The Expert Committee noted the recent data from the Global Antimicrobial Resistance Surveillance System which indicate very high levels of resistance to amoxicillin of E. coli in urinary tract infections, and that for this reason the empiric use of amoxicillin for treatment of lower urinary tract infections is now discouraged in multiple international treatment guidelines.
The Committee therefore recommended that the indication of treatment of lower urinary tract infections be removed from the listings of amoxicillin on the EML and EMLc.
Amoxicillin was recommended as a first-choice treatment option for empiric treatment of lower urinary tract infections in adults and children in 2017, as part of the comprehensive review of antibiotics for common infectious syndromes (1).
The EML and EMLc currently include alternative first-choice treatment options for lower urinary tract infection (nitrofurantoin, sulfamethoxazole + trimethoprim, amoxicillin + clavulanic acid, and single-agent trimethoprim).
Public health relevance
Lower urinary tract infections are very common worldwide and can affect people of any age. According to the Global Burden of Disease study, in 2017 for all ages and both sexes combined, an estimated 274 million new cases of urinary tract infections (lower and upper) occurred globally (2). The incidence of urinary tract infections is highest in women and increases with age and frequency of sexual activity. However, after 65 years of age, rates of lower urinary tract infections in men and women tend to be more similar (3).
Evidence supporting the requested change relies on data from a 2020 report by the Global Antimicrobial Resistance Surveillance System (GLASS) on global antimicrobial resistance (4). GLASS data from 22 countries indicate that a median of 75% (range 45–100%) of Escherichia coli urinary isolates are resistant to amoxicillin.
In addition, the empiric use of amoxicillin for treatment of lower urinary tract is explicitly discouraged in multiple guidelines because of high rates of antimicrobial resistance to amoxicillin (5–7).
GLASS data are not reported for amoxicillin + clavulanic acid or nitrofurantoin. However, several sources indicate that susceptibility of E. coli in urinary isolates remains generally high, in both adults and children (8–10). GLASS data indicate a median of 55% (range 40–70%) of E. coli urinary isolates are resistant to sulfamethoxazole + trimethoprim (4).
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2. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.
3. Tandogdu Z, Wagenlehner FM. Global epidemiology of urinary tract infections. Curr Opin Infect Dis. 2016;29(1):73–9.
4. Global antimicrobial resistance surveillance system (GLASS) report: early implementation 2020. Geneva: World Health Organization; 2020 (https://apps.who.int/iris/handle/10665/332081, accessed 13 August 2021).
5. Urological infections [internet]. Arnhem: European Association of Urology; 2020 (https://uroweb.org/guideline/urological-infections/#3, accessed 13 August 2021).
6. Diagnostic et antibiothérapie des infections urinaires bactériennes communautaires de l’adulte [Diagnosis and antibiotic therapy for community bacterial urinary tract infections in adults]. Paris: Société de Pathologie Infectieuse de Langue Française; 2015 (https://www.infectiologie.com/UserFiles/File/spilf/recos/infections-urinaires-spilf-argumentaire.pdf, accessed 13 August 2021).
7. 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.
8. Bruyndonckx R, Latour K, Atud GA, Dubovy P, Jaspers S, Hens N, et al. Time trend of prevalence and susceptibility to nitrofurantoin of urinary MDR Escherichia coli from outpatients. J Antimicrob Chemother. 2019;74(11):3264–7.
9. Sanchez GV, Baird AM, Karlowsky JA, Master RN, Bordon JM. Nitrofurantoin retains antimicrobial activity against multidrug-resistant urinary Escherichia coli from US outpatients. J Antimicrob Chemother. 2014;69(12):3259–62.
10. Bryce A, Hay AD, Lane IF, Thornton HV, Wootton M, Costelloe C. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis. BMJ. 2016;352:i939.