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PubMed1996

Double-blind, multicenter, placebo-controlled evaluation of clarithromycin and omeprazole for Helicobacter pylori-associated duodenal ulcer.

BACKGROUND: Eradication of Helicobacter pylori leads to faster ulcer healing and a significant decrease in ulcer recurrence. Clarithromycin is the most effective monotherapy for eradicating H. pylori from the gastric mucosa, and omeprazole frequently is used for the treatment of duodenal ulcer disease, prompting the interest to investigate rigorously the combination of clarithromycin and omeprazole for eradicating H. pylori. MATERIALS AND METHODS: The aim of this double-blind, randomized, multicenter (n = 30), multinational (n = 10) study was to compare clarithromycin and omeprazole with omeprazole monotherapy for the eradication of H. pylori from the gastric mucosa, endoscopic healing, and reduction of symptoms and ulcer recurrence in patients with active duodenal ulcer. Patients with active duodenal ulcer associated with H. pylori infection were randomized to receive omeprazole, 40 mg every morning for 14 days, with either clarithromycin, 500 mg, or placebo three times daily, which was followed by omeprazole, 20 mg every morning for 14 days. Patients underwent endoscopy before enrolling in the study, immediately after finishing treatment, and at 4- to 6-week and 6-month follow-up evaluations or at the recurrence of symptoms. RESULTS: Two hundred and eight patients with active duodenal ulcer associated with confirmed H. pylori infection were randomized to treatment with either clarithromycin and omeprazole (n = 102) or omeprazole and placebo (n = 106). Four to six weeks after treatment was completed, H. pylori was eradicated in 74% (95% confidence interval, 63.0%-82.4%) of patients receiving clarithromycin and omeprazole, compared with 1% (0.0%-6.2%) of patients receiving omeprazole monotherapy (p < .001). Clarithromycin resistance developed in eight patients treated with clarithromycin and omeprazole and in none given omeprazole and placebo. Ulcers, which were healed following treatment in more than 95% of study patients, recurred by the 6-month follow-up visit in 10% (5%-19%) of dual therapy recipients, compared with 50% (39%-61%) of those who took omeprazole alone (p < .001). CONCLUSION: Clarithromycin and omeprazole dual therapy is simple and well-tolerated and leads to consistently high eradication rates for patients with duodenal ulcer associated with H. pylori infection.

Adult↗
PubMed2000

Pharmacokinetic interaction between amprenavir and clarithromycin in healthy male volunteers.

The P450 enzyme, CYP3A4, extensively metabolizes both amprenavir and clarithromycin. To determine if an interaction exists when these two drugs are coadministered, the pharmacokinetics of amprenavir and clarithromycin were investigated in healthy adult male volunteers. This was a Phase I, open-label, randomized, balanced, multiple-dose, three-period crossover study. Fourteen subjects received the following three regimens: amprenavir, 1,200 mg twice daily over 4 days (seven doses); clarithromycin, 500 mg twice daily over 4 days (seven doses); and the combination of the above regimens over 4 days (seven doses of each drug). Twelve subjects completed all treatments and the follow-up period. The erythromycin breath test (ERMBT) was administered at baseline, 2 h after the final dose of each of the three regimens and at the first follow-up visit. Coadministration of clarithromycin and amprenavir significantly increased the mean amprenavir AUC(ss), C(max,ss), and C(min,ss) by 18, 15, and 39%, respectively. Amprenavir had no significant effect on the AUC(ss) of clarithromycin, but the median T(max,ss)for clarithromycin increased by 2.0 h, renal clearance increased by 34%, and the AUC(ss) for 14-(R)-hydroxyclarithromycin decreased by 35% when it was given with amprenavir. Amprenavir and clarithromycin reduced the ERMBT result by 85 and 67%, respectively, and by 87% when the two drugs were coadministered. The baseline ERMBT value did not correlate with clearance of amprenavir or clarithromycin. A pharmacokinetic interaction occurs when amprenavir and clarithromycin are coadministered, but the effects are not likely to be clinically important, and coadministration does not require a dosage adjustment for either drug.

Adolescent↗
PubMed2003

Short-course therapy of acute bacterial exacerbation of chronic bronchitis: a double-blind, randomized, multicenter comparison of extended-release versus immediate-release clarithromycin.

OBJECTIVE: The objective of this study was to compare the efficacy and safety of two clarithromycin formulations given for 5 days to patients with acute bacterial exacerbation of chronic bronchitis (ABECB). PATIENTS AND METHODS: This was a double-blind, randomized, multicenter study of ambulatory patients between 40 and 75 years of age with a medical history of chronic bronchitis, chronic obstructive pulmonary disease and a presumptive diagnosis of ABECB who met Anthonisen Type 1 criteria (increased dyspnea, increased sputum volume and increased sputum purulence). Eligible patients received a 5-day course of clarithromycin extended-release (ER) 500 mg once daily or clarithromycin immediate-release (IR) 250 mg twice daily. Clinical cure, bacteriological cure and pathogen eradication rates were determined at the end of therapy and at a follow-up visit. RESULTS: Clinical cure rates were similar at the test-of-cure visit for evaluable patients in the clarithromycin ER group (97%, 298/307) and clarithromycin IR group (98%, 300/307) (95% CI (-3.2, 1.9)). The bacteriological cure rate was 89% and the pathogen eradication rate was 90% in both treatment groups. Resolution or improvement in cough, sputum production, sputum volume and sputum appearance was observed in > 90% of evaluable patients in each treatment group. The incidence of study drug-related adverse events was 6.6% (23/351) in the clarithromycin ER group and 5.4% (19/352) in the clarithromycin IR group. The most frequently occurring study drug-related adverse events were abdominal pain, diarrhea and taste perversion. CONCLUSION: Clarithromycin ER 500 mg once daily for 5 days is equivalent to clarithromycin IR 250 mg twice daily for 5 days in treating adults with ABECB. Both regimens were effective in resolving clinical signs and symptoms of ABECB and eradicating the target pathogens, and were well tolerated.

Acute Disease↗
PubMed2004

Comparison of hospitalization rates in patients with community-acquired pneumonia treated with telithromycin for 5 or 7 days or clarithromycin for 10 days.

AIMS: To compare the impact on hospitalization rates and the clinical efficacy of oral telithromycin and clarithromycin treatment in patients with community-acquired pneumonia (CAP). METHODS: A total of 581 patients with CAP were enrolled in this randomized, double-blind, parallel group, multinational study, of whom 575 were evaluated for healthcare resource utilization from a payer perspective (intent to treat [ITT] population). Patients received telithromycin 800 mg once daily for 5 (n = 193) or 7 (n = 195)days, or clarithromycin 500 mg once daily for 10 days (n = 187). The primary efficacy endpoint was clinical outcome at test of cure (Days 17-24) in the per-protocol population. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use were compared by treatment group (ITT) up to late post- for clarithromycin vs dollars 37930 (difference: -26446; therapy (Days 31-36). Study investigators blinded to treatment assessed whether hospital admissions were CAP-related or not. CAP-related hospitalization costs (USdollars) for telithromycin and clarithromycin were compared. RESULTS: Clinical cure rates were similar in patients who received clarithromycin for 10 days and telithromycin for 5 or 7 days: 91.8% (134/146), 89.3% (142/159), and 88.8% (143/161), respectively, and both 5- and 7-day telithromycin were statistically equivalent to clarithromycin (difference: -2.5 and -3.0%, respectively; 95% CI: -9.7, 4.7 and -10.2, 4.3, respectively). There were 7 CAP-related hospital admissions among clarithromycin patients vs 3 (p = 0.283) and 1 (p = 0.021) admissions among 5- and 7-day telithromycin patients, respectively. The number of hospital days/100 patients was 40.1 for clarithromycin vs 17.1 and 7.2 for 5- and 7-day telithromycin, respectively. Projected hospitalization costs/100 patients were dollars 86205 95% CI: -66 654; 13 762) and dollars 16 091 (difference: -37 847; 95% CI: -77953; 2259) for 5- and 7-day telithromycin, respectively. CONCLUSIONS: Data from this study demonstrate that telithromycin 800 mg once daily for 5 or 7 days with fewer hospital days and potentially lower is an effective treatment for CAP,and that telithromycin treatment of CAP may be associated hospitalization costs than clarithromycin treatment.

Administration, Oral↗
PubMed2005

Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized, investigator-blinded study.

OBJECTIVE: To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/ clavulanate in patients diagnosed with acute bacterial sinusitis. RESEARCH DESIGN AND METHODS: In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12 years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000 mg once daily or amoxicillin/ clavulanate 875 mg/l25 mg twice daily for 14 days. MAIN OUTCOME MEASURES: Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10 days following the completion of treatment. Radiological response was assessed at a follow-up visit. RESULTS: The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [-2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [-12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [-4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2 days-5 days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure (p = 0.027) and improvement/resolution rate of nasal congestion (p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was > or = 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER (p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group (p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events. CONCLUSION: In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.

Acute Disease↗
PubMed1999

A time-kill evaluation of clarithromycin and azithromycin against two extracellular pathogens and the development of resistance.

OBJECTIVE: To determine the activity of clarithromycin, its metabolite (14-hydroxyclarithromycin), and azithromycin against Haemophilus influenzae and Staphylococcus aureus using time-kill methodology and to evaluate the susceptibility of the organisms following exposure to various concentrations of the azalide macrolides. DATA SOURCES AND METHODS: Clinical isolates of H. influenzae and S. aureus were obtained from the Clinical Microbiology Laboratory at University Hospital, San Antonio, Texas. Susceptibility testing was performed according to National Committee for Clinical Laboratory Standards guidelines. 14-Hydroxyclarithromycin was added to clarithromycin solutions used for H. influenzae. Time-kill studies were performed using antimicrobial concentrations of 0.25-8x minimum inhibitory concentration (MIC) and an initial inoculum of approximately 10(5) CFU/mL. Samples were plated onto solid agar at 0, 4, 8, 12, and 24 hours. At 0, 12, and 24 hours, samples were then plated onto solid agar incorporated with antibiotic. After incubating plates at 35 degrees C for 24 hours, colony counts were determined. RESULTS: The MICs of clarithromycin and clarithromycin plus 14-hydroxyclarithromycin for H. influenzae were 4 and 2 microg/mL, respectively. For S. aureus, the MIC of clarithromycin was 0.25 microg/mL, and the MIC of azithromycin for both organisms was 1 microg/mL. H. influenzae developed resistance to both macrolides within 12 hours when exposed to sub-MICs of clarithromycin plus 14-hydroxyclarithromycin. However, when exposed to concentrations less than or equal to the MIC of azithromycin, resistance was not conferred to clarithromycin. S. aureus, on the other hand, became resistant to azithromycin and less susceptible to clarithromycin following exposure to sub-MICs of either macrolide. CONCLUSIONS: Clarithromycin and azithromycin elicited a concentration-independent bacteriostatic effect against H. influenzae and S. aureus at concentrations at least two times the MIC. In addition, concentrations maintained above the MIC prevented changes in the susceptibility of H. influenzae and S. aureus to both macrolides.

Anti-Bacterial Agents↗
PubMed1997

Prevention of the selection of clarithromycin-resistant Mycobacterium avium-intracellulare complex.

The prevalence of clarithromycin-resistant mutants in untreated bacterial populations of Mycobacterium avium-intracellulare complex (MAC) has been demonstrated to be between 10(-7) and 10(-8) colony-forming units (CFUs) in the beige mouse model. Selection of these mutants occurred during clarithromycin monotherapy if treatment was initiated when the bacterial population size reached approximately 10(8) CFUs per spleen. Likewise, selection of clarithromycin-resistant MAC was induced in AIDS patients during therapy with clarithromycin alone or in combination with drugs that were ineffective for the treatment or prevention of MAC infection. Because the emergence of clarithromycin resistance during preventive therapy was observed exclusively in AIDS patients with CD4+ cell counts < or = 25 cells/microliter, clarithromycin monotherapy can be recommended for the prevention of MAC infection in AIDS patients with CD4+ cell counts of > or = 50 cells/microliter. However, a clarithromycin-containing combination regimen is recommended for patients with CD4+ cell counts < 50 cells/microliter. Since preliminary animal experiments and clinical trials indicate that amikacin, ethambutol or rifabutin in combination with clarithromycin may prevent, or at least delay, the selection of clarithromycin-resistant mutants, further preventive trials are urgently needed to confirm these observations.

AIDS-Related Opportunistic Infections↗
PubMed1992

Clarithromycin and azithromycin: new macrolide antibiotics.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of clarithromycin and azithromycin are described. Clarithromycin and azithromycin are new macrolide antibiotics that are similar in structure to erythromycin. Compared with erythromycin, clarithromycin demonstrates increased activity against Staphylococcus aureus, streptococci, Legionella pneumophila, Moraxella catarrhalis, and Chlamydia trachomatis. Clarithromycin also has in vitro activity against Mycobacterium avium complex (MAC) and Toxoplasma gondii. Azithromycin has increased gram-negative activity compared with erythromycin, including activity against Haemophilus influenzae, while maintaining activity against gram-positive organisms. Azithromycin also has activity against sexually transmitted organisms including Chlamydia trachomatis. The pharmacokinetic profiles of clarithromycin and azithromycin are characterized by good oral bioavailability, excellent tissue penetration and persistence, and long elimination half-lives, which allow for once-daily or twice-daily dosing. Initial data show that clarithromycin and azithromycin are effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures. Azithromycin has been shown to be effective for the treatment of sexually transmitted diseases caused by Chlamydia trachomatis. Clarithromycin and azithromycin have been used to treat MAC and Toxoplasma infections in patients with the acquired immunodeficiency syndrome. The most frequently reported adverse effects for both agents have been nausea, diarrhea, and abdominal pain. Oral formulations of clarithromycin and azithromycin have recently been approved by the FDA. Clarithromycin and azithromycin are new macrolide antibiotics that have potential advantages over erythromycin; however, the role of these agents will be better defined as results of more ongoing trials become available for evaluation.

Azithromycin↗
PubMed2003

[Meta-analysis of clarithromycin compared with other antimicrobial drugs in the treatment of upper respiratory tract infections].

The goal of this meta-analysis was to evaluate the effectiveness of clarithromycin versus most commonly used treatments for upper respiratory infections. We performed a systematic review of comparative clinical trials found in the literature. Regarding effectiveness, no significant differences were found in comparisons between clarithromycin and amoxicillin-clavulanic acid for upper respiratory infections, nor for cephalosporins, amoxicillin or amoxicillin-clavulanic acid for otitis media, nor oral penicillin for classic streptococcal tonsillitis. Clarithromycin was more effective than betalactam antibiotics for sinusitis (OR: 1.27, 95% CI: 1.01-1.61 in intent-to-treat analysis). The effectiveness of clarithromycin was better than that for azithromycin, but only reached statistical significance in the per-protocol analysis. The global analysis including all 33 clinical trials showed a small benefit for clarithromycin reaching statistical significance in the fixed-effects model (OR: 1.12, 95% CI: 1.01-1.25). Regarding safety, the incidence of adverse events was significantly lower for clarithromycin compared to amoxicillin and amoxicillin-clavulanic acid. No differences were found when comparing adverse events due to cephalosporins, azithromycin and betalactam antibiotics, but the incidence of adverse events for clarithromycin was higher compared to that of oral penicillin for streptococcal tonsillitis treatment. Overall, all the compared drugs were well tolerated; discontinuations due to adverse events were very low: 2.2% for clarithromycin treatment and 2.5% for the other antibiotics. It was concluded that clarithromycin is an effective and safe treatment for upper respiratory infection, and its new formulation in a single daily dose may improve therapeutic compliance.

Anti-Bacterial Agents↗
PubMedDate not supplied

Metabolism and disposition of clarithromycin in man.

The metabolic fate and pharmacokinetics of clarithromycin following a single 250- or 1200-mg oral dose of 14C-clarithromycin were studied in six healthy adult males. Peak plasma levels of clarithromycin averaged 0.6 microgram/ml after the low dose and 2.7 micrograms/ml after the high dose. The AUC of clarithromycin increased 13-fold, with the 4.8-fold increase in dose, while the plasma half-life increased from 4.4 hr to 11.3 hr. The major metabolite in plasma and urine was the microbiologically active 14-hydroxylated-R epimer of clarithromycin. After 5 days, a mean of 38% of the low dose (18% as clarithromycin) and 46% of the high dose (29% as clarithromycin) was recovered in the urine, with approximately one-third eliminated during the first 24 hr. The nature of the urinary and fecal metabolites revealed the involvement of three metabolic pathways, viz. 1) hydroxylation at the 14-position to form the R and S epimers, 2) N-demethylation, and 3) hydrolysis of the cladinose sugar. Secondary metabolism via these pathways was also evident. The overall recovery of metabolites, but not total radioactivity, decreased 42% after the high dose. The nonlinear pharmacokinetic behavior of clarithromycin and the decrease in metabolite production suggest that clarithromycin metabolism can be saturated at high doses.

Adult↗
PubMed1995

Clarithromycin for treatment of Helicobacter pylori infections.

BACKGROUND: A better appreciation of the causal relationship between Helicobacter pylori infection and peptic ulcer disease and the benefit conferred by curing this infection has led to the recommendation that all patients with duodenal ulcer disease receive anti-H. pylori treatment. Multi-drug regimens, including bismuth, metronidazole and tetracycline or amoxycillin with an antisecretory agent, are successful in > 90% of treated patients but the emergence of metronidazole-resistant H. pylori has begun to limit their effectiveness. DESIGN: The search for the optimal anti-H. pylori treatment has focused on simplifying the regimen (to decrease adverse drug-related events and increase patient compliance), while retaining the excellent clinical results of the traditional multi-drug regimens. This article reviews the data concerning clarithromycin for treatment of H. pylori infections. RESULTS: Numerous evaluations have shown that clarithromycin has desirable attributes for anti-H. pylori treatment: clarithromycin is resistant to gastric acid, penetrates in high concentrations into gastric tissue and mucus, shows excellent antimicrobial activity against H. pylori, results in a high cure rate when used in two- and three-drug combinations, is associated with a low incidence of acquired H. pylori resistance and is well tolerated. Successful clarithromycin therapies include clarithromycin+omeprazole, clarithromycin+amoxycillin, or clarithromycin+omeprazole+tinidazole or metronidazole, and clarithromycin triple therapy. CONCLUSION: Clarithromycin may become an integral component of anti-H. pylori therapy.

Anti-Bacterial Agents↗
PubMed1996

Clarithromycin prophylaxis against Cryptosporidium enteritis in patients with AIDS.

Cryptosporidium enteritis (CE) in patients with acquired immunodeficiency syndrome (AIDS) can be a life-threatening opportunistic infection. A retrospective review of 471 charts of patients with AIDS in our clinic, prior to the availability of clarithromycin for the treatment of Mycobacterium avium complex (MAC), revealed that seven patients with CD4 counts < 25/mm3 developed CE. The median survival period from diagnosis to death in these patients was 10.6 days. The incidence of CE in patients with CD4 counts < 50/mm3 treated with clarithromycin prophylaxis for MAC was compared with patients not receiving clarithromycin prophylaxis. Of 136 patients with AIDS, 63 received clarithromycin 500 mg twice daily, and 73 patients not treated with clarithromycin represented the control group. None of the patients who received clarithromycin developed CE compared with four patients who developed CE in the control group. All four patients in the control group who developed CE had CD4 counts < 25/mm3. All patients who received clarithromycin remained stool negative for Cryptosporidium. In a subsequent 2-year follow-up of an additional 217 AIDS patients with CD4 counts < 50/mm3 receiving clarithromycin 500 mg twice daily as MAC prophylaxis, no patient developed CE. These results provide strong evidence supporting the use of clarithromycin as prophylaxis against cryptosporidium enteritis in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2006

Effects of combining extracts (from propolis or Zingiber officinale) with clarithromycin on Helicobacter pylori.

Propolis and Zingiber officinale have been shown to be specifically targeted against Helicobacter pylori strains, to possess antiinflammatory, antioxidant and antitumoral activity and to be used in traditional medicine for the treatment of gastrointestinal ailments. Considering that these natural products could potentially serve as novel therapeutic tools also in combination with an antibiotic, the aim of this work was to evaluate their effect when combined with clarithromycin on clinical H. pylori isolates (n = 25), characterized in respect to both clarithromycin susceptibility and the presence of the cagA gene. The results showed that the combinations of propolis extract + clarithromycin and Z. officinale extract + clarithromycin exhibited improved inhibition of H. pylori with synergistic or additive activity. Interestingly, the susceptibility to combinations was significantly independent of the microbial clarithromycin susceptibility status. Only one H. pylori strain showed antagonism towards the Z. officinale extract + clarithromycin combination. The data demonstrate that combinations of propolis extract + clarithromycin and Z. officinale extract + clarithromycin have the potential to help control H. pylori-associated gastroduodenal disease.

Adult↗
PubMed1999

Clarithromycin attenuates the inflammatory response induced by surgical trauma in a guinea pig model.

The effect of clarithromycin on the systemic and local inflammatory responses after surgical trauma was investigated using a guinea pig model. There was no statistically significant difference in the body temperature and respiratory rate of the guinea pigs between the clarithromycin and control groups, although there was a trend towards a lower temperature in the first 36 h after the operation, and a trend towards a lower respiratory rate on day 1 and day 2 (P=0.07 and 0.18, respectively) in the clarithromycin group. The total leukocyte count of both groups of animals increased from day -1 to day 4, and the increase was more marked in the control group (P=0.06 on day 1). The neutrophil and monocyte counts of the two groups of animals also increased after the operation. The neutrophil count of the control group was significantly higher than the clarithromycin group on day 1 and 2 (P<0.05 and 0.01, respectively), and the monocyte count of the control group was significantly higher than the clarithromycin group on day 1 (P<0.005). Moreover, the platelet count of the animals also increased after the operation, and the count in the control group was significantly higher than the clarithromycin group on day 1, 2 and 4 (P<0.05, 0.005 and 0.005, respectively). There was no difference between the haemoglobin concentration, lymphocyte count, eosinophil count and basophil count between the two groups of animals. The number of animals with wound discharge was lower in the clarithromycin group than the control group throughout the post-operative period, but the difference was not statistically significant. None of the animals developed signs of wound infection. The present observation suggests that clarithromycin suppressed both the systemic and local inflammatory response after surgical trauma, and it prompts further animal experiments for delineation of the mechanism of action, as well as clinical trials in major surgical procedures.

Animals↗
PubMedDate not supplied

In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203 strains of Haemophilus influenzae.

The in vitro activity of clarithromycin alone and in combination with its primary human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains of Haemophilus influenzae. Microdilution broth MICs and MBCs of both clarithromycin and 14-hydroxy-clarithromycin were determined. The clarithromycin MIC50 was 4 mg/l and the MIC90 was 8 mg/l. The hydroxy metabolite was 2-4-fold more active with an MIC50 and MIC90 of 2 mg/l. The MBCs were equal to the MICs. The microbicidal effect of combinations of clarithromycin and 14-hydroxy-clarithromycin was tested using a microdilution checkerboard technique and the fractional inhibitory index was calculated. The combination was additive in 92% and synergistic in 8% of all strains of H. influenzae tested; no antagonism was found. The results were independent of the site of isolation of the strain or presence of beta-lactamase. These findings suggest the potential clinical utility of clarithromycin for the treatment of H. influenzae infections.

Bacterial Typing Techniques↗
PubMed1991

The tolerance and toxicity of clarithromycin.

In a programme of Phase II and III trials, 3437 patients received clarithromycin. Twenty percent of these patients reported adverse events, and three-quarters of these were thought to be possibly or probably linked with the drug. Only 1% of these were severe and most of the adverse events (11% of patients) were digestive system upsets. There was no significant relationship between the dosage of clarithromycin and the incidence of adverse events. Comparison between clarithromycin and the other antibiotics used in controlled trials showed similar side effects reported for beta-lactam agents and clarithromycin but adverse events were reported less frequently with clarithromycin (19%) than with erythromycin (29%) and other macrolides. This was particularly noticeable for adverse events of the digestive system (9% with clarithromycin vs 20% with erythromycin). No significant haematological, hepatic or renal toxicity due to clarithromycin was reported. There may be slight elevation of theophylline levels during concomitant clarithromycin administration.

Adult↗
PubMed2000

Comparison of bacteriologic eradication of Streptococcus pneumoniae by clarithromycin and reports of increased antimicrobial resistance.

OBJECTIVE: To determine whether reported increases in Streptococcus pneumoniae resistance, as determined by in vitro antimicrobial susceptibility testing, correlate with the clinical efficacy of clarithromycin in treating patients with acute exacerbations of chronic bronchitis (AECB) or community-acquired pneumonia (CAP). BACKGROUND: Surveillance data on antimicrobial resistance suggest that the overall rate of S. pneumoniae resistance in vitro in the United States has increased to approximately 45% during the past decade. S. pneumoniae is showing increased resistance to penicillin, other beta-lactams, and macrolides. Despite this increased resistance, the clinical efficacy of clarithromycin does not appear to be diminished to the degree suggested by reported resistance rates. The author examined several studies of clarithromycin in patients with AECB or CAP that demonstrate S. pneumoniae eradication rates in vivo of approximately 92%. The discordance between reported increases in resistance of S. pneumoniae isolates in vitro and the eradication rate with clarithromycin in vivo is discussed in light of 5 observations. RESULTS: First, surveillance data on S. pneumoniae resistance rates to clarithromycin may be overestimated. Second, efflux mutant strains may not be clinically resistant. Third, host immune defenses play a role in treatment outcomes. Fourth, in vitro resistance may not correlate with in vivo clinical success. Finally, clarithromycin and its active metabolite, 14-OH-clarithromycin, attain high concentrations in patients. CONCLUSION: Reported increases in the prevalence of S. pneumoniae resistance do not appear to have had proportional effects on the clinical efficacy of clarithromycin in the treatment of patients with AECB or CAP caused by S. pneumoniae.

Animals↗
PubMedDate not supplied

Erythromycin, clarithromycin, and azithromycin: are the differences real?

Erythromycin, clarithromycin, and azithromycin are clinically effective for the treatment of common respiratory and skin/skin-structure infections. Erythromycin and azithromycin are also effective for treatment of nongonococcal urethritis and cervicitis due to Chlamydia trachomatis. Compared with erythromycin, clarithromycin and azithromycin offer improved tolerability. Clarithromycin, however, is more similar to erythromycin in pharmacokinetic measures such as half-life, tissue distribution, and drug interactions. Misunderstandings about differences among the macrolides (erythromycin and clarithromycin) and the azalide (azithromycin) in terms of pharmacokinetics and pharmacodynamics, spectrum of activity, safety, and cost are common. The uptake and release of these compounds by white blood cells and fibroblasts account for differences in tissue half-life, volume of distribution, intracellular:extracellular ratio, and in vivo potency. Although microbiologic studies reveal that gram-positive pathogens are equally susceptible to these agents, significantly more isolates of Haemophilus influenzae are susceptible to azithromycin than to erythromycin or clarithromycin. Concentrations achieved at the infection site and duration above the minimum inhibitory concentration are as important as in vitro activity in determining in vivo activity against bacterial pathogens. Analysis of safety data indicates differences among these agents in drug interactions and use in pregnancy. Analysis of safety data reveals pharmacokinetic drug interactions for erythromycin and clarithromycin with theophylline, terfenadine, and carbamazepine that are not found with azithromycin. Both erythromycin and azithromycin are pregnancy category B drugs; clarithromycin is a category C drug. The numerous differences in pharmacokinetics, microbiology, safety, and costs among erythromycin, clarithromycin, and azithromycin can be used in the judicious selection of treatment for indicated infections.

Anti-Bacterial Agents↗