Urinary Tract Infections in Kidney Transplant Patients Due to Escherichia coli and Klebsiella pneumoniae-Producing Extended-Spectrum β-Lactamases: Risk Factors and Molecular Epidemiology

Abstract

Urinary tract infection (UTI) is a common complication after kidney transplantation, often associated to graft loss and increased healthcare costs. Kidney transplant patients (KTPs) are particularly susceptible to infection by Enterobacteriaceae-producing extended-spectrum β-lactamases (ESBLs). A retrospective case-control study was conducted to identify independent risk factors for ESBL-producing Escherichia coli and Klebsiella pneumoniae in non-hospitalized KTPs with UTI. Forty-nine patients suffering from UTI by ESBL-producing bacteria (ESBL-P) as case group and the same number of patients with UTI by ESBL negative (ESBL-N) as control-group were compared. Clinical data, renal function parameters during UTI episodes, UTI recurrence and relapsing rate, as well as risk factors for recurrence, molecular characterization of isolates and the respective antimicrobial susceptibility profile were evaluated. Diabetes mellitus (p <0.007), previous antibiotic prophylaxis (p=0.017) or therapy (p<0.001), previous UTI (p=0.01), relapsing infection (p=0.019) and patients with delayed graft function after transplant (p=0.001) represented risk factors for infection by ESBL positive Enterobacteriaceae in KTPs. Interestingly, the period of time between data of transplantation and data of UTI was shorter in case of ESBL-P case-group (28.8 months) compared with ESBL-N control-group (50.9 months). ESBL-producing bacteria exhibited higher resistance to fluoroquinolones (p=0.002), trimethoprim-sulfamethoxazole (p<0.001) and gentamicin (p<0.001). Molecular analysis showed that bla CTX-M was the most common ESBL encoding gene (65.3%), although in 55.1% of the cases more than one ESBL gene was found. In 29.4% of K. pneumoniae isolates, three bla-genes (bla CTX-M-bla TEM-bla SHV) were simultaneously detected. Low estimated glomerular filtration rate (p=0.009) was found to be risk factor for UTI recurrence. Over 60% of recurrent UTI episodes were caused by genetically similar strains. UTI by ESBL-producing Enterobacteriaceae in KTPs represent an important clinical challenge regarding not only hospitalized patients but also concerning outpatients.

Antibiotic Prophylaxis Is Associated with Subsequent Resistant Infections in Children with an Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection

“…Again, our sample size precluded an examination of specific prophylactic agents. Consistent with other studies, 66% of subsequent isolates were concordant with the index isolates (9,11,12). This finding suggests a persistent reservoir of resistant bacteria, likely in the gastrointestinal tract or the genitourinary tract, which was not eliminated during the treatment of the preceding infection.…”

“…Reported rates of subsequent ESC-R infections range between 16% and 45% (7)(8)(9)(10)(11), but few studies have evaluated potential risk factors for subsequent ESC-R infections (9,12). In our prior single-center study, we identified the receipt of Ն14 days of antibiotics in the previous 91 days as an independent predictor for subsequent ESC-R urinary tract infection (UTI) in children.…”

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

“…38 , 39 Bacteria from the family Enterobacteriaceae , particularly Escherichia coli , have been associated with increased systemic lipopolysaccharides 136 , increased risk of obesity, inflammation, reduced glomerular filtration rate, increased serum cystatin C and insulin resistance. 71 , 137 , 138 …”

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“…The prevalence of urinary tract infections is approximately 5% to 36% and may reach up to a 60% during the first year after transplant. 1,2 Immunosuppressive medications are the major causes of infections among organ transplant recipients. 3 Early diagnosis of urinary infections improves long-term graft survival.…”