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H I Seifart

Publications and source records attributed to H I Seifart.

At least 19 recordsLinked to original sources
PubMed2000

Second episode of tuberculosis in an HIV-infected child: relapse or reinfection?

We report a case of an HIV-infected child with a second episode of tuberculosis 22 months after completing antituberculosis treatment. DNA fingerprinting of organisms from both episodes showed an identical strain of Mycobacterium tuberculosis. We believe this to be the first case of confirmed relapsed tuberculosis in an HIV-infected child, and suggest that a longer course of antituberculosis treatment be given to such children. ¿ 2000 The British Infection Society.

AIDS-Related Opportunistic Infections↗
PubMed2000

Early bactericidal activity of paromomycin (aminosidine) in patients with smear-positive pulmonary tuberculosis.

The early bactericidal activity of the aminoglycoside paromomycin (aminosidine) in doses of 7.5 and 15 mg/kg of body weight was measured in 22 patients with previously untreated smear-positive pulmonary tuberculosis. The fall in log(10) CFU per milliliter of sputum per day during the first 2 days of treatment for 7 patients receiving a paromomycin dosage of 7.5 mg/kg/day was 0.066, with a standard deviation (SD) of 0.216 and confidence limits from -0.134 to 0.266, and that for 15 patients receiving 15 mg/kg/day was 0.0924, with an SD of 0.140 and confidence limits from 0.015 to 0.170. The difference between the mean and zero was not significant for the 7. 5-mg/kg dose group but was significant for the 15-mg/kg dose group (t = 2.55, P = 0.023). Since paromomycin has no cross-resistance with streptomycin and has no greater toxicity than other aminoglycosides, these results suggest that it has the potential to substitute for streptomycin in antituberculosis regimens and may be a particularly valuable addition to the drug armamentarium for the management of multidrug-resistant tuberculosis.

Adolescent↗
PubMed1999

Practical management of therapeutic diphenylhydantoin concentrations in children.

OBJECTIVE: Development of easy, practical methods for the management and optimisation of therapeutic diphenylhydantoin (DPH) concentrations in children. DESIGN: Investigation of DPH concentration profiles and pharmacokinetic parameters in children with poorly controlled epilepsy. Subsequent determination of individual-specific DPH maintenance dosage and volume of distribution data suitable for use in routine therapeutic concentration management procedures. SETTING: Department of Paediatrics and Child Health and Department of Pharmacology, University of Stellenbosch, Tygerberg Hospital. SUBJECTS: Children of both sexes between the ages of 4 and 12 years with poorly controlled epilepsy receiving DPH as sole medication. RESULTS: In all subjects evaluated epilepsy was unsatisfactorily controlled because of inadequate DPH dosage regimens. Individual-specific maintenance dosage and volume of distribution data could be calculated for all individuals participating in the trial. The calculated data were suitable for use in routine management procedures and in no instance was it necessary to recalculate parameters in a 12-month follow-up period subsequent to evaluation. CONCLUSIONS: Therapeutic DPH concentration profiles can be managed satisfactorily in children in individual-specific DPH pharmacokinetic parameters are derived and skillfully applied.

Anticonvulsants↗
PubMed1998

Massive posterior fossa tuberculous abscess developing in a young child treated for miliary tuberculosis. Possible role of very rapid acetylation of isoniazid.

A 21-month-old infant presented with acute obstructive hydrocephalus due to a large tuberculous abscess in the posterior fossa 3 months after starting treatment for miliary tuberculosis. Insertion of a ventriculo-peritoneal shunt resulted in some clinical improvement but subsequent neurological deterioration occurred due to massive enlargement of the tuberculous abscess despite apparently adequate antituberculosis therapy. Repeated drainage procedures of the abscess eventually resulted in resolution and clinical improvement. As part of the workup for poor weight gain and the unusual clinical course, the patient's acetylation status for isoniazid was determined and found to be very rapid. Doubling the daily dose of isoniazid was followed by a dramatic weight increase and further clinical improvement. Decreasing the load of tuberculous antigen by draining the abscesses and increasing the pulse exposure of isoniazid is the best possible explanation for the clinical improvement finally seen in this patient.

Abscess↗
PubMed1997

Trimodality of isoniazid elimination: phenotype and genotype in patients with tuberculosis.

The study was undertaken to show that polymorphic isoniazid elimination in humans is trimodal; that the acetylator genotype and eliminator phenotype of the individual patient are concordant; and that the differences in the pharmacokinetic parameters of fast, intermediate, and slow eliminator subgroups are statistically significant. Sixty adult patients of both sexes and of mixed race with tuberculosis participated in the trial. The apparent elimination rate constant (k, h(-1)) and the area under the isoniazid concentration-time curve (AUC, mg/L/h), over the interval 2 to 6 h after oral isoniazid were determined in all patients; NAT2 allele composition was determined in 47 patients. Serum INH concentrations were determined by HPLC and genotypes by PCR/restriction enzyme analysis. Three eliminator phenotypes could be distinguished, and concordance between the phenotype and the genotype of the individual could be demonstrated. The isoniazid concentration-time profiles of the three eliminator subgroups were significantly different (p < 0.05). The NAT2*12A allele, which codes for fast acetylation, has a high frequency in the population studied, the intermediate acetylator genotype is constituted of codominant fast and slow alleles, and the distribution of phenotypes/genotypes in the population is consistent with Hardy-Weinberg predictions. The therapeutic implications of polymorphic isoniazid metabolism are discussed.

Acetylation↗
PubMed1997

The early bactericidal activity of isoniazid related to its dose size in pulmonary tuberculosis.

Collections of sputum from 105 patients with newly diagnosed pulmonary tuberculosis were made before and at 1 and 2 d after the start of chemotherapy with isoniazid (INH) alone given to groups of patients in doses of 600 mg, 300 mg, 150 mg, 75 mg, 37.5 mg, 18.75 mg, and 9 mg daily, as well as from an untreated group. Counts of colony forming units (cfu) of Mycobacterium tuberculosis in the collections were set up on plates of selective 7H10 medium. The early bactericidal activity (EBA) of INH was defined as the decrease in log10 cfu/ml sputum/day during the first 2 d of treatment. A smooth curve relating EBA to log dose was obtained, with 600 mg INH yielding the highest mean EBA of 0.539, and 18.75 mg INH yielding the lowest EBA (0.111) that could be distinguished from the bactericidal activity of the untreated group. The ratio of the usual dose of 300 mg INH to the lowest dose, of 18.75 mg, that produced a detectable EBA, termed the therapeutic margin, was therefore 16, in contrast to the lower therapeutic margin of 4 for rifampin. The EBA was related to the INH acetylator genotype of patients treated with 600 mg or 9 mg INH.

Acetylation↗
PubMed1996

Fluctuation of the volume of distribution of amikacin and its effect on once-daily dosage and clearance in a seriously ill patient.

OBJECTIVE: The main aim of the trial was to determine the extent to which the volume of distribution of amikacin fluctuates in a seriously ill patient receiving copious quantities of i.v. fluid over an extended term of treatment. The impact of the volume fluctuation on amikacin therapeutic peak concentrations was also assessed. DESIGN AND SETTING: The case report describes a young, previously healthy male adult admitted to the surgical ICU of a teaching hospital following trauma to the head and central nervous system. INTERVENTION: The patient received 1 g of amikacin once-daily i.v. for 35 consecutive days as part of an antimicrobial regimen. Blood samples were drawn for routine amikacin concentration determinations on 14 occasions, extending over the entire term of treatment, from which the required pharmacokinetic parameters were determined. RESULTS: The volume of distribution of amikacin varied extensively from 0.27 to 0.61 l/kg (normal range 0.27 +/- 0.06 1/kg) notwithstanding the fact that amikacin clearance remained satisfactorily high throughout the term of treatment. CONCLUSIONS: Once-daily therapeutic amikacin concentrations fluctuate extensively and rapidly in the seriously ill patient receiving copious quantities of i.v. fluids, despite competent renal function. The volume expansion seen in our patient is difficult to account for in terms of the extracellular fluid compartment only. RECOMMENDATIONS: (a) Once-daily regimen amikacin peak concentrations should be frequently monitored in the seriously ill patient; (b) once-daily amikacin regimens are best monitored using blood specimens drawn at 1 and 6-8 h post administration.

Adult↗
PubMed1995

High-performance liquid chromatographic determination of isoniazid, acetylisoniazid and hydrazine in biological fluids.

The basic principle of derivatization of a hydrazide moiety with an aldehyde as applied in the method developed by Lacroix et al. [J. Chromatogr., 307 (1984) 137-144] for the quantitation of isoniazid and acetylisoniazid was improved by modification, standardization and extension to allow quantitation of hydrazine in patient samples. It could be shown that 40 microliters of 1% methanolic cinnamaldehyde per 200 microliters of deproteinized analysate gave maximal chromophoric isoniazid-cinnamaldehyde conjugate, read at 340 nm. The hydrolytic loss of isoniazid, crucial to the quantitation of acetylisoniazid, could be compensated for by introduction of an appropriate set of calibration curves. Although the method described here allows quantitation of monoacetylhydrazine and diacetylhydrazine, in addition to hydrazine, in mono-spiked samples, the method cannot be used for the quantitation of the acetylated metabolites of hydrazine in patient samples because of a lack of specificity. Linear calibration curves in the range 1-25 micrograms/ml for isoniazid and acetylisoniazid, 10-400 ng/ml for hydrazine and 50-1000 ng/ml for monoacetylhydrazine and diacetylhydrazine, could be constructed; analyte recoveries approaching 100% could be achieved in all instances.

Antitubercular Agents↗
PubMed1995

Isoniazid elimination kinetics in children with protein-energy malnutrition treated for tuberculous meningitis with a four-component antimicrobial regimen.

The impact of changing environmental factors--disease, nutrition and a high-dose multi-drug treatment regimen--on isoniazid (INH) elimination kinetics in children of both sexes and various ages was investigated. Thirteen children (mean age 2.3 years), hospitalized for the treatment of tuberculous meningitis, participated in the trial. Although all the children had protein-energy malnutrition, none had marasmus or kwashiorkor. After an oral dose of 20 mg/kg of INH, the concentrations in plasma were determined by the liquid chromatographic method of Lacroix et al. The 2-hour post-dose isoniazid concentration, the apparent first-order elimination rate constant and the corresponding INH half-life were determined in each child on two occasions 6 months apart. All comparisons were tested for significance using the Wilcoxon matched-pair signed-ranks test. There was no significant difference in any of the pharmacokinetic parameters of INH in our patients evaluated at the extremes of the 6-month term of treatment. It was apparent that changing conditions of disease and nutrition and a high-dosage, multi-component antimicrobial agent regimen over a 6-month period of treatment did not significantly influence INH elimination parameters. The trend evident in the pharmacokinetic profile of isoniazid in our children supports a trimodal distribution of acetylator phenotypes.

Anti-Bacterial Agents↗
PubMed1994

Hydrazine production in children receiving isoniazid for the treatment of tuberculous meningitis.

OBJECTIVE: To study the generation of the hepatotoxin hydrazine in 32 malnourished children receiving isoniazid for the treatment of tuberculous meningitis. DESIGN AND SETTING: This observational study was undertaken in the pediatric ward of a teaching hospital admitting children with advanced forms of tuberculous meningitis for treatment and management of complications. METHODS: Thirty-two children (mean age 2.28 years) receiving isoniazid 20 mg/kg/d were studied. Plasma isoniazid, acetylisoniazid, and hydrazine concentrations were determined by an HPLC method. Fourteen children were studied at weekly intervals for the first month of treatment and again after six months of therapy; 18 additional children were studied on one or more occasions during the first month of treatment only. RESULTS: The area under the curve for hydrazine two to five hours after the isoniazid dose correlated with the isoniazid elimination rate and with acetylisoniazid generation. Hydrazine production increased significantly during the first month of treatment, but decreased to approximate initial values at six months. No correlation was found between any clinical or biochemical indicator of liver dysfunction and hydrazine production. CONCLUSIONS: Hydrazine is formed in significant concentrations during the metabolism of isoniazid in young children. However, additional factors such as preexisting liver damage (e.g., from viral hepatitis) may be necessary for it to reach its toxic potential.

Child↗
PubMed1993

Therapeutic monitoring of antituberculosis drugs by direct in-line extraction on a high-performance liquid chromatography system.

A direct in-line pre-column extraction technique in which guanidinium and ammonium sulfate are used, followed by column switching, was employed to analyze serum, plasma and cerebrospinal fluid samples of patients treated for tuberculous meningitis. Resolution of a wide range of polar to non-polar xenobiotics was obtained on a C8 silica column by using a linear gradient from a binary system consisting of solvent A (0.05 M KH2PO4) and solvent B (acetonitrile-isopropanol, 4:1, v/v). Apart from the antituberculosis drugs (isoniazid, pyrazinamide, ethionamide and rifampicin) the patients received up to sixteen different medicines for prevention of complications and the treatment of symptoms. Qualitative resolution of all the drugs was obtained by the chromatographic system. Quantitation of pyrazinamide and ethionamide was achieved with high precision and low inter-sample variation.

Antitubercular Agents↗
PubMed1992

Factors in hydrazine formation from isoniazid by paediatric and adult tuberculosis patients.

An HPLC method is described for measurement of plasma hydrazine (Hz) concentrations (CHz) at the same time as isoniazid (INH) levels (CINH). Study has been made of CHz during 2-5 after dose in healthy adults (A, n = 34), in adult pulmonary TB patients (B, n = 18) and in paediatric tuberculous meningitis patients (C, n = 25). Although the population has about equal proportions of 'slow' (52%) and 'fast' acetylators, in none of the groups could a correlation be shown between CHz levels or rates of Hz accumulation and any measure of acetylator type. Consequently Hz must be derived both from INH and from its metabolites during the first hours post-dose. For group A and ca. 70% of groups B and C a constant and maximal fraction of dose (ca. 0.6% for adults and 0.4% for paediatric patients) appeared as Hz at 4-5 h. For group B patients small pre-dose concentrations increased with duration of treatment. Four patients in group B showed the highest levels of CHz and rates of Hz accumulation some three times greater than the rest; all four had been identified as alcoholics and one showed evidence of hepatotoxicity at CHz (5 h) = 1.3% of dose. Amongst group C (9/25) episodes of high CHz greater than 0.5% of dose occurred during the first weeks of treatment and one developed CHz ca. 100 ng/ml = 1.3% of dose coincidentally with indications of hepatic damage.

Acetylation↗
PubMed1992

Cerebrospinal fluid isoniazid concentrations in children with tuberculous meningitis: the influence of dosage and acetylation status.

Cerebrospinal fluid (CSF) and plasma isoniazid (INH) concentrations were determined on 96 occasions in 38 children (median age 1.5 years) with tuberculous meningitis, and the effects of INH elimination status and test dosages of 10 mg/kg body weight and 20 mg/kg body weight was studied. Maximum cerebrospinal fluid INH concentrations were reached during the period 2 to 4 hours after dosing and cerebrospinal fluid and plasma INH concentrations did not differ significantly during this period. Cerebrospinal fluid INH concentrations following a dosage of 10 mg/kg (4.6 +/- 2.4 micrograms/mL) were, however, significantly lower than those following a dosage of 20 mg/kg (11.6 +/- 2.7 micrograms/mL). Cerebrospinal fluid INH concentrations in faster acetylators at a dosage of 10 mg/kg (3.2 +/- 1.1 micrograms/mL) were significantly lower than in slower acetylators (7.7 +/- 1.3 micrograms/mL), as was the case with a dosage of 20 mg/kg, where faster acetylators had cerebrospinal fluid INH concentrations of 10.5 +/- 2.5 micrograms/mL compared with 14.1 +/- 1.4 microgram/mL in slower acetylators. Following dosages of both 10 mg/kg and 20 mg/kg, INH concentrations in excess of the minimal inhibitory concentration for Mycobacterium tuberculosis persisted in the CSF 12 to 14 hours later. Despite the patients' being young and frequently malnourished, suffering from advanced forms of tuberculous meningitis, and receiving high dosages of INH, rifampicin, and pyrazinamide, none developed any clinical signs of hepatotoxicity and in only one child did the serum bilirubin level rise to 19 micrograms/mL.

Acetylation↗
PubMed1991

Stability of isoniazid, rifampin and pyrazinamide in suspensions used for the treatment of tuberculosis in children.

The stability of monosuspensions, cosuspensions and multisuspensions of isoniazid (INH), pyrazinamide (PZA) and rifampin (RIF) has been evaluated by high pressure liquid chromatography over a period of 28 days both with and without the addition of vitamin C (20 micrograms/ml) and at ambient temperatures of 4 degrees C, 24 degrees C and 40 degrees C. At the end of 28 days greater than 90% of initial concentrations of INH, PZA and RIF in monosuspensions remained unchanged irrespective of ambient temperature as was the case with INH and PZA in cosuspension. The addition of RIF to either INH or PZA in cosuspension or together in multisuspension led to a marked fall in the concentration of one or more of the agents, an effect that was accentuated by the addition of vitamin C. In the case of a multisuspension of INH + RIF + PZA with vitamin C added, 41.7% (4 degrees C), 24.1% (24 degrees C) and 20.3% (40 degrees C) of initial INH concentrations and 1.9% (4 degrees C), 1.3% (24 degrees C) and 0.0% (40 degrees C) of initial RIF concentrations remained detectable after 28 days. The addition of vitamin C to monosuspensions of INH and PZA led to a marked decline in the amount of drug detectable and only in the case of RIF was greater than 90% of initial concentrations of the drug detectable after 28 days. The dispensing of cosuspensions or multisuspensions of antituberculosis agents containing RIF is inadvisable as is the addition of vitamin C in any form.

Ascorbic Acid↗
PubMed1990

Serum gentamicin assay: an assessment of two different Syva EMIT and Abbot TDx instruments.

The accuracy and reproducibility of two different Syva EMIT and Abbot TDx instruments for the determination of gentamicin were assessed. A series of spiked standard serum samples containing gentamicin in concentrations ranging from 0.88-17.82 mg/l were used for this purpose. Both TDx systems evaluated had excellent reproducibility but overestimated gentamicin levels in the clinically important concentration range in an apparent concentration-dependent way by at least 5 and 10%, respectively. In addition both these systems exhibited considerable carryover effects when high concentration gentamicin samples (17.82 mg/l) were alternated with serum blanks. Average gentamicin levels determined by the EMIT systems were much closer to the target values, especially those of EMIT-A, than those measured by the TDx-systems. The reproducibility, as measured by the coefficient of variation (CV), of the semi-automated EMIT systems over the entire concentration range investigated was about half that of the TDx-systems. No carryover effects were observed with the two EMIT-systems. This study has shown that the accuracy and reproducibility of both assay methods vary considerably over the clinically important gentamicin concentration range. In addition there may be a large variation between instruments of the same system especially in the critical trough region for gentamicin.

Fluorescence Polarization↗
PubMed1989

In vitro evaluation of ampicillin-gentamicin interactions.

Ampicillin at a concentration of 100 micrograms/mL was combined in vitro with either gentamicin 10 micrograms/mL in serum, 0.01 mol/L phosphate-buffered saline at 37 degrees C, or water at room temperature (25 degrees C). At these concentrations, which represent the peak prophylactic serum concentrations likely to be achieved by a 70-kg person after parenteral administration of 1.5 mg/kg gentamicin and 2 g of ampicillin, no clinically significant inactivating effects of these antibiotics on each other were observed over a period of six hours.

Ampicillin↗
PubMed1989

Cerebrospinal fluid concentrations of ethionamide in children with tuberculous meningitis.

Cerebrospinal fluid ethionamide concentrations were determined in 18 children (median age 26.5 months) with tuberculous meningitis complicated by raised intracranial pressure. Lumbar spinal fluid specimens were obtained before and after weekly hour-long monitoring of intracranial pressure. Thirty-five paired and four single specimens were evaluated. A dosage schedule of 15 mg/kg was used on 26 occasions, and a spinal fluid ethionamide concentration of 2.5 micrograms/ml, the in vitro minimal inhibitory concentration for Mycobacterium tuberculosis, was exceeded on only seven occasions (27%). A dosage of 20 mg/kg was administered on 13 occasions, and in only two instances (15%) was a concentration of 2.5 micrograms/ml not achieved. Ethionamide in a single daily dosage of 20 mg/kg should be considered for the initial treatment of tuberculous meningitis when the presence of isoniazid-resistant M. tuberculosis cannot be excluded.

Child, Preschool↗