Daptomycin, a lipopeptide antibiotic, is one of the therapeutic options used for the treatment of vancomycin-resistant enterococci (VRE). Recently, the Clinical and Laboratory Standards Institute (CLSI) M100 30th edition has removed the susceptibility (S) breakpoint for Enterococcus faecium and replaced it with a susceptible dose-dependent (SDD) breakpoint of ≤4 μg/mL, with a suggested dosage of 8–12 mg/kg/day. Herein, we aimed to determine the minimum inhibitory concentration (MIC) values of daptomycin against clinical VRE isolates and to study the appropriate daptomycin dosing regimens among critically ill patients based on the new susceptibility CLSI breakpoint. The MIC determination of daptomycin was performed using E-test strips among clinical VRE strains isolated from patients at the Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the ratio of the free area under the curve to MIC (fAUC_0–24/MIC) > 27.4 and fAUC_0–24/MIC > 20 for survival and microbiological response, respectively, at the first day and steady state. Further, we determined that the simulated daptomycin dosing regimen met the minimum concentration (Cmin) requirements for safety of being below 24.3 mg/L. All of the 48 VRE isolates were E. faecium strains, and the percentiles at the 50th and 90th MIC of daptomycin were 1 and 1.5 μg/mL, respectively. At MIC ≤ 2 μg/mL, a daptomycin dosage of 12 mg/kg/day achieved the PTA target of survival and microbiological response at the first 24 h time point and steady state. For a MIC of 4 μg/mL, none of the dosage regimens achieved the PTA target. For CFR, a dosage of 8–12 mg/kg/day could achieve the 90% CFR target at the first day and steady state. All dosing regimens had a low probability of Cmin being greater than 24.3 mg/L. In conclusion, the MIC of VRE against daptomycin is quite low, and loading and maintenance doses with 8 mg/kg/day were determined to be optimal and safe.

Santimaleeworagun W, et al. Infect Chemother. 2021 Jul;53:e42. https://doi.org/10.3947/ic.2021.0034

Enterococci are major causes of bacteremia. Although the mortality rate of ampicillin- susceptible enterococci (ASE) bloodstream infections (BSI) is lower, compared with that of ampicillin-resistant enterococci BSI, the role of treatment regimens in ASE BSI remains to be determined. This retrospective study aimed to evaluate the treatment outcomes and factors associated with mortality among patients with ASE BSI. The charts of 145 enrolled patients with ASE BSI between January 2013 and April 2022 at Phramongkutklao Hospital were reviewed. The 30-day and in-hospital mortality rates were 28.8 and 41.9%, respectively. The 30-day mortality rate was higher in the vancomycin treatment group than in the beta-lactam treatment group (61.5 vs. 26%; p = 0.02). Pitt bacteremia score (OR 1.44, 95% CI 1.20–1.71); age-adjusted Charlson Comorbidity Index (OR 1.34, 95% CI 1.14–1.58); and vancomycin treatment (OR 4.07, 95% CI 1.02–16.22) were independent factors associated with 30-day mortality. The severity of illness, comorbidity and definitive therapy with vancomycin increased the mortality rate of patients with ASE BSI. Anti-enterococcal beta-lactams remain the first line antibiotics for ASE bacteremia.

Thampithak A, et al. Infect Chemother. 2022 Nov;54:e73. https://doi.org/10.3947/ic.2022.0098

Santimaleeworagun W, et al. Infect Chemother. 2020 Sep;52(3):345-351. https://doi.org/10.3947/ic.2020.52.3.345

Pseudomonas aeruginosa associated with hospital-acquired infection is often resistant to various antibiotics and is associated with high mortality worldwide. The appropriate treatment of Pseudomonas aeruginosa resistant to carbapenems but susceptible to traditional antipseudomonal non-carbapenem β-lactam agents (Car-R/NonCar-S P. aeruginosa) remains unclear. This retrospective study evaluated risk factors for 14-day and 30-day mortality among treatment regimens against Car-R/NonCar-S P. aeruginosa. This study enrolled 180 patients with Car-R/NonCar-S P. aeruginosa infection at Phramongkutklao Hospital between January 2019 and December 2023. The 14-day and 30-day mortality rates were 18.3% and 28.9%, respectively. Bloodstream infection (OR 1.97, 95% CI 0.88–4.43), septic shock (OR 3.3, 95% CI 1.30–8.40), Acute Physiology and Chronic Health Evaluation (APACHE) II < 14 (OR 0.13, 95% CI 0.03–0.54), Sequential Organ Failure Assessment (SOFA) <7 (OR 0.25, 95% CI 0.11–0.56), and Pitt bacteremia score <4 (OR 0.16, 95% CI 0.05–0.47) were associated with 14-day mortality. There was a higher 14-day and 30-day mortality in patients treated with piperacillin/tazobactam or aminoglycosides but there was no significant difference among antipseudomonal antimicrobial agents in the treatment of Car-R/NonCar-S P. aeruginosa infection. We supported the use of traditional antipseudomonal β-lactam agents to treat Car-R/NonCar-S P. aeruginosa infections, however the use of piperacillin/tazobactam might be concerned in some cases and further investigations were needed.