Heterogeneous vancomycin-intermediate susceptibility in a community-associated methicillin-resistant Staphylococcus aureus epidemic clone, in a case of Infective Endocarditis in Argentina

Abstract

Background: Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone.

Case presentation: We describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2) was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1) was fully vancomycin susceptible (VSSA). Although MRSA SaB2 was vancomycin susceptible (≤ 2 μg/ml) by MIC (agar and broth dilution, E-test and VITEK 2), a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP). In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL) genes and had indistinguishable PFGE patterns (subtype I2), thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I) detected in our country.

Conclusions: This report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to produce severe and rapidly fatal infections such as IE, in addition to its ability to acquire low-level vancomycin resistance; for these reasons, it constitutes a new challenge for the Healthcare System of this country.

Figures

Figure 1

Transesophageal echocardiography of a patient with infective endocarditis caused by CA-MRSA with phenotype h-VISA, Argentina. Left: On April 12, the highly mobile vegetation on the aortic valve (AV) of 20 × 41 mm (white arrow). Right: On April 24, slight decrease in the aortic valve (AV) vegetation (white arrow) and a new vegetation on the mitral valve (MV) (10 × 4.6 mm) of low motility (white arrow).

Figure 2

Transmission electron microscopy of initial isolate (SaB1)-VSSA vs. after persistent bacteremia isolate (SaB2)-h-VISA. Comparison of the cell thickness among the pair of strains (SaB2 vs SaB1) and one derivative VISA (CIM 4 μg/ml) obtained on PAP (PAPd4). Quality control strains included S. aureus ATCC 29213 and Mu50, control, negative and positive for VISA, respectively. Magnification: × 60,000. Values given under each image are mean ± SD of the cell wall thickness in nanometers. Student's t test demonstrated that this augment in cell wall thickness was statistically significant (p <0.001).