Ceftolozane 1g / Tazobactam 500mg powder for solution for infusion vials

BackgroundThe growing prevalence of multidrug-resistant Gram-negative bacilli poses major challenges to the management of severe paediatric infections. Ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) are newer β-lactam/β-lactamase inhibitor combinations with established efficacy in adults.ObjectiveTo synthesize current evidence on the efficacy, effectiveness, and safety of CZA and C/T in hospitalized children with severe infections.MethodsWe conducted a systematic review, meta-analysis, and evidence map (PROSPERO CRD420251025715). Searches were performed in PubMed, Scopus, CENTRAL, Epistemonikos, LILACS, SciELO, and Web of Science. Eligible designs included randomized controlled trials (RCTs), cohort studies, case series, and case reports evaluating CZA or C/T for complicated intra-abdominal infections, complicated urinary tract infections (cUTI), pneumonia, or bacteraemia in patients aged 0-18 y. The primary outcome was 30-d mortality; secondary outcomes were clinical and microbiological cure and adverse events.ResultsNineteen studies (4 RCTs, 9 case series, 6 case reports) involving 472 patients were included. Sixteen studies evaluated CZA and three evaluated C/T. All RCTs were phase II, industry-sponsored, and excluded critically ill children and carbapenem-resistant infections. According to the updated RoB 2 assessment, two trials had overall low risk of bias, and two presented some concerns, mainly related to missing outcome data. No deaths occurred in RCTs, whereas observational studies reported 8% mortality. Clinical and microbiological cure exceeded 80% across study designs. Adverse events were generally infrequent; neonatal events clustered in case series, but evidence was insufficient for statistical comparison across age groups. Certainty of evidence ranged from moderate (cUTI with susceptible pathogens) to very low (pneumonia and resistant infections).ConclusionsCZA and C/T appear promising for paediatric cUTI and complicated intra-abdominal infections, but the evidence base remains narrow and largely dependent on small, industry-funded trials. Independent RCTs including critically ill children and resistant infections are urgently needed.

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BackgroundInfections caused by multidrug-resistant/difficult-to-treat (MDR/DTR) Pseudomonas aeruginosa present a significant challenge for treatment. Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (C/A) are important options that combine β-lactam and β-lactamase inhibitors, but their effectiveness compared to each other is still unclear.MethodsWe performed a systematic review and meta-analysis, evaluated by Grading of Recommendations Assessment, Development, and Evaluation (GRADE), of comparative observational studies that included hospitalized adults with confirmed MDR/DTR P. aeruginosa infections up to 10 October 2025 (English only). Studies comparing C/T directly with C/A and matched therapies were included. We used random-effects Mantel-Haenszel models to calculate pooled risk ratios (RR) with 95% confidence intervals (CIs), and we assessed heterogeneity with I 2. We reviewed the certainty of evidence using GRADE.ResultsSix observational cohorts (n = 1161) met our criteria. There were no significant differences between C/T and C/A for clinical success (RR: 1.07, 0.89-1.29; I 2 = 40%), 30-day all-cause mortality (RR: 1.02, 95% CI: 0.83-1.27; I 2 = 0%), 30-day recurrence (RR: 0.85, 0.46-1.57; I 2 = 48%), 90-day recurrence (RR: 0.80, 0.63-1.02; I 2 = 0%; P = 0.08), emergence of resistance (RR: 0.73, 0.30-1.81; I 2 = 84%), and microbiological response failure (RR: 0.91, 0.66-1.26; I 2 = 8%). There was a non-significant trend that slightly favored C/T for 90-day recurrence. According to GRADE, the certainty of evidence varied from low to very low, mainly due to non-randomized study designs and variability across studies.ConclusionsIn current comparative cohorts, C/T and C/A show similar outcomes for severe MDR/DTR P. aeruginosa infections. More high-quality randomized trials are needed to better define any potential differences and clarify long-term recurrence and resistance risks.

Abstract licence: CC BY-NC-ND

BackgroundClinical guidelines recommend two novel β-lactam/β-lactamase inhibitor combinations-ceftolozane-tazobactam and ceftazidime-avibactam-as first-line therapies for drug-resistant Pseudomonas aeruginosa infections. This study aimed to compare their efficacy, safety, and emergence of resistance.MethodsA systematic review and meta-analysis was conducted. The primary analysis was based on adjusted data from direct comparisons. To assess robustness, these findings were compared with pooled estimates from unadjusted direct and indirect comparisons. Outcomes included all-cause mortality, clinical response, pathogen clearance, recurrent infection, AKI, and in vivo emergence of resistance. Risk of bias was assessed using the ROBINS-I tool based on prespecified confounders.ResultsTwenty-two studies including 3361 patients were analyzed. No significant differences were observed between the two agents in all-cause mortality, clinical response, AKI, and emergence of resistance. However, ceftolozane-tazobactam was associated with a lower risk of recurrent infection within 30-90 days compared with ceftazidime-avibactam (aOR = 0.46, 95% CI: 0.26-0.78).ConclusionCeftolozane-tazobactam and ceftazidime-avibactam demonstrate comparable efficacy and similar risks of resistance emergence. Moderate-certainty evidence suggests that ceftolozane-tazobactam may reduce the risk of recurrent infection in patients with drug-resistant P. aeruginosa infections.

Abstract licence: CC BY-NC-ND