Drugs

, Volume 37, Issue 1, pp 8–41 | Cite as

Roxithromycin

A Review of its Antibacterial Activity, Pharmacokinetic Properties and Clinical Efficacy
  • Ronald A. Young
  • John P. Gonzalez
  • Eugene M. Sorkin
Drag Evaluation

Summary

Synopsis

Roxithromycin is an acid-stable orally administered antibacterial macrolide structurally related to erythromycin. It has an in vitro antibacterial profile similar to that of erythromycin, with activity against Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, S. pyogenes, Branhamella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Gardnerella vaginalis, Haemophilus ducreyi, some anaerobes and other less common pathogens.

Roxithromycin has a pharmacokinetic profile that is characterised by excellent enterai absorption achieving high concentrations in most tissues and body fluids.

The results of clinical studies with roxithromycin have confirmed the potential for its use in a variety of infections, which was suggested by its antibacterial activity in vitro and pharmacokinetic profile. Clinical efficacy has been confirmed in the treatment of respiratory tract infections, including community-acquired and atypical pneumonias, ear, nose and throat infections, genitourinary tract infections, and skin and soft tissue infections. In a relatively small number of patients roxithromycin has generally been shown to be as effective as erythromycin and other appropriate antibacterial drugs in some of the above indications. Roxithromycin is well tolerated and has less potential than erythromycin to produce clinically significant drug interactions. Thus, roxithromycin is an orally active drug which should prove a useful alternative when selecting antibacterial therapy for indications where macrolides are appropriate.

Antibacterial Activity

Roxithromycin is an acid-stable macrolide with an in vitro spectrum of antibacterial activity closely resembling that of erythromycin. Staphylococcus aureus (excluding methicillin-resistant strains) are sensitive to roxithromycin as well as to erythromycin, josamycin and spiramycin. Roxithromycin is slightly less potent than erythromycin against S. epidermidis including strains resistant to penicillin. Streptococci, including Groups A, B and C and S. pneumoniae, but not Group G and the enterococci, are susceptible to roxithromycin, with erythromycin, clindamycin, cefaclor and amoxycillin showing similar activity.

In common with erythromycin, josamycin and doxycycline, roxithromycin is a potent inhibitor of Branhamella catarrhalis, including β-lactamase-producing strains. Roxithromycin produces potent inhibition of Legionella species with similar activity to that of erythromycin. Against Campylobacter species the in vitro activity of roxithromycin is generally lower than that of erythromycin. Gardnerella vaginalis and Haemophilus ducreyi are highly susceptible to roxithromycin and, like erythromycin, josamycin, amoxycillin and tetracycline, roxithromycin produces varying inhibitory activity against Haemophilus influenzae. Isolates of Neisseria gonorrhoeae, including strains resistant to penicillin, are susceptible or moderately susceptible to roxithromycin, with erythromycin and josamycin showing similar inhibitory activities. Neisseria meningitidis is moderately susceptible to roxithromycin but roxithromycin is less potent than erythromycin against Bordetella pertussis and B. parapertussis while B. bronchiseptica is resistant to both macrolides. Roxithromycin is inactive against the enterobacteriaceae Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Providencia stuartii, Salmonella enteritidis and Shigella spp.

Roxithromycin is less potent than rifampicin and isoniazid against Mycobacterium tuberculosis, with strains of M. avium, M. fortuitum and M. chelonae showing resistance to the macrolide. Bacillus cereus, Corynebacterium and Listeria monocytogenes are susceptible to roxithromycin. Among anaerobic species, Bacteroides oralis, B. melaninogenicus, B. ureolyticus, Eubacterium spp., Peptostreptococcus spp., Propionibacterium acnes, Actinomyces spp. and Bifldobacterium spp. were susceptible to roxithromycin; other anaerobes including Bacteroides spp., Clostridium spp., Fusobacterium spp. and Veillonella spp. were generally resistant. Roxithromycin was active against Chlamydia trachomatis, Mycoplasma pneumoniae and Ureaplasma urealyticum, with similar potencies to erythromycin. In general, bacterial strains selected for their resistance to erythromycin are also resistant to roxithromycin.

The in vitro activity of roxithromycin is affected by the biological source and concentration of sera used in the medium. Increases in the inoculum size up to 105 cfu have little effect on the minimum inhibitory concentration (MIC) of roxithromycin. However, when the inoculum size is increased to 107 cfu considerable increases occur in the MIC.

Killing curve studies using conditions simulating serum pharmacokinetics show roxithromycin to be rapidly bactericidal against S. pneumoniae, producing a kill rate which exceeded those of erythromycin, doxycycline and ofloxacin. Roxithromycin produces a postantibiotic effect of up to 9.6 hours after exposure to S. pneumoniae and S. pyogenes.

Roxithromycin produces its antibacterial effect through inhibition of protein synthesis inside the bacterial cell. Roxithromycin is highly concentrated in polymorphonuclear leucocytes and macrophages, and also enhances the adhesive and chemotactic functions of these cells which in the presence of infection produce phagocytosis and bacterial lysis.

Roxithromycin produces good antibacterial activity in experimental models of infection induced by Gram-positive organisms and other infections such as toxoplasmic encephalitis and syphilis.

Pharmacokinetics

Following administration of a single oral dose of roxithromycin 150mg to healthy volunteers, mean plasma concentrations ranging from 6.6 to 7.9 mg/L are reached within 2 hours. Administration of roxithromycin 150mg before a meal had little effect on maximum plasma concentrations and bioavailability. Multiple-dose administration for up to 11 days in healthy volunteers did not produce accumulation at a dosage of 150mg twice a day or 300mg once a day. The area under the plasma concentration-time curve (AUC) following administration of roxithromycin 150mg was 72.6 to 81 mg/L · h compared with 6.97 mg/L · h for erythromycin 500mg.

Roxithromycin is extensively distributed throughout tissue and body fluids with corresponding plasma concentrations being high and greater than the MIC90 values for susceptible bacteria. Maximum concentrations of roxithromycin in pulmonary tissue were 5.6 mg/L 6 hours after administration of 150mg compared with a maximum of 4.2 mg/ L for erythromycin measured 3 hours after a 1g dose. Roxithromycin concentrations in bronchoalveolar lavage cells were 2 and 10 times higher than corresponding levels in plasma and epithelial fluid, respectively. Less than 0.05% of a single dose of roxithromycin 300mg appears in breast milk, with AUC values for breast milk less than 5% of corresponding plasma AUC values.

In urine and faeces 50 and 55% of recovered drug, respectively, appeared as unchanged roxithromycin; 25 and 22%, respectively, as the descladinose derivative, and 5 and 7%, respectively, as the demethylated derivative, with only unchanged roxithromycin detected in plasma. The elimination half-life of roxithromycin following administration of 150 and 300mg doses ranged from 8.4 to 15.5 hours, compared with 1.5 to 3 hours for a 1g dose of erythromycin. The pharmacokinetics of roxithromycin in infants and children are similar to those in adults. No dosage adjustments are required in elderly patients.

Following single doses, maximum plasma concentrations, AUC values and the elimination half-life were increased in patients with renal insufficiency, whereas urinary elimination and renal clearance were reduced. Following the administration of multiple doses no roxithromycin accummulation occurred and the kinetics were not dependent on the degree of renal impairment suggesting no dosage modifications are required in patients with renal impairment. Furthermore, in patients with severe alcoholic cirrhosis maximum plasma concentrations, time to maximum plasma concentrations and the AUC were similar to those of healthy subjects but the elimination half-life increased 2-fold. In these patients roxithromycin dose adjustments are required.

Therapeutic Trials

Oral roxithromycin 150mg twice a day is therapeutically effective in the treatment of several types of infection. In non-comparative studies of respiratory tract infections roxithromycin produced clinical and bacteriological cure rates of 84 to 100% and 91 to 95%, respectively. In comparative studies roxithromycin produced clinical efficacy rates of 78 to 93%, which were similar to those of erythromycin 1g twice a day or 400mg four times a day, doxycycline 200mg daily, amoxycillin 500 twice a day or 750mg 3 times a day, and cephradine 1g twice a day. Compiled results following roxithromycin treatment reveals that 92% of patients with pneumonia caused by common pathogens, 100% with atypical pneumonia, and 85% with acute episodes of chronic obstructive lung disease were clinically cured. Compiled bacteriological eradication rates were 93% for S.pneumoniae, 74% for H. influenzae, 89% for S. aureus, and 92% for S. pyogenes.

High clinical and bacteriological efficacy rates were also obtained in ear, nose and throat infections. Compilation of the results from published studies reveals cure rates of 97% for tonsillitis and pharyngitis, 95% for otitis, and 85% for sinusitis following roxithromycin treatment. In comparative studies similar clinical cure rates of 83 to 100% and 86 to 100%, respectively, were reported for roxithromycin 150mg twice daily and erythromycin 400mg 4 times daily.

Several open and comparative studies have assessed the efficacy of roxithromycin in the treatment of acute or chronic non-gonococcal urethritis, non-gonococcal sexually transmitted infections and cervicovaginitis. In comparative studies clinical cure rates for twice daily administration of roxithromycin 150 and 300mg were 93 and 99%, respectively, compared with 98% for lymecycline 300mg twice a day and 89% for doxycycline 200mg daily. Bacteriological cure rates for roxithromycin ranged in most indications from 86 to 100%, with 97% of C. trachomatis, 88% of U. urealyticum, 73% of M. horninis and 57% of Gardnerella vaginalis isolates eradicated.

In infants and children roxithromycin 2.5 to 5 mg/kg 12-hourly produced clinical cure rates of 83 to 100% for tonsillitis, pharyngitis, superinfected rhinopharyngitis, pneumococcal pneumonia, impetigo, otitis media and pyodermatitis. Bacteriological cure rates were also high, with elimination of 92.3% of S. pyogenes, 79.2% of S. pneumoniae, and 94.3% of S. aureus isolates.

In patients with skin and soft tissue infections both clinical and bacteriological cure rates were 92% for roxithromycin 150mg twice a day and 82% for doxycycline 200mg daily. Overall, in the treatment of skin and soft tissue infections including pyoderma, infective dermatitis and leg ulcers, clinical and bacteriological cure rates were 79 to 100% and 82 to 100%, respectively.

Adverse Effects

Clinically significant adverse effects following treatment with roxithromycin are uncommon. Of 2,917 adults who took part in multicentre studies 4.1% reported adverse effects that were possibly or probably related to treatment. The most common adverse effects encountered were gastrointestinal in nature, with nausea, abdominal pain and diarrhoea the most frequently reported. A total of 0.9% of patients withdrew from treatment as a result of adverse effects. Tolerance and safety in infants and children, and the elderly, were excellent. Abnormalities in liver function tests due to roxithromycin administration were rare.

Dosage and Administration

The recommended oral adult dosage of roxithromycin for all indications is 150mg administered twice a day at least 15 minutes before meals. In infants and children the recommended dose is 2.5 to 5 mg/kg bodyweight twice daily.

No dosage adjustments are required when roxithromycin is administered concurrently with theophylline and carbamazepine, and the drug can be administered simultaneously with warfarin, ranitidine or antacids.

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References

  1. Acar JF, Saint-Salvi B, Blanc F. Concentration of roxithromycin in tear fluid and saliva after repeat dosing. British Journal of Clinical Practice 42 (Suppl. 55): 82, 1988Google Scholar
  2. Agache P, Amblard P, Moulin G, Barrière H, Texier L, et al. Roxithromycin in skin and soft tissue infections. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 153–156, 1987PubMedGoogle Scholar
  3. Akoun G, Bertrand A, Caubarrère I, Constans P, Dumont R, et al. Clinical evaluation of roxithromycin (RU28965) in the treatment of hospitalized patients with lower respiratory tract infections. In Butzler & Kobayashi (Eds) Macrolides: a review with an outlook on future developments, pp. 95–99, Excerpta Medica, Amsterdam, 1986Google Scholar
  4. Andrews JM, Ashby JP, Wise R. Factors affecting the in vitroactivity of roxithromycin. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 31–37, 1987PubMedGoogle Scholar
  5. Aronoff SC, Laurent C, Jacobs MR. In-vitro activity of erythromycin, roxithromycin and CP 62993 against common paediatric pathogens. Journal of Antimicrobial Chemotherapy 19: 275–276, 1987PubMedGoogle Scholar
  6. Barlam T, Neu HC. In vitro comparison of the activity of RU28965, a new macrolide, with that of erythromycin against aerobic and anaerobic bacteria. Antimicrobial Agents and Chemotherapy 25: 529–531, 1984PubMedGoogle Scholar
  7. Barry AL, Thornsberry C, Jones RN. In vitro activity of a new macroloide, A-56268, compared with that of roxithromycin, erythromycin and clindamycin. Antimicrobial Agents and Chemotherapy 31: 343–345, 1987PubMedGoogle Scholar
  8. Bazet MC, Blanc F, Chumdermpadetsuk S, Fiessinger S, Kafetzis D, et al. Roxithromycin in the treatment of paediatric infections. British Journal of Clinical Practice 42 (Suppl. 55): 117–118, 1988Google Scholar
  9. Bébéar C, Renaudin H, de Barbeyrac B, Cantet P, Quentin C. In vitro sensitivity of Ureaplasma urealyticumto RU28965 compared to erythromycin and josamycin. In Butzler & Kobayashi (Eds) Macrolides: a review with an outlook on future developments, pp. 91–94. Excerpta Medica, Amsterdam, 1986Google Scholar
  10. Bégué P, Kafetzis DA, Albin H, Safran Ch. Pharmacokinetics of roxithromycin in paediatrics. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 101–106, 1987PubMedGoogle Scholar
  11. Bégué P, Lacombe H, Cotin G, Chaviere F, Chretien P. Diffusion of roxithromycin into tonsillar tissue in children. British Journal of Clinical Practice 42 (Suppl. 55): 78–79, 1988Google Scholar
  12. Bergeron MG, Lavoie GY, Boucher FDW. Comparative bactericidal activity of cefixime, carumonam, enoxacin and roxithromycin with those of other antibiotics against resistant Haemophilus influenzaeincluding β-lactam tolerant strains. Journal of Antimicrobial Chemotherapy 20: 663–669, 1987PubMedGoogle Scholar
  13. Bergogne-Bérézin E. Pharmacokinetics of antibiotics in respiratory secretions. In Respiratory infections: diagnosis and management, pp. 461–479, Raven Press, New York, 1983Google Scholar
  14. Bergogne-Bérézin E. Tissue distribution of roxithromycin. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 113–120, 1987PubMedGoogle Scholar
  15. Bergogne-Bérézin E, Berthelot G, Uzzan J, Ravina JH. Evaluation of placental transfer of roxithromycin in late pregnancy. 27th Interscience Congress of Antimicrobial Agents and Chemotherapy, New York, 1987Google Scholar
  16. Bertrand A, Caubarrere I, Chapman A, Clavier J, Constans P, et al. Multicentre comparative study of the efficacy and safety of roxithromycin and erythromycin ethyl succinate in the treatment of lower respiratory tract infections. British Journal of Clinical Practice 42 (Suppl. 55): 98–99, 1988Google Scholar
  17. Blanc F, D’Enfant J, Fiessinger S, Lenoir A, Renault M, et al. An evaluation of tolerance of roxithromycin in adults. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 179–183, 1987PubMedGoogle Scholar
  18. Botto H, Carney M, Chretien P, Safran C. Study of the diffusion of roxithromycin into prostatic tissue after repeat oral dosing. British Journal of Clinical Practice 42 (Suppl. 55): 83, 1988Google Scholar
  19. Bowie WR, Shaw CE, Chan DGW, Black WA. In vitro activity of RO 15-8074, RO 19-5247, A-56268 and roxithromycin (RU 28965) against Neisseria gonorrhoeaeand Chlamydia trachomatis. Antimicrobial Agents and Chemotherapy 31: 470–472, 1987PubMedGoogle Scholar
  20. Brun Y, Forey F, Gammondes JP, Tebib A, Brune J, et al. Levels of erythromycin in pulmonary tissue and bronchial mucus compared to those of amoxycillin. Journal of Antimicrobial Chemotherapy 8: 459–466, 1981PubMedGoogle Scholar
  21. Carlier MB, Zenebergh A, Tulkens PM. Handling of two macrolides, erythromycin and roxithromycin, by human and animal macrophages in culture. 15th International Congress of Chemotherapy, Istanbul, July 19–24, 1987Google Scholar
  22. Carlone NA, Cuffini AM, Tullio V, Sassella D. Uptake of roxithromycin by mouse peritoneal macrophages. 15th International Congress of Chemotherapy, Istanbul, July 19–24, 1987Google Scholar
  23. Casai M. In vitro susceptibility of mycobacteria to roxithromycin. British Journal of Clinical Practice 42 (Suppl. 55): 19–20, 1988Google Scholar
  24. Casellas JM, Goldberg M, Arduiros S, Farinati A, Iribarren M, et al. Comparative MIC and MBC of roxithromycin, A56286 and erythromycin against 600 clinical isolates. 15th International Congress of Chemotherapy, Istanbul, July 19–24, 1987Google Scholar
  25. Casellas JM, Rodriguez HA, Fernandez-MacLoughlin GJ, Lanoël JL, Iribarren A. Efficacy of roxithromycin in the treatment of acute otitis media in infants. British Journal of Clinical Practice 42 (Suppl. 55): 113–114, 1988Google Scholar
  26. Cevenini R, Rumpianesi F, Sambri V, La Placa M. In vitro activity of RU 28965, a new macrolide, against Chlamydia trachomatisand Ureaplasma urealyticum. In Butzler & Kobayashi (Eds) Macrolides: a review with an outlook on future developments, p. 125–127, Excerpta Medica, Amsterdam, 1986Google Scholar
  27. Chabbert YA. Early studies on in vitroand experimental activity of spiramycin: a review. Journal of Antimicrobial Therapy 22 (Suppl. B): 1–11, 1988Google Scholar
  28. Chang HR, Pechère J-CF. In vitro effects of four macrolides (roxithromycin, spiramycin and azithromycin [CP-62,993], and A-56268) on Toxoplasma gondii. Antimicrobial Agents and Chemotherapy 32: 524–529, 1988PubMedGoogle Scholar
  29. Chantot JF, Bryskier A, Gasc JC. Antibacterial activity of roxithromycin: a laboratory evaluation. Journal of Antibiotics 39: 660–668, 1986PubMedGoogle Scholar
  30. Charpin J, Freour P, Marsac J. Etude multicentrique de l’efficacité clinique et de la tolérance de la roxithromycine comparée à la doxycycline dans les infections respiratoires basses. Pathologie Biologie 36: 548–551, 1988PubMedGoogle Scholar
  31. Chastre J, Brun P, Fourtillan JB, Soler P, Basset G, et al. Pulmonary disposition of roxithromycin (RU 28965), a new macrolide antibiotic. Antimicrobial Agents and Chemotherapy 31: 1312–1316, 1987PubMedGoogle Scholar
  32. Chin NX, Neu NM, Labthavikul P, Saha G, Neu HC. Activity of A-56268 compared with that of erythromycin and other oral agents against aerobic and anaerobic bacteria. Antimicrobial Agents and Chemotherapy 31: 463–466, 1987PubMedGoogle Scholar
  33. Concia E, Cruciana M, Barzaghi N, Bartucci F, Sassella D. Diffusion of roxithromycin into suction skin blister fluid. British Journal of Clinical Practice 42 (Suppl. 55): 86–87, 1988Google Scholar
  34. Croize J, Le Noc P, Bryskier A, Duborgel S, Robert J. Activité in vitrode trois macrolides: érythromycine, josamycine et roxithromycine vis-a-visde 349 bactéries aérobies ou anaérobies. Bordeaux Médical 20: 159–162, 1987Google Scholar
  35. Czinn S, Carr H, Aronoff S. Susceptibility of Campylobacter pyloridisto three macrolide antibiotics (erythromycin, roxithromycin [RU 28965], and CP 62,993) and rifampin. Antimicrobial Agents and Chemotherapy 30: 328–329, 1986PubMedGoogle Scholar
  36. Dabernat HJ, Delmas C, Lareng MB. Activité in vitrode la roxithromycine sur Branhamella catarrhaliset Haemophilus influenzae.Réunion Interdisciplinaire de Chimiothérapie Antiinfectieuse, Paris, December 3, 1987Google Scholar
  37. Debbia E, Varaldo PE, Schito GC. In vitro sensitivity of streptococci and staphylococci from clinical material to a novel macrolide: RU 28965. In Butzler & Kobayashi (Eds) Macrolides: a review with an outlook on future developments, pp. 121–124, Excerpta Medica, Amsterdam, 1986Google Scholar
  38. de Grandi P, Comte R, von Moss G, Grutter F, Pechere JC. Concentration of roxithromycin in plasma and gynaecological tissues following repeated oral administrations. British Journal of Clinical Practice 42 (Suppl. 55): 84–85, 1988Google Scholar
  39. Delaforge M, Sartori E, Mansuy D. Effects of roxithromycin on rat hepatic P-450 cytochromes: comparison with troleandomycin and erythromycin. British Journal of Clinical Practice 42 (Suppl. 55): 67–69, 1988Google Scholar
  40. De Rose V, Ferrara A, Mangiarotti P, Nonis A, Bertoletti R, et al. Penetration of roxithromycin in bronchial secretions. International Journal of Clinical Pharmacology Research 8: 107–110, 1988PubMedGoogle Scholar
  41. Dette GA, Knorthe H, Koulen G. Comparative in vitro, serum binding and binding activity interactions of the macrolides A-56268, erythromycin and josamycin. Drugs Under Experimental and Clinical Research 13: 567–576, 1987PubMedGoogle Scholar
  42. Dewever M. Determination of roxithromycin concentration in the mucosa of the maxillary sinus. British Journal of Clinical Practice 42 (Suppl. 55): 81, 1988Google Scholar
  43. Drabu YJ, Mehtar S, Blakemore PH. The in vitroactivity of roxithromycin (RU 28965) compared with four oral antibiotics. Drugs Under Experimental and Clinical Research 13: 201–203, 1987PubMedGoogle Scholar
  44. Dubreuil L. In vitro comparison of roxithromycin and erythromycin against 900 anaerobic bacterial strains. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 13–19, 1987PubMedGoogle Scholar
  45. Dutilh B, Barbeyrac B, Lafferrière C, Bébear C. Activité comparée in vitrod’un nouveau macrolide RU 28965 et de lérythromycine vis-à-vis de Chlamydia trachomatis. Pathologie Biologie 34: 445–447, 1986PubMedGoogle Scholar
  46. Duval J, Acar JF, Cluzel R, Soussy CJ, Kitzis MC, et al. In vitro activity of roxithromycin against hospital bacteria: regression curve. British Journal of Clinical Practice 42 (Suppl. 55): 26–29, 1988Google Scholar
  47. Felmingham D, Robbins MJ, Harais R, Ridgway GL, Gruneberg RN. The effect of carbon dioxide on the invitroactivity of erythromycin and RU-28965 against anaerobic bacteria. Drugs Under Experimental and Clinical Research 13: 195–199, 1987PubMedGoogle Scholar
  48. Fernandez-MacLoughlin GJ, Lanoel JL, Sarachian B. A new macrolide in the treatment of streptococcal throat infections in children. IXth International Congress of Infectious and Parasitic Diseases, Munich, July 20–26, 1986Google Scholar
  49. Fleurette J, Bornstein N. Susceptibility of Legionella species to roxithromycin. 15th International Congress of Chemotherapy, Istanbul, July 19–24, 1987Google Scholar
  50. Fleurette J, Brun Y, Coulet M, Forey F. A comparison of the invitroactivity of roxithromycin and five other macrolides on staphylococci. British Journal of Clinical Practice 42 (Suppl. 55): 13–14, 1988Google Scholar
  51. Fournet M-P, Zini R, Deforges L, Duval J, Tillement J-P. Determination of binding parameters of macrolides, lincosamides, and streptogramins to Legionellapneumophila.Journal of Pharmaceutical Sciences 76: 153–156, 1987PubMedGoogle Scholar
  52. Gerlach EH, Farkas M, Johnson K, Weiler R, Raymon J. Susceptibility of Chlamydia trachomatis to a new macrolide, RU 965. Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, 1986Google Scholar
  53. Goldstein EJC, Citron DM, Vagvolggi AE, Finegold SM. Susceptibility of bite wound bacteria to seven oral antimicrobial agents, including RU-985, a new erythromycin: considerations in choosing empiric therapy. Antimicrobial Agents and Chemotherapy 29: 556–559, 1986PubMedGoogle Scholar
  54. Goossens H, De Moi P, Coignau H, Levy J, Grados O, et al. Comparative invitroactivities of aztreonam, ciprofloxacin, norfloxacin, ofloxacin, HR 810 (a new cephalosporin), RU 28965(a new macrolide), and other agents against enteropathogens. Antimicrobial Agents and Chemotherapy 27: 388–392, 1985PubMedGoogle Scholar
  55. Grassi C, Bartucci F, Sassella D. Efficacy and safety of roxithromycin in respiratory tract infections. British Journal of Clinical Practice 42 (Suppl. 55): 104–105, 1988Google Scholar
  56. Grassi C, Bertoletti R, de Rose V, Manara G, Mangiarotti P. Roxithromycin (RU 28965) in the treatment of respiratory tract infections. Chemioterapia 6: 41–44, 1987PubMedGoogle Scholar
  57. Hand WE, King-Thompson N, Holman JW. Entry of roxithromycin (RU 965), imipenem, cefotaxime, trimethoprim and metronidazole into human polymorphonuclear leukocytes. Antimicrobial Agents and Chemotherapy 31: 1553–1557, 1987PubMedGoogle Scholar
  58. Hara K, Suyama N, Yamaguchi K, Kohno S, Saito A. Activity of macrolides against organisms responsible for respiratory infection with emphasis on Mycoplasmaand Legionella.Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 75–80, 1987PubMedGoogle Scholar
  59. Herron JM. Roxithromycin in the therapy of Streptococcuspyogenesthroat infections. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 139–144, 1987PubMedGoogle Scholar
  60. Hubrechts JM, Kupperberg A, Smets P, Dramaix M, Valante F, et al. Multicentre comparative study of oral roxithromycin and amoxycillin in the treatment of respiratory tract infections. British Journal of Clinical Practice 42 (Suppl. 55): 102–103, 1988Google Scholar
  61. Jones RN, Barry AL. Unpredictable influence of human sera on antimicrobial activity of erythromycin and three oxime ether macrolides. European Journal of Clinical Microbiology 6: 81–82, 1987PubMedGoogle Scholar
  62. Jones RN, Barry AL, Fuchs PC, Thornsberry C. Disk diffusion susceptibility testing of two macrolide antimicrobial agents: Revised interpretative criteria for erythromycin and preliminary guidelines for roxithromycin (RU965). Journal of Clinical Microbiology 24: 233–239, 1986PubMedGoogle Scholar
  63. Jones RN, Barry AL, Thornsberry C. In vitro evaluation of three new macrolide antimicrobial agents, RU 28965, RU 29065, and RU 29702, and comparisons with other orally administered drugs. Antimicrobial Agents and Chemotherapy 24: 209–215, 1983PubMedGoogle Scholar
  64. Jones RN, McDougal LK, Thornsberry C. Inhibition and hydrolysis of beta-lactamases found in Legionellaspecies: antimicrobial activity of new macrolides on legionellae. In Thornsberry (Ed). Legionella, proceedings of an international symposium, pp. 100–103, American Society of Microbiology, Washington, 1984Google Scholar
  65. Jorgensen JH, Redding JS, Howell AW. In vitro activity of the new macrolide antibiotic roxithromycin (RU 28965) against clinical isolates of Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 29: 921–922, 1986PubMedGoogle Scholar
  66. Kafetzis DA, Blanc F: Efficacy and safety of roxithromycin in treating paediatric patients: a European multicentre study. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 171–177, 1987PubMedGoogle Scholar
  67. Kafetzis DA, Krotsi-Laskari M, Tremblay D, Saint-Salvi B. Multiple dose pharmacokinetic in infants and children treated with roxithromycin. British Journal of Clinical Practice 42 (Suppl. 55): 58, 1988Google Scholar
  68. Kafetzis DA, Ligatsikas C, Saint-Salvi B, Lenfant B. Concentrations of roxithromycin in tonsil and adenoid tissues after single and repeated administrations to children. British Journal of Clinical Practice 42 (Suppl. 55): 80, 1988Google Scholar
  69. Karthein P, Spohr M, Traub WH. Josamycin: interpretation of inhibition zones with the Bauer-Kirby agar disk diffusion test as compared with erythromycin. Chemotherapy 32: 336–343, 1986PubMedGoogle Scholar
  70. Kazmierczak A, Pechinot A, Tillement JP, Barre J, Chretien P, et al. Roxithromycin pharmacokinetic compared with those of spiramycin and trolandomycin after a single oral dose. Inter-science Congress on Antimicrobial Agents and Chemotherapy, Los Angeles, 1988Google Scholar
  71. Kees F, Grobecker H, Fourtillan JB, Tremblay D, Saint-Salvi B. Comparative pharmacokinetics of single dose roxithromycin (150mg) versus erythromycin stearate (500mg) in healthy volunteers. British Journal of Clinical Practice 42 (Suppl. 55): 51, 1988Google Scholar
  72. Khurana CM, Deddish PA. Invitroefficacy of RU 965 and erythromycin against clinical isolates of Chlamydia trachomatis(CT). 25th Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, September 29–October 2, 1985Google Scholar
  73. King A, Phillips I. The invitroactivity of roxithromycin, a new macrolide antibiotic, in comparison with that of erythromycin. Drugs Under Experimental and Clinical Research 13: 563–566, 1987PubMedGoogle Scholar
  74. Koopman JP, van den Brink ME, Scholten PM, Hectors MPC. Influence of roxithromycin and erythromycin on the gastrointestinal ecology of mice. British Journal of Clinical Practice 42 (Suppl. 55): 43–46, 1988Google Scholar
  75. Kuenzi B, Segessenmann Ch, Gerber AU. Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against selected Gram-positive bacteria and Haemophilus influenzae. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 39–46, 1987PubMedGoogle Scholar
  76. Kurzynski TA, Boehm DM, Rott-Petri JA, Schell RF, Allison PE. Antimicrobial susceptibilities of Bordetellaspecies isolated in a multicenter pertussis surveillance project. Antimicrobial Agents and Chemotherapy 32: 137–140, 1988PubMedGoogle Scholar
  77. Labro MT, Amit N, Babin-Chevaye C, Hakim J. Synergy between RU 28965 (roxithromycin) and human neutrophils for bactericidal activity invitro. Antimicrobial Agents and Chemotherapy 30: 137–142, 1986PubMedGoogle Scholar
  78. Labro MT, Bryskier A, Babin-Chevaye C, Hakim J. Interaction de la toxythromycine avec le polynucleaire neutrophile humain invitroet exvivo.Pathologie Biologie 36: 711–714, 1988PubMedGoogle Scholar
  79. Lachat JM, Anex JF, Regamey C. Roxithromycin (RU 28965), un nouveau macrolide efficace dans les infections pulmonaires. Schweizerische Medizinische Wochenschrift 116: 1739–1741, 1986PubMedGoogle Scholar
  80. Larrey D, Funck-Brentano C, Breil P, Vitaux J, Theodore C, et al. Effects of erythromycin on hepatic drug-metabolising enzymes in humans. Biochemical Pharmacology 32: 1058–1063, 1983Google Scholar
  81. Larrey D, Tinel M, Pessayre D. Formation of inactive cytochrome P-450 FE(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats. Biochemical Pharmacology 32: 1487–1493, 1983PubMedGoogle Scholar
  82. Lassman HB, Puri SK, Ho I, Sabo R, Barry A. Influence of food on the absorption of RU28965 (a new macrolide antibiotic) from film-coated tablets in healthy men. In Butzler & Kobayashi (Eds) Macrolides: a review with an outlook on future developments, pp. 138–142, Excerpta Medica, Amsterdam, 1986Google Scholar
  83. Lassus A, Seppala A. Roxithromycin in non-gonococcal urethritis. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 157–165, 1987PubMedGoogle Scholar
  84. Lebrec D, Benhamou JP, Fourtillan JB, Tremblay D. Roxithromycin: pharmacokinetics in patients suffering from alcoholic cirrhosis. British Journal of Clinical Practice 42 (Suppl. 55): 63, 1988Google Scholar
  85. ebourg-Pigeonniere G, d’Enfent J, Fiessinger S. Etude multi-centrique de l’efficacite clinique et de la tolerance de la roxithromycine (Rulid) dans les infections respiratoires. Réunion Interdisciplinaire de Chimiothérapie Antiinfectieuse, Paris, December 3, 1987Google Scholar
  86. Ludden TM. Pharmacokinetic interactions of the macrolide antibiotics. Clinical Pharmacokinetics 10: 63–79, 1985PubMedGoogle Scholar
  87. Luft BJ. In vivo and in vitro activity of roxithromycin against Toxoplasma gondii in mice. European Journal of Clinical Microbiology 6: 479–481, 1987PubMedGoogle Scholar
  88. Luft BJ, Hofflin J, Chen J, Remington JS. The activity of RU 28965, a macrolide, in the treatment of toxoplasmic encephalitis. Interscience Congress on Antimicrobial Agents and Chemotherapy, New Orleans, 1986Google Scholar
  89. Lukehart SA, Baker-Zander SA. Roxithromycin (RU 965): effective therapy for experimental syphilis infection in rabbits. Antimicrobial Agents and Chemotherapy 31: 187–190, 1987PubMedGoogle Scholar
  90. Mandell GL. Toxicity of macrolides. In Butzler & Kobayashi (Eds) Macrolides: a review with an outlook on future developments, pp. 30–33, Excerpta Medica, Amsterdam, 1986Google Scholar
  91. Marsac J, Akoun G, Balmes P, Butaeye P, Charpin J, et al. Multi-centre comparative study of the efficacy and safety of roxithromycin and doxycycline in the treatment of lower respiratory tract infection. British Journal of Clinical Practice 42 (Suppl. 55): 100–101, 1988Google Scholar
  92. Matsumoto F, Hara K. Multicentre clinical studies of roxithromycin in respiratory, otorhinolaryngological, skin and dental infections, and chlamydial sexually transmitted diseases. 15th International Congress of Chemotherapy, Istanbul, July 19–24, 1987Google Scholar
  93. Mattina R, Bonfiglio G, Bruno E, Gianni AB, Porcellini A. Distribution of roxithromycin in odontological tissue. International Meeting on the Present and Future of the Therapy of Infections, Punta Ala, September 9, 1988Google Scholar
  94. McDonald PJ, Craig WA, Kunin CM. Persistent effect of antibiotics on Staphylococcusaureusafter exposure for limited periods of time. Journal of Infectious Diseases 135: 217–223, 1977PubMedGoogle Scholar
  95. McLean A, Sutton JA, Salmon J, Chatelet D. Roxithromycin: pharmacokinetic and metabolism study in humans. British Journal of Clinical Practice 42 (Suppl. 55): 52–53, 1988Google Scholar
  96. Meirovich CI, Monkrull H, Strusberg AM, Brizuela N, Forti IN. Roxithromycin levels in synovial fluid. British Journal of Clinical Practice 42 (Suppl. 42): 88, 1988Google Scholar
  97. Melcher GP, Winn RE, Hadfield TL. Comparative efficacy, toxicity and compliance of RU 965 versus erythromycin ethylsuccinate (EES) for streptococcal pharingitis (SP). ASM annual meeting, Atlanta, March 1–6, 1987Google Scholar
  98. Morel P, Claudy A, Forrester JF, Garrel J, Grosshans E, et al. Multicentre study of the efficacy and safety of roxithromycin in comparison with doxycycline in male urethritis and in non-gonococcal cervicovaginitis. British Journal of Clinical Practice 42 (Suppl. 55): 108–109, 1988Google Scholar
  99. NCCLS. Thornsberry C, et al. (Eds). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. National Committee for Clinical Laboratory Standards publication M7-A, NCCLS, Villanova, Pa., 1985Google Scholar
  100. Nicoletti G, Pellegrino MB, Blandino G, Spéciale A. In vitro activity of RU 28965, a new macrolide, in comparison with erythromycin and ampicillin against Haemophilus species. In Butzler & Kobayashi (Eds) Macirolides: a review with an outlook on future development, pp. 118–120, Excerpta Medica, Amsterdam, 1986Google Scholar
  101. Nilsen OG. Comparative pharmacokinetics of macrolides. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 81–88, 1987PubMedGoogle Scholar
  102. Nilsen O, Saint-Salvi B, Lenfant B, Tremblay D, Manuel C. Pharmacokinetics of roxithromycin in the elderly: linearity and repeat dose studies. British Journal of Clinical Practice 42 (Suppl. 55): 59–60, 1988Google Scholar
  103. Pascual A, Borobio V, Garcia-Iglesias MC, Perea EJ. Comparative invitroactivity of cefodizime, cefpirome, carumonam and RU-28965 with other antimicrobials against anaerobes. Journal of Antimicrobial Chemotherapy 19: 701–703, 1987PubMedGoogle Scholar
  104. Pechere J-C, Auckenthaler R. In vitro activity of roxithromycin against respiratory and skin pathogens. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 1–5, 1987PubMedGoogle Scholar
  105. Pedreira W, Bazet C, Galiana A, Fraga F. Efficacy of a new macrolide in genital tract infections caused by Chlamydiatrachomatis. British Journal of Clinical Practice 42 (Suppl. 55): 112, 1988Google Scholar
  106. Plascencia-Hernandez A, Ponce de Leon A, Navarro-Hernandez C, Ortiz-Covarrubias A, De la Cabada FJ, et al. Comparative efficacy and safety of roxithromycin and erythromycin in treatment of upper respiratory tract infections in children. 27th Interscience Congress of Antimicrobial Agents and Chemotherapy, New York, 1987Google Scholar
  107. Prieto Prieto J, Minguez F, Ortega P, Corrales I, Ledesma V. Comparative study of the effects of roxithromycin and other macrolides on polymorphonuclear white cells invitro. British Journal of Clinical Practice 42 (Suppl. 55): 38–39, 1988Google Scholar
  108. Puri SK, Lassman HB. Roxithromycin: a pharmacokinetic review of a macrolide. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 89–100, 1987PubMedGoogle Scholar
  109. Rahlwes M, Wagner J, Schuster L, Berntsson E, Ruckdeschel G, et al. Prospective study of the aetiology of community-acquired pneumonia and comparison of amoxycillin and roxithromycin therapy. 15th International Congress of Chemotherapy, Istanbul, July 19–24, 1987Google Scholar
  110. Ridgway GL. The in vitro activity of macrolides against Chlamydia trachomatis and the genital mycoplasmas. In Butzler & Kobayashi (Eds) Macrolides: a review with an outlook on future developments, pp. 69–73, Excerpta Medica, Amsterdam, 1986Google Scholar
  111. Ridgway GL. A review of the invitroactivity of roxithromycin against genital pathogens. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 7–11, 1987PubMedGoogle Scholar
  112. Rimoldi R, Mangiarotti P, Dc Rose V, Nonis A, Bertoletti R, et al. Penetration of roxithromycin into bronchial secretions. British Journal of Clinical Practice 42 (Suppl. 55): 74–77, 1988Google Scholar
  113. Rolston KVI, LeBlanc B, Ho DH. In vitro activity of RU 28965, a new macrolid, compared to that of erythromycin. Journal of Antimicrobial Chemotherapy 17: 161–163, 1986PubMedGoogle Scholar
  114. Saint-Salvi B, Tremblay D, Surjus A, Lefebvre MA. A study of the interaction of roxithromycin with theophylline and carbamazepine. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 121–129, 1987PubMedGoogle Scholar
  115. Sanson-Le-Pors MJ, Casin IM, Thebault MC, Arlet G, Perol Y. In vitro activities of U-63366, a spectinomycin analog; roxithromycin (RU 28965), a new macrolide antibiotic; and five quinolone derivatives against Haemophilus ducreyi. Antimicrobial Agents and Chemotherapy 30: 512–513, 1986PubMedGoogle Scholar
  116. Santos Ferreira MO, Vital JO. Invitrocomparison of the activity of roxithromycin, a new macrolide compound, with that of erythromycin against clinical isolates in Portugal. 15th International Congress of Chemotherapy, Istanbul, July 19–24, 1987Google Scholar
  117. Sasaki J. Clinical evaluation of roxithromycin in odontogenic orofacial infections. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 167–170, 1987PubMedGoogle Scholar
  118. Segre G, Bianchi E, Zanolo G, Bartucci F, Sassella D. Influence of food on the bioavailability of roxithromycin versus erythromycin stearate. British Journal of Clinical Practice 42 (Suppl. 55): 55–57, 1988Google Scholar
  119. Shah PM, Schäfer V, Hubener T, Metz C, Stille W. Bactericidal activity of ofloxacin versus roxithromycin in the treatment of Streptococcuspneumoniae.Drugs 34 (Suppl. V): 9–13, 1987PubMedGoogle Scholar
  120. Shah PM, Schafer V, Metz C, Stille W. Bactericidal activity of roxithromycin compared with that of erythromycin and doxycycline against Streptococcuspneumoniae. British Journal of Clinical Practice 42 (Suppl. 55): 10–12, 1988Google Scholar
  121. Stamboulian D, Fernandez-MacLoughlin GJ, Lanoël JL, Sarachian B. Clinical evaluation of roxithromycin in 101 children. British Journal of Clinical Practice 42 (Suppl. 55): 115–116, 1988Google Scholar
  122. Stamm WE, Suchland R. Antimicrobial activity of U-70138 F (paldimycin), roxithromycin (RU 965), and ofloxacin (ORF 18489) against Chlamydiatrachomatisin cell culture. Antimicrobial Agents and Chemotherapy 30: 806–807, 1986PubMedGoogle Scholar
  123. Steiner G, Huber W, Wutz R, Neumann M, Janistyn W, et al. Roxithromycin: a safe and efficacious antibiotic in the treatment of lower respiratory tract infections. British Journal of Clinical Practice 42 (Suppl. 55): 96–97, 1988Google Scholar
  124. Tremblay D, Jaeger H, Fourtillan JB, Manuel C. Pharmacokinetics of three single doses (150, 300, 450mg) of roxithromycin in young volunteers. British Journal of Clinical Practice 42 (Suppl. 55): 49–50, 1988Google Scholar
  125. Tremblay D, Meyer B, Saint-Salvi B, Robinet D. Influence of food on bioavailability of roxithromycin (RU 28965). Acta Pharmacologica et Toxicologica 59 (Suppl. V): 191, 1986Google Scholar
  126. Tremblay D, Mignot A, Couraud L, Saux MC, Manuel C. Concentrations of roxithromycin in lung tissue after repeat dosing. British Journal of Clinical Practice 42 (Suppl. 55): 73, 1988Google Scholar
  127. Tremblay D, Verger C, Saint-Salvi B, Robinet D, Manuel C. Pharmacokinetics of roxithromycin in chronic renal insufficiency. British Journal of Clinical Practice 42 (Suppl. 55): 61, 1988Google Scholar
  128. Tsuboi Y, Sakoda T, Mitsuhashi S. In vitro and in vivo antibacterial activity of roxithromycin. British Journal of Clinical Practice 42 (Suppl 55): 30–32, 1988Google Scholar
  129. van der Willigen AH, Tjiam KH, Wagenvoort JHT, Polak-Vogelzang AA, Michel MF, et al. Evaluation of roxithromycin in the treatment of non-gonococcal urethritis in males. European Journal of Clinical Microbiology 5: 612–614, 1986PubMedGoogle Scholar
  130. Vitse M, Orfila J, Lavallard C, Eb F. Study of clinical efficacy and safety of roxithromycin in the treatment of non-gonococcal infections of the lower genital tract. British Journal of Clinical Practice 42 (Suppl. 55): 107, 1988Google Scholar
  131. Vollaard EJ, Clasener HAL, van Griethuysen AJA, Janssen AJ, Sanders-Reijmers AJ. Influence of amoxycillin, erythromycin and roxithromycin on colonization resistance and on appearance of secondary colonization in healthy volunteers. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 131–138, 1987PubMedGoogle Scholar
  132. Wise R, Kirkpatrick B, Ashby J, Andrews JM. Pharmacokinetics and tissue penetration of roxithromycin after multiple dosing. Antimicrobial Agents and Chemotherapy 31: 1051–1053, 1987PubMedGoogle Scholar
  133. Wollmer P, Rhodes CG, Pike VW. Measurement of pulmonary ervthromycin concentrations in patients with lobar pneumoniae by means of positron tomography. Lancet 2: 1361–1363, 1982PubMedGoogle Scholar
  134. Yokota T, Bhattacharya I. Synergy of bactericidal effect between roxithromycin and human leucocytes against .Saureus. British Journal of Clinical Practice 42 (Suppl. 55): 40–42, 1988Google Scholar
  135. Zeluff BJ, Lowe P, Koornhof H, Gentry LO. A comparative study of a new macrolide antibiotic (RU-965) and cephradine in mild to moderate pneumococcal pneumonia. Interscience Congress of Antimicrobial Agents and Chemotherapy, New Orleans, 1986Google Scholar
  136. Zini R, Fournet MP, Barre J, Tremblay D, Tillement JP. In vitro study of roxithromycin binding to serum proteins and erythrocytes in humans. British Journal of Clinical Practice 42 (Suppl. 55): 54, 1988Google Scholar

Copyright information

© ADIS Press Limited 1989

Authors and Affiliations

  • Ronald A. Young
    • 1
    • 2
    • 3
  • John P. Gonzalez
    • 1
    • 2
    • 3
  • Eugene M. Sorkin
    • 1
    • 2
    • 3
  1. 1.University of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Manchester International Office CentreADIS Press International LtdWythenshaweEngland
  3. 3.ADIS Drug Information ServicesAucklandNew Zealand

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