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

Berendina M Roede ^1*, Paul Bresser ², Patrick Bindels ², Annemieke Kok ³, Maria Prins ³, Gerben ter Riet ², Ronald Geskus ², Ron Herings ⁴ and Jan Prins ²

¹ Academic Medical Center - University of Amsterdam, Netherlands
² Academic Medical Center, University of Amsterdam, Netherlands
³ Municipal Health Service, Cluster Infectious Diseases, Amsterdam, Netherlands
⁴ Pharmo Institute Utrecht, Netherlands

^* To whom correspondence should be addressed. E-mail: i.roede{at}amc.uva.nl.

Accepted 8 June 2008

Abstract

Objectives: We evaluated the risk of a subsequent exacerbation after treatment of an exacerbation with oral corticosteroids without (OS) or with antibiotics (OSA), 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 2-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. We compared the times to the second and third exacerbations 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 patients had at least one exacerbation; in 52% antibiotics had been added. OS and OSA groups were comparable for potential confounding factors. The 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 three months following treatment (hazard ratio 0.62; 99%CI 0.60 - 0.65). In the OSA group mortality during follow-up was lower (HR 0.82; 99% CI 0.66-0.98).

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.