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CASE REPORT
Year : 2020  |  Volume : 14  |  Issue : 3  |  Page : 255-256

Fosfomycin for post-renal transplant urinary tract infection: Re-emergence of an old drug - a Case report


Department of Nephrology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

Date of Submission03-May-2020
Date of Acceptance07-Jun-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. Sanjay Vikrant
Department of Nephrology, Indira Gandhi Medical College, Shimla, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_39_20

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  Abstract 


Urinary tract infection (UTI) is a common problem in renal transplant recipients (RTR). It is challenging to treat UTI in RTR, as they are immunosuppressed, prone to allograft dysfunction, and can have adverse drug interactions due to the concomitant use of other immunosuppressant drugs. The UTI in RTR may present as asymptomatic bacteriuria (ASB), cystitis, pyelonephritis, or asymptomatic allograft dysfunction. Many times, UTI is caused by drug-resistant organisms, making it difficult to treat and also limiting the choice of empirical and specific antimicrobial therapy. Besides this, the treatment of ASB is controversial in RTR. Fosfomycin is an old drug which is re-emerging as an empirical antibiotic for UTI. Herein, we report a patient with multidrug-resistant ASB, within 1st month of transplant treated successfully with a single dose of fosfomycin.

Keywords: Asymptomatic bacteriuria, fosfomycin, renal transplant recipient, urinary tract infection


How to cite this article:
Jaryal A, Vikrant S. Fosfomycin for post-renal transplant urinary tract infection: Re-emergence of an old drug - a Case report. Indian J Transplant 2020;14:255-6

How to cite this URL:
Jaryal A, Vikrant S. Fosfomycin for post-renal transplant urinary tract infection: Re-emergence of an old drug - a Case report. Indian J Transplant [serial online] 2020 [cited 2020 Oct 23];14:255-6. Available from: https://www.ijtonline.in/text.asp?2020/14/3/255/296893




  Introduction Top


Urinary tract infection (UTI) is quite common in renal transplant recipients (RTR). It can be symptomatic or asymptomatic. Asymptomatic bacteriuria (ASB) is defined as the presence of bacteriuria without any local or systemic signs or symptoms of UTI. It is more common in 1st-year post-renal transplant and is presumed to increase the risk of UTI.[1] The incidence of ASB in RTR varies from 17% to 51%.[1] In one study, two or more episodes of ASB were one of the independent predictors of allograft pyelonephritis (AGP).[2] With this background, we describe a patient of multi drug-resistant ASB within 1st month of renal transplant, treated with single-dose fosfomycin with long-term remission.


  Case Report Top


We report a 40-year-old female who underwent blood group compatible, live-related renal transplant at our institute. She had negative panel reactive antibodies, negative donor-specific antibodies, negative complement-dependent cytotoxicity crossmatch assay, and HLA match was 5/10. No induction was used, and maintenance immunosuppression consisted of tacrolimus, mycophenolate, and prednisolone, and she achieved normal allograft function after transplant. She had the renal stone disease as a cause of her end-stage renal disease with a history of symptomatic UTIs in the native kidneys and was treated for the same a week before transplant with antibiotic injection. She was on co-trimoxazole prophylaxis post-transplant. In 3rd week post-transplant, her routine urine examination showed 15–20 pus cells/high-powered field with positive nitrite and leukocyte esterase test, and urine culture grew Enterococcus and Klebsiella pneumonia on two separate occasions. She had normal allograft function at that point of time. Drug sensitivity showed that Klebsiella pneumonia was resistant to ampicillin, levofloxacin, piperacillin + tazobactam, amikacin, cefotaxime, and imipenem, whereas enterococcus was resistant to ampicillin, gentamicin, levofloxacin, tetracycline, vancomycin, and linezolid and both the organisms were sensitive only to fosfomycin. It was decided to treat the patient with fosfomycin 3 g single oral dose, as she had multiple, multidrug-resistant pathogens causing UTI and was within 1 month of her renal transplant. Subsequent urine analysis did not show any pus cells and repeat urine culture was also sterile. Over a period of the next 6 months, she did not have any UTI and continued to have normal allograft function.


  Discussion Top


There is a paucity of the evidence whether to treat or not to treat ASB in RTR. Choosing to treat or not to treat has to be weighed against the risk of AGP, graft dysfunction, acute rejection, and the emergence of drug resistance. Drug resistance, including multidrug-resistance is an emerging problem in RTR, causing ASB and UTI. Co-trimoxazole is a first-line suggested drug for prophylaxis against UTI in the first 6 months of the renal transplant by kidney diseases improving global outcomes guidelines.[3] Still, few of the RTR may develop ASB and UTI even on co-trimoxazole.[4] Infectious disease society of America currently recommends against testing for ASB in RTR after 1 month of transplant but does not have any recommendation, for or against of screening and treatment of ASB within 1 month of a kidney transplant.[5]

Hence, there is an ambiguity to treat or not to treat ASB in RTR. It can be more challenging if this ASB is caused by drug-resistant organisms. In our patient, ASB was caused by multidrug-resistant organisms sensitive to fosfomycin only. Fosfomycin is a re-emerging drug in the management of UTI due to its safety and efficacy against urinary pathogens, including drug/multidrug-resistant organisms. It is a bacterial cell wall synthesis inhibitor. Fosfomycin tromethamine is now a preferred formulation of fosfomycin with oral bioavailability varying from 33% to 44%. It achieves biologically relevant distribution in various tissues, including kidneys, prostate, bladder, CSF, lung, bones, and abscesses.[6] It is phosphoenolpyruvate analog and acts by irreversibly inhibiting the enzyme enolpyruvyl transferase, the cytosolic enzyme required for initial steps of peptidoglycan synthesis.[7] Its site of action is different from other cell wall synthesis inhibitors such as beta-lactams and glycopeptides. Due to its unique mechanism of action, the chances of cross-resistance are minimal. Fosfomycin has negligible protein binding, freely water-soluble, not metabolized, minimal drug interactions, and is passed unchanged in the urine (60% after oral and 90% after intravenous) and feces (10%). Oral fosfomycin has an elimination half-life of 3.6–8.28 h.[6],[7] It does not require any dose modification in the elderly, pregnant, and those with hepatic or renal dysfunction.[7] However, according to some authors, elimination half-life of fosfomycin is prolonged to up to 50 h in those with renal failure, especially with creatinine clearance <40 ml/min.[6] A single 3 g dose of fosfomycin is sufficient to achieve efficacious urinary concentration and is optimal for most uncomplicated UTIs. However, multi-dose fosfomycin has also been used successfully for treating complicated and drug-resistant UTIs.[6],[7],[8]

Fosfomycin is active against gram-positive, gram-negative, and drug-resistant bacteria, including many urinary pathogens. This makes it a good choice to deal with UTI and even drug-resistant pathogens in RTR. ASB is one of the UTI syndromes. Although the treatment of ASB in post-renal transplant is controversial, many would treat it (in one study treated 74.6% of the time)[9] and more so if it is in the early post-transplant period and if there is associated allograft dysfunction.[2],[4] Post renal transplant UTI is associated with allograft dysfunction, and many times, UTI can be clinically asymptomatic due to the concomitant use of immunosuppressant drugs. Hence, it may be prudent to treat ASB in RTR, especially in the early post-transplant period. Fosfomycin is old but re-emerging drug to manage various syndromes of UTI in RTR because of its wide spectrum, including activity against multidrug-resistant pathogens, ease of administration, and safe drug interaction profile.

Declaration of patient consent

The authors certify that they have obtained all appropriate 10 patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Coussement J, Scemla A, Abramowicz D, Nagler EV, Webster AC. Antibiotics for asymptomatic bacteriuria in kidney transplant recipients. Cochrane Database Syst Rev 2018;2:CD011357.  Back to cited text no. 1
    
2.
Fiorante S, Fernández-Ruiz M, López-Medrano F, Lizasoain M, Lalueza A, Morales JM, et al. Acute graft pyelonephritis in renal transplant recipients: Incidence, risk factors and long-term outcome. Nephrol Dial Transplant 2011;26:1065-73.  Back to cited text no. 2
    
3.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009;9 Suppl 3:S1-155.  Back to cited text no. 3
    
4.
Olenski S, Scuderi C, Choo A, Bhagat Singh AK, Way M, Jeyaseelan L, et al. Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia. BMC Nephrol 2019;20:479.  Back to cited text no. 4
    
5.
Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis 2019;68:e83-110.  Back to cited text no. 5
    
6.
Dijkmans AC, Zacarías NVO, Burggraaf J, Mouton JW, Wilms EB, van Nieuwkoop C, et al. Fosfomycin: Pharmacological, clinical and future perspectives. Antibiotics (Basel) 2017;6:24.  Back to cited text no. 6
    
7.
Zhanel GG, Walkty AJ, Karlowsky JA. Fosfomycin: A first-line oral therapy for acute uncomplicated cystitis. Can J Infect Dis Med Microbiol 2016;2016:2082693.  Back to cited text no. 7
    
8.
Qiao LD, Zheng B, Chen S, Yang Y, Zhang K, Guo HF, et al. Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: An uncontrolled, open-label, multicentre study. BMJ Open 2013;3:e004157.  Back to cited text no. 8
    
9.
Bohn BC, Athans V, Kovacs CS, Stephany BR, Spinner ML. Impact of asymptomatic bacteriuria incidence and management post-kidney transplantation. Clin Transplant 2019;33:e13583.  Back to cited text no. 9
    




 

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