 Abstract | | |
Urinary tract infections (UTI) are the most common bacterial infections after renal transplantation and are associated with significant morbidity and mortality. Recurrent or relapsing infections are not uncommon in the early post-transplant period and superadded fungal UTI can occur in these patients, posing a difficult therapeutic problem. Literature on recurrent UTI after transplant as well as the ideal approach to such patients is scanty. We present the case of a renal allograft recipient who presented with relapsing bacterial UTI complicated by systemic fungemia; also, a brief review of fungal UTI is attempted. Keywords: Recurrent urinary tract infection, C. glabrata, Voriconazole, Nephrectomy
How to cite this article:
Satish R, Gokulnath. Intractable urinary tract infection in a renal transplant recipient. Saudi J Kidney Dis Transpl 2009;20:458-61 |
How to cite this URL:
Satish R, Gokulnath. Intractable urinary tract infection in a renal transplant recipient. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2023 Jan 30];20:458-61. Available from: https://www.sjkdt.org/text.asp?2009/20/3/458/50779 |
| Introduction | |  |
Urinary tract infection (UTI) is the most common bacterial infection occurring in the post transplant period, particularly in the early post transplant stage. UTI is associated with significant morbidity, whether it occurs in the first few months after transplantation or develops in the late post transplant period (> 6 months). Recurrent UTI is the recurrence of infection within two weeks of completion of antimicrobial therapy. A thorough evaluation of the urinary tract to look for anatomic abnormalities, appropriate antibiotic therapy and continued prophylaxis is advisable in patients with recurrent UTI. Superadded fungal UTI is not uncommon in patients with recurrent UTI and invasive fungal infection of the kidney is difficult to treat. Literature on recurrent UTI after transplant and the ideal approach to such patients is scanty. We present a renal allograft recipient with recalcitrant bacterial and complicating fungal UTI, with a brief review of fungal UTI.
| Case Report | | |
A 23 year old male patient presented to us in July 2006 with advanced renal failure and uremic symptoms. He had not had any prior medical evaluation and did not have any history of repeated UTI in childhood, no dysuria or voiding difficulty, though the urinary volume had reduced of late. On examination, he was malnourished, anemic and mildly dyspneic at rest. The pulse rate was 98 per min and blood pressure was 170/90 mmHg. Cardiovascular examination revealed loud S1, no pericardial rub or gallop rhythm and respiratory system examination revealed bilateral basal crepitations. Abdominal examination did not reveal any abnormalities and the external genitalia were normal. Investigations done revealed hemoglobin of 8.6 gm/dL, total WBC count of 6700/cu mm with normal differential count and platelet count of 1.1 lakh/cu mm. Blood urea was 213 mg/dL, serum createnine was 8.6 mg/dL, sodium was 134 meq/L, potassium was 4.7 meq/L and chloride was 101 meq/L. Liver function tests were normal. Urine analysis revealed 3 + protein, 3-5 RBC per HPF and 10-12 WBC per HPF. Culture of two midstream urine samples grew Escherechia coli with colony count of 105 per mL sensitive to first line antibiotics. Ultrasound of the abdomen revealed a single contracted ectopic pelvic kidney on the right side measuring 7.5 × 2.2 cms; the left kidney was not visualized. A computerized tomographic scan of the abdomen also failed to localize the left kidney and an MCU done did not reveal any active vesico ureteral reflux.
| Course in the Hospital | | |
The patient was hemodialyzed initially though a temporary internal jugular catheter and evaluated for a living related kidney transplant, mother being his donor. He was treated for UTI with 10 days of oral ciprofloxacin three months prior to transplant and the pre-transplant urine and blood cultures were negative. He underwent kidney transplantation on 1/12/2006 and had a smooth post-operative course with brisk diuresis and the serum creatinine reached a nadir of 0.6 mg/dL by the fifth post operative day. He was started on conventional immunosuppression with prednisolone, cyclosporine and azathioprine in view of HLA haplomatch. On the eighth post operative day, he developed high fever with chills. He had leukocytosis with a total white cell count of 14,700 per cu mm and differential count showed 89% polymorphs, 9% lymphocytes and 2% band forms. Blood and urine cultures grew E. coli. His graft functions had worsened, with serum creatinine of 2.6 mg/dL, although he was non oliguric. Graft Doppler revealed good anastomotic flow with no evidence of urinary tract obstruction and the ureteric stent was found in-situ. A diagnosis of gram negative bacteremia secondary to UTI, was made and the patient was treated with cepaperazone sulbactam for a total period of 21 days and the ureteric stent was removed. At discharge, the serum creatinine was 1.1 mg/dL and the urine culture after the course of antibiotic therapy was negative. He was put on antibiotic prophylaxis with trimethoprim-sulfamethoxazole. One week later, he presented with high grade fever and serum creatinine of 2.1 mg/dL. Blood culture was negative for bacteria and fungus, while urine culture grew E. coli. Chest radiograph was normal. CMV IgM antibody was negative. The cause of recurrent UTI was evaluated; no additional information was obtained. He responded to treatment with the same antibiotic and both the patient and graft functions showed improvement. He presented to us again one month later with a history of high grade fever associated with chills, of two days duration. At admission, his blood pressure was 90/60 mm Hg; pulse was feeble, temperature was 103°F; however, systemic examination was non contributory. He was admitted to the ITU with a presumed diagnosis of gram negative septicemia. Urine and blood cultures at this time grew Candida glabrata. His graft functions had again worsened and serum creatinine was 8.0 mg/dL. In view of systemic candidemia, intravenous amphotericin B was started along with Ticarcillin Sulbactam. He was non-oliguric and was managed conservatively. At the end of the first week after hospitalization, the graft functions had improved with a drop in creatinine to 3.5 mg/dL and the 24 hour urine output being 1.5 liters. He could not tolerate amphotericin B and developed repeated episodes of generalized seizures. A blood chemistry including calcium, magnesium, phosphorus levels was normal and CT scan of the brain as well as CSF analysis did not reveal any intra-cerebral pathology. Anti-fungal therapy was changed to intravenous voriconazole. He also had hyperglycemia, which was controlled with insulin infusions. Immunosuppression was slightly reduced given the life threatening nature of the infection. A decision was taken to perform a native kidney nephrectomy in view of the relapsing nature of the infection, although no definite evidence of infection had been found in the native kidney. He tolerated the surgery well, his general condition improved and the serum creatinine reached a baseline of 1.2 mg/dL. He received a total of 21 days treatment with voriconazole and at the end of therapy, blood fungal culture was negative. Histopathology of the nephrectomy specimen revealed evidence of chronic pyelonephritis. Also, no active neutrophilic infiltrates or fungal elements were noted. After discharge, he came for follow-up once after two weeks and was keeping fine. He then traveled to his native town where he apparently developed fever and succumbed to the illness before he could be brought to the hospital. No postmortem was done and the exact cause of death could not be ascertainned.
| Discussion | | |
Urinary tract infection is the most common bacterial infection occurring in renal transplant recipients and is seen in 30-40% of recipients [1] during the first four months after transplantation. The majority of organisms cultured are Gram negative (76%) with approximately 33% being caused by E.coli and 20% by Enterococcus and Klebsiella enterobacter. [2] The major risk factors for UTI after renal transplantation include in dwelling bladder catheters, handling and trauma to the kidney and ureter during surgery, anatomic abnormalities of the native or transplanted kidneys (such as vesicoureteral reflux, calculi or stents), neurogenic bladder especially in diabetic patients and possibly, rejection and immunosuppression. [3],[4],[5],[6],[7]
UTI in the early post transplant period is associated with significant graft dysfunction and relapse. [1] The morbidity associated with UTI appears to be related to the time of occurrence of the infection after transplantation. Infections occurring in the hospital are more serious with bacteremia occurring in approximately 10% and graft infection in 90% of recipients and these infections may be associated with allograft dysfunction and may predispose to development of acute rejection. Recurrence or re-infection occurs often with one study reporting a relapse rate of 73% in the early post-transplant period. [8]
The pre-transplant urine culture was negative in our patient; however, he had three episodes of UTI in the first month after transplant. These episodes were associated with significant graft dyfunction, which recovered once the infection was controlled. We did not perform graft biopsy in our patient, since graft functions improved with antibiotic therapy thus ruling out acute rejection.
Fungal UTI represents a high-risk event in critically ill patients. A prospective multi-centre surveillance study of 861 hospitalized patients identified risk factors such as prior antibiotic therapy (90%), urinary tract pathology (38%), urinary tract devices (83%), diabetes (39%) and malignancies (22%), for the development of fungal infections.
Our patient had received three prolonged courses of antibiotic therapy thus, predisposing him to superadded fungal infection. Invasive fungal infections contribute significantly to patient morbidity and mortality after transplantation and an incidence of 2.3-3.5% has been observed. [9],[10] Over 60% of systemic fungal infections are due to Candida species with Candida albicans being the most common organism. Prolonged fever not responding to antibiotic therapy is the commonest clinical situation and a high index of suspicion is necessary. Data from the US Renal Data System found that the majority of fungal infections occurred in the first six months posttransplant (66%) and by logistic regression analysis, it was seen that end stage renal disease due to diabetes, duration of pre-transplant dialysis, maintenance tacrolimus and allograft rejection were associated with an increased risk of developing fungal infections. [11] Recipients who had developed fungal infections had a relative risk of mortality of 2.88 when compared to other recipients. Other studies have also found a high mortality rate of 75%. [9]
The most common antifungal agents used currently for the treatment of Candidemia are amphotericin B, fluconazole and caspofungin. The choice of agent is guided by the hemodynamic stability of the patient, history of prior exposure to antifungals and the infecting Candida species. Many C. glabrata strains are resistant to fluconazole and they respond less well to therapy. The guidelines of the Infectious Disease Society of America (IDSA) recommend avoiding the use of fluconazole for the treatment of C. glabrata. [12] Amphotericin B remains, therefore, the drug of choice though caspofungin is now preferred due to its better safety profile. Intravenous or oral voriconazole has been recommended for the treatment of invasive aspergillosis, disseminated infections caused by Candida species and in patients who are refractory to, or intolerant to, other antifungal therapy. [12],[13] The appropriate duration of therapy for candidemia has not been widely studied. Serial blood cultures are advised and two weeks of therapy after blood cultures become negative has been advocated.
Certain issues are intriguing in this patient and this case is being presented to highlight a rather uncommonly encountered problem in clinical practice. The native diseased kidney can be a source of persistent infection and was hence removed in this patient. Despite this, he continued to have relapsing infection. The histopathology of the nephrectomy specimen also did not show any fungal elements. Though the final cause of death in this case remains unknown, we believe that metastatic abscesses could have led to the recurrence of infection and ultimate death of the patient.
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Correspondence Address:
Renuka Satish
Department of Nephrology, St. John’s Medical College Hospital, Sarjapura Road, Bangalore
India
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 19414951 
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