Comparative Effectiveness Of Fluoroquinolone Antibiotic Use In Uncomplicated Acute Exacerbations Of COPD: A Multi-Cohort Study

Abstract

Purpose

Fluoroquinolone antibiotics are associated with rare, but severe adverse events. They are frequently used for the treatment of acute exacerbations of COPD (AECOPD). While their effectiveness in severe exacerbations requiring hospitalisation has been well documented, the potential benefit in the ambulatory setting is less clear, especially in uncomplicated patients with COPD.

Patients and characteristics

We carried out a retrospective cohort study using health care databases from six Canadian provinces in subjects visiting their physician for uncomplicated COPD. Subjects dispensed either a quinolone or other antibiotics were compared using inverse probability of treatment weights with high dimensional propensity scores on 30-day outcomes, including repeat visits, hospitalisation for AECOPD and subsequent antibiotic prescription. Results from each province were combined by random effects meta-analysis.

Results

We identified 286,866 AECOPD events among 203,642 unique individuals. The frequency of fluoroquinolone use, mostly levofloxacin and moxifloxacin, varied by province and ranged from 8% to 32% of AECOPD antibiotic prescriptions. The risk of a repeat ambulatory care visit was increased among patients who were dispensed a fluoroquinolone compared with other antibiotics (OR 1.32, 95% CI 1.27–1.36). The risk of a hospitalisation for AECOPD was also higher with fluoroquinolones (OR 1.52, 95% CI 1.33–1.74). There was no difference in subsequent antibiotic prescriptions (OR 1.00, 95% CI 0.94–1.07).

Conclusion

There is no apparent benefit in short-term outcomes with fluoroquinolones as compared to other antibiotics for the ambulatory treatment of AECOPD in uncomplicated patients. These findings support current recommendations that fluoroquinolones be reserved for AECOPD in patients with recurrent exacerbations, significant co-morbidity or requiring hospitalisation.

Keywords:

• chronic obstructive pulmonary disease
• fluoroquinolones
• comparative effectiveness

Acknowledgments

We would like to acknowledge the programming support of Zhihai Ma (Alberta), Hala Tamim, Yan Wang and Steve Doucette (Nova Scotia), Fangyun Wu and Vicky Ling (Ontario), and Nianping Hu (Saskatchewan). We would like to acknowledge the important contributions of the Canadian Network for Observational Drug Effect Studies (CNODES) collaborators and assistants at each site. The CNODES investigators are: Samy Suissa (Principal Investigator); Colin R. Dormuth (British Columbia); Brenda R. Hemmelgarn (Alberta); Gary F. Teare and Jacqueline Quail (Saskatchewan); Patricia Caetano and Dan Chateau (Manitoba); David A. Henry and J. Michael Paterson (Ontario); Jacques LeLorier (Québec); Adrian R. Levy (Atlantic: Nova Scotia, Newfoundland and Labrador, New Brunswick, Prince Edward Island); Pierre Ernst and Kristian B. Filion (UK Clinical Practice Research Datalink (CPRD)); Robert W. Platt (Methods); and Ingrid S. Sketris (Knowledge Translation). CNODES, a collaborating centre of the Drug Safety and Effectiveness Network (DSEN), is funded by the Canadian Institutes of Health Research (Grant Number DSE-146021).

This study was made possible through data-sharing agreements between CNODES member research centres and the respective provincial governments of Alberta, British Columbia, Manitoba (HIPC #2016/2017 – 15), Nova Scotia, Ontario, and Saskatchewan. The BC Ministry of Health approved access to and use of BC data facilitated by Population Data BC for this study. British Columbia data sources were as follows (http://www.popdata.bc.ca/data): British Columbia Ministry of Health [creator] (2018): Medical Services Plan (MSP) Payment Information File. BC Ministry of Health [publisher]. MOH (2018); British Columbia Ministry of Health [creator] (2018): PharmaNet. BC Ministry of Health [publisher]. Data Stewardship Committee (2018); Canadian Institute for Health Information [creator] (2018): Discharge Abstract Database (Hospital Separations). BC Ministry of Health [publisher]. MOH (2018); British Columbia Ministry of Health [creator] (2018): Consolidation File (MSP Registration & Premium Billing). BC Ministry of Health [publisher]. MOH (2018). All inferences, opinions, and conclusions drawn in this manuscript are those of the authors, and do not reflect the opinions or policies of the Data Steward(s). Parts of this material are based on data and/or information compiled and provided by the Canadian Institute for Health information (CIHI). The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by the provinces, data stewards, or CIHI is intended or should be inferred.

Author Contributions

All authors contributed to the data analysis, drafting and revising the article, gave final approval to the published version, and agree to be accountable for all aspects of the work.

Disclosure

Dr Ingrid Sketris reports salary support in part from CIHR for the CNODES project, during the conduct of the study, grants from Nova Scotia Government’s Drug Evaluation Alliance of Nova Scotia, CIHR, and Australian NHMRC, outside the submitted work. The authors report no other conflicts of interest in this work.