Bacterial Resistance to Antimicrobial Agents

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Abstract

Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness. This review briefly summarizes the various antimicrobial resistance mechanisms that are harbored within infectious bacteria.

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Most cited references 191

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The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.

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Extended-Spectrum β-Lactamases: a Clinical Update

David L. Paterson, Robert Bonomo (2005)

Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli . In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

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Author and article information

Contributors

Nahed El-Najjar: Role: Academic Editor

Journal

Journal ID (nlm-ta): Antibiotics (Basel)

Journal ID (iso-abbrev): Antibiotics (Basel)

Journal ID (publisher-id): antibiotics

Title: Antibiotics

Publisher: MDPI

ISSN (Electronic): 2079-6382

Publication date (Electronic): 17 May 2021

Publication date Collection: May 2021

Volume: 10

Issue: 5

Electronic Location Identifier: 593

Affiliations

[1 ]Department of Biology, Eastern New Mexico University, Portales, NM 88130, USA; Manisha.Ojha@ 123456enmu.edu (M.O.); Nicholas.Wenzel@ 123456enmu.edu (N.W.); Leslie.Sanford@ 123456enmu.edu (L.M.S.); Alberto.J.Hernandez@ 123456enmu.edu (A.J.H.)

[2 ]Post-Harvest Technology, ICAR-Central Institute of Fisheries Education, Seven Bungalows, Andheri (W), Mumbai 400061, India; jerusha.phtpa702@ 123456cife.edu.in (J.S.); manjusha@ 123456cife.edu.in (M.L.); sanathkumar@ 123456cife.edu.in (S.H.K.)

[3 ]CSIR-National Institute of Oceanography, Regional Centre, Kochi 682018, India; parvathi@ 123456nio.org

Author notes

[* ]Correspondence: manuel.varela@ 123456enmu.edu

Author information

Manuel F. Varela https://orcid.org/0000-0001-8667-7853

Jerusha Stephen https://orcid.org/0000-0001-9434-3140

Ammini Parvathi https://orcid.org/0000-0001-6916-2671

Sanath H. Kumar https://orcid.org/0000-0003-0223-9069

Article

Publisher ID: antibiotics-10-00593

DOI: 10.3390/antibiotics10050593

PMC ID: 8157006

PubMed ID: 34067579

SO-VID: f29b2afd-3ee3-4551-8c06-6613edbd3874

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

Bacterial Resistance to Antimicrobial Agents

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Bacterial extracellular vesicles

Most cited references 191

The Protein Data Bank.

Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

Extended-Spectrum β-Lactamases: a Clinical Update

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