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ABSTRACT: The in vitro activity of uperin 3.6, alone or combined with six antibiotics, against gram-positive cocci, including Rhodococcus equi, methicillin-resistant staphylococci, and vancomycin-resistant enterococci, was investigated. All isolates were inhibited at concentrations of 1 to 16 mg/liter. Synergy was demonstrated when uperin 3.6 was combined with clarithromycin and doxycycline.
Antimicrobial Agents and Chemotherapy 10/2005; 49(9):3933-6. · 4.84 Impact Factor
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ABSTRACT: MSI-78 is a 22 amino acid amphipathic peptide with potent antimicrobial activity against Gram-positive and Gram-negative organisms, including antibiotic-resistant strains. In this study, we assessed the in vitro activity of MSI-78 alone and in combination with eight clinically used antimicrobial agents against several strains of Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli isolated from blood of neutropenic febrile patients. Antimicrobial activity of MSI-78 was measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill studies and checkerboard titration method. The Gram-negative isolates were susceptible to the peptide at concentrations in the range 0.50-16 mg/L, while staphylococci showed lower susceptibility. MSI-78 demonstrated a higher antimicrobial activity than colistin against Gram-negative organisms. The checkerboard titration method demonstrated synergy when the peptide was combined with beta-lactams. These results provide evidence for the potential use of MSI-78 in the management of severe infections in neutropenic patients.
International Journal of Antimicrobial Agents 10/2005; 26(3):235-40. · 4.13 Impact Factor
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ABSTRACT: The aim of this study was to investigate the in vitro activity of citropin 1.1, an antimicrobial peptide derived from the Australian tree frog Litoria citropa, alone and in combination with ampicillin, ceftriaxone, doxycycline, netilmicin, ciprofloxacin, rifampicin, linezolid, vancomycin, clarithromycin and imipenem against 12 nosocomial isolates of Rhodococcus equi.
Antimicrobial activity of citropin 1.1 was measured by MIC, MBC, time-kill studies and chequerboard titration method.
All isolates were inhibited at concentrations of citropin 1.1 between 2 and 8 mg/L. Combination studies demonstrated synergy only when the peptide was combined with clarithromycin, doxycycline and rifampicin.
Our findings show that citropin 1.1 is active against R. equi and that its activity could be enhanced when it is combined with hydrophobic antibiotics.
Journal of Antimicrobial Chemotherapy 09/2005; 56(2):410-2. · 5.07 Impact Factor
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ABSTRACT: The in vitro activity of citropin 1.1 against gram-positive cocci was measured by MIC, minimal bactericidal concentration, time-kill studies, and a checkerboard titration method. Streptococci and staphylococci were inhibited at concentrations between 1 and 16 mg/liter, respectively. Enterococci showed less susceptibility. Synergy was demonstrated when citropin 1.1 was combined with clarithromycin and doxycycline.
Antimicrobial Agents and Chemotherapy 07/2005; 49(6):2507-9. · 4.84 Impact Factor
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ABSTRACT: The in vitro activity of the histatin derivative P-113, alone or combined with eight antibiotics, was investigated against multidrug-resistant strains isolated from clinical specimens of immunocompromised patients with pneumonia. The gram-negative isolates were susceptible to P-113. S. aureus showed less susceptibility. Synergy was demonstrated when P-113 was combined with beta-lactams against gram-negative organisms.
Antimicrobial Agents and Chemotherapy 04/2005; 49(3):1249-52. · 4.84 Impact Factor
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ABSTRACT: To study the in vitro activity of temporin A, a basic, highly hydrophobic, antimicrobial peptide amide derived from the skin of the European red frog Rana temporaria, alone and in combination with co-amoxiclav, imipenem, ciprofloxacin, linezolid and vancomycin, against 42 nosocomial isolates of Enterococcus faecalis. Fourteen of these were resistant to vancomycin.
Antimicrobial activity of temporin A was measured by MIC, MBC and time-kill studies and by the chequerboard titration method.
All isolates were inhibited at concentrations of 1 to 16 mg/L. Combination studies carried out with E. faecalis ATCC 29212 and ATCC 51299 demonstrated synergy only when the peptide was combined with co-amoxiclav and imipenem.
Our findings show that temporin A is active against E. faecalis and that its activity could be enhanced when it is combined with other antimicrobial agents.
Journal of Antimicrobial Chemotherapy 03/2005; 55(2):272-4. · 5.07 Impact Factor
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Andrea Giacometti,
Oscar Cirioni,
Roberto Ghiselli,
Fiorenza Orlando,
Wojciech Kamysz,
Marco Rocchi, Giuseppina D'Amato,
Federico Mocchegiani,
Carmela Silvestri,
Jerzy Łukasiak,
Vittorio Saba,
Giorgio Scalise
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ABSTRACT: To investigate the efficacy of pexiganan, a 22-residue magainin analog, alone and combined with betalactmas antibiotics in three experimental rat models of Gram-negative septic shock. Adult male Wistar rats were given (i) an intraperitoneal injection of 1 mg Escherichia coli 0111:B4 LPS; (ii) 2x10(10)CFU of E. coli ATCC 25922; and (iii) intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg pexiganan, 1 mg/kg polymyxin B, 20 mg/kg imipenem, 60 mg/kg piperacillin alone and combined with 1 mg/kg pexiganan. Each group included 15 animals. Lethality, bacterial growth in blood or intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma. All compounds reduced the lethality when compared to controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. Pexiganan showed a slightly lower antimicrobial activity than betalactams even though it achieved a substantial higher decrease in endotoxin and TNF-alpha plasma concentrations than imipenem and piperacillin. No statistically significant differences were noted for antimicrobial and antiendotoxin activities between pexiganan and polymyxin B. Combination between pexiganan and betalactams showed to be the most effective treatment in reducing all variables measured. The use of a novel antimicrobial compound able to bind to LPS associated to potent antibiotics such as betalactams may become an important future consideration for sepsis treatment.
Peptides 03/2005; 26(2):207-16. · 2.43 Impact Factor
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Andrea Giacometti,
Oscar Cirioni,
Roberto Ghiselli,
Giorgio Dell'Acqua,
Fiorenza Orlando, Giuseppina D'Amato,
Federico Mocchegiani,
Carmela Silvestri,
Maria Simona Del Prete,
Marco Rocchi,
Naomi Balaban,
Vittorio Saba,
Giorgio Scalise
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ABSTRACT: RNAIII-inhibiting peptide (RIP, YSPWTNF-NH2) is a quorum-sensing peptide inhibitor that prevents Staphylococcus aureus toxin production and biofilm formation. A mouse sepsis model was used to test the efficacy of RIP alone or in combination with conventional antibiotics in suppressing S. aureus-induced sepsis. Mice were injected intravenously with 3.0x10(6)CFU of S. aureus ATCC 25923 or with 3.0x10(6)CFU of S. aureus strain Smith diffuse. All animals were randomized to receive intravenously isotonic sodium chloride solution as a control, or 20 mg/kg RIP alone or combined with 20 mg/kg cefazolin, 10 mg/kg imipenem, or 10 mg/kg vancomycin immediately or 6 h after bacterial challenge. Main outcome measures were bacteremia and lethality. All compounds reduced lethality when compared to controls. Although, in general combined-treated groups had significant lower bacterial counts when associated to singly-treated groups only the combination between RIP and vancomycin with respect to cefazolin gave a statistically significant decrease in the lethality rate. Lowest lethality rates (10%) and bacteremia (<10(2)CFU/ml) were obtained when RIP was administered in combination with vancomycin. Because RIP can be synergistic with current antibiotic therapies and help to reduce S. aureus exotoxins production, it can be considered a promising agent to associate with antibiotics for further clinical research into treatment of sepsis.
Peptides 02/2005; 26(2):169-75. · 2.43 Impact Factor
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Andrea Giacometti,
Oscar Cirioni,
Roberto Ghiselli,
Cristina Bergnach,
Fiorenza Orlando, Giuseppina D'Amato,
Federico Mocchegiani,
Carmela Silvestri,
Maria Simona Del Prete,
Barbara Skerlavaj,
Vittorio Saba,
Margherita Zanetti,
Giorgio Scalise
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ABSTRACT: 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.
Prospective, randomized, controlled animal study.
Research laboratory in a university hospital.
BALB/c male mice.
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.
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.
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.
Critical Care Medicine 01/2005; 32(12):2485-90. · 6.33 Impact Factor
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Andrea Giacometti,
Roberto Ghiselli,
Oscar Cirioni,
Federico Mocchegiani, Giuseppina D'Amato,
Fiorenza Orlando,
Valerio Sisti,
Wojciech Kamysz,
Carmela Silvestri,
Piotr Naldoski,
Jerzy Lukasiak,
Vittorio Saba,
Giorgio Scalise
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ABSTRACT: This study was designed to investigate the antimicrobial and anti-endotoxin activity of MSI-78, a synthetic cationic peptide analogue of magainin 2.
The in vitro antimicrobial activity of MSI-78 was investigated against the commercially available quality control strain Escherichia coli ATCC 25922. In addition, three rat models of septic shock were investigated: (i) rats were injected intraperitoneally with 1 mg Escherichia coli 0111:B4 LPS; (ii) rats were given an intraperitoneal injection of 2 x 10(10) cfu of Escherichia coli ATCC 25922; (iii) intra-abdominal sepsis was induced via caecal ligation and puncture. All animals were randomized to receive after 360 min intravenously isotonic sodium chloride solution, 1 mg/kg MSI-78, or 60 mg/kg piperacillin. Main outcome measures were: abdominal exudate and plasma bacterial growth, plasma endotoxin and tumour necrosis factor alpha (TNF-alpha) concentrations, and lethality.
Our in vitro data showed that MSI-78 possesses a strong activity against Escherichia coli. The in vivo studies showed that all compounds reduced the lethality when compared to controls. MSI-78 showed a slightly higher antimicrobial activity than piperacillin and achieved a substantial decrease in endotoxin and TNF-alpha plasma concentrations than the beta-lactam.
Because of its strong double anti-endotoxin and antimicrobial activities MSI-78 could be an interesting compound for Gram-negative septic shock treatment.
Journal of Antimicrobial Chemotherapy 10/2004; 54(3):654-60. · 5.07 Impact Factor
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Andrea Giacometti,
Oscar Cirioni,
Roberto Ghiselli,
Fiorenza Orlando, Giuseppina D'Amato,
Wojciech Kamysz,
Federico Mocchegiani,
Valerio Sisti,
Carmela Silvestri,
Jerzy Łukasiak,
Marco Rocchi,
Vittorio Saba,
Giorgio Scalise
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ABSTRACT: 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.
Antimicrobial Agents and Chemotherapy 09/2004; 48(8):3162-4. · 4.84 Impact Factor
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ABSTRACT: The in vitro activity of CA(1-7)M(2-9)NH(2), a 15-residue synthetic hybrid peptide derived from the sequences of cecropin A and melittin, alone and in combination with amoxicillin-clavulanate, imipenem, clarithromycin, ciprofloxacin, rifampin, and vancomycin, was investigated against 40 nosocomial isolates of methicillin-resistant Staphylococcus aureus. Antimicrobial activity of CA(1-7)M(2-9)NH(2) was measured by minimal inhibitory concentration, MBC, and time-kill studies. All isolates were inhibited at concentrations of 1 to 16 microg/mL. Combination studies performed with S. aureusATCC 43300 demonstrated synergy only when CA(1-7)M(2-9)NH(2) was combined with amoxicillin-clavulanate and imipenem. Our findings show that CA(1-7)M(2-9)NH(2) is active against methicillin-resistant S. aureusand that its activity is enhanced when it is combined with several antimicrobial agents.
Diagnostic Microbiology and Infectious Disease 08/2004; 49(3):197-200. · 2.53 Impact Factor
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Oscar Cirioni,
Andrea Giacometti,
Roberto Ghiselli,
Fiorenza Orlando,
Wojciech Kamysz, Giuseppina D'Amato,
Federico Mocchegiani,
Jerzy Lukasiak,
Carmela Silvestri,
Vittorio Saba,
Giorgio Scalise
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ABSTRACT: Morbidity and mortality from Pseudomonas aeruginosa sepsis remain high despite the availability of antibiotics to which the microorganism is sensitive.
The in vitro activity of histatin derivative P-113d was investigated against Pseudomonas aeruginosa. In addition, its in vivo efficacy was studied in 3 rat models of infection: intraperitoneal injection of 1 mg of P. aeruginosa 10 lipopolysachharide, intraperitoneal injection of 2 x 10(10) cfu of P. aeruginosa ATCC 27853, and intra-abdominal sepsis induced by cecal ligation and puncture. Rats received isotonic sodium chloride solution parenterally (control groups), 1 mg of P-113d/kg of body weight, 1 mg of polymyxin B/kg of body weight, or 20 mg of imipenem/kg of body weight. Main outcomes measured were abdominal exudate and plasma bacterial growth, plasma concentrations of endotoxin and tumor necrosis factor (TNF)- alpha, and lethality.
The in vivo studies showed that all compounds reduced lethality, when compared with results for the control group. Overall, P-113d exhibited a slightly lower antimicrobial activity than did imipenem, even though P-113d achieved a substantial decrease in plasma concentrations of endotoxin and TNF- alpha, compared with the imipenem. No statistically significant differences for antimicrobial and antiendotoxin activities were noted between P-113d and polymyxin B.
These results provide evidence for double antiendotoxin and antimicrobial activity for P-113d and point to its potential use for the treatment of severe infections.
The Journal of Infectious Diseases 08/2004; 190(2):356-64. · 6.41 Impact Factor
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Naomi Balaban,
Yael Gov,
Andrea Giacometti,
Oscar Cirioni,
Roberto Ghiselli,
Federico Mocchegiani,
Fiorenza Orlando, Giuseppina D'Amato,
Vittorio Saba,
Giorgio Scalise,
Sabina Bernes,
Amram Mor
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ABSTRACT: Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K(4)-S4(1-13)(a) is a 13-residue dermaseptin derivative (DD(13)) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD(13)-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD(13)-RIP and DD(13) were equally effective, and that the chimeric peptide but not DD(13) was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD(13) act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections.
Antimicrobial Agents and Chemotherapy 08/2004; 48(7):2544-50. · 4.84 Impact Factor
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ABSTRACT: To investigate the efficacy of imipenem, piperacillin combined with cecropin B in the prevention of lethality in 2 rat models of septic shock. Main outcome measures were bacterial growth in blood and intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma, and lethality.
Sepsis remains a serious clinical problem despite intense efforts to improve survival. It is a major cause of morbidity and mortality in hospitalized patients. The primary cause of Gram-negative shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of Gram-negative bacteria.
Adult male Wistar rats were given (1). an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 LPS or (2). 2 x 1010 CFU of E. coli ATCC 25922. All animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg cecropin B, 20 mg/kg imipenem, and 120 mg/kg piperacillin alone and combined with 1 mg/kg cecropin B. Each group included 20 animals. RESULTS All compounds reduced the lethality when compared with controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. On the other hand, each betalactam determined an increase of plasma endotoxin and TNF-alpha concentration. Combination between cecropin B and betalactams showed to be the most effective treatment in reducing all variables measured.
Cecropin B enhances betalactams activities in Gram-negative sepic shock rat models.
Annals of Surgery 03/2004; 239(2):251-6. · 7.49 Impact Factor
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Andrea Giacometti,
Oscar Cirioni,
Roberto Ghiselli,
Federico Mocchegiani, Giuseppina D'Amato,
Raffaella Circo,
Fiorenza Orlando,
Barbara Skerlavaj,
Carmela Silvestri,
Vittorio Saba,
Margherita Zanetti,
Giorgio Scalise
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ABSTRACT: The present study was designed to investigate the antiendotoxin activity and therapeutic efficacy of sheep myeloid antimicrobial peptide (SMAP)-29, a cathelicidin-derived peptide. The in vitro ability of SMAP-29 to bind LPS from Escherichia coli 0111:B4 was determined using a sensitive limulus chromogenic assay. Two rat models of septic shock were performed: (1) rats were injected intraperitoneally with 1 mg E. coli 0111:B4 LPS and (2) intraabdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg/kg SMAP-29, 1 mg/kg polymyxin B or 20 mg/kg imipenem. The main outcome measures were: abdominal exudate and plasma bacterial growth, plasma endotoxin and tumor necrosis factor-alpha concentrations, and lethality. The in vitro study showed that SMAP-29 completely inhibited the LPS procoagulant activity at approximately 10 microM peptide concentration. The in vivo experiments showed that all compounds reduced the lethality when compared with control animals. SMAP-29 achieved a substantial decrease in endotoxin and tumor necrosis factor-alpha plasma concentrations when compared with imipenem and saline treatment and exhibited a slightly lower antimicrobial activity than imipenem. No statistically significant differences were noted between SMAP-29 and polymyxin B. SMAP-29, because of its double antiendotoxin and antimicrobial activities, could be an interesting compound for septic shock treatment.
American Journal of Respiratory and Critical Care Medicine 02/2004; 169(2):187-94. · 11.08 Impact Factor
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Andrea Giacometti,
Oscar Cirioni,
Roberto Ghiselli,
Federico Mocchegiani,
Claudio Viticchi,
Fiorenza Orlando, Giuseppina D'Amato,
Maria Simona Del Prete,
Wojciech Kamysz,
Jerzy łLukasiak,
Vittorio Saba,
Giorgio Scalise
[show abstract]
[hide abstract]
ABSTRACT: The therapeutic efficacy of protegrin peptide IB-367 was investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 1mg Escherichia coli 0111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 X 10(10) CFU of E. coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1mg/kg of IB-367, 60mg/kg piperacillin and 1mg/kg of IB-367 plus 60mg/kg piperacillin. The peptide demonstrated lower level of antimicrobial activity than piperacillin, nevertheless it exhibited the dual properties of antimicrobial and antiendotoxin agent. Finally IB-367 and piperacillin association showed to be the most effective therapeutic approach.
Peptides 12/2003; 24(11):1747-52. · 2.43 Impact Factor
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ABSTRACT: A rat model was used to investigate the efficacy of linezolid, alone or in combination with levofloxacin and vancomycin, in the prevention of vascular prosthetic graft infection resulting from methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides.
Graft infections were established in the subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses, followed by topical inoculation with S. epidermidis. The study comprised: one group without inoculation; one inoculated group without prophylaxis; six inoculated groups that received intraperitoneal linezolid (8 mg/kg), levofloxacin (7 mg/kg) or vancomycin (7 mg/kg) alone or in combination at the dosages mentioned above. Each group included 20 animals. The grafts were removed after 7 days and evaluated by quantitative culture.
Quantitative graft cultures from animals treated with a single drug showed a significant efficacy only for linezolid. The efficacy of levofloxacin was similar to that of vancomycin. Combination studies demonstrated that only the treatments that included linezolid produced no evidence of staphylococcal infection.
Linezolid as perioperative prophylaxis can be useful for the prevention of graft infections caused by multiresistant staphylococcal strains.
Journal of Antimicrobial Chemotherapy 11/2003; 52(4):724-6. · 5.07 Impact Factor
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ABSTRACT: The in vitro activity of three polycationic peptides, cecropin A, melittin, and cecropin A-melittin hybrid peptide CA(1-7)M(2-9)NH2, alone and in combination with various clinically used antimicrobial agents, was investigated against 32 nosocomial isolates of Acinetobacter baumannii. Antimicrobial activities were measured by MIC, MBC and bacterial killing assay. The peptides demonstrated different ranges of inhibitory values: overall, the organisms were more susceptible to CA(1-7)M(2-9)NH2 (MIC range, 0.25-16 mg/l) than to cecropin A (0.50-32 mg/l) and melittin (0.50-32 mg/l). Synergy was observed when CA(1-7)M(2-9)NH2 and melittin were combined with beta-lactam antibiotics.
Peptides 10/2003; 24(9):1315-8. · 2.43 Impact Factor
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Oscar Cirioni,
Andrea Giacometti,
Roberto Ghiselli,
Giorgio Dell'Acqua,
Yael Gov,
Wojciech Kamysz,
Jerzy Lukasiak,
Federico Mocchegiani,
Fiorenza Orlando, Giuseppina D'Amato,
Naomi Balaban,
Vittorio Saba,
Giorgio Scalise
[show abstract]
[hide abstract]
ABSTRACT: 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.
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 2x10(7) colony-forming units of bacterial strains. The study included, for each staphylococcal strain, a control group (no graft contamination), a contaminated group that did not receive antibiotic prophylaxis, and 6 contaminated groups that received grafts soaked with temporin A, RIP, rifampin, temporin A plus RIP, RIP plus rifampin, or temporin A plus RIP. The infection was evaluated by quantitative agar culture. When tested alone, temporin A and RIP showed comparable efficacies, and their efficacies were significantly higher than that of rifampin against both strains. All combinations showed efficacies significantly higher than that of each single compound. The combinations of temporin A and RIP exerted the strongest antistaphylococcal efficacies, eliminating infection by 100%.
The results of the present study make these molecules potentially useful for antimicrobial chemoprophylaxis in vascular surgery.
Circulation 09/2003; 108(6):767-71. · 14.74 Impact Factor
