Dataset Information

Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India.

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important clinical concern in patients, and is often associated with significant disease burden and metastatic infections. There is an increasing evidence of heterogeneous vancomycin-intermediate S. aureus (hVISA) associated treatment failure. In this study, we aim to understand the molecular mechanism of teicoplanin resistant MRSA (TR-MRSA) and hVISA. A total of 482 MRSA isolates were investigated for these phenotypes. Of the tested isolates, 1% were identified as TR-MRSA, and 12% identified as hVISA. A highly diverse amino acid substitution was observed in tcaRAB, vraSR, and graSR genes in TR-MRSA and hVISA strains. Interestingly, 65% of hVISA strains had a D148Q mutation in the graR gene. However, none of the markers were reliable in differentiating hVISA from TR-MRSA. Significant pbp2 upregulation was noted in three TR-MRSA strains, which had teicoplanin MICs of 16 or 32 ?g/ml, whilst significant pbp4 downregulation was not noted in these strains. In our study, multiple mutations were identified in the candidate genes, suggesting a complex evolutionary pathway involved in the development of TR-MRSA and hVISA strains.

SUBMITTER: Bakthavatchalam YD

PROVIDER: S-EPMC6936811 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India.

Bakthavatchalam Yamuna Devi YD Babu Priyanka P Munusamy Elakkiya E Dwarakanathan Hariharan Triplicane HT Rupali Priscilla P Zervos Marcus M John Victor Peter P Veeraraghavan Balaji B

PloS one 20191230 12

Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important clinical concern in patients, and is often associated with significant disease burden and metastatic infections. There is an increasing evidence of heterogeneous vancomycin-intermediate S. aureus (hVISA) associated treatment failure. In this study, we aim to understand the molecular mechanism of teicoplanin resistant MRSA (TR-MRSA) and hVISA. A total of 482 MRSA isolates were investigated for these phenotypes. Of the te ...[more]

PMID: 31887179

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Project description:Although methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (RVS-MRSA; including vancomycin-intermediate S. aureus [VISA] and heterogeneous VISA [hVISA]) have been linked with vancomycin treatment failure, it is unclear whether they are more pathogenic than vancomycin-susceptible MRSA (VS-MRSA). We prospectively assessed patients with clinical MRSA isolates during a 10-month period to determine clinical status (infection versus colonization) and therapeutic outcome before correlating these findings with the results of detailed in vitro assessment of vancomycin susceptibility, including population analysis profile (PAP) testing. hVISA and VISA were defined by standard PAP criteria (area-under-the-curve ratio compared to that of the reference hVISA strain Mu3 [>or=0.9]) and routine CLSI criteria (vancomycin MIC, 4 to 8 microg/ml), respectively. Among the 117 patients assessed, 58 had RVS-MRSA isolates (56 hVISA and 2 VISA) and 59 had VS-MRSA isolates; the patient demographics and comorbidities were similar. RVS-MRSA was associated with a lower rate of infection than VS-MRSA (29/58 versus 46/59; P = 0.003), including a lower rate of bacteremia (3/58 versus 20/59, respectively; P < 0.001). The cure rates in RVS-MRSA and VS-MRSA groups were not statistically different (16/26 versus 31/42; P = 0.43), but the post hoc assessment of treatment regimes and study size made detailed conclusions difficult. The results of the macro method Etest correlated well with the PAP results (sensitivity, 98.3%, and specificity, 91.5%), but broth microdilution and our preliminary RVS-MRSA detection method correlated poorly. All isolates were susceptible to linezolid and daptomycin. These data suggest that detailed prospective laboratory identification of RVS-MRSA isolates may be of limited value and that, instead, such in vitro investigation should be reserved for isolates from patients who are failing appropriate anti-MRSA therapy.

Project description:BACKGROUND:Globally, methicillin resistant Staphylococcus aureus (MRSA) is one of the most common pathogens that causes hospital- and community-acquired infections. The use of molecular typing methods is essential for determining the origin of the isolates, their clonal relations, and also epidemiological investigations. OBJECTIVE:The purpose of this study was to determine the prevalence of antibiotic-resistant MRSA investigate the accessory gene regulator (agr) and staphylococcal cassette chromosome mec (SCCmec) types and perform multilocus sequence typing (MLST). Furthermore, the minimum inhibitory concentration of MRSA isolates was determined for vancomycin and daptomycin. MATERIALS AND METHODS:Two hundred and fifty-nine MRSA isolates were collected from Tertiary Care Hospitals in Coimbatore. Disk diffusion method was employed to assess the sensitivity of MRSA isolates to selected antibiotics and genetic analysis was performed using SCCmec, agr, and MLST typing by multiplex-polymerase chain reaction strategy. Minimal inhibitory concentration (MIC) was determined using Ezy MIC (vancomycin) and Biomerieux (daptomycin) E-test strip. RESULTS:Of 259 MRSA isolates, 209 (80.7%) were confirmed as methicillin resistant. Antibiotic susceptibility pattern revealed that all the MRSA isolates were 100% sensitive to linezolid, rifampicin, teicoplanin, and vancomycin. MIC results showed that of 209 MRSA isolates, 10 were found to be vancomycin intermediate S. aureus and 100% of the MRSA isolates were daptomycin-susceptible. The agr group I and SCCmec Type III were the major type among MRSA isolates. In addition to these MLST typing revealed the prevalence of sequence type (ST) 239 (SLV of ST8) among the MRSA isolates. CONCLUSION:This study confirms that ST239 (Brazilian clone) of MRSA is predominant in this region which is responsible for the hospital-acquired MRSA infections. Thus, the study also suggests that vancomycin and daptomycin can still be used as an alternative drug for treating severe MRSA infections.

Dataset Information

Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India.

Publications

Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India.

Similar Datasets

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