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Evaluation of Factors Predictive of Efficacy Among Patients With Complicated Urinary Tract Infection and/or Acute Pyelonephritis.
Open Forum Infect Dis
September 2024
Spero Therapeutics, Inc., Cambridge, Massachusetts, USA.
Background: Antibiotic treatment for complicated urinary tract infections (cUTI)/acute pyelonephritis (AP) is often followed by recurrent bacteriuria in the absence of clinical symptoms. To understand factors predictive of clinical and microbiologic outcomes in patients with cUTI/AP, multivariable analyses were undertaken using pooled data from a global, phase 3 cUTI study.
Methods: Using data from 366 tebipenem pivoxil hydrobromide- and 378 ertapenem-treated patients from the Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) infected with Enterobacterales uropathogens, multivariable analyses for dichotomous efficacy endpoints were performed using logistic regression and pharmacokinetic-pharmacodynamic relationships were evaluated.
Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.
Sci Immunol
March 2024
Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the basis for these bacteria-independent bladder symptoms, we examined the bladders of patients with rUTI.
View Article and Find Full Text PDFSecretory leukocyte protease inhibitor protects against severe urinary tract infection in mice.
mBio
February 2024
Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Millions suffer from urinary tract infections (UTIs) worldwide every year with women accounting for the majority of cases. Uropathogenic (UPEC) causes most of these primary infections and leads to 25% becoming recurrent or chronic. To repel invading pathogens, the urinary tract mounts a vigorous innate immune response that includes the secretion of antimicrobial peptides (AMPs), rapid recruitment of phagocytes, and exfoliation of superficial umbrella cells.
View Article and Find Full Text PDFImpact of antibiotic pharmacokinetics in urine on recurrent bacteriuria following treatment of complicated urinary tract infections.
Antimicrob Agents Chemother
October 2023
Institute for Clinical Pharmacodynamics, Inc. , Schenectady, New York, USA.
The clinical relevance of bacteriuria following antibiotic treatment of complicated urinary tract infections in clinical trials remains controversial. We evaluated the impact of urine pharmacokinetics on the timing of recurrent bacteriuria in a recently completed trial that compared oral tebipenem pivoxil hydrobromide to intravenous ertapenem. The urinary clearance and urine dwell time of ertapenem were prolonged relative to tebipenem and were associated with a temporal difference in the repopulation of bladder urine with bacteria following treatment, potentially confounding the assessment of efficacy.
View Article and Find Full Text PDFSulopenem: An Intravenous and Oral Penem for the Treatment of Urinary Tract Infections Due to Multidrug-Resistant Bacteria.
Drugs
April 2022
Clinical Microbiology, Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, Health Sciences Centre, University of Manitoba, MS673-820 Sherbrook Street, Winnipeg, Manitoba, MB, R3A 1R9, Canada.
Sulopenem (formerly known as CP-70,429, and CP-65,207 when a component of a racemic mixture with its R isomer) is an intravenous and oral penem that possesses in vitro activity against fluoroquinolone-resistant, extended spectrum β-lactamases (ESBL)-producing, multidrug-resistant (MDR) Enterobacterales. Sulopenem is being developed to treat patients with uncomplicated and complicated urinary tract infections (UTIs) as well as intra-abdominal infections. This review will focus mainly on its use in UTIs.
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