Green, M

Nour, B

Reyes, J

Starzl, TE

Todo, S

Tzakis, A

PubMed

Name not available

Infectious Complications of pediatric liver transplantation under FK 506

D-Scholarship@Pitt

12'71 Infectious Complications of Pediatric Liver Transplantation Under FK 506 M. Green. A. Tzakis, J. Reyes. 8. Nour. S. Todo. and T.E. Starzl THE introduction of cyclosponne (CyA) has been as-sociated with the evolution of liver transplantation as an effective therapy for children with end-stage liver disease. However. long-term toxicity of CyA and failures due to chronic rejection have prompted evaluation of the new immunosuppressant. FK 506. in pediatric liver trans-plant recipients at the Children' s Hospital of Pittsburgh. The pu~se of the following case-control study was to compare the infectious complications seen in patients treated with FK 506 to randomly assigned recent historical controls treated with conventional immunosuppression. METHODS Beginning In October 1989. children undergoing first-lime ortho-tOPIC liver transplantation IOLT) were eligible to participate In a histoncallv controlled. clanical evaluation of the new immunosup-pressant. FK 506. A sangle control was randomly selected from a set of matched candidate controls for each pallent treated with FK 506. Matching was performed for age (within 6 months). primary diagnOSIS. and "UNOS" seventy score as soon as poSSible after the transplant. Inpatient and outpatient chans were systematically reViewed ulilizing standardized datasheets and definitions I 10 compare 9O-day outcome. Datapoants from the inpatient chart review included patient outcome. immunosuppressive therapy. episodes of rejection. and episodes of infection. Maintenance immunosuppressive management. as well as the treatment of rejection In the two groups of patients was as prevlOuslv descnbed. ".J Proportions were analvzed with the chi-square test. and means were compared with the Student's I test. RESULTS Sixty-one children were treated with FK 506 as their primarY Immunosuppressant between October 1989 and October 1990. Fifty-one controls were identified for these patients. No control was Identified for 10 patients because of either an unusual diagnOSIs or a common diagnosis presenting for transplant at an unusual age. However. for the purpose of this analvsls. these unmatched patients were meluded in the FK 506 group. Congenital diseases. including biliary atresia and neona-tal hepatitis. were the most common diagnoses 10 both groups. The mean age of the FK 506 group was 4,4 years compared to 3.4 years 10 control patients IP :: NS1. This difference 10 age IS accounted for by the 10 unmatched patients who tended to be older I mean = 8.7 yearsl. Six of the 61 pallents treated wllh FK 506 died in the first 90 days posnransplant compared to 13 of 51 control patients I P = 06) Two io the deaths In control pallents occurred during the pnmary transplant procedure. Six of 61 children treated with FK 506 required retransplantation compared to 10 of 51 control patients (P = NS). An overview of the infectious complications seen in both treatment groups is shown in Table I. The mean number of infectious episodes was significantly less in patients treated with FK S06 compared to controls (1.2 vs 1.8. P < .05). The type and timing of infection were similar in the two groups. The mean onset of bactenal infection was 23 days after the transplant. and was not different between the two groups. The most common infection in each group was bacteremia (Table 1 l. and the most common pathogens were gram-positive organisms. The major difference be-tween the two groups of patients was the frequency of Table 1. Overvtew of Inftlctlou. Complication. During the Firat 90 0 • .,. Aft., Pediatric OLT FK508 CanIraI No. patients 61 51 Infectious epiSOdes 78 98 EpiSOdeS/palient 1.2 18· Fatal Infections 2 r Blldenal 38 55 Bacteremia 13 32 Une-asaoc1ated 5 19 Other source identified 4 10 Intra·abdomlnal (nonbacteremlc) 5 8 Ententls 4 4 Wouno 4 2 Pneumonia InonbacteremlCl 3 3 Otitis medla'SlnuSltIS 8 4 U nnary tract 2 4 Viral infectIOns 30 33 CytomegaloVIrus 12 13 InvUlve 9 9 AdenoviruS 4 7 Invulve 0 5 EBV'PTLO 1 1 Fungal Infections 7 6 Mixed infection' 3 2 . p < 05. r p. 08: 'n"xeQ llaC:I8tIal ana fungal anledIOn. From the University of PittSburgh Schoof of Medicine Decan-ments of Pedlatncs and Surgery. Children s Hospital of PittSburgh. 3705 Fifth Avenue. Pittsburgh. Pennsytvarna. Address repnnt requescs to M. Green. MD. MPH. DiviSion of InfectIOUS Dis ...... Childrens H05;)ItaJ of PittsbUrgh. 3705 Fifth Avenue. PittSbUrgh. PA 15213. ~ 1991 bV APPleton & Lange 0041·1345.911$3.001+0 3038 TranspIat1ttJtIOtI Proceet1l1'1t}S. s~ 23. No 6 (OecemDerI. 1991: pp 3038-3039 INFECTIOUS COMPLICATIONS catheter-associated bacteremia. and is explained by a change In our usage of central venous catheters_ After exclusion of catheter-associated bacteremias. the differ-ence in the mean number of infections is no longer signif-icant. The overall incidence of viral infection was similar in the two groups (Table I). The mean onset of viral infection was 33 days after transplantation and was not different 10 either treatment group. CMV was the most common pathogen. and caused invasive disease in the majority of episodes in both groups. AdenOVirus was the next most common pathogen: invasive disease appeared to be more common in controls. Isolated fungal infections were noted in seven of the children treated with FK 506 compared to six control patients. Mixed infections. consisting of Candida species and bacteria. were additionally noted in three FK 506 and two control patients. Infection due to Aspt'rgil/us /umiga-/IIS contnbuted to the death of one and caused pneumonia in another child with cystic fibrosis transpla.nted under FK 506. The remaining fungal infections were due to Candida species. Despite the fact that five episodes of invasive candidiaSIS were noted in both treatment groups. the only death due to fungal disease identified during the study period was the previously mentioned child who had con-current asperillosis of his hean and disseminated candidi-asis <Table 2). Pathogens and clinical syndromes associated with infec-tious deaths are shown in Table 2. A trend toward an increase in fatal infections was observed in the control group 12 of 61 vs 7 of 51. P =08). Severe pneumonitis. associated with adult respiratory distress syndrome. was the most common fatal infectious syndrome observed in this study. DISCUSSION This study suggests that the type. timing. and frequency of infections seen after liver transplantation are similar in children receiving FK 506 as immunosuppression com-pared to recent historical controls treated with conven-tional immunosuppression. The decreased rate of bactenal mfectlons among patients treated with FK 506 is likely explained by a dramatic reduction in our current use of central venous catheters. which preceded the onset of this clinical tnaL 3039 Table 2. InhK:tloua DMtha Arter Pedlatrtc OLTx Immunosuooressaon PaltlOgen Clinical SyndrOme FK506 Aspergttius Carclltls Candida Disseminated disease FK 506 CMV Pneumonla'ARDS Control S.aUI8fJS Septic shOCk. Control £. cloacae SepbC ShOCK Control E. cloacae Pneumonia ARDS Control Adenovirus Pneumonia ARDS Controt Adenovirus Pneumonia ARDS CMV Control CMV Pneumonia ARDS Control Influenza A PneumonlaARDS A trend toward an increase in fatal infections was observed in the control group in this study suggesting that patients transplanted under FK 506 may experience less infection-associated mortality than those treated with tra-ditional immunosuppressive regimens. Although limited by the small number of patients observed in thIS study. the trend appeared to hold for both bacterial and mal infec-tions. This observation may be explained by a decreased use of conicosteroids and OKT3 in the children treated with FK 506. 4 Evaluation of the first 3 months after pediatric liver transplant demonstrates no increase. and perhaps. a de-crease in infectious disease morbidity and mortality in pediatric liver transplant recipients treated with FK 506. These findings. along with a trend toward increased sur-vival and the previously reponed benefits of less steroid and anllhypenensive requirement in these chIldren. sug-gests (hat FK 506 is superior to conventional immunosup-pression. Conllnued follow-up for late mfectlous sequelae, including the development of posttransplant I"mphoprolif-c:ratlve disease. are necessary to complete these observa-tions. REFERENCES I. Kusne S. Dummer JS. SinlZh N. et al: MedICine a7: 132. 1988 2. Tzakis AG. Fung JJ. Todo S. el al: Transplanl Proc 23:924. 1991 3. Bowman JS. Green M. Scantlebury VP. el al: Clin Tr.1ns-plant 5:294. f~f 4. Tzakis AG. Reyes J. Todo S. et al: Transplant Proc lin press) 

Infectious complications of pediatric liver transplantation under FK 506

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Infectious complications of pediatric liver transplantation under FK 506

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