Effect of Food and Formulation on Bioavailability of Azithromycin

Willavize, William J. Curatolo, Hylar L. Friedman, M. J. Gardner, R. A. Hansen, R. Teng, and J. Vincent Pfizer Central Research Groton, Connecticut Based on a study with a research capsule formulation of azithromycin, the labeling for azithromycin capsules reads ZITHROMAX (azithromycin) should be given at least 1 hour before or 2 hours after a meal. We now report studies of the influence of high-fat breakfasts on the bioavailability of azithromycin from tablets,...

Materials And Methods

Six healthy male volunteers with no evidence of clinically active gastrointestinal disease, documented allergic reactions to macrolides or cardiovascular, hepatic, or neurological diseases were enrolled in the study. Subjects were determined to be in good health by means of physical examination and clinical laboratory tests. Subjects were restricted from all standard prescription and nonprescription drugs for 2 weeks prior to participation and throughout the study period. Subjects also...

Patients And Methods

Patients of both sexes, aged between 17 and 72 years, with clinical symptoms such as epigastric pain, dyspepsia, heartburn, or anorexia, were enrolled in this open, noncomparative study. They were included in the study on the basis of endoscopic findings (endoscopic appearance of duodenal ulcer, measuring between 5 and 20 mm in longest dimension, or endoscopic appearance of antral erosions, spotty erythema of antral mucosa, pale areas, goose-pimple-like appearance of antral mucosa, fine spotty...

Material And Methods

A total of 247 staphylococcal strains freshly isolated from clinical material was tested. Only one isolate per patient was included. In addition, because methicillin-resistant Staphylococcus aureus strains can cause epidemics, we used several criteria to avoid multiple copies of the same strain (i) strains were from different geographic locations (both within hospitals and from different hospitals), which would reduce the chance of obtaining a single clone, (ii) collecting strains over a period...

Resistance to Quinupristin Dalfopristin Biochemical Mechanisms and Detection

The rapidity with which resistance genes are disseminated through a bacterial population, especially in the hospital setting, is unpredictable. Both the frequency at which genes encoding proteins involved in resistance appear and the hardiness and transfer capacity of the genetic element carrying such genes are involved. The gene erm encodes a methylase that modifies a base in 23S ribosomal RNA, reducing the affinity of the ribosome for macrolides, lincosamides, and group B streptogramins, such...

Development Of Streptogramins And Macrolides

The streptogramins belong to the peptide group of antibiotics and include the mikamycins, ostreomycins, virginiamycins, and pristinamycins. The latter naturally occurring antibiotics derived from Slreptomyces pristinae-spira. Pristinamycin and virginiamycin have been used in continental Europe as oral agents for the treatment of staphylococcal and streptococcal infections. The past few years have seen major developments in both the macrolide and peptide classes of compounds, most notably with...

Haemophilus influenzae

Against the 6 strains tested (including 2 strains producing -lactamases), RPR 106972 was bactericidal at the concentrations of 2 or 4 mg L (2 or 4 x the MIC according to the strain tested) in a 3- to 6-h period (5 strains) or in a 6- to 24-h period (1 strain). RPR 106972 has potent in vitro bacteriostatic activity against aerobic grampositive cocci, including staphylococci resistant to oxacillin and macrolides-lincosamides-streptograminB (MLSB), gram-positive anaerobes, certain gram-negative...

In Vivo Postantibiotic Effects

The neutropenic mouse thigh model is the only model that has been used to evaluate the in vivo postantibiotic effects of macrolides, azalides, and streptogramins (12-16), An example of a typical in vivo postantibiotic effect study in this animal model is illustrated in Fig. 1, Exposure of a Table I In Vitro Postantibiotic Effects with Erythromycin, Clarithromycin, Azithromycin, and Streptogramins Against Staphylococcus aureus ATCC 25923 and Streptococcus pneumoniae ATCC 10813 Source Data from...

Concluding Remarks

Whatever the in vivo mechanisms (effects on phagocyte numbers and functions, cytokine production, or other inflammatory parameters) there is a worldwide consensus that in addition to their antibacterial properties, some macrolide antibiotics are also endowed with anti-inflammatory activity. The host target in most studies is the phagocyte, which is a corner stone in host defenses and inflammation, whereas there is no concern for a beneficial anti-inflammatory activity of macrolides in the case...

Methods

A total of 11 healthy male subjects (mean age, 28 years age range, 2039 years mean weight, 75,2 kg weight range, 64.9-89.4 kg) completed this study. Subjects were determined to be in good health by means of physical examination and standard clinical laboratory tests. They received no known prescription or nonprescription drugs for at least 2 weeks prior to participation and throughout the study period. Subjects fasted overnight for 12 h prior to each dose of azithromycin and for 4 h afterward....

In Vitro Activity

The spectrum of activity of the recently available macrolides and streptogramins is sufficiently distinctive among the major classes of anti-infectives, perhaps with the exception of tetracyclines, in that it encompasses not only many common bacterial pathogens but also includes atypical pathogens, Mycobacteria spp., spirochaetes, and selective protozoa. Furthermore, the observed high tissue and intracellular concentrations broaden their clinical utility. The growing importance of drug...

Discussion And Summary

The nearly 100 efficacy of azithromycin 50 mg kg per day in the primary cure of brucellosis following 1 and 2 weeks of therapy, demonstrated in the present experiment, has not yet been reported with any single antibiotic agent. This therapeutic effect was maintained for 1 month and prevented relapses, an effect hitherto undescribed. In view of these results and the therapeutic failures with other macrolides and fluoroquinolones, plus the drug's known safety and tolerance profiles, we suggest a...

Inflammation From The Greeks To The Cytokines

From Celsus (30 b.c.-a.d.38), Rubor, Dolor, Calor, Tumor the four cardinal signs of inflammation to which Galen (or Wirchow ) added Functio laesa have stood the test of time. But the fundamental approach to the humoral cellular factors involved in this phenomenon only began in the 19th century with the work of so many illustrious scientists as Cohnheim, Metchnikoff, Ehrlich, Von Behring, and Landsteiner. Today, our vision of the scenario of events which occurs each time host integrity is...

Early Clinical Results with Quinupristin Dalfopristin for the Therapy of Bacteremia Due to Resistant Gram Positive

Beth Isra l Deaconess M dical Center Boston, Massachusetts Rh ne-Poulenc Rorer Collegeville, Pennsylvanie Quinupristin dalfopristin (Synercid ) is a novel streptogramin antibiotic with potent activity against gram-positive organisms, including methicillin-resistant staphylococci and vancomycin-resistant Bnterococcus faecium (VREF) (1,2). Even though the drug has yet to be released for clinical use, it has attracted widespread attention in the infectious diseases community, as it is often the...

Results

Baseline patient characteristics are summarized in Table 1, The time elapsing between the tick bite and the appearance of EM was 3 days to 4 months, 17 days on average. Seasonal appearance of and erythema migrans is shown in Fig. 1. The geographic region was identical for patients presenting with either of the findings. Clinical response to azithromycin treatment is presented in Table 2. Fourteen days after treatment, fatigue, malaise, and periodic headaches were present in seven patients, and...

Single Dose Azithromycin in the Treatment of Genital Chlamydial Infections

Chmurny Comenius University Bratislava, Slovak Republic Pliva-Bratislava Bratislava, Slovak Republic Chlamydial infection is the most frequently encountered sexually transmitted disease and causes serious sequelae. Azithromycin is an azalide antibiotic with a very low minimal inhibitory concentration (MIC) for Chlamydia trachomatis and achieves high intracellular concentration which may be beneficial in eradicating this obligate intracellular pathogen....

Haemophilus influenzae Enterococci and Anaerobes

Yale University School of Medicine New Haven, Connecticut United Medical and Dental Schools of Guy's and St. Thomas's Hospitals London, United Kingdom The difficulties of in vitro susceptibility testing in relation to the MAS group of antibiotics in general, and this otherwise heterogeneous group of microorganisms in particular, were repeatedly stressed throughout the session. Wide discrepancies in results obtained by any of the conventional susceptibility-testing methods may be related to...

Theophylline Table

The first clinical report of theophylline-erythromycin interaction appeared in 1977. In this report, the blood levels of theophylline increased 37 and 46 after the addition of 4.5-5.0 mg kg q6h of erythromycin A in two children. In healthy volunteers, after a 10-day course of erythromycin stearate (250 mg tid orally), the half-life of serum theophylline increased from 4.79 to 7.53 h, whereas drug clearance decreased from 91.6 to 54.8 ml h kg. Theophylline metabolites 3-methylxanthine and 1.3...

Drug Interactions of Macrolides and Azalides

Sheba Medical Center Tel-Aviv University, School of Medicine Tel-Hashomer, Israel The macrolides and azalides are antibiotics in common use in a large number of patients. Due to the fact that these antibiotics are frequently prescribed to patients with respiratory tract infections who receive many other agents such as bronchodilatators, mucolytic agents, cardiac medications, diuretics, and so forth, drug interactions of this group of agents are of particular importance. In addition, at the...

Legionella and Spirochetes

University Hospital Utrecht, The Netherlands Baylor College of Medicine and Veterans' Affairs Medical Center Houston, Texas Depending on the season and location, about 2-10 of community-acquired pneumonias (CAPs) are caused by Legionella spp. Most cases of Legionnaires' disease are caused by Legionella pneumophila, although infections by other species are well documented, Legionella spp. belong to the group of supposedly atypical organisms, together with Chlamydia pneumoniae, Coxiella burnetii,...

Conclusion On Streptococcus Pneumoniae

H. influenzae is pharmacologically resistant to erythromycin, poorly susceptible to roxithromycin (resistant to the concentrations obtained in vivo), whereas it is pharmacologically more susceptible to clarithromycin (susceptible to the concentrations obtained in vivo) and both pharmacologically and micro biologically more susceptible to azithromycin. There are major pitfalls associated with in vitro testing but they can be overcome. The E-test is an interesting alternative to the agar dilution...

Acknowledgments

I thank K, Pepper for helpful comments, and J.F. Desnottes and N. Ber-thaud for providing new data from their laboratory. 1. Barriere JC, Bouanchaud DH, Desnottes JF, Paris JM. Streptogramin analogues. Exp Opin Invest Drugs 1994 3(2) 115-131. 2. Aumercier M, Bouhallab S, Capmau ML, Le Goffic F RP 59500 a proposed mechanism for its bactericidal activity. J Antimicrob Chemother 1992 30 (suppl A) 9-14, 3- Cocito C, Di Giambattista M, Vannufel P. The mechanism of action of streptogramins. 3rd...

Could Clarithromycin Prevent Asthma

Kundsin, and Sharon A. Poulin Brig ham and Women's Hospital, The Children's Hospital Medical Center and Harvard Medical School Boston, Massachusetts Asthma is the most disabling of all chronic diseases in childhood, and one of the commonest. About 30 of individuals who are subsequently diagnosed, in middle childhood or later, as having asthma began with symptoms of recurrent wheezing, cough, and bronchospasm in the first year of life, A longitudinal study of infants...

Hi Mycoplasma Chlamydia

A Comparison of the In Vitro Sensitivity of Chlamydia pneumoniae to M aero Ii des and a New Benzoxazinorifamycin, KRM-1648 C.-C. Kuo, J. Thomas Grays ton, T. Hidaka, and L. M, Rose Susceptibilities to Azithromycin of Isolates of Chlamydia pneumoniae from Patients with Community-Acquired Pneumonia P. M. Roblin, N. Sokolovskaya, and M. R. Hammerschlag Azithromycin in Control of Trachoma Julius Schachter Microbiologic Efficacy of Azithromycin for the Treatment of Community-Acquired Pneumonia Due...

Staphylococci Streptococci and Pneumococci

Fondation H pital Saint-Joseph Paris, France University of Lisbon Lisbon, Portugal The authors of abstracts and discussants developed an overview of S. aureus, S. pneumoniae, and S. pyogenes reporting on susceptibility and susceptibility testing epidemiology of resistant strains and insights on therapy of infections. The susceptibility and susceptibility testing of S. aureus to the macro-lides and macrolide-related antibiotics should be considered regarding the different classes of compounds...

The Mechanism Of Action Of Type B Streptogramins

Cell Free Nirenberg And Matthaei

Unlike type A components, type B components are ineffective in the Nirenberg system 18 . This observation has prompted the development of other cell-free systems with copolymers as messengers. In these models, polypeptides with diverging properties are synthesized charged and hydro-philic, those primed by adenine polymers and neutral and hydrophobic, those directed by uracil-containing messengers. Indeed, the system containing poly A, C copolymers as templates are highly sensitive to inhibition...

MICs of Macrolides on H pylori

Pylori Mutation

When MICs were determined on strains of H. pylori, a small group of resistant strains was identified e.g., 10 in France 14 . The MICs of susceptible strains to clarithromycin at neutral pH range from 0.015 to 0.06 mg L. This compound is the most effective macrolide with a MIC of 0.03 mg L i.e., almost as low as amoxicillin . Other macrolides with good activity are azithromycin and roxithromycin 15 . When MICs are determined at a lower pH, their values increase, but, again, clarithromycin is the...

Macrolides As Antiinflammatory Agents In Vivo Studies

Low-dose, long-term erythromycin treatment has been reported effective in patients with chronic lower respiratory tract disease including diffuse pan-bronchiolitis 25-27 . Diffuse panbronchiolitis is characterized by chronic inflammation of the respiratory bronchioles and infiltration of chronic inflammatory cells, accompanied by repeated episodes of respiratory infections, especially due to Pseudomonas aeruginosa, which finally result in respiratory failure. The clinical effectiveness of...

Ketolides New Semisynthetic 14Membered Ring Macrolides

Macrolides Resistance Thylation

Andr Bryskier, Constantin Agouridas, and Jean-Fran ois Chantot Erythromycin A was discovered at a time when a new drug active against penicillinase-producing S. aureus strains was needed. Penicillinase-producing resistant strains appeared in London hospitals very shortly after the first clinical use of penicillin G, and soon spread worldwide 1 . This led to parallel research projects by the pharmaceutical industry and generated semisynthetic methicillin and isoxazolylpenicillins oxacillin,...