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Evaluation of Cyclic Lipopeptide(s) Formulations on the Proliferation of Methicillin Resistant Staphylococcus Aureus USA300 in a Porcine Deep Partial Thickness Wound Model

Background: Chronic and acute wound infections can be difficult to treat and very costly. Novel broad-spectrum cationic antimicrobial cyclic lipopeptides (CLP) have been designed to provide broad spectrum activity against both Gram-positive and Gram-negative. Their therapeutic potential was studied using a multi-functional graft polyelectrolyte lipopeptide nanocomplex. This nanocomplex may protect CLPs from serum degradation, control their release rate and enhance their penetration into biofilms.

Purpose: The objective of this study was to determine the antimicrobial effects of CLPs incorporated into a nanocomplex formulation.  

Methods: A Methicillin Resistant Staphylococcus aureus (MRSA) biofilm porcine wound model was used. Two animals each received forty-eight deep partial thickness wounds.  Wounds were inoculated with 106 Log CFU/ml of MRSA USA300. All wounds were randomly designated to one of the six treatments groups: 1) Nanoformulation + CLP2579-4 (7mg/ml) or Nanoformulation + CLP2579-7 (7mg/ml), 2) Nanoformulation Vehicle, 3) DMSO + CLP2579-4 (7mg/ml) or DMSO + CLP2579-7 (7mg/ml), 4) DMSO Vehicle, 5) Mupirocin Positive Control and 6) Untreated Control. Wounds from each group were assessed on Days 1 and 5 after treatment application.

Results: Overall, the results demonstrated that Mupirocin Positive Control exhibited the least bacterial counts on both assessment days (p<0.05) compared to all treatment groups. On Day 1, Nanoformulation + CLP2579-7 (7mg/ml) displayed a 5.39 Log CFU/ml Nanoformulation + CLP2579-4 (7mg/ml) dropped almost 2 Logs from Day 1 to Day 5. While there wasn’t any significant difference between Nanoformulation + CLP2579-4 (7mg/ml) and Nanoformulation + CLP2579-7 (7mg/ml) on Day 5, both had more bacterial reductions than all DMSO formulations, Nanoformulation Vehicle and Untreated Control.

Conclusion: This data may have some important clinical implications and additional studies are warranted.

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