Letter to the Editor Animal Model of Helicobacter pylorz Infection Westblom and colleagues have recently reported on an animal model for antibiotic secretion across gastric mucosa which could reliably predict the pharmacokinetics of antibiotics in humans and that could thus be valuable for the selection and the dose regimens of various antimicrobial agents in the treatment of Helicobacter pylori gastritis (T. U. Westblom, D. E. Duriex, E. Madan, and R. B. Belshe, Antimicrob. Agents Chemother. 34:25-28, 1990). According to these authors, clindamycin achieved sustained high levels in gastric mucosa after parenteral administration of 10 and 100 mg/kg (body weight) to adult Hilltop guinea pigs. Since the drug concentrations in mucosa after 8 h remained above the MIC for 90% of the H. pylori strains tested, clindamycin would be expected to be effective in the treatment of H. pylori gastritis on a three-times-daily-administration basis. Unfortunately, the authors did not present convincing evidence that the two dose regimens selected in animals were relevant to humans. Moreover, their animal model was designed only for studying the pharmacology of antibiotics in gastric mucosa, and a therapeutic experiment was not attempted. We have good clinical evidence that data from guinea pigs cannot readily be extrapolated to humans. Clindamycin treatment (four 300-mg capsules per day for 21 days) failed to eradicate H. pylori from gastric mucosa in a group of 13 adult patients (7 males and 6 females; age range, 25 to 71 years) with nonulcer dyspepsia and H. pylori gastritis. None of the patients was cleared of H. pylori 1 week after the end of treatment, nor did any significant variation of the histological inflammatory score occur after completion of treatment. Although susceptibility tests were not systematically performed in this study, two posttreatment isolates (of five strains tested) were resistant to clindamycin (MIC > 8 p,g/ml) (Y. Glupczynski, A. Burette, and C. De Prez, Klin. Wochenschr. 67[Suppl. 18]:24, 1989). Additional data presented by Westblom and colleagues at the same meeting also convincingly documents ! the fact that, even when combined with a bismuth salt (Pept -Bismol), clindamycin did not prove effective in clearing H. pylori from the stomach (H. pylori was eradicated in only 1 of 15 patients 4 weeks after the end of therapy). We were thus surprised that the authors did not make reference at least to their own data. One might perhaps argue that they were not aware of them by the time of submission of their article. By this reply, we wish to stress that it may be hazardous to extrapolate pharmacokinetics of antibiotics in animals to the treatment of H. pylori infection in humans. Clearly, other factors are important (potential for development of resistance to an antimicrobial agent, stability of a compound at a wide range of pH, lack of inactivation of a drug by gastric mucus) and need better understanding before the selection of a suitable agent and dose regimen can be proposed for the treatment of H. pylori infection.

Alain Burette Department of Gastroenterology Nouvelle Clinique de La Basilique B-1080 Brussels, Belgium

Author's Reply We have never claimed the guinea pig model to be a substitute for human clinical studies. On the contrary, our final statement in the paper reads, "These findings will now have to be further investigated in controlled clinical trials." The reason should be obvious. The guinea pig model is a model of pharmacokinetics in the gastric mucosa. We feel confident that the data it provides have good correlation to the human mucosa, as was found when clindamycin concentrations were measured in gastric aspirates from patients being treated with intravenous clindamycin (1). However, obtaining adequate tissue concentrations is only one of many important characteristics of a therapeutically successful antibiotic. We see the guinea pig model as an important screening step. Clearly, there is no point in conducting clinical studies with an antibiotic that has no in vitro activity against Helicobacter pylori. By the same token, we should not waste time studying drugs that cannot achieve sufficient levels in the mucosa. The guinea pig model can identify antibiotics suitable for clinical studies but is no substitute for them, as has been illustrated by the two preliminary studies on clindamycin treatment of H. pylori infections in humans (2, 4), available after the submission of our manuscript. Like Glupczynski and Burette, we suspect that development of resistance during treatment may have played a vital role in the reduced efficacy of clindamycin, something the same authors have already proved takes place during treatment with another antibiotic, ofloxacin (3). LITERATURE CITED 1. Duriex, D. E., and T. U. Westblom. 1989. Clindamycin secretion across human gastric mucosa. J. Clin. Gastroenterol. 11:601-602. 2. Glupczynski, Y., A. Burette, and C. Deprez. 1989. Evaluation of clindamycin in patients with non-ulcer dyspepsia and Campylobacter pylori-associated gastritis. Klin. Wochenschr. 67(Suppl. 18):24. 3. Glupczynski, Y., M. Labbe, A. Burette, M. Delmee, V. Avesani, and C. Bruck. 1987. Treatment failure of ofloxacin in Campylobacter pylori infection. Lancet i:1096. 4. Westblom, T. U., E. Madan, D. E. Duriex, and M. A. Subik. 1989. Double-blind placebo controlled trial of clindamycin and PeptoBismol for C. pylori gastritis: preliminary report. Klin. Wochenschr. 67(Suppl. 18):71-72. T. Ulf Westblom Robert B. Belshe Division ofInfectious Diseases St. Louis University School of Medicine St. Louis, Missouri 63104

Elio Madan Dennis E. Duriex Departments of Pathology and Medicine Marshall University School of Medicine Huntington, West Virginia 25701

Youri Glupczynski Department of Microbiology Brugmann University Hospital B-I020 Brussels, Belgium

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