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Clarithromycin inhibits NF-kappaB activation in human peripheral blood mononuclear cells and pulmonary epithelial cells.

Macrolide antibiotics modulate the production of proinflammatory cytokines in vivo and in vitro. Transcription of the genes for these proinflammatory cytokines is regulated by nuclear factor kappaB (NF-kappaB). We examined whether or not clarithromycin inhibits the activation of NF-kappaB induced by tumor necrosis factor alpha (TNF-alpha) or staphylococcal enterotoxin A (SEA) in human monocytic U-937 cells, a T-cell line (Jurkat), a pulmonary epithelial cell line (A549), and peripheral blood mononuclear cells (PBMC). Flow cytometry revealed that clarithromycin suppresses NF-kappaB activation induced by TNF-alpha in U-937 and Jurkat cells in a concentration-related manner. Western blot analysis also demonstrated that clarithromycin inhibits NF-kappaB activation induced by TNF-alpha in U-937, Jurkat, and A549 cells and PBMC and by SEA in PBMC. Western blot analysis of cytoplasmic extracts of A549 cells revealed that this inhibition is not linked to preservation of expression of the IkappaBalpha protein. The chloramphenicol acetyltransferase assay indicated that NF-kappaB-dependent reporter gene expression is suppressed in U-937 cells pretreated with clarithromycin. These findings are consistent with the idea that clarithromycin suppresses the production of proinflammatory cytokines via inhibition of NF-kappaB activation.

Anti-Bacterial Agents↗

The phagosomal environment protects virulent Mycobacterium avium from killing and destruction by clarithromycin.

Murine bone marrow-derived macrophages (Mphis) infected with virulent strains of Mycobacterium avium (TMC 724 and a human clinical isolate) or with an avirulent opaque variant that spontaneously dissociates from the virulent human clinical isolate were subjected to a prolonged and continuous treatment with clarithromycin added at the MIC. The efficiency of this antibiotic in terms of inhibition of bacterial growth and bacterial degradation was evaluated during a 21-day treatment period. Growth was assessed by determination of CFU of intracellular bacteria and by a quantitative ultrastructural analysis which allowed us also to determine the extent of bacterial degradation. A similar treatment was applied to the same strains growing in liquid medium. Our data show that in liquid medium, clarithromycin caused a 90% decrease in CFU within 7 days of treatment. When applied to Mphis infected with virulent M. avium, clarithromycin immediately arrested bacterial growth but was unable to fully kill and degrade intracellularly growing virulent bacteria. After 21 days of treatment, 25% of intracellular bacteria were still morphologically intact. These bacteria resumed growth upon removal of the antibiotic, with a normal replication rate. These bacteria had not become more resistant to the drug, since the MIC was unchanged as compared to the one determined for the initial stock used to infect Mphis. Our data therefore suggest that the intraphagosomal environment protects bacteria from degradation. We propose that the inability of the drug to completely destroy bacteria is the result of a limited accessibility of the drug due to prevention of fusions between the immature phagosomes in which virulent bacteria reside and lysosomes in which clarithromycin accumulates. In accord with our proposal, we show that the avirulent opaque variant, which does not prevent phagosome-lysosome fusions (unpublished data), is finally destroyed by clarithromycin even within the phagosomal environment.

Clarithromycin↗

High levels of resistance to metronidazole and clarithromycin in Helicobacter pylori strains in children.

The aim of the study was to evaluate the prevalence of resistance to amoxicillin, metronidazole, and clarithromycin before treatment of Helicobacter pylori infection in children and to assess the evolution of resistance with time. The study was carried out between 1994 and 1999 with 150 H. pylori-positive children through gastric culture (antimicrobial susceptibility) and histology. All cultured H. pylori strains were sensitive to amoxicillin, 64 (43%) were resistant to metronidazole, 32 (21%) were resistant to clarithromycin, and 14 (9%) were resistant to both metronidazole and clarithromycin. The overall prevalence of resistance to metronidazole and clarithromycin did not change significantly with time. The study highlights the generalized high-level and stable metronidazole and clarithromycin resistance of H. pylori strains from children.

Adolescent↗

Novel real-time PCR assay for detection of Helicobacter pylori infection and simultaneous clarithromycin susceptibility testing of stool and biopsy specimens.

A biprobe real-time PCR protocol, followed by hybridization melting point analysis, to detect point mutations in the 23S rRNA gene of Helicobacter pylori associated with clarithromycin resistance was established and evaluated in a clinical study. Of 92 patients who underwent endoscopy, 45 were found to be H. pylori infected and invariably were also culture positive. Of the 45 isolates, 11 were shown to be resistant to clarithromycin by E-test. With respect to the detection of H. pylori infection, PCR showed sensitivities of 100% in biopsies and 98% in stool specimens and a specificity of 98% in both biopsy and stool samples. All clarithromycin-sensitive cases were identified as such by PCR in both biopsy and stool samples. Of the cases with a resistant strain, eight were identified as such in stool DNA and nine were identified in biopsy DNA. Failure of PCR to detect the resistant genotype in the biopsy DNA, stool DNA, or both (one case) was associated with mixed populations. In these cases, patients had not been treated for H. pylori infection before, and the sensitive population showed to be present in considerably higher numbers than the resistant population. In five of six cases in which infection with a resistant genotype only was identified by PCR, the patients had received clarithromycin-based eradication therapy in the past. Thus, the assay presented provides a highly accurate noninvasive method to detect H. pylori infection in stool and at the same time allows for culture-independent clarithromycin susceptibility testing.

Adult↗

Effect of clarithromycin treatment on Chlamydia pneumoniae in vascular tissue of patients with coronary artery disease: a randomized, double-blind, placebo-controlled trial.

Several small clinical trials have indicated that antibiotic treatment of Chlamydia pneumoniae infection is associated with a better outcome in patients with coronary artery disease (CAD). It has not been demonstrated whether antibiotic treatment eradicates C. pneumoniae from vascular tissue. The aim of the present study was to assess the effect of clarithromycin on the presence of C. pneumoniae in the vascular tissue of patients with CAD. Patients who had CAD and who were waiting for coronary artery bypass graft surgery were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were treated with clarithromycin at 500 mg or placebo once daily from the day of inclusion in the study until surgery. Several vascular tissue specimens were obtained during surgery. The presence of C. pneumoniae in vascular tissue specimens was examined by immunohistochemical staining (IHC) and two PCR assays. Chlamydia immunoglobulin G (IgG) titers were determined by an enzyme-linked immunosorbent assay at the time of inclusion in the study and 8 weeks after surgery. A total of 76 patients were included, and 180 vascular tissue specimens were obtained (80 specimens from the group treated with clarithromycin and 100 specimens from the group treated with placebo). Thirty-five patients received clarithromycin (mean duration, 27 days; standard deviation [SD], 12.2 days), and 41 patients received placebo (mean duration, 27 days; SD, 13.9 days). IHC detected the C. pneumoniae major outer membrane protein antigen in 73.8% of the specimens from the group treated with clarithromycin and 77.0% of the specimens from the group treated with placebo (P was not significant). Chlamydia lipopolysaccharide antigen was found in only one specimen from the group that received placebo. C. pneumoniae DNA was not detected in any specimen. Baseline Chlamydia-specific IgG titers were equally distributed in both groups and were not significantly different after treatment. There was no indication of an active C. pneumoniae infection in vascular tissue. Chlamydia-specific IgG titers remained unchanged throughout the study in both the antibiotic- and the placebo-treated patients.

Aged↗

Simultaneous colonisation of Helicobacter pylori with and without mutations in the 23S rRNA gene in patients with no history of clarithromycin exposure.

BACKGROUND: It was recently reported that A to G transition mutations at positions 2143 and 2144 in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori. AIMS: To study the incidence and mechanism of development of clarithromycin resistance by analysing these mutations. SUBJECTS: Eighty two H pylori positive patients who had an endoscopic examination and no history of treatment with macrolide antibiotics. METHODS: Clarithromycin resistance was screened for by polymerase chain reaction-restriction fragment length polymorphism of the 23S rRNA gene coupled with antibiotic susceptibility testing. In clinical isolates with mutations or resistance, mutations in individual colonies were analysed by direct sequencing. RESULTS: Of the 79 amplicons (DNA fragments amplified by polymerase chain reaction), Alw26I and MboII digestion disclosed the mutation in four (5%) and one (1%) respectively. However, the Alw26I cleavage was incomplete in two of the four amplicons, as was the MboII cleavage. Individual colony analysis of the isolates with incomplete cleavage patterns showed the presence of both wild type and mutated strains in the 23S rRNA genes. CONCLUSIONS: Both clarithromycin sensitive and resistant strains colonised in some patients with no history of exposure to macrolides. The results suggest that resistant strains may not be formed but selected by clarithromycin administration.

Adult↗

Penetration of clarithromycin in experimental pleural empyema model fluid.

BACKGROUND: The degree of penetration of clarithromycin into the pleural fluid has not been studied. OBJECTIVE: To determine the degree to which clarithromycin penetrates into empyemic pleural fluid using a new rabbit model of empyema. METHODS: An empyema was created via the intrapleural injection of 1 ml turpentine followed 24 h later by instillation of 5 ml (10(10)) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, clarithromycin 30 mg/kg was administered intravenously. Antibiotic levels were determined on samples of pleural fluid and blood samples collected serially over 12 h. Antibiotic levels were estimated using HPLC. RESULTS: The antibiotic penetrated well into the empyemic pleural fluid (AUC(PF)/AUC(serum) ratio of 1.57). The time to equilibration between the pleural fluid and blood antibiotic levels was 8 h. The peak pleural fluid level (Cmax(PF) of 2.88 microg/ml) occurred 1 h (Tmax(PF) of 1 h) after infusion and decreased thereafter. The Cmax(serum) was 3.53 microg/ml at 1 h after administration. CONCLUSION: The levels of clarithromycin in the pleural fluid after intravenous administration are inhibitory for most of the usual pathogens causing empyema. The degree of penetration of clarithromycin should be considered when macrolides are selected for the treatment of patients with empyema.

Animals↗

Initial clarithromycin monotherapy for Mycobacterium avium-intracellulare complex lung disease.

Sputum conversion rates in Mycobacterium avium-intracellulare (MAI) complex lung disease have ranged from only 50 to 80% despite the use of three to five antituberculosis agents. We initiated a prospective, open, noncomparative trial of initial clarithromycin monotherapy at 500 mg twice a day for 4 months in HIV-negative patients with MAI lung disease. The primary study end point was microbiologic improvement. Of 30 patients enrolled, 20 completed therapy. This latter group was predominantly male (60%), smokers (70%), older than 45 yr of age (90%), infected with Mycobacterium intracellulare (70%) and with bilateral disease (85%). Of 19 patients with pretreatment minimum inhibitory concentrations (MIC) for clarithromycin < 16 micrograms/ml, 58% became sputum-negative, and 21% showed significant reductions in sputum positivity. Heavily positive sputum cultures (> 200 colonies) were reduced from 30 to 47 samples pretherapy (64%) to three of 54 (6%) post-therapy (p < 0.0001); 18 of 19 patients (95%) showed an improvement in sputum cultures, chest radiographs, or both. Only two patients (7%) discontinued the drug because of adverse events. Only three (16%) of 19 isolates developed clarithromycin resistance (MIC > 32 micrograms/ml). Clarithromycin-susceptible and -resistant MAI isolates from the same patient had identical DNA large-restriction fragment patterns. Clarithromycin is the first single agent to be shown efficacious in the treatment of MAI lung disease.

Adult↗

Efficacy and safety of clarithromycin versus josamycin in the treatment of hospitalized patients with bacterial pneumonia.

The efficacy and safety of 500 mg clarithromycin and 1000 mg josamycin both given twice daily for a maximum of 14 days were compared in the treatment of 72 hospitalized patients with bacterial pneumonia. The predominant pathogens isolated were Streptococcus pneumoniae and Staphylococcus aureus. Clinical success was reported for 91.5% of patients treated with clarithromycin and for 87.0% of those treated with josamycin. Eradication of the causative pathogen was noted in 85.7% of patients receiving clarithromycin and in 90% of those receiving josamycin. Adverse events considered probably to relate to therapy were experienced by 2% of patients treated with clarithromycin and by 12.5% of those treated with josamycin; one patient treated with josamycin was withdrawn because of severe nausea and moderate vomiting. Treatment with clarithromycin at half the dosage of josamycin was found to have comparable efficacy and to be associated with a lower incidence of adverse events.

Adolescent↗

Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: a multicentre, double-blind, randomized study. The Canadian Sinusitis Study Group.

Adult patients with acute sinusitis (n = 236) were randomized in a double-blind study to levofloxacin 500 mg orally once daily (n = 119) or clarithromycin 500 mg orally twice daily (n = 117) for 10-14 days. Between 2 and 5 days after therapy participants were evaluated as cured (no symptoms), improved (symptoms improved, no further therapy required), or failed (further therapy required). Clinical response rates (cured plus improved) for clinically evaluable patients were 93.9% for levofloxacin (n = 98) and 93.5% for clarithromycin (n = 93). The proportion of patients evaluated as cured was higher in the levofloxacin (40.8%) than in the clarithromycin arm (29.0%) and individual symptoms showed higher rates of resolution. Of patients receiving levofloxacin and clarithromycin, 22.5% and 39.3%, respectively, experienced adverse events related or possibly related to the study therapy. This study showed that, in the treatment of acute sinusitis, daily levofloxacin therapy is as effective as twice-daily clarithromycin therapy with more complete clearing of symptoms and a more tolerable side-effect profile.

Acute Disease↗

Delirium probably induced by clarithromycin in a patient receiving fluoxetine.

BACKGROUND: Clarithromycin is a macrolide antibiotic very similar to erythromycin in structure and spectrum of activity. It has gained increasing use since its release in Canada in May 1992, partly because it is promoted as having less potential for drug interactions and adverse effects. However, as with all new medications, a high degree of vigilance for unreported adverse effects is advisable. CASE SUMMARY: A healthy 53-year-old lawyer was receiving long-term fluoxetine 80 mg hs and nitrazepam 10 mg hs for depression and mild sleep apnea. Subsequent to initiation of treatment with clarithromycin for a respiratory infection, he rapidly developed delirium, which cleared quickly after stopping all 3 medications. The delirium and psychosis did not recur when the infection was treated with erythromycin alone or after restarting fluoxetine and nitrazepam therapy at previous dosages in the absence of antibiotics. DISCUSSION: This man's delirium is consistent with fluoxetine intoxication, which appears to have resulted from inhibition of hepatic cytochrome P450 metabolism by clarithromycin. Undiagnosed, this serious drug reaction could have lead to serious medical and social consequences. CONCLUSIONS: As the use of clarithromycin increases, the potential for interactions with other drugs metabolized by the P450 enzyme system may be realized. Clinicians should consider which other medications a patient is receiving before prescribing clarithromycin or any macrolide antibiotic with potential to influence the P450 system.

Clarithromycin↗

Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion.

The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media.

Anti-Bacterial Agents↗

Levofloxacin versus clarithromycin in COPD exacerbation: focus on exacerbation-free interval.

Antibiotic treatment of bacterial exacerbation of chronic obstructive pulmonary disease (COPD) shows some immediate clinical benefits and may also minimise the frequency of further recurrences. Patients (n=511) were enrolled into a randomised double-blind multicentric study comparing the exacerbation-free interval (EFI), efficacy and safety of 7-day levofloxacin versus 10-day clarithromycin in patients with COPD exacerbation. Patients were monitored over a 1-yr period. A total of 434 patients (per protocol population) received the medication for > or =5 days. The median EFI in the per protocol population was 300 days for levofloxacin and 350 days for clarithromycin. For patients with a new documented exacerbation during follow-up (n=223), the median EFI was 100.5 days in the levofloxacin group and 95 days for clarithromycin. No significant differences in EFI between groups could be observed when stratifying the study population according to microbial aetiology and severity of bronchial obstruction. Levofloxacin and clarithromycin showed similar clinical success rates. The bacteriological success rate was significantly higher in the levofloxacin group. Both antibiotics were well tolerated. In summary, levofloxacin was associated with a significantly higher bacteriological eradication rate but similar exacerbation-free interval in patients with chronic obstructive pulmonary disease exacerbation compared to clarithromycin.

Administration, Oral↗

The levels of clarithromycin and its 14-hydroxy metabolite in the lung.

Clarithromycin is a new macrolide that has a longer half-life than erythromycin and is claimed to reach higher tissue concentrations. We aimed to investigate whether, following oral administration, the drug and its 14-hydroxy metabolite reach levels in lung tissue that are likely to be clinically effective against common respiratory pathogens. Ten patients undergoing diagnostic bronchoscopy received seven doses of clarithromycin, 500 mg b.i.d. orally. Bronchoscopy was performed at a mean time of 4.25 h after the last dose. At bronchoscopy, bronchial biopsies and bronchoalveolar lavage were performed. Clarithromycin and its 14-OH metabolite were measured in serum, bronchial biopsies, epithelial lining fluid (ELF) and alveolar cells. Mean levels of clarithromycin were 4.0 mg.l-1 in serum, 16.8 mg.kg in bronchial biopsies, 20.5 mg.l-1 in ELF and 372.7 mg.l-1 in alveolar cells. The equivalent levels of 14-OH metabolite were 0.7, 2.7, 1.9 and 38.6 mg.l-1, respectively. We conclude that there is considerable concentration of clarithromycin and its 14-OH metabolite in alveolar cells, and to a lesser extent in bronchial tissue and ELF; this implies efficacy against susceptible organisms at these sites.

Clarithromycin↗

Comparison of 5 days of extended-release clarithromycin versus 10 days of penicillin V for the treatment of streptococcal pharyngitis/tonsillitis: results of a multicenter, double-blind, randomized study in adolescent and adult patients.

OBJECTIVE: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes. RESEARCH DESIGN AND METHODS: A total of 539 patients, aged 12-75 years, were randomized to receive either clarithromycin extended-release (ER) 500 mg once daily for 5 days or penicillin V 500 mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial. Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture. MAIN OUTCOME MEASURES: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8-12; visit 4: study days 13-20; and visit 5: study days 40-50). RESULTS: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (-8.2, 5.1)). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (-10.0, 4.4)). Clinical cure was achieved in > or = 94% of patients in each treatment group. The most commonly reported study drug-related adverse events (< or = 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea. CONCLUSION: Clarithromycin ER 500 mg once daily for 5 days is equally effective as penicillin V 500 mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.

Adolescent↗

Fulminant liver failure associated with clarithromycin.

OBJECTIVE: To report a patient developing fulminant liver failure while being treated with clarithromycin for pneumonia. CASE SUMMARY: A 58-year-old white woman developed fulminant liver failure while being treated with the macrolide antibiotic clarithromycin for pneumonia. Comedication included N-acetylcysteine, atenolol, and isradipine. Other causes of liver failure, such as viral hepatitis, autoimmune hepatitis, toxins, and heart failure, were excluded by appropriate diagnostic means. All drugs were stopped, and the patient was transferred to another hospital for liver transplantation. She recovered spontaneously within several days, making transplantation unnecessary. A liver biopsy obtained 10 days after the initial presentation revealed centroacinar necrosis and beginning fibrous reorganization, compatible with recent centroacinar damage. DISCUSSION: Since no other cause could be identified, liver injury was considered to be drug related. Fulminant liver failure has not previously been described with concomitant use of atenolol and N-acetylcysteine. Although isradipine has been associated with hepatocellular injury, there are no reports of fulminant liver failure with this agent, and our patient had been treated for >2 years without signs of toxicity. The most likely cause of liver failure in this patient was, therefore, clarithromycin, which undergoes hepatic metabolism and has been reported to cause fulminant hepatic failure. A second possibility is an interaction between clarithromycin and isradipine, potentially increasing the hepatic toxicity of isradipine. CONCLUSIONS: Clarithromycin may be a cause of fulminant liver failure either alone or by inhibiting the metabolism of other drugs.

Anti-Bacterial Agents↗

Oral absorption of clarithromycin in acute illness and during convalescence in patients with community-acquired pneumonia.

STUDY OBJECTIVE: To compare the extent of oral clarithromycin absorption in patients during an illness and in health. DESIGN: Sequential two-phase prospective study including an acutely ill pneumonia phase (PP) and a subsequent convalescent phase (CP). STUDY POPULATION: Patients >/= 18 years old with radiographically confirmed community-acquired pneumonia (CAP) who were admitted to the hospital. METHODS: During both study phases, patients received one single 500-mg dose of oral clarithromycin. Serial blood samples were drawn over a 24-h period in order to characterize the plasma concentration-time curves. Area under the curve from zero to 24 h (AUC(0-24)), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) were determined for both clarithromycin and its metabolite, 14-hydroxyclarithromycin, and compared between the two phases. RESULTS: Twelve patients completed both phases of the study. For clarithromycin, there was a significant increase AUC(0-24) (47.37 +/- 8.51 microg/h/mL vs 36.22 +/- 6.09 microg/h/mL) in favor of the PP. There were no significant differences detected with respect to Cmax (4.32 +/- 0.63 microg/mL vs 3.57 +/- 0.46 microg/mL), or Tmax (3.50 +/- 0.50 h vs 2.83 +/- 0.59 h) between PP and CP. For 14-hydroxyclarithromycin, the AUC(0-24) and Cmax were significantly higher (5.84 +/- 1.08 microg/h/mL vs 8.84 +/- 1.92 microg/h/mL; 0.42 +/- 0.08 microg/mL vs 0.76 +/- 0.23 microg/mL) in the CP as compared to the PP. Tmax remained unchanged. CONCLUSION: The extent of absorption of oral clarithromycin was not diminished during an acute illness with CAP.

Absorption↗

Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma.

Prolonged use of prednisone is associated with serious side effects, such as osteoporosis, particularly among elderly individuals. Macrolide antibiotics exhibit anti-inflammatory effects that are distinct from their antimicrobial properties. Thus, the purpose of this case report is to describe the effects of prolonged treatment with clarithromycin, 500 mg bid, in reducing prednisone requirements in three elderly patients with prednisone-dependent asthma. Three patients (one woman and two men) aged 63 to 69 years, who had been treated with 5 to 10 mg prednisone daily for at least the last 12 months, were given clarithromycin, 500 mg bid. They were followed regularly for changes in daily prednisone dose, spirometry, quality of life, and adverse events. The prednisone dose was tapered in a stepwise fashion at each clinic visit. Within 3 to 6 months of initiation of treatment with clarithromycin, and throughout the 12-month follow-up, two of three patients discontinued prednisone therapy, while the third patient displayed increased spirometry readings and noted an increasingly better quality of life. Pulmonary function tests were stable or improved over this time period, with no reported adverse events, including increased rate of infections. One patient relapsed upon discontinuation of clarithromycin therapy but has since responded to re-initiation of treatment. Long-term oral clarithromycin may have a role in reducing prednisone requirements in elderly patients with prednisone-dependent asthma.

Administration, Oral↗