Minimum inhibitory concentration distribution of Mecillinam in clinical Staphylococcus saprophyticus isolates from Europe

Abstract

Objectives: Staphylococcus saprophyticus ( S. saprophyticus ) is the second most common bacteria causing uncomplicated urinary tract infections (UTIs). It is considered non-susceptible to mecillinam, with no defined breakpoint and only few available minimal inhibitory concentration (MIC) observations. However, this consideration does not correlate with clinical outcome. With this study, we aimed to provide a comprehensive MIC distribution analysis of mecillinam for S. saprophyticus , which could be useful for determining potential breakpoints. Methods: We studied 112 isolates of S. saprophyticus from human urine samples from 4 European countries. The broth microdilution and MIC test strip methods were used to determine mecillinam MIC. Results: Broth microdilution MICs ranged from 4 to >= 256 mg/L, with a binary clustering at 32 to 64 and >= 256 mg/L. The MICs were duplicated for each isolate with similar results. The MIC distribution from the test strip method aligned well with the results from the broth microdilution method. Disc diffusion test yielded an 8 mm inhibitory zone in three isolates with MIC of 32 mg/L. Conclusions: Considering mecillinam concentration in the urine usually reach 200 mg/L in conventional treatment, the clinical success frequently seen with pivmecillinam treatment for UTIs caused by S. saprophyticus may be explained by the MIC cluster of 32 to 64 mg/L. This cluster might be identified by an 8 mm inhibitory zone in disc diffusion tests. Clinical studies with MIC data are needed to examine potential breakpoints. As of now, clinicians should not switch empirical pivmecillinam treatment to other antibiotics based solely on the presence of S. saprophyticus. (c) 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. (c) 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial ( http://creativecommons.org/licenses/by/4.0/ )