Outcomes of Kidney Transplantation Using Organs From A Donor Infected with Carbapenem-Resistant Klebsiella Pneumoniae in A Chinese Hospital: A Molecular Epidemiological Study

Introduction: Although the high mortality rates and adverse events related to the post-operative infection have been extensively reported worldwide, to date, few studies have investigated the transmission of CRKP isolates between the Kidney Transplant Donors (KTDs) and Kidney Transplant Recipients (KTRs) with the aid of genetic and molecular study in mainland China. We sought to describe the antibiotic susceptibility, microbiological and clinical characteristics of CRKPs in donors and recipients admitted to our hospital, focusing on the clonal transmission between the donor and recipient in renal transplantation. Method: A retrospective analysis of clinical data of CRKP-BSIs in KTRs and the corresponding cadaveric donors admitted to a Chinese hospital in Beijing, China, between January 1, 2012 and December 31, 2017 was performed. The microbiology, clinical characteristics, antimicrobial susceptibility of both donors and recipients were analyzed. The genetic relatedness and sequencing type of the strains was determined by whole genome sequencing. Results: During the study period, there are total 297 KTRs from DCD performed in our hospital. Ten incidences of CRKP-BSIs in KTRs, and one CSKP-urinary tract infection in R3, were identi�ed, and two of them (R1, R4) from the same foreign hospital. The incidence of CRKP-BSIs in the early stage (within 3 months) following kidney transplantation (KTx) from DCD was about 2.7% (8/297). Seven KTRs (R1-2, R4, R6-8, R10) associated with rupture of renal artery, occurring on the median 19th (16th-74th) day after KTx respectively, with the rate of rupture of renal artery of 63.6% (7/11), and in R4-5, the thrombus of renal transplant artery was presented on the 43th and 13th day after KTx respectively. Besides, Seven KTRs (R1-2, R4-5, R7-8, R10) underwent excision of transplanted graft on the median 19th(14th-43th) day after the KTx respectively in order to prevention of the further spread of CRKP to the remaining vital organs. Genomic analysis showed there existed two sequence types, ST290 strains and ST11, which fell into two separate clusters, with resistant genes including NDM, KPC and other carbapenemases genes identi�ed. The bla NDM−1 gene was only detected in the ST290 isolates, while the bla KPC−1 gene detected in most isolates. Few SNPs were identi�ed in isolates from donors and recipients. Conclusions: The CRKP positive result of various cultures from DCD donors can contribute to the transmission of infection to the recipients. It is mandatory to perform pre-donation screening for CRKP colonization whether or not the result of culture, not excluding the possibility of false negativity, and, if positive, donation should be contraindicated. The effective infection control strategy was the application of combinational antibiotic scheme including ceftazidime-avibactam plus carbapenem, in conjunction with source control techniques such as allograft nephrectomy and/or thorough debridement. that 2 KTRs (R8, R10) the antibiotic salvage treatment right after the rupture of renal with the result of the recovery of dialysis. By 1 KTR (R9) died from sepsis, partly attributed to delay of application of Avibatan. 1 KTR (R11) the preemptive antibiotic therapy after noti�ed the warning of CRKP infection of the other recipient from the same donor on the 19th day post-operation, with the recovery of function of kidney. To sum up, the effective strategy to treat CRKP cadaveric donor-derived infection can be the application of combinational antibiotic therapy (Ceftazidine Avibatan+Meropenem) in conjunction with surgical source control. ceftazidime-avibactam plus carbapenem, in conjunction with source control techniques such as allograft nephrectomy and/or thorough debridement. Nevertheless, the drug toxicology, pharmacodynamics and pharmacokinetics of the new pharmacotherapeutic scheme, ceftazidime-avibactam, are required to be further investigated.