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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 12  |  Issue : 4  |  Page : 243-246

Noisy orchestra - Renal transplant and urinary tract infections


1 Department of Medicine and infectious Diseases, Sher-i-kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
2 Department of Nephrology, Sher-i-kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
3 Department of Urology, Sher-i-kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
4 Department of Microbiology, Sher-i-kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Date of Web Publication18-Dec-2018

Correspondence Address:
Dr. Ajaz Nabi Koul
Department of Medicine and Infectious Diseases, SKIMS, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_28_18

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  Abstract 


Introduction: Kidneys are the most frequently transplanted organs; renal transplantation is the preferred method for treating patients with chronic kidney disease; and posttransplantation urinary tract infection (UTI) is still a source of morbidity and graft failure. Materials and Methods: This prospective study was conducted during the period of August 2016 to February 2018. A total of 35 renal transplant recipients were included in the study. Results: The most common symptom associated with the infection was dysuria (71%). Only 66% of the cases were febrile. Almost 17% of the cases presented with shock. Urine culture was positive in 23 (65%) cases, with bacteria in 22 (96%) and fungus in 1 (4%). Predominant bacteria grown from cultures were Klebsiella pneumoniae 32%, Pseudomonas aeruginosa 18%, Escherichia coli 14%, Enterococcus faecalis 13%, Acinetobacter 10%, Staphylococcus aureus 9%, and Enterobacter 4%. Antibiotic resistance profiles showed a high resistance patterns to ceftriaxone 60%, levofloxacin 53%, nitrofurantoin 53%, ciprofloxacin 40%, cotrimoxazole 40%, piperacillin–tazobactam 26%, amikacin 26%, gentamicin 26%, meropenem 26%, and imipenem 13%. Patients were followed up over a period of 4 weeks. At the 2nd week of follow-up, 2 (5%) cases were still culture positive, and the symptoms of UTI persisted in 6 (17%) cases. Of 35 cases, 25 were followed up till the 4th week. Culture positive was noted in 6 (24%) cases, and the symptoms persisted in 10 (40%) cases. In recurrent infections, relapses were noted in 3 (50%) cases and reinfections in 3 (50%). Conclusion: In these high-risk patients, antibiotic selection, duration, and stewardship need to be readdressed. Microbial profile and sensitivity patterns in such patients are different from the usual UTIs.

Keywords: Renal transplant, resistance, urinary tract infection, urosepsis


How to cite this article:
Koul AN, Rather AR, Wani IA, Wani M S, Fomda BA. Noisy orchestra - Renal transplant and urinary tract infections. Indian J Transplant 2018;12:243-6

How to cite this URL:
Koul AN, Rather AR, Wani IA, Wani M S, Fomda BA. Noisy orchestra - Renal transplant and urinary tract infections. Indian J Transplant [serial online] 2018 [cited 2019 May 23];12:243-6. Available from: http://www.ijtonline.in/text.asp?2018/12/4/243/247791




  Introduction Top


While kidneys are the most frequently transplanted organs and renal transplantation is the preferred method for treating patients with end-stage renal disease, posttransplantation urinary tract infection (UTI) is still a cause of morbidity and graft failure. The importance of this issue is further emphasized by the fact that UTI is the most common infection in renal transplant recipients,[1],[2],[3] ranging from 6% to 86%[4],[5],[6],[7] and accounting for approximately 40%–50% of all infectious complications. Renal transplant recipients develop UTIs more frequently than the general population.[8],[9],[10] There are many issues which need to be addressed while dealing with UTIs in a renal transplant recipient. They include interaction of antibiotic medication with immunosuppressive drugs, infection with drug-resistant bacteria, fungal UTI, and recurrent UTI. Urosepsis with impairment of graft function can be sequelae of recurrent UTI in kidney transplant recipients.

There are several risk factors associated with UTI among kidney transplant patients, including female gender, old age, diabetes mellitus, immunosuppression, history of vesicoureteral reflux, history of polycystic kidney disease, and other risk factors related to the graft and the operation.[7] According to the published studies, UTIs were found to be more frequent in patients who received deceased grafts compared with live grafts and female patients were more susceptible in general.[7],[11] Moreover, a 5-year follow-up recorded at least one episode of UTI among kidney recipients, and acute pyelonephritis represented an independent risk factor associated with declining renal function.[12]


  Materials and Methods Top


  • Urine samples were collected by standard mid-stream “clean-catch” method
  • The samples were examined for pus cells and red blood cells
  • All the samples were processed on the Hicrome agar by standard loop method and incubated at 37°C overnight, to analyze the bacterial growth
  • Culture results were interpreted as being significant and insignificant.


Antibiotic susceptibility tests were carried out for bacterial isolates by Kirby–Bauer disc diffusion method. Mueller–Hinton agar plates were incubated for 24 h after inoculation with organisms and placement of discs. After 24 h, the inhibition zones were measured and interpreted as per the latest Clinical and Laboratory Standards Institute guidelines. Cultures were considered positive if 100 colony-forming units or more of pure growth were obtained on the plates according to the Infectious Diseases Society of America guidelines.[13]


  Results Top


A total of 35 cases were included in the study. All of them were hospitalized postrenal transplant recipients. Twenty-four were male and 11 were female. The mean age was 30.5 years. The most common symptom associated with the infection was dysuria (71%), followed by fever (66%). Almost 17% of the cases presented with shock. Around 69% of UTI cases were community acquired and 31% were hospital acquired, and the classification was devised as per the Friedman's criteria.[14]

Average kidney functions showed urea level of 77 mg/dl and creatinine level of 2.96 mg/dl. Complete blood counts showed an average hemoglobin level of 11.6 g/dl and total leukocyte count of 8.34 cells/mm3 with differential of 77% neutrophils and 12% lymphocytes. Blood cultures were sterile in 97% of cases. Urine culture was positive in 23 (65%) cases, with bacteria in 22 (96%) and fungus in 1 (4%). The average duration of dialysis before transplant was 1.2 years. Pretransplant UTI was present in 18 (51%) cases. The average time duration from renal transplant to UTI was 4 months.

Our study showed an organism profile very different from literature published from rest of the world. Predominant bacteria grown from cultures were Klebsiella pneumoniae 32%, Pseudomonas aeruginosa 18%,  Escherichia More Details coli 14%, Enterococcus faecalis 13%, Acinetobacter 10%, Staphylococcus aureus 9%, and Enterobacter 4% [Figure 1]. Among fungus, Candida glabrata was the only fungus seen. The drug susceptibility profile [Figure 2] showed high sensitivity to polymyxin 36%, piperacillin–tazobactam 32%, tigecycline 22%, amikacin 23%, levofloxacin 22%, imipenem 18%, vancomycin 18%, and nitrofurantoin 18%.
Figure 1: Etiology

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Figure 2: Antibiotic sensitivity profile

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Antibiotic resistance profile [Figure 3] showed a high resistance patterns to ceftriaxone 60%, levofloxacin 53%, nitrofurantoin 53%, ciprofloxacin 40%, cotrimoxazole 40%, piperacillin–tazobactam 26%, amikacin 26%, gentamicin 26%, meropenem 26%, and imipenem 13%. Patients were followed up over a period of 4 weeks. At the 2-week follow-up, 2 (5%) cases were still culture positive and the symptoms of UTI persisted in 6 (17%) cases. Of 35 cases, 25 were followed up till the 4th week [Figure 4]. Culture positive was observed in 6 (24%) cases and the symptoms persisted in 10 (40%) cases. In recurrent infections, relapses were noted in 3 (50%) and reinfections 3 (50%) cases. Fifty percent of diabetic patients had recurrent UTIs. In 4 cases, native kidney nephrectomy had to be done as a last resort to eradicate the infection.[15]
Figure 3: Antibiotic resistance profile

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Figure 4: Symptomatic cases on follow-up

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  Discussion Top


UTIs are a common health concern, which is the most infectious disease (ID) physicians experience while dealing with renal transplant patients. This patient group is prone to get infected with resistant organisms which during the course of time tend to narrow down the antibiotic susceptibility spectrum. Important proposed risk factors include pretransplant UTI, prolonged period of hemodialysis before hospitalization, postoperative bladder catheterization, immunosuppression, diabetes mellitus, allograft trauma, and polycystic kidney disease. Risk factor profile in our study is given in [Table 1]. Most infections occur in the 1st month after transplantation, but patients with serum creatinine level of ≥2 mg/dL, a daily prednisone dose of ≥20 mg, multiple rejection therapy, or chronic viral infection may continue to have infection problems even after the first 6 months. Most ID physicians agree on the fact that a febrile renal transplant recipient, with abrupt deterioration of renal function, without any evident source of infection, should be treated with empiric antibacterial therapy aimed at Gram-negative bacteria, after blood and urine samples have been obtained.[16]
Table 1: Probable risk factor profile

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Presentation can be typical of a nontransplant UTI, i.e., dysuria, urinary frequency, urgency, and an occasional fever, but most often, symptoms are masked due to ongoing immunosuppression. In our study, only about 66% of cases were febrile. Seventeen percent of patient population presenting in shock depicts the enormous morbidity associated with the disease. The admissions and readmissions that occur due to various reasons such as azotemia, gastroenteritis, and metabolic derangements add to the chances of acquiring hospital borne microbes, as is depicted in our study that around one-third of patient population got the infection from health-care facilities.

Although studies on renal transplant UTI in India are largely lacking, the world literature has tried to figure out the likely reasons and predominant microorganisms associated with the infection. A study done by Gondos et al. in Yemen in 2015 depicted most prevalent bacteria causing UTI as E. coli with a percentage of 44%, followed by Staphylococcus saprophyticus 34%, Enterobacter spp. 12%, Klebsiella spp. 6%, and finally P. aeruginosa 4%.[17] Another study done by Rivera-Sanchez et al. in 2010 showed the organisms: E. coli 32%, Candida albicans 21%, Enterococci 10%, and K. pneumoniae 5%.[11] However, our study showed an organism profile quite different from the rest of the world, with K. pneumoniae being the most common bacteria involved. Klebsiella UTI is very difficult to eradicate, in particular carbapenem-resistant K. pneumoniae. The narrow antibiotic susceptibility spectrum makes them an important cause of recurrent UTIs.

Immunosuppression (100%) was a predominant risk factor followed by urinary catheterization (18%). Due to the fact that urinary stent deployed during renal transplantation remains an important source of infection, nowadays early removal is preferred. A study done in this regard states that early removal (at 1 week) of double-J (DJ) ureteral stents decreases the risk of UTI compared with the routine removal of these stents (at 4 weeks). Ureteral stent removal at 1 week has the same impact on the rate of leakage or obstruction as routine stent removal at 4 weeks.[18] However, in our study, all the DJ stents were removed at 6 weeks contributing to the infections who had indications to keep them for extended periods.

Bacteria in our study were highly resistant to the usual antibiotics used in the UTIs such as ceftriaxone 60%, levofloxacin 53%, and ciprofloxacin 40%. Even resistance against carbapenems was high (meropenem 26% and imipenem 13%). High relapse rate was seen in the study. Around 57% of recurrent UTIs were relapses. As the patients were followed, it was seen that antibiotic susceptibility spectrum of the organism becomes more and more limited, compelling the physician to prescribe high-end toxic antibiotics. Native kidney nephrectomy done in four cases successfully resolved the infection which had become refractory to even sensitive antibiotics.


  Conclusion Top


UTIs in renal transplant patients are the most important morbidity factor posttransplantation. The tendency to develop odd organisms such as Klebsiella is increasing, and the resistance patterns of antibiotics are heading toward the narrow susceptibility.

Recommendations

Although the study is statistically small, the following factors are to be kept in mind at kidney transplantation unit:

  • Premorbid UTI to be treated effectively
  • Early removal of urinary stents and catheters
  • Early discharge from hospital
  • Effective infection control practices
  • Urinary culture-based prolonged antibiotic stewardship.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Schmaldienst S, Hörl WH. Bacterial infections after renal transplantation. Contrib Nephrol 1998;124:18-33.  Back to cited text no. 1
    
2.
Takai K, Tollemar J, Wilczek HE, Groth CG. Urinary tract infections following renal transplantation. Clin Transplant 1998;12:19-23.  Back to cited text no. 2
    
3.
Schmaldienst S, Dittrich E, Hörl WH. Urinary tract infections after renal transplantation. Curr Opin Urol 2002;12:125-30.  Back to cited text no. 3
    
4.
Rubin RH. Infectious disease complications of renal transplantation. Kidney Int 1993;44:221-36.  Back to cited text no. 4
    
5.
Karakayali H, Emiroğlu R, Arslan G, Bilgin N, Haberal M. Major infectious complications after kidney transplantation. Transplant Proc 2001;33:1816-7.  Back to cited text no. 5
    
6.
Giral M, Pascuariello G, Karam G, Hourmant M, Cantarovich D, Dantal J, et al. Acute graft pyelonephritis and long-term kidney allograft outcome. Kidney Int 2002;61:1880-6.  Back to cited text no. 6
    
7.
Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: A retrospective review at two US transplant centers. Clin Transplant 2005;19:230-5.  Back to cited text no. 7
    
8.
Chan PC, Cheng IK, Wong KK, Li MK, Chan MK. Urinary tract infections in post-renal transplant patients. Int Urol Nephrol 1990;22:389-96.  Back to cited text no. 8
    
9.
Rabkin DG, Stifelman MD, Birkhoff J, Richardson KA, Cohen D, Nowygrod R, et al. Early catheter removal decreases incidence of urinary tract infections in renal transplant recipients. Transplant Proc 1998;30:4314-6.  Back to cited text no. 9
    
10.
Glazier DB, Jacobs MG, Lyman NW, Whang MI, Manor E, Mulgaonkar SP, et al. Urinary tract infection associated with ureteral stents in renal transplantation. Can J Urol 1998;5:462-6.  Back to cited text no. 10
    
11.
Rivera-Sanchez R, Delgado-Ochoa D, Flores-Paz RR, García-Jiménez EE, Espinosa-Hernández R, Bazan-Borges AA, et al. Prospective study of urinary tract infection surveillance after kidney transplantation. BMC Infect Dis 2010;10:245.  Back to cited text no. 11
    
12.
Pellé G, Vimont S, Levy PP, Hertig A, Ouali N, Chassin C, et al. Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. Am J Transplant 2007;7:899-907.  Back to cited text no. 12
    
13.
Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643-54.  Back to cited text no. 13
    
14.
Horcajada JP, Shaw E, Padilla B, Pintado V, Calbo E, Benito N, et al. Healthcare-associated, community-acquired and hospital-acquired bacteraemic urinary tract infections in hospitalized patients: A prospective multicentre cohort study in the era of antimicrobial resistance. Clin Microbiol Infect 2013;19:962-8.  Back to cited text no. 14
    
15.
Ajaz K, Adil R, Imtiyaz W, Salim WM, Basharat K, Arif H. Urged nephrectomy in a renal transplant recipient. J Microbiol Infect Dis 2018;8:27-9.  Back to cited text no. 15
    
16.
Peterson PK, Anderson RC. Infection in renal transplant recipients. Current approaches to diagnosis, therapy, and prevention. Am J Med 1986;81:2-10.  Back to cited text no. 16
    
17.
Gondos AS, Al-Moyed KA, Al-Robasi AB, Al-Shamahy HA, Alyousefi NA. Urinary tract infection among renal transplant recipients in Yemen. PLoS One 2015;10:e0144266.  Back to cited text no. 17
    
18.
Liu S, Luo G, Sun B, Lu J, Zu Q, Yang S, et al. Early removal of double-J stents decreases urinary tract infections in living donor renal transplantation: A prospective, randomized clinical trial. Transplant Proc 2017;49:297-302.  Back to cited text no. 18
    


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