Effect of the urinary pH in urinary tract infections in kidney transplant recipients

Abstract

Urinary tract infection remains a major problem in kidney recipients because of the related high incidence and the economical costs. Most of the last studies keep on showing that most symptomatic events and asymptomatic bacteriuria have no influence on the graft survival, mortality, rejection, renal function, or any other adverse outcomes when bacteriuria occur after the firsts months of transplantation. As well, screening and treating asymptomatic bacteriuria on this special population seems without benefit after that time. So on, we need to change our standard management and establish antibiotic stewardship programs in this field. Apart from that, there is low data about the gold-standard of the empirical antibiotic treatment, alternative antibiotics or non-antimicrobial strategies for the management of UTI events, recurrent UTIs, security of the short regimens, and the use of new drugs against multidrug resistant uropathogens (like fosfomycin-trometamol). New clear data about UTI events in the kidney transplant background would help in the improvement of the management, lowering the associated costs, and secondarily raising recipients’ life quality.

Ciprofloxacin and fosfomycin are two antibiotics commonly used against this type of infections in clinical practice. However, resistance to ciprofloxacin is becoming worrisome. In addition, there is a lack of data using fosfomycin in renal transplant recipients. Recently, it has been described the presence of low-level-resistant bacteria to ciprofloxacin and fosfomycin in urine samples, with minimal inhibitory concentrations under the resistant breakpoint. In the ciprofloxacin case, low-level-resistant strains are able to acquire full resistance in in vitro environments like acidic urine, anaerobic media, or sub-optimal antibiotic concentrations, leading ultimately to treatment failure. The acidic and anaerobic media would have the opposite effect with fosfomycin. But no data about it has been reported yet, neither its low-level-resistant strains rate.

We suggest that the antibiotic chosen, the physiological urine conditions, and the low-level-resistant population rate participation, might be responsible for the antimicrobial failure due to resistances development when treating uropathogens in vivo. In this context, this thesis describes a prospective observational clinical study in renal recipients to demonstrate and elucidate the role of acidic pH in urine and low-level-resistant mutants, when receiving ciprofloxacin or fosfomycin. It is mainly focused in bacteriuria by Escherichia coli, which is the most frequent uropathogen aetiology.