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Brian T. Tsuji - One of the best experts on this subject based on the ideXlab platform.
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sequential evolution of vancomycin Intermediate Resistance alters virulence in staphylococcus aureus pharmacokinetic pharmacodynamic targets for vancomycin exposure
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Justin R. Lenhard, Michael J. Rybak, Tanya Brown, Calvin J. Meaney, Nicholas B. Norgard, Zackery P. Bulman, Daniel A. Brazeau, Steven R. Gill, Brian T. TsujiAbstract:Staphylococcus aureus possesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined the in vitro evolution of S. aureus in response to escalating vancomycin exposure by evaluating bacterial killing and the progression of Resistance. A hollow-fiber infection model was utilized to simulate human doses of vancomycin increasing from 0.5 to 4 g every 12 h (q12h) versus a high inoculum (10(8) CFU/ml) of methicillin-resistant S. aureus (MRSA) USA300 and USA400. Host-pathogen interactions using Galleria mellonella and accessory gene regulator (agr) expression were studied in serially obtained isolates. In both USA300 and USA400 MRSA isolates, vancomycin exposure up to 2 g q12h resulted in persistence and regrowth, whereas 4 g administered q12h achieved sustained killing against both strains. As vancomycin exposure increased from 0.5 to 2 g q12h, the bacterial population shifted toward vancomycin-Intermediate Resistance, and collateral increases in the MICs of daptomycin and televancin were observed over 10 days. Guideline-recommended exposure of a ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC ratio) of 200 displayed a 0.344-log bacterial reduction in area, whereas fAUC/MICs of 371 and 554 were needed to achieve 1.00- and 2.00-log reductions in area, respectively. The stepwise increase in Resistance paralleled a decrease in G. mellonella mortality (P = 0.021) and a gradual decline of RNAIII expression over 10 days. Currently recommended doses of vancomycin resulted in amplification of Resistance and collateral damage to other antibiotics. Decreases in agr expression and virulence during therapy may be an adaptive mechanism of S. aureus persistence.
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Sequential Evolution of Vancomycin-Intermediate Resistance Alters Virulence in Staphylococcus aureus: Pharmacokinetic/Pharmacodynamic Targets for Vancomycin Exposure
Antimicrobial agents and chemotherapy, 2015Co-Authors: Justin R. Lenhard, Michael J. Rybak, Tanya Brown, Calvin J. Meaney, Nicholas B. Norgard, Zackery P. Bulman, Daniel A. Brazeau, Steven R. Gill, Brian T. TsujiAbstract:Staphylococcus aureus possesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined the in vitro evolution of S. aureus in response to escalating vancomycin exposure by evaluating bacterial killing and the progression of Resistance. A hollow-fiber infection model was utilized to simulate human doses of vancomycin increasing from 0.5 to 4 g every 12 h (q12h) versus a high inoculum (10(8) CFU/ml) of methicillin-resistant S. aureus (MRSA) USA300 and USA400. Host-pathogen interactions using Galleria mellonella and accessory gene regulator (agr) expression were studied in serially obtained isolates. In both USA300 and USA400 MRSA isolates, vancomycin exposure up to 2 g q12h resulted in persistence and regrowth, whereas 4 g administered q12h achieved sustained killing against both strains. As vancomycin exposure increased from 0.5 to 2 g q12h, the bacterial population shifted toward vancomycin-Intermediate Resistance, and collateral increases in the MICs of daptomycin and televancin were observed over 10 days. Guideline-recommended exposure of a ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC ratio) of 200 displayed a 0.344-log bacterial reduction in area, whereas fAUC/MICs of 371 and 554 were needed to achieve 1.00- and 2.00-log reductions in area, respectively. The stepwise increase in Resistance paralleled a decrease in G. mellonella mortality (P = 0.021) and a gradual decline of RNAIII expression over 10 days. Currently recommended doses of vancomycin resulted in amplification of Resistance and collateral damage to other antibiotics. Decreases in agr expression and virulence during therapy may be an adaptive mechanism of S. aureus persistence.
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Evaluation of Accessory Gene Regulator (agr) Group and Function in the Proclivity towards Vancomycin Intermediate Resistance in Staphylococcus aureus
Antimicrobial agents and chemotherapy, 2006Co-Authors: Brian T. Tsuji, Michael J. Rybak, Kerry L. Lau, George SakoulasAbstract:Simulated therapeutic vancomycin exposures were evaluated against agr wild-type and knockout Staphylococcus aureus groups I, II, III, and IV using an in vitro pharmacodynamic model. All agr groups developed Intermediate Resistance to vancomycin after subtherapeutic exposure. The free unbound fraction of the area under the concentration-time curve (fAUC/MIC) required to suppress Resistance was fourfold higher (P < 0.001) in agr dysfunctional strains (112 to 169) than that in parent wild-type strains (28).
Andrea Giacometti - One of the best experts on this subject based on the ideXlab platform.
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Experimental study on the efficacy of combination of α-helical antimicrobial peptides and vancomycin against Staphylococcus aureus with Intermediate Resistance to glycopeptides
Peptides, 2006Co-Authors: Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Fiorenza Orlando, Federico Mocchegiani, Carmela Silvestri, Vittorio Saba, Leonardo Chiodi, Agnese Della Vittoria, Giorgio ScaliseAbstract:An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A, two α-helical antimicrobial peptides, and vancomycin against Staphylococcus aureus with Intermediate Resistance to glycopeptides. In vitro experiments included MIC determination, time-kill and synergy studies. For in vivo studies, a mouse model of staphylococcal sepsis has been used. Main outcome measures were: lethality, quantitative blood cultures and detection of TNF-alpha and interleukin-6 (IL-6) plasma levels. Combinations of α-helical antimicrobial peptides showed in vitro synergistic interaction. Significant increase in efficacy was also observed in vivo: combined-treated groups had significant lower bacteremia when compared to single-treated groups. Magainin II combined with vancomycin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide future therapeutic alternative in infections due to glycopeptides resistant staphylococci in the coming years.
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Temporin A Soaking in Combination with Intraperitoneal Linezolid Prevents Vascular Graft Infection in a Subcutaneous Rat Pouch Model of Infection with Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides
Antimicrobial agents and chemotherapy, 2004Co-Authors: Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Fiorenza Orlando, Giuseppina D'amato, Wojciech Kamysz, Federico Mocchegiani, Valerio Sisti, Carmela Silvestri, Jerzy ŁukasiakAbstract:The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with Intermediate Resistance to glycopeptides was investigated in a subcutaneous rat pouch model. Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs.
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Prophylactic Efficacy of Topical Temporin A and RNAIII-Inhibiting Peptide in a Subcutaneous Rat Pouch Model of Graft Infection Attributable to Staphylococci With Intermediate Resistance to Glycopeptides
Circulation, 2003Co-Authors: Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Fiorenza Orlando, Wojciech Kamysz, Federico Mocchegiani, Giorgio Dell'acqua, Yael Gov, Jerzy Lukasiak, Giuseppina D'amatoAbstract:Background— Bacteria that adhere to implanted medical devices play an important role in industry and in modern medicine. Staphylococci are among the most common pathogens that cause biomaterial infections. Vascular prosthetic graft infection is one of the most feared complications that the vascular surgeon treats, frequently resulting in prolonged hospitalization, organ failure, amputation, and death. A rat model was used to investigate the topical efficacies of temporin A and the quorum-sensing inhibitor RNAIII-inhibiting protein (RIP) as prophylactic agents of vascular prosthetic graft infections caused by Staphylococcus aureus and Staphylococcus epidermidis with Intermediate Resistance to glycopeptides. Methods and Results— Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses 1 cm2 followed by topical inoculation with 2×107 colony-forming units of bacterial strains. The study included, for each staphylococcal strain, a control ...
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Efficacy of Quinupristin-Dalfopristin in Preventing Vascular Graft Infection Due to Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides
Antimicrobial agents and chemotherapy, 2002Co-Authors: Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Fiorenza Orlando, Federico Mocchegiani, Alessandra Riva, Maria Simona Del Prete, Vittorio Saba, Giorgio ScaliseAbstract:A rat model was used to investigate the efficacy of quinupristin-dalfopristin (Q-D) in the prevention of vascular prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with Intermediate Resistance to glycopeptides. The in vitro activity of the compound was compared to that of vancomycin by MIC determination and time-kill study. Moreover, the efficacy of collagen-sealed Q-D-soaked Dacron was evaluated in a rat model of graft infection. Graft infections were established in the subcutaneous tissue of the backs of 120 adult male Wistar rats. The in vivo study included a control group, one contaminated group that did not receive any antibiotic prophylaxis, two contaminated groups that received grafts soaked with 10 and 100 micro g of Q-D per ml, respectively, and two contaminated groups that received grafts soaked with 10 and 100 micro g of vancomycin per ml, respectively. Rats that received Dacron grafts soaked with 100 micro g of Q-D per ml showed no evidence of infection (
Oscar Cirioni - One of the best experts on this subject based on the ideXlab platform.
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Experimental study on the efficacy of combination of α-helical antimicrobial peptides and vancomycin against Staphylococcus aureus with Intermediate Resistance to glycopeptides
Peptides, 2006Co-Authors: Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Fiorenza Orlando, Federico Mocchegiani, Carmela Silvestri, Vittorio Saba, Leonardo Chiodi, Agnese Della Vittoria, Giorgio ScaliseAbstract:An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A, two α-helical antimicrobial peptides, and vancomycin against Staphylococcus aureus with Intermediate Resistance to glycopeptides. In vitro experiments included MIC determination, time-kill and synergy studies. For in vivo studies, a mouse model of staphylococcal sepsis has been used. Main outcome measures were: lethality, quantitative blood cultures and detection of TNF-alpha and interleukin-6 (IL-6) plasma levels. Combinations of α-helical antimicrobial peptides showed in vitro synergistic interaction. Significant increase in efficacy was also observed in vivo: combined-treated groups had significant lower bacteremia when compared to single-treated groups. Magainin II combined with vancomycin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide future therapeutic alternative in infections due to glycopeptides resistant staphylococci in the coming years.
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Temporin A Soaking in Combination with Intraperitoneal Linezolid Prevents Vascular Graft Infection in a Subcutaneous Rat Pouch Model of Infection with Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides
Antimicrobial agents and chemotherapy, 2004Co-Authors: Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Fiorenza Orlando, Giuseppina D'amato, Wojciech Kamysz, Federico Mocchegiani, Valerio Sisti, Carmela Silvestri, Jerzy ŁukasiakAbstract:The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with Intermediate Resistance to glycopeptides was investigated in a subcutaneous rat pouch model. Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs.
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Prophylactic Efficacy of Topical Temporin A and RNAIII-Inhibiting Peptide in a Subcutaneous Rat Pouch Model of Graft Infection Attributable to Staphylococci With Intermediate Resistance to Glycopeptides
Circulation, 2003Co-Authors: Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Fiorenza Orlando, Wojciech Kamysz, Federico Mocchegiani, Giorgio Dell'acqua, Yael Gov, Jerzy Lukasiak, Giuseppina D'amatoAbstract:Background— Bacteria that adhere to implanted medical devices play an important role in industry and in modern medicine. Staphylococci are among the most common pathogens that cause biomaterial infections. Vascular prosthetic graft infection is one of the most feared complications that the vascular surgeon treats, frequently resulting in prolonged hospitalization, organ failure, amputation, and death. A rat model was used to investigate the topical efficacies of temporin A and the quorum-sensing inhibitor RNAIII-inhibiting protein (RIP) as prophylactic agents of vascular prosthetic graft infections caused by Staphylococcus aureus and Staphylococcus epidermidis with Intermediate Resistance to glycopeptides. Methods and Results— Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses 1 cm2 followed by topical inoculation with 2×107 colony-forming units of bacterial strains. The study included, for each staphylococcal strain, a control ...
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Efficacy of Quinupristin-Dalfopristin in Preventing Vascular Graft Infection Due to Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides
Antimicrobial agents and chemotherapy, 2002Co-Authors: Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Fiorenza Orlando, Federico Mocchegiani, Alessandra Riva, Maria Simona Del Prete, Vittorio Saba, Giorgio ScaliseAbstract:A rat model was used to investigate the efficacy of quinupristin-dalfopristin (Q-D) in the prevention of vascular prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with Intermediate Resistance to glycopeptides. The in vitro activity of the compound was compared to that of vancomycin by MIC determination and time-kill study. Moreover, the efficacy of collagen-sealed Q-D-soaked Dacron was evaluated in a rat model of graft infection. Graft infections were established in the subcutaneous tissue of the backs of 120 adult male Wistar rats. The in vivo study included a control group, one contaminated group that did not receive any antibiotic prophylaxis, two contaminated groups that received grafts soaked with 10 and 100 micro g of Q-D per ml, respectively, and two contaminated groups that received grafts soaked with 10 and 100 micro g of vancomycin per ml, respectively. Rats that received Dacron grafts soaked with 100 micro g of Q-D per ml showed no evidence of infection (
Michael J. Rybak - One of the best experts on this subject based on the ideXlab platform.
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sequential evolution of vancomycin Intermediate Resistance alters virulence in staphylococcus aureus pharmacokinetic pharmacodynamic targets for vancomycin exposure
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Justin R. Lenhard, Michael J. Rybak, Tanya Brown, Calvin J. Meaney, Nicholas B. Norgard, Zackery P. Bulman, Daniel A. Brazeau, Steven R. Gill, Brian T. TsujiAbstract:Staphylococcus aureus possesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined the in vitro evolution of S. aureus in response to escalating vancomycin exposure by evaluating bacterial killing and the progression of Resistance. A hollow-fiber infection model was utilized to simulate human doses of vancomycin increasing from 0.5 to 4 g every 12 h (q12h) versus a high inoculum (10(8) CFU/ml) of methicillin-resistant S. aureus (MRSA) USA300 and USA400. Host-pathogen interactions using Galleria mellonella and accessory gene regulator (agr) expression were studied in serially obtained isolates. In both USA300 and USA400 MRSA isolates, vancomycin exposure up to 2 g q12h resulted in persistence and regrowth, whereas 4 g administered q12h achieved sustained killing against both strains. As vancomycin exposure increased from 0.5 to 2 g q12h, the bacterial population shifted toward vancomycin-Intermediate Resistance, and collateral increases in the MICs of daptomycin and televancin were observed over 10 days. Guideline-recommended exposure of a ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC ratio) of 200 displayed a 0.344-log bacterial reduction in area, whereas fAUC/MICs of 371 and 554 were needed to achieve 1.00- and 2.00-log reductions in area, respectively. The stepwise increase in Resistance paralleled a decrease in G. mellonella mortality (P = 0.021) and a gradual decline of RNAIII expression over 10 days. Currently recommended doses of vancomycin resulted in amplification of Resistance and collateral damage to other antibiotics. Decreases in agr expression and virulence during therapy may be an adaptive mechanism of S. aureus persistence.
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Sequential Evolution of Vancomycin-Intermediate Resistance Alters Virulence in Staphylococcus aureus: Pharmacokinetic/Pharmacodynamic Targets for Vancomycin Exposure
Antimicrobial agents and chemotherapy, 2015Co-Authors: Justin R. Lenhard, Michael J. Rybak, Tanya Brown, Calvin J. Meaney, Nicholas B. Norgard, Zackery P. Bulman, Daniel A. Brazeau, Steven R. Gill, Brian T. TsujiAbstract:Staphylococcus aureus possesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined the in vitro evolution of S. aureus in response to escalating vancomycin exposure by evaluating bacterial killing and the progression of Resistance. A hollow-fiber infection model was utilized to simulate human doses of vancomycin increasing from 0.5 to 4 g every 12 h (q12h) versus a high inoculum (10(8) CFU/ml) of methicillin-resistant S. aureus (MRSA) USA300 and USA400. Host-pathogen interactions using Galleria mellonella and accessory gene regulator (agr) expression were studied in serially obtained isolates. In both USA300 and USA400 MRSA isolates, vancomycin exposure up to 2 g q12h resulted in persistence and regrowth, whereas 4 g administered q12h achieved sustained killing against both strains. As vancomycin exposure increased from 0.5 to 2 g q12h, the bacterial population shifted toward vancomycin-Intermediate Resistance, and collateral increases in the MICs of daptomycin and televancin were observed over 10 days. Guideline-recommended exposure of a ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC ratio) of 200 displayed a 0.344-log bacterial reduction in area, whereas fAUC/MICs of 371 and 554 were needed to achieve 1.00- and 2.00-log reductions in area, respectively. The stepwise increase in Resistance paralleled a decrease in G. mellonella mortality (P = 0.021) and a gradual decline of RNAIII expression over 10 days. Currently recommended doses of vancomycin resulted in amplification of Resistance and collateral damage to other antibiotics. Decreases in agr expression and virulence during therapy may be an adaptive mechanism of S. aureus persistence.
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Alternative Mutational Pathways to Intermediate Resistance to Vancomycin in Methicillin-Resistant Staphylococcus aureus
The Journal of infectious diseases, 2013Co-Authors: Céline Vidaillac, George Sakoulas, Susana Gardete, Ryan Tewhey, Glenn W. Kaatz, Warren E. Rose, Alexander Tomasz, Michael J. RybakAbstract:Background. We used 2 in vitro experimental systems to compare phenotypic and genotypic changes that accompany selection of mutants of methicillin-resistant Staphylococcus aureus (MRSA) strain JH1 with low-level vancomycin Resistance similar to the type found in vancomycin-Intermediate S. aureus (VISA). Methods. The previously described MRSA strain JH1 and its vancomycin-Intermediate mutant derivative JH2, both of which were recovered from a patient undergoing vancomycin chemotherapy, were used in this study. Mutants of JH1 were selected in vitro by means of a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs) and by exposure to vancomycin in laboratory growth medium. Phenotypic abnormalities of JH1 mutants generated by each in vitro experimental system were compared to those of JH2, and whole genomes of 2 in vitro JH1 mutants were sequenced to identify mutations that may be associated with an increased vancomycin minimum inhibitory concentration. Results. JH1R1 was selected from the PK/PD model, and JH1R2 was selected in laboratory growth medium. Both mutants displayed reduced vancomycin and daptomycin susceptibility and phenotypic alterations (eg, thicker cell walls and abnormal autolysis) that are typical of in vivo VISA mutants. Genome sequencing of JH1R1 identified point mutations in 4 genes, all of which were different from the mutations described in JH2, including 1 mutation in yycG, a component of the WalKR sensory regulatory system. Sequencing of the JH1R2 genome identified mutations in 7 genes, including 2 in rpoB. Conclusion. Our findings indicate that JH1 is able to develop VISA-type Resistance through several alternative genetic pathways.
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Evaluation of Accessory Gene Regulator (agr) Group and Function in the Proclivity towards Vancomycin Intermediate Resistance in Staphylococcus aureus
Antimicrobial agents and chemotherapy, 2006Co-Authors: Brian T. Tsuji, Michael J. Rybak, Kerry L. Lau, George SakoulasAbstract:Simulated therapeutic vancomycin exposures were evaluated against agr wild-type and knockout Staphylococcus aureus groups I, II, III, and IV using an in vitro pharmacodynamic model. All agr groups developed Intermediate Resistance to vancomycin after subtherapeutic exposure. The free unbound fraction of the area under the concentration-time curve (fAUC/MIC) required to suppress Resistance was fourfold higher (P < 0.001) in agr dysfunctional strains (112 to 169) than that in parent wild-type strains (28).
Roberto Ghiselli - One of the best experts on this subject based on the ideXlab platform.
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Experimental study on the efficacy of combination of α-helical antimicrobial peptides and vancomycin against Staphylococcus aureus with Intermediate Resistance to glycopeptides
Peptides, 2006Co-Authors: Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Fiorenza Orlando, Federico Mocchegiani, Carmela Silvestri, Vittorio Saba, Leonardo Chiodi, Agnese Della Vittoria, Giorgio ScaliseAbstract:An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A, two α-helical antimicrobial peptides, and vancomycin against Staphylococcus aureus with Intermediate Resistance to glycopeptides. In vitro experiments included MIC determination, time-kill and synergy studies. For in vivo studies, a mouse model of staphylococcal sepsis has been used. Main outcome measures were: lethality, quantitative blood cultures and detection of TNF-alpha and interleukin-6 (IL-6) plasma levels. Combinations of α-helical antimicrobial peptides showed in vitro synergistic interaction. Significant increase in efficacy was also observed in vivo: combined-treated groups had significant lower bacteremia when compared to single-treated groups. Magainin II combined with vancomycin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide future therapeutic alternative in infections due to glycopeptides resistant staphylococci in the coming years.
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Temporin A Soaking in Combination with Intraperitoneal Linezolid Prevents Vascular Graft Infection in a Subcutaneous Rat Pouch Model of Infection with Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides
Antimicrobial agents and chemotherapy, 2004Co-Authors: Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Fiorenza Orlando, Giuseppina D'amato, Wojciech Kamysz, Federico Mocchegiani, Valerio Sisti, Carmela Silvestri, Jerzy ŁukasiakAbstract:The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with Intermediate Resistance to glycopeptides was investigated in a subcutaneous rat pouch model. Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs.
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Prophylactic Efficacy of Topical Temporin A and RNAIII-Inhibiting Peptide in a Subcutaneous Rat Pouch Model of Graft Infection Attributable to Staphylococci With Intermediate Resistance to Glycopeptides
Circulation, 2003Co-Authors: Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Fiorenza Orlando, Wojciech Kamysz, Federico Mocchegiani, Giorgio Dell'acqua, Yael Gov, Jerzy Lukasiak, Giuseppina D'amatoAbstract:Background— Bacteria that adhere to implanted medical devices play an important role in industry and in modern medicine. Staphylococci are among the most common pathogens that cause biomaterial infections. Vascular prosthetic graft infection is one of the most feared complications that the vascular surgeon treats, frequently resulting in prolonged hospitalization, organ failure, amputation, and death. A rat model was used to investigate the topical efficacies of temporin A and the quorum-sensing inhibitor RNAIII-inhibiting protein (RIP) as prophylactic agents of vascular prosthetic graft infections caused by Staphylococcus aureus and Staphylococcus epidermidis with Intermediate Resistance to glycopeptides. Methods and Results— Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses 1 cm2 followed by topical inoculation with 2×107 colony-forming units of bacterial strains. The study included, for each staphylococcal strain, a control ...
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Efficacy of Quinupristin-Dalfopristin in Preventing Vascular Graft Infection Due to Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides
Antimicrobial agents and chemotherapy, 2002Co-Authors: Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Fiorenza Orlando, Federico Mocchegiani, Alessandra Riva, Maria Simona Del Prete, Vittorio Saba, Giorgio ScaliseAbstract:A rat model was used to investigate the efficacy of quinupristin-dalfopristin (Q-D) in the prevention of vascular prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with Intermediate Resistance to glycopeptides. The in vitro activity of the compound was compared to that of vancomycin by MIC determination and time-kill study. Moreover, the efficacy of collagen-sealed Q-D-soaked Dacron was evaluated in a rat model of graft infection. Graft infections were established in the subcutaneous tissue of the backs of 120 adult male Wistar rats. The in vivo study included a control group, one contaminated group that did not receive any antibiotic prophylaxis, two contaminated groups that received grafts soaked with 10 and 100 micro g of Q-D per ml, respectively, and two contaminated groups that received grafts soaked with 10 and 100 micro g of vancomycin per ml, respectively. Rats that received Dacron grafts soaked with 100 micro g of Q-D per ml showed no evidence of infection (