Molecular epidemiology of heteroresistant vancomycin-intermediate Staphylococcus aureus in Brazil

Abstract

To determine the epidemiological and molecular characteristics of 12 Staphylococcus aureus isolates presenting heteroresistance to vancomycin in laboratories of two cities in Santa Catarina, southern Brazil. Epidemiological data, including the city of isolation, health institution, and date of isolation were considered, as well as the associated clinical specimen. For molecular characterization, we analyzed the staphylococcal cassette chromosome types, the erm gene presence, and the genomic diversity of isolates using pulsed-field gel electrophoresis. The 12 isolates of S. aureus were previously confirmed as heteroresistance to vancomycin using the population analysis profile-area under curve. Regarding genetic variability, two clones were detected: the main one (clone A) composed of four isolates and the clones B, with two isolates. For clone A, two isolates presented identical band patterns and were related to the same hospital, with an interval of 57 days between their isolation. The other isolates of this clone showed no epidemiological link between them because they were isolated in different hospitals and had no temporal relationship. The other clone showed no detectable epidemiological relationship. The heteroresistance to vancomycin recovered in Santa Catarina State from 2009 to 2012 had, in general, heterogeneous genomic patterns based on pulsed-field gel electrophoresis results, which is in accordance with the fact that these isolates had little or no epidemiological relationship among them. Due to the characteristic phenotypic instability and often prolonged vancomycin therapy for selection, clonal spread is not as common as for other resistance mechanisms disseminated through horizontal gene transfer.

Occurrence of the vanA gene in Staphylococcus epidermidis from nasopharyngeal secretion of Health-Care Workers, Recife, Brazil

“…In 2006, three strains were reported, two S. aureus and one CoNS, with resistance to both antibiotics vancomycin and methicillin 45 . A potential emergence of vancomycin resistance may occur in hospitals in Brazil, as reported in recent studies 9,28 . This suggests the need for constant monitoring of susceptibility patterns to vancomycin, application of molecular methods and heteroresistance detection, as well as adoption of control measures to avoid the spread of these strains in the hospital environment.…”

“…The cell wall thickening has been reported for glycopeptide-resistant VRS and VRSA 12,17,28 . The nasopharynx microbiota of health professionals harboring resistant strains to vancomycin have already been described in the literature 13,31 ; however, the first Brazilian report of S. epidermidis, harboring the vanA gene, and colonizing a health professional from ICU occurred at an University Hospital in Recife, Brazil 12 .…”

“…Additionally, the emergence of hetero-VRSA strains occurred in the 80s after the introduction of vancomycin use for treatment of staphylococcal infections in Japan 27 . Several research studies related to the molecular analysis of heteroresistance vancomycin-intermediate S. aureus worldwide have been performed, following associations of these strains with persistent infections and treatment failure 28 .…”

Discerning the role of polymicrobial biofilms in the ascent, prevalence, and extent of heteroresistance in clinical practice

“…Studies have also described various pathways involved in glycopeptides HR, namely cell wall thickening (Cui et al 2003), slow growth rate (Basco et al 2019), and altered peptidoglycan cross-linking (Di Gregorio et al 2017). Genes related to bacterial cell regulation pathways (vraSR, graSR, saeSR, agr) (Bakthavatchalam et al 2016(Bakthavatchalam et al , 2018Di Gregorio et al 2016;Kim et al 2017), as well as the presence of the mobile genomic island staphylococcal cassette chromosome (SCCmec) types I and/or II, carrying genes related to methicillin (and other drugs) resistance (Silveira et al 2015;Da Costa et al 2016;Huang et al 2016) have been documented.…”

“…They are related to the selection of the resistant cells within biofilms and the dissemination of resistance traits due to facilitated interactions among microorganisms Valvano 2011, 2015). HR within a clonal cell population, despite rarely reported in biofilms, has been documented for several opportunistic pathogens with prominent roles in these infections, dramatically impacting the chronicity of such illnesses (Fusco et al 2009;Cheong et al 2011;Sola et al 2011;Campanile et al 2012;El-Halfawy et al 2013;Silveira et al 2015;Band et al 2016Band et al , 2018Huang et al 2016). Predictably, highly resistant cells that make up heteroresistant subpopulations may further complicate polymicrobial infections by affording protection to more susceptible cells (from the same or different species), either by counteracting antimicrobial effects through the release of neutralising elements or by means of metabolic (cooperative) interplay and cell-cell communication via sharing genetic material/ resistance genes (Dufour and Rao 2011).…”