Scanning electron micrograph of MRSA (yellow) surrounded by cellular debris (orange). [NIAID]
Scanning electron micrograph of MRSA (yellow) surrounded by cellular debris (orange). [NIAID]

The thought of an aggressive bacterial infection that is resistant to the arsenal of antimicrobial compounds is frightening, to say the least. Yet, this is currently an issue for a handful of microbial pathogens, and there is an ever looming threat of more bacteria emerging to become multidrug resistant.

However, now a new experimental antibiotic developed by a team of scientists at Rutgers University has been observed to treat deadly methicillin-resistant Staphylococcus aureus (MRSA) infections successfully and restore the efficacy of a commonly prescribed antibiotic that has become ineffective against MRSA. In their current study, the researchers show that 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.

“This is important because even though 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,” explained senior study author Daniel Pilch, Ph.D.,associate professor in the department of pharmacology at Robert Wood Johnson Medical School.

The findings from this study were published recently in Antimicrobial Agents and Chemotherapy in an article entitled “TXA709, an FtsZ-Targeting Benzamide Prodrug with Improved Pharmacokinetics and Enhanced In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus.”

MRSA infections are responsible for up to 19,000 deaths annually and represent $3 billion in annual health care costs. Thus, many investigators, including the team from Rutgers, have been racing to develop a new class of antibiotics to treat the deadly infection. The World health Organization has taken the threat of MRSA and other antibiotic-resistant infectious outbreaks extremely seriously, predicting that common infections and minor injuries could become life-threatening because of a lack of drug treatments available to destroy these bacterial infections. Adding to the already heightened urgency, last month the first case in the United States of a patient with an infection resistant to all known antibiotics was reported by the U.S. Centers for Disease Control and Prevention.

“Current standard-of-care drugs for the treatment of MRSA infections are limited,” noted Dr. Pilch. “Furthermore, resistance to these drugs is on the rise, and their clinical effectiveness is likely to diminish in the future.”

The research team outlined that TXA709 kills MRSA bacteria in a unique manner unlike any other antibiotic in current clinical use—through the inhibition of a protein called FtsZ, which is 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—a significant finding because it decreases the potential for any drug-induced toxicity and side effects that might occur from a higher dosage.

“What is also good about this experimental treatment is that both drugs can be taken orally, which means they can be administered on an outpatient basis,” Dr. Pilch remarked. “All but two of the current antibiotics being used clinically to treat MRSA need to be administered intravenously.”

The Rutgers team was excited by their findings and say 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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