Evaluation of the Minimum Inhibitory Concentration of Meropenem and New Therapeutic Options for Serratia Marcescens and Morganellaceae Enterobacterales With Reduced Susceptibility to Meropenem

Serratia marcescens and Enterobacterales of the Morganellaceae family are associated with infections in different sites and exhibit an expected phenotype of resistance to several antimicrobials, making therapeutic options very limited. Meropenem in modified therapy for bacteria with minimum inhibitory concentration (MIC) < 32.0 μg/mL has been used in clinical practice, and new therapeutic options, such as meropenem-vaborbactam (MV) and ceftazidime-avibactam (CZA), have emerged as effective therapeutic alternatives. Therefore, the objective of this study was to evaluate the susceptibility to meropenem, MV, and CZA, as well as carbapenemase production, in isolates of Serratia marcescens and Morganellaceae Enterobacterales with reduced susceptibility to meropenem by disk-diffusion method, and to assess the institutional consumption of meropenem and CZA. A total of 188 bacterial isolates of S. marcescens and Morganellaceae with reduced susceptibility to meropenem, obtained from clinical samples collected in a tertiary hospital between 2021 and 2024, were analyzed. A total of 129 isolates (68.6%) presented a meropenem MIC < 32 μg/mL, with MIC50 and MIC90 of 8.0 μg/mL and 256.0 μg/mL, respectively. Of the 188 isolates evaluated, 71 were non-producers of metallo-β-lactamases. Among these, 69 (97.8%) were susceptible to CZA and 57 (80.3%) were susceptible to MV, with MIC50 of 0.5 μg/mL and MIC90 of 256.0 μg/mL. Regarding therapeutic options for non-producers of metallo-β-lactamases with meropenem MIC ≥ 32 μg/mL, 97.9% (47/48) were susceptible to CZA and 70.8% (34/48) were susceptible to MV. Meropenem consumption at the institution remained at similar levels to those observed during the COVID-19 pandemic, while CZA consumption increased significantly (p = 0.007) during the analyzed period. This study found a high percentage of isolates that, although resistant in vitro to meropenem, presented low MICs, suggesting that they could potentially be treated with meropenem in modified therapy. It also identified 14 isolates resistant to MV and 2 isolates resistant to CZA. Most studies on KPC variants resistant to MV and CZA are focused on Klebsiella pneumoniae ; therefore, it would be relevant to investigate the resistance mechanisms involved in these other species.