Summary of major changes in the 1997 Red Book: Report of the Committee on Infectious Diseases.
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Biomedical subjects
Publications and source records attributed to G Peter.
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Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by a throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) remains the treatment of choice, because it is cost effective, has a narrow spectrum of activity, has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. Various macrolides, oral cephalosporins, and other beta-lactam agents are acceptable alternatives, particularly in penicillin-allergic individuals. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The duration of prophylaxis depends on the number of previous attacks, the time lapsed since the last attack, the risk of exposure to streptococcal infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or erythromycin are acceptable alternatives in penicillin-allergic individuals. This report is an update of a 1988 statement by this committee. It expands on the previous statement, includes more recent therapeutic modalities, and makes more specific recommendations for the duration of secondary prophylaxis.
The tolerability and pharmacokinetics of azelastine hydrochloride (CAS 73907-93-0, A-05610) after single and multiple dosing (4.4 mg as tablet, tau = 12 h) were investigated in 14 volunteers (6 female, 8 male) older than 65 years (70 +/- 5 years, mean +/- SD). The medication was administered as tablets in the morning of days 1 and 11, and b.i.d. on days 4 to 10 in a randomized, open-labelled, uncontrolled study. Tolerance proved to be very good. Reported number of adverse events was independent from height of plasma levels measured, which showed pronounced inter- and intraindividual variation. When comparing pharmacokinetic parameters from plasma levels (determined with a radioimmunoassay (RIA)) of the elderly with those of young volunteers (26 +/- 5 years), there is a difference in half lives (t1/2 elderly vs young: single dose: 38.5 +/- 15.3 h vs 25.0 +/- 5.2 h; multiple dose: 35.5 +/- 16.3 h vs 55.4 +/- 24.9 h), and also after a single dose AUC and after multiple dosing AUCss tau, tssmax, Cssmax, Cssmin (pre dose levels), and the ratios of accumulation Rmax and Rmin (calculated from Cssmax/Cmax and Cssmin/Cmin) are approximately twice as high in elderly as those in young volunteers. The RIA co-detects besides azelastine the pharmacodynamically active metabolite N-demethyl-azelastine and thus, the parameters describe the pharmacokinetic behaviour as a resultant from both compounds, i.e. the "active principle". N-Demethylated metabolites are known to have longer half-lives usually than their parent compounds and thus, accumulate in a higher degree during multiple dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
rac-a-Lipoic acid (CAS 62-46-4, thioctic acid) is used in human therapy besides the parenteral route also orally in gastric juice soluble galenic formulations in patients suffering from diabetic polyneuropathy which also involves the gastrointestinal tract (GI) tract in about 20% of the diabetic population. In those patients the most common manifestation of the disease due to small intestine dysfunction is diarrhoea as a consequence of which malabsorption of orally administered drugs may result. Due to the importance of the knowledge on absorption characteristics, in preclinical studies on pharmacokinetics the extent of [14C]absorption from a solution of [7,8-14C]rac-a-lipoic acid was investigated in the rat after oral administration by means of comparison of the AUCs from the [14C]plasma concentrations vs those from the intravenous route, yielding 66%. An alternative evaluation by comparison of [14C]material excreted into the urine yielded 93% [14C]absorption. Despite this high and nearly complete absorption, due to the gastroenteral disturbances mentioned above, the question was investigated if the absorption is restricted to only a small area of the GI tract or is extended over a wider area. The latter is expected to make the absorption less sensitive against variations caused by gastrointestinal disturbances due to longer residence times in the GI tract. In order to approach most closely the physiological situation--as compared with different in vitro incubation techniques using isolated GI tract sacs--the in situ technique on 5 ligated areas of the GI tract of the aneasthetized rat (stomach, duodenum, jejunum, ileum, and colon with caecum) was established.(ABSTRACT TRUNCATED AT 250 WORDS)
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In a double-blind, randomized, 4-period crossover study, single oral doses of azelastine hydrochloride tablets (A-05610, Allergodil, Radethazin, Azeptin, CAS 79307-93-0) were ingested by 12 healthy volunteers (6 males, 6 females, mean age 25.2 +/- 3.5 years). Dose linearity was demonstrated for 2.2, 4.4, 8.8 and 17.6 mg of azelastine hydrochloride. The values of AUC0-infinity and Cmax increased linear to the dose (means of AUC0-infinity: 47.3, 93.7, 208.0 and 405.90 ng-eq h/ml; means of Cmax: 1.5, 3.3, 6.0 and 12.5 ng-eq/ml), whereas tmax and the terminal half-life of elimination (t1/2 beta) were obviously not influenced by the dose. Mean values over all doses and subjects amounted to 4.6 h (tmax) and 25.5 h (t1/2 beta). Plasma levels showed relatively high inter- and somewhat less intraindividual variations. This is most likely due to a varying degree of enterohepatic circulation resulting from alimentary factors. As for the co-detection of azelastine and the pharmacodynamically active metabolite N-desmethyl-azelastine by the radio-immuno-assay (RIA) used, the parameters describe the pharmacokinetic behaviour as a resultant from both compounds and thus the active principle of the drug. Independently of the dosages administered the overall tolerance proved to be very good. According to this trial the therapeutic range is wide enough to recommend 4.4 mg b.i.d. or single doses of 8.8 mg of azelastine hydrochloride per day for therapy in adult patients.
OBJECTIVE: To determine if upper respiratory tract infection (URI) affects the seroconversion rate or quantitative response to each component of a combined measles-mumps-rubella-varicella vaccine. SUBJECTS AND METHODS: One hundred forty-nine children between 15 and 18 months of age were prospectively divided into two groups according to the presence of URI or recent history of URI symptoms within the 4 weeks before vaccination. Once stratified, 74 children in the healthy group and 75 children in the URI group were randomly assigned to receive one of three lots of measles-mumps-rubella varicella vaccine by subcutaneous injection into the deltoid area. Serum was obtained from each child just before vaccination and 4 to 6 weeks later for measuring antibody levels against each virus. RESULTS: Prevaccination antibody levels against each virus in the URI and healthy groups did not differ. Nine children had pre-existing antibodies to varicella and six to mumps; no child had positive serologies for measles or rubella before vaccination. Children with pre-existing antibody were excluded from analysis of seroconversion for that virus. Seroconversion to measles, mumps, and rubella occurred in 100% of children in both groups. Mean antibody levels did not differ between the healthy and URI groups for measles (111 vs 122), mumps (97 vs 108), or rubella (96 vs 102). Three (4%) of 70 children with URIs in whom varicella serologies were available failed to seroconvert to varicella vaccine although none of the 69 healthy children had vaccine failure (P = .24). The mean varicella antibody level was 11.3 +/- 1.4 in the healthy children, which did not differ significantly from the level of 9.5 +/- 0.9 in the URI group. CONCLUSIONS: Seroconversion to measles, mumps, rubella, and varicella was not significantly affected by the presence of a concurrent or recent URI in 15- to 18-month-old children.
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Penicillin has been the recommended drug of choice in most cases of group A streptococcus (GAS) pharyngitis for nearly 40 years based on its efficacy in the prevention of acute rheumatic fever. Since trials of other drugs for the prevention of rheumatic fever are no longer feasible in the United States, eradication of GAS pharyngitis has become the surrogate for their evaluation. On the basis of this criterion, specific therapeutic regimens have been recommended, and numerous other drugs have gained approval as alternatives to penicillin. Current therapeutic issues include possible decreased efficacy of penicillin, timing of the initiation of therapy, and drugs of choice for patients whose treatment fails, who are chronic carriers, or who have frequent infections. Criteria for assessment of new drugs include clinical response, likelihood of prevention of rheumatic fever, rates of relapse and recurrent infection, and drug safety. The establishment of uniform guidelines and definitions of response for new drug evaluations by the Infectious Diseases Society of America should aid in the further assessment of new antibacterial agents as therapy for GAS pharyngitis. However, no data yet suggest that any of these drugs should replace penicillin as the drug of choice.