Pre-treatment of central venous catheters with the cathelicidin BMAP-28 enhances the efficacy of antistaphylococcal agents in the treatment of experimental catheter-related infection.
An in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms developed on 96-well polystyrene tissue culture plates was performed to elucidate the activity of the 27 residues cathelicidin peptide BMAP-28, quinupristin/dalfopristin (Q/D), linezolid, and vancomycin. Efficacy studies were performed in a rat model of staphylococcal CVC infection. Silastic catheters were implanted into the superior cava. Twenty-four hours after implantation the catheters were filled with BMAP-28. Thirty minutes later rats were challenged via the CVC with 1.0x10(6) CFU of S. aureus strain Smith diffuse. Administration of antibiotics into the CVC at a concentration equal to the MBC observed using adherent cells, or at a much higher concentration (1024 microg/mL) began 24 h later. The inhibition activities of all antibiotics against adherent bacteria were at least two-four-fold lower that against freely growing cells. When antibiotics were used in BMAP-28 pre-treated wells, they showed higher activities. The in vivo studies showed that when CVCs were pre-treated with BMAP-28 or with a high dose of antibiotics, biofilm bacterial load was reduced from 10(7) to 10(3) CFU/mL and bacteremia reduced from 10(3) to 10(1) CFU/mL. When CVCs were treated with both BMAP-28 and antibiotics, biofilm bacterial load was further decreased to 10(1) CFU/mL and bacteremia was not detected. These results suggest that CVC pre-treated with BMAP-28 represents an attractive choice for the treatment of device-related infections caused by staphylococci.
Cirioni
Oscar
O
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Giacometti
Andrea
A
Ghiselli
Roberto
R
Bergnach
Cristina
C
Orlando
Fiorenza
F
Mocchegiani
Federico
F
Silvestri
Carmela
C
Licci
Alberto
A
Skerlavaj
Barbara
B
Zanetti
Margherita
M
Saba
Vittorio
V
Scalise
Giorgio
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000627:therapeutic use; D002405:Catheterization, Central Venous; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D011506:Proteins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000378:metabolism; D016896:Treatment Outcome; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C102360:BMAP-28; D011506:Proteins; D054804:Cathelicidins