martes, 21 de octubre de 2014

Spread of Streptococcus pneumoniae Serotype 8-ST63 Multidrug-Resistant Recombinant Clone, Spain - Volume 20, Number 11—November 2014 - Emerging Infectious Disease journal - CDC


Spread of Streptococcus pneumoniae Serotype 8-ST63 Multidrug-Resistant Recombinant Clone, Spain - Volume 20, Number 11—November 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 11—November 2014


Spread of Streptococcus pneumoniae Serotype 8-ST63 Multidrug-Resistant Recombinant Clone, Spain

Carmen ArdanuyComments to Author , Adela G. de la Campa, Ernesto García, Asunción Fenoll, Laura Calatayud, Emilia Cercenado, Emilio Pérez-Trallero, Emilio Bouza, and Josefina Liñares
Author affiliations: Hospital Universitari de Bellvitge–Universitat de Barcelona–Fundació Privada Institut d'Investigació Biomèdica de Bellvitge, Barcelona, Spain (C. Ardanuy, L. Calatayud, J. Liñares)Centros de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain (C. Ardanuy, A.G. de la Campa, A. Fenoll, L. Calatayud, E. Cercenado, E. Pérez-Trallero, E. Bouza, E. García, J. Liñares)Instituto de Salud Carolos II, Madrid (A. G. de la Campa, A. Fenoll)Consejo Superior de Cientificas, Madrid (A.G. de la Campa, E. García);Hospital Gregorio Marañón–Universidad Complutense, Madrid (E. Cercenado, E. Bouza)Hospital Universitario Donostia, Donostia, Spain (E. Pérez-Trallero)


Since 2004, a total of 131 isolates of Streptococcus pneumoniae multidrug-resistant invasive serotype 8 have been detected in Spain. These isolates showed resistance to erythromycin, clindamycin, tetracycline, and ciprofloxacin. All isolates were obtained from adult patients and shared a common genotype (sequence type [ST]63; penicillin-binding protein 1a [pbp1a], pbp2b, and pbp2x gene profiles; ermB and tetM genes; and a ParC-S79F change). Sixty-eight isolates that required a ciprofloxacin MIC ≥16 μg/mL had additionalgyrA gene changes. Serotype 8-ST63 pbp2x sequences were identical with those of antimicrobial drug–susceptible serotype 8-ST53 isolates. Serotype 8-ST63 pbp2b sequences were identical with those of the multidrug-resistant Sweden 15A-ST63 clone. Recombination between the capsular locus and flanking regions of an ST53 isolate (donor) and an ST63 pneumococcus (recipient) generated the novel 15A-ST63 clone. One recombination point was upstream of pbp2x and another was within pbp1a. A serotype 8-ST63 clone was identified as a cause of invasive disease in Spain.
Streptococcus pneumoniae is a frequent cause of community-acquired pneumonia, meningitis, bacteremia, and otitis media in children. The diverse biochemical composition of the capsular polysaccharide results in ≥94 serotypes (1). However, only a few serotypes cause most invasive disease episodes worldwide. Serotype 8 pneumococci cause invasive pneumococcal disease in adults and have been occasionally associated with outbreaks. Nevertheless, isolates of this serotype are rarely found in children as a cause of invasive disease or as colonizers of the nasopharynx (2,3). Few lineages have been identified among serotype 8 pneumococci; the major clone is Netherlands 8-ST53, which has been detected worldwide and is typically susceptible to antimicrobial drugs (4).
The capsular polysaccharide is the major virulence factor of pneumococci and usually determines their ability to act as invasive or colonizing microorganisms (3). In addition to exhibiting the capsule, pneumococci can show low or high genetic diversity, but genotype–serotype association is common. However, this association could be disrupted because of capsular switching caused mainly by recombination of capsular genetic loci. This finding could be a sporadic event, but the recombinant occasionally spreads and could cause pneumococcal disease.
Capsular switching was associated with emergence of a serotype 19A variant of a formerly serotype 4 clone (5) related to immunity pressure sustained after a 7-valent pneumococcal conjugate vaccine was introduced into the United States. This well-known phenomenon was the origin of the major penicillin-resistant clone (serotype 14 variant of the Spain 9V-ST156 clone), which caused invasive pneumococcal disease in Spain in the 2000s (4,6).
Data from the Spanish Reference Laboratory for Pneumococci, which has received pneumococci from Spain since 1979, showed rates of 2.5% to 6.5% for serotype 8 invasive isolates in the last 3 decades. These rates did not show any association with introduction of therapeutic or preventive measures (7,8). Over these decades, serotype 8 pneumococci were usually susceptible to antimicrobial drugs, although some isolates were resistant to erythromycin or tetracycline. Moreover, serotype 8 pneumococci were isolated mainly from adult patients (7,8). However, since 2004, serotype 8 pneumococci have been identified that showed resistance to erythromycin, clindamycin, tetracycline, and ciprofloxacin.
In the present study, we analyzed the evolution and molecular epidemiology of these multidrug-resistant serotype 8 pneumococci. We determined whether the increase in these isolates was associated with dissemination of a new recombinant clone (serotype 8-ST63) capable of causing invasive pneumococcal disease in different areas of Spain.

Dr Ardanuy is a clinical microbiologist and researcher at the Microbiology Department, Hospital Univesitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain. Her research interests are molecular epidemiology and antimicrobial drug resistance in bacteria.


We thank Imperial College, London, for use of the S. pneumoniae MLST website (supported by the Wellcome Trust), and Montserrat Alegre and Meritxell Cubero for excellent technical support.
This study was supported by a grant from Fondo de Investigaciones Sanitarias de la Seguridad Social (PI11/00763), Plan Nacional de I + D + I of the Ministerio de Ciencia e Innovación of Spain (BIO2011-25343), and Centros de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias (CIBERES-CB06/06/0037), an initiative of the Instituto de Salud Carlos III, Madrid, Spain. C.A., A.F., and J.L. received support from Pfizer for a project independent of the present study.


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Suggested citation for this article: Ardanuy C, de la Campa AG, García E, Fenoll A, Calatayud L, Cercenado E, et al. Spread of Streptococcus pneumoniaeserotype 8-ST63 multidrug-resistant recombinant clone, Spain. Emerg Infect Dis [Internet]. 2014 Nov [date cited].
DOI: 10.3201/eid2011.131215

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