Empiric combination therapy for gram-negative bacteremia.
BACKGROUND
Empirical combination antibiotic regimens consisting of a β-lactam and an aminoglycoside are frequently employed in the pediatric population. Data to demonstrate the comparative benefit of empirical β-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 β-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.
Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;
Anna C
AC
Sick
Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland;
Sarah
S
Tschudin-Sutter
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
Alison E
AE
Turnbull
Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington; and.
Scott J
SJ
Weissman
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland ptamma1@jhmi.edu.
Pranita D
PD
Tamma
D000617:Aminoglycosides / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D015142:Baltimore; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D019348:Empiricism; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009503:Neutropenia / Q000188:drug therapy / Q000401:mortality; D016017:Odds Ratio; D009894:Opportunistic Infections / Q000188:drug therapy / Q000401:mortality; D057216:Propensity Score; D012189:Retrospective Studies; D016019:Survival Analysis; D047090:beta-Lactams / Q000528:radiation effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D047090:beta-Lactams
Gram-negative bacteremia; aminoglycoside; combination therapy; empiric therapy; β-lactam