1581. Risk Factors for gyrA and parC Mutations in Pseudomonas aeruginosa: A Case-Case-Control Study
Session: Poster Abstract Session: Multidrug-Resistant Gram Negative Rods
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background: Approximately 25% of Pseudomonas aeruginosa (PSA) isolates exhibit phenotypic resistance to fluoroquinolones (FQs). The major mechanism of FQ resistance is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits, respectively. However, multi-drug efflux pumps and other resistance mechanisms may also confer phenotypic FQ resistance. While prior studies have identified risk factors for phenotypic FQ resistance in PSA, risk factors for specific FQ resistance mechanisms may differ and have not yet been described. We sought to determine the association between antibiotic exposure and gyrA/parCmutations in PSA.

Methods: A case-case-control study design was used to compare two case patient groups (case1 and case2) with controls.  Cases were inpatients at an academic medical center from 5/23/08-11/10/09 with a length of stay of at least three days and a first PSA clinical isolate on hospital day three or later. Case1 patients were subjects with an isolate with any gyrA or parC mutation. Case2 patients were subjects with an isolate with no such mutations.  A 10% incident density sample of all patients hospitalized for at least 3 days during the time period were included as controls.  Mutations in gyrA and parCwere assessed by PCR amplification and sequencing.  Data were collected on prior antibiotic use and potential confounders (i.e., patient demographics,illness severity, time in hospital).  Each case group was compared to the control group in separate multivariable models. Identified risk factors were then qualitatively compared between the two models. 

Results: Of 298 PSA study isolates, 172 (57.7%) had at least one gyrA or parCmutation.  After controlling for other factors, exposure to non-anti-Pseudomonal antibiotics was a significant risk factor for both cases (Case1 odds ratio (OR): 1.06, 95% confidence interval (CI): 1.02-1.10; case2 OR: 1.05, 95% CI: 1.00-1.10), but the risks did not differ between case groups. Other antimicrobials were not associated with study outcomes.

Conclusion: Exposure to non-anti-Pseudomonal antibiotics is a risk factor for isolation of PSA, but this risk does not differ between the isolates with gyrA/parC mutations and those without mutation.  This study has a novel focus on risk factors for genotypic resistance.

Valerie Cluzet, MD1, Ebbing Lautenbach, MD, MPH, MSCE2, Irving Nachamkin, DrPH, MPH3, Mark Cary, PhD4, Knashawn H. Morales, ScD5, Darren R. Linkin, MD, MSCE2 and the CDC Prevention Epicenter Program, (1)Infectious Diseases, Hospital of the University of Pennsylvania, Philadelphia, PA, (2)University of Pennsylvania School of Medicine, Philadelphia, PA, (3)Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, (4)Department of Biostatistics and Epidemiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, (5)Hospital of the University of Pennsylvania, Philadelphia, PA

Disclosures:

V. Cluzet, None

E. Lautenbach, None

I. Nachamkin, None

M. Cary, None

K. H. Morales, None

D. R. Linkin, None

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