Evaluation of the ratio of the estimated area under the concentration-time curve to minimum inhibitory concentration (estimated AUIC) as a predictor of the outcome for tigecycline treatment for pneumonia due to multidrug-resistant bacteria in an intensive care unit

Abstract

Objectives: Based on pharmacokinetics/pharmacodynamics (PK/PD) and the minimum inhibitory concentration (MIC) of tigecycline (TGC), dose increases have been advocated to maximize the efficacy against pneumonia that is suspected to be due to multidrug-resistant (MDR) bacteria in an intensive care unit. This practice-based study explored the relationship between the predicted PK parameter, the ratio of the area under the concentration-time curve to the 24 h of dosing/minimum inhibitory concentration (AUC0–24/MIC or AUIC), and the clinical and microbiological outcomes in critically ill patients with pneumonia due to MDR bacteria. Methods: We conducted a prospective cohort study of the treatment of pneumonia due to MDR bacteria in an intensive care unit. The study patients were recruited and assigned to either TGC standard dose (SD, 50 mg q12 h) or high dose (HD, 100 mg q12 h) for the treatment of pneumonia due to MDR bacteria depending on the doctors’ decisions. The relationships between the PK/PD parameters and outcomes were examined. Results: Over the study period, 105 patients were included in the study. Whereas C1/2, Cmin, MIC and AUC were dramatically higher in the HD group than in the SD group (all P 0.05). The patients in the HD group had a higher clinical cure rate than those in the SD group (P = 0.029), but the bacterial eradication rate and survival rate of the patients in the HD group were not better than those in SD group (P = 0.279 and 0.416, respectively). The Cmax, C1/2, Cmin and AUC in the cured group were higher than those in failure group (all P < 0.05). The MICs were dramatically higher in the failure group than those in cure group (P = 0.0001), which led to significantly lower AUICs (P = 0.0001). In the ROC analysis, the areas of Cmax, C1/2, Cmin, AUC, negative-MIC and AUIC under the ROC curve were 0.64, 0.69, 0.67, 0.66, 0.73 and 0.82, respectively. The sensitivity was ascertained to be 75% and the specificity was 89% when the AUIC cut-off value was considered to be 10.12. Moreover, the sensitivity was ascertained to be 63% and the specificity was 80% when the MIC cut-off value was considered to be 1.75 mg/L. Conclusions: The AUIC and MIC are associated with tigecycline treatment outcomes in pneumonia due to MDR bacteria, and aiming to achieve an individualized AUIC ≥ 10.12 when MIC < 1.75 mg/L could improve outcomes. Keywords: Tigecycline, Area under the concentration-time curve, Minimum inhibitory concentration, Multidrug-resistant bacteria, High dose