The antimicrobial peptide BMAP-28 reduces lethality in mouse models of staphylococcal sepsis.
OBJECTIVE
A mouse model of staphylococcal sepsis was used to compare the efficacy of the bovine antimicrobial peptide BMAP-28, a compound of the cathelicidin family, with that of conventional antibiotics.


METHODS
Prospective, randomized, controlled animal study.


METHODS
Research laboratory in a university hospital.


METHODS
BALB/c male mice.


METHODS
BALB/c mice were injected intravenously with 2.0 x 10(6) colony-forming units of live Staphylococcus aureus ATCC 25923 or with 5.0 x 10(8) heat-killed cells of the same strain. All animals were randomized to receive intravenously isotonic sodium chloride solution, 2 mg/kg BMAP-28, 7 mg/kg imipenem, 7 mg/kg vancomycin, 7 mg/kg clindamycin, and 7 mg/kg clarithromycin immediately and at 6 hrs after bacterial challenge.


RESULTS
Lethality, quantitative blood cultures, and detection of tumor necrosis factor-alpha and interleukin-6 plasma levels. In the experiments performed with live bacteria, all compounds reduced lethality rates and bacterial growth compared with controls. Imipenem and vancomycin exhibited the highest efficacy on these main outcome measures. In the experiments performed using heat-killed organisms, only BMAP-28 demonstrated significant efficacy on lethality rates, tumor necrosis factor-alpha, and interleukin-6 plasma levels compared with controls.


CONCLUSIONS
These results highlight the capacity of BMAP-28 to reduce the effects of components of the bacterial cells and suggest that it may be beneficial in the treatment of severe staphylococcal infections in concert with other antimicrobial agents.
Giacometti
Andrea
A
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Cirioni
Oscar
O
Ghiselli
Roberto
R
Bergnach
Cristina
C
Orlando
Fiorenza
F
D'Amato
Giuseppina
G
Mocchegiani
Federico
F
Silvestri
Carmela
C
Del Prete
Maria Simona
MS
Skerlavaj
Barbara
B
Saba
Vittorio
V
Zanetti
Margherita
M
Scalise
Giorgio
G
D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011336:Probability; D011506:Proteins / Q000494:pharmacology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; C102360:BMAP-28; D015850:Interleukin-6; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha