Author:
Hansen Bjørn Åsheim,Grude Nils,Lindbæk Morten,Stenstad Tore
Abstract
Abstract
Background
The role of oral beta-lactam antibiotics in treating febrile urinary tract infections (UTI) is not yet definite. Today, fluoroquinolones together with trimethoprim–sulfamethoxazole (TMP–MTX) are considered standard of care and often the only available evidence-based oral treatment for febrile UTI. This study clarifies the efficacy and safety of pivmecillinam (PIV) used as step-down therapy for bacteremic urinary tract infection (UTI).
Methods
A single-arm, uncontrolled treatment trial was conducted in the period September 2017–March 2020. Candidates for inclusion were men and women suffering from E. coli bacteremia due to UTI and were consecutively included in a Norwegian hospital. Exclusion criteria were among others: other ongoing bacterial infection, septic shock, pyonephrosis/abscess and pregnancy. After 3 days of parenteral antibiotic, the treatment was converted to the study drug; oral PIV 400 mg QID for 1 week. Primary endpoint was a combination of three elements; afebrility, no need for retreatment and improvement in self-reported health status. Test Of Cure (TOC) was 1 week post-treatment. Secondary endpoints included among others microbiological efficacy and CRP value < 30 mg/L.
Results
Of 476 screened subjects, 53 patients were included. Median age was 67 years, 28 (56%) were women. 50 patients were evaluated for per-protocol analysis. 44 of 50 patients (88%) (95% CI [75.7–95.5]) reached the primary endpoint on TOC. 14 of 48 patients (29.2%) had significant growth (> 103 CFU/mL) of E.coli on TOC. CRP-level was strongly associated to treatment outcome, (OR 0.006 [95% CI 0.00–0.11], p < 0.001).
Conclusions
This trial documents that PIV 400 mg QID given for 1 week following 3 days of parenteral antibiotics, is a suitable treatment option in patients suffering from bacteremic UTI due to E. coli. Randomised clinical trials studying the efficacy of PIV vs standard of care of febrile UTI are warranted.
Trial registration The trial was registered at ClinicalTrials.gov under the identifier: NCT03282006 13/09/2017 and approved by The Regional Committees for Medical Research Ethics South East Norway (2015/2384/REK sør-øst) and the Norwegian Medicines Agency (SLV; reference No 16/06018-09; EudraCT No 2016-000984-18) before initiation
Publisher
Springer Science and Business Media LLC
Reference30 articles.
1. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103–20.
2. EAU Guidelines on Urological Infections. 2018. http://uroweb.org/guidelines/compilations-of-all-guidelines/. Accessed Oct 2020.
3. EMA. Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics. 2019. https://www.ema.europa.eu/en/news/disabling-potentially-permanent-side-effects-lead-suspension-restrictions-quinolone-fluoroquinolone. Accessed Sept 2020.
4. Adriaenssens NC, Versporten S, Muller A, Minalu A, Faes G, Vankerckhoven C, Aerts V, Hens M, Molenberghs N, Goossens G. European Surveillance of Antimicrobial Consumption (ESAC): outpatient quinolone use in Europe (1997–2009). J Antimicrob Chemother. 2011;66(Suppl 6):vi47-56.
5. NORM/NORM-VET 2019. Usage of antimicrobial agents and occurrence of antimicrobial resistance in Norway. Tromsø/Oslo 2019. www.antibiotikaresistens.no. Accessed Aug 2020.
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献