Methicillin-resistant Staphylococcus aureus (MRSA) causes invasive infections and is associated with community-acquired infections (CAIs) and hospital-associated infections (HAIs). In 2020, 315 S. aureus isolates, including 145 methicillin-susceptible S. aureus (MSSA) and 170 MRSA, mainly associated with bacteremia and mostly CAIs, were collected from 16 hospitals in different regions of Taiwan. Minimum inhibitory concentrations (MICs) were determined using the Sensititre™ complete automated AST system. Staphylococcal cassette chromosome mec (SCCmec) types were analysed using multiplex polymerase chain reaction. The median age of patients infected with MRSA was significantly higher than that of patients infected with MSSA (72.5 years vs. 67.0 years, P=0.027). MIC50/MIC90 values of eravacycline and omadacycline were 0.06/0.12, and 0.25/0.5, respectively. Of the MRSA isolates, 4.1% presented susceptible dose-dependence to ceftaroline, most of which (85.7%) were HAI- and Panton-Valentine leukocidin (PVL)-negative. Among the MRSA isolates, 7.1% were not susceptible to telavancin and tedizolid (mainly type IV, PVL-negative, and CAI), 0.6% were not susceptible to daptomycin (type III, PVL-negative, and HAI), and 1.8% were not susceptible to quinupristin/dalfopristin (three isolates were type III, IV, and VT, respectively, and all were PVL-negative), but all were susceptible to dalbavancin. In conclusion, patients with bacteremia caused by MRSA were older than those with bacteremia caused by MSSA, SCCmec type IV was more predominant in CAI than in HAI, and MRSA isolates not susceptible to novel anti-MRSA antimicrobials belonged to types II, III, or IV. Further studies that include comprehensive demographics and more detailed descriptions of other antimicrobial-resistant genes are urgently needed.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered an important public health problem, and treatment options are limited. Accordingly, in this meta-analysis, we analyzed published studies to survey in vitro activity of recently approved antibiotics against MRSA isolates.
METHODS: We searched electronic databases; PubMed, Scopus, and Web of Science to identify relevant studies (until November 30, 2020) that have focused on the in vitro activity of telavancin, dalbavancin, oritavancin, and tedizolid against MRSA isolates. Statistical analyses were conducted using STATA software (version 14.0).
RESULTS: Thirty-eight studies were included in this meta-analysis. Overall in vitro activity of tedizolid on 12,204 MRSA isolates was 0.250 and 0.5 µg/mL for MIC50 and MIC90, (minimum inhibitory concentration at which 50% and 90% of isolates were inhibited, respectively), respectively. The overall antibacterial activity of dalbavancin on 28539 MRSA isolates was 0.060 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of oritavancin on 420 MRSA isolates was 0.045 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of telavancin on 7353 MRSA isolates was 0.032 and 0.060 µg/mL for MIC50 and MIC90, respectively. The pooled prevalence of tedizolid, telavancin, and dalbavancin susceptibility was 100% (95% CI: 100-100).
CONCLUSIONS: Telavancin, dalbavancin, oritavancin, and tedizolid had potent in vitro activity against MRSA isolates. The low MICs and high susceptibility rates of these antibiotics recommend a hopeful direction to introduce useful antibiotics in treating MRSA infections in the future.

OBJECTIVE: U.S. Food and Drug Administration (FDA) recommended telavancin dosing is based on total body weight (TBW) but lacks adjusted regimens for obese subjects with varying renal function. Our aim was to develop a physiologically based pharmacokinetic (PBPK) model of telavancin to design optimized dosing regimens for obese patients with hospital-acquired pneumonia (HAP) and varying renal function.
METHODS: The PBPK model was verified using clinical pharmacokinetic (PK) data of telavancin in healthy populations with varying renal function and obese populations with normal renal function. Then, the PBPK model was applied to predict the PK in obese HAP patients with renal impairment (RI).
RESULTS: The fold error values of PK parameters (AUC, Cmax, Tmax) were all within 1.5. The telavancin AUC0-inf was predicted to increase 1.07-fold in mild RI, 1.23-fold in moderate RI, 1.41-fold in severe RI, and 1.57-fold in end-stage renal disease (ESRD), compared with that in obese HAP with normal renal function. The PBPK model combined with Monte Carlo simulations (MCS) suggested that dose adjustment based on a 750-mg-fixed dose could achieve effectiveness with reduced risk of toxicity, compared with current TBW-based dosing recommendations.
CONCLUSIONS: The PBPK simulation proposed that using TBW-based regimen in obesity with RI should be avoided. Dose recommendations in obesity from the PBPK model are 750 mg daily for normal renal function and mild RI, 610 mg daily for moderate RI, 530 mg daily for severe RI, and 480 mg daily for ESRD.

Objective: Telavancin is approved to treat complicated skin and skin structure infections, hospital-acquired, and ventilator-associated bacterial pneumonia caused by Staphylococcus aureus. A previous meta-analysis of randomized controlled trials suggested that it might be an alternative to vancomycin in cases of difficult-to-treat meticillin-resistant S. aureus infections. We did a meta-analysis including one new trial to access the efficacy and safety of telavancin. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, EMBASE and ClinicalTrials.gov up to December 30, 2015 to identify randomized controlled trials that assessed the clinical efficacy, eradication efficiency, adverse events and laboratory abnormalities of telavancin vs. other antibiotic agents for bacterial infection. Meta-analysis was performed using Review Manager 5.3.0. Results: Five studies (3790 participants) were included in the meta-analysis. There was no significant difference in treatment success with telavancin than with control antibiotic agents. The pooled pathogen eradication for the telavancin group was numerically higher than that for the control groups, but there was no significant difference. While all-cause mortalities and serious adverse events were comparable between telavancin and control antibiotic agents, adverse event-related withdrawals (OR 1.47, 95% CI 1.13-1.91) were higher in telavancin group. The total number adverse events were more in the telavancin group than in the control groups, especially in the digestive system (OR 1.57, 95% CI 1.37-1.79), nervous system (OR 2.14, 95% CI 1.86-2.47) and urogenital system (OR 2.54, 95% CI 1.99-3.25). Serum creatinine increase (OR 2.25, 95% Cl 1.78-2.85) and hypokalemia (OR 1.74, 95% CI 1.19-2.53) occurred more frequently in telavancin group compared to control groups. Conclusion: Telavancin may be as effective as but no better than the comparison therapy for S. aureus infection. However, because of the high risk of adverse event-related withdrawals and potential nephrotoxicity, prudence with the clinical use of telavancin in infections is required.