Urinary tract drugs
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Advances in Urinary Tract Drugs: Efficacy, Safety, and Emerging Therapies
Lower Urinary Tract Symptoms (LUTS) in Older Adults: Drug Efficacy and Safety
FORTA Classification of LUTS Drugs
A systematic review aimed at evaluating the efficacy, safety, and tolerability of drugs used for treating lower urinary tract symptoms (LUTS) in older adults has highlighted significant findings. The Fit fOR The Aged (FORTA) classification was used to categorize these drugs. Notably, no drug was rated as indispensable (FORTA-A). However, dutasteride, fesoterodine, and finasteride were classified as beneficial (FORTA-B) 1. The majority of drugs, including darifenacin, mirabegron, and extended-release oxybutynin, were rated as questionable (FORTA-C), while alfuzosin, doxazosin, and immediate-release oxybutynin were advised against (FORTA-D) 1.
Emerging Therapies for Urinary Tract Infections (UTIs)
Antibiotic Resistance and New Drug Development
Urinary tract infections (UTIs) are prevalent and often lead to high morbidity and mortality, especially due to the rise of multidrug-resistant (MDR) uropathogens. The FDA has encouraged the development of new antibiotics to combat these resistant strains. Current research is focused on both approved antibiotics and emerging therapies in phase II and III trials, particularly for complicated UTIs (cUTIs) 2. Despite the development of new drugs, many lack a full spectrum of activity against MDR Gram-negative organisms, such as Pseudomonas aeruginosa 2.
Non-Antibiotic Therapeutic Options
Given the global emergence of MDR uropathogens, there is a pressing need for alternative non-antibiotic therapies. Research has explored various phases of UTI pathogenesis, including colonization and pathogen adherence. Promising non-antibiotic treatments include vaccines, small compounds, nutraceuticals, immunomodulating agents, probiotics, and bacteriophages. Among these, Lactobacillus-containing products and cranberry products with propolis have shown the most robust results 7.
Combination Drug Therapy for LUTS
Efficacy of Combination Therapies
Combination drug therapies have been studied for their efficacy in treating LUTS in both men and women. The most researched combination is the α1-adrenoceptor antagonist/5α-reductase inhibitor, which has shown significant efficacy, particularly in men with moderate-to-severe LUTS at risk of disease progression. Another effective combination is antimuscarinics (e.g., solifenacin) with mirabegron, which has shown improvements in urinary incontinence and urgency without a significant increase in adverse events 4.
Revisiting Older Antimicrobials
Role of Older Antimicrobials
The resurgence of older antimicrobials like temocillin, fosfomycin, mecillinam, methenamine, and cycloserine is being considered due to the rise in MDR pathogens. These older drugs have shown effectiveness against resistant strains and offer a potential solution in the current antibiotic resistance crisis 6. Specifically, nitrofurantoin and fosfomycin have been highlighted for their high urinary concentrations and minimal toxicity, making them viable options for treating uncomplicated UTIs 8.
Methenamine for Recurrent UTIs
Methenamine, a forgotten drug, is gaining attention for its role in preventing recurrent UTIs, especially in the context of MDR. It is FDA-approved and can be used as methenamine hippurate or methenamine mandelate. Its unique antiseptic properties make it a valuable option when conventional antibiotics fail 10.
Conclusion
The landscape of urinary tract drugs is evolving with a focus on both new and old therapies to combat the rising challenge of multidrug resistance. While some drugs for LUTS in older adults are beneficial, many remain questionable or should be avoided. Emerging therapies and the revival of older antimicrobials offer promising alternatives to traditional antibiotics, highlighting the need for continued research and development in this critical area of healthcare.
Sources and full results
Most relevant research papers on this topic
Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014)
Dutasteride, fesoterodine, and finasteride are beneficial for older individuals with lower urinary tract symptoms, while most other drugs are questionable or should be avoided.
Systematic Review
Rigorous Journal
Highly CitedAn update on emerging therapies for urinary tract infections
Emerging therapies for urinary tract infections show promise, but most lack full spectrum activity against multidrug-resistant organisms like Pseudomonas aeruginosa.
Systematic ReviewDrug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections
Urinary tract infections (UTI) cause significant morbidity and require alternative therapeutic and preventative strategies, with new drugs and vaccines needed to combat multi-drug resistant pathogens and address recurrence.
Highly CitedSystematic Review of Combination Drug Therapy for Non-neurogenic Lower Urinary Tract Symptoms.
Combination therapy, such as 1-adrenoceptor antagonist/5-reductase inhibitor combination, may improve lower urinary tract symptoms in men and women without increasing adverse events.
Systematic ReviewOral immunotherapy of recurrent urinary tract infections: a double-blind placebo-controlled multicenter study.
Oral immunotherapy with bacterial extract effectively reduces recurrent urinary tract infections and their associated symptoms, while maintaining good tolerance and reducing the need for antibiotics.
RCTHighly CitedRole of old antimicrobial agents in the management of urinary tract infection
Older antimicrobial agents, such as temocillin, fosfomycin, mecillinam, methenamine, and cycloserine, may still be useful in managing urinary tract infections, highlighting the need for rational use and antibiotic stewardship.
Systematic ReviewAlternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections
Lactobacillus-containing products and cranberry products in conjunction with propolis show the most promising non-antibiotic alternatives to antibiotics for treating urinary tract infections.
Nitrofurantoin and fosfomycin for resistant urinary tract infections: old drugs for emerging problems.
Nitrofurantoin and fosfomycin are potential treatment options for resistant urinary tract infections, offering high urinary concentrations and minimal toxicity compared to newer antibiotics.
Highly CitedTreatment and Prevention of Urinary Tract Infection with Orally Active FimH Inhibitors
Mannoside compounds effectively treat and prevent urinary tract infections in mice, potentially bypassing antibiotic resistance and improving treatment options for women with chronic UTIs.
Highly CitedMethenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era
Methenamine may be an effective preventive therapy for recurrent urinary tract infections in the era of multidrug resistance, offering unique antibacterial properties.
Highly Cited