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Evaluation of in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against MDR Pseudomonas aeruginosa isolates from Qatar
Örebro University, School of Science and Technology. Microbiology Division, Hamad Medical Corporation, Doha, Qatar. (The Life Science Centre)
Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar.
Division of General Medicine, Wayne State University, Detroit, MI, USA.
Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar.
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 12, p. 3497-3504Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To investigate the in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against clinical isolates of MDR Pseudomonas aeruginosa from Qatar, as well as the mechanisms of resistance.

METHODS: MDR P. aeruginosa isolated between October 2014 and September 2015 from all public hospitals in Qatar were included. The BD PhoenixTM system was used for identification and initial antimicrobial susceptibility testing, while Liofilchem MIC Test Strips (Liofilchem, Roseto degli Abruzzi, Italy) were used for confirmation of ceftazidime/avibactam and ceftolozane/tazobactam susceptibility. Ten ceftazidime/avibactam- and/or ceftolozane/tazobactam-resistant isolates were randomly selected for WGS.

RESULTS: A total of 205 MDR P. aeruginosa isolates were included. Of these, 141 (68.8%) were susceptible to ceftazidime/avibactam, 129 (62.9%) were susceptible to ceftolozane/tazobactam, 121 (59.0%) were susceptible to both and 56 (27.3%) were susceptible to neither. Twenty (9.8%) isolates were susceptible to ceftazidime/avibactam but not to ceftolozane/tazobactam and only 8 (3.9%) were susceptible to ceftolozane/tazobactam but not to ceftazidime/avibactam. Less than 50% of XDR isolates were susceptible to ceftazidime/avibactam or ceftolozane/tazobactam. The 10 sequenced isolates belonged to six different STs and all produced AmpC and OXA enzymes; 5 (50%) produced ESBL and 4 (40%) produced VIM enzymes.

CONCLUSIONS: MDR P. aeruginosa susceptibility rates to ceftazidime/avibactam and ceftolozane/tazobactam were higher than those to all existing antipseudomonal agents, except colistin, but were less than 50% in extremely resistant isolates. Non-susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam was largely due to the production of ESBL and VIM enzymes. Ceftazidime/avibactam and ceftolozane/tazobactam are possible options for some patients with MDR P. aeruginosa in Qatar.

Place, publisher, year, edition, pages
Oxford University Press, 2019. Vol. 74, no 12, p. 3497-3504
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:oru:diva-78572DOI: 10.1093/jac/dkz379ISI: 000501732800012PubMedID: 31504587Scopus ID: 2-s2.0-85075093622OAI: oai:DiVA.org:oru-78572DiVA, id: diva2:1377648
Funder
Swedish Research Council Formas, 219-2014-837
Note

Funding Agencies:

Medical Research Centre at Hamad Medical Corporation, Doha, Qatar  IRGC-01-51-033

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA

NIH National Institute of Allergy & Infectious Diseases (NIAID) R01AI100560 R01AI063517 R01AI072219

Cleveland Department of Veterans Affairs from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development  1I01BX001974

Cleveland Department of Veterans Affairs from the Geriatric Research Education and Clinical Center VISN 10  1I01BX001974

Available from: 2019-12-12 Created: 2019-12-12 Last updated: 2020-11-24Bibliographically approved
In thesis
1. Molecular Epidemiology and Mechanisms of Antibiotic Resistance in Clinical Isolates of Pseudomonas aeruginosa from Qatar
Open this publication in new window or tab >>Molecular Epidemiology and Mechanisms of Antibiotic Resistance in Clinical Isolates of Pseudomonas aeruginosa from Qatar
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inappropriate and excessive use of antibiotics promotes antimicrobial resistance (AMR), particularly in Gram-negative bacteria (GNB). There is a noticeable increase in nosocomial infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa, which is associated with significant morbidity, mortality, and an increase in cost management. Although this is a global problem, there is a lack of sufficient data on regional differences that can contribute towards effective AMR management. This thesis presents a study of MDR-P. aeruginosa at five different hospitals in Qatar conducted prospectively between October 2014 - September 2017. The aim was to study the epidemiology, microbiological and clinical characteristics of MDR-P. aeruginosa infections as well as investigate the activity of new antibiotic combinations against these bacteria. The prevalence of MDR-P. aeruginosa isolates in the first year was 8.1% (205/2533), isolated from different clinical specimens, but the majority were from respiratory infections (44.9%, n=92). Most cases were exposed to antibiotics during the 90 days prior to isolation (85.4%, n=177), and the resistance to cefepime, ciprofloxacin, piperacillin/tazobactam, meropenem was >90%. To compare pre- and post-Antimicrobial Stewardship Program, there was a significant reduction in antibiotic consumption by 30.4% of total inpatient antibiotic prescriptions (p=0.008) and the prevalence of MDR-P. aeruginosa significantly declined from 9% to 5.4% (p=0.019). The in vitro investigation of ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) against MDR-P. aeruginosa isolates, showed promising results with susceptibility of 68.8% (n=141/205) and 62.9% (n=129/205), respectively, which was higher than other antipseudomonal agents except colistin. Seventy-five isolates that were sequenced belonged to 29 different sequence types, with ST235 being predominant at 21.3% (16/75). Among the 42 isolates that were resistant to CZA and/or C/T, the most prevalent genes were blaOXA-488 and blaVEB-9 detected in 45.2% (19/42) of isolates. Spearman’s analysis showed that resistance to CZA and C/T were positively correlated with the presence of blaOXA-10, blaPDC-2a, blaVIM-2, and blaVEB-9 , respectively. The study highlights potential key mechanisms that could explain the resistance of MDR-P. aeruginosa to the new antibiotic combinations.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 92
Series
Örebro Studies in Life Science, ISSN 1653-3100 ; 17
Keywords
Antibiotics, C/T, CZA, MDR, Pseudomonas aeruginosa, ST235, VEB, VIM
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-85159 (URN)978-91-7529-353-0 (ISBN)
Public defence
2020-12-16, Örebro universitet, Långhuset, Hörsal L2, Fakultetsgatan 1, Örebro, 13:15 (English)
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I den fysiska versionen av avhandlingen är den angivna tidpunkten för avhandlingen 21 oktober, 2020, 13:00 med plats Hörsal F, Forumhuset, Örebro universitet. Disputationen blev dock inställd och fick nytt datum och plats (dessa anges ovan).

Available from: 2020-08-26 Created: 2020-08-26 Last updated: 2023-01-26Bibliographically approved

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Sid Ahmed, MazenSöderquist, BoJass, Jana

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