Metallopharmaceuticals based on silver(I) and silver(II) polydiguanide complexes: activity against burn wound pathogens.

Abstract

OBJECTIVES:

The in vitro pharmacodynamics of silver(I) and silver(II) complexes of a polydiguanide ligand, chlorhexidine, were assayed to examine the value of the bactericidal endpoint as an alternative means of evaluating their antibacterial activities against burn wound pathogens.

METHODS:

Synthesis of silver(I) chlorhexidine [Ag(I)CHX] was accomplished by in situ precipitation of the complex from a feebly acidic or neutral aqueous solution of AgNO(3) and chlorhexidine, whereas silver(II) chlorhexidine [Ag(II)CHX] was synthesized by oxidation of Ag(I), followed by complexation of the oxidized metal with chlorhexidine. Their antibacterial potencies were assessed in vitro by determining the MICs and MBCs for four Gram-positive and four Gram-negative bacteria. Time-kill assays using three different concentrations of these agents were also performed.

RESULTS:

The MICs of Ag(I)CHX and Ag(II)CHX were much lower than those of chlorhexidine, AgNO(3) and silver sulfadiazine. The time-kill study provided quantitative information on actual times required to reach the bactericidal endpoint using a particular concentration of the active agent. The lethality rates of Ag(I)CHX and Ag(II)CHX against the tested bacteria were 2× to 8× faster than those of chlorhexidine or AgNO(3) at a concentration equal to or 4× MIC.

CONCLUSIONS:

Ag(I)CHX and Ag(II)CHX showed superior antibacterial activity and faster killing kinetics compared with chlorhexidine and AgNO(3). These complexes may serve as new-generation antibacterial agents in wound care.

• Authors: Sukdeb Pal, Eun Jeong Yoon, Sun Hee Park, Eung Chil Choi, Joon Myong Song
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 65 Issue 10 Pg. 2134-40 (Oct 2010) ISSN: 1460-2091 [Electronic] England
• PMID: 20705628 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Silver Compounds
• Chlorhexidine

Topics

• Anti-Bacterial Agents (chemical synthesis, pharmacology)
• Burns (complications)
• Chlorhexidine (analogs & derivatives, pharmacology)
• Gram-Negative Bacteria (drug effects)
• Gram-Positive Bacteria (drug effects)
• Microbial Sensitivity Tests
• Microbial Viability (drug effects)
• Silver Compounds (chemical synthesis, pharmacology)
• Time Factors
• Wound Infection (microbiology)