Comparative in vitro activity of thiamphenicol-glycinate and thiamphenicol-glycinate-acetylcysteinate and other antimicrobials against respiratory pathogens.

Thiamphenicol-glycinate-acetylcysteinate (TGA; CAS 20192-91-0) is widely used for the treatment of infections of varied aetiology. The aim of this study was to compare the antibacterial activity of thiamphenicol-glycinate (TG; CAS 15318-45-3), TGA, amoxicillin (CAS 61336-70-7) plus clavulanic acid (CAS 58001-44-8), azithromycin (CAS 83905-01-5) and ceftriaxone (CAS 104376-79-6). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined against Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae according to the National Committee for Clinical Laboratory Standards (NCCLS) methods. The effects of changes in assay conditions were also examined. The activity of TG and TGA was similar to that of amoxicillin plus clavulanic acid, with the exception of methicillin resistant S. aureus. Azithromycin and ceftriaxone were characterised by a limited activity against gram-positive cocci and methicillin resistant and cefinase-positive S. aureus, respectively. TG and TGA are characterized by a wide spectrum of activity, comparable to that of recent commercialized antibiotics for treatment of respiratory tract infections.

In vitro antimicrobial activity of propolis dry extract.

In this study the antibacterial and antifungal properties of propolis, a natural product of bees, have been investigated against different pathogens. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined according to NCCLS standards on 320 strains including Staphylococcus aureus, Group A beta-hemolytic streptococci, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Candida albicans. Time-kill curves were assessed for susceptible microorganisms, testing 0, 0.5, 1, 2, 4 x MIC for propolis, by counting viable bacteria after 0, 3, 6, 24 hours and viable yeasts after 0, 3, 6, 24 and 48 hours. Propolis showed good antimicrobial activity against most of the isolates, particularly S. pneumoniae, H. influenzae and M. catarrhalis, but not against Enterobacteriaceae. Time-kill curves demonstrated bacteriostatic rather than bactericidal activity of propolis, the latter being evident only at high concentrations.

Candida albicans cellular internalization: a new pathogenic factor?

The preliminary results of a study to show the possibility that Candida albicans can internalize into epithelial cells are reported. The study was performed on buccal, vaginal and HeLa cells. Buccal and vaginal cells, at a concentration of 5 x 10(4) cells/ml and HeLa monolayers were incubated for 2, 3 and 4 h with 10(5) colony forming units of a Candida albicans isolate. After incubation, non-internalised yeasts were eliminated and samples were processed for examination by Scanning Electron Microscopy. Results suggest that receptor-mediated endocytosis could be involved in the pathogenesis of recurrent oral and vaginal infections. This phenomenon could represent an interesting experimental model to testing drug interference in the development of therapeutic strategies against C. albicans infections.

Comparative effect of thiamphenicol glycinate, thiamphenicol glycinate N-acetylcysteinate, amoxicillin plus clavulanic acid, ceftriaxone and clarithromycin on pulmonary clearance of Haemophilus influenzae in an animal model.

BACKGROUND: Thiamphenicol glycinate (TG) and its derivative thiamphenicol glycinate N-acetylcysteinate (TGA) could be a valid therapeutic option in the treatment of respiratory tract infections. METHODS: Time-kill curves of TG and TGA and pulmonary clearance in Haemophilus influenzae infected guinea pigs were compared with those of clarithromycin, ceftriaxone and amoxicillin plus clavulanic acid. RESULTS: The bacterial activities of the tested antibiotics were comparable. When compared to the control group, lung bacterial counts were significantly lower for the TGA group at 3 h vs. controls, while for the other treatments, significant decreases were recorded after 6 h. All drugs showed a log count of <2.0 at 24 h with respect to the control while at 48 h all groups demonstrated a log count of <2.0. CONCLUSIONS: Although the in vitro activity of the tested drugs evaluated by time-kill curves seemed comparable, some pharmacokinetic and pharmacodynamic characteristics of TGA contribute to improving the resolution of the infective process.

Lack of in vitro and in vivo selection of bacterial resistance by roxithromycin.

The in vitro and in vivo selective pressure exerted by roxithromycin on Lancefield group A beta-haemolytic streptococci (GABHS) was investigated. In vitro antimicrobial activity on fifty GABHS strains was determined by the microdilution method and by boundary concentration (BC) determination. Insorgence of resistance was evaluated by redetermining MIC and BC after exposure to 16 x MIC roxithromycin concentration. In vivo insorgence of resistance was evaluated by MIC and BC determinations on the GABHS strain recovered from infected mice peritoneum, after treatment with 20 mg/kg roxithromycin. The roxithromycin serum kinetics was established in healthy and infected mice. Neither significant changes in GABHS MIC or BC after in vitro or in vivo exposure to roxithromycin nor a difference in roxithromycin serum levels between healthy and infected mice were detected, suggesting that the roxithromycin selection of resistance in GABHS is low.

Serum and lung levels of thiamphenicol after administration of its glycinate N-acetylcysteinate ester in experimentally infected guinea pigs.

Thiamphenicol is an analogue of chloramphenicol and is characterised by a broad spectrum of action. In this study, serum and lung levels of thiamphenicol (TAP) were studied in infected guinea pigs after the administration of thiamphenicol glycinate N-acetylcysteinate (TGA). Animals received a single dose of TGA (15 mg/kg, subcutaneously) immediately after intra-tracheal infection with Haemophilus influenzae (about 10(7) CFU/animal). Serum and lung concentrations of TAP were determined at 0, 1, 3, 6, 12 and 24 h after drug administration by means of HPLC. TAP serum levels were elevated at 1 h and remained detectable for 24 h after drug administration. Tissue lung levels were comparable to peak serum concentrations but remained higher and decreased more slowly than serum concentrations.

Antimycotic activity and phagocytosis effects of econazole in combination with ibuprofen isobuthanolammonium against vaginal strains.

Vaginal infections caused by Candida spp., other yeasts and Trichomonas vaginalis are problematic mainly due to the various factors involved in development of infection and to the failure of common treatments. In this study we investigated the presence of synergistic activity of econazole and ibuprofen isobuthanolammonium against 310 different vaginal isolates, by using the microdilution broth assay to test in vitro antimicrobial activity and the effect of the two drugs on phagocytosis and intramacrophagic cellular killing of mouse peritoneal macrophages. The effect of sub-inhibitory concentrations of econazole / ibuprofen isobuthanolammonium combination on Candida albicans germ tube formation was also evaluated. The in vitro antifungal activity of econazole was notably improved by addition of ibuprofen isobuthanolammonium. Macrophage killing of C. albicans was significantly increased by the two drugs and also germ-tube formation was significantly affected. We conclude that the addition of ibuprofen isobuthanolammonium to econazole provides better in vitro antifungal activity. However, further studies are needed to elucidate the in vivo action of this formulation.

Immunostimulating effect of oral glutamine.

Glutamine represents the principal metabolic substrate for all rapidly proliferating cells. Since part of the glutamine efficacy could be related to immunoregulating properties, we assessed the effects of orally administered glutamine on serum interleukin-2 (IL-2) levels and intestinal T-cell populations in 48 athymic (nude) mice. Twenty-four mice received a standard diet enriched by glutamine (added to drinking water at a 4% concentration), while the other 24 served as the control group and received the same diet without glutamine. In glutamine-fed animals, we observed a marked increase in IL-2 concentrations after 10 days of treatment in comparison with control group and a modest but significant increase in intestinal T-cell counts. These results suggest that oral glutamine is able to exert local and systemic immunostimulating activity that could be of relevance in the prevention of gut integrity and immune defense loss associated, for example, with trauma, surgery, and starvation.

Interference on Helicobacter pylori growth and adhesion by omeprazole and other drugs.

Helicobacter pylori is the causative agent of gastritis and a co-agent in other gastroduodenal diseases. Gastroduodenal ulcer and MALT-lymphoma in particular, regress when patients are administered antimicrobial agents to eradicate infection. Sometimes eradication is not definitive and is difficult to check. The aim of our study was to test the antimicrobial activity of omeprazole on H. pylori in comparison with ampicillin and other anti-H2 drugs (ranitidine and famotidine), and to evaluate their interference with bacterial adhesion of H. pylori. We also compared results of the agar dilution antibacterial sensitivity test on H. pylori to those obtained using a bacteria adherence to cell monolayers model, to see if drug activity was different against adhered bacteria. We evaluated omeprazole and ampicillin MIC90s (minimum inhibitory concentrations) against 20 H. pylori isolates by traditional agar dilution method and by exposing previously adhered bacteria to an Hep-2 monolayer to different drug concentrations. The activity against bacteria adhered to cell lines was evaluated by counting viable adhered bacteria after 1, 6, 12 hours of contact with drug. Interference with adherence to Hep-2 cells was also tested. Omeprazole and ampicillin MICs were comparable to other findings (omeprazole MIC90 was 12.5 microg/ml and ampicillin MIC90 was 0.016 microg/ml), while higher concentrations were necessary (4 x MIC90) against adhered bacteria. These findings suggest that MICs evaluated with traditional assays can have different predictivity than tests on adhered H. pylori.

Serum and bone concentrations of teicoplanin and vancomycin: study in an animal model.

Teicoplanin and vancomycin are antibiotics widely used in the therapy of bone and joint infections. The aim of this study was to compare bone and serum concentrations of each antibiotic in guinea pigs after administration of 50 mg/kg of teicoplanin or vancomycin by the intravenous route. Serum and bone concentrations were determined immediately before and 0.5, 1, 2, 6, 12 and 24 h after drug administration by means of high performance liquid chromatography. Teicoplanin concentrations were always higher than vancomycin levels. Area under the concentration/time curve was significantly greater for teicoplanin than for vancomycin. In bone, teicoplanin concentration increased up to 6 h, while vancomycin reached its peak after 2 h. Moreover, teicoplanin showed markedly higher levels at 6, 12 and 24 h than vancomycin. In conclusion, the ability of teicoplanin to penetrate bone in greater amount than vancomycin confirms the potential use of teicoplanin in the treatment of bone infections and in the prophylaxis of orthopedic surgery.

[Antimicrobial and sporicidal efficacy of various disinfectant solutions]. / Efficacia antimicrobica e sporicida di varie soluzioni disinfettanti.

The often indiscriminate use of antimicrobial agents has led to increased bacterial resistance over the past years. This phenomenon is above all evident in nosocomial environments but also at a community level. It is therefore important that, in addition to the rational use of antibiotics, an accurate prophylaxis is performed which includes the correct use of disinfectants. This study examines the antimicrobial activity of various commercially available disinfectant solutions consisting of one or more active ingredients. An analysis of the results reveals that products consisting of an association of individual components (quaternary ammonium chloride with o-phenylphenol and/or isopropyl alcohol; chlorhexidine with benzalkonium chloride or with diazolidinylurea and isopropanol) demonstrate a greater efficacy in terms of microbicidal concentration and contact times.