C-reactive protein predicts persistent bacteremia caused by community-acquired methicillin-resistant Staphylococcus aureus strain.

There is limited data on persistent bacteremia (PB) caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Here, we aimed to investigate the clinical and microbiological characteristics of PB caused by the major CA-MRSA strain in Korea (ST72-SCCmecIV). All adult patients with S. aureus bacteremia were prospectively investigated from August 2008 to December 2018. Patients with ST72 MRSA bacteremia were included in the study. Patients were stratified into the PB group (defined as positive blood cultures for ≥ 3 days) and short bacteremia (SB) group. A total of 291 patients were included, comprising 115 (39.5%) with PB and 176 (60.5%) with SB. Although the 30-day mortality did not differ between PB and SB, recurrent bacteremia within 12 weeks was significantly more common in PB (8.7% vs 1.7%; P = 0.01). Multivariate analysis showed risk factors of PB were liver cirrhosis (adjusted odds ratio [aOR], 3.27; 95% confidence interval [CI], 1.50-7.12), infective endocarditis (aOR, 7.13; 95% CI, 1.37-37.12), bone and joint infections (aOR, 3.76; 95% CI, 1.62-8.77), C-reactive protein ≥ 10 mg/dL (aOR, 2.20; 95% CI, 1.22-3.95), metastatic infection (aOR, 7.35; 95% CI, 3.53-15.29), and agr dysfunction (aOR, 2.47; 95% CI, 1.05-5.81). PB occurred in approximately 40% of bacteremia caused by ST72 MRSA with a significantly higher recurrence rate. Patients with risk factors of PB, including liver cirrhosis, high initial CRP, infective endocarditis, or bone and joint infections, might require early aggressive treatment.

Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

Vancomycin MIC and agr dysfunction in invasive MRSA infections in southern Brazil.

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.

Complete genome sequence of an agr-dysfunctional variant of the ST239 lineage of the methicillin-resistant Staphylococcus aureus strain GV69 from Brazil.

Staphylococcus aureus is a versatile Gram-positive coccus frequently found colonizing the skin and nasal membranes of humans. The acquisition of the staphylococcal cassette chromosome mec was a major milestone in the evolutionary path of methicillin-resistant S. aureus. This genetic element carries the mecA gene, the main determinant of methicillin resistance. MRSA is involved in a plethora of opportunistic infectious diseases. The accessory gene regulator is the major S. aureus quorum sensing system, playing an important role in staphylococcal virulence, including the development of biofilms. We report the complete genome sequence (NCBI BioProject ID: PRJNA264181) of the methicillin-resistant S. aureus strain GV69 (= CMVRS P4521), a variant of the ST239 lineage that presents with a natural attenuation of agr-RNAIII transcription and a moderate accumulation of biofilm.