Oral Antibiotics in Clinical Development for Community-Acquired Urinary Tract Infections

The treatment of urinary tract infections (UTIs) has been complicated by the emergence of multidrug-resistant, beta-lactamase-expressing pathogens. As a result of the limited treatment options, patients often require hospitalization and intravenous therapy. In essence, a strong unmet need for oral antibiotics, active against extended-spectrum beta-lactamase (ESBL) uropathogens has emerged. Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/beta-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI. Tebipenem, if approved, will be the first oral treatment for complicated UTI while sulopenem will be for uncomplicated UTI. The beta-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins. The combination ceftibuten-QPX7728 has potential broad-spectrum coverage against carbapenemase producers including metallo beta-lactamase producers. Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniae carbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy.

Automated summary

The treatment of urinary tract infections is complicated by multidrug-resistant pathogens expressing beta-lactamase. The emergence of oral antibiotics active against extended-spectrum beta-lactamase uropathogens is needed, with various drugs in clinical development. These new drugs have potential broad-spectrum coverage against resistant strains and will strengthen outpatient therapy.