Cecropin B enhances betalactams activities in experimental rat models of gram-negative septic shock.
OBJECTIVE
To investigate the efficacy of imipenem, piperacillin combined with cecropin B in the prevention of lethality in 2 rat models of septic shock. Main outcome measures were bacterial growth in blood and intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma, and lethality.


BACKGROUND
Sepsis remains a serious clinical problem despite intense efforts to improve survival. It is a major cause of morbidity and mortality in hospitalized patients. The primary cause of Gram-negative shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of Gram-negative bacteria.


METHODS
Adult male Wistar rats were given (1). an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 LPS or (2). 2 x 1010 CFU of E. coli ATCC 25922. All animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg cecropin B, 20 mg/kg imipenem, and 120 mg/kg piperacillin alone and combined with 1 mg/kg cecropin B. Each group included 20 animals. RESULTS All compounds reduced the lethality when compared with controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. On the other hand, each betalactam determined an increase of plasma endotoxin and TNF-alpha concentration. Combination between cecropin B and betalactams showed to be the most effective treatment in reducing all variables measured.


CONCLUSIONS
Cecropin B enhances betalactams activities in Gram-negative sepic shock rat models.
Ghiselli
Roberto
R
Department of General Surgery, INRCA IRRCS, University of Ancona, Ancona, Italy.
Giacometti
Andrea
A
Cirioni
Oscar
O
Mocchegiani
Federico
F
Orlando
Fiorenza
F
D'Amato
Giuseppina
G
Sisti
Valerio
V
Scalise
Giorgio
G
Saba
Vittorio
V
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004731:Endotoxins; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy; D015378:Imipenem / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D019476:Insect Proteins / Q000008:administration & dosage*; D008070:Lipopolysaccharides; D008297:Male; D010878:Piperacillin / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004731:Endotoxins; D019476:Insect Proteins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D015378:Imipenem; C031162:cecropin B protein, Insecta; D010878:Piperacillin