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Several studies have demonstrated that the ideal therapeutic effect of linezolid cannot be achieved in critically ill patients with the recommended standard dosing regimen of 600 mg every 12 h (q12h). Moreover, the optimal strategy for successful treatment is still lacking. This study analysed factors influencing the efficacy of linezolid treatment and determined the target for successful treatment by logistic regression in 27 critically ill patients with staphylococcal infection who received linezolid 600 mg q12h. The results showed that only the 24-h area under the concentration–time curve to minimum inhibitory concentration (AUC 24 /MIC) ratio was significantly associated with staphylococcal eradication. Reaching 80% bacterial eradication required an AUC 24 /MIC of 120.5, defining the therapeutic target. Different dosing regimens were evaluated using Monte Carlo simulation to determine the optimal dosage strategy for linezolid. Although the probability of target attainment (PTA) was high (>99.9%) for the standard dosing regimen at MIC ≤ 1 mg/L, the PTA was almost 0 at MIC = 2 mg/L, thus the dosing regimen required adjustment. In addition, if the dosing regimen was adjusted to 600 mg every 8 h or 600 mg every 6 h, the major staphylococci (except for MRSA and MSSA) exhibited a cumulative fraction of response of >80%, showing a higher treatment success. These findings indicate that a strategy of high linezolid dosage may be needed to increase the probability of successful treatment at MIC > 1 mg/L. The role of therapeutic drug monitoring should be encouraged for optimising linezolid exposure in critically ill patients. [ABSTRACT FROM AUTHOR]

This study evaluated whether contemporary echinocandin regimens achieved pharmacokinetic/pharmacodynamic targets in ICU patients and general patient populations (GPPs) and assessed caspofungin (CAS) regimens in hepatic impairment (HI) patients. A Monte Carlo simulation was performed using previously published data. Recommended dosing regimens of echinocandins in ICU patients, GPPs and healthy volunteers were evaluated: 70 mg loading dose then 50 mg maintenance dose (70/50 mg) for CAS; 100 mg q24h for micafungin (MCF); and 200/100 mg for anidulafungin (ANF). Moreover, CAS 70 mg and 100 mg q24h in GPPs, and CAS 70/50 mg and 70/35 mg in mild and moderate HI patients, respectively, were evaluated. Cumulative fraction of response (CFR) was calculated for each dosing regimen. For Candida albicans , CFRs for the recommended doses of CAS, MCF and ANF were 95.8%, 13.5% and 50.5% in ICU patients and 96.3%, 42.4% and 61.6% in GPPs, respectively; for Candida glabrata , CFRs were 99.4%, 90.6% and 44.6% in ICU patients and 99.5%, 97.1% and 59.8% in GPPs. For Candida parapsilosis , CFRs of echinocandins for standard regimens were <70%; only CAS 100 mg q24h achieved the target CFR. CAS 70/50 mg and 70/35 mg in mild and moderate HI patients were appropriate. Considerable interindividual variability was observed. For C. albicans and C. glabrata , CAS is good choice both for ICU and other patient populations, but for C. parapsilosis an increased dose should be considered. For MCF and ANF, administering higher doses with longer dosing intervals achieves better target attainment and should be investigated in clinical trials. [ABSTRACT FROM AUTHOR]