Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clarithromycin suspension was given at a dosage of 7.5 mg/kg bd for 7 days to 31 children with secretory otitis media, scheduled for insertion of grommets. The fifth dose was given approximately 2.5 h before myringotomy and aspiration of the middle ear effusion at which time a blood sample also was taken. In addition, in 16 children blood samples were taken at 1, 1.5 and 4 h after the fifth dose. The concentrations of clarithromycin and its active 14-hydroxylated metabolite, in middle ear effusion and serum, were determined by HPLC. Before therapy, at surgery on day 3 and after completion of treatment, nasopharyngeal samples were taken for culture and susceptibility testing. In the middle ear effusions mean concentrations of clarithromycin (2.5 mg/L) and metabolite (1.3 mg/L) were considerably higher than the serum concentrations (1.7 and 0.8 mg/L, respectively). The mean concentrations in middle ear effusion exceeded the MICs for most respiratory pathogens. Complete eradication of Streptococcus pneumoniae, Moraxella catarrhalis and Streptococcus pyogenes from the nasopharynx was achieved after three days of therapy. Approximately 50% of the isolates of Haemophilus influenzae were eradicated from approximately 50% of the patients and the growth of the persisting strains was decreased from abundant or moderate to sparse. Adverse events were mild and transient and were experienced by only two of the 31 children.
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PMID:Penetration of clarithromycin and its 14-hydroxy metabolite into middle ear effusion in children with secretory otitis media. 818 11

MICs of erythromycin, clarithromycin, and azithromycin for 852 recent clinical isolates were determined by broth microdilution methods. Frequency distribution curves, scattergrams, and regression analyses were used to compare in vitro activities and describe cross-resistance. Clarithromycin was the most active drug against Bacteroides spp. but the least active against Haemophilus influenzae. Azithromycin was most active against H. influenzae, Moraxella catarrhalis, Pasteurella multocida, and Fusobacterium spp. but the least active against Streptococcus spp. and Enterococcus spp. All three drugs had equivalent activities against Staphylococcus spp. and gram-positive anaerobes. None of the three drugs was particularly active against members of the family Enterobacteriaceae or nonfermentative gram-negative bacilli, although concentrations of 4 micrograms of azithromycin per ml inhibited some strains of the family Enterobacteriaceae (particularly Escherichia coli and Citrobacter diversus) and Acinetobacter baumannii. Although relative drug activities varied by organism, organisms relatively susceptible to one were relatively susceptible to all and organisms relatively resistant to one were relatively resistant to all; an exception was fusobacteria, which were usually susceptible only to azithromycin. Cross-susceptibility and cross-resistance were, therefore, the rule (except for Fusobacterium spp.), although the percentage of susceptible organisms could be varied considerably on the basis of the selection of breakpoints.
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PMID:Erythromycin, clarithromycin, and azithromycin: use of frequency distribution curves, scattergrams, and regression analyses to compare in vitro activities and describe cross-resistance. 825 27

Clarithromycin is a new macrolide antibiotic that is active in vitro against a variety of organisms that are responsible for acute otitis media in children. The parent compound is metabolized to microbiologically active 14-hydroxy clarithromycin, which is especially active against Haemophilus influenzae. The safety and efficacy of clarithromycin and amoxicillin suspensions were compared in the treatment of acute otitis media in children 1 to 12 years of age inclusive. This was a Phase III, single blind (investigator-blind), randomized, multicenter clinical trial. Clarithromycin oral suspension was given in a dose of 7.5 mg/kg (maximum, 500 mg) twice daily, and amoxicillin suspension in a dose of 20 mg/kg (maximum, 750 mg) was given twice daily for 7 to 10 days in a 1:1 ratio. Clinical evaluations were performed pretreatment, within 48 hours posttreatment and 10 to 14 days posttreatment. Myringotomy was performed in every child to obtain a microbiologic sample pretreatment and at subsequent visits as clinically indicated. A total of 79 children were enrolled, 39 in the clarithromycin and 40 in the amoxicillin treatment group. Thirty-two children were excluded from the efficacy analysis for various reasons. Clinical success (cure and improvement) rates at 0 to 4 days posttreatment were 93% for clarithromycin and 90% for amoxicillin (P > 0.999). Altogether 17 children (10 receiving clarithromycin, 7 receiving amoxicillin) experienced some adverse event, with gastrointestinal disorders being the most common complaint. No clinically significant differences in laboratory tests were found between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clarithromycin vs. amoxicillin suspensions in the treatment of pediatric patients with acute otitis media. 829 12

Clarithromycin is a new macrolide with a broad spectrum of activity against Gram-positive cocci, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma, Chlamydia and selected Mycobacteria, Legionella and protozoa. The drug has a half-life of more than 4 hours and thus can be administered in a twice daily schedule. Clarithromycin is well-tolerated in children and adults and produces fewer gastrointestinal side effects than erythromycin. High concentrations of the drug are achieved in plasma and in cells and tissues including tonsil, lung and middle ear fluids. Clinical efficacy has been demonstrated in randomized multicenter trials of infants and children with acute otitis media, streptococcal pharyngitis and infections of skin and skin structures. Results of these comparative trials with randomized patients receiving clarithromycin or standard drugs identified equivalent clinical and bacteriologic outcomes. A higher rate of eradication of group A Streptococcus from the pharynx was achieved with clarithromycin than with penicillin VK. The potential advantages provided by high concentrations of clarithromycin in cells and tissues such as more rapid clinical improvement or shortened dosage schedules are still to be identified.
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PMID:Clarithromycin: where do we go from here? 829 17

Clarithromycin, a new semisynthetic macrolide, is lipophilic and achieves concentrations in tissue that are generally 10 times greater than concentrations achieved in serum. Its binding to serum proteins is low and reversible. Clarithromycin has in vitro and in vivo activity against a variety of Gram-positive and Gram-negative bacteria, Mycoplasma, Chlamydia and mycobacteria. 14-Hydroxyclarithromycin, the major metabolite of clarithromycin in humans, is generally as active as clarithromycin against these organisms but is more active in vitro and in vivo than clarithromycin against Haemophilus influenzae. Organisms resistant to erythromycin by plasmid or transposon-encoded methylase, macrolide-lincosamide-streptogramin resistance, are also resistant to clarithromycin. Unlike older macrolides, however, clarithromycin has in vitro and in vivo activity against atypical mycobacteria. The antimicrobial activities of clarithromycin and 14-hydroxyclarithromycin are reviewed in this article.
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PMID:Extent and spectrum of the antimicrobial activity of clarithromycin. 829 18

Macrolides have been in use since the early 1950s. In recent years new macrolides have been developed to try to overcome the problems associated with erythromycin. In general they have fairly similar in-vitro activity, although azithromycin has superior activity against Haemophilus influenzae and some Gram-negative organisms. Clarithromycin shows superior in-vitro activity against Legionella spp. and against the type strain of Chlamydia pneumoniae. The pharmacology of macrolides produces many interpretive problems, and macrolides show marked variation in their pharmacokinetic parameters, tissue affinity and intracellular penetration. Newer macrolides such as clarithromycin, roxithromycin, dirithromycin and azithromycin only need to be taken once or twice a day, which is likely to improve patient compliance. Few objective side-effect studies have been performed with the newer macrolides. Clinical efficacy studies are essential to elucidate the significance of the complex pharmacology of macrolides.
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PMID:Comparison of macrolide antibiotics. 847 1

Erythromycin, clarithromycin, and azithromycin are clinically effective for the treatment of common respiratory and skin/skin-structure infections. Erythromycin and azithromycin are also effective for treatment of nongonococcal urethritis and cervicitis due to Chlamydia trachomatis. Compared with erythromycin, clarithromycin and azithromycin offer improved tolerability. Clarithromycin, however, is more similar to erythromycin in pharmacokinetic measures such as half-life, tissue distribution, and drug interactions. Misunderstandings about differences among the macrolides (erythromycin and clarithromycin) and the azalide (azithromycin) in terms of pharmacokinetics and pharmacodynamics, spectrum of activity, safety, and cost are common. The uptake and release of these compounds by white blood cells and fibroblasts account for differences in tissue half-life, volume of distribution, intracellular:extracellular ratio, and in vivo potency. Although microbiologic studies reveal that gram-positive pathogens are equally susceptible to these agents, significantly more isolates of Haemophilus influenzae are susceptible to azithromycin than to erythromycin or clarithromycin. Concentrations achieved at the infection site and duration above the minimum inhibitory concentration are as important as in vitro activity in determining in vivo activity against bacterial pathogens. Analysis of safety data indicates differences among these agents in drug interactions and use in pregnancy. Analysis of safety data reveals pharmacokinetic drug interactions for erythromycin and clarithromycin with theophylline, terfenadine, and carbamazepine that are not found with azithromycin. Both erythromycin and azithromycin are pregnancy category B drugs; clarithromycin is a category C drug. The numerous differences in pharmacokinetics, microbiology, safety, and costs among erythromycin, clarithromycin, and azithromycin can be used in the judicious selection of treatment for indicated infections.
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PMID:Erythromycin, clarithromycin, and azithromycin: are the differences real? 885 53

Macrolide antibiotics have proven to be valuable alternatives to penicillins and cephalosporins for the treatment of a number of infections. Currently, a number of macrolides are available. When choosing a particular macrolide, the types of organisms causing the infection, the tolerability of the drug, convenience of dosing and possible drug interactions all must be taken into account. Erythromycin, azithromycin and clarithromycin are equally effective against most gram-positive organisms. However, clarithromycin and azithromycin have much better activity against Haemophilus influenza and Moraxella catarrhalis. Thus, these 2 drugs are better choices for the treatment of community-acquired pneumonia. However, the low serum concentrations of azithromycin may be a problem in patients with bacteraemia associated with with community-acquired pneumonia. Clarithromycin appears to be effective for the treatment and prophylaxis of Mycobacterium avium complex (MAC) in patients with AIDS, while azithromycin appears to be effective for prophylaxis. Treatment of MAC with azithromycin is currently undergoing study. Although clarithromycin is the macrolide of choice for the treatment of Helicobacter pylori, azithromycin is the preferred macrolide for the treatment of Chlamydia trachomatis infections. The major factor limiting the use of azithromycin and clarithromycin has been their cost. However, these drugs may be cost effective if compliance is improved due to better tolerability and more convenient dosing regimens.
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PMID:Choosing the right macrolide antibiotic. A guide to selection. 907 39

Clarithromycin activity can be influenced by the pH of the surrounding environment. Evidence supports a reduced pH of middle ear fluid (MEF) and lung tissues in patients with otitis media and pneumonia, respectively. To evaluate the influence of pH on clarithromycin activity, an in vitro pharmacodynamic chamber model (PDCM) was used to generate bacterial time-kill curves for clarithromycin and a 2:1 ratio of clarithromycin and 14-hydroxyclarithromycin (HC) against Haemophilus influenzae at three different pH values: 7.2, 6.8, 6.4. Concentrations observed in MEF and lung tissues were simulated for clarithromycin alone and clarithromycin plus HC. Differences in activity at each pH were identified by comparing initial kill curve slopes and total log reduction. Experiments with amoxicillin-clavulanate were conducted as a reference. In simulated MEF regimens at pH 7.2, activity of clarithromycin alone improved by adding HC (additional 2 log10 reduction at 8 h); however, at pH values of 6.8 and 6.4, kill curves resembled growth controls. In simulated lung regimens, differences between clarithromycin alone and clarithromycin plus HC were insignificant; both produced a 2 log10 reduction at pH 7.2, and activity dramatically dropped to < 0.4 log10 as pH declined. In contrast, amoxicillin-clavulanate consistently produced a 3 log10 reduction over each pH value with more rapid initial kill relative to all clarithromycin regimens. These findings suggest the activity of clarithromycin against H. influenzae may be significantly compromised in respiratory tract infections involving a reduced pH. Trials with emphasis on clinical outcomes analysis will assist further in determining the significance of these experimental findings.
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PMID:Influence of pH on the antimicrobial activity of clarithromycin and 14-hydroxyclarithromycin against Haemophilus influenzae using an in vitro pharmacodynamic model. 915 10

The National Committee for Clinical Laboratory Standards (NCCLS) methods for susceptibility testing of Haemophilus influenzae in Haemophilus test medium allow a pH range of 7.2 to 7.4. However, it is known that bacteria may appear to be less susceptible to macrolides at lower pHs. Forty-four strains of H. influenzae were tested for their susceptibilities to clarithromycin and azithromycin by the disk diffusion and broth microdilution methods. The isolates appeared to be less susceptible at pH 7.2 than at pH 7.4 by both methods. Clarithromycin was less active at pH 7.2 against 43% of the isolates by the disk diffusion method and against 52% of the isolates by the broth microdilution method. Similarly, azithromycin was less active at pH 7.2 against 41 and 45% of the isolates by the disk diffusion and broth microdilution methods, respectively. Forty-two isolates were classified as clarithromycin susceptible and all isolates were classified as azithromycin susceptible by the disk diffusion method, regardless of the medium pH. However, only 21 isolates were clarithromycin susceptible at pH 7.2 and 34 isolates were susceptible at pH 7.4 by the broth microdilution method, even though quality control results indicated valid testing at both pHs. This study indicated that the results of tests of the susceptibility of H. influenzae with clarithromycin and azithromycin are highly dependent on the pH of the medium. Test results and their interpretations varied even when the medium pH was within the NCCLS-approved range and, coupled with the current NCCLS breakpoint of 8 microg/ml in the case of clarithromycin, may explain some of the observed discordances between the disk diffusion and broth microdilution methods.
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PMID:Variability in susceptibilities of Haemophilus influenzae to clarithromycin and azithromycin due to medium pH. 916 35


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