Given the scarcity, or even absence, of effective therapies for the treatment of infections caused by multidrug-resistant (MDR) K. pneumoniae and/or A. baumannii in Brazil, combinations of β-lactams with next-generation β-lactamase inhibitors and tetracycline derivatives have emerged as promising antimicrobials.

To evaluate the in vitro activity of new antimicrobials against MDR isolates obtained from patients hospitalized in ICUs of six hospitals in the metropolitan region of São Paulo.

A total of 121 isolates of K. pneumoniae and 27 of A. baumannii, prospectively collected from patients hospitalized in six ICUs of the metropolitan region of São Paulo between 08/01/2023 and 10/31/2024, resistant to carbapenems, were analyzed. MICs for polymyxin B/E (POL), omadacycline (OMC), and eravacycline (ERV) were determined by broth microdilution (Sensititre, Thermo Fisher). For K. pneumoniae, 118 isolates without evidence of metallo-β-lactamase production were additionally tested for ceftazidime-avibactam (CZA), imipenem-relebactam (IMR), and meropenem-vaborbactam (MEV). Resistance genes of 55 K. pneumoniae and 21 A. baumannii were correlated with phenotypes.

The susceptibility rates of K. pneumoniae to CZA, IMR, and MEV were 87.29%, 74.58%, and 82.20%, respectively. Among the 59 isolates resistant to amikacin (AMI) and POL, these rates were 96.91%, 75.86%, and 82.76%. Applying FDA breakpoints, 6 isolates (4.96%) were resistant to OMC (MIC > 8 mg/L) and 12 (9.92%) were intermediate (8 mg/L). Even among AMI/POL-resistant isolates, OMC susceptibility was 91.53%. For ERV, the MIC₉₀ was 1 mg/L in the overall group and 2 mg/L among resistant isolates. Of the 55 genomes analyzed, 92.73% carried blaKPC-2, 3.64% blaNDM-1, and 1.82% both. Two isolates with blaNDM-1 showed favorable MICs for ERV (0.5 mg/L) and OMC (≤ 4 mg/L). In A. baumannii, MIC₅₀/MIC₉₀ values were 2/8 mg/L for OMC and 0.5/2 mg/L for ERV. Among the 10 isolates resistant to POL, OMC showed an increased MIC₉₀ to 8 mg/L, but ERV maintained a profile similar to the overall group.

K. pneumoniae strains showed excellent activity to CZA, IMR, and MEV. MDR K. pneumoniae and A. baumannii strains were also susceptible to OMC and ERV, including subgroups resistant to POL, reinforcing the potential of these drugs as therapeutic options in highly resistant settings such as Brazilian ICUs.