헬리코박터 치료를 위한 레보플록사신 3제/4제 요법, Levofloxacin triple/quadruple therapy for H. pylori eradication

헬리코박터 치료를 위한 레보플록사신 요법은 나라에 따라 2차 치료 또는 3차 치료로 사용되고 있습니다.

해리슨 20판과 Goldman-Cecil 26판에서는 500 mg bid로 나와 있지만 UpToDate와 레보플록사신이 포함된 여러 헬리코박터 관련 논문에서는 bid가 아닌 500 mg qd로 연구가 진행되었습니다. 레보플록사신 3제 요법에 bismuth를 포함시킨 4제 요법은 3제 요법과 efficacy는 비슷하였지만, 레보플록사신에 대한 내성이 있는 균주 박멸률은 4제 요법에서 더 높았습니다(71% vs 37%).

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Levofloxacin triple therapy – Levofloxacin triple therapy consists of levofloxacin, amoxicillin, and a PPI for 10 to 14 days. In a network meta-analysis eradication rates with levofloxacin triple therapy for 10 to 14 days were significantly higher than clarithromycin triple therapy for seven days (90 versus 73 percent). Although not directly compared, the pooled eradication rate of levofloxacin triple therapy was also higher than clarithromycin triple therapy for 10 to 14 days (81 percent, 95% CI, 78 to 84 percent). Metronidazole can be substituted for amoxicillin in penicillin-allergic individuals.

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Salvage therapies for H. pylori infection

Regimen	Drugs (doses)*	Dosing frequency	Duration (days)	FDA approval
Bismuth quadruple	PPI (standard dose¶)	Twice daily	14	NoΔ
	Bismuth subcitrate (120 to 300 mg [not available in US] or 420 mg [available in North America and elsewhere as part of Pylera combination pill])[1] or Bismuth subsalicylate (300 or 524 mg)[1]	Four times daily
	Tetracycline (500 mg)	Four times daily
	Metronidazole (250 to 500 mg)	Three to four times daily
Levofloxacin triple	PPI (standard dose¶)	Twice daily	14	No
	Levofloxacin (500 mg)	Once daily
	Amoxicillin (1 gram)	Twice daily
Concomitant	PPI (standard dose¶)	Twice daily	10 to 14	No
	Clarithromycin (500 mg)	Twice daily
	Amoxicillin (1 gram)	Twice daily
	Metronidazole or tinidazole (500 mg)	Two or three times daily
Rifabutin triple◊	PPI (standard dose¶)	Twice daily	10	No
	Rifabutin (300 mg)	Once daily
	Amoxicillin (1 gram)	Twice daily
High-dose dual	PPI (standard to double dose¶)	Three to four times daily	14	No
	Amoxicillin (1 gram three times daily or 750 mg four times daily)	Three to four times daily

FDA: United States Food and Drug Administration; PPI: proton pump inhibitor.

* Doses are for adults with normal renal function. Dose adjustment is warranted in patients with renal impairment for certain antibiotics (eg, levofloxacin, rifabutin, clarithromycin if end-stage disease).

¶ Standard dose of orally administered proton pump inhibitors include: Lansoprazole 30 mg daily, omeprazole 20 mg daily, pantoprazole 40 mg daily, rabeprazole 20 mg daily, or esomeprazole 20 mg daily.

Δ PPI, bismuth, tetracycline, and metronidazole prescribed separately is not an FDA-approved treatment regimen. However, Pylera, a combination product containing bismuth subcitrate, tetracycline, and metronidazole combined with a PPI for 10 days is an FDA-approved treatment regimen.

◊ Rifabutin-containing regimens should be reserved for patients with ≥3 previous eradication failures.

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Reference:

Fallone CA, Chiba N, van Zanten SV, et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastro 2016; 151:51.

Adapted by permission from Macmillan Publishers Ltd: American Journal of Gastroenterology. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017; 112:212. Copyright © 2017. www.nature.com/ajg.

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aThe recommended first-line regimens for most of the world are shown in bold type.

bThis regimen should be used only for populations in which the prevalence of clarithromycin-resistant strains is known to be <20%. In practice, this restriction limits the regimens’ appropriate range mainly to northern Europe.

cMany authorities and some guidelines recommend doubling this dose of omeprazole, as trials show resultant increased efficacy with some antibiotic combinations. Omeprazole may be replaced with any proton pump inhibitor at an equivalent dosage. Because extensive metabolizers of PPIs are prevalent among Caucasian populations, many authorities recommend esomeprazole (40 mg bid) or rabeprazole (20 mg bid), particularly for regimens 4 and 5.

dData supporting this regimen come mainly from Europe and are based on the use of bismuth subcitrate (1 tablet qid) and metronidazole (400 mg tid). This is a recommended first-line regimen in most countries and is the recommended second-line regimen in northern Europe.

eThis regimen may be used as an alternative to regimen 3.

fMetronidazole (500 mg bid) may be used as an alternative.

gThis regimen is used as second-line treatment in many countries (particularly where quadruple or concomitant therapy is used as the first-line regimen) and as third-line treatment in others. It may be less effective where rates of fluoroquinolone use are high and is more likely to be ineffective if there is a personal history of fluoroquinolone use for previous treatment of other infections.

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REF. Harrison's 20th edition

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* Triple therapy consists of a proton pump inhibitor or bismuth compound, together with two of the listed antibiotics, usually given for 7 to 14 days.

† Bismuth-based quadruple therapy consists of a proton pump inhibitor plus the combination of a bismuth compound and two antibiotics, usually given for 7 to 14 days.

‡ Non-bismuth-based quadruple therapy consists of a proton pump inhibitor, plus three antibiotics usually given for 10 days and sometimes extended to 14 days. The three forms of non-bismuth-based quadruple therapy differ in their antibiotic dosing schedules: (1) sequential therapy gives amoxicillin for the first half of the course, and then metronidazole and clarithromycin for the second half; (2) hybrid therapy starts with amoxicillin for the first half, and then continues the second half with amoxicillin, clarithromycin, and metronidazole; (3) concomitant therapy combines all three antibiotics throughout the usual 10- to 14-day therapy. Other combinations of antibiotics are occasionally used.

§ Proton pump inhibitor dose equivalent to omeprazole 20 to 40 mg bid. (See Table 129-1 for doses of other proton pump inhibitors).

‖ Bismuth subsalicylate or subcitrate.

¶ An alternative is tinidazole 500 mg bid.

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REF. Goldman-Cecil Internal Medicine, 26th edition

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World J Gastroenterol. 2018 Oct 28; 24(40): 4548–4553.

 

 

 

Fluoroquinolone-based triple/quadruple therapy

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The most commonly used fluoroquinolone-based triple therapy is composed of levofloxacin 500 mg daily, amoxicillin 1 g twice daily and a PPI (standard dose) twice daily for 10 to 14 d (Table ​(Table1).1). Meta-analyses revealed that levofloxacin-amoxicillin triple therapy and bismuth quadruple therapy had comparable eradication rates, whereas the former had fewer adverse effects than the latter. A systemic review and meta-analysis revealed that levofloxacin-amoxicillin triple therapy achieved an overall eradication rate of 78% after failure of a non-bismuth quadruple therapy. It was similarly effective after failure of sequential and concomitant therapies (81% vs 78%, respectively), and the cure rate of levofloxacin-amoxicillin triple therapy following hybrid therapy was 50%.

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An important drawback of levofloxacin-amoxicillin triple therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. Bismuth salts have a synergistic effect on antibiotics and have been used to increase eradication rates. The Maastricht V/Florence Consensus Report also recommended the application of fluoroquinolone-amoxicillin quadruple therapy as a second-line therapy for H. pylori infection. Levofloxacin-amoxicillin quadruple therapy is composed of levofloxacin 500 mg daily, amoxicillin 1 g twice daily, PPI (standard dose) twice daily and bismuth 240 mg twice daily for 10 to 14 d. A randomized controlled trial showed there were no significant differences between the eradication rates of second-line 14-d levofloxacin-amoxicillin quadruple therapy and 14-d levofloxacin-amoxicillin triple therapy (87% vs 83%, respectively). However, the former had a higher eradication rate for levofloxacin-resistant strains than the latter (71% vs 37%).

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