Efficacy of the bovine antimicrobial peptide indolicidin combined with piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis.
OBJECTIVE
To investigate the efficacy of piperacillin/tazobactam combined with indolicidin in the prevention of lethality in two rat models of polymicrobial peritonitis.


METHODS
Prospective, randomized, controlled animal study.


METHODS
Research laboratory in a university hospital.


METHODS
Adult male Wistar rats.


METHODS
Adult male Wistar rats were given an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 lipopolysaccharide or had intraabdominal sepsis induced by cecal ligation and puncture. For each model, all animals were randomized to receive isotonic sodium chloride solution intraperitoneally, 1 mg/kg indolicidin, 120 mg/kg piperacillin/tazobactam, and 1 mg/kg indolicidin combined with 120 mg/kg piperacillin/tazobactam. Each group included 20 animals.


RESULTS
Main outcome measures were: bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin, interleukin-6, and tumor necrosis factor-alpha concentrations in plasma; and lethality. All compounds reduced significantly bacterial growth and lethality compared with saline treatment. Treatment with indolicidin resulted in significant decrease in plasma endotoxin and cytokine levels, whereas piperacillin/tazobactam exerted the opposite effect. The combination between indolicidin and piperacillin/tazobactam proved to be the most effective treatment in reducing all variables measured.


CONCLUSIONS
Indolicidin may have potential therapeutic usefulness alone and when associated with piperacillin/tazobactam in polymicrobial peritonitis.
Ghiselli
Roberto
R
Department of General Surgery, INRCA-IRRCS, Università Politecnica delle Marche, Ancona, Italy.
Giacometti
Andrea
A
Cirioni
Oscar
O
Mocchegiani
Federico
F
Orlando
Fiorenza
F
Silvestri
Carmela
C
Di Matteo
Fabio
F
Abbruzzetti
Alessandra
A
Scalise
Giorgio
G
Saba
Vittorio
V
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010538:Peritonitis / Q000188:drug therapy*; D010878:Piperacillin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy; D000078142:Tazobactam; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C073143:indolicidin; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin