Alessiani, M

Kusne, S

Manez, R

Martin, M

Starzl, TE

Torre-Cisneros, J

PubMed

D-Scholarship@Pitt

The Spectrum of Aspergillosis in Liver Transplant Patients: Comparison of FK 506 and Cyclosporine Immunosuppression J. Torre-Cisneros, A. Manez. s. Kusne. M. Alessiani. M. Martin, and T.E. StarzJ ASPERGILLOSIS is the second most imponant cause of fungal. infection after liver transplantaUon (LTx). with a mortality approaching 100%. In a previous study, we observed a 4% frequency of invasive aspergillosis in 101 consecutive LTx recipients. I Outcome depends on early treatment. however. the diagnosis of this disease is very difficult.2 The introduction of FK 506. allowed us to evaluate the impact of this new immunosuppressive agent on the inci-dence and outcome of aspergillosis following L Tx. and to compare this to a group of patients under traditional cyclosporine (Cy A) therapy. METHODS Patient Selection Pathology and microbiology records were reviewed during the period from 1981 to 1990. and 32 cases of invasive aspergillosis occurring after liver transplantation were identified. Their inpa-tient and outpatient charts were reviewed. Definitions a~finiDiv~ diagnosIS: Histologic evidence of tissue invasion at biopsy or autopsy (24 of 32. 75%). mrobabl~ diagnosIS: Characteristic clinical picture combined with laclt of response to antibacterial agents and presence of repeated positive cultures for Aspergillus species (8 of 32.25%). aisD~m;naI~d aAp~rglllosiA: Histologic proven invasion in au-topsy of two or more noncontiguous organs (16 of 32. 50%). Immunosuppression Two protocols were used: (a) CyA and steroids. and (b) FK 506 with low-dose steroids (20 mg/d). Rejection episodes were treated with a I-g dose or S-da y recycle of methylprednisolone. OKT3 monoclonal antibody was used for treatment of steroid-resistant rejection. AntIbIotic: ProphytaxiS Perioperauve IV cefotaxime and aml'icillin 4 g/d were adminis· tered to all l'8tients. Funp! prophylaxis included oral nystatin 2 millions uniu daily. Risk Factors We analyzed four prettansl'lant (hel'8tocellular disease. ALT >60 and steroid usel and seven posltransplant vanables (I V antibiotics >5 days. cumulative SUrgical time> 12 hours. re.trans. plantation. additional abdominal operations. choledochoJeJunos-tomy. OKT3. and additional steroids I. Statistics Prol'Orttons were analyzed with chi-square test or Fisher's Exact Test when data were scarce. RESULTS The characteristics of the popUlation are shown in Table I. During the 100year study period. 2180 patients underwent OLT at our institution. and 32 patients developed invasive aspergillosis for an overall rate of 1.5%. Cy A and steroid immunosuppression were used in 1247 patients. and 30 patients were identified with invasive aspergillosis. for an incidence of 2.4%, and a monality of 94% (29 of 30). Two cases of aspergillosis occurred from among 933 patients receiving FK 506 and low-dose ste-roids for an incidence of 0.2% (P < .01). and a monality of 50% (\ of 21. The mean time to diagnosis after OLT was 101 :!: 160 days in the Cy A group and 31 :!: 13 days in the FK 506 group. The median time of dia.gnosis was 35 days in the Cy A group and 31 days in FK 506 group. One FK 506 patient died of disseminated aspergillosis on day 219. which was significantly longer than the mean survival time of 119 days seen in CyA patients. The other patient is free of disease after completing 6 months of treatment that included amphotericin Band itraconazole. The presenting symptoms in FK 506 patients included fever and respiratory complaints in both. and skin involve-ment in one. Fever. respiratory. and neurological manifes-tations were the most frequent presenting symptoms in the CyA group. In both FK 506 and CyA patients. concomi-tant bacterial. fungal, and viral infections were frequent. When four pretransplant risk factors were analysed .... higher occurrence of hepatocellular disease in FK 506 patients was found. No pallent receIving FK S06 reqUIred Table 1. ComparilOn at Aspergilioais on FK 508 and CyA Total CyA FK506 Total OlT 2180 1247 93 AspergIllus 32 (1.5%) 30 (2.4%)" 2 (0.2"10)· Time diagnostS 97:t 162 101 :t 166 31 :t 13 (mean=: SO) Time diagnostS 34.5 35 31 (median) Died 30(94%) 29(97%) 1 (50%1 'p< .01. From the Depanrnems of Surgery and Inf9CllOUs Disease. University of Pittsburgh, Pittsburgh. Pennsylvatll8. Address repnnt requests to Or. Maureen Martin. 3601 Fifth Avenue. 5C Falk Clinic. Pittsburgh. PA 15213. Q 1991 by Appleton & Lange 0041.13451911$3.001+0 3040 TraMtJI8IltaflOn PI'OCIHIthntJS. Vol 23. No 6 (Decemoerl. 1991: PI' 3040-3041 --ASPERGILLOSIS IN LTx PATIENTS OKTI or retransplantation. whereas in the eyA group, 73% of patients were treated with OKTI and 70% needed retransplantation. These findings were the most significant of the seven posttransplant variables analysed. DISCUSSION Aspergillosis continues to be associated with very high mortality after liver transplantation. In this series. only two patients survived. and in only 56% of patients was the diagnosis made before death. Variables found to be corre-lated with higher rates of fungal infection in our previous repons 1.3 are also associated with aspergillosis in this series. The typical patient at risk for aspergillosis is rela-tively young, has undergone a long cumulative surgical time. and demonstrates persistent fever despite antimicro-bial therapy in the first months after transplantation. With the introduction the new immunosuppressive agent. FK 506. we observed a decrease in the incidence of 3041 aspergillosis. This phenomenon occurred in spite of the potent immunosuppressive properties of FK. 506. suggest-ing that this new drug has the ability to decrease other factors for infection. such as lowering steroid usage with-out increasing the risk of rejection and the subsequent need for augmented immunosuppression and/or retrans-plantation. Improvement in patient management after LTx has allowed us to increase patient and graft survival to levels unparalleled only a few years ago. The introduction of novel agents such as fK 506 will contribute to a funher improvement in overall morbidity. REFERENCES l. Kusne S. Dummer JS. Singh N. et at: Medicine 67: 132. 1988 2. Denning OW. Stevens DA: Rev Infect Dis 12:1147.1990 3. Kusne S. Dummer JS. Singh N. et at: Transplant Pro<: :0:650. 1988 

The spectrum of aspergillosis in liver transplant patients: Comparison of FK 506 and cyclosporine immunosuppression

Name not available

J. TORRECISNEROS

R. MANEZ

S. KUSNE

M. MARTIN

T. E. STARZL

ALESSIANI, MARIO

Archivio Istituzionale della Ricerca - Università degli Studi di Pavia

The Spectrum of Aspergillosis In Liver-transplant Patients - Comparison of Fk-506 and Cyclosporine Immunosuppression

http://d-scholarship.pitt.edu/4691/1/31735062118587.pdf

The spectrum of aspergillosis in liver transplant patients: Comparison of FK 506 and cyclosporine immunosuppression

Abstract

Similar works

Full text

Available Versions

D-Scholarship@Pitt

Name not available

Archivio Istituzionale della Ricerca - Università degli Studi di Pavia

Name not available