#3722 CARBAPENEM-RESISTANT ENTEROBACTERIACEAE URINARY TRACT INFECTION IN RENAL TRANSPLANT RECIPIENTS: ROLE OF A NOVEL ANTIBIOTIC REGIMEN
Authors: Bhadauria Dharmandr , Veeranki Vamsidhar 
Published: June 2023

Abstract

Background and Aims
Urinary tract infection (UTI), the most common bacterial infection among renal transplant recipients (RTRs), remains a challenge, particularly given the increased incidence of MDR organisms, including Carbapenem-resistant Enterobacteriaceae (CRE). CRE infections were associated with inferior patient and graft outcomes compared to other bacterial infections. Paradoxically, there have been no guidelines on managing CRE in RTRs besides multiple challenges, including the bacteriostatic nature, poor urinary concentration, and dose-limiting adverse effects of various antibiotics. The current study designed and assessed the outcomes of protocol-based therapy consisting of high-dose Meropenem in combination with other antibiotics followed by prolonged oral administration.

Method
This is a single-centre retrospective study conducted in the department of Nephrology and Renal transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, India, between 1st August 2016 till 31st July 2022. All the RTRs aged $ \ge $ 18 years admitted between 1st August 2016 and 31st July 2018 with symptomatic UTI and a urine culture positive for CRE were included in the study. Patients who received various antibiotics conventionally based on the treating physician's decision from August 2016 to July 2017 were considered under the Best available treatment (BAT) group, while the Standardized Therapeutic Antibiotic Regimen (STAR) group included patients treated from August 2017 to July 2018. The treatment of the STAR group consists of a therapeutic phase for at least six weeks (IV therapeutic phase for two weeks total or one week after the clinical recovery, whichever is later + Oral Therapeutic phase for four weeks) followed by an oral chemoprophylaxis phase for three months. Following the treatment of index UTI episodes due to CRE, follow-up both groups’ follow-up data until a minimum of four years were collected. Appropriate statistical tools were applied, and analyses were performed by SPSS software, version 25.

Results
A total of 37 patients fulfilling the inclusion criteria were included in the study, of which 13 patients were under the BAT group, and 24 were treated by the STAR-based protocol. The mean age of the study population was 37.6 $ \pm \ $12.3 years, and all were males. Most patients (70.2%) had the UTI due to CRE within one-month post-transplant, and the median duration of UTI post-transplant was 6.1 days (IQR: 4.5 – 33). The primary outcome, recurrence rates of UTI at 48-month follow-up among the patients in the STAR group, was significantly lower than those in the BAT group (30.4% vs 77.8%, p = 0.01). The death-censored graft survival was also significantly better among the STAR group than the BAT group (100% vs 75%, p = 0.03) after 48 months. Graft function at 48 months was also better in the STAR group (Serum creatinine- 1.4 ± 0.8 mg/dl vs 2.9 ± 2.2 mg/dl, p = 0.007). The patient survival, however, was similar among the two groups (95.8% vs 88.9%, p = 0.47).

Conclusion
Prolonged and combination antibiotic therapy followed by long-term antibiotic prophylaxis significantly reduced the recurrence of UTI due to CRE among the RTRs. Graft function and death-censored graft survival were also considerably better. Hence, the current study may pave the path for future RCTs based on combination antibiotic therapy as a solution to combat the challenge of CRE in RTRs.