Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154.

The Relationship of Comorbid Diseases and Empirical Antibiotic Usage with Superinfection in COVID-19 Patients.

OBJECTIVE: To identify the microorganisms responsible for superinfections in patients admitted with COVID-19 and evaluate the impact of empirical antibiotic regimen and comorbid disease on superinfections comparing COVID-19 patients with and without secondary infection. STUDY DESIGN: A descriptive study. Place and Duration of the Study: Department of Microbiology, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkiye, from March to July 2020. METHODOLOGY: This study was conducted with patients diagnosed with COVID-19 disease based on radiological or quantitative RT-PCR test results. Culture results, demographic characteristics, clinical variables, and therapeutic regimen were collected from medical records. RESULTS: Superinfection developed in 48 (26.96%) of 178 cultures (24 of 101 patients) followed up in the COVID-19 clinics. Infections were determined as 25 (52.08%) bloodstream, 11 (22.9%) urinary tract, 10 (20.8%) respiratory tract and 2 (4.16%) soft tissue infections, respectively. Secondary infectious agents were E.coli in 11 (22.9%), A.baumannii in 8 (16.7%), S.homminis in 7 (14.6%), S.epidermidis in 6 (12.5%), K.pneumoniae in 4 (8.3%), C.albicans in 2 (4.1%), and other bacterial and fungal agents in 10 (20.8%). The median range from admission to the hospital to detecting microorganism growth was the longest with piperacillin/tazobactam with moxifloxacin and azithromycin. Secondary microorganism detection was delayed, mostly due to the empirical use of moxifloxacin, azithromycin, and piperacillin/tazobactam. CONCLUSION: Demographic characteristics, comorbidity and antibiotic use of patients were not directly related to secondary infections. In addition, the empirical use of azithromycin and moxifloxacin with piperacillin/tazobactam appeared to delay the development of superinfection. KEY WORDS: Superinfection, COVID-19, Comorbidity.

Piperacillin-tazobactam induced immune hemolytic anemia led to increased renal impairment and eventual death from multiple organ failure in a patient with hypertensive nephropathy: case report and literature review.

BACKGROUND: Piperacillin is one of the most common drugs that cause drug-induced immune hemolytic anemia, but a complete description of the serological features and course of the disease is rare. This study completely describes the serological characteristics and course of a patient with hypertensive nephropathy who developed drug-induced immune hemolytic anemia and worsened renal function during repeated administration of piperacillin-tazobactam. CASE PRESENTATION: A 79-year-old male patient with hypertensive nephropathy who developed severe hemolytic anemia and worsened renal function during intravenous piperacillin-tazobactam anti-infective treatment due to lung infection. Serological tests showed that the result of the direct antiglobulin test for anti-IgG was positive (4 +) and anti-C3d was negative, and the irregular red blood cell antibody screening test was negative. Plasma samples collected at different times from 2 days before to 12 days after the discontinuation of piperacillin-tazobactam administration were incubated with piperacillin solution and red blood cells of O-type healthy blood donors at 37 °C, IgG piperacillin-dependent antibodies were detected, and the highest titer was 128. However, no tazobactam-dependent antibody was detected in any plasma samples. Therefore, the patient was diagnosed with piperacillin-induced immune hemolytic anemia. Although blood transfusion and continuous renal replacement therapy were given, the patient died of multiple organ failure 15 days after the administration of piperacillin-tazobactam was stopped. CONCLUSION: This is the first complete description of the disease course and serological changes of piperacillin-induced immune hemolytic anemia, which is bound to help deepen the understanding of drug-induced immune hemolytic anemia and draw profound lessons from it.

Efficacy and safety of piperacillin-tazobactam compared with meropenem in treating complicated urinary tract infections including acute pyelonephritis due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

Introduction: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs. Methods: A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae. Results: Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01). Discussion: In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients.

BACKGROUND: Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU. RESEARCH QUESTION: Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury? STUDY DESIGN AND METHODS: This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission. RESULTS: Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy. INTERPRETATION: VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU.

Cross-reactivity between piperacillin-tazobactam and cefoperazone-sulbactam in drug-induced immune thrombocytopenia.

Beta-lactam antibiotics commonly cause immune thrombocytopenia. Cross-reactivity in patients with drug-induced immune thrombocytopenia has rarely been reported. In this study, we describe the case of a 79-year-old man who developed thrombocytopenia after receiving piperacillin-tazobactam for an acute exacerbation of chronic obstructive pulmonary disease, and he was successfully treated with meropenem and cefotiam. However, thrombocytopenia recurred after cefoperazone-sulbactam administration. This indicated that cross-reactivity of platelet-specific antibodies occurred between piperacillin-tazobactam and cefoperazone-sulbactam. However, the responsible drug structures remain unknown, requiring further investigation. Likewise, chemical structure similarities among beta-lactam antibiotics must be examined to determine the risk of immune thrombocytopenia in the clinical setting.

Protocol and statistical analysis plan for the Antibiotic Choice On ReNal outcomes (ACORN) randomised clinical trial.

INTRODUCTION: Antibiotics are time-critical in the management of sepsis. When infectious organisms are unknown, patients are treated with empiric antibiotics to include coverage for gram-negative organisms, such as antipseudomonal cephalosporins and penicillins. However, in observational studies, some antipseudomonal cephalosporins (eg, cefepime) are associated with neurologic dysfunction while the most common antipseudomonal penicillin (piperacillin-tazobactam) is associated with acute kidney injury (AKI). No randomised control trials have compared these regimens. This manuscript describes the protocol and analysis plan for a trial designed to compare the effects of antipseudomonal cephalosporins and antipseudomonal penicillins among acutely ill patients receiving empiric antibiotics. METHODS AND ANALYSIS: The Antibiotic Choice On ReNal outcomes trial is a prospective, single-centre, non-blinded randomised trial being conducted at Vanderbilt University Medical Center. The trial will enrol 2500 acutely ill adults receiving gram-negative coverage for treatment of infection. Eligible patients are randomised 1:1 to receive cefepime or piperacillin-tazobactam on first order entry of a broad-spectrum antibiotic covering gram-negative organisms. The primary outcome is the highest stage of AKI and death occurring between enrolment and 14 days after enrolment. This will be compared between patients randomised to cefepime and randomised to piperacillin-tazobactam using an unadjusted proportional odds regression model. The secondary outcomes are major adverse kidney events through day 14 and number of days alive and free of delirium and coma in 14 days after enrolment. Enrolment began on 10 November 2021 and is expected to be completed in December 2022. ETHICS AND DISSEMINATION: The trial was approved by the Vanderbilt University Medical Center institutional review board (IRB#210591) with a waiver of informed consent. Results will be submitted to a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT05094154.

Evaluation of the safety of piperacillin-tazobactam extended infusion in pediatric cystic fibrosis patients.

BACKGROUND: Patients with cystic fibrosis (CF) may be treated with piperacillin-tazobactam (PZT) for acute pulmonary exacerbations. Extending the infusion of PZT is one strategy to increase efficacy. Direct comparison, with respect to the incidence of acute kidney injury (AKI), between these two strategies has not been evaluated in pediatric patients with CF. The primary objective of this study was to compare the incidence of AKI in pediatric CF patients receiving extended infusion (EI) PZT versus traditional infusion (TI). METHODS: This IRB-approved, retrospective analysis included patients ages 30 days to 18 years that received PZT for at least 48 h between January 1, 2008, and January 1, 2020. PZT was infused over 30 min (TI group) or 4 h (EI group). RESULTS: Two hundred and four patients were included (TI: 109, EI: 95). Median age was 8 years (4-13) and 7 years (3-12) in the TI and EI groups (p = 0.15). The groups did not differ significantly in their baseline characteristics. There were 12 (11%) AKIs in the TI group and 8 (8.4%) in the EI group (p = 0.53). There was one occurrence of serum sickness in the TI group and none in the EI group. The incidence of thrombocytopenia was similar between the two groups. Median treatment duration was 8 days (5-11) and 9 days (5-13) for the TI and EI groups, respectively (p = 0.24). CONCLUSIONS: There was no significant increase in AKI in pediatric patients with CF receiving PZT by EI compared with TI. EI may be utilized to optimize the pharmacokinetics of PZT in pediatric CF patients.

Piperacillin/tazobactam and risk of acute kidney injury in adults hospitalized with infection without vancomycin: a multi-centre real-world data analysis.

BACKGROUND: There is uncertainty about whether piperacillin/tazobactam (PT) increases the risk of acute kidney injury (AKI) in patients without concomitant use of vancomycin. This study compared the risk of hospital-acquired AKI (HA-AKI) among adults treated with PT or antipseudomonal ß-lactams (meropenem, ceftazidime) without concomitant use of vancomycin. METHODS: This real-world study analysed the data from China Renal Data System and assessed the risk of HA-AKI in adults hospitalized with infection after exposure to PT, meropenem or ceftazidime in the absence of concomitant vancomycin. The primary outcome was any stage of HA-AKI according to the Kidney Disease Improving Global Outcomes guidelines. A multi-variable Cox regression model and different propensity score (PS) matching models were used. RESULTS: Among the 29,441 adults [mean (standard deviation) age 62.44 (16.84) years; 17,980 females (61.1%)] included in this study, 14,721 (50%) used PT, 9081 (31%) used meropenem and 5639 (19%) used ceftazidime. During a median follow-up period of 8 days, 2601 (8.8%) develped HA-AKI. The use of PT was not associated with significantly higher risk of HA-AKI compared with meropenem [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.97-1.19], ceftazidime (aHR 1.09, 95% CI 0.92-1.30) or both agents (aHR 1.07, 95% CI 0.97-1.17) after adjusting for confounders. Results were consistent in stratified analyses, PS matching using logistic regression or random forest methods to generate a PS, and in an analysis restricting outcomes to AKI stage 2-3. CONCLUSIONS: Without concomitant use of vancomycin, the risk of AKI following PT therapy is comparable with that of meropenem or ceftazidime among adults hospitalized with infection.

Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury.

BACKGROUND: Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown. OBJECTIVE: Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI. PATIENTS AND METHODS: We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI. RESULTS: Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25). CONCLUSIONS: We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.

Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam.

BACKGROUND: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS: We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS: We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS: Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Impact of Piperacillin-Tazobactam Dosing in Septic Shock Patients Using Real-World Evidence: An Observational, Retrospective Cohort Study.

BACKGROUND: Sepsis and septic shock are associated with significant morbidity and mortality. Rapid initiation of appropriate antibiotic therapy is essential, as inadequate therapy early during septic shock has been shown to increase the risk of mortality. However, despite the importance of appropriate antibiotic initiation, in clinical practice, concerns for renal dysfunction frequently lead to antibiotic dose reduction, with scant evidence on the impact of this practice in septic shock patients. OBJECTIVE: The purpose if this article is to investigate the rate and impact of piperacillin-tazobactam dose adjustment in early phase septic shock patients using real-world electronic health record (EHR) data. METHODS: A multicenter, observational, retrospective cohort study was conducted of septic shock patients who received at least 48 hours of piperacillin-tazobactam therapy and concomitant receipt of norepinephrine. Subjects were stratified into 2 groups according to their cumulative 48-hour piperacillin-tazobactam dose: low piperacillin-tazobactam dosing (LOW; <27 g) group and normal piperacillin-tazobactam dosing (NORM; ≥27 g) group. To account for potential confounding variables, propensity score matching was used. The primary study outcome was 28-day norepinephrine-free days (NFD). RESULTS: In all, 1279 patients met study criteria. After propensity score matching (n = 608), the NORM group had more median NFD (23.9 days [interquartile range, IQR: 0-27] vs 13.6 days [IQR: 0-27], P = 0.021). The NORM group also had lower rates of in-hospital mortality/hospice disposition (25.9% [n = 79] vs 35.5% [n = 108]), P = 0.014). Other secondary outcomes were similar between the treatment groups. CONCLUSIONS AND RELEVANCE: In the propensity score-matched cohort, the NORM group had significantly more 28-day NFD. Piperacillin-tazobactam dose reduction in early phase septic shock is associated with worsened clinical outcomes. Clinicians should be vigilant to avoid piperacillin-tazobactam dose reduction in early phase septic shock.

Definitive antibiotic treatment with a third-generation cephalosporin and with piperacillin-tazobactam worked well for some children with Serratia bacteraemia.

AIM: This study aimed to describe epidemiological and clinical characteristics of Serratia bacteraemia and to identify factors associated with mortality. METHODS: The microbiology database of Schneider Children's Medical Centre of Israel was examined for Serratia marcescens positive blood cultures, between January 2007 and May 2020. Demographic, clinical and microbial characteristics were analysed. RESULTS: Of the 81 patients files that met the inclusion criteria, 64 (80%) were of patients hospitalised in paediatric intensive care units. The median age was 78 days and 54% were male. In-hospitalisation mortality was 26%, 62% died under 90 days old. Underlying conditions including prematurity, congenital cardiac defects and malignancies were noted in 95% of patients. Prior to the bloodstream infections, 62% of patients underwent procedures, 64% were on ventilatory support and 77% had central lines. Thrombocytopenia and elevated C-reactive protein levels were found in 60% of the children. Twenty-eight children received definitive monotherapy as either piperacillin-tazobactam or a third-generation cephalosporin; survival rates were similar between the two antibiotic treatment groups. CONCLUSION: In our cohort, 26% died. Death was more common in young infants. Mortality was associated with hospitalisation in intensive care units and thrombocytopenia. Survival rates following definitive monotherapy were similar for patients treated with piperacillin-tazobactam and those treated with third-generation cephalosporin.

A Meta-Analysis on Clinical Outcomes of Ceftolozane versus Piperacillin in Combination with Tazobactam in Patients with Complicated Urinary Tract Infections.

Objective: To evaluate efficacy and adverse events of ceftolozane/tazobactam in complicated UTI including acute pyelonephritis. Method: Databases that include PubMed, Embase, Scopus, and TRIP were searched. All randomized controlled trials and cohort studies were considered for the study. Statistical analysis was done using a fixed effects model, and results were expressed in proportion for dichotomous data and risk ratio for continuous data with 95% confidence intervals (CI). Results: A clinical cure of ceftolozane/tazobactam was found to be 92% with 95% CI of 90-94 while that of piperacillin/tazobactam was only 78% (95% CI, 74-82) in patients with complicated UTI. Microbiological eradication was still higher in the ceftolozane/tazobactam group (83%, 95% CI 81-88) when compared with piperacillin/tazobactam (63% 95% CI, 58.77-65.2). Ceftolozane/tazobactam was more effective in the treatment of complicated urinary tract infections other than acute pyelonephritis as compared to piperacillin/tazobactam (RR = 1.21, 95% CI, 1.07-1.23). Serious adverse events were found comparable in both groups (RR = 1.15, 95% CI, 0.64-2.09). Conclusion: The analysis showed that ceftolozane/tazobactam has better clinical outcomes including cure rates and low resistance for the treatment of complicated urinary tract infection.