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Peritoneal Fluid Penetration of Tigecycline

Infectious Diseases Pharmacist, Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL

Pavani Reddy, MD

Infectious Diseases Fellow, Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University and Northwestern Memorial Hospital

David P Nicolau, PharmD FCCP

Director for the Center for Anti-Infective Research and Development and Coordinator for Research in the Department of Medicine, Division of Infectious Diseases and Pharmacy, Hartford Hospital, Hartford, CT

Gary A Noskin, MD

Associate Professor, Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University and Northwestern Memorial Hospital

Michael J Postelnick, BSPharm BCPS

Clinical Coordinator, Department of Pharmacy, Northwestern Memorial Hospital

Valentina Stosor, MD

Assistant Professor, Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University and Northwestern Memorial Hospital

Teresa R Zembower, MD MPH

Assistant Professor, Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University and Northwestern Memorial Hospital

Reprints: Dr. Scheetz, Department of Pharmacy, Northwestern Memorial Hospital, 251 E. Huron St., Feinberg Pavilion LC 700, Chicago, IL 60611-2908, fax 312/926-7956, mscheetz{at}nmh.org

OBJECTIVE: To describe the peritoneal fluid penetration of tigecycline.

CASE SUMMARY: A 33-year-old critically ill man who had undergone orthotopic liver and cadaveric renal transplant presented with sepsis. The patient required empiric antimicrobial coverage, continuous veno-venous hemofiltration, prolonged mechanical ventilation, tracheostomy placement, and maintenance immunosuppressive therapy. After multiple infections with multidrugresistant pathogens, the patient developed vancomycin-resistant Enterococcus faecium peritonitis. Tigecycline 50 mg was administered every 12 hours, and ascites fluid drug concentrations were obtained. Drug concentrations in the peritoneal fluid were determined by high-performance liquid chromatography and revealed a tigecycline concentration of 0.074 µg/mL. Despite aggressive measures, the patient's condition continued to decline; he died 2 weeks after tigecycline initiation.

DISCUSSION: As of October 3, 2006, these are the first data to describe tigecycline peritoneal fluid penetration. Tigecycline was aggressively administered at twice the recommended dosage for overt liver failure in light of the severity of this patient's condition. A tigecycline peritoneal fluid concentration of 44-54% of serum concentration was calculated based on the patient's peritoneal fluid drug concentration and previously published serum concentrations from a similar population.

CONCLUSIONS: Peritoneal penetration of tigecycline was approximately 50% in this critically ill patient. Establishment of site-specific breakpoints for tigecycline may be necessary. Future studies will need to evaluate the penetration of tigecycline into peritoneal fluid and other tissues.

Key Words: peritoneal penetration, tigecycline

Published Online, October 17, 2006. www.theannals.com, DOI 10.1345/aph.1H229