Staphylococcus aureus Skin Infections
Staphylococcus aureus (S. aureus) is the leading cause of skin and soft tissue infections (SSTI), also referred to as skin and skin structure infections. Methicillin-resistant S. aureus (MRSA) is a predominant cause of hospital- and community-acquired SSTI. Recent studies conducted by the US Department of Defense Tricare health system have estimated rates of S. aureus SSTIs (54% MRSA) among their non-active duty population that would correspond to about 300,000 cases in the US population annually. Active duty military personnel were at a five-fold higher risk for S. aureus SSTIs (63% MRSA).1 Patients with S. aureus SSTIs have been reported to have a 50% rate of recurrent infections within six months.2
Preclinical research has demonstrated that NDV-3 is efficacious against SSTI due to MRSA, inducing robust immune system responses.3 In pursuit of this finding, a Phase 2a clinical study of NDV-3A in military recruits susceptible to S. aureus colonization and SSTI was initiated in Jan 2018. This study will evaluate NDV-3A versus placebo in 420 recruits to evaluate the impact of NDV-3A in preventing acquisition of S. aureus nasal colonization in those not previously colonized and, as a secondary outcome, reduction in S. aureus nasal colonization in those already colonized.4 This research supports NovaDigm’s continued development and evaluation of the NDV-3 vaccine to protect against S. aureus SSTI infections in groups at increased risk for infection.
Approximately two million nosocomial (hospital-acquired) infections occur in the United States every year, resulting in 90,000 deaths.5 Drug-resistant Candida species and S. aureus have been found to cause an increasing number of life-threatening invasive infections and are included in the 2013 CDC list of Antibiotic Resistant Threats in the United States. In a recent CDC survey of US acute care hospitals Candida species and S. aureus were the first and third most common nosocomial bloodstream infections, respectively.6 Click here to learn more about S. aureus infections, and click here to learn more about Candida infections.
In preclinical studies, NDV-3 has demonstrated efficacy in reducing the mortality of otherwise highly lethal disseminated bloodstream infections caused by either Candida or MRSA. These studies underscore the promise of NDV-3A as a clinically useful vaccine targeting these extremely common, increasingly antibiotic-resistant and highly lethal pathogens. Several common risk factors lead to serious invasive infections in hospitals, including the underlying diseases and immunocompetence of patients, colonization by Candida or S. aureus, the use of invasive medical devices such as venous catheters and feeding tubes, recent surgery and the recent use of broad-spectrum antibiotics.6,7 Due to the already established risk factors in hospitalized patients, the efficacy of NDV-3A in nosocomial indications could be determined by vaccinating patients at high risk for Candida or S. aureus infections and assessing the vaccine’s ability to reduce infection and mortality rates.
- Landrum ML, Neumann C, Cook C, Chukwuma U, Ellis MW, Hospenthal DR and Murray CK, Epidemiology of Staphylococcus aureus Blood and Skin and Soft Tissue Infections in the US Military Health System 2005-2010. JAMA; 308(1): 50-59.
- Fritz SA, Camins BC, Eisenstein KA, Fritz JM, Epplin EK, Burnham C-A, Dukes J and Storch GA, Effectiveness of Measures to Eradicate Staphylococcus aureus Carriage in Patients with Community-Associated Skin and Soft-Tissue Infections: A Randomized Trial. Infect Control Hosp Epidemiol 2011; 32(9): 872-880.
- Yeaman MR, Filler SG, Chaili S, Barr K, Wang H, Kupferwasser D, Fu Y, Hennessey JP, Schmidt CS, Edwards JE Jr., Xiong YQ and Ibrahim AS, Efficacy and Immunologic Mechanisms of the NDV-3 Vaccine in a Murine Model of MRSA Skin/Skin Structure Infection. PNAS 2014; www.pnas.org/cgi/doi/10.1073/pnas.1415610111.
- Clinicaltrials.gov identifier NCT03455309.
- Klevens, RM, Edwards, JR, Richards, CL. Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002. Public Health Reports 2007; 122 (2): 160-166.
- Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, Ray, SM, Thompson DL, Wilson LE, Fridkin SK, Multistate Point-Prevalence Survey of Health Care-Associated Infections. NEJM 2014; 370: 1198-1208.
- Safdar N, and Maki DG, The Commonality of Risk factors for Nosocomial Colonization and Infection with Antimicrobial-Resistant Staphylococcus aureus, Enterococcus, Gram-Negative Bacilli, Clostridium difficile and Candida. Ann Intern Med 2002; 136: 834-844.