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Biomedical subjects

H Mattie

Publications and source records attributed to H Mattie.

At least 91 records · Page 5Linked to original sources
PubMed1987

Quantitative effect of granulocytes on antibiotic treatment of experimental staphylococcal infection.

The quantitative relation between granulocytopenia and antibiotic treatment was established for a short-term Staphylococcus aureus infection in the thighs of mice, using rifampin, benzylpenicillin, and erythromycin. Granulocytopenia was induced by total-body irradiation; the number of granulocytes decreased gradually during the first 5 days after irradiation to 10% of the number in normal mice. Experimental infections were established on each of the 5 days after irradiation. In animals not treated with antibiotics, the number of granulocytes in peripheral blood and the number of CFU at the site of infection exhibited a strong negative correlation. The influence of granulocytes on the effect of antibiotics on the number of CFU differed for the three antibiotics. For erythromycin the slope of the dose-effect relation was rather flat, but a decrease in the number of granulocytes caused a significant, nearly parallel, shift in the dose-effect relation, resulting in an increase in the number of CFU. For benzylpenicillin the slope of the dose-effect relation for normal mice was also flat, but as the number of granulocytes decreased the slope became significantly steeper, resulting in a diminishing influence of granulocytes at higher dosages. For rifampin the slope of the dose-effect relation, which was already steep for nonirradiated animals, increased significantly. Here too the effect of granulocytes decreased as the dose increased.

Agranulocytosis↗
PubMed1986

Determination of benzylpenicillin and probenecid in human body fluids by high-performance liquid chromatography.

A method for the determination of benzylpenicillin and probenecid concentrations in human body fluids using ion-pair reversed-phase chromatography with UV detection has been developed. For plasma samples two extraction techniques were investigated. Precipitation of the plasma proteins with acetonitrile followed by liquid-liquid extraction offered the best results. The limits of detection were 0.5 microgram/ml for benzylpenicillin and 0.25 microgram/ml for probenecid, which offer sufficient sensitivity for application in pharmacokinetic experiments.

Body Fluids↗
PubMed1986

Effect of penicillin G on Staphylococcus aureus phagocytosed by human monocytes.

The effect of penicillin G on Staphylococcus aureus after phagocytosis by human monocytes was compared with the effect on nonphagocytosed bacteria. Intracellular S. aureus was obtained by incubation of monocytes and preopsonized S. aureus for 3 min at 37 C; phagocytosis was stopped by cooling the test tubes in crushed ice. Nonphagocytosed bacteria were removed by differential centrifugation followed by two washes of the cells. Morphological studies with lysostaphin confirmed the intracellular localization of approximately 70% of the bacteria after this procedure. The antibacterial activity of penicillin G was assessed by incubation of monocytes containing ingested S. aureus with the drug at 37 C, and determination of the number of viable cell-associated bacteria was assessed microbiologically at various intervals. Inactivation of the intracellular killing mechanism of the monocytes by omission of serum during incubation allowed measurement of the effect of penicillin G apart from the bactericidal activity of the cells. The effect of penicillin G on nonphagocytosed bacteria was assessed after incubation of preopsonized S. aureus in medium with the drug. The results show that the effect of penicillin G on intracellular S. aureus is two to seven times stronger than the effect on nonphagocytosed S. aureus.

Humans↗
PubMed1986

Pharmacokinetics of aztreonam in infected patients.

Pharmacokinetic parameters of aztreonam were determined in 22 patients with severe Gram-negative infections, treated with 0.5 or 1 g tid as an infusion of 30 min duration. Plasma concentrations were determined microbiologically. Most patients had various degrees of renal impairment and they showed a wide variety of age and body weight. The mean calculated volume of distribution was 17.31 or 260 ml/kg. The total plasma clearance correlated well with the creatinine clearance; the mean plasma clearance was 82 ml/min and the extrapolated extrarenal clearance was 9 ml/min. Actually measured half lives of aztreonam varied between 1 h 20 min, in a patient with normal renal function, and 9 h 40 min in a patient with severely impaired renal function. The results differ from predictions by other authors. Based on our results a dosage adjustment schedule for renal impairment is suggested.

Adult↗
PubMed1986

Comparison of the effect of phenoxymethylpenicillin, cloxacillin, and flucloxacillin on Staphylococcus aureus phagocytosed by human monocytes.

The antibacterial effect of phenoxymethylpenicillin, cloxacillin, and flucloxacillin on pre-opsonized Staphylococcus aureus ingested by human monocytes and on preopsonized S. aureus in suspension was compared. The antibiotics were 1.7-3 times more effective against intracellular S. aureus than against S. aureus in suspension. No influence of acid stability or lipid solubility of the drugs on the antibacterial effect against intracellular S. aureus was demonstrated.

Cloxacillin↗
PubMed1985

Role of granulocytes and monocytes in the prevention and therapy of experimental Staphylococcus epidermidis endocarditis in rabbits.

Rabbits with endocarditis caused by Staphylococcus epidermidis were studied to determine the parts played by granulocytes and monocytes in the prevention or outcome of therapy with cloxacillin. Both monocytes and granulocytes influenced prophylaxis with cloxacillin. The amount of cloxacillin needed to prevent infection in 50% of the rabbits was significantly less in control rabbits than in those selectively depleted of monocytes, as it was also in rabbits selectively depleted of monocytes compared with those that had both granulocytopenia and monocytopenia. Granulocytes strongly potentiated the effect of cloxacillin during prophylaxis, whereas the contribution of monocytes was merely additive. Monocytes also contributed to the effect of therapy with cloxacillin, partially via a cloxacillin-independent mechanism and partially by potentiation of the effect of cloxacillin. Granulocytes did not appear to affect cloxacillin therapy. Results of this study suggest that currently used regimens for prophylaxis and treatment of S. epidermidis endocarditis may need to be adjusted for neutropenic patients.

Animals↗
PubMed1985

Combined activity of metronidazole and gentamicin on Bacteroides fragilis in vivo and in vitro.

A mixed aerobic/anaerobic infection in mice was established by co-injecting Bacteroides fragilis and Escherichia coli into a thigh muscle. Metronidazole administration 6 h after this inoculation resulted in a dose-dependent decrease of Bact. fragilis at 18 h after drug administration. Co-administration of gentamicin with metronidazole resulted in a significant decrease of the numbers of E. coli but did not markedly influence the effect of metronidazole on Bact. fragilis.

Animals↗
PubMed1985

Pharmacokinetics of vibunazole (BAY n 7133) administered orally to healthy subjects.

The role of gastric acidity in the absorption of the new antifungal drug vibunazole was studied in six healthy volunteers. Vibunazole was administered orally as 400 mg tablets to fasting subjects under three conditions: after 400 mg cimetidine orally, after 30 ml diluted hydrochloric acid orally, and alone. Plasma concentrations of vibunazole were determined with HPLC. The plasma concentration profile of vibunazole could be described adequately by a one-compartmental open model with first-order absorption. Kinetic parameters after oral administration did not differ between the three modes of administration. The mean peak time was 1 h 29 min (after lag-time). The mean peak concentration was 2.76 mg/l. The mean elimination half-life of vibunazole was 2 h 22 min. The mean absorption lag-time was 30 min, with considerable variation.

Administration, Oral↗
PubMed1985

Comparison of the antibacterial activity of azlocillin and ticarcillin in vitro and in irradiated neutropenic mice.

The antibacterial efficacy of azlocillin against Pseudomonas aeruginosa was quantitatively assessed in short-term growth curves in vitro and in a short-term thigh muscle infection in granulocytopenic mice. Ticarcillin was used as the reference drug. The antibacterial effect in vitro was expressed as the difference between the logarithms of the numbers of cfu in the presence and absence of antibiotics (log ratio). The log ratio-time curves could be described by a concentration-dependent parameter, i.e., the inhibition constant (i). According to a standard parallel line bio-assay, based on values of i, azlocillin was 3.80 times more active than ticarcillin (coefficient of variation 27%). Tobramycin in a concentration of 0.19 mg/l, which is not effective in itself, potentiated both drugs by a factor of 3.85 (coefficient of variation 26%). In the in vivo model ticarcillin showed a dose-dependent antibacterial effect, whereas the effect of azlocillin was limited and not dose dependent. The effect of tobramycin in a dose of 4 mg/kg was additive for both penicillins. The results obtained in vivo were less favourable for azlocillin than would be predicted on the basis of the in-vitro results.

Animals↗
PubMed1985

Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

In this study the antimicrobial effects of phenoxymethylpenicillin (PM) and pheneticillin (PE) in vitro and in an experimental animal infection model were compared as well as the pharmacokinetic properties of both drugs in patients. For the inhibitory effect of PM on short-term (3 h) growth of S. aureus in vitro, this drug was 2.13 times more potent than PE. The protein binding of both drugs was similar (78-80%). The potency ratio of PM to PE against S. aureus in an experimental mouse-thigh infection was only 1.25 to 1. This is explained by the difference in the AUC after subcutaneous administration of PM (0.47 mg 1(-1) h) and PE (0.92 mg 1(-1) h). The plasma clearance after intravenous administration of PM was 476.4 ml/min and that of PE was 295.1 ml/min; the plasma clearance of both drugs was strongly correlated with the creatinine clearance. The volume of distribution in the steady state of PM was 35.41 and that of PE 22.51. In 10 patients, the absorption after oral administration of PM as the acid was 48% and that of the potassium salt of PE was 86% of the dose. From the present results it can be concluded that a difference in effectiveness of different formulations of PM and PE would depend entirely on differences in absorption.

Adult↗
PubMed1985

Relative antibacterial efficacy of clindamycin and metronidazole against Bacteroides fragilis in vitro and in experimentally infected mice.

The antibacterial activity of clindamycin and metronidazole against Bacteroides fragilis was quantitated in vitro by MIC determination and colony counting at 24 h and in vivo from the effects on an experimental B. fragilis infection in mice; this infection was established after co-inoculation of B. fragilis and Escherichia coli. In vitro, clindamycin was 8 to 16 times more effective than metronidazole in terms of MIC values, and more than 30 times according to colony counts at 24 h. In vivo clindamycin was almost 8 times less effective than metronidazole according to dose. This was partly due to its less favorable pharmacokinetic properties, but clindamycin was still only 1.6 times more effective than metronidazole according to free plasma concentrations. In vivo neither clindamycin nor metronidazole had any antibacterial effect against E. coli. The discrepancy between the in vivo and in vitro results for B. fragilis is discussed.

Animals↗
PubMed1985

Renal clearance of temocillin in volunteers.

After administration of a loading dose, temocillin was infused intravenously into 5 volunteers for 3 hours (250 and 750 mg/h). A urine flow of more than 500 ml/h was maintained. The mean plasma concentrations were 131.4 and 220.7 mg/L during the lower dose and higher dose infusions, respectively, and protein binding decreased from 83% to 74% with this increase in plasma concentration. The renal clearance of the total drug increased from 29.0 ml/min (low dose) to 50.5 ml/min (high dose) [p less than 0.001], but after correction for protein binding the renal clearance of the unbound drug only increased from 169.1 to 197.0 ml/min (not statistically significant). The extrarenal clearance of temocillin was negligible. Blocking of tubular excretion by probenecid caused a maximum decrease of the renal clearance of temocillin from 34.1 to 22.4 ml/min. This maximum effect of 12.3 ml/min subsided by 1.7 ml/min/h. The renal clearance of the free drug decreased to 134.6 ml/min, slightly less than the creatinine clearance (158.1 ml/min). It may be concluded that even at high plasma concentrations of temocillin there is no saturation of the tubular transport mechanism, and that tubular excretion plays a relatively minor role in the renal excretion of the drug.

Adult↗
PubMed1985

Efficacy of amoxycillin and benzylpenicillin combined with clavulanic acid against Bacteroides fragilis in vitro and in experimentally infected mice.

Because the insensitivity of Bacteroides fragilis to penicillins is due to betalactamase formation, the potentiating effect of the betalactamase inhibitor clavulanic acid on the action of amoxycillin and benzylpenicillin against this bacterium was studied in vitro and in an experimental infection in mice. The addition of clavulanic acid to amoxycillin and benzylpenicillin resulted in a marked synergistic effect against B. fragilis, as assessed by both MIC determinations and in 4-h growth curves. In the experimental infection, where co-inoculation with Escherichia coli was obligatory for the outgrowth of B. fragilis, both penicillins had a dose-dependent effect on both species. However, the addition of clavulanic acid to amoxycillin and benzylpenicillin did not increase the effect of the penicillins against B. fragilis or against E. coli. Because a synergistic effect might have remained undetected in vivo, the experimental conditions were varied, i.e. the drugs were administered in the proliferation phase of B. fragilis, the clavulanic acid to betalactam ratios were varied, and the drugs were given after inoculation of B. fragilis in which betalactamase production has been induced. However, even after variation of the experimental conditions the addition of clavulanic acid to benzylpenicillin did not result in a potentiation of the effect of benzylpenicillin against B. fragilis.

Amoxicillin↗
PubMed1985

Antibiotics.

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Aminoglycosides↗
PubMed1984

Quantification of the effect of anti-anaerobic drugs in experimental Bacteroides fragilis infection in mice.

As a basis for the quantitation of the effect of anti-anaerobic drugs in vivo, an experimental thigh infection in mice was developed in which co-inoculation of Bacteroides fragilis and Escherichia coli is obligatory for proliferation of Bact. fragilis. The inhibitory effect of metronidazole and tinidazole on the proliferation of Bact. fragilis was assessed in this model. Both metronidazole and tinidazole showed a significant dose-effect relationship with respect to the outgrowth of Bact. fragilis but not that of E. coli. The effect of both drugs on Bact. fragilis was similar and at all dosage levels a significant correlation was found between the numbers of Bact. fragilis and E. coli.

Animals↗
PubMed1984

Comparative clinical study on the absorption of orally administered amoxycillin and bacampicillin.

In nine consecutive hospitalized patients treated with either ampicillin or amoxycillin, studies on the pharmacokinetics of orally administered amoxycillin and bacampicillin gave a mean absorption of 73% (+/- 15%) of the dose for amoxycillin and 65% (+/- 17%) for bacampicillin. An analysis of variance showed that the difference between the two drugs has only borderline significance (P less than 0.10). These mean values are lower than those reported in the literature for healthy volunteers, and the variation between patients is also larger. The mean absorption rates found for the two drugs did not differ from those found in healthy volunteers, amoxycillin being absorbed significantly more slowly than bacampicillin (P less than 0.02), but there were also large differences between patients.

Administration, Oral↗