The changing pattern of methicillin-resistant staphylococcus aureus clones in Latin America: implications for clinical practice in the region

The changing pattern of methicillin-resistant Staphylococcus aureus clones in Latin America: implications for clinical practice in the region ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) clones belonging to the Brazilian, Pediatric, Cordobes/Chilean and New York/Japan clonal complexes are widely distributed across Latin America, although their individual distribution patterns and resistance to antimicrobial drugs are constantly changing. Furthermore, clones with increased virulence are beginning to appear more frequently both in hospital and community settings, and there is evidence that virulence factors can be transferred between hospital- and community-associated clones through recombination. These changing patterns have significant implications for clinical practice in the region. Most importantly, clinicians need to be aware of the changing antimicrobial resistance profile of circulating MRSA clones in their region in order to choose the most appropriate empiric antimicrobial therapy. Thus, regional molecular epidemiology programs are required across the region to provide accurate identification and characterization of circulating MRSA clones. Authors Eduardo RodríguezNoriega1 Carlos Seas2 on behalf of the Latin American Working Group on Gram Positive Resistance. 1 Hospital Civil de Guadalajara, Universidad de Guadalajara, Jalisco, Mexico. 2 Universidad Peruana Cayetano Heredia, Lima, Peru. Keywords: MRSA, clones, molecular epidemiology, Latin America. Introduction Methicillin-resistant Staphylococcus aureus (MRSA) poses a major threat to public health worldwide, due to the rapid spread and diversification of pandemic MRSA clones with increasing virulence and antimicrobial resistance. In Latin America, MRSA is a leading cause of nosocomial infections, and the prevalence of MRSA in community-acquired infections is growing.1 Although relatively few studies have addressed the molecular epidemiology of MRSA clones across Latin America, it is clear that several clones circulate in the region and that these differ in their virulence, antimicrobial resistance profile and geographical distribution.1,2 Characterization of these clones is important if appropriate local treatment strategies are to be developed. For example, a thorough knowledge of clones circulating within a region may be used to assess the relationship between clonal types, disease symptoms, antibiotic choice and clinical outcomes. Furthermore, understanding why specific clones predominate in different regions of Latin America is an important and necessary step towards developing the most effective strategies for controlling the spread of MRSA in the region. Here, we summarize current understanding of the spread of pandemic MRSA clones and highlight the distribution of major clones across Latin America, both in hospitals and in the community. Specific virulence factors and bacterial resistance patterns are highlighted, and their impact on clinical outcome is discussed. Evolution of MRSA clones Evolution of bacterial clones Bacterial clones are genetically identical cells descended from a single common ancestor. Over time, members of a single clone may differentiate through point mutations, recombination, and the acquisition or deletion of mobile genetic elements. This differentiation provides additional means for the acquisition of pathogenic charac- Correspondence to: Dr Eduardo Rodríguez-Noriega Hospital Civil de Guadalajara Fray Antonio Alcalde Instituto de Patología Infecciosa y Experimental Centro Universitario Ciencias de la Salud Universidad de Guadalajara Jalisco, México Hospital 308, Colonia El Retiro C.P. 44280, Guadalajara Jalisco, México Phone: +52-33-36145568 Fax: +52-33-36850501 E-mail: idfcolima@ yahoo.com S87 MRSA clones in Latin America teristics, such as antibiotic resistance. Thus, genetic variation gives rise to extensive genomic and phenotypic diversity. Emergence of antibiotic resistant S. aureus clones Clones of S. aureus have a history of antibiotic resistance that began within 4 years of the introduction of penicillin into clinical practice,3 and by 1944, clones of S. aureus resistant to penicillin had been isolated. In the subsequent years, S. aureus became resistant to all of the natural penicillins. MRSA was first reported in the early 1960s, shortly after the introduction of methicillin.4 Early MRSA clones had similar genetic properties to the methicillin-susceptible S. aureus (MSSA) clones that were epidemic in Europe.5 MRSA exhibits resistance to methicillin through a penicillin-binding protein encoded by the gene mecA, which was acquired by successful clones of MSSA from an unknown heterologous source. The mecA gene is carried by a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec). Multiple forms of SCCmec have arisen through the horizontal transfer of mecA in independent events, and, to date, seven main forms have been identified (I, II, III, IV, V, VI and VII).6 All types of SCCmec confer resistance to β-lactam antibiotics, and SCCmec types II and III provide resistance to multiple classes of antibiotics.7 During the evolution of MRSA clones, independent excision of SCCmec is a common phenomenon, resulting in the loss of methicillin-resistance and the transformation of a MRSA clone into a MSSA clone. Hence, clones may evolve from MSSA into MRSA, or from MRSA into MSSA, through the acquisition and excision of SCCmec, respectively.8 Several molecular typing methods are used routinely to characterize MRSA clones, including pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and SCCmec typing.9 These methods have helped researchers to map the spread and evolutionary path of MRSA clones.7,8 MRSA has traditionally been regarded as a nosocomial pathogen,10 but more recently, MRSA infections have appeared in community settings.11 The clones typically responsible for hospital- and community-acquired MRSA infections have been classified as healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA), respectively.12 These clones can be distinguished based on specific microbiologic and genetic characteristics, and often have different epidemiologic, clinical and therapeutic characteristics (Table 1).10,11 Occasionally, hospital-acquired infections may be derived from CA-MRSA strains, and infections acquired in the community may carry healthcareassociated risk factors. Definitive HA-MRSA and CA-MRSA designations for individual clones, therefore, rely on microbiologic and genetic characterization, and the terms ‘healthcare-acquired’ and ‘community-acquired’ refer to the location at which the infection was acquired.12 International spread of MRSA clones S. aureus clones spread quickly around the world,13 disseminating efficiently between countries, within countries and in smaller geographic areas, and usually with concomitant evolution from a methicillin-sensitive to a methicillin-resistan (...truncated)