Abstract
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 citropin 1.1, rifampin and minocycline. 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 citropin 1.1 (10 μg/mL). Thirty minutes later the rats were challenged via the CVC with 1.0 × 106 CFU of S. aureus strain Smith diffuse. Administration of antibiotics into the CVC (the antibiotic lock technique) began 24 h later. The study included: one control group (no CVC infection), one contaminated group that did not receive any antibiotic prophylaxis, one contaminated group that received citropin 1.1-treated CVC, two contaminated groups that received citropin 1.1-treated CVC plus rifampin and minocycline at concentrations equal to MBCs for adherent cells and 1024 μg/mL in a volume of 0.1 mL that filled the CVC and two contaminated groups that received rifampin or minocycline at the same concentrations. All catheters were explanted 7 days after implantation. Main outcome measures were: minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), synergy studies, quantitative culture of the biofilm formed on the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. MICs of conventional antibiotics against the bacteria in a biofilm were at least four-fold higher than against the freely growing planktonic cells. In contrast, when antibiotics were used on citropin 1.1 pre-treated cells they showed comparable activity against both biofilm and planktonic organisms. The in vivo studies show that when CVCs were pre-treated with citropin 1.1 or with a high dose of antibiotics, biofilm bacterial load was reduced from 107 to 103 CFU/mL and bacteremia reduced from 103 to 101 CFU/mL. When CVCs were treated both with citropin 1.1 and antibiotics, biofilm bacterial load was further reduced to 101 CFU/mL and bacteremia was not detected, suggesting 100% elimination of bacteremia and a log 6 reduction in biofilm load. Citropin 1.1 significantly reduces bacterial load and enhances the effect of hydrophobic antibiotics in the treatment of CVC-associated S. aureus infections.
| Original language | English |
|---|---|
| Pages (from-to) | 1210-1216 |
| Number of pages | 7 |
| Journal | Peptides |
| Volume | 27 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2006 |
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Keywords
- Antibiotic-lock technique
- Antimicrobial peptides
- Biofilm
- Citropin 1.1
- CVC
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
- Cellular and Molecular Neuroscience
Cite this
Citropin 1.1-treated central venous catheters improve the efficacy of hydrophobic antibiotics in the treatment of experimental staphylococcal catheter-related infection. / Cirioni, Oscar; Giacometti, Andrea; Ghiselli, Roberto; Kamysz, Wojciech; Orlando, Fiorenza; Mocchegiani, Federico; Silvestri, Carmela; Licci, Alberto; Chiodi, Leonardo; Łukasiak, Jerzy; Saba, Vittorio; Scalise, Giorgio.
In: Peptides, Vol. 27, No. 6, 06.2006, p. 1210-1216.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Citropin 1.1-treated central venous catheters improve the efficacy of hydrophobic antibiotics in the treatment of experimental staphylococcal catheter-related infection
AU - Cirioni, Oscar
AU - Giacometti, Andrea
AU - Ghiselli, Roberto
AU - Kamysz, Wojciech
AU - Orlando, Fiorenza
AU - Mocchegiani, Federico
AU - Silvestri, Carmela
AU - Licci, Alberto
AU - Chiodi, Leonardo
AU - Łukasiak, Jerzy
AU - Saba, Vittorio
AU - Scalise, Giorgio
PY - 2006/6
Y1 - 2006/6
N2 - 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 citropin 1.1, rifampin and minocycline. 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 citropin 1.1 (10 μg/mL). Thirty minutes later the rats were challenged via the CVC with 1.0 × 106 CFU of S. aureus strain Smith diffuse. Administration of antibiotics into the CVC (the antibiotic lock technique) began 24 h later. The study included: one control group (no CVC infection), one contaminated group that did not receive any antibiotic prophylaxis, one contaminated group that received citropin 1.1-treated CVC, two contaminated groups that received citropin 1.1-treated CVC plus rifampin and minocycline at concentrations equal to MBCs for adherent cells and 1024 μg/mL in a volume of 0.1 mL that filled the CVC and two contaminated groups that received rifampin or minocycline at the same concentrations. All catheters were explanted 7 days after implantation. Main outcome measures were: minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), synergy studies, quantitative culture of the biofilm formed on the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. MICs of conventional antibiotics against the bacteria in a biofilm were at least four-fold higher than against the freely growing planktonic cells. In contrast, when antibiotics were used on citropin 1.1 pre-treated cells they showed comparable activity against both biofilm and planktonic organisms. The in vivo studies show that when CVCs were pre-treated with citropin 1.1 or with a high dose of antibiotics, biofilm bacterial load was reduced from 107 to 103 CFU/mL and bacteremia reduced from 103 to 101 CFU/mL. When CVCs were treated both with citropin 1.1 and antibiotics, biofilm bacterial load was further reduced to 101 CFU/mL and bacteremia was not detected, suggesting 100% elimination of bacteremia and a log 6 reduction in biofilm load. Citropin 1.1 significantly reduces bacterial load and enhances the effect of hydrophobic antibiotics in the treatment of CVC-associated S. aureus infections.
AB - 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 citropin 1.1, rifampin and minocycline. 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 citropin 1.1 (10 μg/mL). Thirty minutes later the rats were challenged via the CVC with 1.0 × 106 CFU of S. aureus strain Smith diffuse. Administration of antibiotics into the CVC (the antibiotic lock technique) began 24 h later. The study included: one control group (no CVC infection), one contaminated group that did not receive any antibiotic prophylaxis, one contaminated group that received citropin 1.1-treated CVC, two contaminated groups that received citropin 1.1-treated CVC plus rifampin and minocycline at concentrations equal to MBCs for adherent cells and 1024 μg/mL in a volume of 0.1 mL that filled the CVC and two contaminated groups that received rifampin or minocycline at the same concentrations. All catheters were explanted 7 days after implantation. Main outcome measures were: minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), synergy studies, quantitative culture of the biofilm formed on the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. MICs of conventional antibiotics against the bacteria in a biofilm were at least four-fold higher than against the freely growing planktonic cells. In contrast, when antibiotics were used on citropin 1.1 pre-treated cells they showed comparable activity against both biofilm and planktonic organisms. The in vivo studies show that when CVCs were pre-treated with citropin 1.1 or with a high dose of antibiotics, biofilm bacterial load was reduced from 107 to 103 CFU/mL and bacteremia reduced from 103 to 101 CFU/mL. When CVCs were treated both with citropin 1.1 and antibiotics, biofilm bacterial load was further reduced to 101 CFU/mL and bacteremia was not detected, suggesting 100% elimination of bacteremia and a log 6 reduction in biofilm load. Citropin 1.1 significantly reduces bacterial load and enhances the effect of hydrophobic antibiotics in the treatment of CVC-associated S. aureus infections.
KW - Antibiotic-lock technique
KW - Antimicrobial peptides
KW - Biofilm
KW - Citropin 1.1
KW - CVC
UR - http://www.scopus.com/inward/record.url?scp=33646768929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646768929&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2005.10.007
DO - 10.1016/j.peptides.2005.10.007
M3 - Article
C2 - 16289474
AN - SCOPUS:33646768929
VL - 27
SP - 1210
EP - 1216
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 6
ER -