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Molecular analysis of clinical isolates of ceftazidime-avibactam-resistant Klebsiella pneumoniae.
Clin Microbiol Infect. 2021 Jul; 27(7):1040.e1-1040.e6.CM

Abstract

OBJECTIVES

To analyse the strains collected during a 1-year survey of ceftazidime-avibactam-resistant KPC-producing Klebsiella pneumoniae, in order to investigate the molecular mechanisms potentially responsible for their resistant phenotype.

METHODS

Clinical KPC-producing K. pneumoniae isolates were collected from 31 patients in six different hospitals in Rome. For eight of the patients, an additional strain grown before the start of treatment was also available, bringing the total of isolates studied to 39. Antimicrobial susceptibility was determined by automated system, broth microdiluition and E-test as appropriate. In silico analysis of acquired resistance genes was achieved by whole-genome sequencing, while multilocus sequence typing and core genome multilocus sequence typing were employed for molecular typing. Mutations associated with ceftazidime-avibactam resistance were identified by Sanger sequencing of the blaKPC gene. Possible mutations in OmpK35 and OmpK36 outer membrane proteins were also investigated.

RESULTS

Molecular analyses highlighted the circulation of the ST512, 101 and 307 high-risk clones; 26 of the 31 patients carried a mutated KPC variant, five had a wild-type KPC-3. Among the KPC variants detected, 11 were different mutations within the blaKPC-3 gene, four of which were novel mutational changes.

CONCLUSIONS

Different mutations including single amino-acid substitutions, insertions or deletions within the blaKPC gene were found in 26/31 ceftazidime-avibactam-resistant KPC-producing K. pneumoniae strains belonging to high-risk clones circulating in Italy. Of note, in 14/31 cases the isolates displayed resistance to both ceftazidime-avibactam and carbapenems, raising concerns for the possible selection of a multidrug-resistant phenotype.

Authors+Show Affiliations

National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.San Filippo Neri Hospital, Rome, Italy.Santa Lucia Hospital, Rome, Italy.S. Eugenio Hospital, Rome, Italy.TorVergata University, Rome, Italy.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy. Electronic address: carla.nisii@inmi.it.National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33775814

Citation

Venditti, Carolina, et al. "Molecular Analysis of Clinical Isolates of Ceftazidime-avibactam-resistant Klebsiella Pneumoniae." Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, vol. 27, no. 7, 2021, pp. 1040.e1-1040.e6.
Venditti C, Butera O, Meledandri M, et al. Molecular analysis of clinical isolates of ceftazidime-avibactam-resistant Klebsiella pneumoniae. Clin Microbiol Infect. 2021;27(7):1040.e1-1040.e6.
Venditti, C., Butera, O., Meledandri, M., Balice, M. P., Cocciolillo, G. C., Fontana, C., D'Arezzo, S., De Giuli, C., Antonini, M., Capone, A., Messina, F., Nisii, C., & Di Caro, A. (2021). Molecular analysis of clinical isolates of ceftazidime-avibactam-resistant Klebsiella pneumoniae. Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, 27(7), e1-e6. https://doi.org/10.1016/j.cmi.2021.03.001
Venditti C, et al. Molecular Analysis of Clinical Isolates of Ceftazidime-avibactam-resistant Klebsiella Pneumoniae. Clin Microbiol Infect. 2021;27(7):1040.e1-1040.e6. PubMed PMID: 33775814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular analysis of clinical isolates of ceftazidime-avibactam-resistant Klebsiella pneumoniae. AU - Venditti,Carolina, AU - Butera,Ornella, AU - Meledandri,Marcello, AU - Balice,Maria Pia, AU - Cocciolillo,Giulio Cesare, AU - Fontana,Carla, AU - D'Arezzo,Silvia, AU - De Giuli,Chiara, AU - Antonini,Mario, AU - Capone,Alessandro, AU - Messina,Francesco, AU - Nisii,Carla, AU - Di Caro,Antonino, Y1 - 2021/03/26/ PY - 2020/10/02/received PY - 2021/03/08/revised PY - 2021/03/17/accepted PY - 2021/3/30/pubmed PY - 2021/3/30/medline PY - 2021/3/29/entrez KW - Antibiotic-resistance KW - Ceftazidime/avibactam resistance KW - KPC mutations KW - Klebsiella pneumoniae KW - Molecular typing SP - 1040.e1 EP - 1040.e6 JF - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases JO - Clin Microbiol Infect VL - 27 IS - 7 N2 - OBJECTIVES: To analyse the strains collected during a 1-year survey of ceftazidime-avibactam-resistant KPC-producing Klebsiella pneumoniae, in order to investigate the molecular mechanisms potentially responsible for their resistant phenotype. METHODS: Clinical KPC-producing K. pneumoniae isolates were collected from 31 patients in six different hospitals in Rome. For eight of the patients, an additional strain grown before the start of treatment was also available, bringing the total of isolates studied to 39. Antimicrobial susceptibility was determined by automated system, broth microdiluition and E-test as appropriate. In silico analysis of acquired resistance genes was achieved by whole-genome sequencing, while multilocus sequence typing and core genome multilocus sequence typing were employed for molecular typing. Mutations associated with ceftazidime-avibactam resistance were identified by Sanger sequencing of the blaKPC gene. Possible mutations in OmpK35 and OmpK36 outer membrane proteins were also investigated. RESULTS: Molecular analyses highlighted the circulation of the ST512, 101 and 307 high-risk clones; 26 of the 31 patients carried a mutated KPC variant, five had a wild-type KPC-3. Among the KPC variants detected, 11 were different mutations within the blaKPC-3 gene, four of which were novel mutational changes. CONCLUSIONS: Different mutations including single amino-acid substitutions, insertions or deletions within the blaKPC gene were found in 26/31 ceftazidime-avibactam-resistant KPC-producing K. pneumoniae strains belonging to high-risk clones circulating in Italy. Of note, in 14/31 cases the isolates displayed resistance to both ceftazidime-avibactam and carbapenems, raising concerns for the possible selection of a multidrug-resistant phenotype. SN - 1469-0691 UR - https://www.unboundmedicine.com/medline/citation/33775814/Molecular_analysis_of_clinical_isolates_of_ceftazidime_avibactam_resistant_Klebsiella_pneumoniae_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1198-743X(21)00135-X DB - PRIME DP - Unbound Medicine ER -