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Clarithromycin

A Review of its Efficacy in the Treatment of Respiratory Tract Infections in Immunocompetent Patients

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Summary

Synopsis

Clarithromycin is a broad spectrum macrolide antibacterial agent active in vitro and effective in vivo against the major pathogens responsible for respiratory tract infections in immunocompetent patients. It is highly active in vitro against pathogens causing atypical pneumonia (Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp.) and has similar activity to other macrolides against Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis and Streptococcus pneumoniae. Haemophilus influenzae is susceptible or intermediately susceptible to clarithromycin alone, but activity is enhanced when the parent drug and metabolite are combined in vitro.

Absorption of clarithromycin is unaffected by food. More than half of an oral dose is systemically available as the parent drug and the active 14-hydroxy metabolite. Pharmacokinetics are nonlinear, with plasma concentrations increasing in more than proportion to the dosage. First-pass metabolism results in the rapid appearance of the active metabolite 14-hydroxy-tiarithromycin in plasma. Clarithromycin and its active metabolite are found in greater concentrations in the tissues and fluids of the respiratory tract than in plasma. Dosage adjustments are required for patients with severe renal failure, but not for elderly patients or those with hepatic impairment. Drug interactions related to the cytochrome P450 system may occur with clarithromycin use.

In addition to the standard immediate-release formulation for administration twice daily, a modified-release formulation of clarithromycin is now available for use once daily.

In dosages of 500 to 1000 mg/day for 5 to 14 days, clarithromycin was as effective in the treatment of community-acquired upper and lower respiratory tract infections in hospital and community settings as β-lactam agents (with or without a β-lactamase inhibitor), cephalosporins and most other macrolides. Clarithromycin was similar in efficacy to azithromycin in comparative studies and is as effective as and better tolerated than erythromycin. Adverse events are primarily gastrointestinal in nature, but result in fewer withdrawals from therapy than are seen with erythromycin.

Clarithromycin provides similar clinical and bacteriological efficacy to that seen with β-lactam agents, cephalosporins and other macrolides. It offers a cost-saving alternative to intravenous erythromycin use in US hospitals and is available in both once-daily and twice-daily formulations. The spectrum of activity of clarithromycin against common and emerging respiratory tract pathogens may make it suitable for use in the community as empirical therapy of respiratory tract infections in both children and adults.

Antibacterial Activity

The activity of clarithromycin against most respiratory pathogens in vitro is similar to that of other macrolides. Streptococcus pyogenes isolates showed excellent susceptibility to clarithromycin. Clarithromycin is very active against pathogens causing atypical pneumonia (Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila) and against Moraxella catarrhalis. The only characterised resistance pattern results in cross-resistance between macrolides, as seen in strains of Staphylococcus aureus and Streptococcus pyogenes. Isolates that are susceptible to erythromycin or penicillin are also susceptible to clarithromycin. Haemophilus influenzae is susceptible or intermediately susceptible to clarithromycin alone. The combination of the parent drug and metabolite shows at least additive if not synergistic activity, such that Haemophilus influenzae is susceptible in vitro to the combination. 14-Hydroxy-clarithromycin was also active against L pneumophila isolates.

In vitro studies in blood show that clarithromycin is active against bacteria both intra-and extracellularly. Postantibiotic effects may occur with some species and bactericidal effects are seen with H. influenzae, Streptococcus pneumoniae, and possibly M. catarrhalis. In addition to its antimicrobial effects, clarithromycin appears to improve immune function and improves the viscoelastic properties of mucus and sputum.

Pharmacokinetic Properties

Absorption of clarithromycin is unaffected by food, oral bioavailability of the parent drug is 52 to 55% and first-pass metabolism produces the active 14-hydroxy metabolite. Pharmacokinetics are nonlinear as a result of hepatic elimination, with capacity-limited formation of the active 14-hydroxy metabolite occurring at doses >600mg. Total body clearance decreases and the elimination half-life increases with increasing dose, whereas plasma concentrations and the area under the plasma concentration-time curve (AUC) increase more than proportionately with increases in the dose. However, once steady-state is reached, no accumulation occurs with additional doses administered.

Clarithromycin is not extensively protein bound but has a volume of distribution of 191 to 306L. Concentrations of the drug in respiratory tract tissues and fluids greatly exceed those in plasma. Furthermore, tissue concentrations of both clarithromycin and 14-hydroxy-clarithromycin exceed the MICs for most respiratory pathogens. About 40% of the drug is removed from the body in the faeces and ≈53% in the urine.

Reductions in clarithromycin clearance seen in elderly patients and those with hepatic disease were well tolerated and do not appear to require dosage adjustments. In patients with renal failure, however, plasma concentrations and AUC values of the parent drug and active metabolite increase markedly, necessitating dosage reductions in patients with creatinine clearance (CLCR) values of ≤30 ml/min (≤1.8 L/h). Clarithromycin is found in breastmilk of nursing mothers treated with the drug.

A modified-release formulation of clarithromycin has been developed to allow administration of the drug once daily. This formulation delivers the same peak and trough concentrations of the parent drug and metabolite and reaches equivalent AUC values to those seen with the twice-daily immediate-release formulation in the 24 hours after administration. The elimination half-life of clarithromycin and its 14-hydroxy metabolite are unaltered by formulation, although peak plasma concentrations are delayed with the once-daily dosage form.

Clinical Efficacy

Results of comparative trials in adults have shown similar efficacy for clarithromycin and other antibacterial drugs in the treatment of community-acquired pneumonia, acute bronchitis, acute exacerbations of chronic bronchitis (AECB), sinusitis, pharyngitis and otitis media. Comparator agents included the β-lactam agents ampicillin, amoxicillin with or without clavulanic acid, phenoxymethyl-penicillin (penicillin V), the cephalosporins cefaclor, cefuroxime axetil, cefpodoxime proxetil, ceftibuten and cefixime, and the macrolides erythromycin, azithromycin, dirithromycin, roxithromycin and josamycin.

Clarithromycin 250mg twice daily for 5 days was as effective in the treatment of acute bronchitis as a 10-day course of the same daily dosage. No statistically significant differences in efficacy were apparent between smoking and nonsmoking patients or between elderly (≥65 years) and younger patients receiving clarithromycin. In hospitalised patients with community-acquired pneumonia who were also receiving intravenous cefuroxime, oral clarithromycin was as effective as intravenous erythromycin, and intravenous clarithromycin followed by oral clarithromycin was as effective as intravenous followed by oral erythromycin.

In children aged 5 months to 16 years, comparative trials have shown generally similar efficacy for clarithromycin and other antibacterial drugs in the treatment of pneumonia, acute bronchitis, pharyngitis and otitis media. Comparator agents with similar efficacy included amoxicillin, azithromycin, erythromycin, cefaclor, cefixime, clindamycin, cefadroxil and benzathine penicillin. A recent non-comparative Japanese study has shown clarithromycin to be an effective treatment of sinusitis associated with otitis media in children. Clarithromycin tended to produce better clinical success and bacteriological eradication than amoxicillin/clavulanic acid in patients with streptococcal pharyngitis and acute bronchitis and produced similar clinical efficacy but superior bacterial eradication to phenoxymethylpenicillin in patients with streptococcal pharyngitis.

Tolerability

Clarithromycin is generally well tolerated, with most adverse events being mild to moderate. The most common events were diarrhoea, abnormal taste, nausea, dyspepsia, headache and abdominal pain or discomfort, leading to treatment withdrawal rate of <3%. A similar pattern but slightly higher incidence of events occurs in children, but leads to treatment discontinuation in <2% of patients.

Fewer digestive tract adverse events and withdrawals from treatment occur with clarithromycin than erythromycin or amoxicillin/clavulanic acid.

Drug Interactions

Clarithromycin inhibits the cytochrome P450 3A enzyme (CYP3A) and its metabolism is affected by P450 enzyme induction. Thus, interactions increasing plasma concentrations and possible adverse effects of theophylline, cyclosporin, tacrolimus, carbamazepine, digoxin and rifabutin may necessitate therapeutic drug monitoring and dosage adjustments. Both rifampicin and rifabutin may induce clarithromycin metabolism. Clarithromycin may inhibit metabolism of omeprazole and omeprazole may inhibit the metabolism and/or increase the absorption of clarithromycin. Concomitant clarithromycin may also interact with zidovudine, ritonavir, methylprednisolone and loratidine, and can reduce the tolerability of fluoxetine, nitrazepam, ergotamine and possibly terfenadine and oral anticoagulants.

Pharmacoeconomic Considerations

Variations in drug acquisition costs and antimicrobial susceptibility patterns for clarithromycin relative to other alternative therapeutic agents mean that local conditions must always be considered when assessing costs of clarithromycin use. However, in US hospitals, switching patients from intravenous erythromycin or cefuroxime to oral clarithromycin appears to reduce costs without affecting outcomes.

Dosage and Administration

Clarithromycin is usually administered orally, with or without food. Adult dosages for pharyngitis and tonsillitis (10-day courses) and for pneumonia or AECB (7-to 14-day courses) are 500 mg/day (as 1 or 2 doses, depending on the formulation used). AECB caused by H. influenzae (7-to 14-day course) and acute maxillary sinusitis (14-day course) are treated with 1000 mg/day. Paediatric dosages are usually 15 mg/kg/day for 10 days. Dosage adjustments are not usually needed in elderly patients or those with hepatic disease. Dose reductions or prolonged dosage intervals should be used in patients with renal failure (CLCR ≤30 ml/min or ≤1.8 L/h), in whom the use of the once-daily modified-release formulation should be avoided. The safety of clarithromycin has not been established in children <6 months old and the drug should be avoided during pregnancy and in patients with previous hypersensitivity to macrolide drugs. Breastmilk from mothers receiving clarithromycin should not be given to infants until treatment is completed.

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References

  1. Peters DH, Clissold SP. Clarithromycin: a review of its antimicrobial activity, pharmacokinetic properties and therapeutic potential. Drugs 1992 Jul; 44: 117–64

    PubMed  CAS  Google Scholar 

  2. Barradell LB, Plosker GL, McTavish D. Clarithromycin: a review of its pharmacological properties and therapeutic use in Mycobacterium avium-intracellulare complex infection in patients with acquired immune deficiency syndrome. Drugs 1993 Aug; 46: 289–312

    PubMed  CAS  Google Scholar 

  3. Markham A, McTavish D. Clarithromycin and omeprazole: as Helicobacter pylori eradication therapy in patients with H. pylori-associated gastric disorders. Drugs 1996 Jan; 51: 161–78

    PubMed  CAS  Google Scholar 

  4. NCCLS. Performance standards for antimicrobial susceptibility testing; sixth information supplement. NCCLS document M100-S 6. NCCLS, 771 East Lancaster Avenue, Villanova, PA 19085, USA

  5. Barry AL, Fuchs PC, Brown SD. Relative potencies of azithromycin, clarithromycin and five other orally administered antibiotics. J Antimicrob Chemother 1995 Apr; 35: 552–5

    PubMed  CAS  Google Scholar 

  6. Fass RJ. Erythromycin, clarithromycin, and azithromycin: use of frequency distribution curves, scattergrams, and regression analyses to compare in vitro activities and describe cross-resistance. Antimicrob Agents Chemother 1993 Oct; 37: 2080–6

    PubMed  CAS  Google Scholar 

  7. Loza E, Martínez-Beltrán J, Baquero F, et al. Comparative in vitro activity of clarithromycin. Spanish Collaborative Group. Eur J Clin Microbiol Infect Dis 1992 Sep; 11: 856–66

    PubMed  CAS  Google Scholar 

  8. Mortensen JE, Egleton JH. Comparative in vitro activity of furopenem against aerobic bacteria isolated from pediatric patients. Diagn Microbiol Infect Dis 1995 Jul; 22: 301–6

    PubMed  CAS  Google Scholar 

  9. Ono T, Numata K, Nagate T, et al. In vitro and in vivo antibacterial activities of clarithromycin. Chemotherapy (Basel) 1996 May–Jun; 42: 159–69

    CAS  Google Scholar 

  10. Ritchie DJ, Hopefl AW, Milligan TW, et al. In vitro activity of clarithromycin, cefprozil, and other common oral antimicrobial agents against gram-positive and gram-negative pathogens. Clin Ther 1993 Jan–Feb; 15: 107–13

    PubMed  CAS  Google Scholar 

  11. Sader HS, Jones RN, Washington JA, et al. In vitro activity of cefpodoxime compared with other oral cephalosporins tested against 5556 recent clinical isolates from five medical centers. Diagn Microbiol Infect Dis 1993 Aug-Sep; 17: 143–50

    PubMed  CAS  Google Scholar 

  12. Fass RJ. In vitro activity of Bay y 3118, a new quinolone. Antimicrob Agents Chemother 1993 Nov; 37(11): 2348–57

    PubMed  CAS  Google Scholar 

  13. Neu HC, Chin N-x, Gu JW. The in-vitro activity of new streptogramins, RP59500, RP57669 and RP54476, alone and in combination. J Antimicrob Chemother 1992 Jul; 30 Suppl. A: 83–94

    PubMed  CAS  Google Scholar 

  14. Bauernfeind A. In-vitro activity of dirithromycin in comparison with other new and established macrolides. J Antimicrob Chemother 1993; 31 Suppl. C: 39–49

    PubMed  CAS  Google Scholar 

  15. Appelbaum PC, Visalli MA, Ednie LM, et al. Activity of erythromycin, azithromycin and clarithromycin against penicillin susceptible and resistant pneumococci from the US by MIC and time-kill. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  16. Doern GV, Brueggemann A, Holley Jr HP, et al. Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30-center national surveillance study. Antimicrob Agents Chemother 1996 May; 40(5): 1208–13

    PubMed  CAS  Google Scholar 

  17. Waites K, Gray B, Swaitlo E, et al. Susceptibilities of penicillin-resistant Streptococcus pneumoniae collected over a 10 year period to clarithromycin other oral antimicrobials [abstract no. E21]. Presented at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco

  18. Block S, Hedrick J, Harrison CJ, et al. MICs of penicillin-resistant S. pneumoniae (PRSP) from acute otitis media (AOM) [abstract no. E20]. Presented at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco

  19. Neal TJ, O’Donoghue MAT, Ridgway EJ, et al. In-vitro activity of ten antimicrobial agents against penicillin-resistant Streptococcus pneumoniae. J Antimicrob Chemother 1992 Jul; 30: 39–46

    PubMed  CAS  Google Scholar 

  20. Barry AL, Fuchs PC. In vitro activities of a streptogramin (RP59500), three macrolides, and an azalide against four respiratory tract pathogens. Antimicrob Agents Chemother 1995 Jan; 39(1): 238–40

    PubMed  CAS  Google Scholar 

  21. Brown S, Barry AL, Burton P. Susceptibility surveillance of U. S. respiratory pathogen isolates to newer macrolide and azalide antibiotics. Int J Antimicrob Agents 1996; 7(1): 53–8

    PubMed  CAS  Google Scholar 

  22. Prado V, Romero J, Herrera N, et al. Comparative in vitro activity of new oral macrolides against Streptococcus pyogenes strains isolated in chile between 1990 and 1992 [in Spanish]. Rev Med Chil 1993 Oct; 121: 1128–34

    PubMed  CAS  Google Scholar 

  23. Coonan KM, Kaplan EL. In vitro susceptibility of recent North American group A streptococcal isolates to eleven oral antibiotics. Pediatr Infect Dis J 1994 Jul; 13: 630–5

    PubMed  CAS  Google Scholar 

  24. Van Asselt GJ, Sloos JH, Mouton RP, et al. Susceptibility of Streptococcus pyogenes to azithromycin, clarithromycin, erythromycin and roxithromycin in vitro. J Med Microbiol 1995 Nov; 43: 386–91

    PubMed  Google Scholar 

  25. Platsouka E, Constantoulaki S, Dimitropoulos N, et al. A comparison of in vitro activity of ten oral antimicrobial agents against respiratory tract pathogens. J Chemother 1995 Nov; 7 Suppl. 4: 58–60

    PubMed  Google Scholar 

  26. Verbist L, Dhoore F. In vitro susceptibility of recently isolated respiratory tract pathogens to minocycline and comparable antibiotics: a multicentre study. Acta Clin Belg 1994 Dec; 49: 268–73

    PubMed  CAS  Google Scholar 

  27. Hartog B, Degener JE, Van Benthem PPG, et al. Microbiology of chronic maxillary sinusitis in adults: isolated aerobic and anaerobic bacteria and their susceptibility to twenty antibiotics. Acta Otolaryngol 1995; 115: 672–7

    PubMed  CAS  Google Scholar 

  28. Chen SCA, Paul ML, Gilbert GL. Susceptibility of Legionella species to antimicrobial agents. Pathology 1993 Apr; 25: 180–3

    PubMed  CAS  Google Scholar 

  29. Nimmo GR, Bull JZ. In vitro susceptibility of Legionellapneu-mophila and Legionella longbeachae to roxithromycin and other antimicrobials [abstract]. Can J Infect Dis 1995 Jul; 6 Suppl. C: 336

    Google Scholar 

  30. Reda C, Quaresima T, Castellani PM. In-vitro activity of six intracellular antibiotics against Legionella pneumophila strains of human and environmental origin. J Antimicrob Chemother 1994 Apr; 33: 757–64

    PubMed  CAS  Google Scholar 

  31. Johnson DM, Erwin ME, Barrett MS, et al. Antimicrobial activity of ten macrolide, linsosamine and streptogramin drugs tested against Legionella species. Eur J Clin Microbiol Infect Dis 1992 Aug; 11(8): 751–5

    PubMed  CAS  Google Scholar 

  32. Hammerschlag MR, Qumei KK, Roblin PM. In vitro activities of azithromycin, clarithromycin, L-ofloxacin, and other antibiotics against Chlamydia pneumoniae. Antimicrob Agents Chemother 1992 Jul; 36: 1573–4

    PubMed  CAS  Google Scholar 

  33. Roblin PM, Montalban G, Hammerschlag MR. Susceptibilities to clarithromycin and erythromycin of isolates of Chlamydia pneumoniae from children with pneumonia. Antimicrob Agents Chemother 1994 Jul; 38: 1588–9

    PubMed  CAS  Google Scholar 

  34. Welsh L, Gaydos C, Quinn TC. In vitro activities of azithromycin, clarithromycin, erythromycin, and tetracycline against 13 strains of Chlamydia pneumoniae. Antimicrob Agents Chemother 1996 Jan; 40(1): 212–4

    PubMed  CAS  Google Scholar 

  35. Ishida K, Kaku M, Irifune K, et al. In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. Antimicrob Agents Chemother 1994 Apr; 38: 790–8

    PubMed  CAS  Google Scholar 

  36. Focht J, Noesner K. Mycoplasma spp. in respiratory tract infections–incidence and sensitivity to clarithromycin. Poster presented at the Third International Conference on Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  37. Cassell GH, Drnec J, Waites KB, et al. Efficacy of clarithromycin against Mycoplasma pneumoniae. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 47–59

    PubMed  CAS  Google Scholar 

  38. Markham A, Faulds D. Roxithromycin: an update of its antimicrobial activity, pharmacokinetic properties and therapeutic use. Drugs 1994; 48(2): 297–326

    PubMed  CAS  Google Scholar 

  39. Vogel F. A guide to the treatment of lower respiratory tract infections. Drugs 1995; 50(1): 62–72

    PubMed  CAS  Google Scholar 

  40. Ball P. Epidemiology and treatment of chronic bronchitis and its exacerbations. Chest 1995 Aug; 108 (2 Suppl.): 43S–52S

    PubMed  CAS  Google Scholar 

  41. Spiritus EM. Diagnosis and treatment of acute lower respiratory tract infections. Res Staff Phys 1994 Jan; 40(1): 28–34

    Google Scholar 

  42. Niederman MS, Bass JJB, Campbell GD, et al. Guidelines for the initial management of adults with community-acquired pneumonia: diagnosis, assessment of severity, and initial antimicrobial therapy. Am Rev Respir Dis 1993 Nov; 148: 1418–26

    PubMed  CAS  Google Scholar 

  43. Fox RA. Treatment recommendations for respiratory tract infections associated with aging. Drugs Aging 1993 Jan–Feb; 3: 40–8

    PubMed  CAS  Google Scholar 

  44. Quenzer RU, Guay DRP. Antimicrobial management strategies for patients with community-acquired respiratory tract infections. Curr Ther Res 1995 May; 56: 466–77

    Google Scholar 

  45. Reuler JB, Lucas LM, Kumar KL. Sinusitis: a review for generalists. West J Med 1995; 163: 40–8

    PubMed  CAS  Google Scholar 

  46. Craft JC, Siepman N, Palmer RN, et al. Treatment of acute otitis media in children comparing clarithromycin and amoxicillin suspension. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  47. Steigbigel NH. Macrolides and clindamycin. In: Mandell GL, Bennett JE, Dolin R, editors. Mandall, Douglas and Bennett’s Principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995: 334–46

    Google Scholar 

  48. Pozzi E, Grossi E, Pecori A, et al. Azithromycin versus clarithromycin in the treatment of acute exacerbations of chronic bronchitis. Curr Ther Res 1994 Jul; 55(7): 759–64

    Google Scholar 

  49. Barry AL, Fuchs PC, Pfaller MA. Susceptibility of Haemophilus influenzae to clarithromycin alone and in combination with its 14-hydroxy metabolite. Eur J Clin Microbiol Infect Dis 1991 Dec; 10: 1080–1

    PubMed  CAS  Google Scholar 

  50. Barry AL, Brown SD. Reconsideration of the interpretive criteria for clarithromycin against Haemophilus influenzae [abstract]. Presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  51. Bottger EC. Resistance to drugs targeting protein synthesis in mycobacteria. Trends Microbiol 1994 Oct; 2: 416–21

    PubMed  CAS  Google Scholar 

  52. Guggenbichler JP, Georgopoulos A, Scharrer P, et al. Antimicrobial activity of josamycin against erythromycin-resistant staphylococci as compared to roxythromycin and clarithromycin. Infection 1993 Jul–Aug; 21: 259–61

    PubMed  CAS  Google Scholar 

  53. Lonks JR, Medeiros AA. High rate of erythromycin and clarithromycin resistance among Streptococcus pneumoniae isolates from blood cultures from Providence, R.I. Antimicrob Agents Chemother 1993 Sep; 37: 1742–5

    PubMed  CAS  Google Scholar 

  54. Scaglione F, Demartini G, Dugnani S, et al. A new model examining intracellular and extracellular activity of amoxicillin, azithromycin, and clarithromycin in infected cells. Chemotherapy 1993 Nov–Dec; 39: 416–23

    PubMed  CAS  Google Scholar 

  55. Scaglione F, Dugnani S, Demartini G, et al. The postantibiotic effect of clarithromycin and its major human metabolite, 14-hydroxy clarithromycin [letter]. J Antimicrob Chemother 1993 Sep; 32: 507–9

    PubMed  CAS  Google Scholar 

  56. Odenholt-Tornqvist I, Löwdin E, Cars O. Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin on respiratory tract pathogens. Antimicrob Agents Chemother 1995 Jan; 39: 221–6

    PubMed  CAS  Google Scholar 

  57. Lemmen SW, Anding K, Engels I, et al. Bactericidal activity of clarithromycin and cefaclor against Streptococcus pneumoniae and Moraxella catarrhalis in healthy volunteers. J Antimicrob Chemother 1994 Mar; 33: 673–4

    PubMed  CAS  Google Scholar 

  58. Fong IW, Noda D, Zakhari R, et al. Serum bactericidal activity of clarithromycin against respiratory pathogens [abstract]. 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 1993 Jun 12–17; Milan

  59. Tamaoki J, Takeyama K, Tagaya E, et al. Effect of clarithromycin on sputum production and its rheological properties in chronic respiratory tract infections. Antimicrob Agents Chemother 1995 Aug; 39: 1688–90

    PubMed  CAS  Google Scholar 

  60. Rubin BK, Druce H, Ramirez OE, et al. Clarithromycin therapy normalizes nasal mucus properties in patients with sinusitis [abstract]. Am J Respir Crit Care Med 1994 Apr; 149 Pt 2: A605

    Google Scholar 

  61. Tanimoto H, Komatsuzaki K, Okano H, et al. Efficacy of clarithromycin on mucous hypersecretion in chronic airway diseases [abstract]. Can J Infect Dis 1995 Jul; 6 Suppl. C: 405

    Google Scholar 

  62. Tanimoto H, Komatsuzaki K, Okano H, et al. Inhibitory effects of clarithromycin on mucous hyperexcretion in chronic airway diseases [abstract]. 9th Mediterranean Congress of Chemotherapy 1994: 89

  63. Akamatsu H, Niwa Y, Sasaki H, et al. Enhanced effect of clarithromycin on neutrophil function in vitro. J Int Med Res 1996 Mar–Apr; 24: 185–9

    PubMed  CAS  Google Scholar 

  64. Moutard I, Gressier B, Brunet C, et al. Comparison of the in vitro effect of two macrolides (spiramycin and clarythromycin) on neutrophil Superoxide generation [abstract]. Pharmacol Res 1995; 31 Suppl.: 219

    Google Scholar 

  65. Scaglione F, Ferrara F, Dugnani S, et al. Immunostimulation by clarithromycin in healthy volunteers and chronic bronchitis patients. J Chemother 1993 Aug; 5: 228–32

    PubMed  CAS  Google Scholar 

  66. Morikawa K, Watabe H, Araake M, et al. Modulatory effect of antibiotics on cytokine production by human monocytes in vitro. Antimicrob Agents Chemother 1996 Jun; 40: 1366–70

    PubMed  CAS  Google Scholar 

  67. Morikawa K, Oseko F, Morikawa S, et al. Immunomodulatory effects of three macrolides, midecamycin acetate, josamycin, and clarithromycin, on human T-lymphocyte function in vitro. Antimicrob Agents Chemother 1994 Nov; 38: 2643–7

    PubMed  CAS  Google Scholar 

  68. Maeda K, Sawaki M, Kita E, et al. Change in cytokine production in patients with lower respiratory tract infections after chemotherapy with erythromycin or clarithromycin [in Japanese]. Jpn J Chemother 1995 Sep; 43: 825–9

    CAS  Google Scholar 

  69. Chu S-Y, Park Y, Locke C, et al. Drug-food interaction potential of clarithromycin, a new macrolide antimicrobial. J Clin Pharmacol 1992 Jan; 32: 32–6

    PubMed  CAS  Google Scholar 

  70. Chu S-Y, Deaton R, Cavanaugh J. Absolute bioavailability of clarithromycin after oral administration in humans. Antimicrob Agents Chemother 1992 May; 36: 1147–50

    PubMed  CAS  Google Scholar 

  71. Chu S-Y, Sennello LT, Bunnell ST, et al. Pharmacokinetics of clarithromycin, a new macrolide, after single ascending oral doses. Antimicrob Agents Chemother 1992 Nov; 36: 2447–53

    PubMed  CAS  Google Scholar 

  72. Chu S-Y, Wilson DS, Deaton RL, et al. Single-and multipledose pharmacokinetics of clarithromycin, a new macrolide antimicrobial. J Clin Pharmacol 1993 Aug; 33: 719–26

    PubMed  CAS  Google Scholar 

  73. Gan VN, Chu S-Y, Kusmiesz HT, et al. Pharmacokinetics of a clarithromycin suspension in infants and children. Antimicrob Agents Chemother 1992 Nov; 36: 2478–80

    PubMed  CAS  Google Scholar 

  74. Davey PG. The pharmacokinetics of clarithromycin and its 14-OH metabolite. J Hosp Infect 1991 Sep; 19 Suppl. A: 29–37

    PubMed  Google Scholar 

  75. Carbon C. Clinical relevance of intracellular and extracellular concentrations of macrolides. Infection 1995; 23 Suppl. 1: 10–4

    Google Scholar 

  76. Bergogne-Bérézin E. Predicting the efficacy of antimicrobial agents in respiratory infections: is tissue concentration a valid measure? J Antimicrob Chemother 1995; 35: 363–71

    PubMed  Google Scholar 

  77. Wüst J, Hardegger U. Penetration of clarithromycin into human saliva. Chemotherapy (Basel) 1993 Sep–Oct; 39: 293–6

    Google Scholar 

  78. Scaglione F, Pintucci JP, Tassi GF, et al. Penetration of clarithromycin into oral and respiratory tissues. Drug Invest 1993 Aug; 6: 104–9

    Google Scholar 

  79. Tsang KWT, Roberts P, Read RC, et al. The concentrations of clarithromycin and its 14-hydroxy metabolite in sputum of patients with bronchiectasis following single dose oral administration. J Antimicrob Chemother 1994 Feb; 33: 289–97

    PubMed  CAS  Google Scholar 

  80. Fish DN, Gotfried MH, Danziger LH, et al. Penetration of clarithromycin into lung tissues from patients undergoing lung resection. Antimicrob Agents Chemother 1994 Apr; 38: 876–8

    PubMed  CAS  Google Scholar 

  81. Honeybourne D, Kees F, Andrews JM, et al. The levels of clarithromycin and its 14-hydroxy metabolite in the lung. Eur Respir J 1994 Jul; 7: 1275–80

    PubMed  CAS  Google Scholar 

  82. Patel KB, Xuan D, Tessier P, et al. Comparison of the bronchopulmonary pharmacokinetics of clarithromycin, 14-hydroxy-CLA, and azithromycin in healthy volunteers at steady state [abstract]. Can J Infect Dis 1995 Jul; 6 Suppl. C: 254

    Google Scholar 

  83. Gotfried MH, Rodvold KA, Danzinger LH, et al. Intrapulmonary concentrations of clarithromycin and azithromycin at steady-state in normal healthy adults [abstract]. Presented at the 10th Mediterranean Congress of Chemotherapy 1996 Oct 20–25; Antalya

  84. Conte Jr JE, Golden J, Duncan S, et al. Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin and cefuroxime in volunteer subjects. Antimicrob Agents Chemother 1996; 40(7): 1617–22

    PubMed  CAS  Google Scholar 

  85. Conte Jr JE, Golden JA, Duncan S, et al. Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin. Antimicrob Agents Chemother 1995 Feb; 39: 334–8

    PubMed  CAS  Google Scholar 

  86. Gan VN, McCarty JM, Chu S-Y, et al. Penetration of clarithromycin into middle ear fluid of children with acute otitis media. Pediatr Infect Dis J 1997; 16(1): 39–43

    PubMed  CAS  Google Scholar 

  87. Sundberg L, Cederberg Å. Penetration of clarithromycin and its 14-hydroxy metabolite into middle ear effusion in children with secretory otitis media. J Antimicrob Chemother 1994 Feb; 33: 299–307

    PubMed  CAS  Google Scholar 

  88. Kees F, Wellenhofer M, Grobecker H. Serum and cellular pharmacokinetics of clarithromycin 500 mg q.d. and 250 mg b.i.d. in volunteers. Infection 1995 May–Jun; 23: 168–72

    PubMed  CAS  Google Scholar 

  89. Ferrero JL, Bopp BA, Marsh KC, et al. Metabolism and disposition of clarithromycin in man. Drug Metab Dispos 1990 Jul–Aug; 18: 441–6

    PubMed  CAS  Google Scholar 

  90. Nilsen OG, Aamo T, Zahlsen K, et al. Macrolide pharmacokinetics and dose scheduling of roxithromycin. Diagn Microbiol Infect Dis 1992 May–Jun; 15 Suppl. 4: 71S–6S

    PubMed  CAS  Google Scholar 

  91. Chu S-Y, Wilson DS, Guay DRP. Clarithromycin pharmacokinetics in healthy young and elderly volunteers. J Clin Pharmacol 1992 Nov; 32: 1045–9

    PubMed  CAS  Google Scholar 

  92. Chu S-Y, Granneman GR, Pichotta PJ, et al. Effect of moderate or severe hepatic impairment on clarithromycin pharmacokinetics. J Clin Pharmacol 1993 May; 33: 480–5

    PubMed  CAS  Google Scholar 

  93. Sedlmayr T, Peters F, Raasch W, et al. Clarithromycin — pharmacokinetics, clinical effectiveness transmission into breast milk of a new macrolide antibiotic in patients with puerperal infections [in German]. Geburtshilfe Frauenheilkd 1993 Jul; 53: 488–91

    PubMed  CAS  Google Scholar 

  94. Sclar DA, Tartaglione TA, Fine MJ. Overview of issues related to medical compliance with implications for the outpatient management of infectious diseases. Infect Agent Dis 1994; 3(5): 266–73

    CAS  Google Scholar 

  95. Stamler DA. Pharmacokinetics of a new controlled-release formulation of clarithromycin [abstract]. 5th Western Pacific Congress of Chemotherapy and Infectious Disease; 1996 Dec 3; Singapore

  96. Bogossian M. Use of clarithromycin for respiratory infections in general practice [in Portuguese]. Rev Bras Med 1995 May; 52: 500–9

    Google Scholar 

  97. Farhat CK. Use of clarithromycin in respiratory infections in pediatrics. Mod Pediatr 1995 Apr; 31(2): 1–8

    Google Scholar 

  98. Endo LH. The use of clarithromycin in respiratory infections in otorhinolaryngology. Otorrinolaringologia 1995 Jul; 2: 1–8

    Google Scholar 

  99. Bradbury F. Comparison of azithromycin versus clarithromycin in the treatment of patients with lower respiratory tract infections. J Antimicrob Chemother 1993 Jun; 31 Suppl. E: 153–62

    PubMed  Google Scholar 

  100. Fong IW, Laforge J, Dubois J, et al. Clarithromycin versus cefaclor in lower respiratory tract infections. Clin Invest Med 1995 Apr; 18: 131–8

    PubMed  CAS  Google Scholar 

  101. Neu HC, Chick TW. Efficacy and safety of clarithromycin compared to cefixime as outpatient treatment of lower respiratory tract infections. Chest 1993 Nov; 104: 1393–9

    PubMed  CAS  Google Scholar 

  102. Adam D. Clarithromycin in the treatment of respiratory tract infections. Clarithromycin 250 mg b.i.d. for 5 or 10 days in the treatment of adult patients with purulent bronchitis. Infection 1993 Jul–Aug; 21: 265–71

    PubMed  CAS  Google Scholar 

  103. Vincken W, Yernault JC. Efficacy and tolerability of clarithromycin versus azithromycin in the short-course treatment of acute bronchitis. Drug Invest 1993 Sep; 6: 170–5

    Google Scholar 

  104. Wettengel R, Vetter N, Waardenburg FA. Clarithromycin versus cefaclor for the treatment of mild-to-moderate acute bacterial bronchitis. J Antimicrob Chemother 1993 Jun; 31: 963–72

    PubMed  CAS  Google Scholar 

  105. Notario G, Siepman N, Devcich K, et al. Comparative safety and efficacy of clarithromycin and three oral cephalosporins in the treatment of outpatients with bacterial bronchitis. Curr Ther Res 1993 Dec; 54: 628–40

    Google Scholar 

  106. Hosie J, Quinn P, Smits P, et al. A comparison of 5 days of dirithromycin and 7 days of clarithromycin in acute bacterial exacerbation of chronic bronchitis. J Antimicrob Chemother 1995 Jul; 36: 173–83

    PubMed  CAS  Google Scholar 

  107. Fraschini F. Clinical efficacy and tolerance of two new macrolides, clarithromycin and josamycin, in the treatment of patients with acute exacerbations of chronic bronchitis. J Int Med Res 1990 Mar–Apr; 18: 171–6

    PubMed  CAS  Google Scholar 

  108. Bachand Jr RT. Comparative study of clarithromycin and ampicillin in the treatment of patients with acute bacterial exacerbations of chronic bronchitis. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 91–100

    PubMed  Google Scholar 

  109. Aidons PM. A comparison of clarithromycin with ampicillin in the treatment of outpatients with acute bacterial exacerbation of chronic bronchitis. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 101–8

    Google Scholar 

  110. Guay DRP, Craft JC. Comparative safety and efficacy of clarithromycin and ampicillin in the treatment of out-patients with acute bacterial exacerbation of chronic bronchitis. J Intern Med 1992 Mar; 231: 295–301

    PubMed  CAS  Google Scholar 

  111. Ziering W, McElvaine P, Taglieti M. Cedax (Rm) (ceftibuten) in the treatment of acute exacerbation of chronic bronchitis [abstract]. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20: San Francisco

  112. Anzueto A, Jenkinson SG, the Clarithromycin Chronic Bronchitis Study Groups. Safety and efficacy of clarithromycin vs cefuroxime axetil in the treatment of acute bacterial exacerbation of chronic bronchitis. Immunol Infect Dis 1993 Jun; 3: 231–7

    Google Scholar 

  113. Spiritus E. Clarithromycin in the treatment of bacterial exacerbations of chronic bronchitis in smokers. Curr Ther Res 1995 Jan; 56: 16–23

    Google Scholar 

  114. Vogel F. Efficacy and tolerability of clarithromycin in the short-course treatment of acute respiratory tract infections. Drug Invest 1991; 3(4): 205–9

    Google Scholar 

  115. Craft JC, Olson C, Pizzuti D. Clarithromycin in the treatment of lower respiratory tract infection by age. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  116. Leophante P, Chauvin JP. Safety and efficacy of clarithromycin compared with cefpodoxime proxetil in the treatment of acute exacerbation of chronic obstructive pulmonary disease. Poster presented at the Third International Conference on the Macrlides, Azalides and Streptogramins; 1996 Jan; Lisbon

  117. Rizzato G, Montemurro L, Fraioli P, et al. Efficacy of a three day course of azithromycin in moderately severe communityacquired pneumonia. Eur Respir J 1995 Mar; 8: 398–402

    PubMed  CAS  Google Scholar 

  118. Jang TN, Liu CY, Wang FD, et al. A randomized comparative study on the safety and efficacy of clarithromycin and erythromycin in treating community-acquired pneumonia. Chung Hua I Hsueh Tsa Chih Taipei 1995 Apr; 55: 302–6

    PubMed  CAS  Google Scholar 

  119. Chien S-M, Pichotta P, Siepman N, et al. Treatment of community-acquired pneumonia: a multicenter, double-blind, randomized study comparing clarithromycin with erythromycin. Chest 1993 Mar; 103: 697–701

    PubMed  CAS  Google Scholar 

  120. Anderson G, Esmonde TS, Coles S, et al. A comparative safety and efficacy study of clarithromycin and erythromycin stearate in community-acquired pneumonia. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 117–24

    PubMed  Google Scholar 

  121. Gotfried MH, Killian A, Servi R, et al. Oral clarithromycin versus intravenous erythromycin for the treatment of community-acquired pneumonia in hospitalised patients. Poster presented at the Third International Conference on Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  122. Skupien D, Margulis A, Kaczander N, et al. Randomized comparative trial of the safety, efficacy and cost of intravenous cefuroxime plus erythromycin vs intravenous cefuroxime plus oral clarithromycin in the therapy of community-acquired pneumonia. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  123. Straneo G, Scarpazza G. Efficacy and safety of clarithromycin versus josamycin in the treatment of hospitalized patients with bacterial pneumonia. J Int Med Res 1990 Mar-Apr; 18: 164–70

    PubMed  CAS  Google Scholar 

  124. Poirier R. Comparative study of clarithromycin and roxithromycin in the treatment of community-acquired pneumonia. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 109–16

    PubMed  Google Scholar 

  125. Winter JH, Dhillon DP, Coles SJ. Comparison of intravenous clarithromycin (CLAR) with erythromycin/cefuroxime (ERY/CEF) in hospitalised patients with community acquired pneumonia [abstract]. Thorax 1995 Dec; 50 Suppl. 2: A45

    Google Scholar 

  126. Hamedani P, Ali J, Hafeez S, et al. The safety and efficacy of clarithromycin in patients with Legionella pneumoniae. Chest 1991 Dec; 100: 1503–6

    PubMed  CAS  Google Scholar 

  127. Parola D, De Maio F, Minniti R, et al. Clarithromycin in legionnaire’s disease [abstract]. Presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  128. Müller O. Comparison of azithromycin versus clarithromycin in the treatment of patients with upper respiratory tract infections. J Antimicrob Chemother 1993 Jun; 31 Suppl. E: 137–46

    PubMed  Google Scholar 

  129. de Campora E, Camaioni A, Leonardi M, et al. Comparative efficacy and safety of roxithromycin and clarithromycin in upper respiratory tract infections. Diagn Microbiol Infect Dis 1992 May-Jun; 15 (4 Suppl.): 119S–22S

    PubMed  Google Scholar 

  130. Scaglione F. Comparison of the clinical and bacteriological efficacy of clarithromycin and erythromycin in the treatment of streptococcal pharyngitis. Curr Med Res Opin 1990 Jan; 12: 25–33

    PubMed  CAS  Google Scholar 

  131. Schrock CG. Clarithromycin vs penicillin in the treatment of streptococcal pharyngitis. J Fam Pract 1992 Dec; 35: 622–6

    PubMed  CAS  Google Scholar 

  132. Still JG, Palmer R. An evaluation of clarithromycin and penicillin in patients with streptococcal pharyngitis [poster]. Presented at the Second International Conference on the Macrolides, Azalides and Streptogramins; 1994 Jan; Venice

  133. Levenstein JH. Clarithromycin versus penicillin in the treatment of streptococcal pharyngitis. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 67–74

    PubMed  Google Scholar 

  134. Bachand Jr RT. A comparative study of clarithromycin and penicillin VK in the treatment of outpatients with streptococcal pharyngitis. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 75–82

    PubMed  Google Scholar 

  135. Stein GE, Christensen S, Mummaw N. Comparative study of clarithromycin and penicillin V in the treatment of streptococcal pharyngitis. Eur J Clin Microbiol Infect Dis 1991 Nov; 10: 949–53

    PubMed  CAS  Google Scholar 

  136. Dubois J, Saint-Pierre C, Tremblay C. Efficacy of clarithromycin vs. amoxicillin/clavulanate in the treatment of acute maxillary sinusitis. Ear Nose Throat J 1993 Dec; 72: 804–10

    PubMed  CAS  Google Scholar 

  137. Géhanno P, Barry B, Chauvin JP, et al. Clarithromycin versus amoxicillin-clavulanate in acute maxillary sinusitis [in French]. Pathol Biol Paris 1996 Apr; 44: 293–7

    PubMed  Google Scholar 

  138. Calhoun KH, Hokanson JA. Multicenter comparison of clarithromycin and amoxicillin in the treatment of acute maxillary sinusitis. Arch Fam Med 1993 Aug; 2: 837–40

    PubMed  CAS  Google Scholar 

  139. Marchi E. Comparative efficacy and tolerability of clarithromycin and amoxycillin in the treatment of out-patients with acute maxillary sinusitis. Curr Med Res Opin 1990 Jan; 12: 19–24

    PubMed  CAS  Google Scholar 

  140. Karma P, Pukander J, Penttila M, et al. The comparative efficacy and safety of clarithromycin and amoxycillin in the treatment of outpatients with acute maxillary sinusitis. J Antimicrob Chemother 1991 Feb; 27 Suppl. A: 83–90

    PubMed  Google Scholar 

  141. Goumas P, Naxakis S, Bassaris C, et al. Comparative efficacy and tolerability of clarithromycin and cefaclor in the treatment of outpatients with acute maxillary sinusitis. Clin Drug Invest 1997; 13(3): 128–33

    CAS  Google Scholar 

  142. Macklin JL, James I, Kearsley NJ, et al. A single-blind, randomised, comparative study of clarithromycin and amoxycillin suspensions in the treatment of children with lower respiratory tract infections. J Chemother 1993 Jun; 5: 174–80

    PubMed  CAS  Google Scholar 

  143. Padilla N, Figueroa R, Rivera R, et al. Clarithromycin and amoxicillin/clavulanate in the management of streptococcal pharyngotonsillitis. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  144. Castano E, Ortega C, Vallarino D, et al. Comparison of four antibiotics for the treatment of children with streptococcal pharyngitis. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  145. Still JG, Hubbard WC, Poole JM, et al. Comparison of clarithromycin and penicillin VK suspensions in the treatment of children with streptococcal pharyngitis and review of currently available alternative therapies. Pediatr Infect Dis J 1993 Dec; 12 Suppl.: S134–41

    PubMed  CAS  Google Scholar 

  146. Ramet J, Belgian Pediatrician Clarithromycin Workgroup. A comparative safety and efficacy study of clarithromycin and amoxicillin/clavulanate suspensions in the short course treatment of children with acute otitis media. Poster presented at the Third International Conference on Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  147. Coles SJ, Addlestone MB, Kamdar MK, et al. A comparative study of clarithromycin and amoxycillin suspensions in the treatment of pediatric patients with acute otitis media. Infection 1993 Jul–Aug; 21: 272–8

    PubMed  CAS  Google Scholar 

  148. Ramet J, Belgian Pediatrician Clarithromycin Workgroup. Comparative safety and efficacy of clarithromycin and azithromycin in the short course treatment of children with acute otitis media. Clin Drug Invest 1995; 9(2): 61–6

    Google Scholar 

  149. Arguedas AG, Loaiza C, Rodriguez F, et al. Azithromycin versus clarithromycin in the treatment of children with bacteriologically documented acute otitis media with effusions: preliminary results [abstract]. Presented at the 19th International Congress of Chemotherapy; 1995 Jul 16–22; Montreal

  150. Kafetzis DA, Bairamis T, Apostolopoulos N. Five days treatment of acute otitis media in children with clarithromycin. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  151. Syriopoulou V, Pavlopoulou J, Theodoridou M, et al. Clarithromycin vs cefaclor suspension in the treatment of acute otitis media in children. Poster presented at the Third International Conference on Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  152. Zarkovic J, Haider-Salaberger I. Efficacy and safety of clarithromycin compared with amoxicillin/clavulanic acid in children with lower respiratory tract infections. Poster presented at the Third International Converence on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  153. Block S, Hedrick J, Hammerschlag MR, et al. Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate. Pediatr Infect Dis J 1995 Jun; 14: 471–7

    PubMed  CAS  Google Scholar 

  154. Scholz H, Study Group Colleagues. Study of the efficacy and toleration of clarithromycin suspension in children with acute otitis media. Pediatrician 1996 Apr; 27(4): 540–2

    Google Scholar 

  155. Tachibana F, Hiraga S, Ishida T, et al. Clinical efficacy of clarithromycin therapy for chronic sinusitis and secretory otitis media in children. [in Japanese]. Jibi to Rinsho 1994; 87(3): 421–7

    Google Scholar 

  156. Aoyama T, Sunakawa K, Iwata S, et al. Efficacies of short-term treatments of pertussis by clarithromycin (CAM) and azithromycin (AZM): comparisons with the standard regimen by erythromycin (EM) [abstract]. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20: San Francisco

  157. Abbott Laboratories. Clarithromycin prescribing information. North Chicago, Illinois, USA. 1996

  158. Craft JC, Siepman N. Overview of the safety profile of clarithromycin suspension in pediatric patients. Pediatr Infect Dis J 1993 Dec; 12 Suppl. 3: S142–7

    PubMed  CAS  Google Scholar 

  159. Spiritus E. Safety and efficacy evaluation of clarithromycin in elderly patients [abstract]. Presented at the Second International Conference on the Macrolides, Azalides and Streptogramins; 1994 Jan; Venice

  160. Shaheen N, Grimm IS. Fulminant hepatic failure associated with clarithromycin. Am J Gastroenterol 1996 Feb; 91: 394–5

    PubMed  CAS  Google Scholar 

  161. Yew WW, Chau CH, Lee J, et al. Cholestatic hepatitis in a patient who received clarithromycin therapy for a Mycobacterium chelonae lung infection [letter]. Clin Infect Dis 1994 Jun; 18: 1025–6

    PubMed  CAS  Google Scholar 

  162. Nightingale SD, Koster FT, Mertz GJ, et al. Clarithromycin-induced mania in two patients with AIDS. Clin Infect Dis 1995 Jun; 20: 1563–4

    PubMed  CAS  Google Scholar 

  163. Steinman MA, Steinman TI. Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1996 Jan; 27: 143–6

    PubMed  CAS  Google Scholar 

  164. Oteo J A, Gomez-Cadinanos RA, Rosel L, et al. Clarithromycin-induced thrombocytopenic purpura [letter]. Clin Infect Dis 1994 Dec; 19: 1170–1

    PubMed  CAS  Google Scholar 

  165. De Vega T, Blanco S, López C, et al. Clarithromycin-induced leukocytoclastic vasculitis [letter]. Eur J Clin Microbiol Infect Dis 1993 Jul; 12: 563

    PubMed  Google Scholar 

  166. Ohmori S, Ishii I, Kuriya S-I, et al. Effects of clarithromycin and its metabolites on the mixed function oxidase system in hepatic microsomes of rats. Drug Metab Dispos 1993 Mar–Apr; 21: 358–63

    PubMed  CAS  Google Scholar 

  167. Tinel M, Descatoire V, Larrey D, et al. Effects of clarithromycin on cytochrome P-450. Comparison with other macrolides. J Pharmacol Exp Ther 1989 Aug; 250: 746–51

    PubMed  CAS  Google Scholar 

  168. Gersema LM, Porter CB, Russell EH. Suspected drug interaction between cyclosporine and clarithromycin. J Heart Lung Transplant 1994 Mar–Apr; 13: 343–5

    PubMed  CAS  Google Scholar 

  169. Sketris IS, Wright MR, West ML, et al. Possible role of the intestinal P-450 enzyme system in a cyclosporine-clarithromycin interaction. Pharmacotherapy 1996 Mar–Apr; 16: 301–5

    PubMed  CAS  Google Scholar 

  170. Ferrari SL, Goffin E, Mourad M, et al. The interaction between clarithromycin and cyclosporine in kidney transplant recipients. Transplantation 1994 Sep 27; 58: 725–7

    PubMed  CAS  Google Scholar 

  171. Treille S, Quoidbach A, Demol H, et al. Kidney graft dysfunction after drug interaction between clarithromycin and cyclosporin. Nephrol Dial Transplant 1996 Jun; 11: 1192–3

    PubMed  CAS  Google Scholar 

  172. Wolter K, Wagner K, Philipp T, et al. Interaction between FK 506 and clarithromycin in a renal transplant patient. Eur J Clin Pharmacol 1994; 47(2): 207–8

    PubMed  CAS  Google Scholar 

  173. O’Connor NK, Fris J. Clarithromycin-carbamazepine interaction in a clinical setting. J Am Board Fam Pract 1994 Nov–Dec; 7: 489–92

    PubMed  Google Scholar 

  174. Albani F, Riva R, Baruzzi A. Clarithromycin-carbamazepine interaction: a case report. Epilepsia 1993 Jan–Feb; 34: 161–2

    PubMed  CAS  Google Scholar 

  175. Wallace RJ Jr, Brown BA, Griffith DE, et al. Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection. J Infect Dis 1995 Mar; 171: 747–50

    PubMed  Google Scholar 

  176. Griffith DE, Brown BA, Girard WM, et al. Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. Clin Infect Dis 1995 Sep; 21: 594–8

    PubMed  CAS  Google Scholar 

  177. Gustavson LE, Kaiser JF, Edmonds AL, et al. Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state. Antimicrob Agents Chemother 1995 Sep; 39: 2078–83

    PubMed  CAS  Google Scholar 

  178. Gustavson LE, Shi H, Palmer RN, et al. Drug interaction between clarithromycin and fluconazole in healthy subjects [abstract]. Clin Pharmacol Ther 1996 Feb; 59: 185

    Google Scholar 

  179. Ford A, Crocker Smith L, Baltch AL, et al. Clarithromycin-induced digoxin toxicity in a patient with AIDS. Clin Infect Dis 1995 Oct; 21: 1051–2

    PubMed  CAS  Google Scholar 

  180. Midoneck SR, Etingin OR. Clarithromycin-related toxic effects of digoxin [letter]. N Engl J Med 1995 Nov 30; 333: 1505

    PubMed  CAS  Google Scholar 

  181. Ouellet D, Hsu A, Granneman GR, et al. Assessment of the pharmacokinetic interaction between ritonavir (R) and clarithromycin (C) [abstract]. Clin Pharmacol Ther 1996 Feb; 59: 143

    Google Scholar 

  182. Vance E, Watson-Bitar M, Gustavson L, et al. Pharmacokinetics of clarithromycin and zidovudine in patients with AIDS. Antimicrob Agents Chemother 1995 Jun; 39: 1355–60

    PubMed  CAS  Google Scholar 

  183. Pollak PT, Sketris IS, MacKenzie SL. Delirium probably induced by clarithromycin in a patient receiving fluoxetine. Ann Pharmacother 1995 May; 29: 486–8

    PubMed  CAS  Google Scholar 

  184. Horowitz RS, Dart RC, Gomez HF. Clinical ergotism with lingual ischemia induced by clarithromycin-ergotamine interaction. Arch Intern Med 1996 Feb 26; 156: 456–8

    PubMed  CAS  Google Scholar 

  185. Raschal S, Moy J, Richmond GW. Steroid enhancing effects of clarithromycin [abstract]. J Allergy Clin Immunol 1996 Jan; 97 Pt 3: 253

    Google Scholar 

  186. Carr RA, Gustavson LE, Palmer RN, et al. Pharmacokinetic and pharmacodynamic interaction potential between clarithromycin and loratidine. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  187. Honig PK, Wortham DC, Zamani K, et al. Comparison of the effect of the macrolide antibiotics erythromycin, clarithromycin and azithromycin on terfenadine steady-state pharmacokinetics and electrocardiographic parameters. Drug Invest 1994; 7(3): 148–56

    CAS  Google Scholar 

  188. Dempsey CL, Kaley TC, Zenkel J. Drug usage evaluation: clarithromycin as sequential therapy. Hosp Formul 1993 Dec; 28: 999–1001

    PubMed  CAS  Google Scholar 

  189. Ramirez JA, Ahkee S. Early switch from intravenous antimicrobials to oral clarithromycin in the treatment of hospitalized patients with community-acquired pneumonia. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  190. Garrelts JC, Herrington AM. Cost-effective treatment of lower respiratory tract infections. PharmacoEconomics 1996 Jul; 10: 36–58

    PubMed  CAS  Google Scholar 

  191. Stein GE, Mantz SL. Antibiotic utilization and cost analysis in hospitalised patients with community-acquired pneumonia. Hosp Pharm 1995; 30(2): 132–4, 137

    PubMed  CAS  Google Scholar 

  192. Ramirez JA, Ahkee S. Cost-savings associated with early switch from intravenous antimicrobials to oral clarithromycin for the treatment of hospitalized patients with community-acquired pneumonia. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins l996 Jan; Lisbon

  193. Sesin P, Mucciardi N. Rational conversion to oral clarithromycin following IV antibiotic therapy. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  194. Sternon J, Leclerq P, Knepper C. Azithromycin compared with clarithromycin in the treatment of adult patients with acute purulent tracheobronchitis: a cost of illness study. J Int Med Res 1995 Nov–Dec; 23: 413–22

    PubMed  CAS  Google Scholar 

  195. Wool C, Cerutti R, Garbagna N, et al. A cost-effectiveness study of four different antibiotics in the treatment of acute exacerbations of chronic obstructive pulmonary disease. Br J Med Econ 1996; 10: 159–68

    Google Scholar 

  196. Reinharz D, Tessier G, Laurier C, et al. Pharmacoeconomic evaluation of clarithromycin for the treatment of communityacquired pneumonia. Presented at the Second International Conference on the Macrolides, Azalides and Streptogramins; 1994 Jan; Venice

  197. Vogel F, Oberender P. Pharmacoeconomical evaluation: therapy with clarithromycin vs. other antibiotics in the treatment of lower respiratory tract infections. Poster presented at the Third International Conference on the Macrolides, Azalides and Streptogramins; 1996 Jan; Lisbon

  198. Abbott Laboratories. Klaricid XL data sheet. Data on file. Abbott House, Norden Road, Maidenhead, Berkshire, SL6 4XE, England, 1996

  199. Abbott Laboratories. Klaricid U.D. Package Insert. Data on file. Abbott Laboratories Argentina S.A., Sarmiento 1113, 9 Piso, Buenos Aires, Argentina, 1996

  200. Finch RG. Pneumonia: the impact of antibiotic resistance on its management. Microb Drug Resist 1995; 1(2): 149–58

    PubMed  CAS  Google Scholar 

  201. O’Neill SJ, Millar ED, Coles SJ, et al. Safety and efficacy of clarithromycin in the treatment of acute mild to moderate respiratory tract infections. Ir Med J 1991 Mar; 84: 33–5

    PubMed  Google Scholar 

  202. Coles SJ, Macklin JM, Humphreys JM, et al. Safety and efficacy of clarithromycin confirmed in large adult and paediatric UK populations [abstract]. Poster presented at the Third International Conference on Macrolides, Azalides and Slreplogramins 1996 Jan; Lisbon

  203. Barlett JG. IDCPGuidelines: lower respiratory tract infections. Infect Dis Clin Pract 1996 Mar–Apr; 5: 147–66

    Google Scholar 

  204. Edelstein PH. Legionnaires’ disease. Clin Infect Dis 1993 Jun; 16: 741–7

    PubMed  CAS  Google Scholar 

  205. Pfizer Inc. Zithromax (azithromycin capsules). In: Physician’s Desk Reference. Medical Economics: Montvale, New York 1996: 1944-6

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    Heather D. Langtry & Rex N. Brogden

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Various sections of the manuscript reviewed by: A. Anzueto, Department of Pulmonary Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA; E. Bergogne-Berezin, CHU Bichat — Laboratoire de Microbiologie, Paris, France; C. Carbon, Assistance Publique, CHU Bichat — Claude Bernard, Paris, France; R.J. Fass, Division of Infectious Diseases, Department of Internal Medicine, University Hospitals Clinic, Columbus, Ohio, USA; R.G. Finch, Department of Microbiology and Infectious Disease, The City Hospital and University of Nottingham, Nottingham, England; F. Fraschini, Dipartmento di Farmacologia, Università degli Studi di Milano, Milan, Italy; H. Kobayashi, First Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan; J.A. Ramirez, Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA; K.A. Rodvold, Department of Pharmacy Practice, College of Pharmacy, The University of Illinois at Chicago, Chicago, Illinois, USA; W. Vincken, Respiratory Division, Academisch Zeikenhuis, Vrije Universiteit Brussel, Brussels, Belgium; F. Vogel, Krankenhaus Hofheim, Hofheim im Taunus, Germany.

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Langtry, H.D., Brogden, R.N. Clarithromycin. Drugs 53, 973–1004 (1997). https://doi.org/10.2165/00003495-199753060-00006

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