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 ~  Abstract
 ~ Introduction
 ~ Patients and Methods
 ~ Results
 ~ Discussion
 ~  References
 ~  Article Tables

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  Table of Contents  
BRIEF COMMUNICATION
Year : 2017  |  Volume : 35  |  Issue : 4  |  Page : 604-606
 

Infections in live donor liver transplant recipients: A study of timeline, aetiology and antimicrobial resistance of bacterial and fungal infections from the developing world


1 Department of Microbiology, Institute of Liver and Biliary Sciences, New Delhi, India
2 Department of Hepato-Pancreatico-Biliary Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
3 Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

Date of Web Publication1-Feb-2018

Correspondence Address:
Dr. Vikas Khillan
Department of Microbiology, Institute of Liver and Biliary Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_17_295

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 ~ Abstract 

Infections are the leading cause of morbidity and mortality in liver transplant (LT) recipients. We studied timeline, spectrum of infection, system involved, and antimicrobial resistance in 64 patients undergoing live donor LT with 6-month follow-up. Of 64 patients, 38 (59.5%) patients had 103 infectious episodes, 10 patients had single infectious episode and 28 patients had two or more infectious episodes. 96 (93.2%) were bacterial and Candida infections were in 7 (6.8%). Early phase had 30 (29.1%) episodes; intermediate phase 25 (24.2%) and late phase 48 (46.6%). Mortality was 11/64 (17.1%). Knowledge of timeline, aetiological agent and antimicrobial resistance is useful to guide empirical therapy and infection prevention.


Keywords: Antimicrobial resistance, live donor liver transplant, post-transplant infections


How to cite this article:
Khillan V, Kale P, Pamecha V, Rathor N, Sarin SK. Infections in live donor liver transplant recipients: A study of timeline, aetiology and antimicrobial resistance of bacterial and fungal infections from the developing world. Indian J Med Microbiol 2017;35:604-6

How to cite this URL:
Khillan V, Kale P, Pamecha V, Rathor N, Sarin SK. Infections in live donor liver transplant recipients: A study of timeline, aetiology and antimicrobial resistance of bacterial and fungal infections from the developing world. Indian J Med Microbiol [serial online] 2017 [cited 2019 Aug 22];35:604-6. Available from: http://www.ijmm.org/text.asp?2017/35/4/604/224432



 ~ Introduction Top


Infections are the leading cause of morbidity and mortality in solid organ transplant recipients.[1],[2] Liver transplant (LT) recipients are more prone to infections owing to complex, prolonged surgery and access to the hepatobiliary system.[2] Ours is a tertiary care centre for hepatobiliary diseases performing about 100 LTs per year, of which 70% are living donor LTs (LDLTs). We contemplated this study to assess the burden of bacterial and fungal infections within 6 months of LDLT with respect to timeline of occurrence of infections and attributed mortality in LDLT.


 ~ Patients and Methods Top


Sixty-four patients undergoing LDLT during January 2014 to January 2015 were enrolled, and data were collected and recorded from the date of surgery to 6 months post-surgery. All bacterial and fungal infections occurring after surgery were considered for the study, defined by isolation of infectious agent from a documented site of infection. Samples received were blood, respiratory samples, intra-abdominal fluid samples and urine. Identification and antimicrobial susceptibility testing were performed by Vitek II (Biomerieux, India Limited) in accordance with the Clinical Laboratory Standards Institute guidelines.[3]


 ~ Results Top


We prospectively documented the infectious episodes in the 64 patients (males – 53 [82.81%], females – 11 [17.1%]) undergoing LDLT with 6-month follow-up. Of 64 patients, 38 (59.5%) developed at least one infectious episode during the first 6 months. A total of 103 infectious episodes were reported. Ten patients developed a single episode of infection and 28 had two or more episodes. Bacterial infections were most frequent with 96 (93.2%) events and fungal infections with Candida species were in 7 (6.8%). The early phase was marked with 30 (29.1%) episodes of infections, the intermediate phase had 25 (24.2%) events and the late phase had 48 (46.6%) episodes. Of 64 patients, 14 (21.8%) died, three of which had no infectious episode during illness; thus, mortality attributable to infectious causes was 11/64 (17.1%).

Analysis of the aetiological agent

Bacterial infections

Klebsiella pneumoniae (KPN) was the most frequent pathogen isolated in 43 (41.74%) events, followed by  Escherichia More Details coli 20 (19.41%), Pseudomonas aeruginosa 10 (9.7%), Acinetobacter baumannii 11 (10.67%), Enterococcus spp. 7 (6.7%) and Stenotrophomonas maltophilia 5 (4.8%).

K. pneumonia was isolated from 14 respiratory, 12 intra-abdominal, 6 urinary tract and 11 bloodstream infections. E. coli was isolated from 5 respiratory, 4 intra-abdominal, 7 urinary tract and 4 bloodstream infections. P. aeruginosa was isolated from 4 respiratory, 3 intra-abdominal, 1 urinary tract and 2 surgical site infections. A. baumannii was isolated in 5 respiratory, 3 intra-abdominal and 2 bloodstream infections and 1 surgical site infection. S. maltophilia was predominantly isolated from respiratory samples. The sensitivity pattern is elucidated in [Table 1].
Table 1: Antimicrobial susceptibility pattern of bacterial isolates

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Enterococcus spp. was predominantly isolated in 7 (6.75) events from intra-abdominal samples (4), blood (2) and urine (1) and exhibited sensitivity to teicoplanin (78.9%), vancomycin (78.9%), tigecycline (100%) and linezolid (94.75%).

Fungal infections

Candida species was the predominant fungal pathogen isolated in 7 (6.7%) episodes from blood and bile samples. Candida albicans and Candida tropicalis were predominantly isolated with one episode of Candida parapsilosis from blood sample. The antifungal sensitivity is summarised in [Table 2].
Table 2: Antifungal susceptibility of Candida species

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 ~ Discussion Top


Infections in LT patients are preventable and treatable if suspected at appropriate time. There was a male preponderance in our study. The incidence of post-LDLT infections was 59.5%, much higher than 48.5% reported by Chiereghin et al. with 1-year follow-up and 41% by Antunes et al. with 2-year follow-up in LT subjects.[4],[5] Souza et al. have reported an infection incidence rate of 55.3%; Vera et al. reported an incidence of 55.3%.[6],[7] The timeline study shows that majority of the infections occurred in the early post-operative period (<1 week) (30/103 [29.1%]) or in the late follow-up period (>1–6 months) (48/103 [46.6%]). Chiereghin et al. have shown higher incidence (63%) of infections within the 1st month of surgery.[4] The late-phase insurgence in infections in our patients could be due to waning vigilance and patient care as the patient is discharged and returns to normal living by this time. All 11 patients whose death was attributable to infectious aetiology had >1 infectious episode during the 1st post-operative week.

Early phase was marked with predominance of bloodstream infections, while in the intermediate and late phase, there was preponderance of respiratory and intra-abdominal infections. Bacterial infections were most frequent (93.2%) with predominance of Gram-negative bacteria (GNBs) accounting for 92.7% infections as compared to Gram-positive cocci in 7.3% of the bacterial infections.

KPN was the most frequently isolated GNB (41.74%). However, E. coli is the most common pathogen reported in most other studies.[5],[8] Varghese et al. have reported E. coli (20%) as the most common pathogens in both deceased donor LT and LDLT, followed by KPN (11.4%) and P. aeruginosa (5.7%).[8]

Extended-spectrum beta-lactamase (ESBL) production was seen in 62% of Enterobacteriaceae isolates. Men et al. have reported 42.3% ESBL-producing pathogens from one of the largest transplant centres; other studies have also reported ESBL production in 43.3% of GNB in LT.[9] Chiereghin et al. have shown the incidence of ESBL-producing KPN as high as 68.4% and carbapenemase production in 47.4% isolates and virtually absent polymyxin resistance.[4] Carbapenemase-producing KPN (CRKP) was isolated in 65.1% which is significantly higher compared to other studies. 22.9% CRKP was reported with 71% mortality in LT recipients by Kalpoe et al.[10] In a large retrospective study of around 10 years' duration including 330 LT recipients, Barchiesi et al. reported infections in 27%, with KPN being the most commonly isolated pathogen (29%) and CRKP as high as 67%.[11]

P. aeruginosa was isolated in 9.7%, of which 30% were multidrug resistant (MDR). Previous studies reported 2.8% infections, MDR P. aeruginosa 46.3% and mortality ranging from 33.3% to 38.5%.[12]

Candida spp. were isolated in 6.7% cases which is comparable to a 6-year analysis of fungal infections in LTs by Zicker et al. (7%).[13] The most common species were C. albicans (3/7) and C. tropicalis (3/7) followed by C. parapsilosis (1/7). Conditions that predispose a patient to Candida colonisation are frequent in LT recipients and can lead to overgrowth in the hepatobiliary, gastrointestinal and genitourinary tracts and facilitate fungaemia and dissemination.

We conclude that bacteria are accountable for majority of infections in LDLT, especially the MDR Gram-negative Enterobacteriaceae and Pseudomonas species with a rising trend. The infections occurring early are related to surgical procedure, medical devices or prolonged hospitalisation. The intermediate-phase infections are attributed to the hospital-acquired factors and the immunosuppressive therapy given to the patient. The late-phase surge in infections is unanticipated caused by variety of patient-related factors as it is difficult to monitor the patient after discharge. This study gives an overview of the sequential infectious complications in post-transplant patient, and the risk factors in development of these complications need to be analysed. It is essential to have in place an effective approach for infection prevention, based on the predicted infection risk, local antimicrobial resistance and surveillance of specific risk factors and infection control measures to limit and reduce infectious complications in transplant recipients.

Financial support and sponsorship

The study was supported by the Departmental Fund.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

1.
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;357:2601-14.  Back to cited text no. 1
    
2.
Patel R, Paya CV. Infections in solid-organ transplant recipients. Clin Microbiol Rev 1997;10:86-124.  Back to cited text no. 2
    
3.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; 16th Informational Supplement. M100-S27. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.  Back to cited text no. 3
    
4.
Chiereghin A, Petrisli E, Ravaioli M, Morelli MC, Turello G, Squarzoni D, et al. Infectious agents after liver transplant: Etiology, timeline and patients' cell-mediated immunity responses. Med Microbiol Immunol 2017;206:63-71.  Back to cited text no. 4
    
5.
Antunes M, Teixeira A, Fortuna P, Moya B, Martins A, Bagulho L, et al. Infections after liver transplantation: A Retrospective, single-center study. Transplant Proc 2015;47:1019-24.  Back to cited text no. 5
    
6.
Souza MV, Barth AL, Alvares-da-Silva MR, Machado AR. Infections after liver transplantation in adults: Data from a university hospital in Southern Brazil (1996-2000). Arq Gastroenterol 2007;44:128-32.  Back to cited text no. 6
    
7.
Vera A, Contreras F, Guevara F. Incidence and risk factors for infections after liver transplant: Single-center experience at the University Hospital Fundación Santa Fe de Bogotá, Colombia. Transpl Infect Dis 2011;13:608-15.  Back to cited text no. 7
    
8.
Varghese J, Gomathy N, Rajashekhar P, Venugopal K, Olithselvan A, Vivekanandan S, et al. Perioperative bacterial infections in deceased donor and living donor liver transplant recipients. J Clin Exp Hepatol 2012;2:35-41.  Back to cited text no. 8
    
9.
Men TY, Wang JN, Li H, Gu Y, Xing TH, Peng ZH, et al. Prevalence of multidrug-resistant gram-negative bacilli producing extended-spectrum β-lactamases (ESBLs) and ESBL genes in solid organ transplant recipients. Transpl Infect Dis 2013;15:14-21.  Back to cited text no. 9
    
10.
Kalpoe JS, Sonnenberg E, Factor SH, del Rio Martin J, Schiano T, Patel G, et al. Mortality associated with carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients. Liver Transpl 2012;18:468-74.  Back to cited text no. 10
    
11.
Barchiesi F, Montalti R, Castelli P, Nicolini D, Staffolani S, Mocchegiani F, et al. Carbapenem-resistant Klebsiella pneumoniae influences the outcome of early infections in liver transplant recipients. BMC Infect Dis 2016;16:538.  Back to cited text no. 11
    
12.
Su H, Ye Q, Wan Q, Zhou J. Predictors of mortality in abdominal organ transplant recipients with Pseudomonas aeruginosa infections. Ann Transplant 2016;21:86-93.  Back to cited text no. 12
    
13.
Zicker M, Colombo AL, Ferraz-Neto BH, Camargo LF. Epidemiology of fungal infections in liver transplant recipients: A six-year study of a large Brazilian liver transplantation centre. Mem Inst Oswaldo Cruz 2011;106:339-45.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2]



 

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