Empiric combination therapy for gram-negative bacteremia.

BACKGROUND: Empirical combination antibiotic regimens consisting of a ß-lactam and an aminoglycoside are frequently employed in the pediatric population. Data to demonstrate the comparative benefit of empirical ß-lactam combination therapy relative to monotherapy for culture-proven Gram-negative bacteremia are lacking in the pediatric population. METHODS: We conducted a retrospective cohort study of children treated for Gram-negative bacteremia at The Johns Hopkins Hospital from 2004 through 2012. We compared the estimated odds of 10-day mortality and the relative duration of bacteremia for children receiving empirical combination therapy versus empirical monotherapy using 1:1 nearest-neighbor propensity-score matching without replacement, before performing regression analysis. RESULTS: We identified 226 matched pairs of patients well balanced on baseline covariates. Ten-day mortality was similar between the groups (odds ratio, 0.84; 95% confidence interval [CI], 0.28 to 1.71). Use of empirical combination therapy was not associated with a decrease in the duration of bacteremia (-0.51 days; 95% CI, -2.22 to 1.48 days). There was no survival benefit when evaluating 10-day mortality for the severely ill (pediatric risk of mortality III score ≥15) or profoundly neutropenic patients (absolute neutrophil count ≤100 cells/mL) receiving combination therapy. However, a survival benefit was observed when empirical combination therapy was prescribed for children growing multidrug-resistant Gram-negative organisms from the bloodstream (odds ratio, 0.70; 95% CI, 0.51 to 0.84). CONCLUSIONS: Although there appears to be no advantage to the routine addition of an aminoglycoside to a ß-lactam as empirical therapy for children who have Gram-negative bacteremia, children who have risk factors for MDRGN organisms appear to benefit from this practice.

Sustained savings from a longitudinal cost analysis of an internet-based preapproval antimicrobial stewardship program.

OBJECTIVE: To evaluate an internet-based preapproval antimicrobial stewardship program for sustained reduction in antimicrobial prescribing and resulting cost savings. DESIGN: Retrospective cohort study and cost analysis. METHODS: Review of all doses and charges of antimicrobials dispensed to patients over 6 years (July 1, 2005-June 30, 2011) at a tertiary care pediatric hospital. RESULTS: Restricted antimicrobials account for 26% of total doses but 81% of total antimicrobial charges. Winter months (November-February) and the oncology and infant and toddler units were associated with the highest antimicrobial charges. Five restricted drugs accounted for the majority (54%) of charges but only 6% of doses. With an average approval rate of 91.5% (95% confidence interval [CI], 91.1%-91.9%), the preapproval antibiotic stewardship program saved $103,787 (95% CI, $98,583-$109,172) per year, or $14,156 (95% CI, $13,446-$14,890) per 1,000 patient-days. CONCLUSIONS: A preapproval antimicrobial stewardship program effectively reduces the number of doses and subsequent charges due to restricted antimicrobials years after implementation. Hospitals with reduced resources for implementing postprescription review may benefit from a preapproval antimicrobial stewardship program. Targeting specific units, drugs, and seasons may optimize preapproval programs for additional cost savings.