- The drug-resistant bacteria causes infection by inactivating penicillin antibiotics using enzymes called beta-lactamases and in particular the metallo-beta-lactamases (MBLs).
- The new combination therapy uses two antibiotic drugs to protect each other from being rendered inactive by the problematic bacterial enzymes.
- The antibiotics interferes with the others activity to fight infections.
Penicillin-resistant bacteria causes infection by using enzymes known as beta-lactamases to chop up the antibiotics rendering them useless.
There is a particular group of bacterial beta-lactamases known as metallo-beta-lactamases (MBLs), that is able to destroy even the newest penicillins.
MBLs are often made by bacteria in conjunction with other enzymes, including other beta-lactamases that allow certain bacteria to destroy the entire penicillin arsenal.
When combined, the antibiotics interferes with the other's activity to fight infections.
This equips the doctors with a new weapon to overcome one of the most pernicious infections caused by deadly bacteria endemic to hospitals.
According to a multicenter epidemiologic study, carbapenem-resistant enterobacteriaceae (CRE), causes approximately one-third of healthcare-associated infections in the United States and kills nearly half its victims
The new findings state that the novel combination antibiotic drug regimen proved effective against 81% of CRE specimens tested.
The study was conducted under the leadership of Robert A. Bonomo, MD, Professor of Medicine, Pharmacology, Biochemistry, Molecular Biology, and Microbiology at Case Western Reserve University School of Medicine and Chief of Medical Service at the Louis Stokes Cleveland Veterans Affairs Medical Center.
The strategy uses two antibiotic drugs to protect each other from being neutralized by CRE's problematic enzymes.
An antibiotic combination regimen of ceftazidime/avibactam is used in the first combination strategy and these are vulnerable to the neutralizing effect of the metallo-beta-lactamases.
The next half uses aztreonam, which is not vulnerable to the neutralizing effect of the metallo-beta-lactamases but is vulnerable to other types of CRE enzymes, which are in turn neutralized by ceftazidime/avibactam.
When used in combination, the two antibiotics run interference for each other and in tag-team fashion defeat the infection.
The novel combination helps doctors overcome the antibiotic neutralizing metallo-beta-lactamases.
As the other half of the regimen offers protection, "aztreonam skirts around the metallo-beta-lactamase and hits its target--the penicillin-binding proteins," Bonomo explained in a Center for Infectious Disease Research and Policy feature.
Aztreonam attaches to their penicillin-binding proteins of the bacteria, and prevents it from building effective cell walls with the drug in the way, and this causes them to die quickly.
Bonomo said, "If we understand the fundamental mechanisms by which bacteria become resistant to antibiotics, we can use what we know to help design better therapies."
The combination approach still needs to go through clinical trials and undergo additional research before it can become a commonly used treatment. It is however extremely promising news for doctors worldwide low on options to treat patients with antibiotic-resistant infections.
The findings are published in Antimicrobial Agents and Chemotherapy.
- Robert A. Bonomo et al. Bacteremia due to Carbapenem-resistant Enterobacteriaceae (CRE): A Multicenter Clinical and Molecular Epidemiologic Analysis in the Nation's Epicenter for CRE. Antimicrobial Agents and Chemotherapy; (2017) doi: 10.1128/AAC.02349-16