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283 Comparative Effectiveness of Tigecycline, Polymyxin B, and Aminoglycosides in Eradicating Carbapenem-resistant Klebsiella pneumoniae (CRKP) from the Urine

Saturday, April 2, 2011
Trinity Ballroom (Hilton Anatole)
Michael J. Satlin, MD , Weill Cornell Medical College, New York, NY
Christine J. Kubin, PharmD, BCPS , Columbia University; NewYork-Presbyterian Hospital, New York, NY
Jill S. Blumenthal, MD , New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
Andrew B. Cohen, MD , New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
E. Yoko Furuya, MD, MS , Columbia University, New York, NY
Stephen J. Wilson, MD, MPH , Weill Cornell Medical College, New York, NY
Stephen G. Jenkins, PhD , Weill Cornell Medical College, New York, NY
David P. Calfee, MD, MS , Weill Cornell Medical College, New York, NY
Background: CRKP is an increasingly common cause of healthcare-associated urinary tract infections.  Treatment options with in vitro activity against CRKP are limited.  Tigecycline (TG) and polymyxin B (PB), antibiotics commonly used to treat CRKP infections, achieve low urine concentrations and their efficacy in treating CRKP urinary tract infections has not been evaluated.

Objective: To determine the microbiologic effectiveness of TG, PB, and aminoglycosides amikacin and gentamicin (AG) for CRKP bacteriuria.

Methods: We conducted a retrospective cohort study of all cases of CRKP bacteriuria (≥ 104 CFU/mL) at New York-Presbyterian Hospital from January 2005 to June 2010.  Cases were included if (1) TG, PB, or AG was initiated within 7 days after the index bacteriuria; (2) a follow-up urine culture was performed 3-21 days after antibiotic initiation; (3) ≥ 3 days of the antibiotic was given between the index bacteriuria and the follow-up urine culture; (4) the CRKP was susceptible in vitro to the antibiotic.  Cases that received two antibiotics with in vitro activity were excluded.  Microbiologic clearance was defined as the absence of CRKP on follow-up urine culture.  We compared characteristics of cases treated with TG and PB to cases treated with AG, including measures of acute and chronic illness, pyuria, and urinary tract catheterization.  We then compared microbiologic clearance rates and performed multivariate logistic regression to estimate the odds of microbiologic failure when using TG or PB compared to AG.  We also determined rates of developing resistance to the antibiotic used, defined as a non-susceptible CRKP isolate, within 30 days after antibiotic initiation.

Results: Eighty-seven cases met the inclusion criteria.  The microbiologic clearance rate was 88% for AG (n=41), compared to 43% for TG (p < 0.001, n=21) and 64% for PB (p = 0.02, n=25).  Compared to cases treated with AG, cases treated with PB were more likely to also receive an inactive beta-lactam antibiotic, less likely to be on a medical service, and received fewer days of therapy before the follow-up urine culture.  No significant differences were identified between cases treated with TG and cases treated with AG.  Clearance rates were higher for AG than for TG and PB for all subgroups analyzed, including catheter-associated cases, cases with pyuria, and cases where no additional gram-negative agents were used.  In multivariate analysis, use of TG (OR 14.8; 95% CI, 3.0-73.0, p=0.001) and use of PB (OR 5.7; 95% CI, 1.2-27.8, p =0.03) were associated with microbiologic failure.  Antibiotic resistance developed more frequently in cases treated with TG than cases treated with AG (43% vs. 20%, p=0.05).

Conclusions: For CRKP bacteriuria, use of AG was associated with significantly higher clearance rates than use of PB or TG.  In addition to being ineffective, TG use frequently led to TG resistance.