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Biomedical subjects

C Carbon

Publications and source records attributed to C Carbon.

At least 253 records · Page 14Linked to original sources
PubMed1987

Bactericidal effect of ofloxacin alone and combined with fosfomycin or vancomycin against Staphylococcus aureus in vitro and in sera from volunteers.

The bactericidal activity of ofloxacin alone and in combination was evaluated against strains of Staphylococcus aureus by measuring MBCs, FBC indexes and by the killing curve technique. Bactericidal titres were determined in sera from volunteers given ofloxacin alone or in combination with fosfomycin or vancomycin. FBC indices less than 0.75 were observed with fosfomycin, showing moderate synergy. FBC indices of 1 were seen with vancomycin. Killing kinetic experiments indicated that ofloxacin (1 and 4 mg/l) exerted a rapid bactericidal effect (99.9% killing in 4 h); the combination of ofloxacin and fosfomycin was synergistic for one of three strains, while killing kinetics of ofloxacin were unaltered by fosfomycin for two of three strains or by vancomycin for the three strains. Sera collected two hours after ofloxacin or fosfomycin had been administered had bactericidal titres less than 1/2. Bactericidal titres were significantly greater in sera from volunteers given the combination of these two drugs. Similar bactericidal titres were obtained in sera after the administration of vancomycin alone or in combination with ofloxacin. A loading dose of 400 mg ofloxacin with subsequent doses of 200 mg had no significantly prolonged effect on bactericidal titres.

Adult↗
PubMed1987

Value of antibiotic levels in serum and cardiac vegetations for predicting antibacterial effect of ceftriaxone in experimental Escherichia coli endocarditis.

In a rabbit model of Escherichia coli endocarditis, we studied the penetration into infected vegetations and the antibacterial effect of ceftriaxone. Ceftriaxone was given at different dosages, alone or with an interfering agent, diclofenac, a nonsteroidal anti-inflammatory drug, to determine the predictive value of the antibiotic levels in serum or infected vegetations on the antibacterial efficacy. Diclofenac increased the serum terminal half-life of ceftriaxone and increased its extravascular diffusion in tissue cage fluid, as well as in infected vegetations, allowing us to obtain various antibiotic concentrations in the infected site. Two hours after the fourth injection, around the time of peak level in serum, we observed a linear relationship between (i) serum and local antibiotic levels in vegetations, (ii) local antibiotic levels in a range of 142 to 600 X MBC and bacterial titer (log10 CFU/g) in vegetations, and (iii) serum antibiotic levels in a range of 800 to 1,400X MBC and bacterial titer in vegetations. In vivo, antibacterial effect was obtained only with high antibiotic levels in vegetations (greater than or equal to 220X MBC). This was confirmed by incubating vegetations sampled from infected animals in rabbit serum containing ceftriaxone (ex vivo experiment). Given once daily at a therapeutic dosage (30 mg/kg) for 4 days, ceftriaxone exhibited good efficacy (log10 CFU/g of vegetation = 2.41 +/- 2.7 versus 7.41 +/- 0.92 in control animals) and prevented regrowth of bacteria until 24 h after the last injection. We concluded that (i) provided the dose is sufficient, a long-acting cephalosporin can prove effective in severe gram-negative infections even when given infrequently, and (ii) serum antibiotic levels around the peak value, reflecting high effective local levels, could predict the therapeutic efficacy and represent a simple test to monitor the clinical course of a severe infectious process.

Animals↗
PubMed1987

Comparative efficacy of cefotiam, cefmenoxime, and ceftriaxone in experimental endocarditis and correlation with pharmacokinetics and in vitro efficacy.

To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three cephalosporins, cefotiam, cefmenoxime, and ceftriaxone, in a rabbit model of experimental Escherichia coli endocarditis after 4 days of treatment. The MBCs of cefotiam, cefmenoxime, and ceftriaxone for the E. coli strain were 0.5, 0.125, and 0.06 microgram/ml, respectively. Killing curves at 10 times the MBC were similar for the three cephalosporins. In serum, the elimination half-life of ceftriaxone was twice as much as the elimination half-life of cefotiam or cefmenoxime (2.8 +/- 0.45 versus 1.4 +/- 0.25 or 1.3 +/- 0.4 h, respectively). Ceftriaxone was much more effective than cefotiam. The bacterial titer in the vegetations (log10 CFU per gram of vegetation) was 7.56 +/- 1 with cefotiam and 2.41 +/- 2.6 with ceftriaxone, as their concentrations were 18 and 466 times higher, respectively, than their MBCs. Although ceftriaxone and cefmenoxime exhibited a similar rate of killing and percentage of protein binding, ceftriaxone was more effective than cefmenoxime at the same regimen of 15 mg/kg twice a day (3.08 +/- 1.1 versus 4.82 +/- 3.2 log10 CFU/g of vegetation). When antibiotic was given as a single daily injection of 30 mg/kg, the antibacterial effect persisted for ceftriaxone, but not for cefmenoxime. The longer elimination half-life and the higher local concentration/MBC ratio of ceftriaxone explained these results. The bacterial titer measured 24 h after the fourth injection of 30 mg of ceftriaxone per kg confirmed that this regimen prevented regrowth of bacteria. These results suggest that the local antibiotic level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed between the drugs in vivo. They also demonstrate that, provided that the dose is sufficient, a long-acting broad-spectrum cephalosporin may be effective in severe gram-negative infections, even when given at relatively long dosing intervals, in contrast with a rapidly cleared drug with the same intrinsic activity.

Animals↗
PubMed1987

Alteration of gentamicin and cefazolin kinetics with control of the hypothyroid state in humans.

We studied the effect of the control of the hypothyroid state in humans on the pharmacokinetic parameters of cefazolin and gentamicin after a single intravenous injection. These two antibiotics were chosen because of their different patterns of binding to serum albumin (0% for gentamicin and 82% for cefazolin). In hypothyroidism, the behavior of cefazolin only was altered, with a decrease in the total body clearance, possibly due to reduced urinary excretion, and a decrease in the volume of distribution without a significant alteration of cefazolin binding to serum protein.

Cefazolin↗
PubMed1987

Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide.

Two monoclonal immunoglobulin G1 antibodies reacting with Cryptococcus neoformans capsular polysaccharide (CNPS) were produced in mice by using a carefully defined procedure for immunization with unmodified CNPS purified from C. neoformans serotype A. Since the antibodies were found to have the same pattern of specificity, only one of them (E1) is described. This anti-CNPS monoclonal antibody reacted with the glucuronoxylomannan component of CNPS but not with the constituent monosaccharides or with the mannose alpha(1----3)-linked oligosaccharide structures present on CNPS. E1 appeared to be specific for C. neoformans serotype A by agglutination of whole cells; it was specific for soluble CNPS A by gel immunoprecipitation. However, indirect immunofluorescence and competitive-binding enzyme-linked immunosorbent assay experiments showed low levels of cross-reactivity with serotypes B and D but not with serotype C. Concentrations 10,000 times higher for serotypes B and D cells than for serotype A cells were required for a 50% inhibition of E1 anti-CNPS A activity as measured by enzyme-linked immunosorbent assay. Among the other yeasts tested, a cross-reaction was only detected with Trichosporon beigelii. The four serotypes of C. neoformans could be distinguished based on intensities and patterns of fluorescence in an indirect immunofluorescence assay using the monoclonal anti-CNPS A antibody. Monoclonal anti-CNPS A antibodies could be useful for fundamental studies on the glucuronoxylomannan structure, as well as for clinical applications such as serotyping and possibly the serological diagnosis of cryptococcosis.

Animals↗
PubMed1987

Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody.

Humoral immunity does not play a prominent role during experimental cryptococcosis. However, previous studies have shown that immunoglobulin G (IgG) anti-Cryptococcus neoformans antibodies can mediate cell-dependent yeast killing in vitro. Therefore, the protective effect of a previously described monoclonal IgG1 anti-C. neoformans antibody (E1) administered intraperitoneally 24 h before intravenous infection with a C. neoformans serotype A strain was evaluated in mice. Heavily infected (3 X 10(6) cells) untreated mice died in 2.9 +/- 0.5 (standard deviation) days. Survival time was 17.9 +/- 1.6 days for mice treated with 100 micrograms of E1 and 3.0 +/- 0.7 days for mice treated with 100 micrograms of a monoclonal IgG1 anti-thyroglobulin antibody used as a control. Protection was dose dependent and required at least 10 micrograms of E1 (mean antibody concentration in serum +/- standard deviation, 6.6 +/- 2.3 micrograms/ml). Insufficient concentrations of IgG anti-C. neoformans antibody could explain previous negative results obtained with polyclonal immune serum. After infection with a smaller inoculum (5 X 10(3) to 5 X 10(4)), the protective effect of E1 was confirmed by the presence of fewer CFUs in the spleens and brains of treated mice than in those of controls. CFU were still detected in the brains of protected mice 5 days after infection, although soluble antigen was negative in sera. These results suggest that passive serotherapy with monoclonal IgG antibodies could participate in the prevention or treatment of experimental cryptococcosis.

Animals↗
PubMed1986

[Is systematic syphilis serology still useful in a department of internal medicine? A one-year prospective study using a diagnostic and therapeutic decision algorithm].

During one year syphilis serology was systematically studied, using the TPHA and VDRL tests, in each of the 1,279 patients hospitalized in an Internal Medicine department. In all cases diagnosis and treatment were analyzed by means of a decision algorithm. Only 37 patients were found to have one or both serological tests positive. No evolutive syphilis was observed, and none of these positive tests was contributive to the diagnosis of another disease. Only 14 patients received a specific antibiotic treatment on the grounds that their positive test confirmed a late asymptomatic syphilis. We conclude that systematic syphilis serological tests are not useful in an Internal Medicine department, except in some patients epidemiologically at high risk of syphilis.

Algorithms↗
PubMed1986

Kinetics and bactericidal effect of gentamicin and latamoxef (moxalactam) in experimental Escherichia coli endocarditis.

The pharmacokinetics of gentamicin and latamoxef (moxalactam) were examined in serum, normal heart valves, sterile cardiac vegetations and vegetations infected with Escherichia coli. Penetration of antibiotics into heart valves and vegetations was rapid; the maximum concentration was achieved in both sites at the end of a 20 min iv infusion. However, both antibiotics penetrated better into vegetations than into normal heart valves. In rabbits with left-sided endocarditis, similar antibiotic levels were found in infected vegetations after one or 22 im injections. After 11 im injections (one every 8 h) of latamoxef (15 mg/kg) the bacterial titre (cfu/g) was significantly reduced, but not nil, despite concentrations about 40 times the MBC for this antibiotic in the vegetations. Afer 22 im injections, vegetations in rabbits receiving latamoxef were sterile and were significantly reduced in those receiving gentamicin (1.5 mg/kg/im), concentrations of which in the vegetations were inferior to the MBC. Our results suggest that the in-vivo antibacterial effect depends on local antibiotic levels, kinetics of killing and duration of contact between antibiotic and bacteria.

Animals↗
PubMed1986

Pharmacokinetic and pharmacodynamic interactions between nifedipine and propranolol or betaxolol.

Pharmacokinetic and pharmacodynamic interactions between nifedipine and two beta-blocking agents were investigated. Eighty mg propranolol twice daily, and 20 mg betaxolol once daily, were randomly administered orally to six young healthy male volunteers, either singly for four days, or combined with nifedipine for the two subsequent days. Nifedipine had similar effects on the pharmacodynamics of both drugs. Nifedipine significantly enhanced propranolol bioavailability and Cmax, but reduced its tmax, in three out of six subjects who were also good absorbers of beta-blockers when taken alone. These effects might be due to enhanced intestinal absorption and/or enhanced first-pass effect, induced by nifedipine.

Adrenergic beta-Antagonists↗
PubMed1986

[Evaluation of the posology of antibiotics].

The determination of the dose regimen of a new antibiotic is difficult because a dose/effect relationship cannot be established in patients with an infectious disease. The optimal dose is usually extrapolated from combined data provided by in vitro and in vivo microbiologic toxicologic and kinetic studies. Additional data ought to be produced in the future such as: kinetics of cidal effect in vitro, of the post antibiotic effect, of drug concentrations at the sit of infections itself, of the cidal serum activity in volunteers and patients; how these parameters are modified when modulating the mode of administration of the drug ought to be studied as well. The optimal dose, once it is roughly evaluated from classical studies, has to be adjusted: either by decreasing the dose, through an appropriate program of clinical trials with non-threatening life infections; or by increasing the dose in severe infections, through an in-depth analysis of new data available because of the improvement of: the design of clinical trials, the sensitivity of analytical techniques, the standardized serum bactericidal tests, the sophisticated monoparametric animal models simulating human infections, our knowledge of drugs mechanisms of toxicity. Establishing a rational dose regimen obviously requires a long-term multidisciplinary approach of the problem.

Animals↗