Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales as a cause of community-acquired uncomplicated urinary tract infection (UTI) is on the rise. Currently, minimal oral treatment options exist. New combinations of existing oral third generation cephalosporins paired with clavulanate may overcome resistance mechanisms seen in these emerging uropathogens. Ceftriaxone-resistant E. coli and Klebsiella pneumoniae containing CTX-M-type ESBLs or AmpC, in addition to narrow-spectrum OXA and SHV enzymes, were selected from blood culture isolates obtained from the MERINO trial. Minimum inhibitory concentration (MIC) values of third generation cephalosporins (cefpodoxime, ceftibuten, cefixime, cefdinir) both with and without clavulanate were determined. One hundred and one isolates were used with ESBL, AmpC and narrow-spectrum OXA genes (e.g. OXA-1, OXA-10) present in 84, 15 and 35 isolates, respectively. Susceptibility to oral third generation cephalosporins alone was very poor. Addition of 2 mg/L clavulanate lowered the MIC values (cefpodoxime MIC 2 mg/L, ceftibuten MIC 2 mg/L, cefixime MIC 2 mg/L, cefdinir MIC 4 mg/L) and restored susceptibility (33%, 49%, 40%, and 21% susceptible, respectively) in a substantial number of isolates. This finding was less pronounced in isolates co-harbouring AmpC. In vitro activity of these new combinations may be limited in real world Enterobacterales isolates co-harbouring multiple antimicrobial resistance genes. Pharmacokinetic/pharmacodynamic data would be useful in further evaluating their activity.
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