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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,

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 (Spain^23F-1, Spain^6B-2, Spain^9V-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.

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).