Objectives: To evaluate the in vitro activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparators against KPC-producing Klebsiella pneumoniae (KPC-Kp) clinical isolates collected from a multicentre study in Italy (2022–23) and genomic characterization of the molecular mechanisms causing resistance. Methods: Consecutive KPC-Kp isolates from blood cultures (n= 264) were collected from 14 hospital centres in the period 2022–23. Antimicrobial susceptibility testing was performed using broth microdilution. WGS was used to investigate KPC-Kp strains resistant to the new approved β-lactam/β-lactam inhibitor combinations (BLICs). Results: Overall, meropenem/vaborbactam (95.1% susceptible by EUCAST and 93.9% susceptible by CLSI; MIC50 = 0.5 mg/L; MIC90 = 4 mg/L) and imipenem/relebactam (97% susceptible by EUCAST and 92.8% susceptible by CLSI; MIC50 = 0.25 mg/L; MIC90 = 0.5 mg/L) showed similar activity, followed by ceftazidime/avibactam (93.9% susceptible by both EUCAST and CLSI; MIC50 = 2 mg/L; MIC90 = 8 mg/L). Ten out of 13 (76.9%) KPC-Kp resistant to ceftazidime/avibactam carried a blaKPC variant including blaKPC-31, blaKPC-205, blaKPC-203 and blaKPC-93. Among KPC-Kp resistant to meropenem/vaborbactam and imipenem/relebactam, 90.9% (10/11) and 80% (4/5) harboured a WT carbapenemase (i.e. blaKPC-2 or blaKPC-3), respectively. All strains resistant to meropenem/ vaborbactam and/or imipenem/relebactam carried truncated OmpK35 and/or mutated (ins135GD) OmpK36. Conclusions: New BLICs were shown to be the most widely active therapeutic option against KPC-Kp clinical isolates collected in Italy. Ceftazidime/avibactam resistance is mainly driven by the expression of KPC variants, whereas the loss of function of the OmpK35 and OmpK36 porins appears to play a key but not exclusive role in the development of meropenem/vaborbactam and/or imipenem/relebactam resistance.
In vitro activity and genomic characterization of KPC-producing Klebsiella pneumoniae clinical blood culture isolates resistant to ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam: an Italian nationwide multicentre observational study (2022–23) / Bianco, G., Boattini, M., Lupo, L., Ambretti, S., Greco, R., Degl'Innocenti, L., Chiatamone Ranieri, S., Fasciana, T., Mazzariol, A., Gibellini, D., Antonelli, G., Sacco, F., Quirino, A., Farina, C., Paglietti, B., Comini, S., Fiamma, M., Broccolo, F., Cavallo, R., Costa, C., et al.. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 80:2(2025), pp. 583-592. [10.1093/jac/dkae450]
In vitro activity and genomic characterization of KPC-producing Klebsiella pneumoniae clinical blood culture isolates resistant to ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam: an Italian nationwide multicentre observational study (2022–23)
Paglietti, Bianca;Fiamma, Maura;
2025-01-01
Abstract
Objectives: To evaluate the in vitro activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparators against KPC-producing Klebsiella pneumoniae (KPC-Kp) clinical isolates collected from a multicentre study in Italy (2022–23) and genomic characterization of the molecular mechanisms causing resistance. Methods: Consecutive KPC-Kp isolates from blood cultures (n= 264) were collected from 14 hospital centres in the period 2022–23. Antimicrobial susceptibility testing was performed using broth microdilution. WGS was used to investigate KPC-Kp strains resistant to the new approved β-lactam/β-lactam inhibitor combinations (BLICs). Results: Overall, meropenem/vaborbactam (95.1% susceptible by EUCAST and 93.9% susceptible by CLSI; MIC50 = 0.5 mg/L; MIC90 = 4 mg/L) and imipenem/relebactam (97% susceptible by EUCAST and 92.8% susceptible by CLSI; MIC50 = 0.25 mg/L; MIC90 = 0.5 mg/L) showed similar activity, followed by ceftazidime/avibactam (93.9% susceptible by both EUCAST and CLSI; MIC50 = 2 mg/L; MIC90 = 8 mg/L). Ten out of 13 (76.9%) KPC-Kp resistant to ceftazidime/avibactam carried a blaKPC variant including blaKPC-31, blaKPC-205, blaKPC-203 and blaKPC-93. Among KPC-Kp resistant to meropenem/vaborbactam and imipenem/relebactam, 90.9% (10/11) and 80% (4/5) harboured a WT carbapenemase (i.e. blaKPC-2 or blaKPC-3), respectively. All strains resistant to meropenem/ vaborbactam and/or imipenem/relebactam carried truncated OmpK35 and/or mutated (ins135GD) OmpK36. Conclusions: New BLICs were shown to be the most widely active therapeutic option against KPC-Kp clinical isolates collected in Italy. Ceftazidime/avibactam resistance is mainly driven by the expression of KPC variants, whereas the loss of function of the OmpK35 and OmpK36 porins appears to play a key but not exclusive role in the development of meropenem/vaborbactam and/or imipenem/relebactam resistance.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
