pylori would likely result in the development of more resistant strains of Mycobacterium tuberculosis. It has already been illustrated that its efficacy

may be reduced somewhat by past rifampicin treatment [47]. Finally, serious myelotoxicity and ocular adverse events have been reported with this treatment [48,49]. Sequential therapy has been proposed as an alternative to standard triple therapy MK2206 for the eradication of H. pylori [50]. The primary goal of this regimen is to overcome clarithromycin resistance. Hypothetically, during the first 5 days of therapy, amoxicillin would weaken the bacterial cell wall, which prevents the formation of the channels that block clarithromycin from entering the bacterium and hence cause resistance to the antibiotic. Then, in the second phase of therapy, clarithromycin and a nitroimidazole are added for a further 5 days. Proton-pump inhibitor is continued throughout treatment. A meta-analysis demonstrated that eradication rates with sequential therapy are 93.4%

compared with 76.9% for standard triple therapy [19]. Another meta-analysis concluded that the number needed to treat (NNT) for sequential therapy to achieve eradication that would not have otherwise been achieved with standard triple therapy was 8 [51]. All of the studies in this meta-analysis were on Italian patients. Several studies in the last 12–18 months, however, have focussed on the efficacy of sequential therapy in other populations. In a Korean cohort, the eradication rate of sequential BAY 80-6946 nmr therapy was 91.8% by ITT [52]. In treatment naive patients in Turkey, ITT eradication rates were 82.1% in a trial which used sequential isothipendyl therapy with tetracycline [53]. Other forms of sequential therapy have also been trialed including a 14-day version, which substituted levofloxacin for clarithromycin. This also appears to be a viable option based on ITT eradication rates of over 80% in trials in Spain and Turkey [22,54]. Concomitant therapy has also been proposed. It is intended to reduce the complexity associated with sequential therapy by having the patient take all three antibiotics for the entire ten-day duration of therapy. When compared

to standard triple therapy in a meta-analysis, concomitant therapy had an ITT eradication rate of 89.7%, superior to standard triple therapy with a pooled odds ratio of 2.86 [55]. It must be noted that although it is designed to overcome clarithromycin resistance, clarithromycin is central to both sequential and concomitant therapy and would still be at the mercy of changes in patterns of clarithromycin resistance which are probably primarily contingent on the rates of prescription of clarithromycin in the community for non-gastrointestinal infections [56,57]. In addition, there exists a body of opinion that clarithromycin and metronidazole ought not be used together for H. pylori eradication as those who fail to have eradication will subsequently have at least single and often double resistance [58].