title: Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027.
abstract: Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P < 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0; P = 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001). Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain.
authors.affiliation: Hines VA Hospital, Hines, Illinois, USA Midwestern University Chicago College of Pharmacy, Downers Grove, Illinois, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Wieczorkiewicz
authors.affiliation: Intermountain Medical Center and the University of Utah, Salt Lake City, Utah, USA.
authors.forename: Bert K
authors.initials: BK
authors.lastname: Lopansri
authors.affiliation: Hines VA Hospital, Hines, Illinois, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Cheknis
authors.affiliation: Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Osmolski
authors.affiliation: Hines VA Hospital, Hines, Illinois, USA Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Hecht
authors.affiliation: Hines VA Hospital, Hines, Illinois, USA Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: Dale N
authors.initials: DN
authors.lastname: Gerding
authors.affiliation: Hines VA Hospital, Hines, Illinois, USA Loyola University Medical Center, Maywood, Illinois, USA stuart.johnson2@va.gov.
authors.forename: Stuart
authors.initials: S
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001427:Bacterial Toxins / Q000276:immunology / Q000302:isolation & purification; D016022:Case-Control Studies; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D004269:DNA, Bacterial / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D004768:Enterotoxins / Q000276:immunology / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D018942:Macrolides / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D000091402:Prohibitins; D012189:Retrospective Studies; D016019:Survival Analysis; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D004768:Enterotoxins; D024841:Fluoroquinolones; D018942:Macrolides; C000717331:PHB2 protein, human; D000091402:Prohibitins; C041348:tcdA protein, Clostridium difficile