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Molecular Epidemiology and Mechanisms of Antibiotic Resistance in Clinical Isolates of Pseudomonas aeruginosa from Qatar
Örebro University, School of Science and Technology.ORCID iD: 0000-0002-6186-7770
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 [en]
Antibiotics, C/T, CZA, MDR, Pseudomonas aeruginosa, ST235, VEB, VIM
National Category
Other Biological Topics
Identifiers
URN: urn:nbn:se:oru:diva-85159ISBN: 978-91-7529-353-0 (print)OAI: oai:DiVA.org:oru-85159DiVA, id: diva2:1461091
Public defence
2020-12-16, Örebro universitet, Långhuset, Hörsal L2, Fakultetsgatan 1, Örebro, 13:15 (English)
Opponent
Supervisors
Note

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
List of papers
1. Emergence of Multidrug- and Pandrug- Resistant Pseudomonas aeruginosa from Five Hospitals in Qatar
Open this publication in new window or tab >>Emergence of Multidrug- and Pandrug- Resistant Pseudomonas aeruginosa from Five Hospitals in Qatar
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2019 (English)In: Infection Prevention in Practice, E-ISSN 2590-0889, Vol. 1, no 3-4, article id 100027Article in journal (Refereed) Published
Abstract [en]

Background: A global rise in multidrug-resistant (MDR) nosocomial infections has led to a significant increase in morbidity and mortality. MDR Gram-negative bacteria (GNB) are recognised for rapidly developing drug resistance. Despite Pseudomonas aeruginosa being the second most common GNB isolated from healthcare associated infections, the magnitude of MDR P. aeruginosa (MDR-PA) has not been evaluated in Qatar.

Aim: To assess the prevalence and antimicrobial susceptibility patterns of MDR-PA from 5major hospitals in Qatar.

Methods: A total of 2533P. aeruginosaclinical isolates were collected over a one-year period. MDR-PA was defined as resistance to at least one agent of3 antibiotic classes. Clinical and demographic data were collected prospectively.

Findings: The overall prevalence of MDR-PA isolates was 8.1% (205/2533); the majority of isolates were from patients exposed to antibiotics during 90 days prior to isolation (85.4%,177/205), and the infections were mainly hospital-acquired (95.1%, 195/205) with only 4.9% from the community. The majority of MDR-PA isolates were resistant to cefepime (96.6%, 198/205), ciprofloxacin, piperacillin/tazobactam (91%, 186/205), and meropenem (90%, 184/205). Patient comorbidities with MDR-PA were diabetes mellitus (47.3%, n¼97), malignancy (17.1%, n¼35), end-stage renal disease (13.7%, n¼28) and heart failure (10.7%, n¼22).

Conclusion: There was a significant prevalence of MDR-PA in Qatar, primarily from healthcare facilities and associated with prior antibiotic treatment. There was an alarming level of antimicrobial resistance to carbapenems. Our results are part of a national surveillance of MDR to establish effective containment plans.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Gram-negative bacteria, Antibiotic resistance, Antimicrobial susceptibility, Carbapenem, Cephalosporin, Hospital-acquired infections
National Category
Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-87548 (URN)10.1016/j.infpip.2019.100027 (DOI)001024904500001 ()2-s2.0-85107459189 (Scopus ID)
Funder
Swedish Research Council Formas, 219-2014-837
Note

Funding Agency:

Hamad Medical Corporation RGC-01-51-033

Available from: 2020-11-24 Created: 2020-11-24 Last updated: 2023-12-08Bibliographically approved
2. Impact of an antimicrobial stewardship programme on antimicrobial utilization and the prevalence of MDR Pseudomonas aeruginosa in an acute care hospital in Qatar
Open this publication in new window or tab >>Impact of an antimicrobial stewardship programme on antimicrobial utilization and the prevalence of MDR Pseudomonas aeruginosa in an acute care hospital in Qatar
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2020 (English)In: JAC - Antimicrobial Resistance, E-ISSN 2632-1823, Vol. 2, no 3, article id dlaa050Article in journal (Refereed) Published
Abstract [en]

Background: The excessive and inappropriate use of antibiotics is universal across all healthcare facilities. In Qatar there has been a substantial increase in antimicrobial consumption coupled with a significant rise in antimicrobial resistance (AMR). Antimicrobial stewardship programmes (ASPs) have become a standard intervention for effective optimization of antimicrobial prescribing.

Methods: A before–after study was conducted in Hamad General Hospital (603 bed acute care hospital): 1 year before implementation of a comprehensive ASP compared with the following 2 years. The ASP included a hospital-wide pre-authorization requirement by infectious diseases physicians for all broad-spectrum antibiotics. Prevalence of MDR Pseudomonas aeruginosa was compared with antimicrobial consumption, calculated as DDD per 1000 patient-days (DDD/1000 PD). Susceptibility was determined using broth microdilution, as per CLSI guidelines. Antibiotic use was restricted through the ASP, as defined in the hospital’s antibiotic policy.

Results: A total of 6501 clinical isolates of P. aeruginosa were collected prospectively over 3 years (2014–17). Susceptibility to certain antimicrobials improved after the ASP was implemented in August 2015. The prevalence of MDR P. aeruginosa showed a sustained decrease from 2014 (9%) to 2017 (5.46%) (P"0.019). There was a significant 23.9% reduction in studied antimicrobial consumption following ASP implementation (P"0.008). They early consumption of meropenem significantly decreased from 47.32 to 31.90 DDD/1000 PD (P"0.012), piperacillin/tazobactam from 45.35 to 32.67 DDD/1000 PD (P,0.001) and ciprofloxacin from 9.71 to 5.63 DDD/1000 PD (P"0.015) (from 2014 to 2017).

Conclusions: The successful implementation of the ASP led to a significant reduction in rates of MDR P. aeruginosa, pointing towards the efficacy of the ASP in reducing AMR.

Place, publisher, year, edition, pages
Oxford University Press, 2020
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-87546 (URN)10.1093/jacamr/dlaa050 (DOI)000733832600011 ()34223010 (PubMedID)2-s2.0-85103645662 (Scopus ID)
Funder
Swedish Research Council Formas, 219-2014-837
Note

Funding Agencies:

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

Qatar National Library

Available from: 2020-11-24 Created: 2020-11-24 Last updated: 2024-06-24Bibliographically approved
3. Clinical outcomes, molecular epidemiology and resistance mechanisms of multi-drug resistant Pseudomonas aeruginosa isolated from blood stream infections from Qatar
Open this publication in new window or tab >>Clinical outcomes, molecular epidemiology and resistance mechanisms of multi-drug resistant Pseudomonas aeruginosa isolated from blood stream infections from Qatar
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-87550 (URN)
Available from: 2020-11-24 Created: 2020-11-24 Last updated: 2020-11-24Bibliographically approved
4. Evaluation of in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against MDR Pseudomonas aeruginosa isolates from Qatar
Open this publication in new window or tab >>Evaluation of in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against MDR Pseudomonas aeruginosa isolates from 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
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-78572 (URN)10.1093/jac/dkz379 (DOI)000501732800012 ()31504587 (PubMedID)2-s2.0-85075093622 (Scopus ID)
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
5. Characterization of β-lactamase genes blaVIM-2, blaPDC-2, blaOXA-10 and blaVEB-9 associated with resistance to ceftazidime/avibactam and ceftolozane/tazobactam in multidrug-resistant Pseudomonas aeruginosa from Qatar
Open this publication in new window or tab >>Characterization of β-lactamase genes blaVIM-2, blaPDC-2, blaOXA-10 and blaVEB-9 associated with resistance to ceftazidime/avibactam and ceftolozane/tazobactam in multidrug-resistant Pseudomonas aeruginosa from Qatar
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-87551 (URN)
Available from: 2020-11-24 Created: 2020-11-24 Last updated: 2020-11-24Bibliographically approved
6. β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar
Open this publication in new window or tab >>β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-87552 (URN)
Available from: 2020-11-24 Created: 2020-11-24 Last updated: 2020-11-24Bibliographically approved

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