1678. Activity of mecillinam against urinary tract clinical isolates from the United States during 2017-2020 including isolates resistant to comparator antibiotics and multi-drug resistant isolates


 
 
 Mecillinam is a first-in-class amidinopenicillin antibiotic, being the only β-lactam to exert its antibacterial activity through exclusive binding to penicillin-binding protein 2. Pivmecillinam is the oral prodrug of mecillinam recommended as a first-line therapy by the Infectious Disease Society of America guidelines for uncomplicated urinary tract infections (uUTIs) and is approved for the treatment of uUTI in Europe and Canada though not yet in the USA. To support the clinical development of mecillinam and pivmecillinam in the USA for the treatment of cUTI and uUTI, this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolates from patients with UTI in the US during 2017-2020
 
 
 
 A total of 3303 Enterobacterales clinical isolates from UTIs from hospitals throughout the USA during 2017-2020 were tested. MIC tests were performed by agar dilution in line with CLSI susceptibility testing standards.
 
 
 
 Overall, susceptibility was highest for fosfomycin (97.1% susceptible) and mecillinam (94.9% susceptible). Against isolates resistant to ceftriaxone, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim/sulfamethoxazole susceptibility to mecillinam was high with 89.6 %, 90.9 %, 82.4 %, 86.7 % and 93.6 %, respectively. Only fosfomycin exhibited similar activity to mecillinam. The most active antibiotics against MDR Enterobacterales were fosfomycin (86% susceptible) and mecillinam (79.2 % susceptible). Of the 288 MDR Enterobacterales, the majority were E. coli (n = 128) and K. pneumoniae (n = 103). The most active agents against MDR E. coli and MDR K. pneumoniae were fosfomycin and mecillinam that had susceptibilities of 93.8 % and 92.2 % and 79.6 % and 72.8 %, respectively.
 
 
 
 Mecillinam exhibited promising activity against the majority of Enterobacterales tested. The drug was notably active against isolates resistant to antibiotics in routine clinical use and notably was similarly active against many MDR isolates. The data from our study strongly support the clinical utility of mecillinam and pivmecillinam in the USA for the treatment of cUTI and uUTI.
 
 
 
 Anne Santerre Henriksen, PhD, UTILITY therapeutics Ltd: Advisor/Consultant.
