EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: This study aimed to compare renal transplant recipients with and without infection with respect to demographic and clinical characteristics as well as risk factors; to determine the incidence of posttransplant infections; and to study the antibiotic resistance patterns of bacterial species identified as the causative organisms in posttransplant infections.

Materials and Methods: This study included a total of 136 patients undergoing renal transplant in a 4-year period. The patients were categorized into 2 groups. The 2 groups were compared with each other with respect to general clinical and demographic variables and the number and frequency of infectious attacks within a 1-year follow-up, infection type, and antibiotic resistance patterns.

Results: Ninety-two (67.6%) of the subjects were male and 44 (32.4%) were female. A total of 57 (41.9%) patients developed 128 infectious attacks. Urinary tract infections were the most common infections (42.1%). There was a significant correlation between a clinically relevant urinary culture proliferation and postoperative infection rate (P = .002). There was a significant correlation between antimicrobial resistance and the number of infectious attacks (P = .023). There was a significant correlation between the proliferation of Extended Spectrum Beta Lactamase-positive Enterobactericeae species and the number of infectious attacks (P = .000).

Conclusions: Presence of a clinically relevant proliferation in the preoperative urinary culture, which was identified as a risk factor for infection, increased the number of infectious attacks. Moreover, Extended Spectrum Beta Lactamase-positive Enterobactericeae species increased the number of infections. These 2 principle results should be taken into account in patient management.

Key words : Enterobacteriaceae, Urinary system, Kidney

Renal transplant (RT) represents the best treatment for patients with end-stage renal failure. However, serious complications, including graft rejection, infections, or neoplasms, may develop after RT.¹ Infections are one of the commonest complications after RT.^2,3 In particular, immunosuppressive therapy leads to patients being more prone to infections. The most common infection after RT is urinary tract infection (UTI), which has an incidence rate of 45% to 72%.^4-6 In addition to UTIs, sepsis, pneumonia, and surgical field infections are also common.^7-10 Posttransplant infections create significant morbidity and mortality for affected patients. They also cause prolonged hospital stays, create susceptibility for new infections, and increase treatment costs. Therefore, awareness of the risk factors causing infection in RT recipients is important for preventing and accurately and effectively treating potential infections.

In this study, our aim was to compare infection risk factors in RT recipients with and without infection during the first year after transplant to determine the incidence of posttransplant infection and to study the antibiotic resistance patterns of bacterial species identified as the causative organisms of posttransplant infections.

Materials and Methods

The study was conducted according to the guidelines of the Declaration of Helsinki, and the study protocol was approved before the beginning of the study by the Ethics Committee of our university. This study included 136 patients who underwent RT at Baskent University Adana Research and Training Center between July 2010 and 2014. The patients were categorized into 2 groups: those who developed infection (group 1) and those who did not (group 2). Age, sex, dialysis method, presence of positive urine culture before transplant, resistance pattern of the microorganisms causing infections, the underlying cause of renal failure, and mortality rates were compared between the 2 groups. In addition, the overall study population was analyzed for isolating bacterial species, source of infection, number of infections, and morbidity rate. The overall patient population and the groups of patients subcategorized as below or above 18 years of age were compared with respect to the determined parameters. The recipient immunosuppressive protocols included various combinations of prednisolone, cyclosporine or tacrolimus, and mycophenolate mofetil. All patients received trimethoprim-sulfamethoxazole for at least 6 months after transplant as prophylaxis against Pneumocystis carinii pneumonia.

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 17.0, IBM Corporation, Armonk, NY, USA). The categorical variables between the groups were analyzed by using chi-square test.

Our study population comprised 92 male patients (67.6%) and 44 female patients (32.4%). The mean age of the RT recipients in our study was 28 years, with the youngest being 5 years old and the oldest 71. One hundred patients (73.5%) were adults (≥ 18 y old), and 36 (26.4%) were pediatric patients (< 18 y old). Of 136 total patients, 79 (58.1%) did not develop any infection within the 1-year period after transplant (group 1), whereas 57 patients (41.9%) developed an infection (group 2).

When we compared group 1 with group 2 by age, no significant differences were shown between adult and pediatric patients with respect to infection rate (P = .302). The 2 group were also similar in terms of sex, cause of renal failure (anatomic disorders, congenital abnormalities, and others), dialysis method, and mortality rate. Table 1 summarizes the demographic and clinical characteristics of the 2 groups within a 1-year period after RT. Table 1 also shows the number of positive cultures documented in patients with confirmed infection (group 2 patients). One year after RT, 128 infections had been documented in 57 patients. The urinary system was the most common source of infection (87 documented, 42.0%). Of these 87 infections, 14 were characterized by isolation as the same organism in both urine and blood cultures. Fifteen infections (7.2%) were catheter related, 14 (6.7%) were due to bacteremia, 6 (2.8%) were related to the surgical field, and 5 (2.4%) were related to other sources (eg, abscess). One patient had a Mucor species isolated from a fungal paranasal sinus infection.

Regarding the number of infections, 79 patients (38.3%) developed no infections, 23 patients (11.2%) had 1 infection, 14 patients (6.8%) had 2 infections, 9 patients (4.4%) had 3 infections, and 11 patients (5.3%) had more than 3 infections. There was a significant correlation between a clinically relevant positive urine culture before transplant and risk of infection after transplant (P = .05). Of 13 patients with clinically relevant positive urine culture before transplant, 3 patients (23%) had more than 3 infectious attacks.

The most frequent episodes of infection were observed 0 to 15 days after RT (45 infections), with 30 episodes recorded 15 to 30 days, 36 episodes recorded 1 to 2 months, and 17 episodes recorded 2 to 3 months after transplant.

Among 128 positive cultures after transplant, Escherichia coli was the most common organism with a rate of 22.7%, followed by Klebsiella pneumoniae (9.2%), Candida and coagulase-negative staphylococcus species (7.7.%), and Acinetobacter baumannii (5.8%).

When we grouped antibiotic susceptibility of the isolating microorganisms into susceptible (n = 24, 20.5%) and resistant (n = 93, 79.4%), we observed a significant correlation between antimicrobial resistance and the number of infections (P = .0). There was a significant correlation between the extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae family and the number of infections (P = .0). The number of infections was higher in patients who had infections caused by ESBL-positive Enterobacteriaceae family, with 56 infections due to ESBL-positive Enterobacteriaceae and 16 due to ESBL-negative Enterobacteriaceae. Extended-spectrum β-lactamase-positive isolates of UTIs in RT recipients are shown in Table 2. Five patients (3.6%) died, with 3 of these patients (2.2%) having documented infection.

Urinary tract infections are one of the most common and most serious infections after transplant.^3,7,11-13 Immunosuppressive agents and contamination by outside environmental sources are the 2 major risk factors that reportedly affect UTI rate, especially within the first 6 months after RT.2,7,14 Studies have reported UTI rates of 35% to 79% after transplant.^2,7,12,14-17 Urinary tract infections are the cause of infectious complications and hospital admissions and 70% of deaths associated with sepsis (48%) and pneumonia (22%).18 During the past 25 years, however, infection-related deaths have been decreasing.

In this study, we investigated the infections at our hospital in 136 patients within a 1-year period after RT and found that, as most of the previous studies have reported, UTIs were the most common infectious source (42.1%). Among UTIs in our study, 14 progressed into bacteremia.

A study by Ak and associates⁷ from Turkey reported that 40.3% of 124 patients developed infections, of which 85% were UTIs, 10% were bacteremia, 4.5% were intra-abdominal infections, 3.4% were surgical field infections, and 3.4% were central venous catheter infections. The most common causative microbial agents were Escherichia coli (56.6%) and Klebsiella pneumoniae (13.2%).⁷ Compared with the above study reported from Turkey, our UTI rate was lower (42.1% of the 128 documented infections). Other infections that we observed were catheter related (7.2%) and surgical field infections (2.9%). It should be noted that infection rates and site of infection may vary by transplant center.

Published data suggest that the most common bacteria encountered in UTIs are, in descending order, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.^{2,7,11-14,16-17,19} We also observed that Escherichia coli (22.7%) and Klebsiella pneumoniae (9.2%) were the most common microbial agents. We found a rate of 5.8% for Acinetobacter baumannii, which reportedly shows antibiotic resistance and causes hospital infection outbreaks.

There was a significant correlation between antibiotic resistance of the bacteria isolated from infections after transplant and the number of infections, with the resistant bacteria having been isolated from 72.6% of all infections. Lim and associates¹³ reported that Escherichia coli (64.1%) was the most common pathogen in UTIs, as also reported by our group. They also reported that, in patient groups with recurrent infections, the rate of ESBL-positive Escherichia coli species was significantly higher in their study.¹³

One of the most notable results of our study is that the number of infections was significantly higher in patients who had ESBL-positive Enterobacteriaceae isolated as the infectious agent (P = .0). Extended-spectrum β-lactamase-positive Enterobacteriaceae are especially more common in nosocomial infections. They have also been identified as a major source of morbidity and mortality in solid-organ transplant recipients²⁰ because the management of infections caused by these agents is challenging as a result of a much higher likelihood of resistance to other antibiotics.^21,22 In our study, ESBL-positive Enterobacteriaceae were the causative organism is 56 infections, whereas ESBL-negative Enterobacteriaceae were the causative organism in 16 infections. One other interesting finding of our study is that there was a significant correlation between the presence of 104 colony-forming units/mL in urine cultures taken before transplant and the frequency of infections after transplant (P = .002). Rizvi and associates also reported that patients with preoperative UTI had positive urine cultures after transplant. A UTI before transplant reportedly constitutes a major risk factor for UTI at posttransplant (P < .05).²³

Transplant is a demanding and important surgical procedure. Postoperative care and follow-up, as well as detection and management of potential problems after transplant, are crucial. Treatment of infections in patients, which are among the most important complications, may reduce patient mortality and morbidity and costs. During patient care, clinicians should take into account our findings that suggest a significant correlation between a clinically relevant preoperative positive urine culture and the number of infections posttransplant and the occurrence of a higher number of postoperative infections with ESBL-positive Enterobacteriaceae as the causative microorganism. We believe that the implementation of a more meticulous care and follow-up in patients with these 2 conditions would reduce morbidity and mortality rates.

Volume: 13 Issue: 3 November 2015 - Supplement - 3

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