The Association between GABA-Modulators and Clostridium difficile Infection - A Matched Retrospective Case-Control Study

• Published in: PloS one Vol. 12; no. 1; p. e0169386
• Main Authors: Ström, Jonathan, Tham, Johan, Månsson, Fredrik, Ahl, Jonas, Savidge, Tor C, Dann, Sara M, Resman, Fredrik
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.01.2017; Public Library of Science (PLoS)
• Subjects: Adult; Age; Analysis; Antibiotics; Baclofen; Benzodiazepines; Biology and Life Sciences; Butyric acid; Case-Control Studies; Cephalosporins; Clindamycin; Clinical Medicine; Clostridioides difficile; Clostridium difficile; Clostridium infections; Clostridium Infections - diagnosis; Clostridium Infections - epidemiology; Clostridium Infections - etiology; Clostridium Infections - therapy; Comorbidity; Development and progression; Drugs; Endocrinology and Diabetes; Endokrinologi och diabetes; Epidemiology; Fluoroquinolones; GABA; GABA Agents - adverse effects; GABA Agents - therapeutic use; Gabapentin; Gender; Hospitalization; Hospitals; Humans; Infections; Infectious diseases; Klinisk medicin; Laboratories; Ligands; Medical and Health Sciences; Medical records; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Metabolomics; Modulators; Mortality; Nervous system; Neuromodulation; Nosocomial infections; Nursing; Nursing homes; Odds Ratio; Pathogenesis; Penicillin; Population Surveillance; Recurrence; Regression analysis; Regression models; Research and Analysis Methods; Retrospective Studies; Risk analysis; Risk factors; Severity of Illness Index; Sweden - epidemiology; Treatment Outcome; Variables; Zolpidem; Zopiclone; γ-Aminobutyric acid; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0169386

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. 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. 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). 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.