Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure: a randomized crossover clinical trial.
BACKGROUND
Patients with non-apposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with "open abdomens" would have bioavailability similar to that of matched patients with closed fascial edges.


METHODS
Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15.


RESULTS
Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51% +/- 30% in the open abdomen and 63% +/- 19% (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30%-100% in both groups. Three patients developed rectal colonization with Candida krusei.


CONCLUSIONS
The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy.
Barquist
Erik S
ES
DeWitt Daughtry Family Department of Surgery, University of Miami School of Medicine, Miami, Florida 33176, USA. ebarquis@med.miami.edu
Gomez-Fein
Eleanor
E
Block
Ernest F J
EF
Collin
Gary
G
Alzamel
Heythem
H
Martinez
Octavio
O
D000007:Abdominal Injuries / Q000382:microbiology / Q000601:surgery*; D034861:Abdominal Wall / Q000601:surgery*; D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D016638:Critical Illness; D018592:Cross-Over Studies; D004750:Enteral Nutrition; D005243:Feces / Q000382:microbiology; D015725:Fluconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007263:Infusions, Parenteral; D007408:Intestinal Absorption; D008875:Middle Aged; D010288:Parenteral Nutrition; D014948:Wounds, Gunshot / Q000382:microbiology / Q000601:surgery
D000935:Antifungal Agents; D015725:Fluconazole