Urinary tract infections in men - Emerging treatments

Cefepime/enmetazobactam

Cefepime/enmetazobactam is a combination of the fourth-generation cephalosporin cefepime with the beta-lactamase inhibitor enmetazobactam. The Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved cefepime/enmetazobactam for the treatment of adults with complicated urinary tract infections (UTIs), including pyelonephritis, caused by susceptible gram-negative microorganisms (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex) in adults. One randomized clinical trial (RCT) showed cefepime/enmetazobactam to be noninferior to, and even superior to, piperacillin/tazobactam for clinical cure and microbiologic eradication in cases of complex UTI and acute pyelonephritis.[105]

Ceftolozane/tazobactam

Ceftolozane/tazobactam is a combination of the fifth-generation cephalosporin ceftolozane with tazobactam (a beta-lactamase inhibitor). It is active against Pseudomonas, including multidrug-resistant strains, as well as many extended spectrum beta-lactamases Enterobacterales.[106] The FDA and EMA have approved ceftolozane/tazobactam for the treatment of complicated UTIs (cUTIs) in adults and children. One meta-analysis showed ceftolozane/tazobactam to be more effective in treating cUTIs than piperacillin/tazobactam.[107] The 2024 Infectious Diseases Society of America guidelines noted that newer data indicate that ceftolozane/tazobactam is likely to be effective against extended-spectrum beta-lactamase producing Enterobacterales; however, it suggested that this drug be preserved for the treatment of difficult-to-treat aeruginosa or polymicrobial infections.[81]

Tebipenem

Tebipenem is an oral carbapenem antibiotic with activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase-producing and fluoroquinolone-resistant strains. In one recent phase 3 trial, tebipenem was noninferior to ertapenem (an intravenous carbapenem antibiotic) in the treatment of cUTI and acute pyelonephritis.[108] The FDA has granted fast-track designation to the drug, but states further clinical trials are needed. Tebipenem (formulated as tebipenem pivoxil) is currently only approved in Japan.

Cefepime/taniborbactam

Cefepime/taniborbactam is an investigational combination of the fourth-generation cephalosporin cefepime with taniborbactam (a beta-lactamase inhibitor). Studies have demonstrated activity against Enterobacterales species and Pseudomonas. In one phase 3 RCT, cefepime/taniborbactam was superior to meropenem (a carbapenem antibiotic) for the treatment of cUTI that included acute pyelonephritis, with a safety profile similar to that of meropenem.[109]

Vaccines

Vaccines against E coli and other uropathogens are a promising emerging treatment. Mucosal and parenteral vaccines targeted at E coli and other uropathogens are being investigated, and oral immunostimulation with E coli extracts has proven to be a safe and effective method for preventing recurrent UTIs compared with placebo at short-term follow-up.[49][110][111][112][113] There is a high level of patient interest in vaccines for the prevention of UTIs. Vaccines targeted at E coli are not yet available for widespread clinical use in the US. MV140 (also known as Uromune®) is a polyvalent, bacterial, whole cell-based, sublingual vaccine that has been developed for prevention of recurrent UTI and is currently available under special access programs or is approved for use in some countries.[114] One systematic review looking at vaccines for the treatment of recurrent UTI noted that vaccines do seem to have a short-term role in their prevention. However, more studies are needed along with inclusion of other high-risk patient groups.[115]

D-mannose

D-mannose, found in several fruits and vegetables including cranberries, is a simple sugar that may hinder bacterial adhesion to the urothelium. One meta-analysis found D-mannose to be more effective in preventing recurrent UTIs in women than placebo and similar to antibiotic prophylaxis.[116] More studies are needed to determine whether D-mannose can be an effective aid in acute cystitis symptom management and/or as a successful prophylactic agent in a selected population.[117]

Cranberry

At this time there are no quality studies that show conclusive evidence on the use of cranberries for the treatment of UTIs. More studies in this area are needed.[118] Note that cranberry studies are difficult to interpret due to variability in the cranberry formulation, variable study populations, and varying outcome measures. There is some evidence to support soluble cranberry with a high level of proanthocyanidins in the prevention of recurrent UTIs.[119]