Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin

Background: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. Methods: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. Results: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n= 74) or to omeprazole plus placebo (n= 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72–91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0–7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71–91%) and at 4 weeks in 100% (95% CI: 95–100%), compared with 77% (95% CI: 66–86%) and 97% (95% CI: 91–100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1–16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63–86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P= 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. Conclusions: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.     

Influence of clarithromycin dosage on pantoprazole combined triple therapy for eradication of Helicobacter pylori

Background:

Low-dose clarithromycin (250 mg b.d.) in combination with omeprazole and metronidazole has been recommended for the eradication of Helicobacter pylori. Whether the substitution of omeprazole by pantoprazole requires adjustment of the clarithromycin dose is not known.

Aim:

To directly compare the efficacy and tolerability of two different dosages of clarithromycin in combination with pantoprazole and metronidazole.

Methods:

One hundred and sixty-three patients with endoscopically confirmed gastritis, gastric or duodenal ulcers and positive H. pylori findings in the rapid urease test were randomized and treated for 7 days with pantoprazole (40 mg b.d.), metronidazole (500 mg b.d.) and clarithromycin using either a regimen of 500 mg b.d. (group PMC 500) or 250 mg b.d. (group PMC 250). Eradication success was determined no less than 4 weeks after concluding therapy using the ¹³C-urea breath test.

Results:

One-hundred and thirty-nine patients completed the study. Based on a per protocol analysis, successful eradication was documented in 63/70 patients (90.0%) in group PMC 500 and in 62/69 patients (89.9%) in group PMC 250. Based on the intention-to-treat analysis, eradication rates were 78.8% (group PMC 500) and 75.6% (group PMC 250). The incidence of adverse effects was significantly higher in patients receiving PMC 500 (50.0%) than in those receiving PMC 250 (25.4%).

Conclusions:

Triple therapy with pantoprazole, metronidazole and clarithromycin provides an efficient eradication regimen for H. pylori infection. A low dose of clarithromycin is equal to a higher dose in therapeutic efficacy and it offers the advantage of improved tolerance and lower cost.

     

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

SUMMARY

Objective: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes.

Research design and methods: A total of 539 patients, aged 12–75 years, were randomized to receive either clarithromycin extended-release (ER) 500?mg once daily for 5 days or penicillin V 500?mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial. Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture.

Main outcome measures: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8–12; visit 4: study days 13–20; and visit 5: study days 40–50).

Results: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (?8.2, 5.1)). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (?10.0, 4.4)). Clinical cure was achieved in > 94% of patients in each treatment group. The most commonly reported study drug-related adverse events (< 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea.

Conclusion: Clarithromycin ER 500?mg once daily for 5 days is equally effective as penicillin V 500?mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.     

A randomized prospective comparison of clarithromycin versus amoxycillin in combination with omeprazole for eradication of Helicobacter pylori

Aim: To compare H. pylori eradication rates using omeprazole in conjunction with either amoxycillin or clarithromycin. Background: Omeprazole with amoxycillin is the most widely used dual therapy regimen for eradication of H. pylori. A recent open study suggested a high eradication rate combining omeprazole with the newer macrolide, clarithromycin. Methods: A randomized prospective trial in 54 patients was conducted to compare 2 weeks of treatment with omeprazole 40 mg once daily and either amoxycillin 500 mg three times daily or clarithromycin 500 mg three times daily. H. pylori eradication was assessed using the ¹³C urea breath test. Results: Eradication was achieved in 18/26 (69.2%) of subjects treated with omeprazole and amoxycillin and 18/25 (72.0%) of those treated with omeprazole and clarithromycin (P= N.S.). Minor side effects, most commonly altered taste, were reported by 16% of patients and were more frequent in those randomized to clarithromycin (P= 0.01). Conclusions: These regimens are similarly effective. However, clarithromycin is more expensive, associated with a greater frequency of side effects and, unlike amoxycillin, resistance by H. pylori has been reported. This suggests that clarithromycin may be a useful alternative when there is penicillin allergy or previous treatment failure, but it should not replace amoxycillin as first choice in omeprazole-based dual therapy.     

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

SUMMARY

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.     

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

SUMMARY

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).

Patients and methods: Outpatients aged >18 years (n?=?448) with CAP were enrolled in a randomized, double-blind, multinational study and received telithromycin 800?mg once daily (n?=?224) or clarithromycin 500?mg twice daily (n?=?224) for 10 days. The primary outcome measure was clinical efficacy at post-therapy/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 (intent to treat population) up to the late post-therapy visit (Days 31-36). Study investigators who were blinded to the treatment arm assessed whether hospital admissions were CAP related or not. Hospitalization costs (US$) associated with telithromycin and clarithromycin treatment were compared.

Results: Per-protocol clinical cure rates for telithromycin and clarithromycin were statistically equivalent (88.3% [143/162] vs 88.5% [138/156] - difference: ?0.2%; 95% CI: ?7.8, 7.5). There were four CAP-related hospitalizations (1.8 events/100 patients) among patients treated with telithromycin vs eight (3.6 events/100 patients) among clarithromycin patients (p?=?0.281). The total number of CAP-related hospital days for telithromycin and clarithromycin patients was 23 vs 64 days (10.3 vs 28.6 days/100 patients), respectively (p?=?0.177). CAP-related hospitalization costs per 100 telithromycin and clarithromycin patients were $20360 vs $70567, respectively (difference: ?25182; 95% CI: ?49531; 9168).

Conclusions: This study demonstrates that telithromycin is an effective therapy for outpatients with CAP. There were no significant differences in hospitalization rates between treatments; however, a tendency towards a numerically reduced number of hospitalizations/days required in hospital among telithromycin patients was observed. This could potentially translate into reduced hospitalization costs for telithromycin vs clarithromycin in the treatment of CAP.     

A Preliminary Study of Clarithromycin versus Doxycycline in the Treatment of Nongonococcal Urethritis and Mucopurulent Cervicitis

In a comparison of drug safety and efficacy, 40 adult outpatients with clinical signs and symptoms of nongonococcal urethritis or mucopurulent cervicitis were treated with either clarithromycin 250 mg or doxycycline 100 mg twice/day for 7 days. Clinical and laboratory evaluations were repeated during, at the end, and 3 weeks after the completion of therapy. Isolation and susceptibility tests of Chlamydia and Mycoplasma isolates were performed at each visit. All but one patient who received doxycycline were clinically cured or improved at the end of treatment. Two (10%) patients who received clarithromycin and three (15%) who received doxycycline had clinical relapses of the infection. All isolates of Chlamydia trachomatis were eradicated and did not recur in both groups. Doxycycline was more effective than clarithromycin in eradicating Ureaplasma urealyticum (p<0.01). Both groups reported a high frequency of minor adverse effects, but no patient discontinued therapy. Overall, clarithromycin was clinically safe and effective treatment in patients with nongonococcal urethritis and mucopurulent cervicitis.     

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

ABSTRACT

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/125?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 ≥ 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.     

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

SUMMARY

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 10days (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-therapy (Days 31-36). Study investigators blinded to treatment assessed whether hospital admissions were CAP-related or not. CAP-related

hospitalization costs (US$) for telithromycin and clarithromycin were compared.

Results: Clinical cure rates were similar in patients who received clarithromycin for 10days 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 $86205 for clarithromycin vs $37930 (difference: ?26446; 95% CI: ?66654; 13762) and $16 091 (difference: ?37847; 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 is an effective treatment for CAP, and that telithromycin treatment of CAP may be associated with fewer hospital days and potentially lower hospitalization costs than clarithromycin treatment.     

Metronidazole and clarithromycin resistance amongst Helicobacter pylori isolates from a large metropolitan hospital in the United States

Background: Metronidazole and clarithromycin-based therapies are among the most efficacious treatment regimens for H. pylori infection. Resistance to metronidazole or clarithromycin is associated with impaired therapy with these agents. We conducted a retrospective review of susceptibility data to determine the frequency of primary metronidazole and clarithromycin resistance among H. pylori isolates from a single metropolitan hospital in the United States. The database comprised 933 patients who presented at the Digestive Diseases Clinic at the Veterans Affairs Medical Center in Houston between September 1988 and January 1997 with complaints of dyspepsia, abdominal pain and peptic ulcer disease. One hundred and seventy-nine of these patients had both pharmaceutical records available for evaluation and culture and antimicrobial susceptibility data for analysis. The MICs were determined by both E-test and broth microdilution tests. The frequency of primary metronidazole resistance was 37.4% (67/179). The level of primary clarithromycin resistance was 6.1%. Dual metronidazole and clarithromycin resistance was present in approx. 3%. The high level of primary metronidazole and clarithromycin resistance in H. pylori isolates from this metropolitan hospital is such that antimicrobial susceptibility data should be available so that informed choice can be made for specific eradication therapies, especially in patients who fail treatment.     

One-week triple therapy using omeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia: influence of dosage of omeprazole and clarithromycin

Background:

Triple therapy based upon omeprazole, amoxycillin and clarithromycin for 7 days is the reference treatment used in France for the eradication of Helicobacter pylori. However, optimal dosages of omeprazole and clarithromycin have not been determined.

Aim:

To compare four eradication regimens using this treatment in patients with non-ulcer dyspepsia.

Methods:

Two hundred and seventy-four patients with symptoms of dyspepsia, normal upper GI endoscopy and a positive urease test were included in the study. A ¹³C-urea breath test (UBT) was obtained before and 6 weeks after treatment. Patients were randomized to one of the following 7-day regimens: 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O₂₀AC₅₀₀) or 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O₂₀AC₁₀₀₀) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O₄₀AC₅₀₀) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O₄₀AC₁₀₀₀). Compliance was assessed by returned tablet counts. Eradication was defined as conversion from positive ¹³C-UBT at entry to negative ¹³C-UBT 6 weeks after cessation of therapy.

Results:

Two hundred and fifty-eight patients were included in the intention-to-treat (ITT) analysis. From the least to the most effective regimen, eradication rates were: O₂₀AC₁₀₀₀: 60.0% (95% CI: 47.6–72.4), O₂₀AC₅₀₀: 64.1% (52.3–75.8), O₄₀AC₁₀₀₀: 64.2% (52.7–75.7), O₄₀AC₅₀₀: 74.6% (64.2–85.0) (N.S.). Overall compliance was good in 92% of patients. The most frequent adverse events were diarrhoea and taste impairment, occurring mainly in the high-dose clarithromycin groups.

Conclusions:

Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies. This study supports the use of a double dose of omeprazole, although the difference between groups was non-significant, but provides no argument in favour of a high dose of clarithromycin.

     

Short report: clarithromycin, an alternative to metronidazole in the triple therapy of Helicobacter pylori infection

Background: Triple therapy for Helicobacter pylori using metronidazole is less effective in patients with a metronidazole resistant strain. Moreover, metronidazole is responsible for many side-effects. This open study examined the efficacy and side-effects of a triple treatment regimen substituting clarithromycin for metronidazole. Methods: 36 patients with a H. pylori infection, proven by culture, were treated with tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 250 mg q.d.s. and clarithromycin 250 mg q.d.s. for 10 days. Eradication was defined as a negative culture and histological examination of antral biopsy specimens, taken at least 6 weeks after completion of the treatment. Results: Eradication was achieved in 26 patients (72%). The treatment was well tolerated with only 4 (11 %) of the patients having significant side-effects. Conclusion: Triple therapy with clarithromycin seems to be less effective than standard triple treatment when the prevalence of metronidazole resistance is low. It is suggested, however, that this combination could be a valuable alternative in areas with a high prevalence of metronidazole resistance.     

Effects of clarithromycin in patients with active rheumatoid arthritis

ABSTRACT

Objective: To evaluate the clinical efficacy, safety, and tolerability of clarithromycin in patients with rheumatoid arthritis.

Research design and methods: This was a 6-month, monocenter, randomized, double-blind, placebo-controlled study. A total of 81 patients with early rheumatoid arthritis were treated with either once-daily oral clarithromycin (500?mg) or daily oral placebo for 6 months.

Main outcome measures: The primary efficacy variable was the percentage of patients who had a 20% improve­ment according to American College of Rheumatology (ACR) criteria (an ACR 20 response) at 6 months. Secondary outcome measures were 50% improvement and 70% improvement according to ACR criteria (an ACR 50 response and an ACR 70 response, respectively).

Results: A significantly greater percentage of patients treated with 500?mg clarithromycin met the ACR 20 response at 6 months compared with patients who received placebo (59 vs. 33%; p < 0.001). Greater percentages of patients treated with 500?mg clarithromycin also achieved ACR 50 responses (34 vs. 10%; p < 0.001) and ACR 70 responses (20 vs. 3%; p = 0.003) compared with patients who received placebo, respectively. Clarithromycin was well tolerated. There were no dose-limiting toxic effects.

Conclusions: In patients with early active rheumatoid arthritis, treatment with clarithromycin significantly improved the signs and symptoms of rheumatoid arthritis. Clarithromycin has been shown to be effective against rheumatoid arthritis.     

Role for 5‑day,once-daily extended-release clarithromycin in acute bacterial exacerbation of chronic bronchitis

ABSTRACT

Background: Clarithromycin is commonly dosed for 7 or more days in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Studies with other antibiotics have shown equivalent efficacy, reduced/similar frequency of adverse events, improved adherence and patient satisfaction, and lower treatment costs with a shorter treatment course.

Patients and methods: The study population was derived from two multicenter, randomized, double-blind (North America)/single-blind (France) comparative trials in which outpatients at least 35 years old with a presumptive diagnosis of obstructive ABECB were randomized to receive clarithromycin extended-release (ER) 1000?mg once daily for 5 days or a comparator agent – clarithromycin immediate-release (IR) 500?mg twice daily for 7 days (in North America) or telithromycin 800?mg once daily for 5 days (in France).

Results: A total of 818 patients were randomized (411 to clarithromycin ER and 407 to a comparator agent). The clinical cure rate in clinically evaluable patients at the follow-up visit was 90% each for the clarithromycin ER group (318/353) and the comparator group (318/355). The patient bacteriological cure rate and the overall target pathogen eradication rate in clinically and bacteriologically evaluable patients were each 92% for the clarithromycin ER group (155/168 and 189/205, respectively) and 93% for the comparator group (147/158 and 183/197, respectively) at the follow-up visit. The study drugs were generally well tolerated, with < 2% of patients discontinuing their treatment prematurely due to a drug-related adverse event. The incidence of drug-related adverse events was 18% (73/411) in the clarithromycin ER group and 24% (97/407) in the comparator group. Clarithromycin ER-treated patients reported statistically significantly fewer episodes of abdominal pain than did patients treated with a comparator agent (0.2% vs. 1.7%, respectively; p = 0.037). This combined analysis is limited by differing blinding methods, comparator agents, and their duration of administration. Furthermore, many patients were excluded from the clinically and bacteriologically evaluable group due to lack of a pretreatment target pathogen.

Conclusion: A once daily, 5?day clarithromycin ER regimen appears to be a suitable choice for treating patients with ABECB.     

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori

Background:

A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens.

Aim:

To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease.

Methods:

Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a ¹³C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment.

Results:

Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n=262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P=0.85, chi-squared test) with regard to the healing of duodenal ulcer disease.

Conclusions:

The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

     

Eradication of Helicobacter pylori with lansoprazole and clarithromycin

Background: Helicobacter pylori eradication with omeprazole and clarithromycin varies between 40 and 80%. The dose, frequency and duration of treatment may account for these differences. Lansoprazole, a recently introduced proton pump inhibitor, is a more potent H. pylori bacteriostat in vitro than omeprazole. The aim of this open, comparative, randomized study was to investigate the efficacy and safety of lansoprazole 30 mg once or twice a day (and for 2 vs. 4 weeks) plus clarithromycin 500 mg t.d.s. for 2 weeks, in the eradication of H. pylori. Methods: Sixty-six patients with H. pylori infection received clarithromycin 500 mg t.d.s. for 2 weeks and one of four lansoprazole regimens: 30 mg once a day for 2 (Group 1, n= 16) or 4 (Group 2, n= 16) weeks, or 30 mg b.d. for 2 (Group 3, n= 18) or 4 (Group 4, n= 16) weeks. H. pylori eradication was determined by the ¹³C-urea breath test 4 weeks after finishing treatment. Results: Per protocol analysis (53 patients) shows that H. pylori was eradicated in 6/13 (46%) in Group 1, 7/13 (54%) in Group 2, 9/14 (64%) in Group 3 and 9/13 (69%) in Group 4. Thirty-one of 68 patients experienced side effects. Analysis on an intention-totreat basis gave similar results. Conclusion: The dose of lansoprazole appears to be more important than the duration of therapy. Dual therapy with lansoprazole and clarithromycin should be investigated further as a possible treatment regimen for H. pylori infection.     

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 Helicobarter 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.     

Current Strategies for the Prevention and Treatment of Disseminated Mycobacterium avium Complex Infection in Patients with AIDS

Disseminated Mycobacterium avium complex (MAC) infection is a common opportunistic disease in patients with acquired immunodeficiency syndrome and is associated with significant morbidity and mortality. Macrolides effectively prevented and treated the disease in clinical trials. In general, prophylaxis with clarithromycin or azithromycin is indicated for patients with CD4 cell counts below 50 cells/mm³. Treatment of disseminated MAC infection is lifelong and must include two agents with antimycobacterial activity. Clarithromycin plus ethambutol is considered the standard regimen. Potential alternatives are azithromycin, rifabutin, ciprofloxacin, clofazamine, and amikacin. Several factors influence drug selection, such as the patient's immune status, evidence of treatment safety and efficacy, drug interactions, and potential for resistance.     

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.

     

Low rate of emergence of clarithromycin-resistant Helicobacter pylori with amoxycillin co-therapy

Background:

Patients with persistent Helicobacter pylori infection following treatment with clarithromycin or omeprazole plus clarithromycin often develop clarithromycin resistance.

Aim:

To assess pre- and post-treatment antibiotic resistance in three double-blind trials of triple therapy with omeprazole, amoxycillin and clarithromycin.

Methods:

Patients with H. pylori and duodenal ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks after completion of therapy in studies 1 and 2, and at 4–6 weeks after therapy in study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by histology, or by culture. Eradication was defined as no positive biopsy test and ≥ 2 negative tests. Susceptibility testing was performed using the Etest.

Results:

In the 91 patients with pre-treatment susceptible isolates who had persistent infection after AC, 10 developed resistance, eight had intermediate susceptibility and 73 continued to have clarithromycin-susceptible H. pylori isolates. In the 10 patients with pre-treatment susceptible isolates who had persistent infection after OAC, three developed clarithromycin resistance and seven still had susceptible isolates.

Conclusions:

Use of amoxycillin co-therapy results in a low rate of clarithromycin resistance developing in patients with persistent H. pylori infection following therapy with a clarithromycin-containing regimen.