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Phages and their derivatives are increasingly being reconsidered for use in the treatment of bacterial infections due to the rising rates of antibiotic resistance. We assessed the antistaphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics. The activity of SAL200 when it was combined with SOC antibiotics was assessed in vitro by checkerboard and time-kill assays and in vivo with murine bacteremia and Galleria mellonella infection models. SAL200 reduced the SOC antibiotic MICs and showed a ≥3-log 10 -CFU/ml reduction of Staphylococcus aureus counts within 30 min in time-kill assays. Combinations of SAL200 and SOC antibiotics achieved a sustained decrease of >2 log 10 CFU/ml. SAL200 significantly lowered the blood bacterial density within 1 h by >1 log 10 CFU/ml in bacteremic mice ( P < 0.05 versus untreated mice), and SAL200 and SOC antibiotic combinations achieved the lowest levels of bacteremia. The bacterial density in splenic tissue at 72 h postinfection was the lowest in mice treated with SAL200 and SOC antibiotic combinations. SAL200 combined with SOC antibiotics also improved Galleria mellonella larva survival at 96 h postinfection. The combination of the phage endolysin SAL200 with SOC antistaphylococcal antibiotics showed synergistic effects in vitro and in vivo The combination of SAL200 with SOC antibiotics could help in the treatment of difficult-to-treat S. aureus infections., (Copyright © 2018 American Society for Microbiology.)

This study was conducted to assess emergence of daptomycin-nonsusceptible (DAP-NS) phenotype in DAP-naive patients with invasive Staphylococcus aureus (ISA) infections in Korea. A total of 208 S. aureus clinical isolates were selected from a previous prospective study on ISA infections and evaluated for DAP-NS. Although DAP has never been introduced in Korea, five DAP-NS S. aureus strains (2.4%) were identified among 208 S. aureus strains collected from ISA infections. The DAP-NS phenotype was observed only in methicillin-resistant S. aureus (MRSA) strains, but not in methicillin-susceptible S. aureus strains. One DAP-NS MRSA strain belonged to sequence type 72 (ST72) and four were ST5 MRSA strains, three of which were heteroresistant vancomycin (VAN)-intermediate S. aureus. All these five DAP-NS MRSA strains were from healthcare-associated infections without prior exposure to VAN within 30 days. While the ST72 MRSA strain exhibited DAP-NS phenotype via charge repulsion mechanism, four ST5 DAP-NS S. aureus strains had charge-independent DAP-NS mechanism. None of the five DAP-NS strains displayed significant increase in cell wall thickness, indicating that altered cell wall thickness was not associated with the observed DAP-NS phenotype.

There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice., (Copyright © 2017 American Society for Microbiology.)

Invasive heteroresistant vancomycin-intermediate Staphylococcus aureus (h-VISA) isolates were identified and characterized in 10 Korean hospitals from July 2009 to June 2011. The prevalence of h-VISA infections was 3.3% (42/1,289). Most (41/42) were health care-associated infections caused by strains belonging to sequence type 5. Cases of persistent bacteremia were frequent (17/42), and 30-day mortality was high (16/40)., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

There have been few clinical studies on the association between the 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. Patients with MRSA bacteraemia between July 2009 and January 2012 were analysed retrospectively. All adult patients treated with vancomycin for ≥72 h without dialysis were included. The MIC was determined by Etest and broth microdilution (BMD). Initial steady-state AUC24 was estimated using a Bayesian model, and the AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by classification and regression tree (CART) analysis. In total, 76 patients were enrolled; vancomycin treatment failure occurred in 20 patients (26.3%). Catheter-related infection was the most frequent (35.5%), followed by surgical site infection (26.3%), whilst 25 (32.9%) had complicated infections. In univariate analysis, decreased MRSA vancomycin susceptibility (MIC≥1.5 mg/L) and vancomycin trough levels (15-20 mg/L) were not associated with treatment outcomes. In the CART analysis, low initial vancomycin AUC24/MIC (<430 by Etest; <398.5 by BMD) was associated with a higher treatment failure rate (50.0% vs. 25.0%, P=0.039 by Etest; 45.0% vs. 23.2%; P=0.065 by BMD). In multivariate analysis, low initial vancomycin AUC24/MIC was a significant risk factor for treatment failure [adjusted odds ratio (aOR)=4.39, 95% confidence interval (CI), 1.26-15.35 by Etest; aOR=3.73, 95% CI 1.10-12.61 by BMD]. In MRSA bacteraemia, a low initial vancomycin AUC24/MIC is an independent risk factor for vancomycin treatment failure., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)