OBJECTIVE: Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSI). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (i.e., β-lactam or vancomycin, if both cannot be administered simultaneously) impacts early mortality for patients with BSI.

METHODS: We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on: demographics, Pitt bacteremia score, ICU status, highest lactate, highest WBC count, Charlson Comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose.

RESULTS: Of 3,376 eligible patients, 2,685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (aOR 0.48 (95% CI: 0.33-0.69)]. Similar results were observed when evaluating 48-hour mortality (aOR 0.45 [95% CI: 0.24-0.83]). Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR 0.93 [95% CI: 0.33-2.63]).

CONCLUSIONS: For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a β-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.

<p><strong>Importance: </strong>National guidelines recommend treating children with pyelonephritis for 7 to 14 days of antibiotic therapy, yet data are lacking to suggest a more precise treatment duration.</p>

<p><strong>Objective: </strong>To compare the clinical outcomes of children receiving a short-course vs a prolonged-course of antibiotic treatment for pyelonephritis.</p>

<p><strong>Design, Setting, and Participants: </strong>Retrospective observational study using inverse probability of treatment weighted propensity score analysis of data from 5 hospitals in Maryland between July 1, 2016, and October 1, 2018. Participants were children aged 6 months to 18 years with a urine culture growing Escherichia coli, Klebsiella species, or Proteus mirabilis with laboratory and clinical criteria for pyelonephritis.</p>

<p><strong>Exposures: </strong>Treatment of pyelonephritis with a short-course (6 to 9 days) vs a prolonged-course (10 or more days) of antibiotics.</p>

<p><strong>Main Outcomes and Measures: </strong>Composite outcome of treatment failure within 30 days of completing antibiotic therapy: (a) unanticipated emergency department or outpatient visits related to urinary tract infection symptoms, (b) hospital readmission related to UTI symptoms, (c) prolongation of the planned, initial antibiotic treatment course, or (d) death. A subsequent urinary tract infection caused by a drug-resistant bacteria within 30 days was a secondary outcome.</p>

<p><strong>Results: </strong>Of 791 children who met study eligibility criteria (mean [SD] age 9.2 [6.3] years; 672 [85.0%]) were girls, 297 patients (37.5%) were prescribed a short-course and 494 patients (62.5%) were prescribed a prolonged-course of antibiotics. The median duration of short-course therapy was 8 days (interquartile range, 7-8 days), and the median duration of prolonged-course therapy was 11 days (interquartile range, 11-12 days). Baseline characteristics were similar between the groups in the inverse probability of treatment weighted cohort. There were 79 children (10.1%) who experienced treatment failure. The odds of treatment failure were similar for patients prescribed a short-course vs a prolonged-course of antibiotics (11.2% vs 9.4%; odds ratio, 1.22; 95% CI, 0.75-1.98). There was no significant difference in the odds of a drug-resistant uropathogen for patients with a subsequent urinary tract infection within 30 days when prescribed a short-courses vs prolonged-course of antibiotics (40% vs 64%; odds ratio, 0.36; 95% CI, 0.09-1.43).</p>

<p><strong>Conclusions and Relevance: </strong>The study findings suggest that short-course antibiotic therapy may be as effective as prolonged-courses for children with pyelonephritis, and may mitigate the risk of future drug-resistant urinary tract infections. Additional studies are needed to confirm these findings.</p>