Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological responses, based on data from 61 evaluable HAP patients who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and for whom there were adequate clinical, pharmacokinetic, and response data.
The final multivariable logistic regression model for clinical response contained albumin and the ratio of the free-drug area under the concentration-time curve from 0 to 24 h (fAUC(0-24)) to the MIC (fAUC(0-24):MIC ratio). The odds of clinical success were 13.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.42 times higher for patients with fAUC(0-24):MIC ratios of ≥0.9 compared to patients with fAUC(0-24):MIC ratios of <0.9 (P = 0.008). Average model-estimated probabilities of clinical success for the albumin/fAUC(0-24):MIC ratio combinations of <2.6/<0.9, <2.6/≥0.9, ≥2.6/<0.9, and ≥2.6/≥0.9 were 0.21, 0.57, 0.64, and 0.93, respectively.
For microbiological response, the final model contained albumin and ventilator-associated pneumonia (VAP) status.
The odds of microbiological success were 21.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.59 times higher for patients without VAP compared to those with VAP (P = 0.003). Among the remaining variables evaluated, the MIC had the greatest statistical significance, an observation which was not surprising given the differences in MIC distributions between VAP and non-VAP patients (MIC(50)and MIC(90) values of 0.5 and 0.25 mg/liter versus 16 and 1 mg/liter for VAP versus non-VAP patients, respectively; P = 0.006). These findings demonstrated the impact of pharmacological and patient-specific factors on the clinical and microbiological responses.