Minocycline and the SPR741 Adjuvant Are an Efficacious Antibacterial Combination for <i>Acinetobacter baumannii</i> Infections
Yonas A. Alamneh,
Vlado Antonic,
Brittany Garry,
Michael J. Pucci,
Rania Abu-Taleb,
Jonathan P. Shearer,
Samandra T. Demons,
Derese Getnet,
Brett E. Swierczewski,
Troy Lister,
Daniel V. Zurawski
Affiliations
Yonas A. Alamneh
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Vlado Antonic
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Brittany Garry
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Michael J. Pucci
Spero Therapeutics, Inc., Cambridge, MA 02139, USA
Rania Abu-Taleb
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Jonathan P. Shearer
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Samandra T. Demons
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Derese Getnet
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Brett E. Swierczewski
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Troy Lister
Spero Therapeutics, Inc., Cambridge, MA 02139, USA
Daniel V. Zurawski
Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Antibiotic resistance, when it comes to bacterial infections, is not a problem that is going to disappear anytime soon. With the lack of larger investment in novel antibiotic research and the ever-growing increase of resistant isolates amongst the ESKAPEE pathogens (Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus sp., and Escherichia coli), it is inevitable that more and more infections caused by extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains will arise. One strategy to counteract the growing threat is to use antibiotic adjuvants, a drug class that on its own lacks significant antibiotic activity, but when mixed with another antibiotic, can potentiate increased killing of bacteria. Antibiotic adjuvants have various mechanisms of action, but polymyxins and polymyxin-like molecules can disrupt the Gram-negative outer membrane and allow other drugs better penetration into the bacterial periplasm and cytoplasm. Previously, we showed that SPR741 had this adjuvant effect with regard to rifampin; however, rifampin is often not used clinically because of easily acquired resistance. To find additional, appropriate clinical partners for SPR741 with respect to pulmonary and wound infections, we investigated tetracyclines and found a previously undocumented synergy with minocycline in vitro and in vivo in murine models of infection.
