Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Clarithromycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1993

Overview of the pharmacology of clarithromycin suspension in children and a comparison with that in adults.

The pharmacokinetics of clarithromycin after oral administration of clarithromycin granules for suspension formulation were investigated in adult volunteers and pediatric patients. A 250-mg single dose study conducted in adults revealed that the extent of absorption of clarithromycin from the suspension formulation was not significantly different from that of the reference tablet formulation, whereas the extent of formation of the active 14-hydroxy (14-OH) metabolite was significantly lower with the suspension formulation. In addition coadministration of the suspension formulation with food did not significantly alter the extent of absorption of clarithromycin or formation of the 14-OH metabolite. A single/multiple dose study conducted in adults revealed a delay in the time to attain peak plasma clarithromycin and 14-OH metabolite concentrations after suspension administration as compared with data obtained after tablet administration in previous studies. Steady state was achieved by Dose 5 in the multiple dose phase (250 mg every 12 hours for seven doses). In addition the mean plasma concentration-vs.-time data after suspension administration compared favorably with that noted after multiple oral dose administration of 250-mg tablets in adults. A single/multiple dose study conducted in pediatric patients revealed that coadministration of the suspension formulation with food did not significantly alter the extent of absorption of clarithromycin or formation of the 14-OH metabolite. During the multiple dose phase (7.5 mg/kg every 12 hours for 4 or 5 days), mean plasma concentration-vs.-time data compared favorably with that noted after multiple oral dose administration of 250-mg and 500-mg tablets in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1996

Clarithromycin or amoxycillin plus high-dose ranitidine in the treatment of Helicobacter pylori-positive functional dyspepsia.

OBJECTIVE: This study was intended to investigate the effect of ranitidine in dual anti-Helicobacter pylori therapy. Simultaneously, it was to evaluate the potential effect of H. pylori eradication on the symptomatology of H. pylori-positive dyspepsia. PATIENTS AND METHODS: Fifty-four patients with H. pylori infection and symptoms of non-ulcer dyspepsia were randomly assigned to treatment with either amoxycillin 500 mg four times daily plus ranitidine 300 mg four times daily, clarithromycin 500 mg twice daily plus ranitidine 300 mg twice daily, clarithromycin 500 mg four times daily plus ranitidine 300 mg twice daily or clarithromycin 500 mg four times daily plus ranitidine 300 mg four times daily for a period of 12 days. In addition, ranitidine 150 mg twice daily was given for a further 16 days. RESULTS: Eradication of H. pylori using the assigned treatments was achieved in 47% (seven out of 15), 50% (five out of 10), 70% (seven out of 10) and 77% (10 out of 13) of patients, respectively. Failure of therapy with clarithromycin was associated with primary or acquired resistance after treatment in 91% (10 out of 11). Symptom improvement was significant (P = 0.0001) and similar in all of the four treatment groups up to week 8. As regards H. pylori status, no differences in the mean symptom score improvement could be found between patients with eradication and those with persistent infection (12.3-7.0, P = 0.0001, n = 29 compared with 13.0-6.5, P = 0.004, n = 19). After 1 year the symptom score had increased both in patients with persistent H. pylori (9.1) and in those remaining free of infection (10.0). No reinfection could be found. CONCLUSION: These results suggest that clarithromycin plus high-dose ranitidine is a combination which achieves reasonably high H. pylori eradication rates. However, treatment failure inevitably leads to clarithromycin resistance. The improvement of non-ulcer dyspepsia symptoms during acute therapy is independent of H. pylori eradication. Long-term benefit of H. pylori eradication with respect to the symptoms of functional dyspepsia was not observed.

Adult↗
PubMed2006

Helicobacter pylori isolated from patients who later failed H. pylori eradication triple therapy readily develop resistance to clarithromycin.

In this study, the ease of selection of clarithromycin resistance was investigated in clarithromycin-susceptible Helicobacter pylori strains isolated from patients with H. pylori infection prior to the administration of triple-combination eradication therapy (clarithromycin plus amoxicillin plus a proton pump inhibitor). Clarithromycin-susceptible strains isolated from ten patients in whom the eradication therapy was successful and from six patients in whom the eradication therapy was unsuccessful were exposed serially to subinhibitory concentrations of clarithromycin. The number of transfers required for the MICs of the strains to increase by 8- and 32-fold were 6.6 and 7.2, respectively, in the successful eradication group, and as few as 2.4 and 1.5, respectively, in the unsuccessful eradication group. The number of transfers required for the A2142G or A2143G point mutation of the 23S rRNA gene to be detected in the strains were 5 and 8, respectively, for the strains in the successful eradication group, and 1 and 2, respectively, for the strains in the unsuccessful eradication group. These results suggest that patients in the unsuccessful eradication group were infected with strains of H. pylori that readily became resistant to clarithromycin on exposure to the drug.

Amoxicillin↗
PubMed1996

Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy).

BACKGROUND: Multi-drug regimens are generally required to reliably cure Helicobacter pylori infection. Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater. METHODS: We evaluated a 14-day combination regimen for H.pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was continued for an additional 4 weeks. H. pylori status was determined by rapid urease testing, histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy. RESULTS: Twenty-seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide-based antimicrobial therapy; none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H. pylori infection was cured. Overall, H. pylori infection was cured in 78% (95% CI = 58-91%). In patients with clarithromycin-sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66-97%); only one of four patients (25%) with clarithromycin-resistant isolates was cured. In contrast, four of five patients with metronidazole-resistant isolates were cured (80%). In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89%, 95% C.I. = 65-99%). Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%. CONCLUSION: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin-sensitive isolates. Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.

Adult↗
PubMed2006

Effect of oral clarithromycin on gall-bladder motility in normal subjects and those with gall-stones.

BACKGROUND: Motilin receptor stimulation with erythromycin has been shown to have a prokinetic effect on gall-bladder motility in human beings. AIM: To find out whether oral clarithromycin has similar prokinetic activity to erythromycin on fasting and postprandial gall-bladder emptying in normal humans and those with gall-stone disease. METHODS: In a blinded two-way crossover study clarithromycin 500 mg and a placebo were administered to 10 normal subjects and 10 subjects with gall-stone disease. Gall-bladder volumes were assessed in the fasting and postprandial state. RESULTS: Fasting volumes were significantly less following clarithromycin administration in both normal subjects and subjects with gall-stones compared with placebo (12.1 +/- 1.8 mL vs. 17.8 +/- 2.0 mL, P < 0.05 and 16.7 +/- 2 mL vs. 26.8 +/- 7.2 mL, P < 0.02, mean +/- S.E.M). Postprandial volumes were also significantly less following clarithromycin administration. Ejection fraction significantly increased following clarithromycin in both normal subjects (66 +/- 5.8% vs. 37 +/- 5.9%, P = 0.02) and subjects with gall-stones (45 +/- 3.2 vs. 20 +/- 1.6%, P < 0.02). CONCLUSION: Clarithromycin enhances both fasting and postprandial gall-bladder contraction in normal humans and also in those with gall-stone disease.

Administration, Oral↗
PubMed2005

Effects of clarithromycin on lansoprazole pharmacokinetics between CYP2C19 genotypes.

AIMS: Lansoprazole is a substrate of CYP2C19 and CYP3A. The aim of this study was to compare the inhibitory effects of clarithromycin, an inhibitor of CYP3A on the metabolism of lansoprazole between CYP2C19 genotypes. METHODS: A two-way randomized double-blind, placebo-controlled crossover study was performed. Eighteen volunteers, of whom six were homozygous extensive metabolizers (EMs), six were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, received two 6-day courses of either clarithromycin 800 mg or placebo daily in a randomized fashion with a single oral dose of lansoprazole 60 mg on day 6 in all cases. Plasma concentrations of lansoprazole and its metabolites, 5-hydroxylansoprazole and lansoprazole sulphone were monitored up to 24 h after dosing. RESULTS: During placebo administration, the mean AUC0, infinity of lansoprazole in homozygous EMs, heterozygous EMs and PMs were 4652 (95% CI, 2294, 7009) ng ml(-1) h, 8299 (4784, 11814) ng ml(-1) h and 25293 (17643, 32943) ng ml(-1) h (P < 0.001), respectively. Clarithromycin treatment significantly increased Cmax by 1.47-fold, 1.71-fold and 1.52-fold and AUC0, infinity of lansoprazole by 1.55-fold, 1.74-fold, and 1.80-fold in these genotype groups, respectively, whereas elimination half-life was prolonged only in PMs. The clarithromycin-mediated percent increase in pharmacokinetic parameters such as Cmax, AUC0, infinity or elimination half-life did not differ between the three CYP2C19 genotypes. CONCLUSIONS: The present study indicates that there are significant drug interactions between lansoprazole and clarithromycin in all CYP2C19 genotype groups probably through CYP3A inhibition. The bioavailability of lansoprazole might, to some extent, be increased through inhibition of P-glycoprotein during clarithromycin treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Metronidazole- and clarithromycin-resistant Helicobacter pylori in dyspeptic patients in western Sydney as determined by testing multiple isolates from different gastric sites.

It is unknown whether antibiotic susceptibility testing of antral isolates alone is representative of Helicobacter pylori susceptibility. We aimed to determine: (i) the prevalence of metronidazole- and clarithromycin-resistant strains in infected dyspeptic patients; and (ii) whether there is consistency in the susceptibility to metronidazole and clarithromycin among isolates cultured from different gastric sites. Antral, body and fundus biopsies were taken from 242 consecutive patients and cultured on blood agar under micro-aerophilic conditions for 5-7 days. Isolates from 66 patients (13 had one, 15 had two and 38 had three isolates) were tested for susceptibility to metronidazole and clarithromycin using previously validated disc diffusion tests. Of the 66 patients, 42 (64%) had strains resistant to metronidazole while four (6.1%) had clarithromycin-resistant strains. The prevalence of metronidazole resistance was not significantly different between men and women (65% vs 60%) or across different age groups. In five (9.4%) of the 53 patients with multiple isolates, discrepant results for metronidazole susceptibility were observed: susceptible antral and body isolates but resistant fundus isolates in two cases and susceptible antral isolates but resistant body and fundus isolates in the others. Clarithromycin susceptibilities were consistent among the isolates cultured from different gastric sites in all patients. It is concluded that metronidazole-resistant strains of H. pylori are common while clarithromycin-resistant strains are rare. Metronidazole susceptibility testing of antral isolates does not appear to be representative of isolates from the body and fundus in a subset of patients.

Adult↗
PubMed1997

Clarithromycin dual therapy regimens for eradication of Helicobacter pylori: a review.

BACKGROUND: Peptic ulcer disease can be cured by eradication of Helicobacter pylori during treatment to heal the ulcer. Dual therapy regimens were among the first to be granted approval for use. Reports of dual therapies including clarithromycin as the sole antibiotic are reviewed. METHODS: Reports were identified from literature up to May 1997. Information reviewed included patient population, medical diagnosis, trial design, eradication regimens, and H. pylori eradication rates. The great diversity between studies limits formal meta-analysis but a measure of relative efficacy has been obtained by comparison of eradication rates derived by clearly defined methods and by pooling data. RESULTS: Seventy-five reports of trials with 104 dual therapy treatment arms were reviewed. H. pylori eradication rates reported with ranitidine bismuth citrate plus clarithromycin range from 70-96% with a pooled observed rate of 85%. With omeprazole plus clarithromycin, reported eradication rates range from 27-90% with the pooled reported rate being 66%. Few data are available with either lansoprazole or ranitidine hydrochloride plus clarithromycin. CONCLUSION: High H. pylori eradication rates derived by consistent and clearly defined methods have been seen with ranitidine bismuth citrate plus clarithromycin. Lower and more variable rates are reported with clarithromycin and either a proton pump inhibitor or a histamine H2-receptor antagonist.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Failed treatment of Helicobacter pylori infection associated with resistance to clarithromycin.

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin is uncommon. Initial studies have suggested that primary resistance has a significant adverse effect on bacteriological cure rates and acquired resistance develops frequently with failure of treatment following regimens containing clarithromycin. MATERIALS AND METHODS: H. pylori isolates were obtained from patients with duodenal ulcer treated with clarithromycin and omeprazole and examined for susceptibility to clarithromycin using the E-test method. A 13C urea breath test was used to confirm infection with H. pylori and successful treatment. RESULTS: H. pylori infection was successfully treated in 101 patients, all with susceptible isolates, and persisted in 30 patients of whom 4 had resistant isolates. Of 16 patients with bacteriological cure failure who had susceptible isolates pretreatment, 11 (68.8%) had resistant isolates post-treatment. CONCLUSIONS: This study confirms previous reports that acquired resistance of H. pylori to clarithromycin develops frequently (68.8-96%) in individuals with failed dual therapy regimens. Primary resistance, although uncommon (3%), was 100% predictive of treatment failure with the regimen used in this study. Effective treatment of H. pylori infection should help to prevent the development of resistance to clarithromycin.

Anti-Bacterial Agents↗
PubMed1998

Ranitidine bismuth citrate with clarithromycin given twice daily effectively eradicates Helicobacter pylori and heals duodenal ulcers.

OBJECTIVE: Ranitidine bismuth citrate (RBC) b.i.d. with clarithromycin q.i.d. eradicates Helicobacter pylori (H. pylori) in 82-94% of patients, and heals duodenal ulcers in 88-90% of patients. This double blind, placebo-controlled study examines the efficacy of a simpler b.i.d. treatment regimen, and examines the potential benefit of including a second antibiotic, metronidazole, to the b.i.d. treatment regimen. METHODS: A total of 648 patients with active duodenal ulcer received RBC 400 mg b.i.d. for 4 wk, coprescribed with clarithromycin 250 mg q.i.d., clarithromycin 500 mg b.i.d., or clarithromycin 500 mg b.i.d. with metronidazole 400 mg b.i.d. for the first 2 wk of treatment. Endoscopies were performed prestudy, after 4 wk of treatment, and at least 4 wk posttreatment. H. pylori status was assessed by CLOtest, 13C-urea breath test (UBT), and histology prestudy, and by UBT and histology at least 4 wk posttreatment. Adverse events were recorded at each visit. RESULTS: All three regimens were highly effective and well tolerated. H. pylori eradication rates were 84-94% and duodenal ulcer healing rates were 92-96% (observed data). Highest H. pylori eradication and ulcer healing rates were achieved with RBC 400 mg b.i.d. with clarithromycin 500 mg b.i.d. CONCLUSION: Ranitidine bismuth citrate with clarithromycin 500 mg b.i.d. provides an effective, simple and well tolerated regimen for the eradication of H. pylori and healing of duodenal ulcers.

Adolescent↗
PubMed1998

Primary and acquired Helicobacter pylori resistance to clarithromycin, metronidazole, and amoxicillin--influence on treatment outcome.

OBJECTIVE: The aim of this study was to evaluate the primary and acquired resistance of H. pylori against clarithromycin, metronidazole, and amoxicillin, and to elucidate the consequential influence on H. pylori eradication. METHODS: A total of 195 patients with positive H. pylori status were consecutively included. In 172 patients, H. pylori could be cultured for evaluation of primary antibiotic resistance. Fifty patients received a 2-wk dual therapy with an acid inhibitor and amoxicillin 2,000 mg daily (A), the other 122 patients a 1-wk modified triple therapy with the acid inhibitor clarithromycin 500-1,000 mg daily, and metronidazole 1,000-1,500 mg daily (B: n = 78), or amoxicillin 2,000 mg daily and metronidazole 1,000 mg daily (C: n = 44), respectively. Acid inhibition was conducted with pantoprazole 40 mg b.i.d. (n = 62), omeprazole 20 mg b.i.d. (n = 50), lansoprazole 30 mg b.i.d. (n = 10), or ranitidine 150 mg t.i.d. (n = 50). After therapy, 36 patients remained H. pylori-positive, 20 after dual therapy (A) and 16 after modified triple therapy (B: n = 7, C: n = 9). In 32 of these patients, H. pylori could be recultured for evaluation of acquired resistance (A: n = 18, B: n = 7, C: n = 7). RESULTS: Primary H. pylori resistance to metronidazole was observed in 36 of 172 patients (21%) and to clarithromycin in three of 172 (2%). Acquired resistance was found in six of 14 (43%) and in two of seven (29%), respectively, whereas neither primary nor acquired H. pylori resistance to amoxicillin was noted. Patients infected with metronidazole resistant H. pylori strains were successfully treated in combination with clarithromycin (eight of nine vs 63 of 67 with sensitive strains, NS), but not with amoxicillin (one of eight vs 32 of 34 with sensitive strains, p < 0.0001). In two patients with acquired combined clarithromycin and metronidazole resistance, modified triple therapy failed. CONCLUSION: The value of modified triple therapy with amoxicillin and metronidazole is significantly limited by metronidazole resistance. However, metronidazole resistance does not negatively influence treatment outcome in modified triple therapy including clarithromycin. H. pylori resistance to amoxicillin still is not present.

Amoxicillin↗
PubMed1998

Clarithromycin-resistant Helicobacter pylori in patients with duodenal ulcer in the United States.

BACKGROUND: Clarithromycin is a key component of several antimicrobial treatment regimens for Helicobacter pylori. Cure rates with clarithromycin-containing regimens are significantly decreased when resistance is present. Resistance develops by a point mutation in the ribosomal RNA of some organisms exposed to clarithromycin. We studied the prevalence of clarithromycin-resistant organisms in patients with duodenal ulcer in the United States from 1993-96. METHODS: Patients with endoscopic evidence of a duodenal ulcer were studied. Gastric biopsies were cultured for H. pylori and antimicrobial sensitivity was determined by the E-test (epsilometer agar diffusion gradient). RESULTS: In 1993-94, three of 78 patients (4%) had clarithromycin-resistant strains of H. pylori. In 1995-96, 44 of 348 patients (12.6%; p = 0.025) had resistant strains of H. pylori. Patients who had previously failed antimicrobial treatment for H. pylori accounted for much of the increase in resistant strains (25%). CONCLUSIONS: Failed therapy with clarithromycin-based regimens is a growing cause of antimicrobial resistance in H. pylori in the United States. Whereas the overall rates of primary resistance are low, the increase in secondary resistance over a short period of time is worrisome. New treatments that prevent the emergence of resistance may be important in the future.

Anti-Bacterial Agents↗
PubMed2006

Involvement of mitochondria and caspase pathways in N-demethyl-clarithromycin-induced apoptosis in human cervical cancer HeLa cell.

AIM: To study the mechanisms by which N-demethyl-clarithromycin (NDC) induces human cervical cancer HeLa cell apoptosis in vitro. METHODS: The viability of N-demethyl-clarithromycin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Measurement of mitochondrial transmembrane potential was analyzed by a FACScan flowcytometer. Caspase-3, poly-(ADP-ribose) polymerase (PARP), caspase-activated DNase (ICAD), Bcl-2, Bax, p53, and SIRT1 protein expression and the release of cytochrome c were detected by Western blot analysis. RESULTS: N-demethyl-clarithromycin, an anti-inflammatory substance, inhibited HeLa cell growth in a dose- and time-dependent manner. N-demethyl-clarithro-mycin induced HeLa cell death through the apoptotic pathways. The pan-caspase inhibitor (z-VAD-fmk), caspase-3 inhibitor (z-DEVD-fmk) and the caspase-9 inhibitor (z-LEHD-fmk) partially enhanced cell viability induced by N-demethyl-clarithromycin, but the caspase-8 inhibitor (z-IETD-fmk) had almost no effect. Caspase-3 was activated then followed by the degradation of caspase-3 substrates, the inhibitor of ICAD and PARP. Simultaneously, mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c in the cytosol was increased. N-demethyl-clarithromycin upregulated the expression ratio of mitochondrial Bax/Bcl-2, and significantly increased the expression of the p53 protein. It also downregulated anti-apoptotic protein SIRT1 expression. CONCLUSION: N-demethyl-clarithromycin induced apoptosis in HeLa cells via the mitochondrial pathway.

Anti-Inflammatory Agents↗
PubMed1989

In vitro and in vivo activities of clarithromycin against Mycobacterium avium.

There is no effective therapy to treat Mycobacterium avium complex infection in patients with acquired immune deficiency syndrome. Clarithromycin (A-56268; TE-031) is a new macrolide which is twofold more active than erythromycin against most aerobic bacteria. In addition, higher levels in serum and tissue are achieved with clarithromycin than with erythromycin. In this study, clarithromycin, erythromycin, difloxacin, temafloxacin, ciprofloxacin, rifampin, amikacin, and ethambutol were tested in vitro and in vivo against the M. avium complex. The MICs for 90% of strains tested were 4 micrograms/ml for clarithromycin, 64 micrograms/ml for erythromycin, 32 micrograms/ml for difloxacin, 8 micrograms/ml for temafloxacin, 4 micrograms/ml for ciprofloxacin, 4 micrograms/ml for rifampin, 32 micrograms/ml for amikacin, and 32 micrograms/ml for ethambutol. Beige mice were infected intravenously with 10(7) CFU of M. avium ATCC 25291. Treatment was started on day 6 after infection and was administered twice a day at 8-h intervals for 9 days. Clarithromycin was the most effective compound in these tests and was effective in reducing the viable bacterial counts in the spleen when it was administered subcutaneously or orally at a dose of 25 mg/kg. Amikacin was the only other compound which showed activity in vivo. The peak concentration in serum at which clarithromycin was active was approximately 1.0 microgram/ml.

Animals↗
PubMed1991

Activity of clarithromycin and its principal human metabolite against Haemophilus influenzae.

Clarithromycin is a new macrolide antibiotic which forms a microbiologically active principal in vivo metabolite, 14-OH-clarithromycin. The in vitro activities of clarithromycin and its metabolite were examined separately and in pharmacokinetically relevant fixed combinations of 4:1 and 2:1 against a group of 50 Haemophilus influenzae isolates. Broth microdilution susceptibility tests indicated that clarithromycin was less active than erythromycin against all but highly erythromycin-susceptible strains, while 14-OH-clarithromycin was generally more active than either antibiotic. An enhancement in activity against the majority of strains was demonstrated when clarithromycin and its metabolite were tested in combination.

Clarithromycin↗
PubMed1992

Activity of clarithromycin compared with those of other drugs against Mycobacterium paratuberculosis and further enhancement of its extracellular and intracellular activities by ethambutol.

Radiometric MICs of clarithromycin, a new macrolide drug, were determined against five mycobactin-dependent strains of Mycobacterium paratuberculosis (including two Crohn's disease clinical isolates) and compared with those of other drugs which included rifampin, ethambutol, amikacin, ofloxacin, ciprofloxacin, and sparfloxacin. Among the drugs screened, clarithromycin was the drug for which MICs were lowest against the five strains tested. As MICs were significantly below the reported Cmax levels (about 4 micrograms/ml), the intracellular activity of clarithromycin against the type strain of M. paratuberculosis maintained in cultured macrophages was screened. Clarithromycin was able to kill the initial inoculum by more than 1 log within 7 days, and this activity was further potentiated by ethambutol. Extracellular drug combination screened by using sublethal concentrations of the drugs showed that ethambutol was able to enhance clarithromycin activity in three out of four M. paratuberculosis strains instead of only one out of four strains (or none in the case of ofloxacin) when associated with other drugs. These results suggest that clarithromycin may be fruitful to treat human disease in which M. paratuberculosis may be etiologically involved.

Animals↗
PubMed1995

Pharmacokinetics of clarithromycin and zidovudine in patients with AIDS.

The interrelationships between the pharmacokinetics of zidovudine alone and of zidovudine plus clarithromycin were evaluated with 18 volunteers with AIDS who had no infection with Mycobacterium avium complex or clinical evidence of gastroenteritis. Patients received 200 mg of zidovudine orally every 8 h on days 1 to 4 and 1,000 mg of clarithromycin every 12 h, given 2 h apart from zidovudine, on days 2 to 4. Concentrations of zidovudine in plasma were measured at steady state both prior to (phase 1, day 1) and during (phase 2, day 4) administration of clarithromycin. Levels of clarithromycin were measured at steady state on day 4. The maximum concentrations of zidovudine in plasma were significantly different in phases 1 and 2 (616.6 and 949.0 ng/ml, respectively), as were the times to the maximum concentrations of zidovudine (2.1 and 1.0 h, respectively). However, the minimum concentrations in plasma and the areas under the concentration-time curves from 0 to 6 h did not differ on days 1 and 4. There is no significant impact on the overall bioavailability of zidovudine from the addition of clarithromycin in patients with AIDS. Clarithromycin may increase the rate of zidovudine absorption, but this is unlikely to have clinical relevance.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Comparative activities of clarithromycin, erythromycin, and azithromycin against penicillin-susceptible and penicillin-resistant pneumococci.

Activities of clarithromycin, erythromycin, and azithromycin against 120 pneumococci from the United States were tested by agar dilution MIC. All three compounds yielded MICs at which 90% of the isolates were inhibited (MIC90S) of < or = 0.125 micrograms/ml against penicillin-susceptible and -intermediate strains, but MIC90S against resistant strains were > 128.0 micrograms/ml. All erythromycin-resistant strains were also resistant to clarithromycin and azithromycin. Clarithromycin yielded MICs which were generally one or two dilutions lower than those of the other two compounds for all strains. The respective bacteriostatic and bactericidal values (micrograms per milliliter) for two susceptible, two intermediate, and two resistant strains were 0.004 to 0.03 and 0.016 to 0.03 (0.004 to 0.03/0.016 to 0.03) (clarithromycin), 0.008 to 0.06/0.016/0.016 to 0.125 (erythromycin), and 0.016 to 0.06/0.03 to 0.125 (azithromycin); clarithromycin yielded the lowest values. All compounds were uniformly bactericidal after 24 h only; erythromycin was bactericidal at eight times the MIC, and azithromycin and clarithromycin were both bactericidal at two time the MIC. The relevance of these in vitro differences requires clarification by clinical trials.

Anti-Bacterial Agents↗