Carbapenem-resistant Enterobacteriaceae (CRE), especially carbapenem-resistant Klebsiella pneumoniae (CRKP), are among the largest pathogenic threats to humans. The available antibiotic treatment options for combating CRKP are limited. Colistin-resistant Enterobacteriaceae (CoRE) have also been reported worldwide, including in Thailand. Therefore, this study aimed (1) to determine minimum inhibitory concentrations (MICs) and synergistic activities of antibiotics of CRKP, and (2) to determine the probability target of attainment (PTA) and cumulative fraction of response (CFR) using pharmacokinetic/pharmacodynamic (PK/PD) data. Clinical CRKP isolates were obtained from Phramongkutklao Hospital (June to November 2020). Broth microdilution and checkerboard techniques were used to determine the mono- and synergistic activities of antibiotics. Carbapenemase and mcr-1 genes were also identified by polymerase chain reaction (PCR). The optimal antibiotic regimens were evaluated using Monte Carlo simulations. Forty-nine CRKP isolates were collected, 40 of which were CoRKP strains. The MIC50 and MIC90 of tigecycline, amikacin, and gentamicin were 1 and 2 µg/mL, 4 and 16 µg/mL, and 0.25 and 4 µg/mL, respectively. None of any isolates expressed the mcr-1 gene, whereas bla_OXA-48 (53.1%) and bla_OXA-48 plus bla_NDM (42.9%) were detected. Synergistic activity was observed in 8.2% of isolates for tigecycline combined with amikacin or gentamicin. Additive activity was observed in 75.5% of isolates for tigecycline-amikacin and 69.4% for tigecycline-gentamicin, and no antagonism was observed. High-dose antibiotic regimens achieved the PTA target. The general recommended dose of combination regimens began with 200 mg tigecycline and 25 mg/kg amikacin, or 7 mg/kg gentamicin, followed by 100 mg tigecycline every 12 h and 15 mg/kg amikacin or 5 mg/kg gentamicin every 24 h. In conclusion, tigecycline plus aminoglycosides might be a potential regimen against CRKP and CoRKP. The appropriate combination regimen based on MIC-based dose adjustment can improve optimal antibiotic dosing. Further research via clinical studies will be necessary to confirm these results.

The spread of carbapenem-resistant Enterobacterales (CRE) constitutes a global health burden. Antimicrobial susceptibility and types of carbapenemase differ by geographic region. This study aimed to (1) examine the minimum inhibitory concentrations (MICs) and antibiotic resistance genes and (2) investigate antibiotic dosing regimens against CRE using Monte Carlo simulation. Clinical carbapenem-resistant Klebsiella pneumoniae (CRKP), Escherichia coli (CREC), and Enterobacter cloacae (CREclo) isolates were collected from various hospitals in western Thailand. Broth microdilution was performed, and the types of carbapenemase and mcr-1 genes were detected using polymerase chain reaction (PCR). Monte Carlo simulation was used to establish optimal antimicrobial dosing regimens meeting the criterion of a cumulative fraction of response (CFR) >90%. A total of 150 CRE isolates from 12 hospitals were included. The proportion of CRKP (76%) was greater than that of CREC (22%) and CREclo (2%). Regional hospitals reported higher rates of resistance than general hospitals. Most isolates were resistant to aztreonam and ceftazidime/avibactam, whereas they were highly susceptible to aminoglycosides. Most carbapenemases were NDM (47.33%), OXA-48 (43.33%) and NDM plus OXA-48 (6.67%); five OXA-48 positive isolates carried mcr-1 genes. Currently, high-dose tigecycline is the only optimal regimen against CRE isolates. Further extensive research on antibiotic synergism or new antibiotics should be conducted.

Apixaban can significantly prevent stroke events in patients with non-valvular atrial fibrillation (NVAF), as can be observed from the large, randomized, controlled trial conducted in the present study. However, the real-world evidence of bleeding events related to the apixaban plasma levels in Asian populations is limited. This study aimed to investigate the apixaban plasma levels and clinical outcomes among NVAF patients receiving apixaban, including determining the risk factors associated with bleeding during routine care. Seventy-one patients were included in the study. The median values were 112.79 (5–95th percentiles: 68.69–207.8) μg/L and 185.62 (5–95th percentiles: 124.06–384.34) μg/L for the apixaban trough (C_trough) and apixaban peak plasma levels (C_peak), respectively. Stroke and bleeding were found in 8 (11.27%) and 14 patients (19.72%), respectively. There was no statistical significance for C_trough and C_peak in the stroke and non-stroke groups, respectively. The median of C_trough (139.15 μg/L) in patients with bleeding was higher than that in the non-bleeding group (108.14 μg/L), but there was no statistical significance. However, multivariate analyses showed that bleeding history (odds ratio (OR): 17.62; 95% confidence interval (CI): 3.54–176.64; and p-value = 0.002) and C_trough (OR: 1.01; 95%: CI 1.00–1.03; and p-value = 0.038) were related to bleeding events. Almost all of the patients presented apixaban plasma levels within the expected range. Interestingly, bleeding events were associated with the troughs of the apixaban plasma levels and bleeding history.

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Background: To our knowledge, no study reported so far has investigated appropriate vancomycin dosing, which is important for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection in Thai patients of various ages and with varying degrees of renal function. Objectives: To predict vancomycin dosing for MRSA in Thai patients of various ages and with varying degrees of renal functions. Methods: Monte Carlo simulation and minimal inhibitory concentration (MIC) distribution of MRSA from a hospital in Thailand were used to predict the area under the curve in 24 h/MIC >400 and trough concentration ( C _trough ) <20 mg/L of 9 vancomycin dosage regimens for Thai patients stratified by age and renal function. Results: Vancomycin dosing at least 2.5 g per day can attain cumulative fraction of response (CFR) of ≥90% in every age group. Vancomycin dosage achieving CFR of ≥90% for simulated patients with creatinine clearance (CL _cr ) was calculated using the Cockcroft–Gault equation. Appropriate vancomycin doses for Thai patients infected with MRSA with CL _cr of 60–80, and >80 mL/min were 1.5 g every 24 h, 1.25 g every 12 h, 1 g every 8 h, and 1.75 g every 12 h, respectively. However, more than a half of patients simulated using these regimens have a vancomycin C _trough of >20 mg/L. Conclusions: Although vancomycin doses attaining a CFR of ≥90% can treat MRSA infection effectively, the regimens may cause kidney injury. The regimens have a probability of target attainment of 100%, and most patients can attain C _trough of <20 mg/L.

Background.: Tacrolimus (TAC) trough-level variability has been associated with patient outcomes and renal graft survival. However, its relationship with posttransplant diabetes mellitus (PTDM) remains unclear. This study aims to evaluate the association between the coefficient of variation (CV) of TAC (TAC-CV) and the incidence of PTDM within the first year after kidney transplantation (KT). Methods.: A multicenter retrospective study was conducted on 516 Thai KT patients who received TAC-based immunosuppressive regimens from 2011 to 2020, with a 1-y post-KT follow-up period. TAC-CV was calculated for the 0–12 mo post-KT period, and optimal cutoff values were determined using receiver operating characteristic analysis. Results.: Of the 516 patients, 208 (40.31%) developed PTDM, whereas 308 (59.69%) did not during the first year post-KT. Significant associations were found between TAC-CV and PTDM throughout the study period ( P < 0.001). The optimal CV cutoff values were identified as 36% (at 0–3 and 0–6 mo), 23% (at 6–12 mo), and 33% (at 0–12 mo) post-KT. High TAC-CV was strongly associated with an increased risk of PTDM during the first year post-KT. Conclusions.: These findings suggest that TAC-CV may serve as a valuable marker for identifying patients at high risk of PTDM and may aid in its prevention and effective management in KT recipients.