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Antimicrobial Agents and Chemotherapy, February 2002, p. 528-530, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.528-530.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Very Low Cefotaxime Concentrations Select for Hypermutable Streptococcus pneumoniae Populations

María-Cristina Negri, María-Isabel Morosini, María-Rosario Baquero, Rosa del Campo, Jesús Blázquez, and Fernando Baquero*

Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain

Received 9 July 2001/ Returned for modification 15 September 2001/ Accepted 29 October 2001

A mixed culture of an hypermutable hexA Streptococcus pneumoniae mutant strain and its hexA+ isogenic ancestor was challenged with low cefotaxime concentrations. Despite identical original cefotaxime MICs, the hexA mutant population was significantly selected at very low concentrations, and all of the tested selected variants harbored the Thr550->Ala mutation in pbp2x. Since cefotaxime selects hypermutators, the risk of secondary acquisition of antibiotic resistance is increased; as expected, the cefotaxime-resistant mutants had a mutation frequency 10 times higher in response to to ciprofloxacin. The present study presents a model (not necessarily reflecting the clinical setting) illustrating the risk of selection of mutators in the evolution of multiple resistance.

* Corresponding author. Mailing address: Departmento de Microbiología, Hospital Ramón y Cajal, Ctra. de Colmenar, Km 9,1. 28034, Madrid, Spain. Phone number: 34-91-3368330. Fax: 34-91-3368809. Email: fbaquero{at}hrc.insalud.es.

Antimicrobial Agents and Chemotherapy, February 2002, p. 528-530, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.528-530.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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