CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study

B M Roede^1,2, P Bresser³, P J E Bindels², A Kok⁴, M Prins^1,4, G ter Riet^2,5, R B Geskus⁶, R M C Herings⁷, J M Prins¹

¹ Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, and Centre for Infection and Immunity Amsterdam (CINIMA), Amsterdam, The Netherlands
² Department of General Practice, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands
³ Department of Pulmonology, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands
⁴ Municipal Health Service, Cluster Infectious Diseases, Amsterdam, The Netherlands
⁵ Horten Centre, University of Zurich, Zurich, Switzerland
⁶ Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre-University of Amsterdam, Amsterdam, The Netherlands
⁷ PHARMO Institute, Utrecht, The Netherlands

B M Roede, Academic Medical Centre-University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, and Centre for Infection and Immunity Amsterdam (CINIMA), F4-217, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; i.roede{at}amc.uva.nl

Objectives: The risk of a subsequent exacerbation after treatment of an exacerbation with oral corticosteroids without (OS) or with (OSA) antibiotics was evaluated in a historical population based cohort study comprising patients using maintenance medication for obstructive lung disease.

Methods: The Pharmo database includes drug dispensing records of more than 2 million subjects in The Netherlands. Eligible were patients 50 years who in 2003 were dispensed 2 prescriptions of daily used inhaled β₂ agonists, anticholinergics and/or corticosteroids, and experienced at least one exacerbation before 1 January 2006. Exacerbation was defined as a prescription of OS or OSA. The times to the second and third exacerbations were compared using Kaplan–Meier survival analysis. Independent determinants of new exacerbations were identified using multivariable Cox recurrent event survival analysis.

Results: Of 49 599 patients using maintenance medication, 18 928 had at least one exacerbation; in 52%, antibiotics had been added. The OS and OSA groups were comparable for potential confounding factors. Median time to the second exacerbation was 321 days in the OS group and 418 days in the OSA group (p<0.001); and between the second and third exacerbation 127 vs 240 days (p<0.001). The protective effect of OSA was most pronounced during the first 3 months following treatment (hazard ratio (HR) 0.62; 99% CI 0.60 to 0.65). In the OSA group, mortality during follow-up was lower (HR 0.82; 99% CI 0.66 to 0.98).

Conclusion: Treatment with antibiotics in addition to oral corticosteroids was associated with a longer time to the next exacerbation, and a decreased risk of developing a new exacerbation.

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