
==== Front
Ann Med Surg (Lond)
Ann Med Surg (Lond)
MS9
Annals of Medicine and Surgery
2049-0801
Lippincott Williams & Wilkins Hagerstown, MD

10.1097/MS9.0000000000000262
00046
3
Correspondence
Carbapenem-resistance worldwide: a call for action – correspondence
http://orcid.org/0000-0001-5573-7905
Mohd Ahmed B. MBBCh aabj.m00hd@gmail.com

Huneiti Nesreen MBBCh Nesreen.alrowad@gmail.com
a
http://orcid.org/0000-0002-6875-2458
Hasan Hanan MBBCh bhananyalu97@gmail.com

Mohd Omar B. MBBCh aob.jamil2001@gmail.com

http://orcid.org/0000-0002-0084-6132
Khaity Abdulrhman MBBCh cabdulrhman.marwan.khaity@gmail.com

http://orcid.org/0000-0003-1462-4204
Albakri Khaled MBBCh akhaledalbakri1999@gmail.com

a Faculty of Medicine, The Hashemite University, Zarqa
b Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan
c Faculty of Medicine, Elrazi University, Khartoum, Sudan
* Corresponding author. Address: Faculty of Medicine, Elrazi University, Khartoum 11115, Sudan. Tel: + 249 999 255 031, Fax: + 249-0-999255031. E-mail address: abdulrhman.marwan.khaity@gmail.com (A. Khaity).
3 2023
9 3 2023
85 3 564566
11 1 2023
26 1 2023
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
2023
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

OPEN-ACCESSTRUE
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pmc Dear Editor,

Antibiotic resistance is one of the major global health concerns that poses a threat on both individual and societal levels. As a result of the emerging novel bacterial pathogen and resistance to several antibiotic classes, many antibiotics have been futile in coping with these infections. In the United States, it is estimated that 23 000 people with antibiotic-resistant infections die due to the limited treatment options and severe symptoms caused by drug-resistant organisms1.

It is interesting to note that carbapenems, a class of antibiotics including doripenem, ertapenem, meropenem, and imipenem, have a significant impact in treating multidrug resistance and hospital-acquired extended-spectrum β-lactamase infections. However, the usage of carbapenem antibiotics around the world is risky due to the evolution of resistance to them2.

Enzyme synthesis, efflux pumps, and porin mutations are the three main methods by which Enterobacteriaceae acquire carbapenem resistance. The primary mode of resistance among them is enzyme synthesis3. The enzymes responsible for hydrolyzing carbapenems in resistant bacteria are called carbapenemases, which are β-lactamases that can hydrolyze carbapenems, penicillin, cephalosporins, and monobactam. Four primary classes of carbapenemases have been classified based on amino acid homology (classes A, B, C, and D)4. β-lactamases which are found in molecular classes A, C, and D, contain serine at their active sites, whereas molecular class B β-lactamases are metalloenzymes with an active site containing zinc4. Metallo-β-lactamases (MBL), Klebsiella pneumonia carbapenemase (KPC), and oxacillinase (OXA-48)-like are the three primary categories of enzymes that cause the majority of carbapenem resistance3. More details are shown in Figure 1.

Figure 1 The figure shows the classification of carbapenem resistance.

Nevertheless, a significant health issue is an alarming rise in resistance to these final resource agents. The primary risk factors for the emergence of resistance are the abuse of antibiotics, genetic mobile elements, worldwide travel, and poor infection control techniques. Saudi Arabia, like other Gulf nations, is under pressure from the emergence of multiple resistant pathogens like carbapenem-resistant Enterobacteriaceae (CRE). Traveling both inside and outside of the Gulf region poses a significant risk for the spread of resistant Enterobacteriaceae strains5. Enterobacteriaceae multiple resistant variants, which typically produce extended-spectrum β-lactamases and carbapenemases like KPC and New Delhi MBL-1 (NDM-1), are resistant to cephalosporins and have recently spread across the globe. However, there are only a few medications, including polymyxins, tigecycline, fosfomycin, and aminoglycosides, either alone or in combination with other antibiotics, that can be used to treat CRE infections. Compared to monotherapy, combination therapy had a better clinical outcome5.

In the United States, Colombia, Argentina, Greece, and Italy, KPC-producing Enterobacteriaceae are widespread. However, in Pakistan, India, and Sri Lanka, the MBL NDM-1 is the major carbapenemase-producing resistance, and OXA-48-like enzyme producers are widespread in North Africa, the Middle East, Turkey, and Malta3. Figure 2 demonstrates the demographical distribution of carbapenem-resistance ambler classes endemicity. Because all three groups of enzymes are plasmid-mediated, the horizontal transmission will likely be simpler, and that carbapenem resistance will spread more quickly throughout the world3.

Figure 2 Demonstrates the demographical distribution of carbapenem resistance ambler classes endemicity. KPC, Klebsiella pneumonia carbapenemase; MBL, metallo-β-lactamases; OXA-48, oxacillinase-48.

Due to the few available alternatives for treatment and inadequate early therapy, CRE infections are associated with poor results. Additionally, evidence suggested that CRE infections have worse outcomes than those caused by sensitive Enterobacterales 6. Moreover, a CRE infection is linked to lengthier hospital stays and higher medical expenses6.

There is little information about the molecular epidemiology of CRE in the Middle East and Gulf countries in particular. Based on the available research, OXA-48 and NDM are the two most common carbapenemase strains in Saudi Arabia. The extensive geographic range of the Arab region and the ongoing influx of both native and foreign pilgrims are possible influences on the dissemination of CRE strains. There is still a lack of clarity regarding the precise molecular epidemiology and consequences of CRE6.

Self-medication is one of the factors that is acknowledged on a global scale as being the most prevalent and obvious contributor to bacteria that are resistant to antibiotics. Self-medication is the phrase used to describe taking medications on one’s own will or at the suggestion of someone who is not a licensed medical expert. Advertisements on television, radio, and print media, as well as recommendations from family and friends, are the most prevalent and important factors that lead people to begin using medications without seeking professional assistance1.

To fight drug-resistant infections and lower the mortality rate related to drug resistance, it is urgently necessary to identify novel antibiotics. This need can be met by promoting global collaborative research projects and raising public awareness of self-medication and the negative effects of antibiotic misuse1. The scientific and medical communities must work together to slow the development of resistance. Also, new therapeutic guidelines for the treatment of CRE infections are urgently needed. This includes the creation of novel medications as well as the repurposing of currently existing antibiotics like fosfomycin, aminoglycosides, and colistin3.

Ethical approval

Not applicable.

Patient consent

Not applicable.

Sources of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contribution

A.B.M.: the conception and design of the study; A.B.M., N.H., O.B.M.: made the first draft; H.H., A.K., and A.B.M.: updated the manuscript; K.A. and A.K.: reviewed the final draft and edited the final manuscript. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.

Conflicts of interest disclosure

The authors declare no conflicts of interest.

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Name of the registry: NA.

Unique identifying number or registration ID: NA.

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Guarantor

All authors.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Acknowledgments

Not applicable.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Published online 9 March 2023
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References

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3 Suay-García B Pérez-Gracia MT . Present and future of carbapenem-resistant Enterobacteriaceae (CRE) infections. Antibiotics (Basel) 2019;8 :122.31430964
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