Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Clarithromycin, lansoprazole, and metronidazole eradicated Helicobacter pylori infection in chronic renal insufficiency

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ACP J Club. 2004 Mar-Apr;140:40. doi:10.7326/ACPJC-2004-140-2-040


Clinical Impact Ratings

GIM/FP/GP: 5 stars

Gastroenterology: 6 stars

Infectious Disease: 4 stars

Nephrology: 6 stars


Source Citation

Sheu BS, Huang JJ, Yang HB, Huang AH, Wu JJ. The selection of triple therapy for Helicobacter pylori eradication in chronic renal insufficiency. Aliment Pharmacol Ther. 2003;17:1283-90. [PubMed ID: 12755841]


Abstract

Question

In patients with dyspepsia and chronic renal insufficiency, is triple therapy consisting of clarithromycin, lansoprazole, and metronidazole (CLM) more effective than one consisting of clarithromycin, lansoprazole, and a reduced dosage of amoxicillin (CLA) for eradicating Helicobacter pylori ?

Design

Randomized {allocation concealed*}†, blinded (outcome assessors),* controlled trial with 6-week follow-up.

Setting

A university hospital in Tainan, Taiwan.

Patients

88 patients (mean age 46 y, 55% men) with dyspepsia who had chronic renal insufficiency and H. pylori infection. Exclusion criteria included use of H2-receptor antagonists, proton-pump inhibitors, bismuth, or antibiotics ≤ 4 weeks before the study; and end-stage renal disease requiring hemodialysis. Follow-up was 89%.

Intervention

44 patients each were allocated to CLM (clarithromycin, 500 mg; lansoprazole, 30 mg; and metronidazole, 500 mg) or CLA (clarithromycin, 500 mg; lansoprazole, 30 mg; and amoxicillin 750 mg), twice daily for 1 week.

Main outcome measures

Success of H. pylori eradication measured at 6 weeks; drug compliance categorized as good (7 d triple therapy completed), modest (≥ 5 d triple therapy completed), or poor (< 5 d of triple therapy completed); and creatinine clearance assessed at 1, 2, and 6 weeks of follow-up.

Main results

Analysis was by intention to treat. The rates of successful H. pylori eradication and complete drug compliance were greater in the CLM group than in the CLA group (Table). The incidence of acute renal failure was lower in the CLM group than in the CLA group (Table). At 6 weeks, percentage decrease in creatinine clearance was greater in the CLA group than in the CLM group (7.7% vs 1.5%, P≤ 0.05).

Conclusion

In patients with dyspepsia and chronic renal insufficiency, triple therapy consisting of clarithromycin, lansoprazole, and metronidazole was more effective, and less nephrotoxic, than one consisting of clarithromycin, lansoprazole, and a reduced dosage of amoxicillin for eradicating H. pylori.

*See Glossary.

†Information provided by author.

Sources of funding: National Health Research Institute and National Scientific Council.

For correspondence: Dr. B.S. Sheu, National Cheng Kung University Hospital, Tainan, Taiwan. E-mail sheubs@mail.ncku.edu.tw.


Table. Clarithromycin, lansoprazole, and metronidazole (CLM) vs clarithromycin, lansoprazole, and a reduced dosage of amoxicillin (CLA) in Helicobacter pylori infection and chronic renal insufficiency at 6 weeks‡

Outcomes CLM CLA RBI (95% CI) NNT (CI)
Successful eradication of H. pylori 84% 66% 28% (0 to 68) 6 (3 to ∞)
Complete compliance (7 d triple therapy completed) 77% 52% 48% (8 to 110) 4 (3 to 21)
RRR (CI)
Acute renal failure 2% 18% 88% (28 to 98) 7 (4 to 26)

‡Abbreviations defined in Glossary; RBI, RRR, NNT, and CI calculated from data in article.


Commentary

The study by Sheu and colleagues compared a metronidazole-clarithromycin–based regimen (CLM) with an amoxicillin-clarithromycin–based regimen (CLA) for eradicating H. pylori in patients with chronic renal insufficiency and dyspepsia. CLM had an eradication rate similar to that reported in patients with normal renal function, but CLA had a rate that was substantially lower (1). This discrepancy probably arises from use of a reduced (renal) dose of amoxicillin. The authors also reported better drug compliance and less deterioration of renal function with the CLM therapy.

Although the study was well done, 2 points should be noted. First, testing and treating for H. pylori prevents recurrent ulcers in patients with peptic ulcer disease, but the benefits of this strategy in nonulcer dyspepsia remain controversial (2). Nearly half the study patients had only gastric inflammation on endoscopy, suggesting a diagnosis of nonulcer dyspepsia. Eradicating H. pylori in such patients may do little to improve symptoms while causing unintended consequences. For example, CLM therapy may select for highly resistant enterococci that can persist for > 3 years (3). Second, regional differences in antibiotic resistance may limit extrapolation of the present study results to other practice settings. In the United States, the overall rate of H. pylori resistance to clarithromycin is about 10%, to metronidazole 37%, and to amoxicillin only 1% (2). In part, because of differences in antibiotic resistance, a 7-day regimen is recommended in Europe but a 14-day course seems to be more effective in the United States and is recommended by the Food and Drug Administration (2). Whereas a 7-day CLM regimen may be the preferred treatment for H. pylori in patients with chronic renal insufficiency in Taiwan, we have little data about what to use in other settings. In the United States, because of relatively high rates of resistance to metronidazole and clarithromycin, it may be worthwhile to consider extending CLM eradication therapy to 14 days in patients with chronic renal insufficiency and proven peptic ulcers.

Edward A. Lew, MD, MPH
Boston Veterans Affairs Healthcare
Brigham and Women's HospitalBoston, Massachusetts, USA


References

1. Laheij RJ, Rossum LG, Jansen JB, Straatman H, Verbeek AL. Evaluation of treatment regimens to cure Helicobacter pylori infection—a meta-analysis. Aliment Pharmacol Ther. 1999;13:857-64. [PubMed ID: 10383518]

2. Suerbaum S, Michetti P.Helicobacter pylori infection. N Engl J Med. 2002;347:1175-86. [PubMed ID: 12374879]

3. Sjölund M, Wreiber K, Andersson DI, Blaser MJ, Engstrand L. Long-term persistence of resistant Enterococcus species after antibiotics to eradicate Helicobacter pylori. Ann Intern Med. 2003;139:483-7. [PubMed ID: 13679325]