Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 27;12(5):820.
doi: 10.3390/antibiotics12050820.

Resistance to Ceftazidime/Avibactam in Klebsiella pneumoniae KPC-Producing Isolates: A Real-Life Observational Study

Laura Campogiani  1   2 , Pietro Vitale  1 , Alessandra Lodi  2 , Alessandra Imeneo  2 , Carla Fontana  3 , Cartesio D'Agostini  4   5 , Mirko Compagno  1   2 , Luigi Coppola  1   2 , Ilaria Spalliera  1 , Vincenzo Malagnino  1   2 , Elisabetta Teti  1 , Marco Iannetta  1   2 , Massimo Andreoni  1   2 , Loredana Sarmati  1   2
Affiliations

Resistance to Ceftazidime/Avibactam in Klebsiella pneumoniae KPC-Producing Isolates: A Real-Life Observational Study

Laura Campogiani et al. Antibiotics (Basel). .

Abstract

Background: Ceftazidime/avibactam (CAZ-AVI) resistance amongst Enterobacterales is worryingly increasing worldwide. Objectives: The aim of this study was to collect and describe real-life data on CAZ-AVI-resistant Klebsiella pneumoniae (KP) isolates in our University Hospital, with the ultimate goal of evaluating possible risk factors related to the acquisition of resistance. Methods: This is a retrospective observational study, including unique Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI (CAZ-AVI-R) and producing only KPC, collected from July 2019 to August 2021 at Policlinico Tor Vergata, Rome, Italy. The pathogen's list was obtained from the microbiology laboratory; clinical charts of the corresponding patients were reviewed to collect demographic and clinical data. Subjects treated as outpatients or hospitalized for <48 h were excluded. Patients were then divided into two groups: S group, if they had a prior isolate of CAZ-AVI-susceptible KP-KPC, and R group, if the first documented isolate of KP-KPC was resistant to CAZ-AVI. Results: Forty-six unique isolates corresponding to 46 patients were included in the study. The majority of patients (60.9%) were hospitalized in an intensive care unit, 32.6% in internal medicine wards and 6.5% in surgical wards. A total of 15 (32.6%) isolates were collected from rectal swabs, representing a colonization. Amongst clinically relevant infections, pneumonia and urinary tract infections were the most commonly found (5/46, 10.9% each). Half of the patients received CAZ-AVI prior to isolation of the KP-KPC CAZ-AVI-R (23/46). This percentage was significantly higher in patients in the S group compared to patients in the R group (69.3% S group vs. 25% R group, p = 0.003). No differences between the two groups were documented in the use of renal replacement therapy or in the infection site. The clinically relevant CAZ-AVI-R KP infections (22/46, 47.8%) were all treated with a combination therapy, 65% including colistin and 55% including CAZ-AVI, with an overall clinical success of 38.1%. Conclusions: Prior use of CAZ-AVI was associated with the emergence of drug resistance.

Keywords: Klebsiella pneumoniae; ceftazidime/avibactam; multidrug resistance.

PubMed Disclaimer

Conflict of interest statement

L.C. received received honoraria for lectures from MICOM Srl and research grants from Gilead Italia, outside the submitted work. E.T. received honoraria for lectures from AbbVie, Gilead, MSD and Jannsen. M.I. received honoraria for lectures from Biogen Italia, AIM Educational, MICOM srl and research grants from Gilead Italia, outside the submitted work. M.A. received funding for membership of Advisory Boards, for the preparation of educational materials, for research and educational grants, for membership of speaker panels and for support for travel to conferences from Gilead Sciences, Janssen-Cilag, Viiv Healthcare, Merck Sharp and Dohme. Abbvie, Angelini, Pfizer, GSK, Menarini, Astra Zeneca, Moderna L.S. received a research grant from Gilead and fee for lectures and expertise from Merck, Gilead, Pfizer, non-financial interest in the subject matter or materials discussed in this manuscript. The other authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Flow chart of patients’ selection criteria.
See this image and copyright information in PMC

References

    1. European Centre for Disease Prevention and Control Antimicrobial Resistance Surveillance in Europe 2022–2020 Data. [(accessed on 28 September 2022)];2022 Available online: https://www.ecdc.europa.eu/en/publications-data/antimicrobial-resistance....
    1. Paul M., Carrara E., Retamar P., Tängdén T., Bitterman R., Bonomo R.A., de Waele J., Daikos G.L., Akova M., Harbarth S., et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine) Clin. Microbiol. Infect. 2022;28:521–547. - PubMed
    1. Tamma P.D., Aitken S.L., Bonomo R.A., Mathers A.J., van Duin D., Clancy C.J. Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa) Clin. Infect. Dis. 2021;72:e169–e183. - PubMed
    1. Tiseo G., Brigante G., Giacobbe D.R., Maraolo A.E., Gona F., Falcone M., Giannella M., Grossi P., Pea F., Rossolini G.M., et al. Diagnosis and management of infections caused by multidrug-resistant bacteria: Guideline endorsed by the Italian Society of Infection and Tropical Diseases (SIMIT), the Italian Society of Anti-Infective Therapy (SITA), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Association of Clinical Microbiologists (AMCLI) and the Italian Society of Microbiology (SIM) Int. J. Antimicrob. Agents. 2022;60:106611. - PubMed
    1. Tumbarello M., Trecarichi E.M., Corona A., DE Rosa F.G., Bassetti M., Mussini C., Menichetti F., Viscoli C., Campoli C., Venditti M., et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients with Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin. Infect. Dis. 2019;68:355–364. doi: 10.1093/cid/ciy492. - DOI - PubMed

LinkOut - more resources