S-thanatin in vitro prevents colistin resistance and improves its efficacy in an animal model of Pseudomonas aeruginosa sepsis.
An experimental study was performed to evaluate the interaction between s-thanatin and colistin both in vitro and in vivo, using two Pseudomonas aeruginosa strains with different patterns of susceptibilities. We evaluated whether selecting for colistin-resistant P. aeruginosa could be prevented in vitro by combining colistin with s-thanatin. The strains were serially exposed in broth to twofold stepwise increasing concentrations of colistin alone or in combination with a fixed concentration [0.25× minimum inhibitory concentration (MIC)] of s-thanatin. We also performed an in vitro synergy study. For in vivo studies, a mouse model of Pseudomonas sepsis has been used. Main outcome measures were lethality and quantitative blood cultures. Exposure to colistin alone gradually selected for Pseudomonas strains with an increased MIC. In vitro studies, s-thanatin showed a positive interaction with colistin, and was able to prevent its resistance. In vivo studies, s-thanatin combined with colistin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of this combination and provide a future therapeutic alternative in severe Pseudomonas infections.
Clinic of Infectious Diseases, Department of Biomedical Sciences, Università Politecnica delle Marche, Ancona, Italy. o.cirioni@univpm.it
Oscar
O
Cirioni
Guoqiu
G
Wu
Linxian
L
Li
Fiorenza
F
Orlando
Carmela
C
Silvestri
Roberto
R
Ghiselli
Zilong
Z
Shen
Eleonora
E
Gabrielli
Lucia
L
Brescini
Giovanni
G
Lezoche
Mauro
M
Provinciali
Mario
M
Guerrieri
Andrea
A
Giacometti
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D003091:Colistin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C098076:thanatin; D003091:Colistin