RESUMEN
OBJECTIVES: 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. METHODS: Antimicrobial activity of citropin 1.1 was measured by MIC, MBC, time-kill studies and chequerboard titration method. RESULTS: 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. CONCLUSIONS: 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.
Asunto(s)
Proteínas Anfibias/farmacología , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Quimioterapia Combinada/farmacología , Rhodococcus equi/efectos de los fármacos , Infecciones por Actinomycetales/microbiología , Infección Hospitalaria/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Rhodococcus equi/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
Proteínas Anfibias/farmacología , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Cocos Grampositivos/efectos de los fármacos , Cocos Grampositivos/crecimiento & desarrollo , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones de los Tejidos Blandos/microbiología , Proteínas Anfibias/síntesis química , Proteínas Anfibias/química , Proteínas Anfibias/metabolismo , Animales , Antibacterianos/metabolismo , Péptidos Catiónicos Antimicrobianos/síntesis química , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/metabolismo , Recuento de Colonia Microbiana , Interacciones Farmacológicas , Farmacorresistencia Bacteriana , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
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.
Asunto(s)
Neumonía Bacteriana/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Proteínas y Péptidos Salivales/farmacología , Staphylococcus aureus/efectos de los fármacos , Stenotrophomonas maltophilia/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Histatinas , Humanos , Huésped Inmunocomprometido , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVE: 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. METHODS: Antimicrobial activity of temporin A was measured by MIC, MBC and time-kill studies and by the chequerboard titration method. RESULTS: 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. CONCLUSIONS: 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.
Asunto(s)
Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Enterococcus faecalis/efectos de los fármacos , Proteínas/uso terapéutico , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos , Infección Hospitalaria/microbiología , Interacciones Farmacológicas/fisiología , Enterococcus faecalis/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana/estadística & datos numéricos , Proteínas/farmacologíaRESUMEN
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.
Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Oligopéptidos/farmacología , Oligopéptidos/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/patología , Infecciones Estafilocócicas/tratamiento farmacológico , Animales , Bacteriemia , Cefazolina/farmacología , Cefazolina/uso terapéutico , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Imipenem/farmacología , Imipenem/uso terapéutico , Masculino , Ratones , Ratones Endogámicos BALB C , Oligopéptidos/efectos adversos , Distribución Aleatoria , Sensibilidad y Especificidad , Sepsis/microbiología , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/efectos de los fármacos , Factores de Tiempo , Vancomicina/farmacología , Vancomicina/uso terapéuticoRESUMEN
OBJECTIVE: 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. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: BALB/c male mice. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSION: 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.
Asunto(s)
Antibacterianos/farmacología , Proteínas/farmacología , Choque Séptico/tratamiento farmacológico , Choque Séptico/mortalidad , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/mortalidad , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Ensayo de Inmunoadsorción Enzimática , Interleucina-6/análisis , Masculino , Ratones , Ratones Endogámicos BALB C , Probabilidad , Distribución Aleatoria , Sensibilidad y Especificidad , Tasa de Supervivencia , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisisRESUMEN
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Linezolid as perioperative prophylaxis can be useful for the prevention of graft infections caused by multiresistant staphylococcal strains.
Asunto(s)
Profilaxis Antibiótica/métodos , Farmacorresistencia Bacteriana , Quimioterapia Combinada/uso terapéutico , Glicopéptidos/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Staphylococcus epidermidis/efectos de los fármacos , Acetamidas/farmacología , Acetamidas/uso terapéutico , Animales , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/fisiología , Quimioterapia Combinada/farmacología , Glicopéptidos/farmacología , Rechazo de Injerto/microbiología , Levofloxacino , Linezolid , Masculino , Pruebas de Sensibilidad Microbiana , Ofloxacino/farmacología , Ofloxacino/uso terapéutico , Oxazolidinonas/farmacología , Oxazolidinonas/uso terapéutico , Ratas , Ratas Wistar , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/crecimiento & desarrollo , Vancomicina/farmacología , Vancomicina/uso terapéuticoRESUMEN
The prevalence of intestinal protozoans and helminths in stool samples of individuals with allergic cutaneous symptoms was evaluated to study a possible link between parasites and allergy. Altogether, 218 patients who had chronic urticaria, atopic dermatitis, or pruritus of unknown origin were included in the study. Standard laboratory tests for the detection of allergic etiology were performed for all patients. The presence of intestinal parasites was investigated using microscopy, immunofluorescence, and immunoenzymatic assays. Overall, protozoans and helminths were recovered from the stools of 48 subjects (P = 0.004), 18 of whom were affected with intestinal symptoms (P = 0.023). The presence of Giardia lamblia in the stools was significantly associated with allergic cutaneous manifestations (P = 0.030). In addition, patients with allergy were significantly more likely to have > or = 5 Blastocystis hominis organisms per field (P = 0.046). There was a set of patients with allergic cutaneous diseases in whom the presence of intestinal parasites may not be incidental.
Asunto(s)
Dermatitis Atópica/complicaciones , Parasitosis Intestinales/epidemiología , Urticaria/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Enfermedad Crónica , Heces/parasitología , Femenino , Helmintiasis/complicaciones , Helmintiasis/epidemiología , Helmintiasis/inmunología , Humanos , Parasitosis Intestinales/complicaciones , Parasitosis Intestinales/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Infecciones por Protozoos/complicaciones , Infecciones por Protozoos/epidemiología , Infecciones por Protozoos/inmunología , Prurito/complicacionesRESUMEN
Staphylococcus aureus is a prevalent cause of bacterial infections associated with indwelling medical devices. RNA III inhibiting peptide (RIP) is known to inhibit S. aureus pathogenesis by disrupting quorum-sensing mechanisms. RIP was tested in the present study for its ability to inhibit S. aureus biofilm formation in a rat Dacron graft model. The activity of RIP was synergistic with those of antibiotics for the complete prevention of drug-resistant S. aureus infections.
Asunto(s)
Biopelículas/crecimiento & desarrollo , Oligopéptidos/farmacología , Prótesis e Implantes/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Animales , Antibacterianos/farmacología , Profilaxis Antibiótica , Biopelículas/efectos de los fármacos , Comunicación Celular/efectos de los fármacos , Recuento de Colonia Microbiana , Sinergismo Farmacológico , Masculino , Pruebas de Sensibilidad Microbiana , Tereftalatos Polietilenos , Ratas , Ratas WistarRESUMEN
Two laboratory methods, a cell culture system and double fluorogenic staining, were used to study the viability and infective ability of Cryptosporidium parvum sporozoites and oocysts after short-term exposure to four cathelicidin peptides. The compounds, SMAP-29, BMAP-28, PG-1 and Bac7(1-35), exerted a strong cytotoxic effect on sporozoites, but did not affect the viability and function of oocysts consistently. Overall, in the sporozoite series, a percentage of the viable population decreased rapidly to less than detectable levels after 15 and 60 min exposure to the peptides at concentrations of 100 and 10 micro g/mL, respectively. In the oocyst series, no compound produced complete inhibition of parasite growth: 60-85% of the oocyst population was viable after 180 min exposure at 100 micro g/mL. SMAP-29 exerted the highest activity against both sporozoites and oocysts.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Antiprotozoarios/farmacología , Cryptosporidium parvum/efectos de los fármacos , Péptidos/síntesis química , Péptidos/farmacología , Síndrome de Inmunodeficiencia Adquirida/parasitología , Secuencia de Aminoácidos , Animales , Catelicidinas , Células Cultivadas , Heces/parasitología , Citometría de Flujo , Pruebas de Sensibilidad Microbiana , Datos de Secuencia MolecularRESUMEN
Staphylococcus epidermidis is a frequent cause of infections associated with foreign bodies and indwelling medical devices. The bacteria are capable of surviving antibiotic treatment through encapsulation into biofilms. RNAIII-inhibiting peptide (RIP) is a heptapeptide that inhibits S. aureus pathogenesis by disrupting quorum-sensing mechanisms. In this study, RIP inhibited drug-resistant S. epidermidis biofilm formation through a mechanism similar to that evidenced for S. aureus. RIP is synergistic with antibiotics in eliminating 100% of graft-associated in vivo S. epidermidis infections, which suggests that RIP may be used to coat medical devices to prevent staphylococcal infections. Disruption of cell-cell communication can prevent infections associated with antibiotic-resistant strains.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas , Oligopéptidos/farmacología , Staphylococcus epidermidis/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales , Animales , Adhesión Bacteriana , Biopelículas/crecimiento & desarrollo , Línea Celular , Resistencia a Medicamentos , Humanos , Masculino , Fosfoproteínas/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus epidermidis/metabolismoRESUMEN
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.
Asunto(s)
Acinetobacter/efectos de los fármacos , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Infección Hospitalaria/microbiología , Resistencia a Múltiples Medicamentos , Meliteno/farmacología , Antibacterianos/química , Péptidos Catiónicos Antimicrobianos/química , Meliteno/químicaRESUMEN
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.
Asunto(s)
Modelos Animales de Enfermedad , Infecciones por Escherichia coli/tratamiento farmacológico , Piperacilina/administración & dosificación , Piperacilina/uso terapéutico , Proteínas/administración & dosificación , Proteínas/uso terapéutico , Choque Séptico/tratamiento farmacológico , Animales , Péptidos Catiónicos Antimicrobianos , Ciego/cirugía , Quimioterapia Combinada , Ligadura , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/farmacología , Masculino , Pruebas de Sensibilidad Microbiana , Péptidos , Peritonitis/tratamiento farmacológico , Peritonitis/etiología , Peritonitis/microbiología , Punciones , Ratas , Ratas Wistar , Choque Séptico/etiología , Choque Séptico/microbiologíaRESUMEN
OBJECTIVE: The purpose of this study was to investigate the efficacy of temporin A as a prophylactic agent in a rat model of vascular graft infection from methicillin sodium-susceptible and methicillin sodium-resistant Staphylococcus epidermidis. METHODS: The prospective, randomized, controlled animal study set in a research laboratory in a university hospital used 280 adult male Wistar rats (weight range, 280 to 350 g). Graft infections were established in the back subcutaneous tissue of rats with implantation of 1-cm(2) sterile Dacron grafts followed by topical inoculation with 2 x 10(7) colony-forming units of S epidermidis. The study for each staphylococcal strain included: one control group (no graft contamination), one contaminated group that did not receive any antibiotic prophylaxis, one contaminated group that received temporin A-soaked graft, two contaminated groups that received perioperative intraperitoneal cefazolin (30 mg/kg) or vancomycin hydrochloride prophylaxis (10 mg/kg), and two contaminated groups that received temporin A-soaked graft and perioperative intraperitoneal cefazolin (30 mg/kg) or vancomycin hydrochloride (10 mg/kg) prophylaxis. All grafts were explanted at 7 days after implantation. The main outcome measure was quantification of bacterial contamination. RESULTS: Overall, the perioperative prophylaxis based on soaked grafts was not significantly different to that of parenteral vancomycin hydrochloride. Only the combination between temporin A and vancomycin hydrochloride produced a complete bacterial inhibition for both strains. CONCLUSION: Temporin A showed a similar antibacterial in vitro activity against the two different strains. The in vivo results suggest its potential use in providing prophylaxis to direct graft contamination when used in combination with parenteral vancomycin hydrochloride.
Asunto(s)
Profilaxis Antibiótica , Resistencia a la Meticilina , Meticilina/farmacología , Infecciones Relacionadas con Prótesis/prevención & control , Proteínas/uso terapéutico , Infecciones Estafilocócicas/prevención & control , Staphylococcus epidermidis/efectos de los fármacos , Animales , Péptidos Catiónicos Antimicrobianos , Prótesis Vascular , Cefazolina/uso terapéutico , Masculino , Ratas , Ratas Wistar , Vancomicina/uso terapéuticoRESUMEN
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 (<10 CFU/ml). In contrast, for rats that received Dacron grafts soaked with 10 micro g of Q-D per ml and Dacron grafts soaked with 10 or 100 micro g of vancomycin per ml, the quantitative graft cultures demonstrated 2.2 x 10(2) +/- 1.3 x 10(2), 2.2 x 10(6) +/- 1.9 x 10(5), and 5.6 x 10(2) +/- 0.3 x 10(2) CFU/ml, respectively. Taken together the results of the study demonstrate that the use of Dacron grafts soaked with Q-D can result in significant bacterial growth inhibition and show that this compound is potentially valuable for prevention of vascular prosthetic graft infection.
Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Prótesis Vascular/efectos adversos , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones Estafilocócicas/prevención & control , Staphylococcus epidermidis , Virginiamicina/uso terapéutico , Animales , Farmacorresistencia Microbiana , Masculino , Pruebas de Sensibilidad Microbiana , Infecciones Relacionadas con Prótesis/microbiología , Ratas , Ratas Wistar , Infecciones Estafilocócicas/microbiología , Resistencia a la VancomicinaRESUMEN
The therapeutic efficacies of buforin II, indolicidin, and KFFKFFKFF were investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 10 microg of Escherichia coli O111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg of buforin II per kg of body weight, 1 mg of indolicidin per kg, 1 mg of KFFKFFKFF per kg, and 20 mg of imipenem per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. Treatment with all peptides resulted in significant reductions in plasma endotoxin and TNF-alpha concentrations compared with those resulting from the imipenem and saline treatments. On the other hand, imipenem treatment significantly reduced the levels of bacterial growth compared with the reductions achieved with the peptide and saline treatments. All compounds reduced the rates of death compared to that for the controls. Although the peptides demonstrated lower levels of antimicrobial activity than imipenem, they exhibited the dual properties of antimicrobial and antiendotoxin agents.
Asunto(s)
Antiinfecciosos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Proteínas/uso terapéutico , Choque Séptico/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Endotoxinas/sangre , Masculino , Pruebas de Sensibilidad Microbiana , Ratas , Ratas Wistar , Choque Séptico/sangre , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
The viability of Cryptosporidium parvum after exposure to peptide antibiotics was studied by two different methods, a cell culture system and a double fluorogenic staining. The peptides KFFKFFKFF and IKFLKFLKFL exerted high cytotoxic effects on sporozoites, as demonstrated by cell cultures (complete inhibition after 60 min at 100 microg/ml) and flow cytometry (30% after 20 min at 100 microg/ml), but did not affect consistently the oocysts. Clarithromycin and rifabutin demonstrated less activity against sporozoites but higher activity against oocysts (30% after 180 min at 10 microg/ml). The combination between peptides and azithromycin or rifabutin exerted the highest activities.
Asunto(s)
Claritromicina/farmacología , Cryptosporidium parvum/efectos de los fármacos , Cryptosporidium parvum/patogenicidad , Péptidos/síntesis química , Péptidos/farmacología , Rifabutina/farmacología , Secuencia de Aminoácidos , Animales , Claritromicina/administración & dosificación , Cryptosporidium parvum/fisiología , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Citometría de Flujo , Oocistos/efectos de los fármacos , Péptidos/administración & dosificación , Péptidos/química , Rifabutina/administración & dosificación , Esporozoítos/efectos de los fármacosRESUMEN
The therapeutic efficacies of three polycationic peptides selected among the class of the magainins (magainin I, magainin II, and magainin II amide), alone and combined with piperacillin, were investigated in a rat model of septic shock. Rats were given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia coli and randomized to receive intraperitoneally isotonic sodium chloride solution, 60 mg of piperacillin per kg of body weight, and 1 mg of each magainin per kg alone and combined with 60 mg of piperacillin per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. Treatments with the magainins achieved significant reductions of bacterial growth and plasma endotoxin and TNF-alpha concentrations. In general, treatments with the combinations of magainins and piperacillin demonstrated the highest efficacies.