• Carbapenem resistant pathogens: a major challenge to public health
  • Maryam Behboudipour,1 Neda Soleimani,2,* Neda Soleimani,3 Negar Azarpira,4 Mehdi Golshan,5
    1. Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
    2. Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
    3. Department of pathology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
    4. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
    5. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran


  • Introduction: Among various beta-lactam antibiotics, carbapenems are highly effective antimicrobial agents for treating important hospital-acquired infections. Carbapenems exert their bactericidal activity by binding to penicillin-binding proteins (PBPs), membrane-associated proteins responsible for the synthesis of peptidoglycan in the cell wall of bacteria. Due to their broad spectrum of activity against both gram-positive and gram-negative bacteria, stability against most beta-lactamases, good safety profile, and appropriate tolerance, carbapenems are commonly considered as the last and most reliable antibiotic option for the treatment of critically ill patients and serious infections caused by multidrug-resistant (MDR) organisms. Excessive use of carbapenems in many countries has given rise to carbapenem resistance, especially among gram-negative bacteria. This article examines the importance of carbapenem-resistant pathogens as a major public health problem.
  • Methods: In this review, we searched and summarized recently published studies related to carbapenem resistance in Google Scholar, PubMed, Scopus, … databases. The search was performed using keywords such as carbapenem, carbapenem resistance, carbapenemase, and public health.
  • Results: Resistance to carbapenem antibiotics can be caused by several mechanisms such as carbapenemase production, porin mutation, or efflux pump upregulation . However, production of carbapenemases is the main mechanism of carbapenem resistance and is a major challenge because these enzymes hydrolyze almost all beta-lactams and are encoded by genes that can be transferred horizontally by mobile genetic elements such as: plasmids, integrons, and transposons. In addition, carbapenemase-producing bacteria are usually resistant to other classes of antibiotics, including aminoglycosides and fluoroquinolones. The KPC, VIM, IMP, NDM, and OXA-48 types are considered to be the most potent carbapenemases due to their strong ability to hydrolyze carbapenems and widespread distribution. However, with the rise of international travel and the growth of medical tourism, the association between a particular resistance mechanism and a specific region or country can change. Some human-related factors such as irrational antibiotic prescription, uncontrolled public access to antibiotics, lack of appropriate infection control measures in healthcare settings and the use of antibiotics as growth promoters in livestock and poultry have played an important role in the emergence and spread of carbapenem resistance. In addition, prolonged use of metronidazole and imipenem drugs, prolonged hospital stays, and the presence of biliary drainage catheters have been identified as effective factors for the acquisition of carbapenem resistance. The rapid spread of antimicrobial resistance is a concerning issue. If resistance continues at this rate, untreatable infections will appear on a large scale, in some cases, the world may experience the uncomfortable pre-antibiotic era. The emergence of carbapenem-resistant pathogens (CRPs), including carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), is a significant and concerning global threat. Because of the reduction of treatment options, the mortality following CRP infection is up to 50%. Due to the importance of this issue, World Health Organization has classified CRPs as critical priority pathogens for the discovery, research and development of new antibiotics. Although many new treatment options, such as carbapenemase inhibitor compounds, are in the process, none of them provide a complete solution for addressing this concerning threat.
  • Conclusion: The rapid spread of carbapenem resistance in the community is a growing and emerging threat to public health. Despite some efforts made in this field, the production of new and effective antibiotics is a time-consuming and expensive process and is not profitable compared to the production of drugs in other medical fields, so it seems that finding a definitive and efficient solution to this problem is complicated and difficult. Therefore, in the absence of a dependable substitute to carbapenems, rational use of antibiotics in humans and animals, implementation of strict infection control measures, and active surveillance for the presence of carbapenemase-encoding genes are among the most crucial actions that can be taken.
  • Keywords: Carbapenem Resistance, Carbapenemase, Public health