Dataset Information

Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin-susceptible/mecA-positive MRSA strains from Africa.

ABSTRACT:

Objectives

Recent surveillance of MRSA colonizing patients and healthcare workers in two African countries (Angola and São Tomé and Príncipe) reported the frequent recovery of oxacillin-susceptible MRSA (OS-MRSA): Staphylococcus aureus strains that gave positive results with the mecA DNA probe, but had low oxacillin MIC values characteristic of susceptible S. aureus. This apparent dissociation of the drug-resistant phenotype from mecA-the primary genetic determinant of resistance-prompted us to perform a more detailed analysis on nine of the African OS-MRSA strains.

Methods

Oxacillin MIC values were determined by Etest and population analysis profiles with and without induction of the stringent stress response by mupirocin. Biochemical profiling using SDS-PAGE followed by western blotting was used for the detection of PBP2A protein produced.

Results

Cultures of the African MRSA strains (ST88-IVa and ST8-V) showed heterogeneous oxacillin resistance in which the majority of cells exhibited low oxacillin MICs (≤0.75 mg/L), but highly resistant subpopulations were also present with oxacillin MIC values up to several hundred mg/L and with frequencies of 10(-4) to 10(-6). The same strains after induction of the stringent stress response by mupirocin 'converted' the heterogeneous phenotypes into a more homogeneous and higher level resistance. After induction by oxacillin and mupirocin, each of the nine African OS-MRSA strains produced PBP2A-the protein product of mecA.

Conclusions

The resistant phenotype of OS-MRSA resembles the phenotypes of historically early MRSA clones. The nature of genetic determinants responsible for the heterogeneous phenotypes of OS-MRSA remains to be determined.

SUBMITTER: Chung M

PROVIDER: S-EPMC5031915 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.