Ceftazidime/avibactam and ceftolozane/tazobactam for severe paediatric infections: A systematic review, meta-analysis, and evidence map

BACKGROUND: The 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. OBJECTIVE: To synthesize current evidence on the efficacy, effectiveness, and safety of CZA and C/T in hospitalized children with severe infections. METHODS: We 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. RESULTS: Nineteen 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). CONCLUSIONS: CZA 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.