Efficacy of the amphibian peptide distinctin in a neutropenic mouse model of staphylococcal sepsis.
OBJECTIVE
To investigate the efficacy of distinctin in a neutropenic mouse model of staphylococcal sepsis.


METHODS
Prospective, randomized, and controlled animal study.


METHODS
Research laboratory in a University Hospital.


METHODS
BALB/c male mice.


METHODS
Mice were rendered neutropenic by injecting cyclophosphamide (200 mg/kg of body weight/day) on days -4 and -2 preinfection. Infection was induced at time 0 by intraperitoneal injection of 1 x 10(9) colony forming units of the staphylococcal strain. For each model, all animals were randomized to receive intravenous isotonic sodium chloride solution, 1 mg/kg distinctin, and 10 mg/kg imipenem, 10 mg/kg vancomycin, 10 mg/kg teicoplanin or 10 mg/kg linezolid alone, or combined with 1 mg/kg distinctin.


RESULTS
Lethality, bacterial growth in blood and peritoneum, spleen, liver, and mesenteric lymph nodes.


RESULTS
All combined regimen showed lower lethality rates than singly treated-groups. Distinctin plus vancomycin or teicoplanin exerted the lowest lethality rate. All regimens were significantly superior to controls at reducing blood, spleen, peritoneum, liver and mesenteric lymph node complex bacterial burdens, whereas all combined treated groups were higher effective than singly treated groups.


CONCLUSIONS
Our data indicate that distinctin alone or combined with other antibiotics may be useful in treating severe staphylococcal infections.
Cirioni
Oscar
O
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy. o.cirioni@univpm.it
Ghiselli
Roberto
R
Orlando
Fiorenza
F
Silvestri
Carmela
C
De Luca
Stefania
S
Salzano
Anna Maria
AM
Mocchegiani
Federico
F
Saba
Vittorio
V
Scalise
Giorgio
G
Scaloni
Andrea
A
Giacometti
Andrea
A
D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001001:Anura; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006461:Hemolysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy*; D011897:Random Allocation; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification
D029845:Amphibian Proteins; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C531945:distinctin