Posted on January 28, 2016
Methicillin-resistant staph aureus (MRSA) is resistant to first line antibiotics, leaving clinicians with limited treatment options. 1 An article published in Nature Chemical Biology shows promise that a novel combination of antibiotics can be used to treat MRSA.2
The researchers showed that the triple beta-lactam combination of meropenem-piperacillin-tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against a MRSA subspecies and 72 other clinical MRSA isolates in vitro and clears the same MRSA subspecies infection in a mouse model. These three antibiotics are not individually effective against drug-resistant staph infections but synergistically are effective, in this stage of research.
Staph aureus infections were first treated in the 1940s with the advent of the beta-lactam antibiotic, penicillin. This drug interfered with cell wall synthesis which prevented bacteria from growing and reproducing. Resistance quickly developed, so Methicillin and other second generation penicillins, which were resistant to those enzymes, were developed. Shortly after clinicians began to use these semi-synthetic penicillins to treat Staph, resistance was reported. These resistant Staph had acquired genes from other bacteria to produce cell walls even in the presence of the beta-lactams.3
In this new study,2 the scientists chose from three separate subclasses of beta-lactam compounds that target different cell wall synthesis mechanisms. They tested for effectiveness against the MRSA strains and the ability of the drug combination to repress resistance development. Bacteria were exposed to low doses of the antibiotic combination for 11 days with no evidence of resistance to ME/PI/TZ. On the other hand, when the drugs were used alone or in pairs, bacteria developed resistance in one to eight days.
Currently, treatment of MRSA infections depends on the site of the infection and other manifestations. In 2011, the Infectious Disease Society of America (IDSA) published guidelines for the treatment of MRSA.4 In our arsenal of MRSA treatment options, we have Clindamycin, Trimethoprim-sulfamethoxazole, Doxycycline, Minocycline, Linezolid, Vancomycin, Daptomycin, Rifampin, and some combinations of the above.
On the surface, it appears we have sufficient drugs to treat MRSA infections but the bacteria have learned how to circumvent changes in the biochemistry of these antimicrobials. It will be interesting to see if this new 3-drug combination will prove effective initially and maintain its effectiveness. As Dr. Dantas, the lead author, states, “We know bacteria eventually develop resistance to antibiotics, but this trio buys us some time, potentially a significant amount of time.” 3
Centers for Disease Control and Prevention – Methicillin-resistant Staph aureus (MRSA) Infections; cited December 14, 2015: http://www.cdc.gov/mrsa/healthcare/clinicians/index.html
Gonzales PR, Pesesky MW, Bouley R, Ballard A, Biddy BA, Suckow MA, Wolter WR, Schroeder VA, Burnham C-AD, Mobashery S, Chang M, Dantas G. Synergistic, collaterally sensitive ?-lactam combinations suppress resistance in MRSA. Nature Chemical Biology, published online September 14, 2015; cited December 14, 2015.
National Institutes of Health. Antibiotic Combinations May Combat MRSA Infections. Cited December 14, 2015: http://www.nih.gov/news-events/nih-research-matters/antibiotic-combinations-may-combat-mrsa-infections
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clinical Infectious Disease. 2011:52 (1 February); 1-38.
Written for clinicians