Peritoneal fluid penetration of tigecycline.
OBJECTIVE
To describe the peritoneal fluid penetration of tigecycline.


METHODS
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 multi-drug resistant 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 microg/mL. Despite aggressive measures, the patient's condition continued to decline; he died 2 weeks after tigecycline initiation.


CONCLUSIONS
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.
Scheetz
Marc H
MH
Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL 60611-2908, USA. mscheetz@nmh.org
Reddy
Pavani
P
Nicolau
David P
DP
Noskin
Gary A
GA
Postelnick
Michael J
MJ
Stosor
Valentina
V
Zembower
Teresa R
TR
D000328:Adult; D001202:Ascitic Fluid / Q000187:drug effects* / Q000378:metabolism*; D016638:Critical Illness / Q000628:therapy; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000502:physiology; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D008911:Minocycline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010539:Permeability / Q000187:drug effects; D000078304:Tigecycline
D000078304:Tigecycline; D008911:Minocycline