Compared with Cotrimoxazole Nitroxoline Seems to Be a Better Option for the Treatment and Prophylaxis of Urinary Tract Infections Caused by Multidrug-Resistant Uropathogens: An In Vitro Study

Abstract

The resistance of uropathogens to various antibiotics is increasing, but nitroxoline remains active in vitro against some relevant multidrug resistant uropathogenic bacteria. E. coli strains, which are among the most common uropathogens, are unanimously susceptible. Thus, nitroxoline is an option for the therapy of urinary tract infections caused by multiresistant bacteria. Since nitroxoline is active against bacteria in biofilms, it will also be effective in patients with indwelling catheters or foreign bodies in the urinary tract. Cotrimoxazole, on the other hand, which, in principle, can also act on bacteria in biofilms, is frequently inactive against multiresistant uropathogens. Based on phenotypic resistance data from a large number of urine isolates, structural characterisation of an MDR plasmid of a recent ST131 uropathogenic E. coli isolate, and publicly available genomic data of resistant enterobacteria, we show that nitroxoline could be used instead of cotrimoxazole for intervention against MDR uropathogens. Particularly in uropathogenic E. coli, but also in other enterobacterial uropathogens, the frequent parallel resistance to different antibiotics due to the accumulation of multiple antibiotic resistance determinants on mobile genetic elements argues for greater consideration of nitroxoline in the treatment of uncomplicated urinary tract infections.

Keywords: horizontal gene transfer; parallel resistance; prophylaxis of uncomplicated UTI; resistance plasmid.

Figure 1

Incidence of resistance in 35,390 E. coli, 6227 K. pneumoniae, and 5088 P. mirabilis urine strains isolated in 2018 (green, susceptible; red, MDR, i.e., resistant against penicillins, 3rd generation cephalosporins and ciprofloxacin; light red, resistant against penicillins and 3rd generation cephalosporins).

Figure 2

Susceptibility or resistance to nitroxoline among 922 urine isolates of various Enterobacterales (green, susceptible; red, resistant).

Figure 3

Multiresistance plasmid pEC394-330266-1 present in E. coli isolate EC394-330266. (a) Plasmid map (resistance genes and MGE-related genes have been highlighted in different colours). (b) Detailed structure of the MDR region of pEC394-330266-1. The different antibiotic resistance genes and multiple MGE-related genes have been indicated. The location of predicted class 1 integron structures, IS elements and conjugative transposons are given in the lower part of the figure.

Figure 4

Presence-absence matrix to visualize parallel resistance in 332 enterobacterial isolates. The presence of resistance determinants conferring resistance to 17 groups of antibiotics was detected in silico (black, resistance gene is present; white, resistance gene is absent).