Efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain.
An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain. In vitro experiments included MIC determination, time-kill, and synergy studies. For in vivo studies, a mouse model of sepsis has been used. The main outcome measures were bacterial lethality, quantitative blood cultures, and plasma levels of lipopolysaccharide, tumor necrosis factor alpha, and interleukin-6. The combination of tachyplesin III or colistin with imipenem showed in vitro synergistic interaction. A significant increase in efficacy was also observed in vivo: combination-treated groups had significantly lower levels of bacteremia than did groups treated with a single agent. Tachyplesin III combined with imipenem exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide therapeutic alternatives for serious infections caused by gram-negative bacteria in the coming years.
Cirioni
Oscar
O
Clinica delle Malattie Infettive, c/o Ospedali Riuniti Ancona, Via Conca 71, 60200 Ancona, AN, Italy. o.cirioni@univpm.it.
Ghiselli
Roberto
R
Silvestri
Carmela
C
Kamysz
Wojciech
W
Orlando
Fiorenza
F
Mocchegiani
Federico
F
Di Matteo
Fabio
F
Riva
Alessandra
A
Lukasiak
Jerzy
J
Scalise
Giorgio
G
Saba
Vittorio
V
Giacometti
Andrea
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003091:Colistin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D010456:Peptides, Cyclic; C057636:tachyplesin peptide, Tachypleus tridentatus; D015378:Imipenem; D003091:Colistin