The purpose was to explore the optimal dosage regimen of colistin using Monte Carlo simulations, for the treatment of carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli based on PK/PD targets in critically ill patients. A total of 116 carbapenem-resistant K. pneumoniae and E. coli were obtained from various clinical specimens at Siriraj Hospital in Bangkok, Thailand. Minimum inhibitory concentrations (MICs) of colistin were determined by broth microdilution method. Monte Carlo simulation was used to calculate the cumulative fraction of response (CFR) for European Medicine Agency (EMA), US-Food and Drug Administration (FDA), Nation et al., Siriraj Hospital and our study regimens. The targeted CFR was 90%. For colistin-susceptible K. pneumoniae, all of the dosage regimens achieved ≥90% CFR in patients with creatinine clearance <80 mL/min except the FDA-approved regimens for patients with creatinine clearance 51–79 and 11–29 mL/min, respectively. While, patients with creatinine clearance ≥80 mL/min, CFR ≥90% was observed in Siriraj Hospital and our study regimen. For colistin-susceptible E. coli, all of the dosage regimens achieved ≥90% CFR regardless of renal function. In contrast, the currently approved regimens achieved CFR target in only 10-50% for colistin-resistant isolates subgroup. These results suggest that currently approved regimens still recommended for colistin-susceptible CRE. For colistin-resistant CRE, alternative approaches such as high dose or combination therapy should be considered.
This study aimed to describe factors and outcomes associated with Candida colonization of critically ill patients. This was a cross-sectional study conducted over 2 weeks in the intensive care unit (ICU) of a tertiary care hospital at the Texas Medical Center, Houston, TX. All Candida samples were prospectively collected with demographic and clinical data collected retrospectively. We examined 48 patients, 32 (67%) were colonized with Candida spp; 25 (52.1%) patients were isolated with Candida albicans and 18 (37.5%) were isolated with a non-albicans species, mostly commonly Candida glabrata. A multivariate analysis identified proton pump inhibitor administration at admission to ICU [odds ratio 5.66; 95% confidence interval 1.12-28.5] as associated with colonization. Patients colonized with Candida had a significantly longer length of ICU and hospital stays (7.6 ± 6.6 vs. 4.2 ± 2.6 days, P = 0.01 and 14.9 ± 12.9 vs. 7.5 ± 6.7 days, P = 0.02, respectively). Clonality testing between C. albicans and C. glabrata strains identified indistinguishable strains among the patient cohort. These data provide additional information on Candida colonization in critically ill patients.
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