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Antimicrob. Agents Chemother. doi:10.1128/AAC.01581-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Risk Factors for the development of S. pneumoniae multiple class resistance in Belgium over a 10-year period: antimicrobial consumption, population density and geographic location

University Hospital Gasthuisberg, Herestraat 49 B-3000, Leuven, Belgium, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA, Pharma Institute of Philadelphia, Philadelphia, 3612 Earlham St. Philadelphia PA 19129, USA

^* To whom correspondence should be addressed. Email: robertino.mera{at}gsk.com.

	Abstract

We investigated the impact of the ambulatory usage of antibiotics in 147 defined geographical circumscriptions in Belgium and at the individual isolate level. The study included 14,448 Streptococcus pneumoniae strains from the Belgium national reference lab collected from 1994 to 2004. Additional risk factors for resistance such as population density/structure and daycare attendance were investigated from the same time-space window.

A statistical model that included resistance to two or more antimicrobial classes offered the best fit for the changes in non-susceptibility to penicillin, macrolides and tetracycline over time and place in Belgium. Analysis at the geographic level identified antimicrobial consumption with a one-year lag (0.5% increase per additional defined daily dose), and population density as independent predictors of multiple resistance. Independent risk factors at the isolate level were age (OR = 1.55 for children < 5 years), population density (7% increase in multiple resistance per 100 inhabitants/km2), conjugate 7-valent vaccine serotype (OR = 14.3), location (OR = 1.55 for regions bordering high resistance France) and isolate source (OR = 1.54 for ear isolates). The expansion of multiple resistant strains explains most of the overall two-fold increase and subsequent decrease in single antimicrobial resistance between 1994 and 2004.

We conclude that factors such as high population density and proximity to high resistance regions favor multiple resistance, in addition to antibiotic use. Regional resistance rates are not linearly related to actual antibiotic use but are linked to past antibiotic use plus a combination of demographic and geographic factors.

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