Extended Infusion of Beta-Lactams and Glycopeptides: A New Era in Pediatric Care? A Systematic Review and Meta-Analysis.

Optimizing antibiotic therapy is imperative with rising bacterial resistance and high infection mortality. Extended infusion defined as a continuous infusion (COI) or prolonged infusion (PI) of beta-lactams and glycopeptides might improve efficacy and safety compared to their intermittent administration (IA). This study aimed to evaluate the efficacy and safety of extended infusion in pediatric patients. Adhering to Cochrane standards, we conducted a systematic review with meta-analysis investigating the efficacy and safety of COI (24 h/d) and PI (>1 h/dose) compared to IA (≤1 h/dose) of beta-lactams and glycopeptides in pediatrics. Primary outcomes included mortality, clinical success, and microbiological eradication. Five studies could be included for the outcome mortality, investigating meropenem, piperacillin/tazobactam, cefepime, or combinations of these. The pooled relative risk estimate was 0.48 (95% CI 0.26-0.89, p = 0.02). No significant differences between the administration modes were found for the outcomes of clinical success, microbiological eradication (beta-lactams; glycopeptides), and mortality (glycopeptides). No study reported additional safety issues, e.g., adverse drug reactions when using COI/PI vs. IA. Our findings suggest that the administration of beta-lactams by extended infusion leads to a reduction in mortality for pediatric patients.

Indwelling catheter vs intermittent catheterization: is there a difference in UTI susceptibility?

BACKGROUND: Patients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC. METHODS: In this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures for prophylactic reasons or due to UTI symptoms. At visit, all patients underwent a standardized interview on current UTI symptoms as well as UTI history and antibiotic consumption within the past year. Patients using an indwelling catheter (n = 206) or IC (n = 299) were included in the analysis. The main outcome was between-group differences regarding UTI characteristics. RESULTS: Patients using an indwelling catheter were older (indwelling catheter vs IC: median 66 (Q1-Q3: 55-77) vs 55 (42-67) years of age) and showed a higher Charlson comorbidity index (indwelling catheter vs IC: median 4 (Q1-Q3: 2-6) vs 2 (1-4) (both p < 0·001). A total of 40 patients from both groups were diagnosed with a UTI at visit (indwelling catheters vs IC: 8% (16/206) vs 8% (24/299); p = 0·782), and the number of UTIs within the past 12 months was not significantly different between groups. Overall, Escherichia coli (21%), Enterococcus faecalis (17%), and Klebsiella spp. (12%) were the most frequently detected bacteria. CONCLUSIONS: In this cohort of patients with NLUTD, we did not find relevant differences in UTI frequency between groups. These results suggest that UTI-related concerns should not be given undue emphasis when counseling patients for catheter-related bladder emptying methods.

Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine.

The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 98%) at a resolution of ≥103 CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application.