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Antimicrobial Agents and Chemotherapy, June 2005, p. 2237-2245, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2237-2245.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

New Mutations and Horizontal Transfer of rpoB among Rifampin-Resistant Streptococcus pneumoniae from Four Spanish Hospitals

María José Ferrándiz,1 Carmen Ardanuy,2 Josefina Liñares,2 José María García-Arenzana,3 Emilia Cercenado,4 Ana Fleites,5 Adela G. de la Campa,1* the Spanish Pneumococcal Infection Study Network,{dagger}

Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid,1 Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona,2 Hospital Donostia, San Sebastián, Guipuzcoa,3 Hospital Gregorio Marañón, Madrid,4 Hospital Central de Asturias, Oviedo, Asturias, Spain5

Received 25 November 2004/ Returned for modification 2 January 2005/ Accepted 12 February 2005

A total of 103 (0.7%) of 14,236 Streptococcus pneumoniae isolates collected in four Spanish hospitals from 1989 to 2003 were resistant to rifampin (MICs, 4 to 512 µg/ml). Only sixty-one (59.2%) of these isolates were available for molecular characterization. Resistance was mostly related to human immunodeficiency virus (HIV) infection in adult patients and to conjunctivitis in children. Thirty-six different pulsed-field gel electrophoresis patterns were identified among resistant isolates, five of which were related to international clones (Spain23F-1, Spain6B-2, Spain9V-3, Spain14-5, and clone C of serotype 19F), and accounted for 49.2% of resistant isolates. Single sense mutations at cluster N or I of the rpoB gene were found in 39 isolates, while double mutations, either at cluster I, at clusters I and II, or at clusters N and III, were found in 14 isolates. The involvement of the mutations in rifampin resistance was confirmed by genetic transformation. Single mutations at clusters N and I conferred MICs of 2 µg/ml and 4 to 32 µg/ml, respectively. Eight isolates showed high degrees of nucleotide sequence variations (2.3 to 10.8%) in rpoB, suggesting a recombinational origin for these isolates, for which viridans group streptococci are their potential gene donors. Although the majority of rifampin-resistant isolates were isolated from individual patients without temporal or geographical relationships, the clonal dissemination of rifampin-resistant isolates was observed among 12 HIV-infected patients in the two hospitals with higher rates of resistance.

* Corresponding author. Mailing address: Unidad de Genética Bacteriana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. Phone: (34) 91-5097057. Fax: (34) 91-5097919. E-mail: agcampa{at}isciii.es.

{dagger} Spanish Pneumococcal Infection Study Network G03/103: general coordination, Román Pallarés; participants and centers, Ernesto García (Centro de Investigaciones Biológicas, Madrid); Julio Casal, Asuncion Fenoll, and Adela G. de la Campa (Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid); Emilio Bouza (Hospital Gregorio Marañon, Madrid); Fernando Baquero (Hospital Ramón y Cajal, Madrid); Francisco Soriano and José Prieto (Fundación Jiménez Díaz y Hospital Clínico, Madrid); Román Pallarés and Josefina Liñares (Hospital Universitari de Bellvitge, Barcelona); Javier Garau and Javier Martínez Lacasa (Hospital Mutua de Terrassa, Barcelona); Cristina Latorre (Hospital Sant Joan de Deu, Barcelona); Emilio Pérez-Trallero (Hospital Donostia, San Sebastian); Juan García de Lomas (Hospital Clínico, Valencia); and Ana Fleites (Hospital Central de Asturias).

Antimicrobial Agents and Chemotherapy, June 2005, p. 2237-2245, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2237-2245.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mullin, S., Rothstein, D. M., Murphy, C. K. (2006). Activity of Novel Benzoxazinorifamycins against Rifamycin-Resistant Streptococcus pyogenes.. Antimicrob. Agents Chemother. 50: 1908-1909 [Full Text]  
  • Ferrandiz, M. J., Perez-Trallero, E., Marimon, J. M., de la Campa, A. G. (2005). Clinical Isolates of the Spain14-5 Clone of Streptococcus pneumoniae Carry a Recombinant rpoB Gene. Antimicrob. Agents Chemother. 49: 4811-4813 [Full Text]  


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