Associate Professor Jackrapong Bruminhent, MD.
Division of Infectious Diseases
Department of Medicine, Faculty of Medicine Ramathibodi Hospital
Mahidol University
Bangkok, Thailand

Most renal transplant recipients could develop infections immediately after the transplant or later within a few months or years afterward.¹ Urinary tract infection (UTI) is the most common posttransplant complication leading to significant morbidities such as prolonged hospitalization, allograft rejection, and occasional mortality.^1,2 The use of immunosuppressants is required to maintain renal allograft; however, exposure to these drugs could place patients at risk of recurrent UTI and opportunistic infections.

Antimicrobial prophylaxis and treatment are the mainstays of UTI management after renal transplantation. However, long-term use often leads to antimicrobial resistance, posing further treatment challenges.^3,4 Pre-transplant evaluation and management of risk factors and improving long-term UTI outcomes are key treatment goals in renal transplant patients.⁴

Associate Professor Jackrapong Bruminhent shares insights into assessing and managing infections post renal transplantation, considering concomitant use of immunosuppressants.

Q1: What are some of the most common infections in posttransplant patients – please describe the infections requiring immediate medical intervention.

Apart from opportunistic infections, UTI is commonly encountered after renal transplantation. The manifestation could be ranging from asymptomatic infection, cystitis, allograft pyelonephritis to complicated conditions such as peri-allograft abscess or bloodstream infection. More importantly, UTI in renal transplant patients is considered a complicated infection due to the complexity of the urological anatomy from the transplant and the underlying immunosuppressive condition. Therefore, immediate intervention is essential to achieve a favorable outcome.

Q2: Several factors, including patient age, type of transplant and medical history may predict response to UTI treatment. What are some of your key considerations when selecting antimicrobial options for transplant recipients?

Antimicrobial agents that provide adequate pathogen coverage, significant urinary excretion, tolerable side effects, convenient administration, and fewer interactions with concurrent immunosuppressive agents are required and needed for consideration.

Importantly, local epidemiology is important to assist clinicians in selecting appropriate antimicrobial agents. For example, extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are responsible for approximately 60-70% of all UTIs in our setting.⁵ We typically start empirical antibiotic therapy with group 2 carbapenems, then later de-escalate to group 1 carbapenems once the urine culture identifies the pathogen and its susceptibility. Furthermore, oral antibiotic agents that provide broader coverage, especially ESBL-producing Enterobacterales, have been in consideration lately in UTI management, especially new generation fluoroquinolones such as sitafloxacin. An oral antibiotic regimen could offer clinicians an option for step-down therapy after a prolonged course of intravenous antibiotic therapy during hospitalization. Microbiological and clinical cure rates among immunocompetent patients diagnosed with acute pyelonephritis initially treated with intravenous carbapenems then switched to oral sitafloxacin as step-down therapy compared to an entire course of carbapenems therapy was studied and seemed to be comparable.⁶ Hence a study on immunocompromised patients such as renal transplant recipients is encouraged to be explored.

Q3: What proportion of your transplant recipients develop recurrent UTIs, and what is the treatment goal, especially when dealing with antimicrobial resistance?

Significant proportions of renal transplant recipients could experience recurrent UTIs and managing this complicated infection could be challenging in clinical practice. Therefore, the goal of treatment for renal transplant recipients who are struggling with recurrent infections is to correct the cause and source of infection, which is mainly related to the genitourinary prosthetic devices or vesicoureteral reflux. Additionally, antimicrobial agents that provide coverage for multi-drug resistant organisms are also essential parts of the management to achieve a successful outcome.

Q4: How do you mitigate risks associated with concomitant use of immunosuppressants and antimicrobials? How do you consider appropriate treatment options, dosing and delivery and are patients routinely monitored for adverse reactions?

Optimizing immunosuppressants is always crucial in renal transplant patients to balance the immunity for allograft protection and infection avoidance. For that reason, providing antimicrobial with appropriate coverage, optimal dosing, and adequate targeted organ penetration is the cornerstone. Tolerable adverse reactions are an advantage during routine monitoring. Furthermore, antimicrobial agents with fewer interactions with concurrent immunosuppressants are vital in avoiding severe adverse reactions or fluctuation of immunosuppressive levels. Sitafloxacin could potentially be an option since the medication has no inhibitory effect on Cytochrome P450 3A4, the primary enzyme for the metabolism of calcineurin inhibitors and mTOR inhibitors.⁷

Q5: As the urinary microbiota gets further characterised, how will treatment approaches likely evolve to address antimicrobial resistance in posttransplant UTI patients?

Urinary microbiota could potentially predict those colonized with multidrug-resistant gram-negative bacteria prior to developing UTI after renal transplant. Therefore, these data could potentially assist clinicians in selecting the right antibiotic based on their urinary microbiota.

References

1. Lenski S, et al. BMC Nephrol. 2019; 20(479).
2. Fiorentino M, et al. J Nephrol. 2019;32(5):751-761.
3. Nambiar P, Silibovsky R & Belden KA (2018). ‘Infection in kidney transplantation’. Contemporary Kidney Transplantation. Springer International Publishing AG. 307-327.
4. Hollyer I & Ison MG. Transpl Infect Dis. 2017; 20(2):e12828.
5. Siritip N, et al. Am J Med Sci. 2021 Mar;361(3):352-357.
6. Malaisri C, et al. J Infect Chemother 2017;23:556-62.
7. Bhagat V. Indian J Crit Care Med. 2021 Jan;25(1):67-76.