Meropenem/vaborbactam
Meropenem has been combined with vaborbactam, a novel beta-lactamase inhibitor, to treat infections caused by bacteria resistant to currently available carbapenems.[70]Castanheira M, Huband MD, Mendes RE, et al. Meropenem-vaborbactam tested against contemporary Gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrug-resistant, and extensively drug-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017 Aug 24; 61: e00567-17.
http://www.ncbi.nlm.nih.gov/pubmed/28652234?tool=bestpractice.com
The US Food and Drug Administration (FDA) has approved the drug for the treatment of adults with complicated UTI, including pyelonephritis. The European Medicines Agency has also recommended approval in patients with complicated UTIs.
Plazomicin
Plazomicin is a next-generation aminoglycoside designed to evade all clinically relevant aminoglycoside-modifying enzymes, the main mechanism of aminoglycoside resistance.[71]Cox G, Ejim L, Stogios PJ, et al. Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect Dis. 2018 Jun 8;4(6):980-7.
http://www.ncbi.nlm.nih.gov/pubmed/29634241?tool=bestpractice.com
[72]Wagenlehner FME, Cloutier DJ, Komirenko AS, et al. Once-daily plazomicin for complicated urinary tract infections. N Engl J Med. 2019 Feb 21;380(8):729-40.
https://www.doi.org/10.1056/NEJMoa1801467
http://www.ncbi.nlm.nih.gov/pubmed/30786187?tool=bestpractice.com
It has been approved by the FDA for the treatment of patients 18 years of age or older with complicated UTIs, including pyelonephritis, that are caused by certain Enterobacteriaceae in patients who have limited or no alternative treatment options.
Vaccines
Vaccines against Escherichia coli and other uropathogens are a promising emerging treatment. Mucosal and parenteral vaccines targeted at E coli and other uropathogens are being investigated.[73]Stapleton A. Novel approaches to prevention of urinary tract infections. Infect Dis Clin North Am. 2003 Jun;17(2):457-71.
http://www.ncbi.nlm.nih.gov/pubmed/12848479?tool=bestpractice.com
[74]Cruz F, Dambros M, Naber KG, et al. Recurrent urinary tract infections: Uro-Vaxom, a new alternative. Eur Urol Suppl. 2009;8(9):762-8.[75]Huttner A, Hatz C, van den Dobbelsteen G, et al. Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial. Lancet Infect Dis. 2017 May;17(5):528-37.
http://www.ncbi.nlm.nih.gov/pubmed/28238601?tool=bestpractice.com
[76]Yang B, Foley S. First experience in the UK of treating women with recurrent urinary tract infections with the bacterial vaccine Uromune®. BJU Int. 2018 Feb;121(2):289-92.
http://www.ncbi.nlm.nih.gov/pubmed/29171130?tool=bestpractice.com
Vaccines targeted at E coli are not yet available for clinical use.
Lactobacillus
Vaginal lactobacilli are an important host defence against UTI. In healthy pre-menopausal women, the vaginal environment is acidic, with Lactobacillus species as the predominant bacteria. Studies to evaluate the probiotic capacity of Lactobacillus species administered by the vaginal route have been carried out in women with UTIs, with mixed but promising results.[77]Abad CL, Safdar N. The role of lactobacillus probiotics in the treatment or prevention of urogenital infections - a systematic review. J Chemother. 2009 Jun;21(3):243-52.
http://www.ncbi.nlm.nih.gov/pubmed/19567343?tool=bestpractice.com
A study showed that oral daily lactobacillus may be as effective as daily trimethoprim/sulfamethoxazole in preventing infections in patients with recurrent UTI.[78]Beerepoot MA, ter Riet G, Nys S, et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012 May 14;172(9):704-12.
http://www.ncbi.nlm.nih.gov/pubmed/22782199?tool=bestpractice.com
Currently there is no reliable product for urogenital application of lactobacillus to prevent UTIs.[79]Reid G, Bruce AW, Taylor M. Influence of three-day antimicrobial therapy and lactobacillus vaginal suppositories on recurrence of urinary tract infections. Clin Ther. 1992 Jan-Feb;14(1):11-6.
http://www.ncbi.nlm.nih.gov/pubmed/1576619?tool=bestpractice.com
[80]Baerheim A, Larsen E, Digranes A. Vaginal application of lactobacilli in the prophylaxis of recurrent lower urinary tract infection in women. Scand J Prim Health Care. 1994 Dec;12(4):239-43.
http://www.ncbi.nlm.nih.gov/pubmed/7863140?tool=bestpractice.com
D-mannose
D-mannose is a simple sugar that may hinder bacterial adhesion to the urothelium. Small studies have looked at D-mannose as a potential UTI prevention strategy.[81]Domenici L, Monti M, Bracchi C, et al. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. Eur Rev Med Pharmacol Sci. 2016 Jul;20(13):2920-5.
http://www.europeanreview.org/article/11121
http://www.ncbi.nlm.nih.gov/pubmed/27424995?tool=bestpractice.com
[82]Kranjčec B, Papeš D, Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2014 Feb;32(1):79-84.
http://www.ncbi.nlm.nih.gov/pubmed/23633128?tool=bestpractice.com
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.