TABLE 1a. Risk Factors for IFI for all fungal pathogens

Transcription

1 LIVER TRANSPLANTATION 16: , 2010 ERRATUM In Liver Transplantation volume 15, number 8 (August 2009), pp , Eschenauer, Lam, and Carver, the tables should be revised as the following: DOI /lt Published online in Wiley InterScience ( TABLE 1a. Risk Factors for IFI for all fungal pathogens Risk Factor N Odds / Hazard ratio (95% CI) Reference Pre-Operative Risk Factors UNOS status 4 (life support in ICU) ( ) George 1997 ( 14 ) Donor CMV þ/recipient ( ) George 1997 ( 14 ) UNOS class I (life support in ICU) ( ) Winston 1999 ( 23 ) Fungal colonization at baseline ( ) Winston 1999 ( 23 ) Pretransplant SCr 3 mg/dl ( ) Collins 1994 ( 11 ) and Per mg/dl increase in pretransplantation ( ) Wade 1995 ( 22 ) bilirubin Pretransplantation HHV-6 seronegativity 247 Not provided Dockrell 1999 ( 12 ) Age 186 Not provided Singh 2001 ( 65 ) Operative Risk Factors Retransplantation ( ) Fortun 2003 ( 13 ) ( ) Winston 1999 ( 23 ) ( ) Collins 1994 ( 11 ) and ( ) 307 Not provided Castaldo 1991 ( 10 ) Choledochojejunostomy ( ) and Hadley 1995 ( 15 ) ( ) Surgical reintervention ( ) Fortun 2003 ( 13 ) Return for Surgery ( ) Wade 1995 ( 22 ) Re-operations (abdominal or intrathoracic) ( ) Collins 1994 ( 11 ) and >40 units blood/platelets transfused in OR ( ) Per unit of blood/platelets transfused in OR ( ) and Hadley 1995( 15 ) Operation time 11h ( ) Collins 1994 ( 11 ) and Post Operative Risk Factors Dialysis post-lt ( ) Rogers 2000 ( 20 ) HD or hemofiltration post-lt 152 Not provided Briegel 1995 ( 9 ) Renal replacement therapy 186 Not provided Singh 2001 ( 65 ) Units of fresh frozen plasma given post-lt 152 Not provided Briegel 1995 ( 9 ) Fungal colonization (within 3 days after LT) ( ) Bacteremia ( ) George 1997 ( 14 ) HHV-6 infection ( ) Rogers 2000 ( 20 ) ICU stay >3 days ( ) Per day of therapy with ciprofloxacin ( ) Wade 1995 ( 22 ) Platelet volume (per unit) ( ) George 1997 ( 14 ) Reintubation 307 Not provided Castaldo 1991 ( 10 ) Any Timepoint CMV infection ( ) Collins 1994 ( 11 ) and ( ) and Hadley 1995( 15 ) Only trials which included an adequate control group, and only risk factors which were found to be significantly associated with IFI on multivariate analysis, are presented. VC 2010 American Association for the Study of Liver Diseases.

2 798 ERRATUM TABLE 1b. Risk Factors for Specific Fungal Pathogens Risk Factor Organism N Odds ratio (95% CI) Reference Pre-Operative Risk Factors Hepatitis C virus infection Aspergillus, late onset (2.1-17) Gavalda 2005 ( 84 ) SBP prophylaxis with FQ Candida ( ) Husain 2003 ( 16 ) Operative Risk Factors Retransplantation Candida ( ) Husain 2003 ( 16 ) Retransplantation Candida 50 Not provided Tollemar 1990 ( 21 ) >18 units cryoprecipitate Candida ( ) Patel 1996 ( 19 ) transfused in OR Long transplantation time Candida 50 Not provided Tollemar 1990 ( 21 ) Class II HLA partial or complete match Candida ( ) Patel 1996 ( 19 ) Donor from male Candida 50 Not provided Tollemar 1990 ( 21 ) Retransplantation Aspergillus ( ) Fortun 2002( 24 ) Post-Operative Risk Factors Posttransplant HD Candida ( ) Husain 2003 ( 16 ) High number of erythrocyte units Candida 50 Not provided Tollemar 1990 ( 21 ) transfused post-transplant Posttransplant bacterial infection Candida ( ) Patel 1996 ( 19 ) CMV disease Aspergillus, late onset ( ) Fortun 2002( 24 ) Use of OKT3 Aspergillus ( ) Kusne 1992 ( 18 ) >6 gram cumulative dose of Aspergillus ( ) Gavalda 2005 ( 84 ) steroids at month 3 Aspergillus antigenemia post-lt Aspergillus ( ) Fortun 2002( 24 ) Renal failure Aspergillus 80 Not provided Gavalda 2005 ( 84 ) Hemodialysis Aspergillus 80 Not provided Gavalda 2005 ( 84 ) Dialysis Aspergillus ( ) Fortun 2003 ( 13 ) Need for dialysis post-lt Aspergillus ( ) Fortun 2002 ( 24 ) CMV ¼ cytomegalovirus; FQ ¼ fluoroquinolone; h ¼ hours; HD ¼ Hemodialysis; HHV-6 ¼ human herpesvirus 6; HLA ¼ human leukocyte antigen; ICU ¼ intensive care unit; IFI ¼ invasive fungal infection; LT ¼ liver transplant; OR ¼ operation room; UNOS ¼ United Network Organ Sharing; SBP ¼ spontaneous bacterial peritonitis; SCr ¼ serum creatinine. LIVER TRANSPLANTATION.DOI /lt. Published on behalf of the American Association for the Study of Liver Diseases

3 TABLE 2. Clinical trials evaluating prophylactic antifungal therapy in liver transplant recipients. Only published trials with systemically available agents included Kung 1995 ( 69 ) Retrospective Tollemar 1995 ( 66 ) Lumbreras 1996 ( 70 ) Winston 1999 ( 23 ) Randomized, prospective randomized, multicenter randomized FLU 100mg Q24H no prophylaxis in historical cohort Prophylaxis initiated at time of admission to liver unit 2/1990-4/1992 AmB 1mg/kg IV Q24H placebo Started during LT and given for 5 days Not noted. FLU 100mg PO Q24H NYS 10 6 units PO Q6H Both received treatment days 3-28 post-lt 5/1992-9/1993 FLU 400mg Q24H (IV initially, PO when able to tolerate oral medications) PLA Prophylaxis started just prior to LT, and continued for 10 weeks after LT. 45 (time period 7/1992-2/1995) 72 (1984-6/1992) Prophylaxis initiated in all patients with fulminant hepatic failure LT recipients > 8 years old who had first LT in prior 24 hours were randomized. Excluded: azole allergy, SCr3 mg/dl, AF within 1 week of study, preexisting FI 13 years old no clinical evidence of fungal infection no systemic AF in the 2 weeks prior to randomization, not allergic to study drug. None Proven FI: autopsy findings or positive cultures from normally sterile body sites or deep organ biopsy in clinically ill patients. IA: Chest radiograph showed pneumonia and bronchoscopy samples showed evidence of Aspergillus presence of organ-specific symptoms and isolation of Candida from blood, tissues, or bloody fluid Colonization: isolation of fungus from stool, throat, urine in absence of clinical findings Thrush: oral lesions, odynophagia, and positive culture for Candida in absence of other pathogens Candida cystitis: dysuria, pyuria, and isolation of Candida in pure growth at least twice (once after catheter replacement) Esophageal candidiasis: compatible endoscopic appearance and isolation of Candida from biopsy specimens Colonization: the presence of a fungus in 1 surveillance cultures of the oropharynx, axillae, inguinal skin folds, urine, and stool or perirectal area in the absence of any clinical symptoms or signs of infection. Colonization was assessed at study entry, weekly during the study period, and at the termination of prophylaxis. Superficial FI: isolation Not provided N/A Mortality attributable to IC: 0 6 (8%) Mortality attributable to IMI: 3 (7%) 2 (3%) Total Proven FI (over 1 st year posttransplant): 4 (10%) 11 (30%) p<0.05 At 30 days: 0 6 (16%) p< days- 1 year: 4 (10%) 5 (14%) no p-value reported. Candida colonization occurring during study period: 25% 53% P¼0.04 Total Candida infection: 9 (12%) 18 (27%) P¼0.022 IC: 1 (1%) 4 (6%) P¼0.12 All FI: 10/108 (9%) 45/104 (43%) 6/108 (6%) 24/104 (23%) Fungal colonization* at week 8: 23/83 (28%) 52/58 (90%) * not all patients were cultured Total mortality in first year: 8 (20%) 8 (22%) Attributable mortality in first year 1 (2.5%) 3 (8%) p> (13%) 9 (13%) Death attributable to Candida: (11%) 15 (14%) Death attributable to FI: 2/108 (2%) 13/104 (13%) P¼0.003 Median operative transfusions: 5 units 10 units p¼ Candida (1), Aspergillus (3) Candida (9), Aspergillus (2) Safety: mean serum alkaline phosphatase level at 30 days post- LT 3.3 X ULN 1.5 X ULN P<0.01 No significant differences between adverse events related to AF Adverse events or laboratory abnormalities possibly or probably related to the study drug: 43/108 (40%) 28/104 (27%) P¼0.05 Neurologic events more common in fluconazole group, including

4 Singhal 2000 ( 63 ) Singh 2001 ( 65 ) Retrospective Prospective 11/ /1997 ABLC 5mg/kg IV Q24H ABLC 2.5mg/kg IV Q24H Group C: 1mg/kg IV Q24H Prophylaxis initiated Day 5 post-transplant and continued until ICU discharge or death Lipid formulation of AmB 5mg/kg IV Q24H no prophylaxis Prophylaxis continued until death, discharge, or discontinuation of RRT Group C: (time period 4/ /2000) 22 (time period /1997 Biancofiore 2002 ( 2 ) Randomized, prospective 1/1999-8/2000 AmB 1 mg/kg IV Q24H X 7 days, then ITR 200mg PO Q24H X 3 weeks. Group B FLU 400 mg IV Q24H X 7 days, then ITR 200mg PO Q24H X 3 weeks. Group C PLA IV X 7 days, then PO X 3 weeks Initiated immediately before surgery Group C: 44 Prophylaxis initiated in all patients requiring either mechanical ventilation or CRRT for 5 days post-lt of a fungus from the skin, oropharynx, vagina, GI tract, wounds, or urine in association with signs of inflammation, ulcerations, plaques, or exudates that could not be explained by other pathogens. the presence of fungus in the blood, pulmonary tissue or secretions, sinuses, peritoneal cavity, or other organ structures in association with symptoms and signs of infection that could not be explained by other pathogens. Proven histological evidence of fungal invasion or isolation of fungus from a single, normally sterile site Possible isolation of Candida from 3 or more nonsterile sites Colonization: isolation of fungus from 1 or 2 nonsterile sites Patients with 1of the following considered high-risk: UNOS Class I, fungal colonization at baseline, repeated transplantation. All FI in high-risk patients: 9/81 (11%) 38/70 (54%) IFI in high-risk patients: 5/81 (6%) 21/70 (30%) 1 case of possible IFI (treatment group unknown) Total: 3 2 Group C: 1 Attributable: 0/30 headache, seizures, and tremors. Candida sp. (6), Aspergillus sp. (1) Candida sp. (20), Coccidioides immitis (2), Aspergillus sp. (4) LT patients requiring RRT post-transplant 129 consecutive LT patients Exclusion: previous systemic antifungals within 2 weeks prior to LT and documented allergy to study drugs IC: histopathological evidence of tissue invasion by biopsy, or on autopsy, or isolation of Candida in one or more blood cultures, or isolation of Candida in normally sterile body fluid or sites Cryptococcus: Isolation in culture Aspergillus: evidence of tissue invasion on biopsy or autopsy plus isolation of Aspergillus in culture FI: histological evidence oftissue invasion at biopsy or autopsy or a positive culture from a deep tissue specimen, or positive cultures from 3 peripheral sites OR the presence of budding yeast, pseudohyphae, or a positive culture from a bronchoalveolar lavage specimen with clinical and/or radiological evidence of 0 8 (36%) p¼0.03 In logistic regression analysis, only prophylaxis associated with protection from IFI (p¼0.017) FI: 10 (24%) 10 (23%) Group C: 13 (30%) Colonization: 15 (36%) 18 (42%) Group C: 30 (68%) P<0.01 One-year total: 6 (55%) 12 (55%) Attributable: 0 3/12 (25%) Total: 3/42 (7%) 2/43 (5%) Group C: 3/44 (7%) Attributable: 1/42 (2%) 2/43 (5%) Group C: 2/44 (5%) Causes of IFIs in C. albicans (2), C. glabrata (2), A. fumigatus (3), C. neoformans (1) Itraconazole oral formulation not specified Candida (10), Other (1) Candida (7), Aspergillus (2) Group C: Candida (11), Other (1)

5 Fortun 2002 ( 68 ) Retrospective Winston 2002 ( 4 ) randomized Fortun 2003 ( 13 ) Retrospective FLU 100mg PO Q24H þ AmBd 100mg PO Q6H for first 20 days after LT FLU 100mg PO Q24H for first 20 days after LT 91 (time period 2/ /1999) 128 (2/1994-1/1997) Not noted. ITR 200mg PO SOLN Q8H for 24H followed by 200mg PO SOLN Q12H FLU 400mg IV Q24H followed by 400mg PO Q24H when able to swallow oral tablets. Prophylaxis initiated as a single preoperative dose and continued for 10 weeks post- LT AmB 100mg IV Q24H (10-15 days) þ FLU 100 mg Q24H for 20 days FLU 100 mg Q24H for 20 days AmB prophylaxis continued for days 149 (time period 1/ /2001) 131 (1/ / 1997) LT recipients: -between 18 and 75 years old- no clinical or microbiological evidence of fungal infection at time of study entry - no allergy to azole AF -not on specified interacting agents After the study was completed, a subgroup of high risk patients was compared: High risk was defined as 1 risk factor: UNOS classification of 1-fungal colonization at time of transplantationrepeat transplantation 70 ITR patients and 73 FLU patients had one or more of these risk factors for fungal infection. AmB prophylaxis given to pts with 4 risk factors: >30units of PRBCs during transplantation, SCr>2.5mg/dL or CrCl < 25 mg/dl, need for RRT, retransplantation, surgical reintervention, CMV antigenemia (>10cells/200000) or disease, acute rejection, mould pneumonitis Colonization: isolation or identification of a mycotic species from a single superficial site or positive serological test results not associated with any clinical or other evidence of invasive disease None clinical signs and symptoms present together with a significant yeast isolation (positive culture from a sample obtained from an sterile place or a positive histology Colonization: the presence of a fungus in 1 surveillance cultures in the absence of any clinical symptoms or signs of infection. Superficial FI: isolation of a fungus from the skin, oropharynx, gastrointestinal tract, or vagina in association with signs of inflammation, ulcerations, plaques, exudates, or other manifestations of infection not explainable by other pathogens. the presence of fungus in the blood, pulmonary tissues or secretions, sinuses, soft tissues, peritoneal cavity, or other organ structure in association with symptoms and signs of infection not explainable by other pathogens. IC: histopathological evidence of tissue invasion or isolation in normally sterile body fluids Proven IA: tissue histopathology with septate, acute branching hyphae OR positive culture obtained by invasive procedure Probable IA: pulmonary disease with new nodules/cavities on chest radiograph and 2 þ sputum cultures or one þ bronchoalveolar Invasive infections due to Candida: 5 (6%) 13 (10%) P¼0.3 Overall FI: 9 (9%) 4 (4%) P¼ (7%) 3 (3%) P>0.05 Fungal colonization significantly decreased in both groups (p<0.001) FI among high risk patients: 7/70 (10%) 2/73 (3%) (P¼0.09). 9 (6%) 22 (17%) p¼0.007 Multivariate analysis: prophylaxis efficacious in preventing IFI in patients with >4 risk factors, OR 0.1 (95% CI ) Not reported 12 (12%) 7 (8%) Death attributable to FI: month overall mortality: 10 (7%) 18 (14%) p¼ month overall mortality: 15 (10%) 24 (18%) p¼0.07 More adverse events in ITR group (51% vs. 21%, p<0.001), mostly due to GI effects Candida sp. (5), Aspergillus sp. (2) Candida sp. (2), Aspergillus sp. (1) Mean trough concentrations of ITR at 2, 4, 8 and 10 weeks of treatment were generally lower in the 8 of 9 patients who failed prophylaxis than in patients who did not develop a fungal infection 23% of patients in Group A qualified for prophylaxis Candida (3), Aspergillus (6) Candida (9), Aspergillus (13) In dialysed patients meeting high-risk criteria, prophylaxis decreased aspergillosis rates from 32% to

6 Sharpe 2003 ( 57 ) randomized, double-blind Hellinger 2005 ( 64 ) Prospective intervention with retrospective chart review Not noted. ITR SOLN 5mg/kg PO X 1 preoperatively, then 2.5mg/kg PO Q12H postoperatively PLA Continued until either fungal endpoint or discharge from hospital or when a total of 56 days of treatment had occurred ABLC 5mg/kg IV q24-48hrs no prophylaxis in historical cohort Prophylaxis continued until hospital discharge 250 (time period 2/1999-4/2001) 58 (2/1998-1/ 1999) colonization, ATB >5days, ICU stay prior to LT >17 years old undergoing LT Excluded: unable to take medications enterally, being treated or had signs/symptoms of FI at time of LT, allergy to azole antifungals, received systemic antifungals within 2 weeks prior to study entry or topical oral therapy within 1 week, history of prior FI unresponsive to azole therapy, HIV þ, or receiving concomitant systemic interacting medications. Prophylaxis suggested for high-risk patients (RRT at time of LT and/or hospital discharge delayed >7 days post-lt due to allograft or renal insufficiency) and intermediate-risk (LT due to fulminant hepatic failure and/or retransplantation) patients Recipients who had either or both of the first 2 risk factors were considered to be at high risk for invasive mold infection, and those who had either or both of the latter 2 risk factors were considered to be at intermediate risk. Recipients with no risk factors were considered to be at low risk. lavage, washing, or brushing cultures Suspected deep FI: 1 of the following - clinical signs and symptoms with fever of unknown origin unresponsive to broad spectrum anti-bacterials - highly suggestive radiological lesions for deep fungal infection, without mycological evidence by culture or histology - clinical signs and symptoms not highly suggestive of fungal infection but associated with a suggestive fungal isolation Superficial FI: clinical signs and symptoms of oral, esophageal, or vaginal candidosis plus þ cultures at site of infection. Only superficial fungal infections treated with systemic antifungal medication were considered a fungal endpoint. EORTC definitions utilized Suspected deep FI (no proven FI): 1 (4%) 6 (16%) P¼0.225 Superficial FI: 0 3 (8%) P¼0.141 IFI through end of 1 st year post-transplant: 24 (10%) 11 (19%) 2/35 high-risk pts (18 received prophylaxis) developed IMI vs. 1/215 non-high-risk pts (p¼0.05) 1 (4%) 6 (16%) p-value > 0.5 Only one death due to IFI occurred, in historical group (not attributable to IFI) 0% (p ¼ 0.03) The one case of suspected FI in itraconazole patient occurred in context of sub-therapeutic plasma levels (<250 ng/ml) Significantly higher incidence of CMV infection and use of pulse corticosteroids for acute rejection in historical group. Only 26% of high-risk pts given prophylaxis, 7% of intermediate-risk Proven aspergillosis (2), probable aspergillosis (1), Candida (21) Proven aspergillosis (2), proven curvuleria infection (1), Candida (8)

7 Shah 2005 ( 62 ) randomized 6/2000-5/2003 AmBd 15mg IV Q24H AmB 50mg IV Q24H Prophylaxis continued until patient discharge from ICU, death on ICU, or suspected/ confirmed IFI Reed 2007 ( 78 ) Retrospective ABLC 5mg/kg IV Q24H X 5 days Or AmBd 1mg/kg IV Q24H X 5 days No prophylaxis. Fortun 2009 ( 6 ) multicenter, noncomparative, open-label trial 4/2004-6/2007 Caspofungin 50 mg IV Q24H (after 70-mg IV LD) x 21 days Patients eligible for prophylaxis: requiring ICU admission beyond post- transplant day 4 (received FLU 100mg IV Q24H until day 4 then study drug from day 5) or transplant due to fulminant hepatic failure (received FLU 100mg IV Q24H until LT then study drug post-lt) or re-admitted to ICU within 3 months of LT (received study drug at time of ICU admission) 18 years All patients defined as at high risk for FI. High risk defined as one of the following factors being present: retransplantation within one month post-lt, pre-lt renal failure, fulminant hepatic failure as primary indication for LT, or underwent reoperation within the first month post-lt Excluded 39 patients who were receiving fluconazole at time of LT for nonprophylaxis indications years 1 of these criteria: a. Retransplantation caused by severe dysfunction of a previous graft, b. need for any renal replacement therapy within a maximum time period of 30 days, c. prior history of fulminate hepatitis leading to LT, or 2 of these criteria a. prior postoperative renal failure (defined as creatinine clearance <50 ml/min) within histological evidence of fungal invasion or isolation of fungus from normally sterile site. Possible simultaneous isolation of fungal organisms from 3 or more non-sterile sites Colonization: isolation of fungus from 1 or 2 non-sterile sites FI: if conformed to definitions from the Mycoses Study Group of the National Institutes of Allergy and Infectious Diseases (Denning et al 1994) and occurred in the period of 3 months pre-lt through entire admission to 3 months post-discharge Fungus isolated from normally sterile site counted as infection. Respiratory isolates were excluded, unless obtained by bronchoscopy and patient had declining respiratory status, clinical signs/symptoms consistent with acute infection, and no other infectious cause apparent EORTC definitions utilized 2 (5%) 3 (6%) Possible 5 (11%) 5 (10%) 3 (5%) 28 (16%) P¼ Absence of breakthrough IFI (proven or probable) during the first 100 days after the onset of caspofungin. Mucor (1), Candida (1) 3-month survival: 60% 72% p¼0.247 All cases of IFI due to Candida Not provided. Significant baseline differences between groups: Pre-LT fulminant hepatic failure: 12% 3% p¼ Pre-LT Hepatitis C: 21% 43% p¼ Candida (3) Candida (22), Aspergillus (6) 8 (11%) Attributable: 0 6 patients discontinued caspofungin because of drug-related altered liver function.

8 Hadley 2009 ( 71 ) multicenter, double-blind, randomized AmB 2 mg/kg Q24H FLU 400 mg IV Q24 Patients randomized within 5 days of LT, and prophylaxis continued for 14 days a maximum time period of 30 days, b. transfusion intraoperatively of 40 units cellular blood products, c. presence of a choledocojejunostomy, d. 2 positive clinical site surveillance culture (nasal, pharyngeal, or rectal) for Candida from 48 hr before to 48 hr after LT, reoperation (laparotomy) within 5 days of LT. Extensive exclusion criteria (see study) Prophylaxis initiated in patients with 2 risk factors within 5 days of LT (retransplantation, preoperative creatinine > 2.0 mg/dl or need for dialysis within 48 H of LT, choledochojejunostomy, intraoperative requirement of 40 units of blood products (excluding cryoprecipitate and plasma), Candida cultured within 48 H before and after LT from 1 site (sputum, urine, wound, Jackson-Pratt drainage, intra-operative recipient bile/biliary tree, T-tube drainage), re-operation within 5 days for intra-abdominal bleeding or repair of bile or other viscous leak, vascular accident other than bleeding, or acute graft failure. IFI definitions based on EORTC/MSG criteria Proven/Probable IFI (within 100 days after LT): 6 (17%) 4 (14%) Overall Mortality: 7 (20%) 4 (14%) Mortality attributable to 0 0 Closed early due to insufficient enrollment 1/3 of patients did not complete 14 days of prophylaxis Candida (6) Candida (3), Cryptococcus (1) Patients with IFI were more likely to have a choledochojejunostomy (60% vs. 31%) and retransplantation (30% vs. 7%) than those without IFI. Rate of IFI among patients with 3 risk factors was higher than those with 2 (27% vs. 10%) ABLC ¼ amphotericin B lipid complex; AF ¼ antifungals; AmB ¼ liposomal amphotericin B; AmBd ¼ amphotericin B deoxycholate; ATB ¼ antibiotics; CI ¼ confidence interval; CMV ¼ cytomegalovirus; CrCL ¼ creatinine clearance; CRRT ¼ continuous renal replacement therapy; EORTC/MSG ¼ European Organization for Research and Treatment of Cancer/ Mycoses Study Group; FI ¼ fungal infection; FLU ¼ fluconazole; GI ¼ gastrointestinal; H ¼ hours; HIV ¼ human immunodeficiency virus; IA ¼ invasive aspergillosis; IC ¼ invasive candidiasis; ICU ¼ intensive care unit; IFI ¼ invasive fungal infection; IMI ¼ invasive mold infection; ITR ¼ itraconazole; IV ¼ intravenous; LD¼loading dose; LT ¼ liver transplant; MELD¼ Model for End-Stage Liver Disease; N/A ¼ not available; NYS ¼ nystatin; PRBC ¼ packed red blood cells; PLA ¼ placebo; PO ¼ by mouth; Q ¼ every; RRT ¼ renal replacement therapy; SCr ¼ serum creatinine; SOLN ¼ solution; ULN ¼ upper limit of normal; UNOS ¼ United Network Organ Sharing.

9 ERRATUM 805 TABLE 3. Meta analyses of antifungal prophylaxis in liver transplant recipients Number Author # Trials of patients Regimens compared Infection reduction (95% CI) Attributable mortality (95% CI) Overall mortality (95% CI) Comments Playford 2006 ( 76 ) Cruciani 2006 ( 75 ) FLU vs. PLA (2), FLU vs. nonsystemic AF (2), ITR vs. PLA (2), AmB vs. PLA (1) AmB vs. PLA (1), FLU vs. nonsystemic AF (1), FLU vs. PLA (2), ITR vs. PLA (1), AmB!ITR vs. FLU!ITR vs. PLA (1) Proven IFI RR 0.39 ( ) Fungal colonization RR 0.51 ( ) Fungal colonization with C. glabrata/c. krusei RR 1.57 ( ) Total proven fungal infections RR 0.31 ( ) IFI RR 0.33 ( ) Not reported RR 0.84 ( ) RR 0.30 ( ) RR 1.06 ( ) Formulated algorithm (based on fluconazole prophylaxis data only and risk factors from studies(11, 14, 19)) in which patients with <2 risk factors (retransplantation, preoperative creatinine > 2.0 mg/dl, choledochojejunostomy, requirement of 40 units of blood products intra-operatively, fungal colonization from 2 days prior to and 3 days after transplant, and reoperation within 5 days for reason other than bleeding) deemed low-risk (4% incidence) for IFI. Conversely, patients with 2 of the above risk factors, fulminant hepatitis, preoperative steroids, dialysis or renal failure, or post-operative bacterial or CMV infection calculated to be at high risk (25% incidence) for IFI. Patients receiving prophylaxis had a higher proportion of non-albicans proven fungal infections (56% vs. 33%), mostly consisting of C. glabrata (26% vs. 14%)Higher incidence of side effects in prophylaxis arm:rr 1.38 ( ) AF ¼ antifungal; AmB ¼ liposomal amphotericin B; CMV ¼ cytomegalovirus; FLU ¼ fluconazole; IFI ¼ invasive fungal infection; ITR ¼ itraconazole; PLA ¼ placebo; RR ¼ relative risk. LIVER TRANSPLANTATION.DOI /lt. Published on behalf of the American Association for the Study of Liver Diseases