The association between benzodiazepines and influenza-like illness-related pneumonia and mortality: a survival analysis using UK Primary Care data

Nakafero, Georgina; Sanders, Robert D.; Nguyen-Van-Tam, Jonathan S.; Myles, Puja R.

Abstract

Purpose: Bacterial superinfections, including pneumonia, are frequent complications of influenza-like illness (ILI). Clinical and laboratory evidence suggests that benzodiazepines and Z-drugs may influence susceptibility to infections and mortality. We investigated whether benzodiazepines and zopiclone modify the occurrence of ILI-related pneumonia and mortality.

Methods: We obtained data on 804 051 ILI patients from a comprehensive primary care database, the Clinical Practice Research Datalink. The follow-up period started from the diagnosis of ILI for 30 days. Pneumonia and deaths occurring within the 30-day follow-up period were considered as potentially ‘ILI related’. Exposure to benzodiazepines and zopiclone was determined in the period preceding a diagnosis of ILI with current use defined as a prescription for benzodiazepines in the month prior to ILI diagnosis. Cox regression was used for the analyses. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) are presented.

Results: Influenza-like illness-related pneumonia and mortality were noted in 1117 and 707 ILI patients, respectively. Current exposure to benzodiazepines was associated with increased occurrence of both ILI-related pneumonia and mortality (ILI-related pneumonia adjusted HR 4.24, 95%CI [2.27, 7.95]; ILI-related mortality adjusted HR 20.69, 95%CI [15.54, 27.54]). A similar increase in ILI-related mortality but not pneumonia was observed with current zopiclone use (ILI-related mortality adjusted HR 10.86, 95%CI [6.93, 17.02]; ILI-related pneumonia adjusted HR 1.97, 95%CI [0.63, 6.12]).

Conclusion: Benzodiazepines may increase the likelihood of pneumonia and mortality related to ILI. A cautionary approach to prescribing benzodiazepine is suggested in people known to be at increased risk of pneumonia or mortality.

Citation

Nakafero, G., Sanders, R. D., Nguyen-Van-Tam, J. S., & Myles, P. R. (2016). The association between benzodiazepines and influenza-like illness-related pneumonia and mortality: a survival analysis using UK Primary Care data. Pharmacoepidemiology and Drug Safety, 25(11), 1263-1273. https://doi.org/10.1002/pds.4028

• Journal Article Type: Article
• Acceptance Date: Apr 20, 2016
• Online Publication Date: May 23, 2016
• Publication Date: 2016-11
• Deposit Date: Jun 16, 2016
• Publicly Available Date: Jun 16, 2016
• Journal: Pharmacoepidemiology and Drug Safety
• Print ISSN: 1053-8569
• Electronic ISSN: 1099-1557
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 11
• Pages: 1263-1273
• DOI: https://doi.org/10.1002/pds.4028
• Keywords: benzodiazepines; zopiclone; influenza-like illness; pneumonia; mortality; pharmacoepidemiology
• Public URL: https://nottingham-repository.worktribe.com/output/788947
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/pds.4028/abstract
• Related Public URLs: http://dx.doi.org/10.1002/pds.4028
• Contract Date: Jun 16, 2016