Fosfomycin-daptomycin and other fosfomycin combinations as alternative therapies in experimental foreign-body infection by methicillin-resistant Staphylococcus aureus.

The efficacy of daptomycin, imipenem, or rifampin with fosfomycin was evaluated and compared with that of daptomycin-rifampin in a tissue cage model infection caused by methicillin-resistant Staphylococcus aureus (MRSA). Strain HUSA 304 was used. The study yielded the following results for MICs (in µg/ml): fosfomycin, 4; daptomycin, 1; imipenem, 0.25; and rifampin, 0.03. The study yielded the following results for minimum bactericidal concentration (MBC) (in µg/ml): fosfomycin, 8; daptomycin, 4; imipenem, 32; and rifampin, 0.5. Daptomycin-rifampin was confirmed as the most effective therapy against MRSA foreign-body infections. Fosfomycin combinations with high doses of daptomycin and rifampin were efficacious alternative therapies in this setting. Fosfomycin-imipenem was relatively ineffective and did not protect against resistance.

Efficacy of tigecycline alone and with rifampin in foreign-body infection by methicillin-resistant Staphylococcus aureus.

OBJECTIVES: Tigecycline appears as an alternative therapy against methicillin-resistant Staphylococcus aureus (MRSA) with limited clinical experience. We evaluate the efficacy of tigecycline and its combination with rifampin in comparison to that for vancomycin in a rat model of foreign-body infection by MRSA. METHODS: A tissue-cage infection model were used; therapy with tigecycline, vancomycin, rifampin, tigecycline plus rifampin and vancomycin plus rifampin was administered intraperitoneally for 7 days. The antibiotic efficacy was evaluated in the tissue-cage fluid and in the coverslips (attached bacteria); the emergence of resistance was screened. RESULTS: Among monotherapies rifampin was the best treatment (decrease in log CFU/ml of tissue-cage fluid, 2.75) (P < 0.05). The addition of rifampin improved the efficacy of vancomycin (decrease, 2.28) and tigecycline (decrease, 1.56) in solitary; there were not significantly differences between tigecycline-rifampin (decrease, 3.39) and vancomycin-rifampin (decrease, 3.70), but only the latter was better than rifampin alone (P < 0.05). Resistant strains were only detected using rifampin alone. CONCLUSIONS: tigecycline alone was the least effective treatment. Tigecycline-rifampin prevented the emergence of rifampin resistance, thus allowing the benefits of rifampin over time against staphylococcal foreign-body infections, but its efficacy needs to be evaluated in comparison with other anti-MRSA combined therapies.

Efficacy of usual and high doses of daptomycin in combination with rifampin versus alternative therapies in experimental foreign-body infection by methicillin-resistant Staphylococcus aureus.

The treatment of prosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to be a challenge for the clinician. The aim of this study was to evaluate the efficacies of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg of body weight/day, respectively, in humans) and in combination with rifampin and to compare the activities to those of conventional anti-MRSA therapies. We used MRSA strain HUSA 304, with the following MICs and minimal bactericidal concentrations (MBCs), respectively: daptomycin, 1 µg/ml and 4 µg/ml; vancomycin, 2 µg/ml and 4 µg/ml; linezolid, 2 µg/ml and >32 µg/ml; and rifampin, 0.03 µg/ml and 0.5 µg/ml. In time-kill curves, only daptomycin and its combinations with rifampin achieved a bactericidal effect in log and stationary phases. For in vivo studies, we used a rat foreign-body infection model. Therapy was administered for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin at 25 mg/kg/12 h, and linezolid at 35 mg/kg/12 h, and each antibiotic was also combined with rifampin. Among monotherapies, daptomycin at 100 mg/kg/day and rifampin performed better than vancomycin and linezolid. In combination with rifampin, both dosages of daptomycin were significantly better than all other combinations, but daptomycin at 100 mg/kg/day plus rifampin achieved better cure rates at day 11 (P < 0.05) than daptomycin at 45 mg/kg/day plus rifampin. Resistant strains were found in monotherapies with rifampin and daptomycin at 45 mg/kg/day. In conclusion, daptomycin at high doses was the most effective monotherapy and also improved the efficacy of the combination with rifampin against foreign-body infections by MRSA. Clinical studies should confirm whether this combination may be considered the first-line treatment for foreign-body infections by MRSA in humans.

Efficacy of high doses of daptomycin versus alternative therapies against experimental foreign-body infection by methicillin-resistant Staphylococcus aureus.

Since the currently approved dose of daptomycin (6 mg/kg of body weight/day) has been associated with clinical failures and resistance development, higher doses for some difficult-to-treat infections are being proposed. We studied the efficacy of daptomycin at high doses (equivalent to 10 mg/kg/day in humans) and compared it to that of reference and alternative treatments in a model of foreign-body infection with methicillin (meticillin)-resistant Staphylococcus aureus. In vitro studies were conducted with bacteria in the log and stationary phases. For the in vivo model, therapy with daptomycin at 100 mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin (rifampicin) at 25 mg/kg/12 h, or linezolid at 35 mg/kg/12 h was administered for 7 days. Antibiotic efficacy was evaluated using either bacteria from tissue cage fluids or those attached to coverslips. We screened for the emergence of linezolid- and rifampin-resistant strains and analyzed the surviving population from the daptomycin-treated group. Only daptomycin was bactericidal in both the log- and stationary-phase studies. Daptomycin (decrease in the log number of CFU per milliliter of tissue cage fluid, 2.57) and rifampin (decrease, 2.6 log CFU/ml) were better (P < 0.05) than vancomycin (decrease, 1.1 log CFU/ml) and linezolid (decrease, 0.9 log CFU/ml) in the animal model. Rifampin-resistant strains appeared in 60% of cases, whereas no linezolid resistance emerged. No daptomycin-resistant subpopulations were detected at frequencies of 10(-7) or higher. In conclusion, daptomycin at high doses proved to be as effective as rifampin, and the two were the most active therapies for this experimental foreign-body infection. These high doses ensured a profile of safety from the development of resistance.

[Oxygen metabolism in isolated rat hepatocytes in obesity. Influence of vitamin C]. / Metabolismo oxigénico en hepatocitos aislados de rata en la obesidad. Influencia de la vitamina C.

Nutritional obesity induced by the ingestion of hyperlipidic diet implies a high consume of lipids, which might be involved in oxygen metabolism. Double bound, in the fatty-acid molecules are a vulnerable point to undergo oxidation reactions-generating lipid peroxidation, that are potentially toxic and can produce serious cell injury (alteration in cell permeability and prostaglandins...). To prevent this oxidative injury the aerobic organisms have intracellular mechanisms of defense, the antioxidant systems, that may be classified as enzymatic and nonenzymatic. Vitamin C belongs to the second group and acts as scavenger of free radicals and other species. The purpose of this study was to evaluate the oxygen metabolism in isolated hepatocytes of rats which obesity has been reached by the ingestion of an hyperenergetic olive-oil rich controlled liquid diet and evaluate the effect of ascorbic acid. Cellular oxidative injury in isolated hepatocytes was induced through a lipid peroxidative and cytotoxic molecule tert-butyl-hydroperoxide (t-BOOH). Results show higher levels of lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) production in obese rats as compared with controls. Otherwise, when these groups are supplemented with ascorbic acid these changes decrease significantly. ATP levels decrease in hepatocytes of obese rats incubated in the presence of 1 mM tert-butylhydroperoxide. While it is maintained in ascorbic acid supplemented animals. GSH values were lower in hepatocytes from obese and control rats, incubated with tert-butyl-hydroperoxide. Supplementation with ascorbic acid also maintained GSH levels thus indicating that ascorbic acid is acting as an efficient antioxidant.

In vitro antibacterial effect of the essential oil of Thymus longiflorus Boiss.

The essential oil of Thymus longiflorus Boiss was tested for its in vitro antibacterial activity. The results showed antibacterial effects against Gram-positive and Gram-negative bacteria, especially against Pseudomonas fluorescens and Mycobacterium phlei.

Glaucium flavum Crantz. IV. Antimicrobial activity.

The extracts obtained from root, stem, leaf and fruit pericarps of Glaucium flavum showed antibacterial activity in an in vitro assay. The root extract was the most active against the Gram-positive bacteria which were investigated.

Seasonal Variation of Essential Oil Yield and Composition of Thymus hyemalis.

The aerial parts of THYMUS HYEMALIS Lange were collected throughout its complete vegetative cycle (April 1981 to March 1982) from the same locality. The yield and composition of essential oil have been determined in eleven samples with special reference to the content of 1,8-cineole, camphor, thymol, and carvacrol. It was found that the yield and composition of the oil changed from month to month. On the basis of the results obtained, July might be proposed as the most suitable month for harvesting T. HYEMALIS, giving the maximum yield in essential oil, which is especially rich in terpenic hydrocarbons at this time. Maximum levels of 1,8-cineole in August, however, might warrent harvesting during this month as well.