Novel Antibiotic Shows Potential for Broad Range of Infections

In order to treat bacterial infections, especially those caused by MDR bacteria, new antibacterial agents are needed that can overcome bacterial resistance, as many more patients die of other conditions complicated by infection with resistant pathogens.

Scientists from Shionogi & Co., Ltd (Osaka, Japan) found that S-649266, which is a parenteral siderophore cephalosporin with a novel mechanism for bacterial cell entry and improved stability to carbapenemases, demonstrates potent activity against a wide variety of Gram-negative pathogens that are resistant to available antibacterials.

The team conducted animal and laboratory studies that found that S-649266 had more robust antibacterial activity than established antibiotics, including ceftazidime and cefepime, against multidrug-resistant Pseudomonas (MDRP), MDR Acinetobacter (MDRA) and carbapenem-resistant Enterobacteriaceae (CRE). They also showed that S-649266 has high stability to serine- and metallo-type carbapenemases. The investigators noted that S-649266 has shown potent efficacy against MDRP and MDRA in rat lung infection models that mimicked human exposure profiles when administered twice daily in an hour-long infusion. The antibiotic has additionally been found to be safe and well tolerated in healthy volunteers in single- and multiple-dose phase 1 studies. S-649266, which was developed by Shionogi, is currently undergoing phase 2 testing. Phase 3 testing is expected to start next year.

Yoshinori Yamano, PhD, vice president, Discovery Research Laboratory for Core Therapeutic Areas at Shionogi said, “S-649266 works via a ‘Trojan horse’ strategy in which a novel siderophore moiety may significantly improve the antibacterial activity by facilitating efficient transport of S-649266 into the bacterium. The use of the iron uptake system may allow S-649266 to effectively treat Gram-negative bacterial infections that are resistant to presently available antibiotics.” Richard P. Wenzel, MD, MSc, a professor of Medicine and former president of the International Society for Infectious Diseases, commented “Multidrug-resistant rod-shaped bacteria are the key threat in hospitals today, and S-649266 is a promising antibiotic to treat these superbugs.” The study was presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy held September 5–9, 2014, in Washington DC (USA).

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