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Risk of Developing Pneumonia Is Enhanced by the Combined Traits of Fluoroquinolone Resistance and Type III Secretion Virulence in Respiratory Isolates of Pseudomonas aeruginosa*

Sullivan, Eva PharmD1,2; Bensman, Joyce PharmD2; Lou, Mimi MS2; Agnello, Melissa BS2; Shriner, Kimberly MD1; Wong-Beringer, Annie PharmD1,2

doi: 10.1097/CCM.0b013e318298a86f
Clinical Investigations

Objectives: To determine the differential association of host characteristics, antimicrobial resistance, and type III secretion system virulence of Pseudomonas aeruginosa isolates with respiratory syndromes in hospitalized adult patients.

Design: Retrospective, cohort study.

Setting: Community teaching hospital.

Patients: Two hundred eighteen consecutive adult patients with respiratory culture positive for P. aeruginosa between January 2005 to January 2010.

Interventions: Medical charts were reviewed to obtain demographic, laboratory, radiographic, and clinical information. Isolates were assayed by polymerase chain reaction for genes encoding the type III secretion system effectors (ExoU, ExoS, and PcrV) and for strain relatedness using randomly amplified polymorphic DNA analysis. Levofloxacin susceptibility was determined by broth microdilution. Patients were grouped by colonization, bronchitis, or pneumonia and were compared for differential risk of developing the clinical syndrome with respect to host and microbial characteristics.

Measurements and Main Results: Half of the study cohort (54%, 117 of 218) had pneumonia, 32% (70 of 218) had bronchitis, and 14% (31 of 218) had colonization; in-hospital mortality was 35%, 11%, and 0%, respectively. Host factors strongly associated with pneumonia development were residence in long-term care facility, healthcare-associated acquisition of P. aeruginosa, higher Acute Physiology and Chronic Health Evaluation II score, presence of enteral feeding tube, mechanical ventilation, and recent history of pneumonia. Fluoroquinolone-resistant (57% vs 34%, 16%; p < 0.0001) and multidrug-resistant (36% vs 26%, 7%; p = 0.0045) strains were more likely to cause pneumonia than bronchitis or colonization, respectively. Analysis of host and microbial factors in a multivariate regression model yielded the combined traits of fluoroquinolone resistance and gene encoding the type III secretion system ExoU effector in P. aeruginosa as the single most significant predictor of pneumonia development.

Conclusions: These results suggest that fluoroquinolone-resistant phenotype in a type III secretion system exoU strain background contributes toward the pathogenesis of P. aeruginosa in pneumonia.

1Huntington Hospital, Pasadena, CA.

2University of Southern California, Los Angeles, CA.

* See also p. 201.

This study was performed at Huntington Hospital and at the University of Southern California.

Supported by award number R21AI073467 from the National Institute of Allergy and Infectious Diseases to AWB.

Dr. Wong-Beringer has received grant support from the National Institute of Health-NIAID, Pfizer, Trius, and Forest Pharmaceuticals and has consulted for Optimer Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Annie Wong-Beringer, PharmD, FIDSA, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90033. E-mail: anniew@usc.edu

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins