Show Me the “Mino:” In Vitro Efficacy of Minocycline on Clinical Gram-Negative Bacterial Isolates

Background: There are limited oral treatment options available for resistant Gram-negative bacterial (GNB) infections. Minocycline, a second-generation tetracycline antibiotic, offers good bioavailability and broad-spectrum coverage that may be an option for GNB infections. Methods: We conducted a retrospective review of minocycline susceptibility testing performed on GNB isolates at the Mayo Clinic reference lab between 2013 and 2022. Minocycline susceptibility was evaluated with a focus on difficult-to-treat organisms and relevant anatomic source. Organisms included resistant isolates of Escherichia coli and Klebsiella pneumoniae; high-risk ampC-derepressors, including Citrobacter freundii, Enterobacter cloacae, and K. aerogenes; and clinically challenging non-Enterobacterales, Acinetobacter species, Achromobacter species, and Stenotrophomonas maltophilia. Results: Of 217,206 GNB isolates, 18,148 Enterobacterales (EB) and 8,190 non-Enterobacter isolates were tested for minocycline susceptibility. Of these, 80% of all EB and 92% of non-EB isolates were susceptible. Among E. coli isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 78%, 76%, 70%, and 70.9%, respectively. Among the K. pneumoniae isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 46%, 38%, 37%, and 39.3%, respectively. 85% of C. freundii, 81% of E. cloacae, and 85% of K. aerogenes isolates were susceptible to Minocycline. 83.5% of Achromobacter species isolates, 66% of Acinetobacter species isolates, and 99.1% of S. maltophilia isolates were susceptible. Conclusions: Our study reports the largest collection of minocycline susceptibility findings in GNB. Minocycline showed in vitro activity against many difficult-to-treat GNB isolates, including ceftriaxone- and multidrug-resistant E. coli and some K. pneumoniae isolates, common Amp-C-producing species, and non-fermenting GNB, including Stenotrophomonas, Acinetobacter, and Achromobacter.