RESUMO
In methicillin-resistant Staphylococcus aureus (MRSA) treatment, the vancomycin minimum inhibitory concentration (MIC) increase, vancomycin heteroresistance (hVISA) presence, and accessory gene regulator (agr) dysfunction are predictors of vancomycin therapy failure. This study evaluated the association between vancomycin MIC (≥ 1.0 µg/mL) and agr dysfunction in invasive MRSA isolates. Vancomycin MIC, hVISA phenotype, agr group, and function were determined in 171 MRSA isolates obtained between 2014 and 2019 from hospitals in Porto Alegre, Brazil. All MRSA were susceptible to vancomycin; 16.4% of these had MIC ≥ 1.0 µg/mL. Seventeen MRSA isolates expressed the hVISA phenotype; 35.3% of them had MIC of 1.5 µg/mL. agr groups I (40.9%) and II (47.1%) were the most found groups for MRSA and hVISA isolates, respectively. The proportion of MRSA with vancomycin MIC ≥ 1.0 µg/mL in agr group II was significantly higher than in agr groups I and III (p = 0.002). agr dysfunction was observed in 4.7% (8/171) of MRSA, especially those with vancomycin MIC ≥ 1.0 µg/mL (p < 0.001). In addition, six isolates (35.3%; 6/17) with hVISA phenotype presented agr dysfunction, which was significantly higher than that in non-hVISA phenotype (p < 0.001). In conclusion, agr dysfunction in MRSA is associated with vancomycin MIC ≥ 1.0 µg/mL and hVISA phenotype, which suggests that agr dysfunction might confer potential advantages on MRSA to survive in invasive infections.
Assuntos
Proteínas de Bactérias/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Transativadores/metabolismo , Vancomicina/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Brasil , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , Fenótipo , Infecções Estafilocócicas/microbiologia , Transativadores/genética , Resistência a Vancomicina/efeitos dos fármacosRESUMO
Introduction. Vancomycin has become the first-line therapy for most infections caused by methicillin-resistant staphylococci.Aim. To evaluate the vancomycin MIC, staphylococcal cassette chromosome mec (SCCmec) types and clonality of coagulase-negative staphylococci (CoNS) isolates recovered from neonates with true primary bloodstream infections (BSI).Methodology. CoNS isolates were prospectively recovered from blood cultures of non-repetitive patients admitted to a neonatal intensive care unit (NICU) in a tertiary-care hospital during a 3-year period. BSI was defined based on established criteria. Micro-organisms were identified phenotypically and by PCR. MIC-values for vancomycin and oxacillin were determined by broth dilution method and E-test. The SCCmec type conferring methicillin resistance was determined by multiplex PCR. The heterogeneous vancomycin (hV) resistance phenotype was screened on brain heart infusion agar containing 4 µg ml-1 of vancomycin. The clonality was investigated by PFGE.Results. Seventy-four CoNS isolates were recovered from blood cultures of neonates during the study period but only 40 (54â%) were associated with true primary BSI. Nine (22.5%) babies died. Staphylococcus epidermidis was the most prevalent species (95â%; 38/40). All S. epidermidis isolates were methicillin-resistant (MR). SCCmec type IV was predominant (55.3â%; 21/38). Most (80.0â%; 32/38) isolates exhibited vancomycin MIC-values of 2-4 µg ml-1 not associated with the SCCmec type or clonality. Sixteen (42.1%) isolates displayed hV resistance. All babies who died were harbouring MR-S. epidermidis exhibiting vancomycin MICs of 2-4 µg ml-1.Conclusion. The findings of this study demonstrated that blood invasive MR-S. epidermidis isolates recovered at NICU tend to show decreased vancomycin susceptibility making therapy of those fragile patients difficult.