Sulfamethoxazole/Trimethoprim

BOSTON, May 22, 2024 /PRNewswire/ -- Researchers from Analysis Group, a global leader in health economics and outcomes research (HEOR), have coauthored a study detailing a novel framework that clinicians can use to inform antibiotic prescribing for patients with E. coli-caused uncomplicated urinary tract infections (uUTIs), the most common outpatient infection in the US. The study, published in the journal Clinical Infectious Diseases, is the first to use predictive modeling to categorize patient risk profiles for antimicrobial resistance (AMR) as low, moderate, and high risk across four commonly prescribed antibiotic classes for uUTI. Despite guideline recommendations from the Infectious Diseases Society of America (IDSA) on appropriate first-line antibiotic agents for the treatment of uUTI, 86% of patients are prescribed antibiotic agents that are not considered first-line therapies. These inappropriate prescribing practices contribute to the growth of AMR, treatment failure, persistent uUTI symptoms, adverse patient health outcomes, and increased health care costs. This study was conducted to help provide clinicians with more reliable and efficient approaches for supporting patients with uUTI. Using electronic health record data from 87,487 patients with confirmed E. coli-related uUTI in the US, study investigators developed and validated predictive models to estimate probabilities of E. coli AMR to four commonly prescribed classes of antibiotics for uUTIs (nitrofurantoin, trimethoprim-sulfamethoxazole, β-lactams, and fluoroquinolones). The models identified key predictors of AMR and were used to create a novel risk categorization framework for contextualizing patients' risk for AMR. The predictive models were found to outperform those in existing literature, and the risk categorization framework provided strong separation of risk between patients with truly resistant and truly not resistant E-coli isolates. The study, "Development of Predictive Models to Inform a Novel Risk Categorization Framework for Antibiotic Resistance in E. coli-Causing Uncomplicated Urinary Tract Infection," was published in April by Clinical Infectious Diseases. Investigators included Analysis Group Managing Principals Lisa Pinheiro and Jimmy Royer, Managers Kalé Kponee-Shovein and Chi Gao, Associate Malena Mahendran, and Senior Research Professional Fernando Kuwer; Ryan K. Shields of the University of Pittsburgh; Richard Colgan of the University of Maryland School of Medicine; and Ashish V. Joshi, Fanny S. Mitrani-Gold, Patrick Schwab, Diogo Ferrinho, Madison T. Preib, and Jennifer Han of GSK. Funding for this study was provided by GSK. To learn more about Analysis Group's HEOR capabilities, visit About Analysis Group's HEOR, Epidemiology & Market Access Practice Founded in 1981, Analysis Group is one of the largest international economics consulting firms, with more than 1,200 professionals across 14 offices. Analysis Group's health care experts apply analytical expertise to health economics and outcomes research (HEOR), clinical research, market access and commercial strategy, and health care policy engagements, as well as drug safety-related engagements in epidemiology. Analysis Group's internal experts, together with our network of affiliated experts from academia, industry, and government, provide our clients with exceptional breadth and depth of expertise and end-to-end consulting services globally. Contact: Analysis Group Eric Seymour, +1 978 273 6049 [email protected] SOURCE Analysis Group

Nearly half of women will get a urinary tract infection in their lifetime. For the first time in more than 20 years the FDA has approved an antibiotic to treat the condition. For the first time in more than 20 years, the FDA has approved a treatment for uncomplicated urinary tract infections (uUTI). And the nod has come for an oral antibiotic that has been available in Europe for more than 40 years. It’s an odd set of circumstances and a dose of foresight by Utility Therapeutics that bring Pivya (pivmecillinam) to the market in the United States in the therapy’s golden years. The London-based company was formed specifically to develop and commercialize pivmecillinam in the U.S. where antimicrobial resistance is growing to standard of care antibiotics. The decreased “utility” of first-line antibiotics and the void the company is attempting to fill in the U.S. were the inspiration of the name of the company. And the void is significant as more than 30 million uUTIs are diagnosed every year in the U.S., with nearly half of all women contracting the infection at some point in their life. Outside of hospital setting, UTIs account for more antibiotic use than any other disorder. In 2018, Utility inked a licensing agreement with LEO Pharma, acquiring the U.S. rights to pivmecillinam and its subcutaneous formulation mecillinam, which the company has submitted for approval as a first-line therapy for complicated urinary tract infections (cUTI) in the hospital setting. The difference between cUTIs and uUTIs is that the former has reached the kidneys while the latter is limited to the bladder. “The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective and Pivya will provide an additional treatment option for uncomplicated UTIs,” Peter Kim, M.D., the director of the Division of Anti-Infectives at the FDA’s Center for Drug Evaluation and Research, said in a release. The year that Utility acquired the rights to pivmecillinam and mecillinam, the FDA signed off on each as a Qualified Infectious Disease Product (QIDP). The status is extended to antibacterial and antifungal drug candidates intended to treat serious or life-threatening infections. When a QIDP treatment is approved, it gains an additional five years of market exclusivity. On the same day in January, when Utility revealed that the FDA had accepted the company’s new drug applications for pivmecillinam and mecillinam, it also announced it had received private funding from the AMR Action Fund. The global initiative—which was established by several prominent drugmakers including Amgen, Bayer, Eli Lilly, GSK, Novo Nordisk and Roche—invests in the development of new antimicrobial therapeutics. In addition to being a prodrug, which means that it is not pharmacologically active until it is digested and absorbed into the system, Pivya has a unique mechanism of action, targeting penicillin binding protein-2 in the cell wall of gram-negative bacteria. Pivya’s efficacy was assessed in separate trials versus placebo, an oral antibacterial and ibuprofen. The primary measure of efficacy in the studies was the composite response rate, which included clinical cure (resolution of the symptoms of the uUTI that were present in patients at trial entry and no new symptoms) and microbiological response (demonstration that the bacteria cultured from patients’ urine at trial entry was reduced). In the placebo trial, 62% of the participants who received Pivya achieved composite response compared to 10% of those on placebo. In the oral antibacterial trial, 72% of the subjects who received Pivya achieved composite response versus 76% of those on the comparator. In the third trial, 66% of the subjects who received Pivya achieved composite response compared to 22% of those on ibuprofen.  Commonly prescribed drugs for uUTIs in the U.S. are bactrim (sulphamethoxazole/trimethoprim), nitrofuranatoin and fluoroquinolones. But more than 1 in 5 who receive these are resistant, which can lead to progression of the disease, including life-threatening sepsis. Last month, Germany’s Allecra Therapeutics scored FDA approval for its antibiotic Exblifep, which is a combination of cephalosporin antibacterial cefepime and the beta-lactamase inhibitor enmetazobactam, to treat cUTI. The approval came days after the U.S. regulator rejected another combo therapy in the same indication from Venatorx Pharmaceuticals and Melinta Therapeutics.