Clarithromycin vs. Levofloxacin First-Line Triple and Sequential Regimens
Clarithromycin vs. Levofloxacin First-Line Triple and Sequential Regimens
BackgroundHelicobacter pylori eradication rates with standard triple therapy have declined to unacceptable levels.
Aim To compare clarithromycin and levofloxacin in triple and sequential first-line regimens.
Methods A total of 460 patients were randomized into four 10-day therapeutic schemes (115 patients per group): (i) standard OCA, omeprazole, clarithromycin and amoxicillin; (ii) triple OLA, omeprazole, levofloxacin and amoxicillin; (iii) sequential OACM, omeprazole plus amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus metronidazole for 5 days; and (iv) modified sequential OALM, using levofloxacin instead of clarithromycin. Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire.
Results Per protocol cure rates were: OCA (66%; 95% CI: 57–74%), OLA (82.6%; 75–89%), OACM (80.8%; 73–88%) and OALM (85.2%; 78–91%). Intention-to-treat cure rates were: OCA (64%; 55–73%), OLA (80.8%; 73–88%), OACM (76.5%; 69–85%) and OALM (82.5%; 75–89%). Eradication rates were lower with OCA than with all the other regimens (P < 0.05). No differences in compliance or adverse effects were demonstrated among treatments.
Conclusions Levofloxacin-based and sequential therapy are superior to standard triple scheme as first-line regimens in a setting with high clarithromycin resistance. However, all of these therapies still have a 20% failure rate.
Evolving research has demonstrated the relationship of Helicobacter pylori infection with chronic gastritis, peptic ulcer disease and gastric adenocarcinoma and MALT lymphoma, as well as the importance of a prompt cure of the infection to change the natural history of these diseases. After the initial high efficacy (eradication rate >90%) of triple standard regimens, we are witnessing within the last decade, a progressive decline in cure rates. The high prevalence of antimicrobial drug resistance, especially to clarithromycin and metronidazole, is believed to be the key factor. For this reason, consensus statements recommend empirical therapeutic regimens that achieve H. pylori cure rates higher than 80% on an intention-to-treat (ITT) basis.
Novel antibiotic regimens have been developed to overcome this troublesome scenario. One recent therapeutic innovation, postulated as an alternative to standard triple therapy, is the so called 'sequential' treatment. Strictly speaking, it is not a new approach, as it uses well-known drugs with approved indication for H. pylori eradication. However, the administration strategy is innovative. The sequential regimen is a simple dual therapy including a proton pump inhibitor (PPI) plus amoxicillin 1 g (both twice daily) given for the first 5 days followed by a triple therapy including a PPI, clarithromycin 500 mg and tinidazole (all twice daily) for the remaining 5 days. Its rationale is based on an initial phase with amoxicillin, which aims to lower the bacterial load in the stomach. Moreover, it has been speculated that amoxicillin may prevent the development of efflux channels for clarithromycin. This induction phase therefore is believed to amplify the efficacy of the second phase of therapy containing clarithromycin and metronidazole. Italian studies regarding this clarithromycin-based sequential therapy have shown promising eradication rates higher than 90%, even in patients with risk factors for triple therapy failure (clarithromycin resistance, non-ulcer dyspepsia, smoking or the absence of the gene CagA). Furthermore, a recent meta-analysis has shown that eradication rate with 10-day sequential therapy (93.4%) is notably higher than that for standard triple therapy (76.9%), with similar adherence in both groups. Thus, it has been questioned whether sequential therapy should be the preferred first line therapy for H. pylori infection albeit the global validation of the sequential scheme outside Italy is awaited.
On the other hand, levofloxacin, a fluoroquinolone with in vivo activity against H. pylori strains resistant to clarithromycin and metronidazole, has also shown promising results in different first-line triple regimens in Italy, Spain and the Netherlands, with an eradication rate on ITT ranging from 83% to 96%. The efficacy of levofloxacin in a sequential eradication scheme for H. pylori infection has been exclusively assessed in a single recent study from Turkey, with an 82% ITT cure rate. Moreover, a head-to-head comparison between similar clarithromycin and levofloxacin regimens has not been addressed yet. Therefore, we aimed to evaluate the cure rate of triple and sequential regimens containing clarithromycin or levofloxacin in a geographical area with a high failure rate of triple classical eradication therapy.
Abstract and Introduction
Abstract
BackgroundHelicobacter pylori eradication rates with standard triple therapy have declined to unacceptable levels.
Aim To compare clarithromycin and levofloxacin in triple and sequential first-line regimens.
Methods A total of 460 patients were randomized into four 10-day therapeutic schemes (115 patients per group): (i) standard OCA, omeprazole, clarithromycin and amoxicillin; (ii) triple OLA, omeprazole, levofloxacin and amoxicillin; (iii) sequential OACM, omeprazole plus amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus metronidazole for 5 days; and (iv) modified sequential OALM, using levofloxacin instead of clarithromycin. Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire.
Results Per protocol cure rates were: OCA (66%; 95% CI: 57–74%), OLA (82.6%; 75–89%), OACM (80.8%; 73–88%) and OALM (85.2%; 78–91%). Intention-to-treat cure rates were: OCA (64%; 55–73%), OLA (80.8%; 73–88%), OACM (76.5%; 69–85%) and OALM (82.5%; 75–89%). Eradication rates were lower with OCA than with all the other regimens (P < 0.05). No differences in compliance or adverse effects were demonstrated among treatments.
Conclusions Levofloxacin-based and sequential therapy are superior to standard triple scheme as first-line regimens in a setting with high clarithromycin resistance. However, all of these therapies still have a 20% failure rate.
Introduction
Evolving research has demonstrated the relationship of Helicobacter pylori infection with chronic gastritis, peptic ulcer disease and gastric adenocarcinoma and MALT lymphoma, as well as the importance of a prompt cure of the infection to change the natural history of these diseases. After the initial high efficacy (eradication rate >90%) of triple standard regimens, we are witnessing within the last decade, a progressive decline in cure rates. The high prevalence of antimicrobial drug resistance, especially to clarithromycin and metronidazole, is believed to be the key factor. For this reason, consensus statements recommend empirical therapeutic regimens that achieve H. pylori cure rates higher than 80% on an intention-to-treat (ITT) basis.
Novel antibiotic regimens have been developed to overcome this troublesome scenario. One recent therapeutic innovation, postulated as an alternative to standard triple therapy, is the so called 'sequential' treatment. Strictly speaking, it is not a new approach, as it uses well-known drugs with approved indication for H. pylori eradication. However, the administration strategy is innovative. The sequential regimen is a simple dual therapy including a proton pump inhibitor (PPI) plus amoxicillin 1 g (both twice daily) given for the first 5 days followed by a triple therapy including a PPI, clarithromycin 500 mg and tinidazole (all twice daily) for the remaining 5 days. Its rationale is based on an initial phase with amoxicillin, which aims to lower the bacterial load in the stomach. Moreover, it has been speculated that amoxicillin may prevent the development of efflux channels for clarithromycin. This induction phase therefore is believed to amplify the efficacy of the second phase of therapy containing clarithromycin and metronidazole. Italian studies regarding this clarithromycin-based sequential therapy have shown promising eradication rates higher than 90%, even in patients with risk factors for triple therapy failure (clarithromycin resistance, non-ulcer dyspepsia, smoking or the absence of the gene CagA). Furthermore, a recent meta-analysis has shown that eradication rate with 10-day sequential therapy (93.4%) is notably higher than that for standard triple therapy (76.9%), with similar adherence in both groups. Thus, it has been questioned whether sequential therapy should be the preferred first line therapy for H. pylori infection albeit the global validation of the sequential scheme outside Italy is awaited.
On the other hand, levofloxacin, a fluoroquinolone with in vivo activity against H. pylori strains resistant to clarithromycin and metronidazole, has also shown promising results in different first-line triple regimens in Italy, Spain and the Netherlands, with an eradication rate on ITT ranging from 83% to 96%. The efficacy of levofloxacin in a sequential eradication scheme for H. pylori infection has been exclusively assessed in a single recent study from Turkey, with an 82% ITT cure rate. Moreover, a head-to-head comparison between similar clarithromycin and levofloxacin regimens has not been addressed yet. Therefore, we aimed to evaluate the cure rate of triple and sequential regimens containing clarithromycin or levofloxacin in a geographical area with a high failure rate of triple classical eradication therapy.
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