Plasmid-Mediated AmpC β-Lactamase  CITM  and  DHAM  Genes Among Gram-Negative Clinical Isolates

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Abstract

Background

Antibiotic resistance mediated by the production of extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases is posing a serious threat in the management of the infections caused by Gram-negative pathogens. The aim of this study was to determine the prevalence of two AmpC β-lactamases genes, bla _CITM and bla _DHAM, in Gram-negative bacterial isolates.

Materials and Methods

A total of 1151 clinical samples were obtained and processed at the microbiology laboratory of Annapurna Neurological Institute and Allied Science, Kathmandu between June 2017 and January 2018. Gram-negative isolates thus obtained were tested for antimicrobial susceptibility testing (AST) using Kirby–Bauer disk diffusion method. AmpC β-lactamase production was detected by disk approximation method using phenylboronic acid (PBA). Confirmed AmpC β-lactamase producers were further screened for bla _CITM and bla _DHAM genes by conventional polymerase chain reaction (PCR).

Results

Out of 1151 clinical specimens, 22% (253/1152) had bacterial growth. Of the total isolates, 89.3% (226/253) were Gram-negatives, with E. coli as the most predominant species (n=72) followed by Pseudomonas aeruginosa (n=41). In the AST, 46.9% (106/226) of the Gram-negative isolates were multidrug resistant (MDR). In disk diffusion test, 113 (50%) isolates showed resistance against cefoxitin, among which 91 isolates (83 by disk test and Boronic acid test, 8 by Boronic test only) were confirmed as AmpC β-lactamase-producers. In PCR assay, 90.1% (82/91) and 87.9% (80/91) of the isolates tested positive for production of bla _CITM and bla _DHAM genes, respectively.

Conclusions

High prevalence of AmpC β-lactamase-producers in our study is an alarming sign. This study recommends the use of modern diagnostic facilities in the clinical settings for early detection and management which can optimize the treatment therapies, curb the growth and spread of the drug-resistant pathogens.

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Most cited references 61

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A-P Magiorakos, A. Srinivasan, R.B. Carey … (2012)

Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided. © 2011 European Society of Clinical Microbiology and Infectious Diseases. No claim to original US government works.

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AmpC beta-lactamases.

George A. Jacoby (2009)

AmpC beta-lactamases are clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and beta-lactamase inhibitor-beta-lactam combinations. In many bacteria, AmpC enzymes are inducible and can be expressed at high levels by mutation. Overexpression confers resistance to broad-spectrum cephalosporins including cefotaxime, ceftazidime, and ceftriaxone and is a problem especially in infections due to Enterobacter aerogenes and Enterobacter cloacae, where an isolate initially susceptible to these agents may become resistant upon therapy. Transmissible plasmids have acquired genes for AmpC enzymes, which consequently can now appear in bacteria lacking or poorly expressing a chromosomal bla(AmpC) gene, such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Resistance due to plasmid-mediated AmpC enzymes is less common than extended-spectrum beta-lactamase production in most parts of the world but may be both harder to detect and broader in spectrum. AmpC enzymes encoded by both chromosomal and plasmid genes are also evolving to hydrolyze broad-spectrum cephalosporins more efficiently. Techniques to identify AmpC beta-lactamase-producing isolates are available but are still evolving and are not yet optimized for the clinical laboratory, which probably now underestimates this resistance mechanism. Carbapenems can usually be used to treat infections due to AmpC-producing bacteria, but carbapenem resistance can arise in some organisms by mutations that reduce influx (outer membrane porin loss) or enhance efflux (efflux pump activation).

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β-Lactams and β-Lactamase Inhibitors: An Overview.

Karen Bush, Patricia Bradford (2016)

β-Lactams are the most widely used class of antibiotics. Since the discovery of benzylpenicillin in the 1920s, thousands of new penicillin derivatives and related β-lactam classes of cephalosporins, cephamycins, monobactams, and carbapenems have been discovered. Each new class of β-lactam has been developed either to increase the spectrum of activity to include additional bacterial species or to address specific resistance mechanisms that have arisen in the targeted bacterial population. Resistance to β-lactams is primarily because of bacterially produced β-lactamase enzymes that hydrolyze the β-lactam ring, thereby inactivating the drug. The newest effort to circumvent resistance is the development of novel broad-spectrum β-lactamase inhibitors that work against many problematic β-lactamases, including cephalosporinases and serine-based carbapenemases, which severely limit therapeutic options. This work provides a comprehensive overview of β-lactam antibiotics that are currently in use, as well as a look ahead to several new compounds that are in the development pipeline.

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Author and article information

Journal

Journal ID (nlm-ta): Infect Drug Resist

Journal ID (iso-abbrev): Infect Drug Resist

Journal ID (publisher-id): idr

Journal ID (pmc): idr

Title: Infection and Drug Resistance

Publisher: Dove

ISSN (Electronic): 1178-6973

Publication date (Electronic): 24 November 2020

Publication date Collection: 2020

Volume: 13

Pages: 4249-4261

Affiliations

[1 ]Golden Gate International College , Kathmandu, Nepal

[2 ]Annapurna Neurological Institute and Allied Sciences , Kathmandu, Nepal

[3 ]Shi-Gan Int’l College of Science and Technology (SICOST) , Kathmandu, Nepal

[4 ]Central Department of Microbiology, Tribhuvan University , Kirtipur, Kathmandu, Nepal

Author notes

Correspondence: Komal Raj Rijal Central Department of Microbiology, Tribhuvan University , Kirtipur, Kathmandu Email rijalkomal@gmail.com

[*]

These authors contributed equally to this work

Author information

Subhas Chandra Aryal http://orcid.org/0000-0002-6457-7621

Anil Kumar Sah http://orcid.org/0000-0001-5428-8503

Meharaj Ansari http://orcid.org/0000-0003-3396-9056

Binod Dhungel http://orcid.org/0000-0002-7193-9109

Nabaraj Adhikari http://orcid.org/0000-0002-5501-9011

Komal Raj Rijal http://orcid.org/0000-0001-6281-8236

Article

Publisher ID: 284751

DOI: 10.2147/IDR.S284751

PMC ID: 7699442

PubMed ID: 33262619

SO-VID: 507b632b-8aea-44f8-b7a6-fbc854bfaded

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 30 September 2020

Date accepted : 06 November 2020

Page count

Figures: 4, Tables: 3, References: 62, Pages: 13

Funding

Funded by: Golden Gate International College;

This study was financially supported by Golden Gate International College, Old Baneshwor, Kathmandu, Nepal.

Plasmid-Mediated AmpC β-Lactamase CITM and DHAM Genes Among Gram-Negative Clinical Isolates

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Abstract

Background

Materials and Methods

Results

Conclusions

Related collections

Point-of-Care Testing for COVID-19

Most cited references 61

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.

AmpC beta-lactamases.

β-Lactams and β-Lactamase Inhibitors: An Overview.

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