Efficacy and Safety of Oral Fosfomycin for Asymptomatic Bacteriuria in Kidney Transplant Recipients: Results from a Spanish Multicenter Cohort

Abstract

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 – 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended‐spectrum β‐lactamase‐producing Enterobacterales [20.4%] and carbapenem‐resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 – 48.9) for the whole cohort and 42.3% (95%CI: 31.2 – 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 – 5.29; P-value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 – 41.35; P-value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.

Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children

“…Furthermore, it is hard to tell if the other adverse reactions reported (fatigue, anorexia, dyspnea and tachycardia) were caused by the antibiotic itself, rather than by the concomitant medications and clinical conditions. These data are consistent with the current literature, which shows a favorable safety profile of fosfomycin, with adverse reactions generally mild and not requiring discontinuation of treatment, [22][23][24][25] although studies in exclusively pediatric populations are still scarce. 26 Our study has many limitations.…”

Extended‐spectrum β‐lactamase‐producing and carbapenem‐resistant Enterobacterales bloodstream infection after solid organ transplantation: Recent trends in epidemiology and therapeutic approaches

“…Half of the isolates had an MDR phenotype (ESBL‐E in 14.0%, CRE in 3.5%), although the odds of microbiological cure were not decreased in these episodes (71.4%) 114 . Similar results have been also reported for asymptomatic bacteriuria within the first post‐transplant months 115 . Concordant with these observational experiences, the administration of a single 4‐g dose of intravenous fosfomycin disodium before the placement or removal of a urinary catheter or a double‐J ureteral stent resulted in a lower incidence of symptomatic UTI or asymptomatic bacteriuria during the first weeks after KT as compared with placebo 116 .…”

“…114 Similar results have been also reported for asymptomatic bacteriuria within the first post-transplant months. 115 Concordant with these observational experiences, the administration of a single 4-g dose of intravenous fosfomycin disodium before the placement or removal of a urinary catheter or a double-J ureteral stent resulted in a lower incidence of symptomatic UTI or asymptomatic bacteriuria during the first weeks after KT as compared with placebo. 116 Evidence supporting the use of intravenous fosfomycin for serious GNB infection is still emerging.…”

Asymptomatic Bacteriuria in Kidney Transplant Recipients—A Narrative Review

“…Only a single study of 185 KTx recipients showed that untreated ASB was significantly more likely to be followed by a subsequent episode of symptomatic UTI in the same organism in comparison to cases of treated ASB [ 40 ]. In a recently published study by Ruiz-Ruigomez, which assessed the rate of microbiological eradication after treatment of ASB episodes with fosfomycin, the treatment failure rate exceeded 40% [ 55 ]. Moreover, the routine use of trimethoprim-sulfametoxazole prophylaxis did not reduce the prevalence of ASB [ 53 ].…”