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Potential factors contributing to the poor antimicrobial efficacy of SAAP-148 in a rat wound infection model

Authors
  • Dijksteel, Gabrielle S.1, 2
  • Ulrich, Magda M. W.1, 2
  • Vlig, Marcel1
  • Nibbering, Peter H.3
  • Cordfunke, Robert A.3
  • Drijfhout, Jan W.3
  • Middelkoop, Esther1, 2
  • Boekema, Bouke K. H. L.1
  • 1 Association of Dutch Burn Centres, Zeestraat 29, Beverwijk, 1941 AJ, The Netherlands , Beverwijk (Netherlands)
  • 2 Amsterdam University Medical Centres, Free University of Amsterdam, Amsterdam Movement Sciences, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands , Amsterdam (Netherlands)
  • 3 Leiden University Medical Centre, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands , Leiden (Netherlands)
Type
Published Article
Journal
Annals of Clinical Microbiology and Antimicrobials
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 03, 2019
Volume
18
Issue
1
Identifiers
DOI: 10.1186/s12941-019-0336-7
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundWe investigated the efficacy of a synthetic antimicrobial peptide SAAP-148, which was shown to be effective against Methicillin-resistant Staphylococcus aureus (MRSA) on tape-stripped mice skin. Unexpectedly, SAAP-148 was not effective against MRSA in our pilot study using rats with excision wounds. Therefore, we investigated factors that might have contributed to the poor efficacy of SAAP-148. Subsequently, we optimised the protocol and assessed the efficacy of SAAP-148 in an adapted rat study.MethodsWe incubated 100 µL of SAAP-148 with 1 cm2 of a wound dressing for 1 h and determined the unabsorbed volume of peptide solution. Furthermore, 105 colony forming units (CFU)/mL MRSA were exposed to increasing dosages of SAAP-148 in 50% (v/v) human plasma, eschar- or skin extract or PBS. After 30 min incubation, the number of viable bacteria was determined. Next, ex vivo skin models were inoculated with MRSA for 1 h and exposed to SAAP-148. Finally, excision wounds on the back of rats were inoculated with 107 CFU MRSA overnight and treated with SAAP-148 for 4 h or 24 h. Subsequently, the number of viable bacteria was determined.ResultsContrary to Cuticell, Parafilm and Tegaderm film, < 20% of peptide solution was recovered after incubation with gauze, Mepilex border and Opsite Post-op. Furthermore, in plasma, eschar- or skin extract > 20-fold higher dosages of SAAP-148 were required to achieve a 2-log reduction (LR) of MRSA versus SAAP-148 in PBS. Exposure of ex vivo models to SAAP-148 for 24 h resulted in a 4-fold lower LR than a 1 h or 4 h exposure period. Additionally, SAAP-148 caused a 1.3-fold lower mean LR at a load of 107 CFU compared to 105 CFU MRSA. Moreover, exposure of ex vivo excision wound models to SAAP-148 resulted in a 1.5-fold lower LR than for tape-stripped skin. Finally, SAAP-148 failed to reduce the bacterial counts in an adapted rat study.ConclusionsSeveral factors, such as absorption of SAAP-148 by wound dressings, components within wound exudates, re-colonisation during the exposure of SAAP-148, and a high bacterial load may contribute to the poor antimicrobial effect of SAAP-148 against MRSA in the rat model.

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