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Accepted Article
Article type : Original Report

Bacterial Infections in Pediatric Patients during Early Post Liver Transplant Period: A
Prospective Study in Iran

Running title: Bacterial Infection in Liver Transplant

Gholamreza Pouladfar1, Zahra Jafarpour1, Seyed Ali Malek Hosseini2, Mohammad

Firoozifar2, Razieh Rasekh2, Leila Khosravifard2

1
Professor Alborzi Clinical Microbiology Research Center, Nemazee Teaching Hospital,
Shiraz University of Medical Sciences, Shiraz, Iran

2
Shiraz Organ Transplant Center, Abu-Ali Sina Hospital, Shiraz, Iran

Correspondence: Z. Jafarpour M.D, Professor Alborzi Clinical Microbiology Research

Center, Nemazee Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
Telephone: +987136474304
Fax: +987136474303
E-mail: zjafarpoor54@yahoo.com

Acknowledgment

Our thanks to H. Khajehei for his linguistic copyediting of the manuscript.

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/tid.13001
This article is protected by copyright. All rights reserved.
 Abstract

Background: Bacterial infection in early period after liver transplant (LT) is the main cause
Accepted Article
of morbidity and mortality; however, data on children is limited.

Methods: To investigate the frequency, characteristics, and the associated factors of bacterial
infection during hospitalization after LT, we prospectively enrolled all consecutive children
with LT for a one-year, case-control study at the unique referral center of pediatric LT in
Iran.

Results: Eighty-five events of bacterial infection were detected among 51 out of 94 LT

recipients (54.3%) (infection group). Forty-three patients without bacterial infection
constituted the control group. The frequency of bacterial infection based on the 51
microbiologically documented events was 31.9% (30 out of 94 patients). Major site of
bacterial isolation were abdomen (43.6%). The following variables were associated with
bacterial infection in univariate analysis: younger age (5.6 vs. 8.9 years old), longer duration
of JP Drain (13.4 vs. 6.3 days), central venous catheter (14.6 vs. 7.6 days), and Foley catheter
insertion (7.3 vs. 4.5 days), reoperation (57% vs. 12% of patients), mean frequency of
reoperation (1.1 vs. 0.1 times), and intensive care unit stay (12.1 vs. 6.5 days). In multivariate
analysis, only longer hospital stay after transplant (23.6 vs. 10.9 days) was independently
associated with bacterial infection. All ten deaths occurred within the infection group and
half of which directly caused by infection.

Conclusions: These infections were associated with longer hospital stay and higher mortality
rate. Conducting further studies with larger sample size and investigating more effective
prophylactic measures should be considered in future studies.

KEYWORDS

Liver transplantation, bacterial infections, child, postoperative complications, Iran

1 INTRODUCTION

Pediatric liver transplant (LT) has become an effective modality for patients with acute or
chronic end-stage liver diseases. Significant progress has been made in the quality of life and
the survival rate following the organ transplant due to the advances in surgical techniques,

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 immunosuppressive therapy, and medical management. Post liver transplant infections are
estimated to occur in more than 50% of liver transplant (LT) recipients.(1) A common
complication and a major cause of death, infections in the early period after LT are usually
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nosocomial and the result of a perioperative complication.(2-5) Bacterial infections account for
most post-transplant infections (up to 70%), followed by viral and fungal infections.(6, 7)

In Iran the first LT was performed on adults in 1993 and on children in 1999 in Nemazee
Teaching Hospital, Shiraz.(8, 9)
Although more than a decade has passed since the
performance of first pediatric LT in Iran, no study has been conducted on the children’s
infection rate, risk factors associated with infections, and their effects on the patients’
outcome in the early period after transplant.

The aims of this prospective study were to determine (i) the frequency, the clinical as well as
microbiological characteristics of bacterial infections among hospitalized children in the early
period after LT, (ii) the associated factors of their occurrence, and (iii) the outcomes of
patients with and without bacterial infections.

2 PATIENTS AND METHODS

We prospectively enrolled all consecutive 96 children under the age of 18 who underwent LT
from October of 2014 to October of 2015 at Nemazee Teaching Hospital, the unique referral
center of LT in Iran. Two patients who survived less than two days after LT were excluded.
The causes of their death were not related to infection. All the other patients were monitored
prospectively for any event related to infectious complications from the day of LT until the
day of hospital discharge or death in hospital immediately after LT. This study was approved
by the ethics committee of Shiraz University of Medical Sciences. All of the protocols
conformed to the ethical guidelines of the 1975 Helsinki Declaration. A written informed
consent was obtained from all the patients.

The medical records of all the patients were reviewed daily. The patients suspected to have
infection underwent a thorough assessment by a subspecialist of pediatric infectious diseases.
We used CDC/NHSN surveillance definition of healthcare-associated infection and criteria
for specific types of infections in the acute care setting to enroll the patients in the infection
group and define the types of infection.(10) Patients were divided into two groups depending
on whether they had any evidence of infection (infection group) or not (control group). We

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 did not treat patients with asymptomatic bacteriuria, so patients with isolated asymptomatic
bacteriuria without any other evidence of infection were classified in the control group.
Gastroenteritis was defined as a health care-associated infection if a patient had an acute
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onset of diarrhea (liquid stools for more than 12 hours) with no likelihood of noninfectious
cause.(10) Diagnosis of sepsis was made according to the 2001
SCCM/ESICM/ACCP/ATS/SIS international sepsis definition, which is a strongly suspected
presence of infection and the systemic response to it, without being microbiologically
confirmed.(11) According to CDC/NHSN surveillance definition, infection episodes were
classified as either “infection as present on admission” (POA) or “healthcare-associated
infection” (HAI). We classified patients to have POA if they had received antibiotics for the
treatment of a suspected or confirmed infection immediately prior to LT. We considered them
free of infection at the time of LT.

The following recipient variables were included in a questionnaire and analyzed in relation to
infections in three phases of pre-transplantation, perioperative, and post-transplantation. In
pre-transplantation phase, age, sex, body mass index (BMI), etiology of end stage LT,
Pediatric End-Stage Liver Disease (PELD) score or the Model for End-Stage Liver Disease
(MELD) score, the result of tuberculin skin test (TST), any history of admission within one
week before LT as well as admission within 3 months prior to LT were recorded. In
perioperative phase, types of liver transplantation, the average operative time, vancomycin
resistant Enterococci (VRE) colonization at the time of admission, and antimicrobial
prophylaxis were recorded. In post-transplantation phase, re-transplantation and its reason,
abdominal reoperation after LT due to surgery complication such as hepatic or portal vein
thrombosis, bleeding, intra-abdominal abscess and leakage, frequency of abdominal
reoperation among explored patients, the need for tracheostomy, chest tube insertion, renal
replacement therapy, the time of removal of endotracheal tube, central vein catheter, Jackson-
Pratt Drain (JP Drain), Foley catheter, the average length of stay in hospital and intensive-
care unit (ICU), evidence of infection, the type of antimicrobial drugs, and the patients’
outcomes were recorded. All available laboratory data including hemoglobin level, total
white blood cell (WBC) and platelet counts, international normalization ratio (INR), serum
creatinine, bilirubin, aspartate transaminase, alkaline phosphatase, and albumin levels at the
time of transplant were recorded. The results of urine analysis and urine culture were
recorded as well.

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 The following data were collected for each episode of infection: date of the event according
to CDC definition, site of infection, isolated organism and its antimicrobial susceptibility
pattern. Antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion
Accepted Article
method and according to CLSI. Multidrug-resistant (MDR) pathogens were defined in
accordance with the Consensus Statement of the European Centre for Disease Prevention and
Control and the American CDC. (12)

The postoperative immunosuppression consisted of tacrolimus, mycophenolate mofetil, and

steroids. Acute graft rejection was treated with an intra-venous bolus of methyl-prednisolone.

All patients received antimicrobial prophylaxis consisting of ampicillin-sulbactam (150

mg/Kg/day) and ceftizoxime (150 mg/Kg/day). Antibiotics were discontinued after 72 hours
in all patients, except in those with bilo enteric anastomosis (continued for 5 days). All
patients received trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis with 2-3 mg per
kilogram TMP daily for the first 6 months after transplantation for prophylaxis of
Pneumocystis jiroveci, fluconazole (3-5mg/Kg/day) for prophylaxis of fungal infection, and
ganciclovir (10 mg/Kg/day) or valagancyclovir (13 mg/Kg/day) for prophylaxis of
cytomegalovirus infection that were commenced and continued for at least one month after
LT.(13)

When recipients developed fever or other evidence that suggested an infection, the following
examinations were performed to detect the focus of infection: sepsis workup including two
sets of blood culture obtained by peripheral venipuncture, either from central venous catheter
(CVC) or arterial line, if in place; other cultures of respiratory specimens (sputum and
endotracheal tube secretions), urine, wound or wound secretions, specimens obtained from
intra-abdominal collection, ascitic fluid, and eye discharge. These examinations, imaging and
exploratory laparotomy were not performed on all the patients, but rather when deemed
necessary and based on the opinion of the attending physician.

2.1 Analysis

Descriptive statistics were used to express data as mean ± SD for continuous variables, the
frequency, and the percentage for categorical variables. We examined the factors affecting
the difference between those with and without infection using binary logistic regression
model and multivariate analyses. The statistical tests used in the univariate analysis were the
Chi-squared test, Fisher’s exact test, Student’s t-test, and Mann-Whitney U test. Covariates

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 significant (P<0.05) in the univariate model were included in the multivariable linear
regression. Results were presented as β coefficient and P value. All analyses were performed
using SPSS 18.0.
Accepted Article
3 RESULTS

3.1 PATIENT’S CHARACTERISTICS

The patient population comprised 94 pediatric patients (48 females and 46 males) aged 1-17
years who underwent 97 liver transplantations with end-stage liver disease in Nemazee
Teaching Hospital, between October of 2014 and October of 2015. Eleven recipients (12%)
underwent Roux-en-Y hepaticojejunostomy anastomoses and others duct-to-duct
anastomoses. Only 3 (3.2%) of the recipients required re-transplantation – two for acute
rejection and one for primary nonfunction in LT. The mean ± SD of the patients' age was 7.2
± 5 years. Demographic and clinical characteristics of patients were shown in Table 1. Forty-
two patients (65.6%) had PELD/MELD scores less than 20. In total, 63 abdominal
reoperation after LT were done on 34 (38.2%) patients, 20 of which were for wound closure,
14 for bleeding, 10 for intestinal perforation, 6 for hepatic artery thrombosis, 6 for portal vein
thrombosis, and 7 for other reasons. The mean frequency of reoperation (ranging from 0 to 6
episodes) was 0.7± 1.2. Kasai procedure (hepatoportoenterostomy) had been performed on 11
(11.5%) recipients during infancy. Metabolic diseases were the most common underlying
diseases in our patients (Table 2).

Laboratory characteristics of patients were shown in Table 3. Tuberculosis skin test (TST)
induration of 10 or more millimeters (mm) was reported in 6 patients (11.8%), 5 or more mm
in 21 (41.2%), and less than 5 mm in 27 (54%) recipients.

3.2 COMPARISON OF THE ASSOCIATED FACTORS

In total, 51 patients (54.3%) were assigned into the infection group and 43 patients (45.7%)
into the control group. The demographic and clinical characteristics, underlying diseases, and
laboratory findings in two groups are shown in tables 1-3. No association between infection
and underlying diseases or laboratory characteristics at the time of transplant was detected.
(Table 2 and 3). As shown in tables 1, in univariate analysis of variables between the

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 infection and the control groups, some demographic and clinical variables were strongly
associated with bacterial infections including younger age, return to operation room due to
surgical complications (reoperation), multiple episodes of reoperation (frequency of
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reoperation), longer duration of JP Drain, CVC and Foley catheter insertion, and longer time
of ICU and hospital stay after transplant. In multivariate analysis, however, only longer
hospital stay after transplant was independently associated with bacterial infection (adjusted
odds ratio: 1.42, 95% confidence interval: 1.15-1.76, and P value: <0.001).

The need for post-transplant renal replacement therapy (RRT) and re-transplantation was
seen in 4 (4.2%) and 3 (3.2%) recipients, respectively; all were in the infection group.
Tracheostomy was performed on three recipients, two in the infection group and one in the
control group. Death occurred in 10 patients (10.6%); all within the infection group. Septic
shock and multiple organ dysfunction syndromes (MODS) were the causes of death in five
patients. The other causes of death were graft failure (n=4) and acute rejection (n=1).The
main presentations of infection in these patients were surgical site infection with secondary
blood stream infection (n=4), and ventilator-associated complication (n=1).

Totally, 21 patients (22.3%) had been hospitalized one week prior to LT. Among ten of them
classified as POA (infection as present on admission), four were in the infection group and
six in the control group. Patients with POA had received a course of proper antibiotics prior
to LT and were considered to be free of infection, based on their clinical and laboratory
evidence. Of whom, nine had sepsis and one spontaneous bacterial peritonitis.

3.3 BACTERIAL INFECTION EPISODES

Among 94 pediatric patients who underwent LT, 85 events of bacterial infections occurred in
(10)
51 patients (54.3%) (Infection group) based on the CDC/NHSN surveillance definition
(Table 4). Fifty-one events were microbiologically documented bacterial infections that
occurred in 31.9% of patients (30 out of 94 patients). The other 34 clinically defined events
consisted of 10 episodes of sepsis, 10 episodes of gastroenteritis, 6 ventilator-associated
complication, 4 intra-abdominal surgical site infections, 2 clinically defined pneumonia, one
deep incisional primary SSI, and one soft tissue infection (Table 4). In patients with
microbiologically documented bacterial infections, the mean days of bacterial isolation in
clinical specimens were 15.57± 11.54 days after LT.

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 Of the 108 bacteria isolates causing infection, 47 strains were isolated from deep or
superficial surgical sites (43.6%), followed by urine (n=25; 23.1%), blood (n=22; 20.4%),
respiratory tract (n=11; 10.2%), soft tissue (n=2; 1.8%) and eye (n=1; 0.9%) (Table 5). The
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isolation of seven bacteria in urine was not associated with pyuria or any clinical sign or
symptom, so we classified these events as asymptomatic bacteriuria.

The most common isolates were Gram-negative rod (n = 55; 51%) with the predominance of
Acinetobacter spp. (n=18; 16.7%), Klebsiella spp. (n=13; 12%), Pseudomonas spp.(n=10;
9.2%), Escherichia coli (n=10; 9.2%), Stenotrophomonas maltophilia (n=3; 2.8%), and
Citrobacter spp. (n=1; 0.9 %) with the median isolation time of 15 days post LT. Gram-
positive bacteria comprised 53 isolates (49.1%), the most common strains of which were
Enterococcus spp. (n=39; 36.1%) including 32 strains of VRE (82%), Staphylococcus
spp.(n=12; 11.1%), and Streptococcus spp. (n=2; 1.8%) with the median isolation time of 12
days after LT (Table 5). The presence of multidrug resistance defined as non-susceptibility to
at least one agent in three or more antimicrobial categories is frequently observed in the
pathogens recovered from children undergoing LT. Overall, 94.4% of Acinetobacter spp.,
82.6% of Enterobacteriaceae and 82%of Enterococcus spp. were multidrug resistance.

DISCUSSION

This one-year, prospective study that was conducted on 94 children who underwent LT is the
first report on bacterial infections during hospitalization in the early period post LT in Iran. In
this study, the high rates of bacterial infection in children hospitalized after LT were detected
(54.3%, 51 out of 94) including 31.9% (30 out of 94) microbiologically documented ones.
This finding is consistent with the limited reports about LT children worldwide (51.9% in
Germany and 70.8% in France).(14-18) During the first weeks after transplantation, bacteria are
the main infectious agents,(19, 20) as they tend to occur due to indwelling catheters (21) and at or
near the transplanted organ, either in the form of a superficial wound or deep space
infections.(17) In another 23-years, single-center, retrospective study conducted in Canada, 49
episodes of microbiologically documented infection were detected among 145 children (34%)
in post LT, and only during their stay in the pediatric critical care unit; 79% of these episodes
had bacterial etiology.(20) Several factors have attributed to the increased risk of bacterial
infection in the early period post LT including the complexity of surgical procedures in LT;
high levels of immune suppression due to rejection; multiple points of entry for

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 microorganisms (e.g. incisions, catheters, probes); and patient's poor health condition. (14, 15, 20,
22, 23)
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In our study, Gram-negative isolates were relatively as frequent as Gram-positive isolates
(51% vs. 49%, P value =0.87). The most frequently observed bacterial organisms in the early
period post transplantation were Enterococcus spp. (36.1%) and Staphylococcus spp. (11.1%)
as Gram-positive bacteria and Enterobacteriaceae (21.3%), Acinetobacter spp. (16.7%), and
Pseudomonas Spp. (9.2%) as Gram-negative ones. Two studies that investigated the bacterial
etiology in this period reported a predominance of Gram-positive bacteria such as
Enterococci, Staphylococci, and Streptococci.(15, 18)
In a French study, bacterial isolates
showed a predominance of Gram-positive bacteria (78%) including Staphylococcus aureus
(32%) and Staphylococcus epidermis (26%) during the early postoperative period.(15) All
patients received polymyxin, gentamicin, and nystatin for selective intestinal
decontamination during their entire PICU stay or until resuming oral intake, so as to reduce
not only Gram-negative aerobic bacteria in intestinal flora, but also the predominance of
Gram-positive bacteria.(15, 24, 25) In a study conducted in Canada, it has been reported that both
Gram-negative and positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and
Pseudomonas aeruginosa) are the causative agents of infections in this period.(20) Ashkenazi-
Hoffnung et al. retrospectively analyzed 133 hospital admissions for fever among 44 LT
children during eight years. Their study revealed that hospitalization was most common in the
first year of post-transplantation. Of those admissions, 73 cases (54.8%) were due to bacterial
infections mainly caused by Gram-negative bacteria of the Enterobacteriaceae family
(57.7%).(14) The different reports on bacterial etiology of post LT infection could be due to
the different prophylaxis regimens in each center as well as the geographic variation of
common pathogens causing nosocomial infections in each hospital.

According to the studies investigating infection in hospitalized children in early period after
LT, blood and abdomen were found to be the two major localizations of infection sites. (15, 18,
20)
Performing complex surgical procedures in LT, and the need for insertion of central vein
catheter and intra-abdominal JP Drain could play a major role in developing infections in
blood and abdomen. In our study 64% of localizations of infection were abdomen and blood.
Two other major localizations of infection were urine (23.1%) and the lungs (10.2%). In a
French study that investigated 63 episodes of infection, the most frequent sites of infection
were blood (36.5%), abdomen (30%), the lungs (11%), and urine (6.3%).(15) In another

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 German study, the major localizations of infection were either the lungs, abdomen, or
catheter- associated.(18) In a Canadian study, the most frequent sources of infection were
blood (53%), the lungs (24%), and abdomen (22%).(20) In some of these studies, the higher
Accepted Article
rate of infection in the pulmonary system could be due to viral as well as bacterial
etiologies.(15, 18, 20) In comparison to other studies, we detected a higher rate of infection in the
urinary tract, which is mainly associated with urinary catheter. The most important
determinant of urinary tract infection is the duration of catheterization. (26) The daily risk of
acquisition of bacteriuria with a Foley catheter in situ is 3–7%.(26) The mean duration of
Foley catheter in our patients with infection was 7 days, which was significantly longer than
those in the control group (4 days; odds ratio, 1.26; P value 0.022). Intervention should focus
on the early removal of the urinary catheters, when feasible, to reduce the risk of UTI in post
LT patients.(27)

We found high incidence of infections caused by multidrug-resistant bacteria in our patients,

including vancomycin-resistant enterococci (82.1%), Acinetobacter spp. (94.4%), and
Enterobacteriaceae (82.6%); this finding is in agreement with other studies that investigated
nosocomial infections both at our center and in Iran.(28, 29) MDR Gram-negative pathogens in
LT recipients are growing worldwide with reporting rates of more than 50 percent.(30) In a
study carried out by Nina Singh, MDR rates were 45% and 65% for Pseudomonas
aeruginosa and Enterobacteriaceae respectively.(31)

Infections with resistant isolates are associated with a significant increase in mortality rate. (30)
Although some studies have reported that infection is not significantly related to increased
(15, 19)
mortality, all 10 mortalities among the 94 children (10.6%) were from the infection
group. In a Canadian study, mortality rate in the first 28 days post LT was 8%.(20) In our
study, infection was the cause of death in five patients (50%). Sanromán Budiño et al. studied
32 liver transplant autopsies and showed that infection was the most common cause of death
among them (59.4%).(32)

Univariate analyses of our data demonstrated that many factors could be associated with a
higher risk of infection including pre-transplant factors (younger age), intra-operative factors
(abdominal reoperation, increased number of abdominal reoperation), and post-transplant
factors (the ongoing presence of indwelling catheters such as central venous catheters, JP
Drain, and urethral catheters, longer stay in ICU and longer hospitalization). Some factors
such as underlying causes of liver failure as well as increased number of abdominal

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 operations have been previously reported to be associated with increased infection in LT.(33,
34)
Additionally, multiple logistic regression analysis showed a significantly longer
hospitalization period in patients with infection. These results are in agreement with those
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reported by other authors. (5, 35, 36)
This study has two limitations: one, it is a single- center study. Two, the number of patients
with the microbiologically documented bacterial infections is low. On the other hand, the
strength of this study is the number of its patients, which is more than most previous studies
carried out on children, and the amount of data prospectively collected.

In conclusion, a high rate of bacterial infection was detected among the hospitalized children
in early period after transplantation. These infections in LT children were associated with
longer hospital stay and higher mortality rate. Apart from longer hospital stay, no other factor
was associated with getting an infection in multivariate analysis. In order to decrease the rate
of infection in the absence of the identified associated factor, conducting further studies with
larger sample size, and investigating more effective prophylactic measures should be
considered in future studies.

Authors’ Contribution:

All authors revised the preliminary draft and approved the final version to be published.
Gholamreza Pouladfar proposed and developed the study idea, supervised the research and
rewrite the manuscript. Zahra Jafarpour gathered data, performed statistical analysis, and
wrote the preliminary manuscript. Seyed Ali Malek Hosseini advised scientifically the
research. Mohammad Firoozifar advised scientifically the research and gathered data. Razieh
Rasekh and Leila Khosravifard gathered data.

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 Table 1: Demographic and clinical characteristics of children who underwent liver transplant,
stratified by infection outcome
Infection Control Unadjusted
Accepted Article
Total group group
Variables Odds ratio
N=94 N=51 N=43 P Value
(45.7%) (95% CI)
(54.3%)
Age, M +/-SD, yr. 7.2±5 5.6±4.8 8.9±4.6 0.86 (0.78-0.94) 0.002*
Male gender, n (%) 46 (48.9) 24 (47.1) 22 (51.2) 0.84 (0.37-1.91) 0.69
PELD/MELD score, M+/-SD 18±10.1 17.9±9.8 17.8±10.3 1.00 (0.95-1.05) 0.87
BMI, M+/-SD, kg/m2 17.9±4.6 17.7±5.1 18.0±4.2 0.98 (0.89-1.09) 0.78
TST>10mm, n (%) 6 (11.8) 4 (15) 2 (8) 2.09 (0.34-12.58) 0.42
Hospitalized 1 wk.PTA, n (%) 21 (22.3) 11 (22) 10 (23) 0.90 (0.34-2.40) 0.84
Infection as POA, n (%) 10 (10.6) 4 (8) 6 (14) 0.52 (0.13-1.99) 0.34
Hospitalized 3 mo. PTA, n (%) 34(36.2) 17 (33) 17 (39) 0.76 (0.32-1.77) 0.53
Cadaver, n (%) 61 (64.9) 29 (57) 32 (74) 2.20 (0.91-5.32) 0.07
Operation time, M+/-SD, hrs. 4.2±1 4.3±1.0 4.2±1.0 1.09 (0.69-1.73) 0.69
Allograft rejection, n (%) 7 (7.4) 5 (10) 2 (5) 2.22 (0.41-12.11) 0.35
Abdominal RO, n (%) 34 (36.2) 29 (57) 5 (12) 9.75 (3.29-28.89) <0.001*
Frequency of RO, M+/-SD 0.7±1.2 1.1±1.3 0.1±0.4 5.16 (2.10-12.65) <0.001*
ETT duration, M+/-SD, d 1.4±3.9 2.1±5.3 0.7±1.5 1.19 (0.90-1.56) 0.21
CVC duration, M+/-SD, d 10.7±6.6 14.6±7.7 7.6±3.3 1.26 (1.10-1.44) 0.001*
Foley duration, M+/-SD, d 5.9±4.4 7.3±5.7 4.5±1.5 1.26 (1.03-1.54) 0.022
JP Drain duration, M+/-SD, d 9.5±7.2 13.4±8.7 6.3±3.3 1.20 (1.07-1.35) 0.001*
Hospital stay, M+/-SD, d 17.8±11.9 23.6±13.5 10.9±2.8 1.38 (1.19-1.60) <0.001*
ICU stay, M+/-SD, d 9.5±7.4 12.1±8.9 6.5±30.5 1.21 (1.09-1.35) <0.001*

* In multivariate analysis, hospital stay was the only variable with significant P value
(<0.001); adjusted odds ratio was 1.42 (95% CI: 1.15-1.76).
Confidence interval, CI; mean, M; years, yr.; standard deviation, SD; Pediatric End-Stage
Liver Disease, PELD; Model for End-Stage Liver Disease, MELD; body mass index, BMI;
tuberculin skin test, TST; prior to admission for transplantation, PTA; month, mo.; present on
admission, POA; hours, hrs.; week, wk.; reoperation; RO; endotracheal tube, ETT; day, d;
central vein catheter, CVC; Jackson-Pratt drain, JP Drain; intensive care unit, ICU.

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 Table 2: Underlying diagnoses for 94 liver transplant recipients, stratified by infection
outcome
Accepted Article
Total
Infection group Control group P
Underlying diagnosis number
number (%) number (%) value
(%)
Metabolic liver disease* 34 (36.2) 15 (29.4) 19 (44.2) 0.20
Intrahepatic biliary disease** 19 (20.2) 14 (27.4) 5 (11.6) 0.10
Biliary atresia 18 (19.1) 11 (21.6) 7 (16.3) 0.67
Chronic hepatitis*** 9 (9.6) 5 (9.8) 4 (9.3) 0.79

Cryptogenic cirrhosis 8 (8.5) 2 (3.9) 6 (14) 0.17

Hepatocellular carcinoma 4 (4.3) 3 (5.9) 1 (2.3) 0.73

Fulminant hepatic failure 2 (2.1) 1 (2) 1 (2.3) 0.54

Total 94 51 43

*Metabolic liver diseases: tyrosinemia, Wilson's disease, Criggler-Najjar disease, maple

syrup urine disease, hyperoxaluria, hypercholesterolemia, Alagille syndrome, polycystic liver
disease; **intrahepatic biliary diseases: progressive familial intrahepatic cholestasis, neonatal
hepatitis; ***chronic hepatitis: autoimmune hepatitis, hepatitis B virus

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 Table 3: Laboratory characteristics* of children who underwent liver transplant, stratified by
infection outcome
Accepted Article
Infection Control Unadjusted
Total group group
Variables Odds ratio P
N=94 N=51 N=43
(45.7%) (95% CI) Value
(54.3%)
TBILI, M+/-SD, mg/dL 9.6±12.9 9.8 ±12.5 9.2 ±13.4 1.00 (0.97-1.03) 0.82
DBILI, M+/-SD, mg/dL 4±5.3 4.0 ±5.4 3.9 ±5.2 1.00 (0.92-1.09) 0.90
Albumin, M+/-SD, g/dL 3.4±0.8 3.4 ±0.9 3.4 ±0.7 0.85 (0.49-1.48) 0.58
TP, M+/-SD, g/dL 6±1.6 5.8 ±1.7 6.3 ±1.5 0.83 (0.62-1.12) 0.23
ALP, M+/-SD, U/L 676±576 737 ±647 597 ±464 1.00 (1.00-1.00) 0.27
ALT, M+/-SD, U/L 217±326 193 ±280 246 ±378 0.99 (0.99-1.00) 0.46
AST, M+/-SD, U/L 256±440 254 ±506 258 ±347 1.00 (0.99-1.00) 0.97
PT, M+/-SD, sec 22±9.8 21 ±10 22 ±1 0.99 (0.94-1.03) 0.65
PTT, M+/-SD, sec 46±21 45 ±23 48 ±19 0.99 (0.97-1.01) 0.64
HGB, M+/-SD, g/dL 10±2.2 9.9 ±2.2 10.2 ±2.1 0.94 (0.77-1.15) 0.58
WBC, M+/-SD, /mL 7964±4952 8646 ±5324 7107 ±4359 1.00 (1.00-1.00) 0.15
PLT, M+/-SD, 109/L 127±94 127 ±94 126 ±96 1.00 (1.00-1.00) 0.95
BUN, M+/-SD, mg/dL 13.2±10.6 14.7 ±13.1 11.3 ±5.7 1.04 (0.98-1.11) 0.16
SCr, M+/-SD, mg/dL 0.4±0.7 0.5 ±0.8 0.4±0.3 1.18 (0.56-2.45) 0.65
VRE colonization, n (%) 16(17) 12 (23.5) 4 (9.3) 3.00 (0.89-10.11) 0.07

 The laboratory results were obtained at the time of transplant.

 Confidence interval, CI; mean, M; standard deviation, SD; Total bilirubin, TBILI;
Direct Bilirubin, DBILI; Total protein, TP; Alkaline phosphatase, ALP; Alanine
transaminase, ALT; Aspartate transaminase, AST; Prothrombin time, PT; Partial
Thromboplastin time, PTT; seconds, sec; Hemoglobin, HGB; White blood count, WBC;
Platelet count, PLT; Blood urea nitrogen, BUN; Serum Creatinine, SCr; Vancomycin
resistant Enterococci, VRE.

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 Table 4: Bacterial infection-related events among pediatric patients who underwent liver
transplant
Number
Accepted Article
Events
(percent)
Surgical Site Infection (SSI) 35 (41.2)

Intra-abdominal SSI 20

Intra-abdominal SSI with secondary blood stream infection (SBSI) 11

Deep incisional primary SSI 4
Pneumonia (P) 14 (16.5)
Proven ventilator-associated P (VAP) 2
Probable VAP 3
Probable VAP with SBSI 1
Ventilator-associated complication 6
Clinically defined P 2
Urinary Tract Infections (UTI) 7 (8.2)
Symptomatic UTI 1
Catheter-associated UTI (CAUTI) 5
CAUTI with SBSI 1
Sepsis 11 (12.9)
Gastroenteritis 11 (12.9)
Central line-associated blood stream infection (CLABSI) 5 (5.9)
Bacterial conjunctivitis 1 (1.2)
Skin infection 1 (1.2)
Total 85

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 Table 5: Bacterial pathogens isolated from different sites among children who underwent
liver transplant
Isolation sites of pathogens, number (percent)
Accepted Article
Causative agents Respiratory Urinary Abdominal/ Soft Total
Blood Eye
tract tract surgical site tissue

Gram positive Bacteria 53 (49.1)

Enterococcus spp. 9 (8.3) ---- 11 (10.2) 17 (15.8) 2 (1.8) ----- 39 (36.1)
Coagulase-negative s. 5 (4.6) ----- ----- 4 (3.7) ----- ----- 9 (8.3)
S. aureus ----- ----- ----- 2 (1.8) ----- 1(0.9) 3(2.8)
Streptococcus spp. ------ ----- ------ 2 (1.8) ----- ----- 2 (1.8)
Non-fermenter Gram-negative bacilli 31 (28.7)
Acinetobacter spp. 2 (1.8) 5 (4.6) 2 (1.8) 9 (8.3) ----- ----- 18 (16.7)
Pseudomonas spp. 1 (0.9) 3 (2.8) 3 (2.8) 3 (2.8) ----- ----- 10 (9.2)
PMA 1 (0.9) ----- ----- 2 (1.8) ----- ----- 3 (2.8)
Enterobacteriaceae 24 (22.2)
Klebsiella spp. ----- 3 (2.8) 6 (5.6) 4 (3.7) ----- ----- 13 (12.0)
Escherichia coli 4 (3.7) ---- 3 (2.8) 3 (2.8) ----- ----- 10 (9.2)
Citrobacter spp. ----- ----- ----- 1 (0.9) ----- ----- 1 (0.9)
22
Total 11 (10.2) 25 (23.1) 47 (43.6) 2 (1.8) 1 (0.9) 108
(20.4)

Spp., species; Staphylococcus, s; Stenotrophomonas maltophilia, PMA.

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