Intrapulmonary pharmacokinetics of high doses of tigecycline in patients with ventilator-associated pneumonia.

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%). Cmax, Cmin, plasma AUC0-12, plasma fAUC0-12 and ELF AUC0-12 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 AUC0-12 achieved with a 200 mg daily tigecycline dose, combined with high ELF penetration, support the effectiveness of off-label high-dose tigecycline in VAP.

Toxic Megacolon and Acute Ischemia of the Colon due to Sigmoid Stenosis Related to Diverticulitis.

We present a rare case of toxic megacolon accompanied by necrosis of the colon due to chronic dilation caused by stenosis of the sigmoid colon as a complication of diverticulitis. The patient presented at the emergency department with diffuse abdominal pain, fever (38.8°C) and tachycardia (120 beats/min). Physical examination revealed distension and tenderness on deep palpation on the left lower quadrant without peritoneal signs. Abdominal computed tomography showed located stenosis in the sigmoid colon and marked dilation of the descending (12 cm diameter) and transverse (7.5 cm diameter) colon. A few hours later, the patient developed severe septic shock with electrolyte abnormalities. He had a history of two prior admissions to our hospital due to crises of acute diverticulitis. Based on Jalan's criteria the diagnosis was compatible with toxic megacolon. The patient's condition deteriorated suddenly and an emergency colectomy was performed. The operative findings revealed a necrotic colon. Histology examination confirmed the diagnosis of ischemia of the colon. To our knowledge this is the first published report in the literature which refers to a rare complication of diverticulitis, namely chronic stenosis which complicated to colonic ischemia and toxic megacolon.