Lysins represent a novel class of anti-infectives derived from bacteriophage. Lysins are bacterial cell-wall hydrolytic enzymes that selectively and rapidly kill (¢3 log c.f.u. in 30 min) specific Gram-positive bacteria providing a targeted therapeutic approach with minimal impact on unrelated commensal flora. The potential for bacterial resistance to lysins is considered low due to targeting of highly conserved peptidoglycan components. Through cutting-edge genetic engineering, lysins can be assembled into large libraries of anti-infective agents tailored to any bacterium of interest including drug-resistant Gram-positive pathogens such as meticillin-and vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, and penicillin-resistant Streptococcus pneumoniae. Lysins can eliminate bacteria systemically and topically from mucosal surfaces and biofilms, as evidenced by experimental models of sepsis, endocarditis, pneumonia, meningitis, and nasopharyngeal, skin and vaginal decolonization. Furthermore, lysins can act synergistically with antibiotics and, in the process, resensitize bacteria to non-susceptible antibiotics. Clinical trials are being prepared to assess the safety and pharmacokinetic properties of lysins in humans.

Staphylococcus aureus is a major human pathogen responsible for a number of serious and sometimes fatal infections. One of its reservoirs on the human body is the skin, which is known to be a source of invasive infection. The potential for an engineered staphylococcus-specific phage lysin (ClyS) to be used for topical decolonization is presented. We formulated ClyS into an ointment and applied it to a mouse model of skin colonization/infection with S. aureus. Unlike the standard topical antibacterial agent mupirocin, ClyS eradicated a significantly greater number of methicillin-susceptible S. aureus (MSSA) and -resistant S. aureus (MRSA) bacteria: a 3-log reduction with ClyS as opposed to a 2-log reduction with mupirocin in our model. The use of ClyS also demonstrated a decreased potential for the development of resistance by MRSA and MSSA organisms compared to that from the use of mupirocin in vitro. Because antibodies may affect enzyme function, we tested antibodies developed after repeated ClyS exposure for their effect on ClyS killing ability. Our results showed no inhibition of ClyS activity at various antibody titers. These data demonstrate the potential of developing ClyS as a novel class of topical antimicrobial agents specific to staphylococcus.

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Methicillin-resistant Staphylococcus aureus (MRSA) in the bloodstream is often fatal. Vancomycin is the most frequently prescribed drug for treatment of MRSA infections with demonstrated efficacy. Recently, however, some MRSA infections have not been responding to vancomycin, even those caused by strains considered susceptible. To provide optimal treatment and avoid vancomycin resistance, therapy should be tailored, especially for patients at highest risk for death. But who are these patients? A study that looked back at medical records and 699 frozen isolates found that risk for death from MRSA infection was highest among certain populations, including the elderly, nursing home residents, patients with severe sepsis, and patients with liver or kidney disease. Risk for death was not affected by the type of MRSA strain (vancomycin susceptible, heteroresistant, or intermediate resistant). Risk was lower among those who had consulted an infectious disease specialist. Thus, when choosing treatment for patients with MRSA infection, it is crucial to look at patient risk factors, not just MRSA strain type. For those at high risk, consultation with an infectious disease specialist is recommended.