Aggressive PK/PD Target Attainment With Beta-lactams in critically Ill Pediatric Patients Having Suspected or Documented Gram-negative Infections-Prevalence, Risk Factors of Nonattainment and Impact on Clinical Outcome: A Systematic Review and Meta-analysis.

OBJECTIVE

To perform a systematic review with meta-analysis for evaluating the prevalence of aggressive beta-lactams pharmacokinetic/pharmacodynamic (PK/PD) target attainment, identifying predictors of aggressive PK/PD target nonattainment, and assessing the impact of attaining aggressive beta-lactams PK/PD targets on clinical efficacy in critical pediatric patients.

METHODS

PubMed-MEDLINE and Scopus databases were independently searched from inception to March 02, 2026. Randomized controlled trials or observational studies evaluating the prevalence of aggressive beta-lactams PK/PD target attainment (defined as 100%fT>4xMIC) in critical pediatric patients were included. Independent predictive factors for aggressive beta-lactams PK/PD target nonattainment and the relationship with clinical outcome were further investigated for qualitative or quantitative analysis. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with an inverse variance method.

RESULTS

A total of 1472 articles were screened, and 8 observational studies were included (724 critical pediatric patients who received 761 beta-lactams treatment courses). The proportion of critical pediatric patients who attained aggressive beta-lactams PK/PD targets was 5.6%-76.2%. An estimated glomerular filtration rate ≥90 mL/min/1.73m2 [OR: 3.01; 95% confidence interval: 1.15-7.90; I2 = 52.5%] and male gender (OR: 1.88; 95% CI: 1.10-3.22; I2 = 17.25%) emerged as significant independent predictors of failure in attaining aggressive PK/PD targets. Meta-analysis for the PICO 2 question was unfeasible due to a lack of adjusted data.

CONCLUSIONS

Our findings showed that a remarkable proportion of critically ill pediatric patients failed in attaining aggressive beta-lactams PK/PD targets, especially when receiving intermittent/extended infusion delivery, identifying an estimated glomerular filtration rate ≥90 mL/min/1.73m2 and male gender as potential independent risk factors.