title: The Association between GABA-Modulators and Clostridium difficile Infection - A Matched Retrospective Case-Control Study.
abstract: OBJECTIVE
  Recently, metabolomics studies have suggested that the neurotransmitter γ-amino butyric acid (GABA) may modulate C. difficile infection (CDI) pathogenesis. In the present study, we investigated the association between GABA-modulating pharmaceuticals and CDI development.
  
  
  METHODS
  In July-December 2013, we performed a matched, retrospective case-control study in Skåne county, Sweden, to assess the association between the use of GABA-modulators (defined as regular use of at least one of the following: zolpidem, zopiclone, benzodiazepines, gabapentin, pregabalin or baclofen) and CDI. Multivariate regression models, adjusted for known risk factors for CDI, were fitted to assess the associations and a propensity score-adjusted analysis was performed.
  
  
  RESULTS
  The study included 292 cases and 292 matched controls. In a multivariate regression model only recent antibiotic use (clindamycin, cephalosporins and fluoroquinolones) and nursing home residency was significantly associated with CDI. The regular use of any GABA-modulator was not associated with CDI (OR = 1.07, 95%CI 0.69-1.66, p = 0.76). The association between regular use of the selective GABA-agonist zolpidem and CDI trended towards significance (OR = 2.31, 95%CI 0.91-5.86, p = 0.078). These associations remained when only cases treated with antibiotics were included. Corresponding findings for zolpidem was observed in a propensity-score adjusted analysis (OR = 2.52, 95% CI 0.91-6.97, p = 0.075). Severe initial CDI was significantly associated with CDI recurrence (OR = 3.77, 95% CU 1.20-11.86, p = 0.023).
  
  
  CONCLUSIONS
  This study did not identify a general association between GABA-modulators and CDI. A trend towards a significant association between zolpidem and CDI was observed, an association that should be re-assessed in a study appropriately powered for this particular hypothesis.
authors.affiliation: Infectious Diseases Unit, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ström
authors.affiliation: Infectious Diseases Unit, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Tham
authors.affiliation: Infectious Diseases Unit, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Månsson
authors.affiliation: Infectious Diseases Unit, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Ahl
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America.|Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas, United States of America.
authors.forename: Tor C
authors.initials: TC
authors.lastname: Savidge
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Dann
authors.affiliation: Infectious Diseases Unit, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Fredrik
authors.identifier: http://orcid.org/0000-0002-3433-512X
authors.initials: F
authors.lastname: Resman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology* / Q000628:therapy; D018682:GABA Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D009026:Mortality; D016017:Odds Ratio; D011159:Population Surveillance; D012008:Recurrence; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D018682:GABA Agents