ABSTRACT
Importance: There is uncertainty about whether prolonged infusions of ß-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective: To determine whether prolonged ß-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of ß-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of ß-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of ß-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged ß-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration: PROSPERO Identifier: CRD42023399434.
ABSTRACT
OBJECTIVES: To describe the prevalence of pediatric acute respiratory distress syndrome (pARDS) and the characteristics of children with pARDS in South African PICUs. DESIGN: Observational multicenter, cross-sectional point-prevalence study. SETTING: Eight PICUs in four South African provinces. PATIENTS: All children beyond the neonatal period and under 18 years of age admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and demographic data were prospectively collected on a single day of each month, from February to July 2022, using a centralized database. Cases with or at risk of pARDS were identified using the 2015 Pediatric Acute Lung Injury Consensus Conference criteria. Prevalence was calculated as the number of children meeting pARDS criteria/the total number of children admitted to PICU at the same time points. Three hundred ten patients were present in the PICU on study days: 166 (53.5%) male, median (interquartile range [IQR]) age 9.8 (3.1-32.9) months, and 195 (62.9%) invasively mechanically ventilated. Seventy-one (22.9%) patients were classified as being "at risk" of pARDS and 95 patients (prevalence 30.6%; 95% CI, 24.7-37.5%) fulfilled pARDS case criteria, with severity classified as mild (58.2%), moderate (25.3%), and severe (17.6%). Median (IQR) admission Pediatric Index of Mortality 3 risk of mortality in patients with and without pARDS was 5.6 (3.4-12.1) % versus 3.9 (1.0-8.2) % ( p = 0.002). Diagnostic categories differed between pARDS and non-pARDS groups ( p = 0.002), with no difference in age, sex, or presence of comorbidities. On multivariable logistic regression, increasing admission risk of mortality (adjusted odds ratio [aOR] 1.02; 95% CI, 1.00-1.04; p = 0.04) and being admitted with a respiratory condition (aOR 2.64; 95% CI, 1.27-5.48; p = 0.01) were independently associated with an increased likelihood of having pARDS. CONCLUSIONS: The 30.6% prevalence of pARDS in South Africa is substantially higher than reports from other sociogeographical regions, highlighting the need for further research in this setting.
