β-Lactam therapy for potential AmpC-producing organisms: a cohort study and an updated systematic review and meta-a#nalysis

Background: Certain organisms, including Serratia, Providentia, Acinetobacter, Citrobacter, Enterobacter, and Morganella species (SPACE-M) may possess an inducible broad-spectrum β-lactamase, AmpC, which is not inhibited by most β-lactamase inhibitors. Our objective was to determine whether treating SPACE-M bloodstream infections (BSI) with potentially hydrolyzable β-lactams was associated with increased risk of 30-day mortality. Methods: A retrospective cohort study was performed including all adult cases of bacteremia attributed to SPACE-M species between April 2010 and June 2015 at the McGill University Health Centre (Montreal, Canada). We used multivariable logistic regression to estimate the odds ratio (OR) of death or recurrence within 30 days for potentially hydrolyzable β-lactams vs. other therapies. We then updated a systematic review and meta-analysis comparing carbapenems to β-lactam/β-lactamase inhibitors (BL/BLIs). We included studies published up to December 31, 2017 and calculated the unadjusted OR for mortality within 30 days comparing BL/BLI vs. carbapenems as definitive therapy. Results: Over the 5-year period, there were 173 BSI involving SPACE-M organisms at our center. After adjusting for patient comorbidities and severity of the initial illness, the use of hydrolyzable β-lactams as definitive therapy was not associated with an increased risk of death or recurrence when compared with other antimicrobial agents (OR 1.20, 95% CI 0.40–3.62). The meta-analysis further suggested that patients treated with BL/BLI therapy have similar outcomes to those treated with carbapenems (30-day mortality OR 1.13, 95% CI 0.58–2.20). Conclusion: The use of β-lactam/β-lactamase inhibitors may remain a viable carbapenem-sparing option for patients with potential AmpC-producing organisms.