Hope on the horizon: Experimental antibiotic to treat deadly MRSA
Wednesday, June 15, 2016
Methicillin-resistant Staphylococcus aureus (MRSA) infection is caused by a type of staph bacteria that has become resistant to many of the antibiotics used to treat ordinary staph infections. Thus, treating MRSA has been a challenge for healthcare professionals.
Healthcare-associated MRSA (HA-MRSA) occurs in settings such as nursing homes and dialysis centers, whereas community-associated MRSA (CA-MRSA) occurs in a wider community among healthy people. According to the U.S. National Institutes of Health, the prognosis of MRSA infection varies according to the severity of the infection and the general condition of the person who has the infection.
Whatever the setting, complications of MRSA can be serious and include sepsis, pneumonia, organ damage, tissue loss and scarring due to necessary surgery. Additionally, a serious complication of antibiotic treatment is intestinal infection by the anaerobic organism Clostridium difficile.
But a new experimental antibiotic developed by a team of scientists at Rutgers University has successfully treated the deadly MRSA infection and restored the efficacy of a commonly prescribed antibiotic that has become ineffective against MRSA.
The combination of their newly developed antibiotic, TXA709, with cefdinir, an antibiotic that has been on the market for almost two decades, successfully treated the MRSA infection in animals.
The advantages over monotherapy include reduction of the drug dose required for efficacy, reduced potential for drug-induced toxicity, and reduced potential for the emergence of resistance. The researchers showed that the active product of TXA709 (TXA707) acts synergistically with cefdinir in vitro against clinical isolates of MRSA, vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA) and linezolid-resistant S. aureus (LRSA).
In addition, the combination of TXA707 and cefdinir significantly reduced or eliminated the detectable emergence of resistance relative to TXA707 alone. They also demonstrated synergy in vivo with oral administration of the prodrug TXA709 and cefdinir in mouse models of both systemic and tissue (thigh) infection with MRSA.
According to Daniel Pilch, lead author and associate professor in the Department of Pharmacology at Robert Wood Johnson Medical School, although TXA709 is effective on its own in treating MRSA, combining it with cefdinir (used to treat a wide range of bacterial infections like strep throat, pneumonia, bronchitis and middle ear and sinus infections) makes it even more efficacious, while also significantly reducing the potential for the MRSA bacteria to become resistant in the future.
In addition, TXA709 kills MRSA bacteria in a unique manner unlike any other antibiotic in current clinical use. It inhibits the function of a protein, FtsZ, essential for the bacteria to divide and survive. By combining TXA709 with cefdinir, a cephalosporin antibiotic that acts much like penicillin, scientists were able to lower the dosage of the new antibiotic required to eradicate the MRSA infection.
All but two of the current antibiotics used to treat MRSA need to be administered intravenously, whereas both TXA709 and cefdinir can be taken orally, which means they can be administered on an outpatient basis. Phase I clinical trials on the new antibiotic, which will assess and evaluate its safety and effectiveness in humans, are expected to begin next spring.
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