Prevention of invasive fungal infections in liver transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients.
BACKGROUND
Invasive fungal infections (IFI) are associated with high mortality in liver transplant recipients. Prevention remains an elusive goal, especially for IFI caused by moulds.


METHODS
From January 1998, patients who fulfilled four or more variables identified as risk factors for IFI received a cumulative dose of 1-1.5 g of lipid formulations of amphotericin B (L-AmpB; AmBisome or Abelcet). The development of IFI in these patients was compared with historical patients.


RESULTS
Two hundred and eighty liver transplant recipients were analysed over a period of 8 years. In the historical group, IFI were observed in 22 of 131 patients (17%) and invasive aspergillosis in 13 of them (10%). After January 1998, IFI were observed in nine of 149 (6%) (P < 0.01) and invasive aspergillosis in six patients (4%) (P = 0.08). In patients with four or more risk factors (high risk) for IFI, the administration of L-AmpB reduced the risk from 36% to 14% (P = 0.07), and the risk of aspergillosis from 23% to 5% (P = 0.08). Notably, prophylaxis reduced the risk of aspergillosis from 32% to 0% in dialysed patients (P = 0.03). Variables independently associated with IFI in high-risk patients were dialysis [odds ratio (OR) 3.9; 95% confidence interval (CI) 1-16.7] and surgical reintervention (OR 5.4; 95% CI 1.2-24.6), while L-AmpB was a protective factor in this multivariate analysis (OR 0.1; 95% CI 0.02-0.8). The analysis in these high-risk patients was not able to demonstrate an association between the administration of L-AmpB and higher survival.


CONCLUSIONS
Selected risk factors are good predictors of IFI in liver transplant recipients. The administration of L-AmpB in high-risk patients is independently associated with a reduction of IFI.
Fortún
Jesus
J
Infectious Disease Department and Liver Transplant Group, Hospital Ramon y Cajal, Crtra Colmenar Km 9.1, Madrid 28034, Spain. fortun@mi.madritel.es
Martín-Davila
Pilar
P
Moreno
Santiago
S
Barcena
Rafael
R
de Vicente
Emilio
E
Honrubia
Alberto
A
García
Miguel
M
Nuño
Javier
J
Candela
Angel
A
Uriarte
Maria
M
Pintado
Vicente
V
D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D001228:Aspergillosis / Q000401:mortality / Q000517:prevention & control*; D002177:Candidiasis / Q000401:mortality / Q000517:prevention & control*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D010715:Phosphatidylglycerols / Q000008:administration & dosage*; D012307:Risk Factors
D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B