TXA11114 is an investigational indole carboxamide efflux pump inhibitor
MIAMI, May 12, 2026 /PRNewswire-PRWeb/ -- TAXIS Pharmaceuticals, a clinical-stage company developing investigational anti-resistance therapies to address antimicrobial resistance (AMR), today announced the publication of preclinical data in the peer-reviewed journal Antibiotics describing TXA11114, an investigational indole carboxamide efflux pump inhibitor (EPI) designed to enhance the activity of existing antibiotics against multidrug-resistant (MDR) Pseudomonas aeruginosa.
The manuscript, titled, "TXA11114: Discovery of an In Vivo Efficacious Efflux Pump Inhibitor (EPI) That Potentiates Levofloxacin Against Pseudomonas aeruginosa," reports in vitro and murine infection model data demonstrating that TXA11114 enhances the antibacterial activity of levofloxacin, a fluoroquinolone commonly used in the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).
In in vitro studies, TXA11114 enhanced levofloxacin activity by ≥8-fold in 90% of multidrug-resistant clinical isolates obtained from the CDC Antibiotic Resistance Isolate Bank and Walter Reed Army Hospital when tested at subinhibitory concentrations. The TXA11114–levofloxacin combination restored susceptibility in approximately 30% of resistant isolates and reduced levofloxacin minimum inhibitory concentrations (MICs) to at or below established clinical breakpoints in a substantial proportion of strains evaluated.
In murine thigh and lung infection models of P. aeruginosa, the TXA11114–levofloxacin combination demonstrated enhanced bacterial killing compared to levofloxacin alone. These findings represent a notable preclinical demonstration of in vivo efficacy for an efflux pump inhibitor in combination with a fluoroquinolone against multidrug-resistant P. aeruginosa.
Mechanistic studies reported in the publication support efflux inhibition as the primary mode of action. TXA11114 increased intracellular accumulation of levofloxacin and ethidium bromide in live bacterial cells in a concentration-dependent manner. Additional assays demonstrated that TXA11114 did not disrupt outer or inner bacterial membrane integrity at concentrations relevant to antibiotic potentiation, nor did it collapse membrane potential or deplete intracellular ATP levels, distinguishing it from previously described compounds associated with membrane-disruptive effects.
The combination also reduced the frequency of spontaneous resistance emergence to undetectable levels under the experimental conditions evaluated, compared to levofloxacin alone.
In preclinical safety screening assays, TXA11114 demonstrated low cytotoxicity and minimal acute toxicity, and pharmacokinetic studies in infected mice indicated plasma and bronchoalveolar lavage fluid exposure profiles complementary to those of levofloxacin.
"Publication of these data in Antibiotics provides peer-reviewed validation of our efflux pump inhibitor program," said Gregory G. Mario, MBA, President and CEO of TAXIS Pharmaceuticals. "These findings reinforce our strategy of developing investigational anti-resistance agents designed to restore and extend the utility of existing antibiotics against multidrug-resistant pathogens."
Pseudomonas aeruginosa is recognized by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) as a serious antimicrobial resistance threat and is a leading cause of hospital-acquired and ventilator-associated pneumonia. Overexpression of resistance-nodulation-division (RND) efflux pumps in P. aeruginosa is a key contributor to multidrug resistance, limiting intracellular antibiotic exposure and reducing treatment effectiveness.
TAXIS Pharmaceuticals is continuing to advance its investigational efflux pump inhibitor platform as part of its broader pipeline of anti-resistance agents targeting priority Gram-negative and Gram-positive pathogens.
About TAXIS Pharmaceuticals
TAXIS Pharmaceuticals is a clinical-stage company developing new classes of anti-resistance therapies to treat life-threatening, multidrug-resistant bacterial infections. Our investigational drug candidates – including efflux pump inhibitors, dihydrofolate reductase inhibitors, and FtsZ inhibitors – aim to combat antimicrobial resistance (AMR). TAXIS' investigational therapies currently target several different bacterial pathogens, many of which are on the WHO Priority Pathogen List. TAXIS is actively pursuing additional funding and collaborations with pharmaceutical manufacturers to facilitate the development and commercialization of its investigational therapies aimed at fighting antimicrobial resistance. Our mission is to reduce and potentially eliminate the threat of current and emergent antimicrobial resistant bacteria across a wide range of infectious diseases and save lives. To learn more, visit: https://taxispharma.com/.
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Media Contact
Jennifer Ringler, TAXIS Pharmaceuticals, 1 973-647-5004, [email protected], https://taxispharma.com/
SOURCE TAXIS Pharmaceuticals
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