Dr. Pham Hung Van
Viet Nam Research and Development Institute of Clinical Microbiology
Title of the talk: Challenging of antibiotic resistance among Gram [-] rods
Abstract
Gram [-] rods are creating a huge treatment challenge due to the evolution of their beta-lactamases. First, bacteria can resist penicillin G and A antibiotics due to the ability to secrete the classical beta-lactamase with genes located on a highly transmissible plasmid. To deal with this, we have a solution: using beta-lactams combined with beta-lactamase inhibitors or 2nd generation cephalosporins or higher. However, the gram [-] rods later evolved to produce beta-lactamase AmpC that is resistant to third generation cephalosporins. Beta-lactamase AmpC was initially inducible AmpC (iAmpC) with a gene on the chromosome that helps bacteria resist the 3rd cephalosporins induced by the use of 3rd generation cephalosporins or cephamycin (cefoxitin) in treatment, then iAmpC evolved into AmpC with genes on the plasmid that help the bacteria actually resist 3rd generation cephalosporins without needing be induced. The antibiotic that can deal with AmpC beta-lactamase is the 4th generation cephalosporin. However, only a short time later, bacteria evolved to secrete extended-spectrum beta-lactamase (ESBL) with genes located on a plasmid that causes us to close the door to using cephalosporin from 1st to 4th generation, and have to deal with carbapenem antibiotics. However, this solution is currently being challenged because Gram [-] rods have evolved to be able to secrete beta-lactamses that can destroy the carbapenems that we are using. These beta-lactamases are carbapenemases with genes located on plasmids that are also highly contagious, causing a huge challenge. To deal with carbapenemase-producing bacteria, we must know the genetic origin of the carbapenemases that bacteria produce. As we know that Ambler classified beta-lactamases based on the amino-acid chain at the active site of these enzymes. Type A includes extended-spectrum beta-lactamases and the carbapenemase KPC. Antibiotics that can deal with KPC carbapenemase are ceftazidime combined with avibactam, imipenem combined with relebactam, meropenem combined with vaborbactam and of course these are also deal with ESBL. Type C are AmpC beta-lactamases with antibiotics that deal with 4th generation cephalosporins, 1st generation carbapenems, ceftazidime combined with avibactam which can also deal with type C beta-lactamases. Type D are beta-lactamases that have acts on narrow-spectrum beta-lactams such as oxacillin with the OXA genes, and among these genes, the OXA-48 has the ability to help bacteria produce carbapenemases, and antibiotics can deal with carbapenemases of the OXA-48 is ceftazidime combined with avibactam, however the combinations imipenem + relebactam or meropenem + vaborbactam all failed. Type B are carbapenemases that have zinc ions at the active site instead of serines like types A, C and D. That’s why only the antibiotic cefiderocol can deal with it. If cefiderocol is not available, aztreonam can be used in combination with other antibiotics such as ceftazidime+avibactam, or fosphomycin, but the effectiveness is uncertain. Type B carbapenemases have the genes such as IMP, VIM, and NDM1, of which currently among Enterobacterales, the NDM1 gene is increasingly common with increasing frequency. Thus we see that the biggest challenge we currently have to deal with Gram [-] bacilli is the risk of bacteria becoming increasingly resistant to carbapenems. The solution to choosing antibiotic treatment requires us to obtain information about the genetic origin of beta-lactamase enzymes including AmpC, ESBL and carbapenemase. There are currently commercially available products based on the ability to detect specific proteins of the beta-lactamase and carbapenemase genes (such as NG-test), or the ability to detect genes by PCR. However, these products are often very expensive and do not cover all the genetic origins that we want to find. That is why the Vietnam Research and Development Institute of Clinical Microbiology has now successfully develop the solution of applying Multiplex real-time PCR (MPL-rPCR) to detect the sources of resistance genes on Gram [-] bacilli. We are currently using this solution on isolated bacterial strains and also directly on patient samples. We are also implementing this solution in a number of laboratories as well as in research projects in which we participate.
Biography
Pham Hung Van completed his MD in 1978 and his PhD in Medical Microbiology in 1995. He was a lecturer at the University of Medicine and Pharmacy from 1978 to 2013. He is the Technical Advisory Board of Nam Khoa Co. from 1999 to now, a member of ANSORP (Asian Network for Surveillance Of Resistant Pathogens) with the role of Principal Investigator and a member of Scientific Advisory Board from 1998 to now, President of Ho Chi Minh City Society of Clinical Microbiology from 2013 to now, President of The International Institute of Gene and Immunology from 2019 to 2022 and Vietnam Research and Development Institute of Clinical Microbiology from 2022 to now. He has published more than 92 papers in international journals and 52 in National.
Publications: ResearchGate.