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)

被引：0

作者：

Bianco, Gabriele ^{[1
,2
]}

Boattini, Matteo ^{[2
,3
,4
]}

Lupo, Laura ^{[5
]}

Ambretti, Simone ^{[6
,7
]}

Greco, Rita ^{[8
]}

Degl'Innocenti, Linda ^{[9
]}

Ranieri, Sofia Chiatamone ^{[10
]}

Fasciana, Teresa ^{[11
]}

Mazzariol, Annarita ^{[12
,13
]}

Gibellini, Davide ^{[12
,13
]}

Antonelli, Guido ^{[14
,15
]}

Sacco, Federica ^{[15
]}

Quirino, Angela ^{[16
,17
]}

Farina, Claudio ^{[18
]}

Paglietti, Bianca ^{[19
]}

Comini, Sara ^{[3
,20
]}

Fiamma, Maura ^{[21
]}

Broccolo, Francesco ^{[1
]}

Cavallo, Rossana ^{[2
,3
]}

Costa, Cristina ^{[2
,3
]}

Gaibani, Paolo ^{[12
,13
]}

机构：

[1] Univ Salento, Dept Expt Med, Lecce, Italy

[2] Univ Hosp Citta Salute & Sci Torino, Microbiol & Virol Unit, Turin, Italy

[3] Univ Torino, Dept Publ Hlth & Paediat, Turin, Italy

[4] Lisbon Acad Med Ctr, Lisbon, Portugal

[5] Vito Fazzi Hosp, Clin Pathol & Microbiol Unit, Lecce, Italy

[6] Alma Mater Studiorum Univ Bologna, Dept Med & Surg Sci, Via Massarenti 9, I-40138 Bologna, Italy

[7] IRCCS Azienda Osped Univ Bologna, Microbiol Unit, I-40138 Bologna, Italy

[8] AORN St Anna & San Sebastiano, UOC Microbiol & Virol, I-81100 Caserta, Italy

[9] AORNA Cardarelli, Clin Pathol Div, UOS Microbiol & Virol, I-80131 Naples, Italy

[10] AUSL 04 Teramo, Dept Serv, Pathol Unit, I-64100 Teramo, Italy

[11] Univ Palermo, Dept Hlth Promot Mother & Child Care Internal Med, I-90127 Palermo, Italy

[12] Azienda Osped Univ Integrata Verona, Dept Pathol, Microbiol & Virol Unit, Verona, Italy

[13] Univ Verona, Dept Diagnost & Publ Hlth, Microbiol Sect, Verona, Italy

[14] Sapienza Univ Rome, Dept Mol Med, I-00161 Rome, Italy

[15] Sapienza Univ, Univ Hosp Policlin Umberto I, Viale Policlin 155, I-00161 Rome, Italy

[16] Magna Graecia Univ Catanzaro, Hlth Sci Dept, I-88100 Catanzaro, Italy

[17] Univ Catanzaro Magna Graecia, Dept Hlth Sci, Unit Clin Microbiol, I-88100 Catanzaro, Italy

[18] ASST Papa Giovanni XXIII, Microbiol & Virol Lab, I-24127 Bergamo, Italy

[19] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy

[20] Carlo Urbani Hosp, Operat Unit Clin Pathol, Ancona, Italy

[21] ASSL Nuoro, Osped San Francesco, Operat Unit Clin Pathol, I-08100 Sardinia, Italy

来源：

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | 2024年 / 80卷 / 02期

关键词：

CARBAPENEM; SUSCEPTIBILITY; EPIDEMIOLOGY;

D O I：

10.1093/jac/dkae450

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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 beta-lactam/beta-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.

引用

页码：583 / 592

页数：10

共 18 条

[1] In vitro activity of imipenem-relebactam against KPC-producing Klebsiella pneumoniae resistant to ceftazidime-avibactam and/or meropenem-vaborbactam
Lombardo, Donatella
Ambretti, Simone
Lazzarotto, Tiziana
Gaibani, Paolo
CLINICAL MICROBIOLOGY AND INFECTION, 2022, 28 (05) : 749 - 751
[2] In vitro synergistic activity of meropenem/vaborbactam in combination with ceftazidime/avibactam against KPC-producing Klebsiella pneumoniae
Gaibani, Paolo
Ambretti, Simone
Viale, PierLuigi
Re, Maria Carla
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2019, 74 (05) : 1457 - 1459
[3] Impact of ompk36 genotype and KPC subtype on the in vitro activity of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam against KPC-producing K. pneumoniae clinical isolates
Rogers, Tara M.
Kline, Ellen G.
Griffith, Marissa P.
Jones, Chelsea E.
Rubio, Abigail M.
Squires, Kevin M.
Shields, Ryan K.
JAC-ANTIMICROBIAL RESISTANCE, 2023, 5 (02):
[4] Review of In Vitro Efficacy of Ceftazidime-Avibactam, Meropenem-Vaborbactam and Imipenem-Relebactam in Carbapenemase Producing Klebsiella pneumoniae Isolates
Aydemir, Ozlem
Koroglu, Mehmet
Sahin, Elif Ozozen
Vural, Sevinc
MEDITERRANEAN JOURNAL OF INFECTION MICROBES AND ANTIMICROBIALS, 2023, 12
[5] Epidemiology and In Vitro Activity of Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam against KPC-Producing K. pneumoniae Collected from Bacteremic Patients, 2018 to 2020
Bovo, Federica
Lombardo, Donatella
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Gaibani, Paolo
ANTIBIOTICS-BASEL, 2022, 11 (11):
[6] Epidemiology and in vitro activity of ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, plazomicin, and comparators against Greek carbapenemase-producing Klebsiella pneumoniae isolates
Sofia Maraki
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Eleni Magkafouraki
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Dimitra Stafylaki
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Infection, 2022, 50 : 467 - 474
[7] Clonal dissemination of Klebsiella pneumoniae resistant to cefiderocol, ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam co-producing KPC and OXA-181 carbapenemase
Bovo, Federica
Amadesi, Stefano
Palombo, Marta
Lazzarotto, Tiziana
Ambretti, Simone
Gaibani, Paolo
JAC-ANTIMICROBIAL RESISTANCE, 2023, 5 (04):
[8] In Vitro Evaluation of Increasing Avibactam Concentrations on Ceftazidime Activity against Ceftazidime/Avibactam-Susceptible and Resistant KPC-Producing Klebsiella pneumoniae Clinical Isolates
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Secci, Benedetta
Bovo, Federica
Gatti, Milo
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ANTIBIOTICS-BASEL, 2023, 12 (12):
[9] Comparative In Vitro Activity of Ceftazidime-Avibactam, Imipenem-Relebactam, and Meropenem-Vaborbactam against Carbapenem-Resistant Clinical Isolates of Klebsiella pneumoniae and Pseudomonas aeruginosa
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Kalu, Michelle
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ANTIBIOTICS-BASEL, 2024, 13 (05):
[10] Correction to: Epidemiology and in vitro activity of ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, plazomicin, and comparators against Greek carbapenemase-producing Klebsiella pneumoniae isolates
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