Sirtuin Activators

Abstract

Pexiganan acetate (MSI 78) is a synthetic cationic peptide (22 amino acids) with antibacterial activity. It is an analogue of magainin 2, which is a host defence peptide isolated from frog skin.

The drug is thought to act by disturbing the permeability of the cell membrane or cell wall.

Pexiganan acetate has good in vitro activity against Gram-positive and Gram-negative aerobes; 99% of strains were susceptible to the agent using a break-point of 64 mg/L. 89 to 97% of anaerobes were susceptible to pexiganan acetate using the same break-point.

After 7 passages in vitro, there was no evidence of resistance to pexiganan acetate among 2 strains of Staphylococcus aureus.

In 2 phase III multicentre randomised double-blind trials in diabetic patients with infected foot ulcers, both topical pexiganan acetate 1% and oral ofloxacin 800 mg/day achieved clinical cure or improvement in about 90% of patients.

Eradication of pathogens in the 2 studies was achieved in 82% of ofloxacin recipients and 66% of pexiganan acetate recipients at the end of therapy.

Limited data indicate that pexiganan acetate is well tolerated.

References

1. Maloy WL, Kari UP. Structure-activity studies on magainins and other host defense peptides. Biopolymers 1995; 37: 105–22
2. Hancock REW. Peptide antibiotics. Lancet 1997 Feb 8; 349(9049): 418–22
3. Committee on Antimicrobial Agents, Fong IW. Management of diabetic foot infection: a position paper. Can J Infect Dis 1996 Nov–Dec; 7: 361–5
4. Swartz MN. Cellulitis and subcutaneous tissue infections. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 4th ed. v. 1. New York: Churchill Livingstone, 1995: 909–29
5. Bechinger B, Zasloff M, Opella SJ. Structure and orientation of the antibiotic peptide magainin in membranes by solid-state nuclear magnetic resonance spectroscopy. Protein Sci 1993; 2: 2077–84
6. Matsuzaki K, Sugishita K, Harada M, et al. Interactions of an antimicrobial peptide, magainin 2, with outer and inner membranes of Gram-negative bacteria. Biochim Biophys Acta 1997; 1327: 119–30
7. Jacob L, Zasloff M. Potential therapeutic applications of magainins and other antimicrobial agents of animal origin. Ciba Found Symp 1994; 186: 197–216, discussion 216–23
8. Wade D, Boman A, Wáhlin B, et al. All-D amino acid-containing channel-forming antibiotic peptides. Proc Natl Acad Sci U S A 1990 Jun; 87: 4761–5
9. Bessalle R, Kapitkovsky A, Gorea A, et al. All-D-magainin: chirality, antimicrobial activity and proteolytic resistance. FEBS Lett 1990 Nov; 274(1/2): 151–5
10. Iwahori A, Hirota Y, Sampe R, et al. Synthesis of reversed magainin 2 analogs enhanced antibacterial activity. Biol Pharm Bull 1997 Mar; 20: 267–70
11. Fuchs PC, Barry AL, Brown SD. In. vitro antimicrobial activity of MSI-78, a magainin analog. Antimicrob Agents Chemother 1998 May; 42(5): 1213–6
12. MacDonald DL, York DW, Jones LM, et al. In vitro activity of MSI-78, an analog of the frog skin antibiotic magainin vs ofloxacin against aerobic and anaerobic clinical isolates from hospitals throughout the United States [abstract F-45]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy 1997 Sep 28–Oct 1; Toronto, 153
13. MacDonald D, Jones L, Messler C. Comparison of topical agents magainin MSI-78 and mupirocin, potential for resistance development in Staphylococcus aureus [abstract no. 1037]. 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy 1993 Oct 17-20: New Orleans, 309
14. MacDonald DL, Weber A, Patterson H, et al. In vivo efficacy of a magainin compound, MSI-78, in a swine model of wound infection [abstract no. 518]. 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy 1992 Oct 11–14: Anaheim (CA), 197
15. Marshall DA, Mertz PM, Cazzaniga AL, et al. The effect of topical magainin (MSI-78) on Staphylococcus aureus proliferation in wounds [abstract]. Clin Res 1991 Apr; 39: 566A
16. Leyden JJ, McGinley KJ, Rowinski CA, et al. In vivo antimicrobial activity of magainin topical cream against mixed skin flora [abstract no. 474 and poster]. 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy 1993 Oct 17–20: New Orleans, 205
17. Lipsky BA, Litka PA, Zasloff M, et al. Microbial eradication and clinical resolution of infected diabetic foot ulcers treated with topical MSI-78 vs oral ofloxacin [abstract no. LM-57]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy 1997 Sep 28–Oct 1: Toronto, 374
18. Lipsky BA, MacDonald D, Litka PA, et al. Treatment of infected diabetic foot ulcers: topical MSI-78 vs. oral ofloxacin [abstract no. 1895]. Diabetologia 1997 Jun; 40 Suppl. 1: 482
19. Magainin Cytolex being considered for wound-healing indication. FDC Rep Pink Sheet 1997 Oct 20: 10–1

Author information

Authors and Affiliations

Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

Harriet M. Lamb and Lynda R. Wiseman

Authors

• Harriet M. Lamb
• Lynda R. Wiseman