Evaluation of Topical Lysostaphin as a Novel Treatment for Instrumented Rhesus Macaques (Macaca mulatta) Infected with Methicillin-Resistant Staphylococcus aureus
| Autor: | Maria Pardos de la Gandara, Christopher E Cheleuitte-Nieves, Leslie Lynn Diaz, Chad W. Euler, Alejandra Gonzalez, Winrich A. Freiwald, Hermínia M de Lencastre, Alexander Tomasz |
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| Rok vydání: | 2020 |
| Předmět: |
General Veterinary
040301 veterinary sciences business.industry Lysostaphin 04 agricultural and veterinary sciences medicine.disease_cause Antimicrobial Methicillin-resistant Staphylococcus aureus General Biochemistry Genetics and Molecular Biology Microbiology 0403 veterinary science Lytic cycle Bacteriocin In vivo Staphylococcus aureus Medicine Implant business |
| Zdroj: | Comparative Medicine. 70:335-347 |
| ISSN: | 1532-0820 |
| Popis: | Lytic enzymes are novel antimicrobial agents that degrade bacterial cell walls, resulting in cell rupture and death. We tested one enzyme, the bacteriocin lysostaphin, for treatment of nonhuman primates (Macaca mulatta) with persistent methicillinresistant Staphylococcus aureus (MRSA) infection of their cranial implant margins. The goal of this study was to determine if topical lysostaphin, either alone or as an adjunct therapy, could eliminate MRSA. Lysostaphin had in vitro lytic activity against all 4 previously identified NHP MRSA clones, as well as against 12 MRSA isolates of the same clonal type (MLST ST3862 and spa type t4167) before and after treatment, with no resistance discovered. In an in vivo pilot study, a 2-d application of lysostaphin alone reduced MRSA in the implant margins by 3-logs during treatment of one animal; however, MRSA titers had returned to control levels by 1 wk after treatment. In the main study, all animals (n = 4) received 10 d of systemic antibiotic treatment and both the animals and their environment (cages, equipment, room) underwent 5-d of decontamination. The experimental animals (n = 2) received 5 doses of topical lysostaphin (15 mg, every other day) applied onto their implant margins. Daily cultures showed that MRSA counts decreased significantly (≤ 25 colony-forming units/mL; P < 0.05). However, sampling of the cranial implant margin 7 d after last treatment showed that MRSA counts had returned to control levels. Our study suggests that lysostaphin, coupled with other treatment modalities, can decrease MRSA infection short-term but do not completely eradicate MRSA in the long-term. This reappearance of MRSA may be due to cross-contamination or reinfection from other infected areas, an inability of the treatment to reach all colonized areas, or insufficient dosing or length of treatment. Topical lysostaphin may be more useful clinically for superficial nonimplant associated wounds in which the lytic enzyme has better access to the infected tissue. |
| Databáze: | OpenAIRE |
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