Metallopharmaceuticals based on silver(I) and silver(II) polydiguanide complexes: activity against burn wound pathogens.
OBJECTIVE
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.
Pal
Sukdeb
S
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Yoon
Eun Jeong
EJ
Park
Sun Hee
SH
Choi
Eung Chil
EC
Song
Joon Myong
JM
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002056:Burns / Q000150:complications; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D018030:Silver Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D013997:Time Factors; D014946:Wound Infection / Q000382:microbiology
D000900:Anti-Bacterial Agents; D018030:Silver Compounds; D002710:Chlorhexidine