JAC Advance Access originally published online on May 31, 2007
Journal of Antimicrobial Chemotherapy 2007 60(2):450-452; doi:10.1093/jac/dkm174
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Correspondence |
Rapid decrease in the prevalence of macrolide-resistant group A streptococci due to the appearance of two epidemic clones in Cantabria (Spain)
1 Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS), Universitat de les Illes Balears (UIB), Palma de Mallorca, Spain 2 Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla, Santander, Spain 3 Servicio de Gestión Farmacéutica, Servicio Cántabro de Salud, Santander, Spain
* Corresponding author. Tel: +34-971-173353; Fax: +34-971-173184; E-mail: sebastian.alberti{at}uib.es
Keywords: group A Streptococcus , macrolide resistance , emm type
An increase in erythromycin resistance rates among group A streptococci (GAS) has been reported in some European countries, including Spain, where in some regions the level of resistance is very high (62.3%).1 Resistance to erythromycin is commonly caused by the presence of an active drug efflux pump (M phenotype) or due to target site modification by inducible or constitutive methylases (MLSB phenotype).
It is well established that the prevalence of resistance to antimicrobials depends in part on their use in the community.2 In the case of GAS, a nationwide study in Finland indicated that a reduction in macrolide use correlated with a decrease in macrolide resistance.3 In contrast with this idea, between 2002 and 2004 there were no relevant variations in the attended population or in the consumption of macrolides in Cantabria (Spain), however, we noted a marked decrease in macrolide-resistant GAS in January–April 2004. This study was undertaken to determine the reasons for this rapid decrease.
Antibiotic consumption data from January 2002 to April 2004 were obtained from SIFARCAN (Pharmaceutical Information System of Cantabria). All GAS collected from January 2002 to April 2004 at the Hospital Marques de Valdecilla of Cantabria (Spain) were identified by conventional methods. More than 95% of these isolates were from pharyngotonsillitis. Susceptibility of isolates to macrolides during this period was routinely tested by disc diffusion according to the CLSI guidelines and phenotypes of resistance were evaluated as previously described.4
The prevalence of GAS resistant to macrolides in Cantabria was high from the second quarter of 2002 until the third quarter of 2003, when the percentage of the resistant isolates varied between 27.4 and 38.6, respectively, reaching a maximum of 53.6 between July and December of 2002 (Figure 1). The prevalence decreased rapidly in the last quarter of 2003, reaching a percentage as low as 3.7 in the first quarter of 2004. In parallel, the total number of GAS isolated from January 2002 did not show significant changes until the first quarter of 2004 when we detected a dramatic increase (Figure 1).
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In this period, macrolide-resistant GAS exhibited two different phenotypes of resistance: the constitutive MLSB (cMLSB) phenotype and the M phenotype. The M phenotype was expressed by 70% and 68% of the isolates in 2002 and 2003, respectively. In contrast, only 48% of the macrolide-resistant GAS isolated in 2004 presented the M phenotype. In parallel, 30% and 32% of the isolates presented the cMLSB phenotype in 2002 and 2003, respectively, while in 2004 52% of the macrolide-resistant isolates expressed the cMLSB phenotype. This rapid inversion of macrolide resistance phenotypes has been described in other regions of Spain5 and in Portugal, where the MLSB phenotype dominated in 1998 whereas the M phenotype prevailed in 2003.6
During January 2002–March 2004, the pattern of macrolide consumption in Cantabria did not exhibit significant changes (Figure 1). However, a sudden decrease in the frequency of erythromycin-resistant strains was observed suggesting the emergence and dissemination of some susceptible strains.
For this purpose, we monitored by emm gene typing, following the protocol previously described,4 the diversity of all GAS isolated during April 2004 at the same hospital (94 isolates; 11 from adult patients and 83 from paediatric patients). All were susceptible to macrolides and caused acute pharyngotonsillitis. It was proved that, emm type 1 and emm type 3 were the most prevalent emm types among GAS isolates susceptible to erythromycin. Besides these emm types, all the other emm types were represented by few isolates. emm type 1 and emm type 3 are the most frequent in Spain, however, the frequency of these emm types was very high (43% emm type 1 and 34% emm type 3) when compared with a previous study (12.4% and 11.4%, respectively).4 For this reason, we investigated whether these emm type 1 and emm type 3 isolates represented only few clones.
Genotypic characterization of the 94 GAS isolates obtained during April 2004 was carried out by genomic DNA macrorestriction with SfiI and PFGE following the protocol described previously.4 All emm type 1 and emm type 3 isolates exhibited the same PFGE patterns, respectively. These results suggest that all emm type 1 and emm type 3 isolates collected from different patients in April 2004 in Cantabria represented only two different clones. Furthermore, it is likely that the rapid decrease in the frequency of the macrolide-resistant GAS isolates was caused by the emergence and successful dissemination of these GAS isolates susceptible to erythromycin.
In summary, we have shown that, without changes in the consumption of macrolides, the frequency of macrolide-resistant GAS in a particular geographical area may be significantly altered by the emergence of successful epidemic clones susceptible to these antimicrobial agents. This indicates that additional studies, including molecular analysis of genes involved in resistance and of clonal relationship of isolates, are required to establish a cause-effect between consumption and resistance.
None to declare.
Acknowledgements
Supported by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III-FEDER, Spanish Network for the Research in Infectious Diseases (REIPI RD06/0008).
References
1
Pérez-Trallero E, García-de-la-Fuente C, García-Rey C, et al. Geographical and ecological analysis of resistance, coresistance, and coupled resistance to antimicrobials in respiratory pathogenic bacteria in Spain. Antimicrob Agents Chemother (2005) 49:1965–72.
2 Baquero F, Blázquez J. Evolution of antibiotic resistance. Trends Ecol Evol (1997) 12:482–7.[CrossRef]
3
Seppala H, Klaukka T, Vuopio-Varkila J, et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N Engl J Med (1997) 337:441–6.
4
Albertí S, García-Rey C, Domínguez MA, et al. Survey of emm gene sequences from pharyngeal Streptococcus pyogenes isolates collected in Spain and their relationship with erythromycin susceptibility. J Clin Microbiol (2003) 41:2385–90.
5 Tamayo J, Pérez-Trallero E, Gómez-Garces JL, et al. Resistance to macrolides, clindamycin and telithromycin in Streptococcus pyogenes isolated in Spain during 2004. J Antimicrob Agents (2005) 56:780–2.
6
Silva-Costa C, Ramirez M, Melo-Cristino J, et al. Rapid inversion of the prevalences of macrolide resistance phenotypes paralleled by a diversification of T and emm types among Streptococcus pyogenes in Portugal. Antimicrob Agents Chemother (2005) 49:2109–11.
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