Maria Teresa Mascellino
Session Speaker
Prof. Maria Teresa Mascellino is an Associate Professor in the Department of Public Health and Infectious Diseases at Sapienza University of Rome, Italy, where she specializes in Clinical Microbiology. She has published more than 120 scientific papers and serves as a reviewer and editorial board member for several international journals.
Her research interests include antimicrobial resistance, carbapenem-resistant pathogens, β-lactamases, the human microbiome, Clostridium difficile infection, colorectal cancer, probiotics, COVID-19, and vaccines. She is a member of ESCMID and the American Society for Microbiology (ASM) and has received recognition for her contributions to scientific publishing and peer review.
Abstract : In vitro activity of fosfomycin against ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae
In recent years, strains of KPC-producing Klebsiella pneumoniae resistant to ceftazidime/avibactam (CZA) have emerged, with in some of these, recovery of meropenem sensitivity (MEM). Knowledge about optimal therapeutic regimens is scarce. Aim of the study was to analyze the in-vitro activity of different antimicrobials focusimg on the microbiological activity of fosfomycin (FOS)-containing combinations against CZA-resistant KPC-producing
K. pneumoniae.
CZA-resistant KPC-Kp strains with resistance or susceptibility to MEM were collected. FOS susceptibility was performed by the agar dilution method whereas for CZA, MEM, meropenem/vaborbactam (MVB) and imipenem/relebactam (IMI/REL) susceptibility, gradient strips were used. The synergistic activity of the FOS-based combinations (MEM+FOS, CZA+FOS, MVB+FOS) was evaluated by gradient strip-agar diffusion method with fixed concentrations of FOS (0.125xMIC and 0.25xMIC). A synergistic interaction was defined as FICI ≤ 0.5. Molecular determination of KPC variants and Whole-Genome Sequencing (WGS) were performed.
A total of 18 KPC-Kp strains were included (10 strains CZA-resistant and MEM-susceptible and 8 KPC-Kp resistant to both CZA and MEM). Seventeen of the 18 strains were susceptible to FOS. Ten out of 18 strains showed full susceptibility to MEM (overall MIC50/90 3/24 µg/mL), eight strains were resistant to MEM. All strains were susceptible to MVB (overall MIC50/90 0.094/1.5 µg/mL) and resistant to CZA (overall MIC50/90 48/>256 µg/mL). Synergy of MEM+FOS was observed in 10/18 (55%), 4/10 in MEM-susceptible and 6/10 in MEM-resistant strains. Inhibition of bacterial growth was present at sub-inhibitory concentrations of FOS in all strains. CZA+FOS showed synergism in 9/18 (50%), with the majority being observed in CZA resistant MEM-resistant KPC-Kp strains (66%). MVB+FOS showed synergism in 4/18 (22%), only in the CZA-resistant MEM-resistant KPC-Kp strains.
Molecular characterisation of the strains: The analysis of the mgrB gene shows that two strains have a mutation that generally confers resistance to colistin while the genes encoding the two main porins, OmpK35 and OmpK36, showed structural alterations and several mutations in almost all the strains.
The addition of FOS to MEM and CZA showed synergism in 55% and 50% of the tested strains, respectively, even in CZA and MEM-resistant strains, whereas the synergism MVB+FOS was lower. FOS+MEM may represent a possible therapeutic option for infections due to CZA-resistant and MEM-susceptible strains while the role of FOS + MVB or IMI/REL should be further investigated.