Spread of epidemic MRSA-ST5-IV clone encoding PVL as a major cause of community onset staphylococcal infections in Argentinean children

Abstract

Background: Community-associated methicillin-resistant Staphylococcus aureus-(CA-MRSA) strains have emerged in Argentina. We investigated the clinical and molecular evolution of community-onset MRSA infections (CO-MRSA) in children of Córdoba, Argentina, 2005-2008. Additionally, data from 2007 were compared with the epidemiology of these infections in other regions of the country.

Methodology/principal findings: Two datasets were used: i) lab-based prospective surveillance of CA-MRSA isolates from 3 Córdoba pediatric hospitals-(CBAH1-H3) in 2007-2008 (compared to previously published data of 2005) and ii) a sampling of CO-MRSA from a study involving both, healthcare-associated community-onset-(HACO) infections in children with risk-factors for healthcare-associated infections-(HRFs), and CA-MRSA infections in patients without HRFs detected in multiple centers of Argentina in 2007. Molecular typing was performed on the CA-MRSA-(n: 99) isolates from the CBAH1-H3-dataset and on the HACO-MRSA-(n: 51) and CA-MRSA-(n: 213) isolates from other regions. Between 2005-2008, the annual proportion of CA-MRSA/CA-S. aureus in Córdoba hospitals increased from 25% to 49%, P<0.01. Total CA-MRSA infections increased 3.6 fold-(5.1 to 18.6 cases/100,000 annual-visits, P<0.0001), associated with an important increase of invasive CA-MRSA infections-(8.5 fold). In all regions analyzed, a single genotype prevailed in both CA-MRSA (82%) and HACO-MRSA(57%), which showed pulsed-field-gel electrophoresis-(PFGE)-type-"I", sequence-type-5-(ST5), SCCmec-type-IVa, spa-t311, and was positive for PVL. The second clone, pulsotype-N/ST30/CC30/SCCmecIVc/t019/PVL(+), accounted for 11.5% of total CA-MRSA infections. Importantly, the first 4 isolates of Argentina belonging to South American-USA300 clone-(USA300/ST8/CC8/SCCmecIVc/t008/PVL(+)/ACME(-)) were detected. We also demonstrated that a HA-MRSA clone-(pulsotype-C/ST100/CC5) caused 2% and 10% of CA-MRSA and HACO-MRSA infections respectively and was associated with a SCCmec type closely related to SCCmecIV(2B&5).

Conclusions/significance: The dissemination of epidemic MRSA clone, ST5-IV-PVL(+) was the main cause of increasing staphylococcal community-onset infections in Argentinean children (2003-2008), conversely to other countries. The predominance of this clone, which has capacity to express the h-VISA phenotype, in healthcare-associated community-onset cases suggests that it has infiltrated into hospital-settings.

Figure 1. Evolution of community-associated Staphylococcus aureus infections from children in Cordoba-Argentina, 2003–2008.

Evolution of the rates of all community-associated Staphylococcus aureus infections: i) methicillin-resistant S. aureus (CA-MRSA) infections [total (squares) and invasive-INVI (circles)], and ii) total methicillin-susceptible S. aureus (CA-MSSA) infections (triangles) in Córdoba children's hospitals, [H1 (CBAH1): 2003–2008: filled figures, and in H1, H2 and H3 (CBAH1-3): 2005 vs 2007–2008: empty figures] iii) methicillin-resistant community-associated Staphylococcus aureus infections caused by the ST5-IV-PVL⁺clone [total (gray squares) and invasive (INVI) (gray circles)] in H1 (CBAH1): 2003–2008.

Figure 2. Molecular characteristics and proportion from different regions of Argentina of dominant community methicillin-resistant-Staphylococcus aureus clones.

A. PFGE pattern analysis for representative isolates belonging to the most prevalent subtypes of community-onset-MRSA clones (CA-MRSA and HA-MRSA) detected in central, eastern and northern regions of Argentina during 2007–2008. The schematic presentation of SmaI restriction patterns (middle) and dendrogram (left) by the unweighted-pair group method using average linkage clusterings are shown. Genotypes are denoted as subtype (by PFGE)-ST (by MLST)-SCCmec type-spa type (right). CA-MRSA clones appear in gray. The presence (+) or absence (−) of pvl genes (by PCR) is also indicated for each subtype; strains with and other without pvl genes belonging to the same PFGE subtype (I9) are indicated as +/−. The PFGE pattern of USA300-0114 (ST8-IVa-t008-ACME+) is shown for comparison purposes. The first (A1-ST5-I-t149-Cordobes/Chilean), second (B1-ST239-IIIA-t037-Brazilian) and third (C1-ST100-IVNv-t002-Pediatric) more frequent HA-MRSA clones in our country, detected among community-onset MRSA infections, are also shown (dotted gray). B: Proportion of CA-MRSA clones among representative isolates from different regions of Argentina in 2007.