. Author manuscript; available in PMC: 2021 Mar 9.

Published in final edited form as: Nat Rev Microbiol. 2020 Feb 18;18(4):211–226. doi: 10.1038/s41579-020-0324-0

Table 2:

Emerging therapeutics for the treatment of urinary tract infections.

Therapeutic	Bacterial target	Disease target	Evidence
Anti-adhesives
Mannosides	UPEC; type 1 pili (FimH)	Acute cystitis	Reduced bacterial burdens in a mouse bladder following treatment and as a prophylactic agent in mouse models^53,143,144
Galactosides	UPEC; Fim-like (Fml) pili	Chronic cystitis and/or pyelonephritis	Reduced bacterial burden in the bladder and kidney in mouse models of chronic UTIs^146,172
Vaccine
FimCH	UPEC expressing type 1 pili	Acute and chronic cystitis	Phase 1 clinical trial showing no safety concerns and a reduction in total UTI recurrence in treatment cohort; approved for compassionate use as an investigational intervention¹⁵⁰
EbpA^NTD	Enterococcus species	CAUTI	Reduces bacterial titers in the bladder and catheter adhesion in in vitro mouse models¹⁵³
Four-component (Two capsular polysaccharides, mutated α-toxin, clumping factor A)	Staphylococcus species	Staphylococcal UTI	Shown efficacy in mouse models, has completed phase I clinical trials with no safety concerns¹⁵⁴
Other
NSAIDs	UPEC	Chronic and recurrent cystitis	In vivo mouse models demonstrate reduced bladder remodeling, and human clinical studies demonstrate effective resolution of symptoms with a reduction in overall antibiotic used when used in place of antibiotics^40,156–158
HIF-1α inhibition (AKB-4924)	UPEC		Decreased UPEC adherence and invasion of cultured human uroepithelial cells, decreased inflammation and bacterial load in mouse models of infection¹⁶⁰
Probiotics	UPEC	rUTI	Reduced frequency of infection in a variety of patient populations with rUTI^161–163
Lactoferrin	UPEC	Cystitis	Reduction in UPEC adherence to human bladder epithelial cell lines and reduced mouse bladder bacterial burdens following treatment with exogenous lactoferrin⁷⁰

CAUTI, catheter-associated urinary tract infection; MRSA, methicillin-resistant Staphylococcus aureus; NSAIDs, nonsteroidal anti-inflammatories; NTD, amino-terminal domain; UPEC, uropathogenic Escherichia coli; UTI, urinary tract infection.