There are limited intravenous fosfomycin disodium (IVFOS) dosing regimens to treat carbapenem-resistant Enterobacterales (CRE) infections. This study aimed to use Monte Carlo simulation (MCS) for evaluation of IVFOS dosing regimens in critically ill patients with CRE infections. The dosing regimens in critically ill patients with various creatinine clearance were evaluated with MCS using minimum inhibitory concentration (MIC) distributions of fosfomycin against CRE clinical isolates in Thailand and the 24 h area under the plasma drug concentration–time curve over the minimum inhibitory concentration (AUC0-24/MIC) of ≥21.5 to be a target for IVFOS. The achieved goal of the probability of target attainment (PTA) and a cumulative fraction of response (CFR) were ≥90%. A total of 129 non-duplicated CRE clinical isolates had MIC distributions from 0.38 to >1024 mg/L. IVFOS 8 g every 8 h, 1 h, or 4 h infusion, could achieve approximately 90% PTA of AUC0-24/MIC target to treat CRE infections with MICs ≤ 128 mg/L. According to PTA target, an IVFOS daily dose to treat carbapenem-resistant Escherichia coli based on Clinical Laboratory Standards Institute (CLSI) breakpoints for urinary tract infections and one to treatment for CRE infections based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were 16 g/day and 8 g/day, respectively. All dosing regimens of IVFOS against CRE achieved CFR ≤ 70%. This study proposes the IVFOS dosing regimens based on CLSI and EUCAST breakpoints for the treatment of CRE infections. However, further clinical studies are needed to confirm the results of these findings.

Drug-resistant Acinetobacter baumannii (A. baumannii) infections are a critical global problem, with limited treatment choices. This study aims to determine the in vitro activities of colistin–sitafloxacin combinations against multidrug-, carbapenem- and colistin-resistant A. baumannii (MDR-AB, CRAB, CoR-AB, respectively) clinical isolates from tertiary care hospitals. We used the broth microdilution checkerboard and time-kill methods in this study. Synergy was found using both methods. The colistin–sitafloxacin combination showed synergy in MDR-AB, CRAB, and CoR-AB isolates (3.4%, 3.1%, and 20.9%, respectively). No antagonism was found in any type of drug-resistant isolate. The majority of CoR-AB isolates became susceptible to colistin (95.4%). The time-kill method also showed that this combination could suppress regrowth back to the initial inocula of all representative isolates. Our results demonstrated that the colistin–sitafloxacin combination might be an interesting option for the treatment of drug-resistant A. baumannii. However, further in vivo and clinical studies are required.

Stenotrophomonas maltophilia is a multidrug-resistant bacterium that is difficult to treat in hospitals worldwide, leading to high mortality. Published data describing the use of monotherapy or combination therapy and which one is better is still unclear. We aimed to investigate the efficacy of monotherapy and combination therapy in the treatment of S. maltophilia infections. We performed a systematic review of combination therapy and additionally a systematic review and meta-analysis to determine the effects of monotherapy versus combination therapy on mortality in S. maltophilia infections. Electronic databases: Cochrane Library, PubMed, Embase, ClinicalTrials.gov, Scopus, and OpenGrey were accessed. Of the 5030 articles identified, 17 studies were included for a systematic review of combination therapy, of which 4 cohort studies were finally included for meta-analysis. We found there is a trend of favorable outcomes with respect to mortality in the use of combination therapy to treat complex or severe S. maltopholia infections. A meta-analysis of monotherapy showed a statistical significance in the decreasing rate of mortality in hospital-acquired pneumonia (hazard ratio 1.42; 95% confidence interval, 1.04–1.94) compared to combination therapy, but not significant in bacteremia (hazard ratio 0.76; 95% confidence interval, 0.18–3.18). Further studies should continue to explore this association.

Sitafloxacin showed potent activity against various respiratory pathogens. Blood and bronchoalveolar lavage (BAL) fluid samples were obtained from 12 subjects after a single oral dose of sitafloxacin 200 mg. The mean ± SD (median) maximum ratio of epithelial lining fluid (ELF) to unbound plasma concentration was 1.02 ± 0.58 (1.33). The penetration ratios based on the mean and median area under the curve from 0 to 8 h (AUC0–8) were 0.85 and 0.79 μg · h/ml, respectively. Sitafloxacin penetrates well into ELF in critically ill Thai patients with pneumonia. (This study has been registered in the Thai Clinical Trials Registry [TCTR] under registration no. TCTR20170222001.)

The emergent issue of carbapenem-resistant Acinetobacter baumannii (A. baumannii) and Pseudomonas aeruginosa (P. aeruginosa) is a major problem in Thailand. The wide use of carbapenems can increase selective pressure of bacterial resistance. The objective of this study was to determine the relationship between carbapenem consumption and the susceptibility rates of A. baumannii and P. aeruginosa, including multi-drug resistance (MDR) strains. This was a retrospective study. Carbapenem consumption and susceptibility profiles were collected from 2007 to 2013 at the Her Royal Highness Princess Maha Chakri Sirindhorn Medical Center, Thailand. We found that the susceptibility rate of A. baumannii to imipenem and meropenem from the sputum and the bronchoalveolar lavage (BAL) specimens was significantly decreased during the study period, but no significant change was found in the P. aeruginosa data. The relationship between carbapenem consumption and the susceptibility rate of A. baumannii had a clear association with the use of ertapenem. We found a statistically significant negative correlation between ertapenem consumption and the susceptibility rate of A. baumannii to imipenem (r = −0.91; p = 0.004) and meropenem (r = −0.97; p = 0.000) in the data from the non-ICU wards. In addition, imipenem use had a moderate negative correlation with the MDR P. aeruginosa data but no statistical significance (r = −0.714; p > 0.05). In conclusion, our study suggested there is an association between carbapenem use and the susceptibility of A. baumannii and P. aeruginosa. Notwithstanding this, information on ecological factors should be considered for further study. These findings showed the need to optimize the carbapenem prescription policy. Avoiding carbapenem overuse and rethinking the appropriate initial therapy might decrease the rate of resistant organisms.