title: Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.
abstract: Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. Five of 27 (19%) strains developed 4-fold increases in azithromycin MICs and reached or exceeded the susceptibility breakpoint (≤4 μg/ml) during exposure. H. influenzae isolates were uniformly susceptible to ciprofloxacin, levofloxacin, and moxifloxacin (MIC90s of 0.015, 0.015, and 0.06, respectively); there were no mutations in quinolone resistance-determining regions. Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides (odds ratio [OR], 16.67; 95% confidence interval [CI], 2.67 to 104.09). There was no difference in H. influenzae eradication when comparing macrolide administration to no antibiotic (OR, 1.89; 95% CI, 0.43 to 8.30). Fluoroquinolones are effective in eradicating H. influenzae in individuals with COPD. Macrolides are ineffective in eradicating H. influenzae, and their use in COPD patients may lead to decreased macrolide susceptibility and resistance.
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Pettigrew
authors.affiliation: Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, the State University of New York, Buffalo, New York, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Tsuji
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: Janneane F
authors.initials: JF
authors.lastname: Gent
authors.affiliation: Department of Molecular Biophysics and Biochemistry, W. M. Keck Foundation Biotechnology Resource Laboratory, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, the State University of New York, Buffalo, New York, USA.
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Holden
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University at Buffalo, the State University of New York, Buffalo, New York, USA Veterans Affairs Western New York Healthcare System, Buffalo, New York, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Division of Infectious Diseases and Clinical and Translational Research Center, University at Buffalo, the State University of New York, Buffalo, New York, USA Department of Microbiology and Immunology University at Buffalo, the State University of New York, Buffalo, New York, USA murphyt@buffalo.edu.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Murphy
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D024841:Fluoroquinolones / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects*; D064704:Levofloxacin / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D018942:Macrolides; D002939:Ciprofloxacin; D064704:Levofloxacin; D000077266:Moxifloxacin