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1.
Peptides ; 55: 17-22, 2014 May.
Article in English | MEDLINE | ID: mdl-24531033

ABSTRACT

The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/administration & dosage , Colistin/administration & dosage , Imipenem/administration & dosage , Acinetobacter baumannii/drug effects , Administration, Topical , Animals , Anti-Bacterial Agents/therapeutic use , Disease Models, Animal , Drug Therapy, Combination , Escherichia coli/drug effects , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Humans , Injections, Intraperitoneal , Klebsiella pneumoniae/drug effects , Mice, Inbred BALB C , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects
2.
Mycoses ; 57(4): 233-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-26058322

ABSTRACT

The occurrence of resistance or side effects in patients receiving antifungal agents leads to failure in the treatment of mycosis. The aim of this experimental study was to investigate the in vitro effects of IB-367 alone and in combination with three standard antifungal drugs, fluconazole (FLU), itraconazole (ITRA) and terbinafine (TERB), against 20 clinical isolates of dermatophytes belonging to three species. Minimum inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), synergy test, time-kill curves, fungal biomass (FB) and hyphal damage using 2,3-bis-(2-methoxy-4-nitro-5-sulfenylamino carbonil)-2H-tetrazolium hydroxide assay (XTT) were performed to study the efficacy of IB-367. In this study, we observed that TERB and ITRA had MICs lower values for all the strains compared to IB-367 and FLU. Synergy was found in 35%, 30% and 25% of IB-367/FLU, IB-367/ITRA and IB-367/TERB interactions respectively. IB-367 exerted a fungicidal activity against Trichophyton mentagrophytes, T. rubrum and Microsporum canis at concentrations starting from 1x MIC. At a concentration of 5x MIC, IB-367 showed the highest rates of hyphae damage for M. canis 53% and T. mentagrophytes 50%; against the same isolates it caused a reduction of 1 log of the total viable count cell hyphae damage. We propose IB-367 as a promising candidate for the future design of antifungal drugs.


Subject(s)
Antifungal Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Arthrodermataceae/drug effects , Drug Synergism , Arthrodermataceae/isolation & purification , Colony Count, Microbial , Dermatomycoses/microbiology , Fluconazole/pharmacology , Humans , Hyphae/drug effects , Itraconazole/pharmacology , Microbial Sensitivity Tests , Microbial Viability/drug effects , Naphthalenes/pharmacology , Terbinafine
3.
Infez Med ; 21(4): 287-95, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24335459

ABSTRACT

An in vitro and in vivo study was performed to quantify adhesion and biofilm formation ability of Pseudomonas aeruginosa slime producer under the effect of sub-minimal inhibitory concentrations (MICs) of pexiganan and imipenem. To evaluate adherence, squares of ureteral stents were placed in six-well tissue-culture plates containing 6 ml of a cell suspension grown in the presence of sub-MICs of study antibiotics. To evaluate biofilm formation sterilized squares were placed in six-well tissue culture plates containing 6 ml of triptic soy broth (TSB) supplemented with 0.25% of glucose and the respective amount of antibiotic. For in vivo study a biofilm infection rat model was performed. The study included an uninfected control group to evaluate the sterility of surgical procedure, a group infected with a slime-producer P. aeruginosa strain not previously treated with antibiotics and two groups infected with the strain previously treated with imipenem or pexiganan. Adherence and biofilm in vitro formation was strongly affected by pre-treatment with pexiganan and imipenem, with the latter being the more effective antibiotic. The in vivo results showed a reduction in bacterial load on the ureteral stent tissue of the pre-treated strain. Differently, urine cultures showed no differences in bacterial growth for the pre-treated strain showing that it retained its ability to cause infection. This study suggests that sub-MIC imipenem and pexiganan could be a good strategy to target the adhesion process during the infection cycle.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Antimicrobial Cationic Peptides/administration & dosage , Bacterial Adhesion/drug effects , Biofilms/drug effects , Imipenem/administration & dosage , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Animals , Female , Humans , In Vitro Techniques , Microbial Sensitivity Tests , Pseudomonas aeruginosa/isolation & purification , Rats , Rats, Wistar , Stents/microbiology
4.
Int J Mol Sci ; 14(8): 16321-32, 2013 Aug 07.
Article in English | MEDLINE | ID: mdl-23965956

ABSTRACT

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Minocycline/analogs & derivatives , Oligopeptides/pharmacology , Prosthesis-Related Infections/prevention & control , Staphylococcal Infections/prevention & control , Staphylococcus aureus/drug effects , Amino Acid Sequence , Animals , Anti-Bacterial Agents/chemistry , Disease Models, Animal , Male , Microbial Sensitivity Tests , Microbial Viability , Minocycline/pharmacology , Oligopeptides/chemistry , Polyethylene Terephthalates/chemistry , Protein Binding , Quorum Sensing/drug effects , Rats , Rats, Wistar , Staphylococcus aureus/physiology , Tigecycline
5.
J Med Microbiol ; 62(Pt 10): 1552-1558, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23813277

ABSTRACT

Antimicrobial peptides are known as immunomodulators and antibiotic enhancers. We report that administration of an antimicrobial peptide, IB-367, was efficacious in increasing the antimicrobial activity of daptomycin and teicoplanin in a mouse model of wound infection caused by meticillin-resistant Staphylococcus aureus (MRSA). Mice were assigned to seven groups: an IB-367 pre-treated group with no antibiotics given after challenge, two IB-367 pre-treated groups plus daptomycin or teicoplanin given after challenge, two groups treated with daptomycin or teicoplanin only after challenge, and two control groups without infection or that did not receive any treatment. The main outcome measures were quantitative bacterial culture and analysis of natural killer (NK) cytotoxicity and leukocyte phenotype. The wound, established through the panniculus carnosus muscle of mice, was infected by MRSA. Bacterial cultures of mice receiving antibiotics alone showed a -2 log decrease, whilst those for IB-367 plus daptomycin or teicoplanin showed a -4 log decrease. IB-367 plus daptomycin showed the highest efficacy. The higher antimicrobial effect exerted by IB-367 was associated with increased levels of NK cytotoxicity but not of NK cell number. IB-367 increased the number of both CD11b and Gr-1 cells 3 days after MRSA challenge, whereas both of these leukocyte populations were reduced at 10 days after challenge. Our data suggest that a combination of IB-367 with antibiotic exerts a therapeutic effect and may be useful for the management of staphylococcal wounds.


Subject(s)
Antimicrobial Cationic Peptides/therapeutic use , Daptomycin/therapeutic use , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/drug therapy , Teicoplanin/therapeutic use , Wound Infection/drug therapy , Animals , Bacterial Load , Disease Models, Animal , Drug Therapy, Combination/methods , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Mice, Inbred BALB C , Treatment Outcome , Wound Infection/microbiology
6.
Infez Med ; 21(1): 34-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23524899

ABSTRACT

Intestinal parasites are a serious problem in developing countries, but should not be underestimated in industrialised countries either. Between January 2006 and December 2011, stool specimens and the scotch tests of 5323 Italian and non Italian patients (adults and children) attending the laboratory of our Infectious Diseases Clinic in a teaching Hospital at Ancona were analyzed specifically for intestinal parasites. The present study shows that, over a six-year period, of a total of 5323 patients 305 harboured at least one species of parasite (5.7%). Among the pathogenic protozoa Giardia lamblia was the most common, the overall prevalence of giardiasis being 1.8 % (99/5323). Helminths were found in 0.9% of the patients (48/5323). In particular, Hymenolepis nana, Strongyloides stercoralis and Trichuris trichiura were most commonly recovered in non-Italian children, suggesting that certain intestinal parasites are restricted to endemic areas in the tropics. Eighteen of the 305 infected patients had more than one parasite in their stools. Our study demonstrates that intestinal parasites must be considered even in industrialised areas and stool examination should be supported by epidemiological data and clinical features.


Subject(s)
Feces/parasitology , Intestinal Diseases, Parasitic/diagnosis , Intestinal Diseases, Parasitic/epidemiology , Adult , Animals , Child , Developed Countries/statistics & numerical data , Developing Countries/statistics & numerical data , Female , Giardia lamblia/isolation & purification , Giardiasis/diagnosis , Giardiasis/epidemiology , Hospitals, University , Humans , Hymenolepiasis/diagnosis , Hymenolepiasis/epidemiology , Hymenolepis nana/isolation & purification , Italy/epidemiology , Male , Prevalence , Strongyloides stercoralis/isolation & purification , Strongyloidiasis/diagnosis , Strongyloidiasis/epidemiology , Trichuriasis/diagnosis , Trichuriasis/epidemiology , Trichuris/isolation & purification
7.
Peptides ; 40: 77-81, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23262356

ABSTRACT

The aim of the study was to investigate the efficacy of the quorum sensing inhibitor FS3 and daptomycin in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×10(7) colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received: (i) intraperitoneal daptomycin, (ii) FS3-soacked graft, and (iii) daptomycin plus FS3-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS3 was coated to the surface of the prosthesis. The in vitro studies showed, that minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for daptomycin were lower in presence of FS3. In in vivo studies, when tested alone, daptomycin and FS3 showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. Daptomycin is an important candidate for prevention of staphylococcal biofilm related infection and FS3 could serve as an interesting anti-staphylococcal antibiotic enhancer.


Subject(s)
Daptomycin/administration & dosage , Quorum Sensing/drug effects , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Animals , Disease Models, Animal , Humans , Male , Prostheses and Implants/adverse effects , Prostheses and Implants/microbiology , Rats , Staphylococcal Infections/microbiology , Staphylococcus aureus/pathogenicity , Vascular Grafting/adverse effects
8.
J Surg Res ; 176(1): 1-6, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21704328

ABSTRACT

BACKGROUND: We investigated the efficacy of tigecycline and rifampin alone or combined in preventing ureteral stent infection due to Enterococcus faecalis. MATERIALS AND METHODS: The activities of the two antibiotics were previously studied in vitro in absence or in presence of biofilm. For in vivo research, the study included a control group without bacterial challenge to evaluate the sterility of surgical procedure, a challenged control group that did not receive any antibiotic prophylaxis and, for each bacterial strain, three challenged groups that received: (1) 2 mg/kg intraperitoneal tigecycline, immediately after stent implantation; (2) rifampin-coated ureteral stents where 0.2 cm(2) sterile ureteral stents were incubated in 10 mg/L rifampin solution for 30 min immediately before implantation; and (3) intraperitoneal tigecycline plus rifampin-coated ureteral stent at the above concentrations. Ureteral stents were explanted at d 5 following implantation and biofilm bacteria enumerated. RESULTS: The in vitro studies showed that the biofilm was strongly affected by the presence of rifampin and, in its presence, tigecycline had MICs and MBCs lower than those obtained in the absence of rifampin. Intraperitoneal tigecycline exerted stronger effect than rifampin on bacterial numbers. The combination rifampin plus tigecycline showed efficacies higher than that of each single compound. CONCLUSION: These results highlight the potential usefulness of tigecycline in preventing enterococcal ureteral stent infections and the role of rifampin as an interesting antibiotic enhancer.


Subject(s)
Antibiotic Prophylaxis , Biofilms , Enterococcus faecalis/isolation & purification , Gram-Positive Bacterial Infections/prevention & control , Minocycline/analogs & derivatives , Rifampin/therapeutic use , Stents/microbiology , Ureter/microbiology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Biofilms/drug effects , Disease Models, Animal , Drug Therapy, Combination , Enterococcus faecalis/drug effects , Female , In Vitro Techniques , Minocycline/pharmacology , Minocycline/therapeutic use , Rats , Rats, Wistar , Rifampin/pharmacology , Tigecycline , Treatment Outcome
9.
J Antimicrob Chemother ; 67(1): 191-201, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22065244

ABSTRACT

OBJECTIVES: We investigated the in vivo efficacy of tigecycline, a new glycylcycline (a tetracycline derivative), in the management of methicillin-resistant Staphylococcus aureus (MRSA)-infected experimental surgical wounds in rats. The main outcome measures were quantitative bacterial culture, histological examination and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9) and collagen IV. METHODS: An animal model was used to compare the in vivo efficacy of teicoplanin and tigecycline in the treatment of burn wound infections by S. aureus. A copper bar, heated in boiling water, was placed on the paraspinal site of each rat, resulting in full thickness burns. A small gauze was placed over each burn and then inoculated with 5 × 10(7) cfu of S. aureus ATCC 43300. To mimic the clinical situation in burn patients, surgical debridement was performed 48 h after the injury. The wounds were left to heal by secondary intention. The study included an uninfected control group that did not receive any treatment, a contaminated group that did not receive any treatment, and two contaminated groups treated with intraperitoneal tigecycline (2 mg/kg) and teicoplanin (7 mg/kg), respectively. RESULTS: All antibiotic treatments were significantly effective. Tigecycline showed the highest antimicrobial activity, with a better impact on histological results. Infected rats treated with tigecycline showed a significant decrease in MMP-9 expression both in epithelium and in dermis compared with rats treated with teicoplanin. CONCLUSIONS: Tigecycline, besides its antimicrobial activity, exerts an important modulatory effect on MMP-9, accelerating wound healing in staphylococcal-infected burns.


Subject(s)
Burns/complications , Matrix Metalloproteinase 9/metabolism , Methicillin-Resistant Staphylococcus aureus/drug effects , Minocycline/analogs & derivatives , Staphylococcal Infections/drug therapy , Wound Healing , Wound Infection/drug therapy , Animals , Bacterial Load , Disease Models, Animal , Histocytochemistry , Immunohistochemistry , Male , Matrix Metalloproteinase Inhibitors , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Minocycline/administration & dosage , Rats , Rats, Wistar , Staphylococcal Infections/microbiology , Teicoplanin/administration & dosage , Tigecycline , Treatment Outcome , Wound Infection/microbiology
10.
J Med Microbiol ; 60(Pt 12): 1806-1812, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21835971

ABSTRACT

A relevant bacterial load in cutaneous wounds significantly interferes with the normal process of healing. Vitamin E (VE) is a known immunomodulator and immune enhancer. Here, it was shown that administration of VE before infection was effective at increasing the antimicrobial activity of daptomycin (DAP) or tigecycline (TIG) in a mouse model of wound infection caused by meticillin-resistant Staphylococcus aureus (MRSA). A wound was established through the panniculus carnosus of mice and inoculated with MRSA. Mice were assigned to six groups: a VE pre-treated group with no antibiotics given after MRSA challenge; two VE pre-treated groups with DAP or TIG given after MRSA challenge; two groups treated with DAP or TIG only after MRSA challenge; and a control group that did not receive any treatment. Mice receiving each antibiotic alone showed a 3 log decrease in the number of c.f.u. recovered compared with the control group, mice treated with VE plus TIG had a 4 log decrease, whilst mice treated with VE plus DAP had the largest decrease in c.f.u. recovered (5 logs). The increased antimicrobial effect seen from treatment with VE plus antibiotics was associated with increased levels of natural killer cell cytotoxicity, with a more pronounced increase in leukocyte populations in mice treated with VE plus DAP. These data suggest that treatment with VE prior to infection and subsequent antibiotic treatment act in synergy.


Subject(s)
Anti-Bacterial Agents/pharmacology , Daptomycin/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Minocycline/analogs & derivatives , Staphylococcal Infections/drug therapy , Vitamin E/pharmacology , Wound Infection/drug therapy , Animals , Anti-Bacterial Agents/therapeutic use , Daptomycin/therapeutic use , Drug Synergism , Drug Therapy, Combination , Immunomodulation/drug effects , Killer Cells, Natural/drug effects , Killer Cells, Natural/metabolism , Male , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Minocycline/pharmacology , Staphylococcal Infections/microbiology , Tigecycline , Vitamin E/therapeutic use , Wound Infection/microbiology
12.
J Med Microbiol ; 60(Pt 9): 1337-1343, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21511888

ABSTRACT

Surgical site infections are the second most common hospital- and community-acquired Gram-positive infections, with the US Centers for Disease Control and Prevention estimating that about 500 000 surgical site infections occur annually in the USA. The aim of this work was to determine the in vitro activity of the saponin diosgenyl 2-amino-2-deoxy-ß-d-glucopyranoside hydrochloride (HSM1) and its bactericidal effect for a large number of Gram-positive cocci, as well as to investigate its in vitro interaction with seven clinically used antibiotics. In vivo, a wound model was established through the panniculus carnosus of BALB/c mice and then inoculated with 5×10(7) c.f.u. Staphylococcus aureus or Enterococcus faecalis. For each bacterial strain, the study included an infected or non-infected group that did not receive any treatment, a group treated with local HSM1, a group treated with intraperitoneal vancomycin, a group treated with intraperitoneal daptomycin and two groups that received HSM1 local treatment plus intraperitoneal vancomycin or daptomycin. All isolates were inhibited by HSM1 at concentrations of 2-32 mg l(-1). Synergy was demonstrated when HSM1 was combined with vancomycin and daptomycin. In in vivo studies, all groups treated with single drugs showed a statistically significant result compared with the control group. The two groups treated with drug combinations showed the highest antimicrobial efficacy. The good in vitro activities and the in vivo efficacy suggest HSM1 as a promising therapeutic candidate in Gram-positive wound infections.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Daptomycin/therapeutic use , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Cocci/drug effects , Saponins/therapeutic use , Surgical Wound Infection/drug therapy , Vancomycin/therapeutic use , Animals , Anti-Bacterial Agents/pharmacology , Daptomycin/pharmacology , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination/methods , Male , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Rodent Diseases/drug therapy , Rodent Diseases/microbiology , Saponins/pharmacology , Surgical Wound Infection/microbiology , Treatment Outcome , Vancomycin/pharmacology
13.
J Antimicrob Chemother ; 66(6): 1318-23, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21406436

ABSTRACT

OBJECTIVES: An experimental study was performed to evaluate both in vitro and in vivo the efficacy of clarithromycin coating combined with systemic amikacin in preventing ureteral stent biofilm infection due to Pseudomonas aeruginosa. METHODS: The activities of the two antibiotics were studied in vitro in the absence or in the presence of biofilm. For the in vivo study we evaluated a control group without bacterial challenge to evaluate the sterility of the surgical procedure, a challenged control group that did not receive any antibiotic prophylaxis and three challenged groups that received (i) 15 mg/kg intraperitoneal amikacin immediately after stent implantation, (ii) clarithromycin-coated ureteral stents where 0.2 cm² sterile ureteral stents were incubated in 10 mg/L clarithromycin solution for 30 min immediately before implantation, and (iii) intraperitoneal amikacin plus a clarithromycin-coated ureteral stent at the above concentrations. RESULTS: The in vitro studies showed that the biofilm was strongly affected by the presence of clarithromycin and, in its presence, amikacin had MICs and MBCs lower than those obtained in the absence of clarithromycin. For the singly treated groups, intraperitoneal amikacin showed the strongest effect on bacterial numbers. A clarithromycin coating combined with systemic amikacin showed an efficacy that was higher than that of each single compound. CONCLUSIONS: The prevention of ureteral stent Pseudomonas biofilm infection was enhanced by impregnation of the stent with clarithromycin combined with systemic amikacin.


Subject(s)
Amikacin/pharmacology , Biofilms/drug effects , Clarithromycin/pharmacology , Pseudomonas Infections/prevention & control , Pseudomonas aeruginosa/drug effects , Stents/microbiology , Ureteral Diseases/prevention & control , Animals , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Coated Materials, Biocompatible , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination/methods , Female , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/growth & development , Rats , Rats, Wistar , Ureteral Diseases/microbiology
14.
J Antimicrob Chemother ; 66(4): 859-62, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21393138

ABSTRACT

OBJECTIVES: An experimental study was performed to evaluate both in vitro and in vivo the kind of interaction between the Laur-CKK-NH2 dimer and daptomycin using two Enterococcus faecalis strains with different patterns of susceptibilities. METHODS: We evaluated whether selection for daptomycin-resistant E. faecalis could be prevented in vitro by combining daptomycin with the Laur-CKK-NH2 dimer. The strains were serially exposed in broth to 2-fold stepwise increasing concentrations of daptomycin alone or in combination with a fixed concentration (0.25×MIC) of the Laur-CKK-NH2 dimer. We also performed an in vitro synergy study. For in vivo studies, a mouse model of enterococcal sepsis was used. RESULTS: In vitro experiments: exposure to daptomycin alone gradually selected for enterococci with increased MICs; and the Laur-CKK-NH2 dimer showed a positive interaction with daptomycin and was able to prevent the resistance. In vivo experiments: the main outcome measures were lethality and quantitative blood cultures; and the Laur-CKK-NH2 dimer combined with daptomycin exhibited the highest efficacy for all main outcome measurements. CONCLUSIONS: These results highlight the potential usefulness of combining daptomycin with the Laur-CKK-NH2 dimer. The combination provides a future therapeutic alternative for the treatment of enterococcal severe infections.


Subject(s)
Daptomycin/administration & dosage , Daptomycin/pharmacology , Enterococcus faecalis/drug effects , Gram-Positive Bacterial Infections/drug therapy , Lipopeptides/administration & dosage , Lipopeptides/pharmacology , Animals , Drug Interactions , Drug Therapy, Combination , Mice , Microbial Sensitivity Tests , Treatment Outcome
15.
Peptides ; 32(4): 697-701, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21262298

ABSTRACT

An experimental study was performed to evaluate the interaction between s-thanatin and colistin both in vitro and in vivo, using two Pseudomonas aeruginosa strains with different patterns of susceptibilities. We evaluated whether selecting for colistin-resistant P. aeruginosa could be prevented in vitro by combining colistin with s-thanatin. The strains were serially exposed in broth to twofold stepwise increasing concentrations of colistin alone or in combination with a fixed concentration [0.25× minimum inhibitory concentration (MIC)] of s-thanatin. We also performed an in vitro synergy study. For in vivo studies, a mouse model of Pseudomonas sepsis has been used. Main outcome measures were lethality and quantitative blood cultures. Exposure to colistin alone gradually selected for Pseudomonas strains with an increased MIC. In vitro studies, s-thanatin showed a positive interaction with colistin, and was able to prevent its resistance. In vivo studies, s-thanatin combined with colistin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of this combination and provide a future therapeutic alternative in severe Pseudomonas infections.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Cationic Peptides/therapeutic use , Colistin/pharmacology , Disease Models, Animal , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/isolation & purification , Sepsis/drug therapy , Animals , Drug Resistance, Microbial , Male , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Pseudomonas Infections/microbiology , Sepsis/microbiology
16.
J Surg Res ; 171(2): 726-33, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20605608

ABSTRACT

BACKGROUND: Gram-negative sepsis ranks as the leading cause of death in intensive care units, and its incidence is increasing steadily and mortality rates has not changed much over recent decades. MATERIALS AND METHODS: We investigated the efficacy of the amphibian peptide, citropin 1.1 alone and in combination with tazobactam-piperacillin (TZP) in two experimental mice models of gram-negative sepsis. Animals were given an intraperitoneal injection of (1) 1 mg Escherichia coli 0111:B4 LPS, and (2) 2×10(10) CFU of E. coli ATCC 25922. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/Kg citropin 1.1 and 120 mg/Kg of TZP, and finally 1 mg/Kg citropin 1.1 plus 60 mg/Kg of TZP. Lethality, bacterial growth in blood and peritoneum, and oxidative stress indices in plasma were evaluated. RESULTS: All compounds reduced the lethality compared with controls. Treatment with citropin 1.1 resulted in significant decrease in plasma endotoxin and cytokine levels, while TZP exerted opposed effect. The combination between citropin 1.1 and TZP proved to be the most effective treatment in reducing all variables measured. CONCLUSION: Due to its multifunctional properties, citropin 1.1 may become an important future consideration to treat conditions in which oxidative organ failure may be present.


Subject(s)
Amphibian Proteins/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Escherichia coli Infections/drug therapy , Escherichia coli/drug effects , Oxidative Stress/drug effects , Penicillanic Acid/analogs & derivatives , Piperacillin/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Disease Models, Animal , Drug Therapy, Combination , Enzyme Inhibitors/pharmacology , Escherichia coli/classification , Escherichia coli/growth & development , Escherichia coli Infections/metabolism , Escherichia coli Infections/mortality , Lipopolysaccharides/pharmacology , Male , Mice , Mice, Inbred BALB C , Penicillanic Acid/pharmacology , Tazobactam
17.
Peptides ; 31(7): 1231-6, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20381561

ABSTRACT

We investigated the efficacy of the peptide s-thanatin alone and in combination with tigecycline in an animal model of sepsis induced by cecal ligation and puncture. Adult male Wistar rats were randomized to receive intravenously isotonic sodium chloride solution, 5mg/kg s-thanatin, 2mg/kg tigecycline, 5mg/kg s-thanatin combined with 2mg/kg tigecycline. The experiment was also performed with administration of the drugs 360 min after the surgical procedure to better investigate the clinical situation where there is an interval between the onset of sepsis and the initiation of therapy. Lethality, bacterial growth in blood, peritoneum, spleen and liver, and NO indices were evaluated. All compounds reduced the lethality when compared to control. In all experiments, the compounds reduced significantly bacterial growth and lethality compared with saline treatment. Treatment with s-thanatin resulted in significant decrease in plasma NO levels compared to tigecycline and control group. The combination between s-thanatin and tigecycline proved to be the most effective treatment in reducing all variables measured. S-thanatin may have potential therapeutic usefulness alone and when associated to tigecycline in polymicrobial peritonitis.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Cationic Peptides/therapeutic use , Minocycline/analogs & derivatives , Peritonitis/drug therapy , Animals , Disease Models, Animal , Male , Minocycline/metabolism , Minocycline/therapeutic use , Models, Animal , Peritonitis/microbiology , Rats , Rats, Wistar , Tigecycline , Treatment Outcome
18.
Crit Care Med ; 37(4): 1403-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19318826

ABSTRACT

OBJECTIVE: To investigate the efficacy of buforin II and rifampin in an experimental rat model of Acinetobacter baumannii sepsis. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The animals received intraperitoneally 1 mL saline containing 2 x 10 colony forming units of A. baumannii ATCC 19606 (model i) or the multiresistant strain (model ii). Immediately after bacterial challenge, animals received intravenously a single dose of isotonic sodium chloride solution (control groups C1 and C2), 1 mg/kg of buforin II, 10 mg/kg of rifampin, and 1 mg/kg of buforin II plus 10 mg/kg of rifampin, respectively. MEASUREMENTS AND MAIN RESULTS: Lethality, bacterial growth in blood and tissue burden, endotoxin, interleukin-6, and tumor necrosis factor-alpha concentrations in plasma. Buforin II showed good antimicrobial activity and achieved a significant reduction of plasma endotoxin and cytokines concentration when compared with control and rifampin-treated groups. Combination among buforin II proved to be the most effective treatment in reducing all variables measured. CONCLUSION: In an experimental model, buforin II and rifampin might have a potential role in the treatment of severe infections due to A. baumannii.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii , Antibiotics, Antitubercular/therapeutic use , Proteins/therapeutic use , Rifampin/therapeutic use , Sepsis/drug therapy , Sepsis/microbiology , Animals , Disease Models, Animal , Male , Rats , Rats, Wistar
19.
Med Mycol ; 47(3): 321-6, 2009 May.
Article in English | MEDLINE | ID: mdl-19115137

ABSTRACT

The minimum inhibitory concentrations (MICs), the minimal fungicidal concentrations (MFCs), the fungal biomass (FB) and hyphal viability employing the dye 3-4,5 dimethyl- 2-thiazolyl- 2,5- diphenyl- 2H tetrazolium bromide (MTT) were used to compare the in vitro effects of fluconazole (FLU) with those of the N-terminal palmitoyl-lipidated peptide, Pal-Lys-Lys-NH(2) (PAL), and a tea tree oil component, gamma-Terpinene (TER), against several clinical isolates of Microsporum canis and Trichophyton rubrum. In general, FLU and PAL MICs were significantly lower than those observed with TER, while no differences in the three drugs were found in the MFCs. However, they were from two to 16-times higher than their respective MICs. FB of M. canis treated with either FLU or PAL, but not with TER, was significantly reduced over untreated controls. Only PAL and TER, in a medium-dependent fashion, but not FLU, reduced the FB of T. rubrum. Finally, PAL was found to be significantly more active than FLU at reducing the hyphal viability against both genera of dermatophytes. This study shows that PAL exerts an in vitro activity against dermatophytes at least similar to that observed with FLU and suggests that this compound might be a promising candidate in the treatment of infections due to dermatophytes.


Subject(s)
Antifungal Agents/pharmacology , Arthrodermataceae/drug effects , Fluconazole/pharmacology , Lipopeptides/pharmacology , Microsporum/drug effects , Monoterpenes/pharmacology , Trichophyton/drug effects , Arthrodermataceae/metabolism , Biomass , Cyclohexane Monoterpenes , Humans , Microbial Sensitivity Tests , Microbial Viability , Microsporum/isolation & purification , Mycoses/microbiology , Tetrazolium Salts/metabolism , Thiazoles/metabolism , Trichophyton/isolation & purification
20.
J Antimicrob Chemother ; 62(6): 1332-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18799470

ABSTRACT

INTRODUCTION: An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A with or without rifampicin against control and multidrug-resistant Pseudomonas aeruginosa strains. METHODS: In vitro experiments included MIC determinations and synergy studies. For in vivo studies, animals were given an intraperitoneal injection of P. aeruginosa lipopolysaccharide, P. aeruginosa ATCC 27853 and one clinical multiresistant P. aeruginosa strain. Groups of animals received intravenously isotonic sodium chloride solution, 10 mg/kg rifampicin, 1 mg/kg magainin II or 1 mg/kg cecropin A. Two groups of animals received a combined treatment with magainin II + rifampicin or cecropin A + rifampicin at the same dosages as the singly treated groups. In addition, a further group was treated with tazobactam/piperacillin (120 mg/kg). Lethality, bacterial growth in blood and peritoneum, and endotoxin and TNF-alpha concentrations in plasma were evaluated. RESULTS: Combinations of alpha-helical antimicrobial peptides showed in vitro synergistic interaction. Magainin II and cecropin A exerted strong antimicrobial activity and achieved a significant reduction in plasma endotoxin and TNF-alpha concentrations when compared with control and rifampicin-treated groups. Rifampicin exhibited no anti-P. aeruginosa activity and good substantial impact on endotoxin and TNF-alpha plasma concentrations. Combined treatment groups had significant reductions in bacterial count, positive blood cultures and mortality rates when compared with singly treated and control groups. CONCLUSIONS: Our results highlight the potential usefulness of these combinations that provide future therapeutic alternatives in P. aeruginosa infections.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Cationic Peptides/therapeutic use , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Rifampin/therapeutic use , Xenopus Proteins/therapeutic use , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/administration & dosage , Antimicrobial Cationic Peptides/pharmacology , Blood/microbiology , Drug Synergism , Drug Therapy, Combination , Endotoxins/blood , Injections, Intravenous , Magainins , Microbial Sensitivity Tests , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/therapeutic use , Peritoneum/microbiology , Piperacillin/therapeutic use , Piperacillin, Tazobactam Drug Combination , Plasma/chemistry , Rats , Rats, Wistar , Rifampin/administration & dosage , Rifampin/pharmacology , Survival Analysis , Treatment Outcome , Tumor Necrosis Factor-alpha/blood , Xenopus Proteins/administration & dosage , Xenopus Proteins/pharmacology
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