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Published on: December 27, 2016
In vivo activity of anprocide alone, and in vitro activity in combination with conventional antibiotics against
Robin K Pettit1, Christine A Weber1, Stacey B Lawrence1
1Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
Abstract:
The alarming spread of multiple drug resistance in Staphylococcus aureus, combined with the frequent occurrence of S. aureus and Staphylococcus epidermidis in biofilm-type infections, indicates a growing need for new therapies. The experimental steroidal amide anprocide [3beta-acetoxy-17beta-(l-prolyl)amino-5alpha-androstane] significantly reduced c.f.u. ml(-1) per suture (P <0.0001) in a murine model of topical S. aureus infection. In chequerboard assays with planktonic-grown S. aureus and S. epidermidis, anprocide was synergistic with bacitracin, oxacillin, clindamycin or ceftriaxone. Anprocide was also synergistic in combination with bacitracin or oxacillin against some isolates of biofilm-grown S. aureus and S. epidermidis.
Insights
The experimental steroidal amide anprocide shows promise against drug-resistant Staphylococcus bacteria. It effectively reduced bacterial counts and demonstrated synergistic effects with existing antibiotics in both planktonic and biofilm models.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Rising antimicrobial resistance in Staphylococcus aureus necessitates novel therapeutic strategies.
- Staphylococcus aureus and Staphylococcus epidermidis are frequently implicated in challenging biofilm infections.
Purpose of the Study:
- To evaluate the efficacy of the steroidal amide anprocide against Staphylococcus species.
- To investigate the synergistic potential of anprocide in combination with established antibiotics.
Main Methods:
- Anprocide's efficacy was assessed in a murine model of topical Staphylococcus aureus infection.
- Checkerboard assays were employed to determine synergistic interactions with antibiotics against planktonic and biofilm-grown bacteria.
Main Results:
- Anprocide significantly reduced bacterial colony-forming units in a murine S. aureus infection model.
- Synergistic effects were observed when anprocide was combined with bacitracin, oxacillin, clindamycin, or ceftriaxone against planktonic bacteria.
- Anprocide also showed synergy with bacitracin or oxacillin against some biofilm-grown S. aureus and S. epidermidis isolates.
Conclusions:
- Anprocide exhibits significant antimicrobial activity against Staphylococcus aureus in vivo.
- Anprocide demonstrates synergistic potential with multiple antibiotics, offering a promising avenue for combating drug-resistant and biofilm-associated staphylococcal infections.
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