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INTRODUCTION
Urinary tract infections (UTIs) are among the most common complications encountered by renal transplant recipients, significantly affecting their overall health and quality of life [1]. Estimates suggest that up to 41.6% of renal transplant patients experience recurrent UTIs [2]. Escherichia coli and Klebsiella pneumoniae are frequently identified as the primary pathogens responsible for these infections [3,4]. UTIs in these patients can lead to a progressive decline in graft function, with an approximately 20% reduction in 5-year graft survival rates [5]. Research indicates that the antibiogram patterns associated with recurrent UTIs influence clinical outcomes and patient survival, especially in the presence of multidrug-resistant (MDR) organisms [4–6]. The emergence of antibiotic-resistant strains—particularly those producing extended-spectrum beta-lactamases—results in ineffective therapies, poses significant therapeutic challenges, and prolongs hospital stays [3,4,7]. Furthermore, these resistance mechanisms often necessitate the use of carbapenems as a last resort, while novel resistance factors such as K. pneumoniae carbapenemase and New Delhi metallo-beta-lactamase are gradually emerging [3,8,9]. These resistance patterns, combined with the immunocompromised status of the host, increase the risk of acute rejection episodes, as well as the likelihood of sepsis and mortality. Therefore, understanding the antibiogram patterns associated with recurrent UTIs in renal transplant recipients is essential for guiding effective treatment strategies and improving patient care. The aim of this study was to assess the antibiogram patterns of microorganisms isolated from renal transplant recipients diagnosed with recurrent UTIs, thereby providing insight into the prevalence of antibiotic resistance among common uropathogens in this vulnerable population.
METHODS
The study protocol was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.REC.1402.121). Written informed consent was waived due to the retrospective nature of the study.
Patient Recruitment
This retrospective study reviewed the medical records of renal transplant recipients diagnosed with subsequent UTIs who had undergone renal transplantation at Montaserieh Transplant Hospital in Mashhad, Iran from 2017 to 2022. Demographic data, pathogen identification, and antibiogram patterns from urine cultures were recorded.
The Diagnosis of Urinary Tract Infections
The diagnosis of UTIs was based on a combination of clinical symptoms and laboratory tests. UTIs include a range of clinical presentations, such as cystitis, prostatitis, pyelonephritis, and catheter-associated UTIs [10]. Clinical manifestations vary according to the site of infection, extent of involvement, and causative microorganisms. Most patients present with dysuria, urinary frequency, urgency, suprapubic pain, incontinence, foul-smelling urine, and changes in urine color (dark, cloudy, or bloody). Additional systemic symptoms may include fever, nausea, vomiting, or malaise [10–12]. Although several laboratory tests may indicate UTIs, urine analysis and urine culture remain the most traditional and widely used methods for the initial assessment of suspected UTIs [13,14]. A vast number of diagnostic methods and guidelines have been introduced for a definite UTI diagnosis. This study employed a combined diagnostic approach defined by the presence of at least two symptoms (dysuria, frequency, urgency, or suprapubic pain) and a positive urine culture demonstrating ≥105 CFU/mL of a single bacterial species [10]. The midstream clean-catch technique was employed to collect urine specimens for urine culture assessment [15]. No distinction was made between upper and lower UTIs. Recurrent UTIs were defined as having two episodes of acute bacterial cystitis with associated symptoms in the past 6 months or three episodes within the past year [16]. Cases not meeting these criteria were classified as isolated or nonrecurrent UTIs.
Inclusion and Exclusion
The inclusion criteria for this study were: (1) renal transplantation within the past 5 years; (2) at least one confirmed UTI episode posttransplantation; and (3) a complete antibiogram and sensitivity profile obtained using the VITEK2 (bioMérieux) system. A UTI diagnosis was not assigned if the urine culture was negative, even in the presence of symptoms such as fever. Similarly, patients with a positive urine culture but no symptoms (e.g., difficulty urinating or fever) were not diagnosed with a UTI. Cases of asymptomatic pyuria were also excluded. Only bacterial infections were classified as UTIs; viral infections were excluded.
Statistical Analysis
Data were analyzed using SPSS ver. 23 (IBM Corp.). Continuous variables are presented as mean±standard deviation, and categorical variables are described using frequencies and percentages. Depending on the data distribution, comparisons of continuous variables were made using either the independent samples t-test or the Mann-Whitney U-test. The Fisher exact test was used to compare categorical variables between the isolated and recurrent UTI groups. Furthermore, one-way analysis of variance was used to assess the resistance of different bacterial groups to the various antibiotics. A P-value of less than 0.05 was regarded as statistically significant.
RESULTS
Out of 359 screened patients, 58 were included in the study. Among these, 34 patients (59%) were diagnosed with a single UTI, and 24 patients (41%) experienced recurrent UTIs. The study cohort comprised 47 females (81%) and 11 males (19%). Table 1 compares baseline characteristics between the isolated and recurrent UTI groups. The body mass index was significantly higher in the isolated UTI group (23.69±3.84 vs. 21.43±1.27 kg/m2; P=0.040). Additionally, sex distribution differed significantly between groups, with a higher prevalence of females in the recurrent UTI group (Fisher test, P=0.001). However, no significant differences were observed between the groups regarding age or blood creatinine levels (P=0.770 and P=0.320, respectively).
E. coli was the predominant microorganism isolated from UTI episodes (58%; n=33), followed by Klebsiella spp. (16%; n=9), K. pneumoniae (10%; n=6), and Enterococcus spp. (9%; n=5). Table 2 presents the frequency of each bacterium identified from the urine cultures.
Fig. 1 illustrates the resistance data for all bacterial isolates from renal transplant patients. The antibiogram for E. coli showed 100% resistance to ampicillin and cefazolin, followed by resistance rates of 97.9% for ceftriaxone and 95% for ciprofloxacin. In contrast, Klebsiella spp. exhibited 100% resistance to ampicillin, with 67.5% resistance observed for both cefazolin and nitrofurantoin. In terms of efficacy, minocycline, fosfomycin, tigecycline, meropenem, ticarcillin, azithromycin, and cephalexin demonstrated the lowest overall resistance (Fig. 2).
A comparison of antibiotic resistance across various microorganisms revealed significant differences in susceptibility to specific antibiotics. While antibiotics such as ampicillin, cefazolin, cefepime, and imipenem did not exhibit statistically significant differences in resistance among microorganisms, others—including nitrofurantoin, doxycycline, tetracycline, vancomycin, clindamycin, moxifloxacin, and erythromycin—showed significant variations. Table 3 compares antibiotic resistance among the seven groups of microorganisms, with marked differences indicating varying degrees of resistance.
DISCUSSION
UTIs are the most common type of infection among renal transplant recipients and a frequent cause of hospitalization in this population [17]. The incidence of UTIs in renal transplant recipients is similar in both developed and developing nations [18]. Reported rates of posttransplant UTIs range from 12% to 75% [19], and in developing countries, higher rates may be observed due to increased epidemiological exposure and substandard hygiene practices [20]. A 2016 meta-analysis reported that UTI prevalence in the USA was higher than in Europe, with rates of 41% and 33%, respectively [21].
This study identified E. coli, Klebsiella spp., and Enterobacter spp. as the primary causative organisms in renal transplant recipients. The microbial etiology of UTIs has been well established and remains relatively consistent over time. For example, studies by Chuang et al. [22] in the USA, Rivera-Sanchez et al. [23] in Mexico, Iqbal et al. [24] in Pakistan, and Barbouch et al. [25] in Saudi Arabia consistently found E. coli to be the most prevalent microorganism. In contrast, Valera et al. [26] in Poland identified Enterococcus faecium (33%) as the most prevalent organism, slightly surpassing E. coli (31%). Additionally, studies by Dantas et al. [27] and Esezobor et al. [28] identified Enterobacter cloacae and Klebsiella spp. as predominant pathogens, accounting for 30.4% and 40.0% of posttransplant UTIs, respectively.
The current study found that UTIs occurred in 19% of male recipients and 81% of female recipients, indicating a higher incidence among females. This observation is consistent with several other studies that reported a significantly higher incidence of UTIs in females (P<0.05) [22,23,25]. However, Khosravi et al. [29] reported similar UTI rates in male (32.67%) and female (33%) recipients, suggesting no significant difference by sex (P>0.05).
Antibiotic susceptibility testing indicated that E. coli and Klebsiella spp.—the most prevalent bacteria—exhibited resistance to many of the tested antibiotics, underscoring the role of MDR organisms in UTIs among renal transplant recipients.
A study in Mexico reported resistance to ciprofloxacin and ampicillin in 22% and 33% of isolated strains, respectively, with most isolates being Gram-negative bacteria [23]. Valera et al. [26], reported that 10 (24%) of the isolated bacteria produced extended-spectrum beta-lactamases. Dantas et al. [27] found that E. cloacae accounted for 30.4% of posttransplant UTIs, exhibiting resistance to multiple antibiotics. A report from Iran by Khotaii et al. [30] observed high resistance rates, with 87.5% resistance to ampicillin and gentamicin, 67.5% to cotrimoxazole, and 57.7% to cephalothin among UTI patients in a transplant center in Tehran.
At our study center, disease-specific antibiograms have been developed for multiple conditions. However, the current empirical antibiotic guidelines recommend ceftriaxone as the primary treatment for pyelonephritis based on annual institutional antibiograms. Our findings indicate that the resistance patterns of uropathogens in postrenal transplant patients differ markedly from the institution’s standard antibiogram. Therefore, using the standard antibiogram for UTI management in this population may be inappropriate. Organizing antibiograms based on specific isolate data and patient characteristics—as suggested previously [31,32] —may be more effective. Notably, the urinary antibiogram revealed increased antimicrobial resistance in E. coli among renal transplant recipients compared to the institution's general data. In response to elevated Gram-negative resistance rates, the empirical antibiotic guidelines will be updated to provide more appropriate recommendations for hospitalized renal transplant patients with suspected UTIs. Our study demonstrates a significant prevalence of infections caused by MDR bacteria, predominantly Gram-negative enteric bacilli. The high rate of antibiotic resistance observed may be attributed to increased antibiotic usage—often without a prescription—and a demographic profile that includes a large proportion of young individuals, among whom UTIs are more common. This trend is not surprising given the global rise of antibiotic resistance, particularly among Gram-negative bacteria. Because microbial sensitivity to antibiotics can change over time and vary by location, antibiotic treatment should be guided by local sensitivity and resistance data obtained from standard susceptibility testing.
This study found a notable prevalence of UTIs among renal transplant recipients, accompanied by elevated levels of antibiotic resistance. Infections caused by MDR bacteria present significant challenges for renal transplantation. Transplant centers should develop disease-specific antibiograms for transplant recipients to guide empirical antibiotic selection and implement targeted prophylactic measures for patients at increased risk.
ARTICLE INFORMATION
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Author Contributions
Conceptualization: HB, RK. Investigation: HB, SJ. Formal analysis: AD. Resources: MA, RK. Project administration: RK, HB. Visualization: AT, AD, RNS. Writing-original draft: AT, RNS. Writing-review & editing: HB, AD, RK, MA, SJ. All authors read and approved the final manuscript.
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