Clinical research projects related to antibacterial resistance (AR) focus on a variety of approaches, including evaluating the safety and effectiveness of new antimicrobial therapeutics, and developing novel prevention strategies. In addition, NIAID supports a number of studies on optimizing use of existing drugs. An important goal of this research is to identify treatment regimens that limit the emergence of drug resistance, which is a growing problem in treating infectious diseases.
Select examples of NIAID-supported AR clinical research activities are listed below. These include ongoing and recently supported trials and studies in development. View definitions of study phases and other words related to clinical research.
- NIAID is supporting studies evaluating new ways to treat gonorrhea, including
- Safety and efficacy of an investigational oral antibiotic (Phase II trial)
- Safety, tolerability, drug absorption and distribution of an oral next generation macrolide (Phase I trial)
- NIAID is partnering with the company developing this macrolide to compare the novel antibiotic to standard treatment: intramuscular ceftriaxone plus oral azithromycin. (Phase III trial)
- Investigational oral antibiotic EDP-788 for methicillin-resistant Staphylococcus aureus (MRSA): Studies of safety, drug absorption, distribution, metabolism, and excretion, as well as evaluation of different formulations of this drug (Phase I study)
- Novel narrow spectrum agent, CRS3123, with activity against intestinal bacterium Clostridium difficile: Safety, drug absorption, distribution, and optimal dosage of drug (Phase I studies)
- Safety, tolerability, drug absorption, and distribution of a new formulation of a drug to treat urinary tract infections (Phase I study)
- Cardiac safety of the experimental TB drug, PA-824, alone or in combination with moxifloxacin (Phase I trial)
- Effect of rifampicin or rifabutin on blood levels and metabolism of the newly approved TB drug Bedaquiline (TMC-207) (Phase I trial)
- Safety and drug metabolism of multiple once a day doses of an investigational TB drug SQ109 (Phase Ib/c trials)
Optimizing Use of Existing Drugs
- Utilization of oral "first-line" antibiotics (such as trimethoprim sulfamethoxazole, clindamycin, and cephalexin) that are no longer under patent to effectively treat skin and soft tissue infections (SSTIs) caused by community-acquired methicillin-resistant S. aureus (CA-MRSA) in order to preserve "last-line" agents. These trials are also evaluating whether certain forms of CA-MRSA can be managed without antibiotics (e.g., through drainage and wound care). (Phase IIb studies)
- Shortened duration of therapy for staphylococcal bloodstream infections, including catheter-related infections, to reduce emergence of resistance (Phase II study)
- Shortened duration of therapy for urinary tract infections in children to reduce emergence of resistance (Phase II study)
- Treatment of acute otitis media in children; strategies include determining the need for antibiotic treatment and shortening duration of therapy to reduce emergence of resistance (Phase II study)
- Optimizing the treatment of ventilator-associated pneumonia caused by Acinetobacter and Pseudomonas (Phase II study)
- Optimal utilization of older antibiotics (such as colistin) to limit toxicity and reduce emergence of resistance. Studies are underway to determine proper dosage and evaluate different formulations and combination therapy.
- Safety, drug absorption, distribution, and optimal dosage of extended duration high-dose cefixime for the treatment of reduced susceptibility gonorrhea (Phase I study)
- Treatment of gonorrhea using two antibiotic therapies in combination (i.e., gentamicin/ azithromycin vs. gemifloxacin/azithromycin) (Phase IV study)
- Safety, efficacy, and drug metabolism of four dosages of levofloxacin to establish the optimal dose for treatment of multidrug-resistant TB in combination with standard drugs (Phase II study)
- Nasal decolonization of S. aureus using novel topical agent, XF-73 (Phase I study)
- Nasal decolonization of MRSA using topical antibiotic in neonatal intensive care units (Phase II study)
- Impact of decolonization on hospital acquired infections (HAIs) in the general inpatient population. The Active Bathing to Eliminate Infection (ABATE Infection) Trial will evaluate 1) universal daily chlorhexidine bathing to prevent infections from all pathogens, combined with 2) nasal decolonization with mupirocin for known carriers of MRSA.
- Decontamination of breathing tubes to reduce healthcare-associated infections and emergence of resistance (Phase I study)
Antibacterial Resistance Leadership Group
In 2013, NIAID launched the Antibacterial Resistance Leadership Group (ARLG), a major new clinical effort to address AR and complement other ongoing AR clinical research activities. The ARLG has developed a clinical research agenda identifying the most pressing clinical questions in AR. Studies conducted by the ARLG may include clinical testing of new drugs to treat multidrug-resistant Gram-negative bacteria, evaluating diagnostic devices in clinical settings, evaluating the effectiveness of new antibacterial stewardship programs, and optimizing treatment regimens to reduce the emergence of resistance. The ARLG is drawing on the creativity of the global research community by inviting concept submissions to identify and address AR priorities. Visit the ARLG website for more information.