Pivmecillinam, the paradigm of an antibiotic with low resistance rates in Escherichia coli urine isolates despite high consumption

Abstract

Objectives Pivmecillinam, the oral version of mecillinam, represents one of the major recommended and used antibiotics for empiric and targeted treatment of urinary tract infections in primary care in Denmark, Norway and Sweden. Mecillinam resistant mutants in Escherichia coli develop easily in vitro, but their fitness cost has been shown to be high. Methods We revisited the resistance and consumption data from the monitoring programmes in the three countries and compared pivmecillinam with ciprofloxacin from 2010 to 2020. Results Mecillinam resistance rates in Escherichia coli remained around 6% in Denmark and Norway relative to a constant consumption in Norway of 1.6–1.8 DID (defined daily doses per 1000 inhabitants per day), and even increasing in Denmark from 1.6 to 2.3 DID. In Sweden resistance was significantly lower at 4% related to the lower consumption of 0.5 DID. For ciprofloxacin, resistance rates fluctuated around 6%–12%, highest in Sweden with the highest consumption (0.8–0.6 DID) and lowest in Denmark (0.55–0.35 DID) and Norway (0.7–0.3 DID), although consumption declined significantly in all three countries. Conclusions Pivmecillinam is an example of an antibiotic, which easily develops resistance in vitro, but apparently can be used broadly in primary care without increase in resistance rates.

Nitroxoline resistance is associated with significant fitness loss and diminishes in vivo virulence of Escherichia coli

“…Thus, in this head-to-head comparison, we found NTX clearly superior in terms of its resistance development properties in vitro . It is important to mention that in vitro FoR does not necessarily reflect in vivo resistance development, which might be especially prominent for Mecillinam, which is characterized by a very high FoR in vitro but still good efficiency in clinical application, where resistance development generally seems to be rare ( 29 – 31 ). However, the most recent study from Germany identified that almost 30% of tested UTI isolates were resistant to PIV (25,850 out of 86,371) ( 9 ) raising doubts regarding the clinical efficiency of PIV.…”

Antibiotic use during pregnancy in Sweden: A nationwide utilization study covering 2007–2019

“…Beyond recommendations to avoid them during pregnancy, the minimal use of quinolones and sulfonamides may be ascribed to their restricted and conservative use, which is subject to antibiotic sensitivity testing in Sweden. Moreover, rates of resistance to pivmecillinam of Escherichia coli , the commonest uropathogen, has remained minimal despite its widespread use in primary care 30 . Phenoxymethypenicillin and amoxicillin use could be explained by other common infections, particularly respiratory infections.…”

“…Moreover, rates of resistance to pivmecillinam of Escherichia coli , the commonest uropathogen, has remained minimal despite its widespread use in primary care. 30 Phenoxymethypenicillin and amoxicillin use could be explained by other common infections, particularly respiratory infections. The observed overall decline was driven by phenoxymethylpenicillin, which had the highest prevalence of use, mirroring trends at population level in Sweden during the study period.…”

Antimicrobial activity of ceftibuten-avibactam against a global collection of Enterobacterales from patients with urinary tract infections (2021)

“…and other Enterobacterales responsible for UTI [9]. Mecillinam is also an old antibiotic that remains very active against E. coil even in regions where it is commonly used to treat UTI; however, a randomized clinical trial comparing this drug with standard of care regimes is warranted [10,11].…”