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PubMed2002

Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.

We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin, sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex (MAC). Clarithromycin potentiated the activities of rifampicin and rifalazil against both extracellular and intramacrophage MAC. In contrast, all the test quinolones exhibited antagonistic effects against extracellular MAC when combined with either clarithromycin or rifamycins. Such an antagonism was not observed for the activity of these combinations against intramacrophage MAC. Combined effects were observed with combinations of these fluoroquinolones with either ethambutol or streptomycin. Similar profiles were seen for the activities of two-drug combinations of clarithromycin or fluoroquinolones with other drugs against intramacrophage MAC isolated from pulmonary and disseminated MAC infections.

Anti-Infective Agents↗
PubMed1999

Effect of clarithromycin and azithromycin on production of cytokines by human monocytes.

We examined the in vitro effect of clarithromycin and azithromycin on cytokine production by LPS and Pansorbin stimulated human monocytes. At concentrations that are physiologically achievable, both antibiotics affected in vitro production of IL-1alpha, IL-1beta, IL-6, IL-10, GM-CSF and TNF-alpha to varying degrees. Of those individuals in whom a significant increase or decrease in cytokine production was noted, clarithromycin treatment resulted in a significant suppression of production of each cytokine in 71% and a significant increase in 29% of the individuals. Similar results were noted with azithromycin. The results with IL-6 and TNF-alpha in the clarithromycin studies were most striking. A significant decrease was noted in 60% of individuals for IL-6 and 86% for TNF-alpha. For azithromycin, the most interesting results were for IL-1alpha (decrease in 100% of individuals) and for TNF-alpha (decrease in 100% of individuals). These results show that both clarithromycin and azithromycin alter cytokine production in human monocytes and thus possess immunomodulatory activity.

Adult↗
PubMed2000

Therapeutic effect of clarithromycin for respiratory-tract infections in children caused by Chlamydia pneumoniae. Research Group of Sapporo for Pediatric Chlamydial Infections.

Children infected with Chlamydia pneumoniae sometimes experience lower respiratory tract infections such as pneumonia and bronchitis. Although numerous anti-microbial compounds have been reported to be active against the organism, most of them have not been in a clinical trial in infants and children with C. pneumoniae infection. Clarithromycin has been shown to express anti-chlamydial effects in vitro. In this study, we evaluated the clinical anti-C. pneumoniae properties of clarithromycin in children with mainly lower respiratory tract infection. We administered clarithromycin orally to 21 infants and children at a dose of 10-15 mg/kg/day divided into two or three doses for 4-21 days. Clinical symptoms, roentgenographic and laboratory abnormal findings improved. The overall clinical efficacy rate was 85.7% (18 of 21 cases). Administration of clarithromycin was considered to be a suitable treatment for improving lower respiratory infections in infants and children caused by C. pneumoniae.

Administration, Oral↗
PubMed2003

Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (SE) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P < 0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3-6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.

Adult↗
PubMed2001

Effects of CYP2C19 gene polymorphism on cure rates for Helicobacter pylori infection by triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin and clarithromycin in Japan.

BACKGROUND: Omeprazole is mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. Rabeprazole, on the other hand, is mainly metabolized to thioether-rabeprazole via a non-enzymatic pathway and partially metabolized to demethylated-rabeprazole by CYP2C19 in liver CYP2C19 status may affect cure rate for Helicobacter pylori infection with proton pump inhibitor triple therapy. AIM: To investigate whether genetic polymorphism of CYP2C19 and selected proton pump inhibitors (omeprazole or rabeprazole) were associated with cure rate for Helicobacter pylori infection using triple therapy with omeprazole or rabeprazole, amoxicillin, and clarithromycin. METHODS: A total of 170 Helicobacter pylori-positive patients with chronic gastritis were randomized to receive one of the following Helicobacter pylori eradication regimens; OAC (omeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week) and RAC (rabeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week). The CYP2C19 genotype; wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both, were identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In DAC regimen, cure rate (per protocol analysis) was 73.3% in homozygous extensive metabolizers, 86.1% in heterozygous extensive metabolizers, and 85.0% in poor metabolizers. In RAC regimen, the cure rate was 81.0% in homozygous extensive metabolizers, 82.9% in heterozygous extensive metabolizers, and 87.5% in poor metabolizers. Cure rate was not significantly different between the CYP2C19 genotypes in both regimens. CONCLUSION: Triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin, and clarithromycin is sufficiently effective in cure of Helicobacter pylori infection regardless of CYP2C19 status.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

The bactericidal effects of Lactobacillus acidophilus, garcinol and Protykin compared to clarithromycin, on Helicobacter pylori.

Chronic infection with Helicobacter pylori causes peptic ulcers, gastric cancer and lymphoma. We evaluated the inhibitory effects of the probiotic Lactobacillus acidophilus DDS-1J, the antibiotic clarithromycin and the natural antioxidants garcinol and Protykin (containing 50% trans-resveratrol) on Helicobacter pylori strain ATCC 49503. The findings of this study indicate that Lactobacillus acidophilus DDS-1J exerts a growth inhibitory effect on H. pylori at a ratio of 1:1 or higher in vitro. In the case of clarithromycin, garcinol and resveratrol, the bactericidal effect is time and concentration dependent. Clarithromycin completely inhibited growth at > or = 62.5 microg/ml at 6 h and at > or = 31.5 microg/ml at 12 h. For garcinol the highest concentration needed for complete inhibition was 31.5 microg/ml at 6 h and 3.9 microg/ml after 12 h incubation. For resveratrol, significant inhibition was noted at 1000 microg/ml at 12 h only. The bactericidal effect of garcinol was reduced by the addition of resveratrol at all concentrations < or = 125 microg/ml at 6 and 12 h. We conclude from this study that Lactobacillus acidophilus DDS-1J inhibits H. pylori at 1:1 and higher ratios. Also, between the two antioxidants, garcinol is much more potent than resveratrol as a bactericidal agent against H. pylori, and that resveratrol may antagonize this effect. Finally, our study showed equivalent or better bactericidal activity of garcinol compared to clarithromycin against H. pylori at 6 and 12 h incubation, indicating a potential role for this antioxidant in treatment for H. pylori infection.

Anti-Bacterial Agents↗
PubMed2003

Characterization of the inhibitory effects of erythromycin and clarithromycin on the HERG potassium channel.

Both erythromycin and clarithromycin have been reported to cause QT prolongation and the cardiac arrhythmia torsade de pointes in humans, however direct evidence documenting that these drugs produce this effect by blocking human cardiac ion channels is lacking. The goal of this study was to test the hypothesis that these macrolide antibiotics significantly block the delayed rectifier current (IKr) encoded by HERG (the human ether-a-go-go-related gene) at drug concentrations, temperature and ionic conditions mimicking those occurring in human subjects. Potassium currents in HEK 293 cells stably transfected with HERG were recorded using a whole cell voltage clamp method. Exposure of cells to erythromycin reduced the HERG encoded potassium current in a concentration dependent manner with an IC50 of 38.9 +/- 1.2 microM and Hill Slope factor of 0.4 +/- 0.1. Clarithromycin produced a similar concentration-dependent block with an IC50 of 45.7 +/- 1.1 microM and Hill Slope factor of 1.0 +/- 0.1. Erythromycin (25-250 microM) and clarithromycin (5 or 25 microM) also produced a significant decrease in the integral of the current evoked by an action potential shaped voltage clamp protocol. The results of this study document that both erythromycin and clarithromycin significantly inhibit the HERG potassium current at clinically relevant concentrations.

Action Potentials↗
PubMed1997

Clarithromycin, amoxycillin and H2-receptor antagonist therapy for Helicobacter pylori peptic ulcer disease in Korea.

BACKGROUND: Effective anti-Helicobacter pylori therapies with few side-effects are needed. We previously showed that the regimen of amoxycillin, clarithromycin and an H2-receptor antagonist was effective in the United States. The current study tested whether this therapy would also be successful in Korea. METHODS: Patients with gastric or duodenal ulcers received amoxycillin (750 mg t.d.s.) plus clarithromycin (500 mg t.d.s.) for 2 weeks and nizatidine 300 mg at bedtime for 6 weeks. Endoscopic examinations were performed before treatment and 4 or more weeks after ending antimicrobial therapy. H. pylori status was confirmed by rapid urease testing and histological examination of gastric antrum and corpus biopsies using the Genta stain. Antibiotic resistance was tested using the E-test method. Cure was defined as no evidence of H. pylori infection 4 or more weeks after ending therapy. RESULTS: Seventy-two patients (59 males and 13 females; mean age 46 years), including 35 with duodenal ulcers, 30 with gastric ulcers and seven with both, were studied. H. pylori infection was cured in 95.8% (69/72 patients; 95% CI = 88.3-99.1%). Two of the treatment failures had culture data and one had pre-treatment resistance to clarithromycin. Smoking did not have an adverse effect on therapy. Ten patients (15%) developed side-effects during treatment, but all were mild and did not require treatment interruption. No case of reinfection was noted during follow-up. CONCLUSION: The combination of amoxycillin, clarithromycin and an H2-receptor antagonist is effective in Korean patients with H. pylori infection.

Adolescent↗
PubMed1997

Efficacy and tolerability of a one-week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin for cure of Helicobacter pylori infection in patients with duodenal ulcer.

BACKGROUND: Previous studies have shown that one-week triple therapy consisting of omeprazole, clarithromycin and amoxycillin may cure Helicobacter pylori infection in the vast majority of patients. The present study was designed to test the hypothesis that a triple therapy with pantoprazole, clarithromycin and amoxycillin cures the infection in > or = 80% of duodenal ulcer patients infected with H. pylori. METHODS: In an open two-centre study, 60 duodenal ulcer patients were treated with pantoprazole 40 mg b.d., clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for 1 week. During the second week patients received pantoprazole 40 mg once in the morning. We assessed H. pylori infection before treatment and 4 weeks after cessation of the study medication by a rapid urease test, histology after Warthin-Starry stain and a 13C-urea breath test. RESULTS: Sixty patients (42 males, mean age 47.4 years) entered the trial. All patients were infected with H. pylori. One patient was withdrawn from the study because of allergy to penicillin and six patients were protocol violators. H. pylori infection was cured in 47 out of 53 patients who completed the trial according to the protocol (89%; 95% CI: 80-97%) and in 49 of 60 patients included in the trial (82%; 95% CI: 72-92%). Four weeks after the last administration of study drugs, 55 out of 60 ulcers had healed (92%). Twenty-nine patients reported 51 adverse events that were mostly mild to moderate. CONCLUSIONS: One-week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin is a simple and effective approach to the cure of H. pylori infection in patients with duodenal ulcer. In those patients who took the drugs as prescribed the H. pylori cure rate was 89%, with the lower 95% confidence limit being 80%.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

One-week therapy for Helicobacter pylori eradication: ranitidine bismuth citrate plus medium-dose clarithromycin and either tinidazole or amoxycillin.

BACKGROUND: One-week ranitidine bismuth citrate (RBC)-based triple regimens may be effective for the eradication of Helicobacter pylori. We evaluated the efficacy of two short-term RBC-based eradicating therapies including RBC plus medium-dose clarithromycin and either tinidazole or amoxycillin. METHODS: Seventy consecutive patients, who underwent gastroscopy for dyspeptic symptoms and were found to be H. pylori-positive, were randomly subdivided into two groups receiving either RBC 400 mg b.d. plus clarithromycin 250 mg t.d.s. and tinidazole 500 mg b.d. (group RBCCT) or RBC 400 mg b.d. plus clarithromycin 250 mg t.d.s. plus amoxycillin 1 g b.d. (group RBCCA). H. pylori status was evaluated by means of histology and rapid urease test at entry, and by 13C-urea breath test alone 8 weeks after treatment. RESULTS: Sixty-nine out of 70 enrolled patients completed the study: 35/35 in group RBCCT and 34/35 in group RBCCA. One patient in group RBCCA was lost to follow-up. In group RBCCT, at the end of treatment, 32 of 35 patients were H. pylori-negative (per protocol analysis 91%, intention-to-treat analysis 91%; 95% CI: 77-98%). In group RBCCA, 31 of 34 patients returned H. pylori-negative (per protocol 91%; 95% CI: 76-98%, intention-to-treat 89%; 95% CI: 73-97%). Slight side-effects occurred in 3/35 patients (9%) in group RBCCT and in 3/34 (9%) in group RBCCA. CONCLUSIONS: One-week regimens consisting of RBC plus clarithromycin and either tinidazole or amoxycillin, combine high eradication rates with modest side-effects. No substantial difference was found between the two treatment regimens tested in this trial.

Adult↗
PubMed1998

Ranitidine bismuth citrate (RBC) based triple therapy for 7 days is more effective than RBC plus clarithromycin for 14 days in dyspeptic patients with Helicobacter pylori infection. H. Pylori Lombardy Group.

BACKGROUND: Ranitidine bismuth citrate (RBC) in co-prescription with clarithromycin for 2 weeks has been shown to be effective for the eradication of Helicobacter pylori. Moreover, several studies have reported good H. pylori eradication rates with RBC plus two antibiotics for 1 week. AIM: To compare the H. pylori eradication rates and safety of two different RBC co-prescription regimens. METHODS: Patients undergoing endoscopy for upper gastrointestinal symptoms were randomized to open treatment with either RBC 400 mg b.d. plus clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 1 week (RbcCT) or RBC 400 mg b.d. plus clarithromycin 500 mg b.d. (RbcC) for 2 weeks. H. pylori infection was detected by CLO-test on antral biopsy and confirmed by histology on antral and corpus biopsies and by 13C-urea breath test (UBT). A further UBT was performed at least 4 weeks after the end of treatment to assess the H. pylori eradication. H. pylori eradication was calculated for an intention-to-treat (ITT) population (all H. pylori-positive patients who received at least one treatment dose) and for an all-patients-treated (APT) population (patients of the ITT population assessed for H. pylori at least 4 weeks after the end of treatment). RESULTS: Two hundred and ninety-five patients (142 males, 153 females, mean age 48 years) were recruited to the study. Of these, 239 had H. pylori infection confirmed by all three tests required by the protocol. The two treatment groups were similar with respect to all the demographic data. H. pylori ITT eradication rates were 85% (104/123) for RbcCT and 67% (78/116) for RbcC. APT eradication rates were 92% (104/113) for RbcCT and 76% (78/103) for RbcC. A significant statistical difference was found between the two treatments, irrespective of the population analysis (P = 0.001). Adverse events occurred in 7% of patients on RbcCT and in 13% on RbcC. No serious adverse events were reported. CONCLUSIONS: The 1-week treatment with RBC plus clarithromycin and tinidazole yielded higher eradication rates than the 2-week treatment with RBC plus clarithomycin. Both treatments were well tolerated.

Adolescent↗
PubMed2000

Pantoprazole, amoxycillin and either azithromycin or clarithromycin for eradication of Helicobacter pylori in duodenal ulcer.

BACKGROUND: Studies have shown that 1-week triple therapy consisting of a proton pump inhibitor, amoxycillin and clarithromycin may cure Helicobacter pylori infection in the majority of patients. AIM: To establish whether pantoprazole plus amoxycillin in association with either azithromycin or clarithromycin is useful in curing H. pylori infection in patients with a duodenal ulcer. METHODS: One hundred and ten patients with active duodenal ulcers and H. pylori infection were treated with pantoprazole (days 1-7, 40 mg b.d.; days 8-28 40 mg o.d.) plus amoxycillin 1 g b.d. for the first 7 days. Patients were randomly assigned to receive either azithromycin 500 mg o.d. for the first 6 days (PAAz group; n=55) or clarithromycin 500 mg b.d. for the first 7 days of treatment (PAC group; n=55). H. pylori status was determined by urease test and histology before the treatment, and again 4 weeks after cessation of any medication. RESULTS: One hundred and three patients completed the study. H. pylori infection was eradicated in 78% (39/50) of patients in the PAAz group (ITT analysis: 71%, 95% CI: 61-83%) vs. 81% (43/53) of patients in the PAC group (ITT analysis: 78%, 95% CI: 69-90%) (N.S.). All ulcers had healed. CONCLUSION: Our study shows that 1-week triple therapy with pantoprazole, amoxycillin and either azithromycin or clarithromycin is not satisfactory (<80% ITT H. pylori eradication rate).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Triple therapy with clarithromycin, omeprazole, and amoxicillin for eradication of Helicobacter pylori in duodenal ulcer patients in Asia and Africa.

BACKGROUND: Studies assessing the efficacy of triple therapy containing clarithromycin and amoxicillin for the eradication of Helicobacter pylori infection and healing of duodenal ulcers in Asian and African countries are limited. AIM: To determine the efficacy and safety of 1-week triple therapy with omeprazole, amoxicillin and clarithromycin for eradicating H. pylori infection in patients with active duodenal ulcer living in Asian and African regions. METHODS: This was an open-label, multicentre study in 11 centres in Asia and Africa. Patients with endoscopy-proven duodenal ulcer and who were H. pylori-positive were treated with clarithromycin 500 mg, omeprazole 20 mg, and amoxicillin 1000 mg, all given twice daily for 7 days. Upper endoscopy was repeated at week 6 to check for ulcer healing and H. pylori status. RESULTS: A total of 117 patients were recruited. H. pylori eradication rates were 85% by per protocol analysis and 80% by intention-to-treat analysis. Ulcer healing was found in 94% of subjects (per protocol analysis). Clinical success, measured by change of pre-treatment ulcer symptoms, was strongly supported by complete resolution or improvement in 100% of the evaluable patients (per protocol analysis). Since treatment-related adverse events, when present, were largely mild or moderate, the triple therapy regimen was considered safe. CONCLUSION: Seven-day triple therapy with omeprazole, amoxicillin, and clarithromycin was efficacious for treating Asian and African patients with duodenal ulcer disease associated with H. pylori infection, and the treatment regimen was well-tolerated.

Amoxicillin↗
PubMed2003

Prevalence of Helicobacter pylori resistance to clarithromycin and metronidazole determined by 23S ribosomal RNA and rdxA gene analyses in Hiroshima, Japan.

BACKGROUND AND AIMS: Resistance to antibiotics in Helicobacter pylori is increasing and becoming a serious problem in eradication treatment of H. pylori. The prevalence of H. pylori infections that are resistant to clarithromycin, metronidazole, or both were determined in H. pylori isolates in Hiroshima, Japan. METHODS: Sixty Japanese patients with H. pylori infection were collected between 1999 and 2000. To detect the resistance to clarithromycin and metronidazole, mutations of the 23S ribosomal RNA (rRNA) and rdxA genes that are responsible for resistance in H. pylori, were examined by direct sequencing analysis. RESULTS: Resistance to clarithromycin and metronidazole was detected in 12 (20.0%) and nine (15.0%) of the patients, respectively. Dual resistance to clarithromycin and metronidazole was detected in five (8.3%) patients. CONCLUSION: These results indicate that the relatively high prevalence of the dual resistance in H. pylori isolates may need special attention and new therapeutic approaches in Japan.

Anti-Bacterial Agents↗
PubMed2001

Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin.

BACKGROUND: Proton pump inhibitors such as omeprazole and lansoprazole are mainly metabolized by CYP2C19 in the liver. The therapeutic effects of proton pump inhibitors are assumed to depend on CYP2C19 genotype status. OBJECTIVE: We investigated whether CYP2C19 genotype status was related to eradication rates of H pylori by triple proton pump inhibitor-clarithromycin-amoxicillin (INN, amoxicilline) therapy and attempted to establish a strategy for treatment after failure to eradicate H pylori. METHODS: A total of 261 patients infected with H pylori completed initial treatment with 20 mg of omeprazole or 30 mg of lansoprazole twice a day, 200 mg of clarithromycin three times a day, and 500 mg of amoxicillin three times a day for 1 week. CYP2C19 genotypes of patients were determined with polymerase chain reaction-restriction fragment length polymorphism analysis. Patients without eradication after initial treatment were retreated with 30 mg of lansoprazole four times daily and 500 mg of amoxicillin four times daily for 2 weeks. RESULTS: Eradication rates for H pylori were 72.7% (95% confidence interval, 64.4%-81.8%), 92.1% (confidence interval, 86.4%-97.3%), and 97.8% (confidence interval, 88.5%-99.9%) in the homozygous extensive, heterozygous extensive, and poor metabolizer groups, respectively. Thirty-four of 35 patients without eradication had an extensive metabolizer genotype of CYP2C19. Nineteen of those patients were infected with clarithromycin-resistant strains of H pylori. However, there were no amoxicillin-resistant strains of H pylori. Re-treatment of H pylori infection with dual high-dose lansoprazole-amoxicillin therapy succeeded in 30 of 31 patients with extensive metabolizer genotype of CYP2C19. CONCLUSION: The majority of patients without initial eradication of H pylori had an extensive metabolizer CYP2C19 genotype but were successfully re-treated with high doses of lansoprazole and an antibiotic to which H pylori was sensitive, such as amoxicillin, even when the patients were infected with clarithromycin-resistant strains of H pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

The new macrolide antibiotics. Azithromycin and clarithromycin.

Azithromycin (Zithromax) and clarithromycin (Biaxin Filmtabs) are new macrolide antibiotics with several advantages over erythromycin. Azithromycin has an expanded spectrum against gram-negative bacilli. Clarithromycin is more active than erythromycin against gram-positive cocci; combination with its 14-hydroxy metabolite enhances its antimicrobial activity. These new agents penetrate well into tissues and concentrate in macrophages and polymorphonuclear leukocytes. They offer improved bioavailability and an extended half-life. The high tissue-to-serum level and extended elimination half-life of azithromycin allow for once-daily dosing and short-course therapy. Clarithromycin and 14-hydroxyclarithromycin maintain high serum levels and tissue-to-serum concentrations. Both of these new agents have been effective in streptococcal pharyngitis, acute sinusitis, acute lower respiratory tract infections, skin and soft-tissue infections, and sexually transmitted diseases. A single dose of azithromycin is effective for genital chlamydial infections. Adverse reactions to these agents have usually been mild and have not included serious organ toxicity. In clinical trials, the rate of premature discontinuation of therapy has been less than observed with erythromycin. Azithromycin and clarithromycin should be used according to the current guidelines of the Food and Drug Administration; their future role will be determined by ongoing laboratory and clinical evaluations.

Anti-Bacterial Agents↗
PubMed2002

Single- and multiple-dose pharmacokinetics of oral moxifloxacin and clarithromycin, and concentrations in serum, saliva and faeces.

Moxifloxacin and clarithromycin are important antibacterial drugs in the treatment of community-acquired respiratory tract infections. In a double-blind, randomized, 2-period cross-over study the pharmacokinetics of moxifloxacin versus clarithromycin were determined after single and multiple doses in 12 healthy male volunteers. The concentrations of the antibiotics in serum, saliva and faeces were measured by validated high-performance liquid chromatographic methods. In serum, moxifloxacin exhibited a mean peak concentration of 3.1 +/- 0.6 mg/l after a time to peak concentration of 1.67 +/- 0.96 h on day 1, with a significant increase to 3.98 +/- 1.10 mg/l on day 7 (p < 0.05). The area under the curve-12 revealed a highly significant increase from 28.2 + 4.1 mg*h/l on day 1 to 39.5 +/- 6.6 mg*h/l on day 7 (p < 0.01). There were also significant differences in terminal half-life between day 1 and day 7 [10.6 h (range 9.0-12.8) vs 14.9 h (range 12.6-28.1); p < 0.01] and in mean residence time (15.1 +/- 1.9 vs 18.2 +/- 2.4 h; p < 0.01). The concentrations of moxifloxacin in saliva were well equilibrated with serum at a relatively constant saliva-serum ratio of about 0.8. Pharmacokinetic parameters of clarithromycin and its metabolite, 14-hydroxy-clarithromycin, were similar to previously published data. Accumulation was found. No serious adverse events were observed with either study drug.

Administration, Oral↗
PubMed1991

In vitro activity of clarithromycin alone or in combination with other antimicrobial agents against Mycobacterium avium-intracellulare. Complex strains isolated from AIDS patients.

The activity of clarithromycin and five other antimicrobial agents, namely amikacin, rifampicin, rifabutin, clofazimine and ciprofloxacin, was assessed both by an agar dilution and a radiometric method in broth on 11 Mycobacterium avium-intracellulare complex (MAC) strains, recently isolated from AIDS patients. Minimum inhibitory concentrations (MICs) radiometrically determined were, in general, several times lower than MICs assessed in agar, probably because of a partial degradation of antimicrobials during the long incubation period needed for tests in solid medium. When tested in broth, rifabutin and clofazimine showed very low MICs 90 (0.24 and 0.78 microgram/ml, respectively). Ciprofloxacin and clarithromycin also had MICs90 in the range of peak serum levels (1.93 and 3.76 micrograms/ml, respectively). Moreover, all these antimicrobials are known to concentrate several times in macrophages. MICs90 were higher for amikacin (11 micrograms/ml) and for rifampicin (8 micrograms/ml). When clarithromycin was tested against three MAC strains in combination with another drug, it showed a synergistic effect only when combined with rifampicin. Some synergistic effect was observed also when combining clarithromycin with rifampicin and amikacin, whereas in combination with rifabutin and clofazimine there was only an additive effect.

Acquired Immunodeficiency Syndrome↗