logo logo
Risk Factors for Tigecycline-Associated Hepatotoxicity in Patients in the Intensive Care Units of 2 Tertiary Hospitals: A Retrospective Study. Journal of clinical pharmacology Tigecycline is a broad-spectrum antibacterial agent. As the incidence of multidrug-resistant bacterial infections has increased in intensive care units (ICUs) over the past decades, tigecycline is often used in ICUs. Information about tigecycline-associated hepatotoxicity in ICU patients is limited. To investigate the potential risk factors for tigecycline-associated hepatotoxicity in ICU patients, 148 patients from 2 centers who had received tigecycline for at least 4 days were retrospectively analyzed. Hepatotoxicity was classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5.0) grading system. As a result, 33.8% of patients experienced hepatotoxicity events in the ICU. The multivariate analysis showed that an albumin concentration <25 g/L at baseline (odds ratio, 3.714; 95%CI, 1.082-12.744; P = .037) and treatment duration (odds ratio, 1.094; 95%CI, 1.032-1.160; P = .003) were significantly correlated with tigecycline-associated hepatotoxicity. The median time to onset of hepatotoxicity was 8.0 days. The median duration ICU stay and the in-hospital mortality rate were not different between the hepatotoxicity group and the nonhepatotoxicity group (33.5 days (interquartile range, 21.0-72.0) vs 31.0 days (interquartile range, 21-62.5), P = .850; 38.0% vs 43.8%; P = .504). Therefore, close monitoring of liver function is recommended for patients with baseline albumin concentrations <25 g/L or for patients who receive tigecycline therapy for >8 days. 10.1002/jcph.2099
Intrapulmonary pharmacokinetics of high doses of tigecycline in patients with ventilator-associated pneumonia. Dimopoulos G,Almyroudi M P,Kapralos I,Apostolopoulou O,Flevari A,Nicolau D P,Dokoumetzidis A International journal of antimicrobial agents Tigecycline is commonly used for infections by multidrug-resistant bacteria. However, it is not approved for ventilator-associated pneumonia (VAP) as increased mortality has been reported in VAP patients treated with conventional doses. The purpose of this study was to prospectively evaluate the intrapulmonary pharmacokinetics of off-label high-dose tigecycline in patients with VAP. Nine mechanically ventilated patients received tigecycline intravenously (loading dose 200 mg followed by 100 mg every 12 h). After ≥5 doses, two bronchoscopies were performed in each patient on consecutive days and eight blood samples were collected. Tigecycline concentrations in plasma and bronchoalveolar lavage fluid were determined by liquid chromatography. The urea dilution method was used to calculate epithelial lining fluid (ELF) concentrations. A two-compartmental pharmacokinetic (PK) model with linear elimination was used to estimate PK parameters. Mean patient age was 69 ± 11.86 years and mean APACHE II score was 21. The estimated population mean PK parameters (relative standard error) were: clearance, 11.64 L/h (54%); volume of distribution in central compartment, 79.01 L (37%); volume of distribution in peripheral compartment, 92.95 L (17%); intercompartmental clearance, 62.81 L/h (34%); and ELF penetration ratio, 2.41 (40%). C, C, plasma AUC, plasma fAUC and ELF AUC were 1.99 ± 1.82 μg/mL, 0.81 ± 1.27 μg/mL, 12.89 ± 17.25 μg•h/mL, 3.24 ± 3.09 μg•h/mL and 7.13 ± 2.61 μg•h/mL, respectively. The increased plasma and ELF AUC achieved with a 200 mg daily tigecycline dose, combined with high ELF penetration, support the effectiveness of off-label high-dose tigecycline in VAP. 10.1016/j.ijantimicag.2021.106487
A pharmacovigilance study of the association between tetracyclines and hepatotoxicity based on Food and Drug Administration adverse event reporting system data. International journal of clinical pharmacy Background While tetracycline antibiotics are commonly prescribed in practice, the risk of drug-induced liver injury (DILI) remains controversial. Aim To evaluate the association of DILI with tetracycline antibiotics. Method All DILI cases of tetracycline antibiotics as primary suspected drugs were extracted from the US Food and Drug Administration adverse event reporting system (FAERS). The outcomes included severe DILI, hepatocellular injury, cholestatic injury, and liver failure. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results A total of 1,435 liver injury cases associated with tetracycline antibiotics were identified. The DILI signal was detected in tigecycline, minocycline, and doxycycline. The RORs and the 95% confidence intervals (95% CI) of tigecycline, minocycline, and doxycycline were (ROR 5.85, 95% CI 4.96-6.91), (ROR 6.4, 95% CI 5.76-7.11), and (ROR 2.07, 95% CI 1.86-2.31), respectively. Compared to minocycline (ROR 5.5, 95% CI 4.94-6.12; IC 2.35, 95% CI 1.98-2.68) and doxycycline (ROR 1.91, 95% CI 1.71-2.12; IC 0.91, 95% CI 0.55-1.26), tigecycline showed a stronger association with hepatocellular injury (ROR 7.11, 95% CI 6.13-8.23; IC 2.68, 95% CI 2.16-3.13). Tigecycline also showed a stronger association with cholestatic injury (ROR 12.16, 95% CI 10.13-14.61; IC 3.51, 95% CI 2.79-4) than minocycline (ROR 3.23, 95% CI 2.59-4.04; IC 1.67, 95% CI 0.9-2.37) or doxycycline (ROR 2.86, 95% CI 2.47-3.31; IC 1.5, 95% CI 1-1.97). Tigecycline (ROR 6.56, 95% CI 4.57-9.41; IC 2.69, 95% CI 1.28-3.64) and minocycline (ROR 4.22, 95% CI 3.14-5.66; IC 2.06, 95% CI 1-2.93) showed a significant association with liver failure. Conclusion The data mining of FAERS suggested an association between DILI and tigecycline, minocycline, and doxycycline. 10.1007/s11096-022-01397-5
Acute liver failure caused by high-dose tigecycline: A case report. International journal of clinical pharmacology and therapeutics High-dose tigecycline is gradually being introduced for the treatment of serious infectious diseases due to the increasing difficulty in treating pan-resistant bacterial infections. However, the safety of high-dose tigecycline is controversial. We report the case of a 76-year-old female patient with cerebral hemorrhage who received high-dose tigecycline (100 mg q12h) with other drugs for ventilator-associated pneumonia. 25 days after admission, she developed acute liver failure, mainly manifested by abnormally high bilirubin, coagulation dysfunction, and gastrointestinal hemorrhage with hemorrhagic shock. According to the updated Roussel Uclaf causality assessment method, the patient's acute liver injury was most likely caused by tigecycline. 10.5414/CP204549