{"id":1168,"date":"2016-10-18T17:07:14","date_gmt":"2016-10-18T17:07:14","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1168"},"modified":"2017-08-21T10:45:16","modified_gmt":"2017-08-21T10:45:16","slug":"primary-care-corner-with-geoffrey-modest-md-h-pylori-regimens-stratified-by-clarithromycin-sensitivity","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/10\/18\/primary-care-corner-with-geoffrey-modest-md-h-pylori-regimens-stratified-by-clarithromycin-sensitivity\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: H pylori regimens, stratified by clarithromycin sensitivity"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest <\/strong><\/p>\n<p>There was a recent systematic review and network meta-analysis of treatments of H Pylori infections in countries with high vs low clarithromycin resistance (see<strong>\u00a0<\/strong>doi:10.1136\/gutjnl-2016-311868). A network meta-analysis is helpful when there are not head-to-head comparisons of all of the therapies, using mathematical assumptions\/manipulations to approximate results across studies in an\u00a0attempt to approximate\u00a0the\u00a0likely results if there were such\u00a0direct\u00a0comparisons. \u00a0There was another recent blog which did a similar analysis of H pylori treatments\u00a0but was not stratified by clarithromycin sensitivity (see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/09\/03\/primary-care-corner-with-geoffrey-modest-md-h-pylori-regimens\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/09\/03\/primary-care-corner-with-geoffrey-modest-md-h-pylori-regimens\/<\/a> from the BMJ in 2015).<\/p>\n<p>Details of the current analysis:<\/p>\n<ul>\n<li>117 trials with\u00a032,852 patients analyzing 17 H pylori\u00a0eradication regimens were included<\/li>\n<li>Mean age 48, trials ranged from 58 to 1463 patients, with mean of 281<\/li>\n<li>All had documented H pylori infections by urea breath test, histologic or bacterial culture exams, or stool antigen<\/li>\n<li>All had documentation of H pylori eradication by intention-to-treat analysis, at least 4 weeks after therapy<\/li>\n<li>The authors\u00a0analyzed results of treatment stratified\u00a0by clarithromycin resistance, ascertained by a literature review of it prevalence by\u00a0the\u00a0countries where the RCTs were done, with a cutpoint of 15% resistance rate.<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>Compared to a 7-day course of clarithromycin-based triple therapy:\n<ul>\n<li>Overall: best was 14 days of sequential therapy, OR= 3.74 (2.37-5.96)<\/li>\n<li>In areas of high clarithromycin-resistance:\u00a0best was 14 days of sequential therapy, OR= 6.53 (3.23-13.63). and this did not diminish in the more recent\u00a0studies where resistance was likely to increase; second best was bismuth, PPI\u00a0and 2 of amoxacillin\/tetracylcine\/metronidazone\/clarithromycin\u00a0for 10 or 14 days, with OR 3.6<\/li>\n<li>In areas of low clarithromycin-resistance:\u00a0best was 10 or more\u00a0days of hybrid\u00a0therapy, OR= 2.85 (1.58-5.37); second best was\u00a0continuous therapy (e.g. PPI, amoxacillin and clarithromycin) at least\u00a010 days<\/li>\n<li>The lowest efficacy overall was triple therapy with metronidazole for 7 days<\/li>\n<li>Overall, better efficacy with longer treatments, which mostly meant 14 days<\/li>\n<li>Severe adverse events were rare in all regimens, though happened more often in the longer courses of therapy<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>Commentary:<\/p>\n<ul>\n<li>H pylori infection is unbelievably common, in &gt;50% of world&#8217;s population, and is associated with peptic ulcer disease, active gastroduodenal ulcer bleeding, gastric MALT (mucosa-associated lymphoid tissue lymphoma) and &gt;75% of\u00a0gastric\u00a0cancers<\/li>\n<li>H pylori eradication is recommended in patients on long-term NSAIDs, anti-platelet agents\/low-dose\u00a0ASA, and\u00a0those with unexplained iron-deficiency anemia or ITP,\u00a0per the Maastrich IV\/Florence Consensus Report in 2012 (see Gut.\u00a02012; 61:646) [as mentioned in prior blogs, see URL at the end of this blog, i saw a dramatic case 20 years ago\u00a0of a person with intractable steroid-resistant ITP, scheduled for surgery, but the Lancet had a small case report showing benefit of H pylori treatment. so I\u00a0tested and treated him for H pylori and the ITP melted away, off all meds, within weeks. and without surgery<\/li>\n<li>The standard therapy has been a PPI, amoxacillin and clarithromycin or metronidazole, but the effectiveness has been waning.<\/li>\n<li>There are some concerns about generalizing the results of the study\u00a0above. For example all of the 14 day sequential therapy trials were done in Asia. and the inherent and different biases in the different studies,\u00a0as well as patient characteristics across studies,\u00a0make confident conclusions difficult (e.g. some studies did not even record smoking prevalence), and studies\u00a0had different levels of blinding<\/li>\n<li>Countries with high\u00a0clarithroresistance: China, Croatia,\u00a0France, Greece,\u00a0Hong\u00a0Kong,\u00a0India,\u00a0Iran,\u00a0Italy,\u00a0Japan, Morocco, Spain,\u00a0Saudi\u00a0Arabia,\u00a0Singapore, Turkey<\/li>\n<li>Countries with low\u00a0clarithroresistance:\u00a0Chile, Ecuador, Finland,\u00a0Kenya, Korea, Kuwait, Mexico, Taiwan, Thailand, UK, US, Kosovo, Palestine, Romania (last 3 with no recorded resistance rate)<\/li>\n<li>Unfortunately, and a bit surprisingly, it was really hard to find out exactly what the therapies\u00a0were (they were all combined into\u00a0categories, such a \u201csequential\u201d or \u201chybrid\u201d therapies), even after scouring this\u00a0article and its supplement. My best guess is the following:\n<ul>\n<li>Sequential therapy for 10 days: first 5 days using PPI (g.omeprazole 20mg) and\u00a0amoxacillin\u00a01gm; followed by\u00a0PPI, clarithromycin 500mg and metronidazole 500mg\u00a0for the remaining 5 days (some studies have substituted\u00a0tinidazole\u00a0500mg for the metronidazole 500mg). all meds given BID<\/li>\n<li>Hybrid therapy for 14 days: first 7 days PPI (g.omeprazole 20mg) and\u00a0amoxacillin\u00a01gm; followed by PPI,\u00a0amoxacillin\u00a01gm,\u00a0clarithromycin\u00a0500mg and metronidazole 500mg for 7 days (again, some studies substituting\u00a0tinidazole\u00a0500mg for metronidazole 500mg). all meds given BID<\/li>\n<li>So, the hybrid therapy seems to be the same as the sequential therapy, with\u00a0amoxacillinfor the whole course instead of just the first half<\/li>\n<\/ul>\n<\/li>\n<li>The\u00a0sequential therapy (which includes clarithromycin at the end)\u00a0works\u00a0even with clarithromycin resistance, with 89% of clarithromycin-resistant strains responding vs 29% with standard therapy &#8212;\u00a0the\u00a0posited mechanism for resistance being that H\u00a0pylori had\u00a0developed efflux channels for clarithro that rapidly remove the drug from the bacteria and that amoxacillin changes the structure of the cell membrane to prevent effective clarithromycin efflux and therefore resistance. (see\u00a0Ann Intern Med 2007; 146:555-563, and\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2013\/11\/25\/primary-care-corner-with-dr-geoffrey-modest-sequential-or-standard-rx-for-h-pylori\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2013\/11\/25\/primary-care-corner-with-dr-geoffrey-modest-sequential-or-standard-rx-for-h-pylori\/<\/a>)<\/li>\n<li>From 9\/9\/15 blog (see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/09\/03\/primary-care-corner-with-geoffrey-modest-md-h-pylori-regimens\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/09\/03\/primary-care-corner-with-geoffrey-modest-md-h-pylori-regimens\/<\/a>): &#8220;and, one very important issue in the US is that we do not have data (at least in Boston) on\u00a0H\u00a0pylori sensitivities.\u00a0Maybe that makes sense. One of our greatest assets in Boston is the wonderful ethnic diversity here. One of the problems (at least as H\u00a0pylori is concerned) is that\u00a0H pylori organisms from different parts of the world are here\u00a0with their different antibiotic sensitivities.\u00a0So applying averaged sensitivities may not really benefit the individual patient in front of you.&#8221;<\/li>\n<li>I personally have been using only the 10-day\u00a0sequential therapy, since it was shown years ago to be superior,\u00a0though there are some differences in different studies. This therapy is certainly\u00a0a bit more complicated: I\u00a0usually have the patient bring back the bottles of pills and either I or a nurse review the regimen in detail. In\u00a0the very few cases of persistent H pylori\u00a0infection post-therapy that I have seen\u00a0(mostly detected by\u00a0stool antigen testing), I\u00a0use the bismuth-based regimen: high dose PPI\u00a0bid, amoxicillin 1gm bid, levofloxacin 500 mg in the evening, and bismuth\u00a0subcitrate240mg bid for 14 days.\u00a0So far, so good.<\/li>\n<li>But, based on the current\u00a0study, I will change to the 14-day sequential therapy\u00a0course. I\u00a0am certainly concerned that many of my patients are getting too many antibiotics, esp azithromycin\u00a0(g., see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/antimicrobial-resistance\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/antimicrobial-resistance\/<\/a>)\u00a0and metronidazole, which are likely to breed resistance in untreated H pylori infections. So, I follow symptoms closely post-therapy, check H pylori antigen when the patient is symptomatic, and retreat with one of the rescue regimens. \u00a0If this resistance happens more often, I will switch to the hybrid regimen above. \u00a0Also, tinidazole\u00a0may be more effective\u00a0than metronidazole, and tinidazole is available in the US\u00a0but mostly with the disincentive of a Prior Approval&#8230;&#8230;.\u00a0[Though, the tinidazole may be more effective\u00a0in the US precisely because\u00a0we use much much more metronidazole]<\/li>\n<\/ul>\n<p><strong>\u00a0<\/strong>Also so see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/gi-h-pylori\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/gi-h-pylori\/<\/a> has a series of blogs on H Pylori infection, including some suggesting eradication leads to lower incidence of gastric cancer, increased bleeding if H Pylori positive and taking NSAIDs (and some studies showing that eliminating H Pylori leads to lower risk of NSAID-associated bleeding), and a review of several studies of different medication regimens.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: H pylori regimens, stratified by clarithromycin sensitivity [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/10\/18\/primary-care-corner-with-geoffrey-modest-md-h-pylori-regimens-stratified-by-clarithromycin-sensitivity\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1168","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1168","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1168"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1168\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1168"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1168"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1168"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}