Abstract
Background In critically ill patients, the use of high tigecycline dosages (HD TGC) (200 mg/day) has been recently increasing but few pharmacokinetic/pharmacodynamic (PK/PD) data are available. We investigated plasmatic and pulmonary concentrations of HD TGC in the treatment of severe infections. Methods This was a single centre, prospective, observational study that was conducted in the twenty-bed mixed ICU of a 1,500- bed teaching hospital in Rome, Italy. In all patients admitted to the ICU between 2015 and 2018, who received TGC (200 mg loading dose, then 100 mg q12) for the treatment of documented infections, serial blood samples were collected to measure TGC concentrations. Moreover, epithelial lining fluid (ELF) concentrations were determined in patients with nosocomial pneumonia. Results Among the 32 non-obese patients included, 11 had a treatment failure, while the other 21 subjects successfully eradicated the infection. There were no between-group differences in terms of demographic aspects and main comorbidities. In nosocomial pneumonia, for a target AUC0-24/MIC of 4.5, 75% of the patients would be successfully treated in presence of 0.5 mg/L MIC value and all the patients obtained the PK target with MIC≤0.12 mg/mL. In intra-abdominal infections, for a target AUC0-24/MIC of 6.96, at least 50% of the patients would be adequately treated against bacteria with MIC≤0.5 mcg/mL. Finally, in skin and soft-tissue infections, for a target AUC0-24/MIC of 17.,9 only 25% of the patients obtained the PK target at MIC values of 0.5 mg/L and less than 10% were adequately treated against germs with MIC value ≥1 mcg/ml. HD TGC showed a relevant pulmonary penetration with a median and IQR ELF/plasma ratio (%) of 152.9 [73.5-386.8]. Conclusions The use of HD TGC is associated with satisfactory plasmatic and pulmonary concentrations for the treatment of severe infections due to fully susceptible bacteria (MIC<0.5 mg/L). Even higher dosages and combination strategies are required in presence of difficult to treat pathogens.
Toe-to-room temperature gradient correlates with tissue perfusion and predicts outcome in selected critically ill patients with severe infections
