Dataset Information

Extended infusion of β-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis.

ABSTRACT:

Background

Paediatric patients are often exposed to subtherapeutic levels or treatment failure of β-lactams, and prolonged infusion may be beneficial. We aimed to investigate the efficacy and safety of extended infusion (EI; defined as ≥3 h) or continuous infusion vs. short, intermittent infusion (SI; defined as ≤60 min) of β-lactams in patients <21 years of age.

Methods

A systematic review and meta-analysis was conducted to compare EI and continuous infusion with SI of β-lactams in children. A systematic search was performed in MEDLINE (via PubMed), Embase, CENTRAL, and Scopus databases for randomised controlled trials (RCTs) and observational studies published from database inception up to August 22, 2023. Any comparative study concerned with mortality, clinical efficacy, adverse events, or plasma concentrations of β-lactams for any infection was eligible. Case reports, case series, and patients aged >21 years were excluded. Odds ratios (OR) and median differences with 95% confidence intervals (CI) were calculated using a random-effects model. Risk of bias (ROB) was assessed using ROB2 and ROBINS-I tools. The protocol was registered with PROSPERO, CRD42022375397.

Findings

In total, 19,980 articles were screened, out of which 19 studies (4195 patients) were included in the meta-analysis. EI administration was associated with a significantly lower all-cause mortality in both RCTs and non-RCTs [OR 0.74; CI 0.55-0.99; I² = 0%; CI 0-58%]. Early microbiological eradication was higher with EI [OR 3.18; CI 2.24-4.51; I² = 0%; CI 0-90%], but the clinical cure did not differ significantly between the two groups [OR 1.20; CI 0.17-8.71; I² = 79%; CI 32-93%]. Achieving the optimal plasma level (50-100% fT > MIC) appeared favourable in the EI group compared to the SI. No significant differences were observed in the adverse events. The overall ROB was high because of the small sample sizes and clinically heterogeneous populations.

Interpretation

Our findings suggest that extended infusion of β-lactams was associated with lower mortality and increased microbiological eradication and was considered safe compared to short-term infusion.

Funding

None.

SUBMITTER: Budai KA

PROVIDER: S-EPMC10651452 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Extended infusion of β-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis.

Budai Kinga Anna KA Tímár Ágnes Eszter ÁE Obeidat Mahmoud M Máté Vanda V Nagy Rita R Harnos Andrea A Kiss-Dala Szilvia S Hegyi Péter P Garami Miklós M Hankó Balázs B Lódi Csaba C

EClinicalMedicine 20231102

<h4>Background</h4>Paediatric patients are often exposed to subtherapeutic levels or treatment failure of β-lactams, and prolonged infusion may be beneficial. We aimed to investigate the efficacy and safety of extended infusion (EI; defined as ≥3 h) or continuous infusion vs. short, intermittent infusion (SI; defined as ≤60 min) of β-lactams in patients <21 years of age.<h4>Methods</h4>A systematic review and meta-analysis was conducted to compare EI and continuous infusion with SI of β-lactams ...[more]

PMID: 38021371

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Project description:IntroductionRespiratory tract infections (RTIs) are a leading cause of morbidity and mortality in children worldwide. Aetiologic virus and bacteria vary geographically. To date, no systematic data on RTI aetiologies have been published from Kyrgyzstan, a country with a high under-five mortality from lower RTIs and a widespread overuse of antibiotics. We aimed to identify the aetiologies of RTI in children in Kyrgyzstan and to assess the pneumococcal conjugate vaccine (PCV) vaccination rate and the correlation with the detection of Streptococcus pneumoniae in our population.MethodsWe collected samples from children aged 6 months to 12 years presenting with symptoms of acute RTI for outpatients or diagnosed with pneumonia for inpatients. Samples were collected from November 2022 to June 2023 and were analysed using standard culture methods and real-time polymerase chain reaction (RT-PCR) to identify bacterial, viral, and atypical bacterial pathogens. We obtained the vaccination status through vaccination records and parents' recollections.ResultsPositive bacteriologic cultures were found for 294 (25.0%) of 1174 outpatients and 83 (27.7%) of 300 inpatients. S. pneumoniae was the most commonly found bacterial pathogen in both groups, making up 44.8% of all cultured bacteria. Furthermore, 445 (64.1%) of 694 outpatients with RT-PCR performed had one or more viral pathogens identified, while this was the case for 162 (54.7%) of 296 inpatients. Mycoplasma pneumoniae was identified in 15.8% of inpatients possibly representing an epidemic in the spring of 2023. Approximately 20% of both in- and outpatients had a viral-bacterial simultaneous detection. 87.1% of outpatients and 75.9% of inpatients had been vaccinated with PCV. We found a higher proportion of unvaccinated children among those under five years of age and a higher carriage rate of S. pneumoniae among unvaccinated inpatients.ConclusionIn this study, we found a high prevalence of viral infections and viral-bacterial simultaneous detections among Kyrgyz children with respiratory tract infections (RTI). The findings from this study can inform new clinical guidelines for local health workers and lead to more targeted use of antibiotics and improved health outcomes for children in Kyrgyzstan.Clinical trialNot applicable.

Project description:ImportanceCurrent evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.ObjectiveTo investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).Design, setting, and participantsThis cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.ExposuresEI-BL (ie, ≥3-hour infusion).Main outcomes and measuresEI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).ResultsAmong the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).Conclusions and relevanceIn this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Dataset Information

Extended infusion of β-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis.

Background

Methods

Findings

Interpretation

Funding

Publications

Extended infusion of β-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis.

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