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Antimicrobial Agents and Chemotherapy, October 2007, p. 3491-3497, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.01581-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Risk Factors for Development of Multiple-Class Resistance to Streptococcus pneumoniae Strains in Belgium over a 10-Year Period: Antimicrobial Consumption, Population Density, and Geographic Location{triangledown}

Johan Van Eldere,1 Robertino M. Mera,2* Linda A. Miller,3 James A. Poupard,4 and Heather Amrine-Madsen2

University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium,1 GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, North Carolina 27709,2 GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426,3 Pharma Institute of Philadelphia, 3612 Earlham St., Philadelphia, Pennsylvania 191294

Received 19 December 2006/ Returned for modification 8 May 2007/ Accepted 20 July 2007

We investigated the impact of the usage of antibiotics in ambulatory patients in Belgium in 147 defined geographical circumscriptions and at the individual isolate level. The study included 14,448 Streptococcus pneumoniae strains collected by the Belgium national reference lab from 1994 to 2004. Additional risk factors for resistance, such as population density/structure and day care attendance, were investigated for the same time-space window. A statistical model that included resistance to two or more antimicrobial classes offered the best fit for measuring the changes in nonsusceptibility to penicillin, macrolides, and tetracycline over time and place in Belgium. Analysis at the geographic level identified antimicrobial consumption with a 1-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 (odds ratio [OR], 1.55 for children aged <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 twofold increase and subsequent decrease in single antimicrobial resistance between 1994 and 2004. We conclude that factors in addition to antibiotic use, such as high population density and proximity to high-resistance regions, favor multiple resistance. 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.

* Corresponding author. Mailing address: 5 Moore Drive, MAI-B252.2E, Research Triangle Park, NC 27709. Phone: (919) 583-6084. Fax: (919) 315-4081. E-mail: robertino.mera{at}gsk.com

{triangledown} Published ahead of print on 6 August 2007.

Antimicrobial Agents and Chemotherapy, October 2007, p. 3491-3497, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.01581-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Patrick, D. M. MD MHSc, Hutchinson, J. MD (2009). Antibiotic use and population ecology: How you can reduce your "resistance footprint". CMAJ 180: 416-421 [Full Text]  
  • Amrine-Madsen, H., Van Eldere, J., Mera, R. M., Miller, L. A., Poupard, J. A., Thomas, E. S., Halsey, W. S., Becker, J. A., O'Hara, F. P. (2008). Temporal and Spatial Distribution of Clonal Complexes of Streptococcus pneumoniae Isolates Resistant to Multiple Classes of Antibiotics in Belgium, 1997 to 2004. Antimicrob. Agents Chemother. 52: 3216-3220 [Abstract] [Full Text]  
  • Flamaing, J., Verhaegen, J., Vandeven, J., Verbiest, N., Peetermans, W. E. (2008). Pneumococcal bacteraemia in Belgium (1994 2004): the pre-conjugate vaccine era. J Antimicrob Chemother 61: 143-149 [Abstract] [Full Text]  


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