carmeli Y, Omrani AS, Moore LSP, Tawadrous M, Irani P . Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review. Infect Dis Ther. 2021;10(4):1989-2034. Villafuerte-Gutierrez P, Villalon L, Losa JE, Henriquez-Camacho C . Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update. Adv Hematol. 2014;2014:986938. Charlson ME, Pompei P, Ales KL, MacKenzie CR . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al.Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4):e56-93. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10. Azam F, Latif MF, Farooq A, Tirmazy SH, AlShahrani S, Bashir S, et al.Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) Score for Cancer Patients by Oncology Healthcare Professionals. Case Rep Oncol. 2019;12(3):728-36. Hansen BA, Wendelbo Ø, Bruserud Ø, Hemsing AL, Mosevoll KA, Reikvam H . Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment. Mediterr J Hematol Infect Dis. 2020;12(1):e2020009. Binkhamis K, Aldakhil I, Alhawas A, Alsaleh A, Albaroudi A, Almuhanna B, et al.Prevalence of bacterial bloodstream infections and association between neutropenia and 30-day mortality among oncology inpatients at a university hospital in Saudi Arabia. Ann Saudi Med. 2023;43(3):172-8. El Omri H, Padmanabhan R, Taha RY, Kassem N, Elsabah H, Ellahie AY, et al.Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009-2019). J Infect Public Health. 2024;17(1):152-62. Al-Tawfiq JA, Hinedi K, Khairallah H, Saadeh B, Abbasi S, Noureen M, et al.Epidemiology and source of infection in patients with febrile neutropenia: A ten-year longitudinal study. J Infect Public Health. 2019;12(3):364-6. Rodriguez-Bano J, Navarro MD, Romero L, Martinez-Martinez L, Muniain MA, Perea EJ, et al.Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol. 2004;42(3):1089-94. Mikulska M, Averbuch D, Tissot F, Cordonnier C, Akova M, Calandra T, et al.Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect. 2018;76(1):20-37. Satlin MJ, Walsh TJ . Multidrug-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2017;19(6). Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al.European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98(12):1826-35. Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, et al.Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018;36(14):1443-53. Groll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, et al.Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol. 2014;15(8):e327-40. Khoo AL, Zhao YJ, Teng M, Ying D, Jin J, Chee YL, et al.Evaluation of a risk-guided strategy for empirical carbapenem use in febrile neutropenia. Int J Antimicrob Agents. 2018;52(3):350-7. Sonya K. Kedzior P, YoungYoon Ham, PharmD, Joseph Bubalo, PharmD, BCPS, BCOP . Overcoming Resistance: Antibiotic Guidance for Multidrug-Resistant Febrile Neutropenia in Patients with Cancer. Journal of Hematology Oncology Pharmacy. 2021;11. Ogura S, Kimura M, Takagi S, Mitsuki T, Yuasa M, Kageyama K, et al.Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis. Eur J Clin Microbiol Infect Dis. 2021;40(5):941-8. Sereeaphinan C, Kanchanasuwan S, Julamanee J . Mortality-associated clinical risk factors in patients with febrile neutropenia: A retrospective study. IJID Reg. 2021;1:5-11. Wanitpongpun C, Teawtrakul N, Lanamtieng T, Chansung K, Sirijeerachai C, Amampai W, et al.Clinical factors predictive of mortality in acute leukemia patients with febrile neutropenia. Am J Blood Res. 2021;11(1):59-65. Jorgensen 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. Herrera F, Torres D, Laborde A, Jordán R, Mañez N, Berruezo L, et al.Ceftazidime-Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia. Microorganisms. 2024;12(1). Castón JJ, Lacort-Peralta I, Martín-Dávila P, Loeches B, Tabares S, Temkin L, et al.Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients. Int J Infect Dis. 2017;59:118-23. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4574482","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":317636534,"identity":"54be55cb-a329-473d-b10b-6578668e3efc","order_by":0,"name":"Jim Abi Frem","email":"","orcid":"","institution":"Brighton and Sussex University Hospitals","correspondingAuthor":false,"prefix":"","firstName":"Jim","middleName":"Abi","lastName":"Frem","suffix":""},{"id":317636535,"identity":"fd49f997-4c19-4f35-941a-71f81de55695","order_by":1,"name":"Alicia Khazzeka","email":"","orcid":"","institution":"American University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Alicia","middleName":"","lastName":"Khazzeka","suffix":""},{"id":317636536,"identity":"d22dfaf4-a8ab-4b6d-9f23-1008b4da3185","order_by":2,"name":"Fatima Allaw","email":"","orcid":"","institution":"American University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Fatima","middleName":"","lastName":"Allaw","suffix":""},{"id":317636537,"identity":"cfadbe9b-5ff6-4081-ad5e-2164b665eed4","order_by":3,"name":"Caren Doueiry","email":"","orcid":"","institution":"American University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Caren","middleName":"","lastName":"Doueiry","suffix":""},{"id":317636538,"identity":"6ca6c294-7175-4ba2-b23d-2deb48adebb2","order_by":4,"name":"Racha Ghoussaini","email":"","orcid":"","institution":"American University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Racha","middleName":"","lastName":"Ghoussaini","suffix":""},{"id":317636539,"identity":"b1bc84f0-cfdd-4e07-984e-29de40bee93c","order_by":5,"name":"Rayan Mohamad","email":"","orcid":"","institution":"American University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Rayan","middleName":"","lastName":"Mohamad","suffix":""},{"id":317636540,"identity":"7155d4b9-b180-41c9-8728-79a5ee880719","order_by":6,"name":"Zeina A. Kanafani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYDACHsaGAx8YGBKATAMGhoIDxGhhbnw4A67FgCgt7M3GPCRpke852CZtU3M4j4G9eZsEg8EdwloYexvbpHOOHS5m4DlWBtTyjLAWZn5GoBa2w4kNEjlmQC2HCWthA2mx+AfUIv+GSC08vI3NxoxtIFt4iNQiwXOw8WFvX3oxG09asUUCMX6R70l/cODHN+s8fvbDG298qCAixOCADUQkkKBhFIyCUTAKRgEeAABvDjc6vyI2dQAAAABJRU5ErkJggg==","orcid":"","institution":"American University of Beirut","correspondingAuthor":true,"prefix":"","firstName":"Zeina","middleName":"A.","lastName":"Kanafani","suffix":""}],"badges":[],"createdAt":"2024-06-13 08:01:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4574482/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4574482/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59747474,"identity":"c86e2c5e-7aa6-4951-805c-c34a400772bc","added_by":"auto","created_at":"2024-07-05 18:18:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":506829,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4574482/v1/1ffd576c-3b46-4ff7-a8dc-cc4ea58225b1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eCeftazidime-Avibactam for the Treatment of Febrile Neutropenia in HSCT Recipients and Acute Leukemia Patients Post Induction Chemotherapy\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePatients with hematological malignancies are at an increased risk of developing serious infections, which significantly affect both their survival and quality of life. More than 80% of patients with hematological malignancies will present with fever during a chemotherapy cycle that has caused neutropenia (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Deficits in components of the innate immune system, as a result of the underlying malignancy, may predispose to the development of invasive bacterial and fungal infections (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The treatment itself, more commonly, can lead to neutropenia, which is a major predisposing factor for infections (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Cytotoxic antineoplastic therapy for hematological malignancies as well as stem cell transplantation are common causes of treatment-induced neutropenia due to a decrease in white blood cell production (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Fever is often the only sign of infection, since the intensity of the neutrophil-mediated inflammatory response may be blunted (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). As such, a high index of suspicion followed by an extensive diagnostic work-up and prompt initiation of antimicrobial therapy are crucial (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe epidemiology of microorganisms isolated from the blood of patients with neutropenic fever has changed over time. While Gram-negative pathogens predominated in the 1960s, the increased use of indwelling catheters in the 1980s and 1990s led to a higher incidence of Gram-positive organisms (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Currently, the most common blood isolates in most centers are coagulase-negative staphylococci (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), although in some cases a trend reversal is being witnessed with the emergence of drug-resistant Gram-negative pathogens (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In our country, however, this variation has not been observed. Over the years, several studies from Lebanon have shown a consistently higher prevalence of Gram-negative infections in febrile neutropenic patients (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In addition, antimicrobial resistance among Gram-negative pathogens in Lebanon is substantial. The proportions of extended-spectrum beta-lactamase (ESBL) producing Enterobacterales exceed 30% (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), while proportions of carbapenem-resistant Enterobacterales range from 3\u0026ndash;6% (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEmpiric therapy for febrile neutropenia, while guided by international guidelines (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), must also take into account the local epidemiology. Ceftazidime-avibactam (CAZAVI), a broad-spectrum beta-lactam/beta-lactamase inhibitor combination, has been increasingly used in patients with febrile neutropenia, whether empirically in patients who fail to respond to first-line therapy, or as directed therapy when a resistant Gram-negative pathogen is recovered from clinical cultures (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe aim of our study is to characterize febrile neutropenia episodes in patients with acute leukemias and those undergoing hematopoietic stem cell transplantation (HSCT), and to compare the outcomes of patients who received traditional antimicrobial therapy to those who received CAZAVI.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cem\u003eStudy design and population:\u003c/em\u003e This is a retrospective case-control study conducted at the American University of Beirut Medical Center (AUBMC), a tertiary care center in Lebanon. Our sample included all adult patients presenting with febrile neutropenia following induction therapy for acute leukemia or during HSCT. The medical records of febrile neutropenic patients admitted to\u0026nbsp;AUBMC between 2009 and 2022 were reviewed. Patients were included more than once if they developed another febrile neutropenia episode at least 14 days after the initial one. Study subjects were classified into cases who received CAZAVI for the treatment of febrile neutropenia, and controls who were treated with the best available therapy (BAT).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDefinitions and severity scores:\u003c/em\u003e We adopted the definitions of fever and neutropenia as set forth by the guidelines of the Infectious Diseases Society of America (IDSA): an oral temperature record of 38.3\u0026deg;C (101\u0026deg;F) or a temperature of \u0026ge; 38.0\u0026deg;C (100.4\u0026deg;F) lasting for at least one hour, and a neutrophil count below 1500/mm\u003csup\u003e3\u003c/sup\u003e (16).\u0026nbsp;Several indices were used to estimate baseline functioning and illness severity and were calculated based on published literature: the Charlson Comorbidity Index predicts the 10-year mortality for patients with a number of comorbidities\u0026nbsp;(17); the Multinational Association for Supportive Care in Cancer (MASCC) score index measures the risk of complications in patients with febrile neutropenia, where a score of \u0026lt; 21 \u0026nbsp;indicates high risk of having a serious infection\u0026nbsp;(18); the Quick Sepsis Related Organ Failure Assessment (qSOFA) is a bedside tool used to screen for sepsis in patients with a suspected infection\u0026nbsp;(19); the Eastern Cooperative Oncology Group (ECOG) performance status is a scale used to determine the disease progression and its effect on daily living habits of cancer patients, with a score ranging from 0 (fully active) to 5 (dead)\u0026nbsp;(20).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis:\u003c/em\u003e Data were entered into SPSS. Bivariable analysis was performed to detect statistical associations using the Chi-square test for categorical variables and the independent samples t-test for continuous variables. Backward stepwise binary logistic regression was performed to test for independent associations, including effect of treatment with CAZAVI on sepsis and mortality, controlling for potential confounders. Variables with a p-value of 0.2 or less on bivariable analysis were included in the regression model.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthical considerations:\u003c/em\u003e The Institutional Review Board at the American University of Beirut approved the study. Informed consent was waived because of the retrospective nature of the analysis.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eDuring the study period, we recorded 339 episodes of neutropenic fever, 39 of which were treated with CAZAVI and 300 with BAT. The baseline characteristics of patients are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Age and sex distribution were similar in both study arms. Compared to the BAT group, there was a higher proportion of patients in the CAZAVI group who were undergoing HSCT (33.3% allo-HSCT and 15.4% auto-HSCT), whereas most patients in the BAT group were receiving induction therapy for acute myeloid leukemia (62.0%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). As far as baseline severity scores, there was no difference in the mean Charlson and ECOG scores between the two study groups. However, the MASCC score, which is calculated upon developing the episode of febrile neutropenia, was significantly lower in the CAZAVI group (19.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1 vs. 21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1; p\u0026thinsp;=\u0026thinsp;0.001), indicating a high risk for developing complications from neutropenic fever. More patients who received CAZAVI treatment had an established source of infection compared to those who received BAT (89.7% vs. 57.0%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients and the febrile neutropenia episodes by treatment group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCAZAVI arm\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBAT arm\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;300)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, \u003cem\u003eyears\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177 (59.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic renal insufficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic pulmonary disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute myeloid leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute lymphocytic leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuto-HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAllo-HSCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital stay*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (41.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e218 (72.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical ventilation*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral line*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123 (41.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary catheter*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSteroid therapy*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery within 30 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharlson score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMASCC score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eqSOFA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstablished source of infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (89.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e171 (57.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinically/radiologically determined\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e149 (49.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrobiologically determined\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (59.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravascular device\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin and soft tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasopharyngeal/oropharyngeal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral nervous system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNumbers indicate n (%) for categorical variables and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for continuous variables\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*More than 48 hours within the past 30 days\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCAZAVI\u0026thinsp;=\u0026thinsp;ceftazidime-avibactam; BAT\u0026thinsp;=\u0026thinsp;best available therapy; Auto-HSCT\u0026thinsp;=\u0026thinsp;autologous hematopoietic stem cell transplantation; Allo-HSCT\u0026thinsp;=\u0026thinsp;allogeneic hematopoietic stem cell transplantation; ECOG\u0026thinsp;=\u0026thinsp;Eastern Cooperative Oncology Group; ICU\u0026thinsp;=\u0026thinsp;intensive care unit; MASCC\u0026thinsp;=\u0026thinsp;Multinational Association for Supportive Care in Cancer\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients in the CAZAVI arm were more likely to have a microbiologically documented infection (59.0% vs. 28.3%). The distribution of isolated organisms is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Gram-negative organisms predominated in both CAZAVI and BAT arms (74.4% and 38.3%, respectively), whereas Gram-positive organisms trailed by a considerable margin (28.2% and 15.7%, respectively). As expected, a larger number of patients who received CAZAVI had antimicrobial-resistant Gram-negative organisms, including ESBL-producing and carbapenem-resistant \u003cem\u003eE. coli\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIsolated microorganisms in 339 febrile neutropenia episodes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrganism\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCAZAVI arm\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBAT arm\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;300)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGram-negatives\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (74.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e115 (38.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21/39 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e79/300 (26.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESBL-producing \u003cem\u003eE. coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/21 (80.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43/79 (54.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarbapenem-resistant \u003cem\u003eE. coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/21 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/79 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/39 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11/300 (3.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESBL-producing \u003cem\u003eKlebsiella\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5/11 (45.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/39 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15/300 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Enterobacterales\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/39 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6/300 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAcinetobacter\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/39 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2/300 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStenotrophomonas maltophilia\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/39 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/300 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSalmonella\u003c/em\u003e non-typhi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/300 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGram-positives\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47 (15.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoagulase-negative staphylococci\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/39 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22/300 (7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/39 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12/300 (4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eviridans streptococci\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10/300 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/39 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2/300 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/300 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eListeria monocytogenes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2/300 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBacillus\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/300 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eClostridium difficile\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/39 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/300 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNumbers indicate n (%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eCAZAVI\u0026thinsp;=\u0026thinsp;ceftazidime-avibactam; BAT\u0026thinsp;=\u0026thinsp;best available therapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eUp to 18.5% of study subjects had received carbapenem therapy for more than 48 hours in the 30 days preceding the febrile neutropenia episode. In addition, 85% of the overall population had received antibacterial and antiviral prophylaxis, and 89% had received antifungal prophylaxis. In the BAT arm, carbapenems were the most commonly used antibiotics for empiric as well as for directed therapy, followed by cefepime, piperacillin-tazobactam, and glycopeptides.\u003c/p\u003e \u003cp\u003eThe febrile neutropenia episodes in our study were associated with various complications, and almost all were significantly more frequent in the CAZAVI group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The most commonly observed complication was sepsis, which occurred in 59.0% of patients in the CAZAVI arm and in 15.0% of patients in the BAT arm (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Other important complications included intensive care unit (ICU) admission, respiratory failure, and persistent bacteremia. Patients who received CAZAVI-based regimens were more likely to have a fatal outcome compared to patients who received BAT (23.1% vs. 3.0%). We conducted a multivariable logistic regression analysis to determine independent risk factors for sepsis and mortality, and we were particularly interested in evaluating whether the type of antibiotic treatment had an effect on patient outcome. The results of the multivariable models are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Receiving CAZAVI was an independent risk factor for both sepsis and mortality, with a large effect size for both outcomes (aOR 6.33 [95% CI 2.81\u0026ndash;14.30] and 7.82 [2.63\u0026ndash;23.26], respectively). Recent receipt of steroids was a significant risk factor for sepsis (aOR 2.12 [95% CI 1.08\u0026ndash;4.15]) but not for mortality. On the other hand, MASCC score was negatively correlated with both sepsis and mortality.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComplications of febrile neutropenia episodes by treatment group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCAZAVI arm\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBAT arm\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;300)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (59.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePersistent bacteremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute kidney injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNumbers indicate n (%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCAZAVI\u0026thinsp;=\u0026thinsp;ceftazidime-avibactam; BAT\u0026thinsp;=\u0026thinsp;best available therapy; ARDS\u0026thinsp;=\u0026thinsp;acute respiratory distress syndrome; ICU\u0026thinsp;=\u0026thinsp;intensive care unit\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic regression models showing independent associations with sepsis and mortality in patients with febrile neutropenia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eaOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eaOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAZAVI therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.33 (2.81\u0026ndash;14.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.82 (2.63\u0026ndash;23.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSteroid therapy*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.12 (1.08\u0026ndash;4.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMASCC score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.75 (0.69\u0026ndash;0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.77 (0.69\u0026ndash;0.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* More than 48 hours within the past 30 days\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eaOR\u0026thinsp;=\u0026thinsp;adjusted odds ratio; CI\u0026thinsp;=\u0026thinsp;confidence interval; CAZAVI\u0026thinsp;=\u0026thinsp;ceftazidime-avibactam; MASCC\u0026thinsp;=\u0026thinsp;Multinational Association for Supportive Care in Cancer\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis is a retrospective case-control study evaluating the effect of CAZAVI on patient outcomes with neutropenic fever compared to other treatment regimens. With the ever-increasing antimicrobial resistance rates among Gram-negative pathogens, broad-spectrum agents are more likely to be prescribed, despite not being traditional treatment options based on IDSA guidelines. This is particularly true for high-risk patients with hematological malignancies or HSCT recipients who experience more profound and prolonged neutropenia.\u003c/p\u003e \u003cp\u003eAs such, evaluating the prevalence of potentially causative organisms in patients with neutropenic fever is crucial, as it facilitates prompt initiation of antimicrobial treatment, preventing rapid progression to sepsis and shock (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). \u003cem\u003eE. coli\u003c/em\u003e was the most common isolated organism among patients with febrile neutropenia in our study, consistent with the trend observed in Lebanon for the past 25 years (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Few studies have been published from the Arab region regarding the epidemiology of febrile neutropenia in cancer patients, yielding variable results. Data from Saudi Arabia indicated a predominance of Gram-negative bloodstream infections in neutropenic patients, with \u003cem\u003eE. coli\u003c/em\u003e being the most common isolated pathogen (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). A retrospective study from Qatar, which included more than 1000 episodes of febrile neutropenia, showed a prevalence of 41% of ESBL-producing organisms (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The findings were different in Kuwait and the UAE, where there was a predominance of Gram-positive infections among febrile neutropenic patients (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe emergence of multi-drug resistant Gram-negative pathogens can be attributed to the use of quinolones as prophylaxis, which in itself is a risk factor for colonization by such organisms (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This correlates with our findings, given that levofloxacin was the most commonly used drug for prophylaxis, as it reduces the incidence of bloodstream infections with no effect on mortality (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatients with acute leukemia usually acquire resistant bacteria due to their immunocompromised state (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). They thus receive broad-spectrum antibiotics, eventually tailored to culture results. Initial empiric treatment in febrile neutropenia includes a beta-lactam with Pseudomonas coverage (\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). In our center, carbapenems were most commonly used as empiric treatment, correlating with the rising number of Gram negative ESBL organisms. Vancomycin and cefepime were equally used due to the rising number of central venous catheters reflecting an increase in the incidence of Staphylococcus coagulase negative bacteremia. This is consistent with clinical practice guidelines (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs expected, a larger number of patients who received ceftazidime-avibactam had antimicrobial resistant organisms. In fact, the increasing incidence of resistant pathogens remains a challenge in the management of febrile neutropenia and preliminary data have shown that CAZAVI can play a role as empiric therapy for those who had carbapenem-resistant \u003cem\u003eKlebsiella\u003c/em\u003e bloodstream infections (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, patients who received CAZAVI-based regimens were more likely to have complications compared to the BAT group. Bacteremia represents 11.7% of all sources of infection, concordant with a study conducted in Saudi Arabia (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). A previous study done in Lebanon showed that bacteremia was the source in 18% of all patients with febrile neutropenia (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), while another study on patients with HSCT showed that the incidence of bacteremia was 41.2% (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), a value much higher than what we currently observed. Septic shock, cardiovascular complications and persistent infection were all significantly associated with increased mortality. A retrospective cohort study conducted in 2021 showed that septic shock is one of the two main independent predictors of mortality in febrile neutropenia (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur multivariable logistic regression analysis also revealed that CAZAVI was an independent risk factor for both sepsis and mortality, with a large effect size for both outcomes. This raises concerns about the role of CAZAVI in treating febrile neutropenia in this population. Some studies have reported similar outcomes with CAZAVI. For instance, a large retrospective study by Jorgensen et al. (2019) reported a 30-day mortality of 17% in patients treated with CAZAVI (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, these results should be interpreted with caution and may be biased due to several limitations. First, a smaller number of patients received CAZAVI compared to BAT. This may have been influenced by the fact that CAZAVI was not always available at our institution during the study period and was provided based on patient need and financial capacity. Additionally, many patients received CAZAVI empirically and may have died from complications or infections unrelated to the administered drug. Nevertheless, CAZAVI has proven effective in several recent studies for febrile neutropenia, particularly in patients with Klebsiella pneumoniae carbapenemase (KPC) (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) and has shown higher clinical cure rates (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003e Limitations of this study include the retrospective nature of its design, the relatively small sample size, and its reliance on data generated from a single tertiary care center.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAwareness of the local patterns of infections and susceptibilities, as well as understanding the predictors for septic shock and mortality in patients with febrile neutropenia pave the way to successful treatment and prevention of neutropenic fever.\u003c/p\u003e \u003cp\u003eReducing the morbidity and mortality risk relies on the above in order to successfully initiate proper empiric treatment. More studies are needed to investigate adverse events related to the introduction of ceftazidime-avibactam and to establish a benefit to risk ratio, as there is still no consensus on appropriate CAZAVI dosage in such scenarios and its efficiency in resolving the febrile neutropenia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e \u003ch2\u003eCONFLICTS OF INTEREST\u003c/h2\u003e \u003cp\u003eNone to declare\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ.A., F.A., and R.M prepared protocol write-up; J.A., F.A., C.D.,R.G.,R.M., and A.K. collected the data; J.A., R.G., and A.K. wrote the main manuscript text and prepared the tables; F.A. edited the manuscript; Z.K. conceptualized the study, designed the study, analyzed the data, revised, and edited the main manuscript text.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLyman GH, Kuderer NM\u003cstrong\u003e. \u003c/strong\u003eEpidemiology of febrile neutropenia. Support Cancer Ther. 2003;1(1):23-35.\u003c/li\u003e\n\u003cli\u003eLogan C, Koura D, Taplitz R\u003cstrong\u003e. \u003c/strong\u003eUpdates in infection risk and management in acute leukemia. Hematology Am Soc Hematol Educ Program. 2020;2020(1):135-9.\u003c/li\u003e\n\u003cli\u003eBaden LR, Swaminathan S, Angarone M, Blouin G, Camins BC, Casper C, et al.Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2016;14(7):882-913.\u003c/li\u003e\n\u003cli\u003eStern A, Carrara E, Bitterman R, Yahav D, Leibovici L, Paul M\u003cstrong\u003e. \u003c/strong\u003eEarly discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution in people with cancer. Cochrane Database Syst Rev. 2019;1(1):CD012184.\u003c/li\u003e\n\u003cli\u003eSatyanarayana G\u003cstrong\u003e. \u003c/strong\u003eWork-up for Fever During Neutropenia for Both the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient. Infect Dis Clin North Am. 2019;33(2):381-97.\u003c/li\u003e\n\u003cli\u003eFreifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al.Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4):e56-93.\u003c/li\u003e\n\u003cli\u003eCattaneo C, Quaresmini G, Casari S, Capucci MA, Micheletti M, Borlenghi E, et al.Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution. J Antimicrob Chemother. 2008;61(3):721-8.\u003c/li\u003e\n\u003cli\u003eOliveira AL, de Souza M, Carvalho-Dias VM, Ruiz MA, Silla L, Tanaka PY, et al.Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2007;39(12):775-81.\u003c/li\u003e\n\u003cli\u003eGhosn M, Dagher E, Nasr F, Chahine G, Taleb N, Nasnas R, et al.[Infections in cancer patients with granulocytopenia. Retrospective studies of 59 febrile episodes with hospitalization]. J Med Liban. 1994;42(3):117-22.\u003c/li\u003e\n\u003cli\u003eHamzeh F, Kanj SS, Uwaydah M\u003cstrong\u003e. \u003c/strong\u003eFebrile neutropenia in cancer patients in a tertiary care medical center in Lebanon: microbial spectrum and outcome. J Med Liban. 2000;48(3):136-42.\u003c/li\u003e\n\u003cli\u003eKanafani ZA, Dakdouki GK, El-Chammas KI, Eid S, Araj GF, Kanj SS\u003cstrong\u003e. \u003c/strong\u003eBloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: a view of the past decade. Int J Infect Dis. 2007;11(5):450-3.\u003c/li\u003e\n\u003cli\u003eMoghnieh RA, Kanafani ZA, Tabaja HZ, Sharara SL, Awad LS, Kanj SS\u003cstrong\u003e. \u003c/strong\u003eEpidemiology of common resistant bacterial pathogens in the countries of the Arab League. Lancet Infect Dis. 2018;18(12):e379-e94.\u003c/li\u003e\n\u003cli\u003eMoussally M, Zahreddine N, Kazma J, Ahmadieh R, Kan SS, Kanafan ZA\u003cstrong\u003e. \u003c/strong\u003ePrevalence of antibiotic-resistant organisms among hospitalized patients at a tertiary care center in Lebanon, 2010-2018. J Infect Public Health. 2021;14(1):12-6.\u003c/li\u003e\n\u003cli\u003eClerici D, Oltolini C, Greco R, Ripa M, Giglio F, Mastaglio S, et al.The place of ceftazidime/avibactam and ceftolozane/tazobactam for therapy of haematological patients with febrile neutropenia. Int J Antimicrob Agents. 2021;57(6):106335.\u003c/li\u003e\n\u003cli\u003eSoriano A, Carmeli Y, Omrani AS, Moore LSP, Tawadrous M, Irani P\u003cstrong\u003e. \u003c/strong\u003eCeftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review. Infect Dis Ther. 2021;10(4):1989-2034.\u003c/li\u003e\n\u003cli\u003eVillafuerte-Gutierrez P, Villalon L, Losa JE, Henriquez-Camacho C\u003cstrong\u003e. \u003c/strong\u003eTreatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update. Adv Hematol. 2014;2014:986938.\u003c/li\u003e\n\u003cli\u003eCharlson ME, Pompei P, Ales KL, MacKenzie CR\u003cstrong\u003e. \u003c/strong\u003eA new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83.\u003c/li\u003e\n\u003cli\u003eFreifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al.Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4):e56-93.\u003c/li\u003e\n\u003cli\u003eSinger M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10.\u003c/li\u003e\n\u003cli\u003eAzam F, Latif MF, Farooq A, Tirmazy SH, AlShahrani S, Bashir S, et al.Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) Score for Cancer Patients by Oncology Healthcare Professionals. Case Rep Oncol. 2019;12(3):728-36.\u003c/li\u003e\n\u003cli\u003eHansen BA, Wendelbo \u0026Oslash;, Bruserud \u0026Oslash;, Hemsing AL, Mosevoll KA, Reikvam H\u003cstrong\u003e. \u003c/strong\u003eFebrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment. Mediterr J Hematol Infect Dis. 2020;12(1):e2020009.\u003c/li\u003e\n\u003cli\u003eBinkhamis K, Aldakhil I, Alhawas A, Alsaleh A, Albaroudi A, Almuhanna B, et al.Prevalence of bacterial bloodstream infections and association between neutropenia and 30-day mortality among oncology inpatients at a university hospital in Saudi Arabia. Ann Saudi Med. 2023;43(3):172-8.\u003c/li\u003e\n\u003cli\u003eEl Omri H, Padmanabhan R, Taha RY, Kassem N, Elsabah H, Ellahie AY, et al.Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009-2019). J Infect Public Health. 2024;17(1):152-62.\u003c/li\u003e\n\u003cli\u003eAl-Tawfiq JA, Hinedi K, Khairallah H, Saadeh B, Abbasi S, Noureen M, et al.Epidemiology and source of infection in patients with febrile neutropenia: A ten-year longitudinal study. J Infect Public Health. 2019;12(3):364-6.\u003c/li\u003e\n\u003cli\u003eRodriguez-Bano J, Navarro MD, Romero L, Martinez-Martinez L, Muniain MA, Perea EJ, et al.Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol. 2004;42(3):1089-94.\u003c/li\u003e\n\u003cli\u003eMikulska M, Averbuch D, Tissot F, Cordonnier C, Akova M, Calandra T, et al.Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect. 2018;76(1):20-37.\u003c/li\u003e\n\u003cli\u003eSatlin MJ, Walsh TJ\u003cstrong\u003e. \u003c/strong\u003eMultidrug-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2017;19(6).\u003c/li\u003e\n\u003cli\u003eAverbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al.European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98(12):1826-35.\u003c/li\u003e\n\u003cli\u003eTaplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, et al.Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018;36(14):1443-53.\u003c/li\u003e\n\u003cli\u003eGroll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, et al.Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol. 2014;15(8):e327-40.\u003c/li\u003e\n\u003cli\u003eKhoo AL, Zhao YJ, Teng M, Ying D, Jin J, Chee YL, et al.Evaluation of a risk-guided strategy for empirical carbapenem use in febrile neutropenia. Int J Antimicrob Agents. 2018;52(3):350-7.\u003c/li\u003e\n\u003cli\u003eSonya K. Kedzior P, YoungYoon Ham, PharmD, Joseph Bubalo, PharmD, BCPS, BCOP\u003cstrong\u003e. \u003c/strong\u003eOvercoming Resistance: Antibiotic Guidance for Multidrug-Resistant Febrile Neutropenia in Patients with Cancer. Journal of Hematology Oncology Pharmacy. 2021;11.\u003c/li\u003e\n\u003cli\u003eOgura S, Kimura M, Takagi S, Mitsuki T, Yuasa M, Kageyama K, et al.Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis. Eur J Clin Microbiol Infect Dis. 2021;40(5):941-8.\u003c/li\u003e\n\u003cli\u003eSereeaphinan C, Kanchanasuwan S, Julamanee J\u003cstrong\u003e. \u003c/strong\u003eMortality-associated clinical risk factors in patients with febrile neutropenia: A retrospective study. IJID Reg. 2021;1:5-11.\u003c/li\u003e\n\u003cli\u003eWanitpongpun C, Teawtrakul N, Lanamtieng T, Chansung K, Sirijeerachai C, Amampai W, et al.Clinical factors predictive of mortality in acute leukemia patients with febrile neutropenia. Am J Blood Res. 2021;11(1):59-65.\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\u003eHerrera F, Torres D, Laborde A, Jord\u0026aacute;n R, Ma\u0026ntilde;ez N, Berruezo L, et al.Ceftazidime-Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia. Microorganisms. 2024;12(1).\u003c/li\u003e\n\u003cli\u003eCast\u0026oacute;n JJ, Lacort-Peralta I, Mart\u0026iacute;n-D\u0026aacute;vila P, Loeches B, Tabares S, Temkin L, et al.Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients. Int J Infect Dis. 2017;59:118-23.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Febrile neutropenia, acute leukemia, hematopoietic stem cell transplant, ceftazidime-avibactam, mortality, morbidity","lastPublishedDoi":"10.21203/rs.3.rs-4574482/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4574482/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFebrile neutropenia is a common and major complication in patients with acute leukemia or those undergoing hematopoietic stem cell transplantation (HSCT). Understanding patient characteristics and patterns of susceptibility in febrile neutropenia is essential to provide the appropriate antimicrobial therapy. First-line agents should have Pseudomonas coverage, but with the increase in multi-drug resistant organisms, ceftazidime-avibactam has emerged as a new therapy in febrile neutropenia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis is a retrospective case-control study of a total of 300 admissions (143 patients) between January 2009 and December 2017. Patients with hematologic neoplasms and patients that underwent HSCT who satisfied the definition of febrile neutropenia and treated with ceftazidime-avibactam (CAZAVI) were included in the study. A bivariate regression model to explore independent predictors of septic shock and mortality was constructed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePatients who received ceftazidime-avibactam (CAZAVI) were more likely to have a microbiologically documented infection (59.0% vs. 28.3%). Almost all complications were significantly more frequent in the CAZAVI group, with sepsis being the most common, occurring in 59.0% of patients in the CAZAVI arm. Our multivariable logistic regression analysis showed that receiving CAZAVI was an independent risk factor for both sepsis and mortality (aOR 6.33 [95% CI 2.81\u0026ndash;14.30] and 7.82 [2.63\u0026ndash;23.26], respectively).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eKnowing the most common organisms isolated during a neutropenic fever episode as well as the patterns of resistance, compounded with an understanding of the risk factors for morbidity and mortality in such a vulnerable population, is key to providing them with appropriate prophylactic and therapeutic management. In addition, more studies should be done on the effectiveness of ceftazidime-avibactam in treating febrile neutropenia in the population at hand.\u003c/p\u003e","manuscriptTitle":"Ceftazidime-Avibactam for the Treatment of Febrile Neutropenia in HSCT Recipients and Acute Leukemia Patients Post Induction Chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-01 13:15:02","doi":"10.21203/rs.3.rs-4574482/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"54436911-f9ff-44f2-8ac4-635efb72d8df","owner":[],"postedDate":"July 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-13T19:29:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-01 13:15:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4574482","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4574482","identity":"rs-4574482","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}