NEW YORK (Reuters Health) - Triple therapy combining a proton-pump inhibitor (PPI), amoxicillin, and high-dose metronidazole (PAM) given thrice daily for 14 days provides Helicobacter pylori eradication rates similar to those with triple-therapy regimens containing clarithromycin (PAC), according to a new report.
Currently, quadruple therapy with three antibiotics (clarithromycin, amoxicillin, and metronidazole) plus a PPI for 10-14 days is the method of choice for H. pylori eradication. With the increasing resistance to clarithromycin in many areas, some have argued that triple therapy with PAM could be a reasonable alternative treatment, researchers note in the Journal of Antimicrobial Chemotherapy, online June 23.
Dr. Xavier Calvet from Universitat Autonoma de Barcelona in Spain and colleagues compared the efficacy and safety of PAM with other schedules for first-line H. pylori treatment in their systematic review and meta-analysis of 94 published reports, including 31 randomized controlled trials (RCTs).
The efficacy of PAM was significantly lower than those of PAC (70% vs. 77.1%, p<0.002) based on 22 randomized trials. It was also lower than that of PMC (PPI, metronidazole, clarithromycin) based on 18 trials (66.4% vs. 77.7%, p=0.0003).
However, PAM offered similar efficacy to PAC and PMC when given for at least 14 days, although total cure rates of all triple therapies remained less than 90%, according to the report.
When observational studies were included in the analysis, efficacy was increased when PAM was administered for 14 days, when PPIs were administered every 12 hours or given at high doses, when antibiotics were administered every eight hours, and when amoxicillin was administered at high doses or every eight hours or every six hours instead of every 12 hours.
Primary metronidazole resistance was present in 32% of patients tested and was associated with significantly lower cure rates (59% vs. 89% without metronidazole resistance).
"Our study shows that although overall per-protocol cure rates with triple PAM therapy were ~80%, the use of high-dose antibiotics, q8h antibiotic therapies and 14 day treatments may increase cure rates," the researchers conclude. "The combination of all these strategies would probably achieve cure rates >90% by partially overcoming the negative effects of primary metronidazole resistance on treatment efficacy. However, the hypothesis-generating data from the present meta-analysis should be confirmed in future clinical trials."
Dr. Francis Megraud, a co-organizer of the European (Maastricht) guidelines for the management of H. pylori from CHU Pellegrin in Bordeaux, France, told Reuters Health by email that PAC "treatment is not recommended anymore in most parts of Europe, essentially because of a high level of resistance to clarithromycin which is the essential determinant of failure, and not taken into account in this article."
Instead, said Dr. Megraud, who was not involved in the new study, physicians should follow the Maastricht guidelines, the fifth edition of which will be published soon.