title: A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality, acute cellular rejection, infections, and changes in the liver function tests while on caspofungin.
abstract: This study is a retrospective analysis of death, adverse events (AE), fungal infections, and hepatic function among recipients of liver transplantation at high risk of fungal infection who received prophylactic treatment with caspofungin. After reviewing data of 105 patients who had received isolated liver transplant between January 2003 and April 2007, we identified and analyzed 82 high-risk patients. Post-transplant patients at high risk for fungal infection are commonly defined by the presence of at least one of the following: (i) re-transplantation; (ii) re-operation; (iii) renal dysfunction. However, in our practice, patients are also considered at high risk for developing fungal infections if they present with the following: (iv) fever of unknown origin; (v) hypothermia; (vi) positive random culture for fungus at the time of transplant (bile and/or ascites); (vii) sepsis; (viii) use of vasopressors; (ix) re-intubation, during the first hospitalization after liver transplant; (x) prolonged intubation (>24 h), and (xi) acute respiratory distress syndrome, until negative fungal cultures are obtained. Exact conditional logistic regression was used to compare the risk of death, AEs, and fungal infections between patients who received caspofungin, other antifungal drugs, and no antifungal drugs. Analyses were then performed with SAS 9.1 (SAS Institute Inc., Cary, NC, USA). Patients were between 27 and 72 yr old (mean = 55), with two-thirds male and three-quarters Caucasian. Sixteen patients received caspofungin (11 preventively), and 32 received other antifungal (26 preventively). There were no proven fungal infections among the patients who received caspofungin, three infections among patients who received other antifungal (3/26 = 12%), and 14 infections among patients who were not preventively treated (14/45 = 31%). These infection rates were significantly different across the three groups (p = 0.029), with caspofungin and other antifungal preventive treatment comparable (p = 0.540), and both better than no preventive treatment at all (OR = 0.15, p = 0.049, for caspofungin versus no preventive treatment; OR = 0.29, p = 0.085, for other antifungal versus no preventive treatment). Caspofungin appears to be an effective preventive agent against fungal infections when used in recipients of liver transplant designated as high risk for fungal infection. Usage of caspofungin in these patients does not carry an apparent increase in risk of death or acute cellular rejection, although we observed a significantly higher risk of AEs, especially acute renal failure (p = 0.001), in patients who received this agent.
authors.affiliation: Division of Transplantation, Department of Surgery, Jefferson Medical College-Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. cataldo.doria@jefferson.edu
authors.forename: Cataldo
authors.initials: C
authors.lastname: Doria
authors.forename: Adam S
authors.initials: AS
authors.lastname: Bodzin
authors.forename: Silvia
authors.initials: S
authors.lastname: Vaccino
authors.forename: Constantine
authors.initials: C
authors.lastname: Daskalakis
authors.forename: Steven
authors.initials: S
authors.lastname: Krawitz
authors.forename: Carlo B
authors.initials: CB
authors.lastname: Ramirez
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D000077336:Caspofungin; D054714:Echinocandins / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D006801:Humans; D055666:Lipopeptides; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin