908. Does Combination Antibiotic Therapy Improve Clinical Outcomes in Children with Pseudomonas Bacteremia?
Session: Poster Abstract Session: Antimicrobial Utilization and Resistance in Children
Saturday, October 22, 2011
Room: Poster Hall B1
Background:  Combination therapy with a β-lactam and an aminoglycoside for the treatment of Pseudomonas bacteremia is commonly prescribed to children; however, its utility and toxicity relative to antipseudomonal β-lactam monotherapy is unknown.  The objective of this study is to determine whether combination therapy for Pseudomonas bacteremia impacts subsequent treatment failure, nephrotoxicity, and the emergence of multi-drug resistant Gram-negative (MDRGN) infections in children compared to monotherapy.

Methods:  We conducted a retrospective, cohort study of children ≤21 years of age with Pseudomonas bacteremia between 2005-2010 at the Johns Hopkins Children’s Center.  Cox proportional hazards models were used to obtain unadjusted and adjusted hazard ratios (HR) for the primary outcome of treatment failure (a composite measure of bacteriologic failure or death within 30 days).  Multivariable logistic regression was used to determine the odds ratios (OR)  of nephrotoxicity (serum creatinine increase of 0.5 mg/dl or 50%, whichever was greater) and subsequent MDRGN infection (resistance to ≥3 classes of antibiotics).  We used propensity scores to adjust for potential differences between children treated with combination therapy versus monotherapy.

Results:  Of 151 eligible children, 104 received combination therapy and 47 received monotherapy.  Baseline characteristics including median number of preexisting conditions and pediatric risk of mortality score were similar between the groups.  After adjusting for potential confounding variables, receipt of combination therapy was not protective against treatment failure [HR 0.98 (0.46-2.06)].  Failure to remove a central line at the time of diagnosis of bacteremia was the only predictor of treatment failure [HR 2.24 (1.12-4.45)].  Children who received combination therapy were more likely to have nephrotoxicity compared to those who received β-lactam monotherapy [OR 5.10 (1.58-16.47)].  Combination therapy was associated with a greater likelihood of subsequent MDRGN infection [OR 5.07 (1.07-24.1)]

Conclusion:  The use of β-lactam monotherapy for Pseudomonas bacteremia in children can reduce subsequent nephrotoxicity and MDRGN infections without compromising clinical outcomes.


Subject Category: P. Pediatric and perinatal infections

Pranita Tamma, MD1, Ketan Jumani, BDS2, Alice Hsu, PharmD3, Aaron Milstone, MD, MHS1 and Sara Cosgrove, MD1, (1)The Johns Hopkins Medical Institution, Baltimore, MD, (2)Department of International Health, Johns Hopkins-Bloomberg School of Public Health, Baltimore, MD, (3) The Johns Hopkins Medical Institution, Baltimore, MD

Disclosures:

P. Tamma, None

K. Jumani, None

A. Hsu, None

A. Milstone, None

S. Cosgrove, Merck: Consultant, Consulting fee
AdvanDx: Grant Investigator, Educational grant
Cubist: Grant Investigator, Educational grant

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.