VRE: Vancomycin-resistant enterococci in purple
Since the introduction of penicillin in the 1940s, a complex array of factors has led to an era in which some bacterial infections no longer respond to any approved antibiotics. The Centers for Disease Control and Prevention estimate that antibiotic-resistant bacteria cause at least 35,000 deaths and 2.8 million illnesses annually in the U.S. alone.
To improve therapeutic options for resistant infections, NIAID provided support to Zavante Therapeutics, Inc. (now Nabriva Therapeutics) for the clinical development of the intravenous (IV) form of the antibiotic fosfomycin (ZTI-01). Fosfomycin is a broad-spectrum antibiotic active against many Gram-positive and Gram-negative bacteria, including multi-drug resistant strains. However, unlike in Europe, where both oral and IV formulations are approved, this therapeutic is only available in oral form in the U.S. IV delivery allows the antibiotic to be delivered directly into the bloodstream, acting much faster than the oral form and reaching the concentrations needed to treat complicated hospital-acquired infections. A NIAID-supported Phase I clinical trial demonstrated the safety of IV fosfomycin in healthy adults and provided insight into the concentrations of fosfomycin reached in blood and urine using different doses of oral and IV fosfomycin.
Following the success of the Phase I trial, Zavante Therapeutics sponsored a Phase II/III clinical trial evaluating the efficacy of IV fosfomycin in treating complicated urinary tract infections (cUTIs). The study compared IV fosfomycin against the standard treatment (piperacillin/tazobactam) and found that IV fosfomycin was safe and worked equally as well in these patients. The U.S. Food and Drug Administration granted Fast Track designation and Qualified Infectious Disease Product designation for the investigation of fosfomycin for cUTIs, hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP), among others. NIAID is now supporting a Phase I trial in healthy volunteers to establish the right dosage for the use of this important investigational antibiotic in patients with HABP and VABP.