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. 1997 Oct;41(10):2218–2223. doi: 10.1128/aac.41.10.2218

Pharmacodynamic effects of antibiotics and acid pump inhibitors on Helicobacter pylori.

M Sörberg 1, H Hanberger 1, M Nilsson 1, L E Nilsson 1
PMCID: PMC164096  PMID: 9333051

Abstract

Pharmacodynamic studies of Helicobacter pylori exposed to amoxicillin, clarithromycin, metronidazole, omeprazole, and lansoprazole were performed with microscopy, viable count determination, and bioluminescence assay of intracellular ATP. The pharmacodynamic parameters determined were change in morphology, change in cell density, postantibiotic effect (PAE), and control-related effective regrowth time (CERT). The PAE is delayed regrowth after brief exposure to antibiotics or acid pump inhibitors. CERT was defined as the time required for the bacteria to resume logarithmic growth and return to the pre-exposure inoculum in the test culture minus the corresponding time for the control culture. CERT measures the combined effect of initial killing and PAE. There was a good concordance between the bioluminescence assay and viable counts for determining CERT, which makes this parameter useful for pharmacodynamic studies of the effects of antibiotics and acid pump inhibitors on H. pylori. Amoxicillin and metronidazole produced a strong, concentration-dependent initial decrease in CFU per milliliter, but there was a less prominent initial change in intracellular ATP in these cultures. Amoxicillin caused a long PAE when assayed by the bioluminescence assay but no PAE or a negative PAE when assayed by viable count determination. However, amoxicillin showed similar long CERTs with both methods. The pharmacodynamic effects of amoxicillin were concentration dependent up to a maximum response, indicating that concentrations above this level do not increase the antibiotic effect. The PAEs and CERTs of clarithromycin and metronidazole were concentration dependent with no maximum response. With omeprazole and lanzoprazole, there was no PAE or CERT.

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Selected References

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  1. Armstrong J. A., Wee S. H., Goodwin C. S., Wilson D. H. Response of Campylobacter pyloridis to antibiotics, bismuth and an acid-reducing agent in vitro--an ultrastructural study. J Med Microbiol. 1987 Dec;24(4):343–350. doi: 10.1099/00222615-24-4-343. [DOI] [PubMed] [Google Scholar]
  2. Baquero F., Culebras E., Patrón C., Pérez-Díaz J. C., Medrano J. C., Vicente M. F. Postantibiotic effect of imipenem on gram-positive and gram-negative micro-organisms. J Antimicrob Chemother. 1986 Dec;18 (Suppl E):47–59. doi: 10.1093/jac/18.supplement_e.47. [DOI] [PubMed] [Google Scholar]
  3. Bell G. D., Powell K. U., Burridge S. M., Bowden A. N., Rameh B., Bolton G., Purser K., Harrison G., Brown C., Gant P. W. Helicobacter pylori eradication: efficacy and side effect profile of a combination of omeprazole, amoxycillin and metronidazole compared with four alternative regimens. Q J Med. 1993 Nov;86(11):743–750. [PubMed] [Google Scholar]
  4. Berry V., Jennings K., Woodnutt G. Bactericidal and morphological effects of amoxicillin on Helicobacter pylori. Antimicrob Agents Chemother. 1995 Aug;39(8):1859–1861. doi: 10.1128/aac.39.8.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bode G., Mauch F., Malfertheiner P. The coccoid forms of Helicobacter pylori. Criteria for their viability. Epidemiol Infect. 1993 Dec;111(3):483–490. doi: 10.1017/s0950268800057216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cederberg C., Andersson T., Skånberg I. Omeprazole: pharmacokinetics and metabolism in man. Scand J Gastroenterol Suppl. 1989;166:33–42. doi: 10.3109/00365528909091241. [DOI] [PubMed] [Google Scholar]
  7. Chu S., Wilson D. S., Deaton R. L., Mackenthun A. V., Eason C. N., Cavanaugh J. H. Single- and multiple-dose pharmacokinetics of clarithromycin, a new macrolide antimicrobial. J Clin Pharmacol. 1993 Aug;33(8):719–726. doi: 10.1002/j.1552-4604.1993.tb05613.x. [DOI] [PubMed] [Google Scholar]
  8. Flamm R. K., Beyer J., Tanaka S. K., Clement J. Kill kinetics of antimicrobial agents against Helicobacter pylori. J Antimicrob Chemother. 1996 Oct;38(4):719–725. doi: 10.1093/jac/38.4.719. [DOI] [PubMed] [Google Scholar]
  9. Goodwin C. S., Blake P., Blincow E. The minimum inhibitory and bactericidal concentrations of antibiotics and anti-ulcer agents against Campylobacter pyloridis. J Antimicrob Chemother. 1986 Mar;17(3):309–314. doi: 10.1093/jac/17.3.309. [DOI] [PubMed] [Google Scholar]
  10. Gottfredsson Magnús, Erlendsdóttir Helga, Gudmundsson Adalsteinn, Gudmundsson Sigurdur. Determination of in vitro postantibiotic effects in Staphylococcus aureus and Escherichia coli by [3H]thymidine incorporation. Clin Microbiol Infect. 1996;2(2):99–104. doi: 10.1111/j.1469-0691.1996.tb00213.x. [DOI] [PubMed] [Google Scholar]
  11. Graham D. Y., Lew G. M., Malaty H. M., Evans D. G., Evans D. J., Jr, Klein P. D., Alpert L. C., Genta R. M. Factors influencing the eradication of Helicobacter pylori with triple therapy. Gastroenterology. 1992 Feb;102(2):493–496. doi: 10.1016/0016-5085(92)90095-g. [DOI] [PubMed] [Google Scholar]
  12. Hanberger H., Svensson E., Nilsson L. E., Nilsson M. Control-related effective regrowth time and post-antibiotic effect of meropenem on gram-negative bacteria studied by bioluminescence and viable counts. J Antimicrob Chemother. 1995 May;35(5):585–592. doi: 10.1093/jac/35.5.585. [DOI] [PubMed] [Google Scholar]
  13. Hanberger H., Svensson E., Nilsson M., Nilsson L. E., Hörnsten E. G., Maller R. Effects of imipenem on Escherichia coli studied using bioluminescence, viable counting and microscopy. J Antimicrob Chemother. 1993 Feb;31(2):245–260. doi: 10.1093/jac/31.2.245. [DOI] [PubMed] [Google Scholar]
  14. Hentschel E., Brandstätter G., Dragosics B., Hirschl A. M., Nemec H., Schütze K., Taufer M., Wurzer H. Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med. 1993 Feb 4;328(5):308–312. doi: 10.1056/NEJM199302043280503. [DOI] [PubMed] [Google Scholar]
  15. Hussein Z., Granneman G. R., Mukherjee D., Samara E., Hogan D. L., Koss M. A., Isenberg J. I. Age-related differences in the pharmacokinetics and pharmacodynamics of lansoprazole. Br J Clin Pharmacol. 1993 Nov;36(5):391–398. doi: 10.1111/j.1365-2125.1993.tb00386.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Iwahi T., Satoh H., Nakao M., Iwasaki T., Yamazaki T., Kubo K., Tamura T., Imada A. Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity against Helicobacter pylori. Antimicrob Agents Chemother. 1991 Mar;35(3):490–496. doi: 10.1128/aac.35.3.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Labenz J., Leverkus F., Börsch G. Omeprazole plus amoxicillin for cure of Helicobacter pylori infection. Factors influencing the treatment success. Scand J Gastroenterol. 1994 Dec;29(12):1070–1075. doi: 10.3109/00365529409094890. [DOI] [PubMed] [Google Scholar]
  18. Lind T., Veldhuyzen van Zanten S., Unge P., Spiller R., Bayerdörffer E., O'Morain C., Bardhan K. D., Bradette M., Chiba N., Wrangstadh M. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study. Helicobacter. 1996 Sep;1(3):138–144. doi: 10.1111/j.1523-5378.1996.tb00027.x. [DOI] [PubMed] [Google Scholar]
  19. Logan R. P., Gummett P. A., Schaufelberger H. D., Greaves R. R., Mendelson G. M., Walker M. M., Thomas P. H., Baron J. H., Misiewicz J. J. Eradication of Helicobacter pylori with clarithromycin and omeprazole. Gut. 1994 Mar;35(3):323–326. doi: 10.1136/gut.35.3.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. MacKenzie F. M., Gould I. M., Chapman D. G., Jason D. Postantibiotic effect of meropenem on members of the family Enterobacteriaceae determined by five methods. Antimicrob Agents Chemother. 1994 Nov;38(11):2583–2589. doi: 10.1128/aac.38.11.2583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mattila J., Männistö P. T., Mäntylä R., Nykänen S., Lamminsivu U. Comparative pharmacokinetics of metronidazole and tinidazole as influenced by administration route. Antimicrob Agents Chemother. 1983 May;23(5):721–725. doi: 10.1128/aac.23.5.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McCarthy L. R., Senne J. E. Evaluation of acridine orange stain for detection of microorganisms in blood cultures. J Clin Microbiol. 1980 Mar;11(3):281–285. doi: 10.1128/jcm.11.3.281-285.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Molin O., Nilsson L., Anséhn S. Rapid detection of bacterial growth in blood cultures by bioluminescent assay of bacterial ATP. J Clin Microbiol. 1983 Sep;18(3):521–525. doi: 10.1128/jcm.18.3.521-525.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nilius M., Ströhle A., Bode G., Malfertheiner P. Coccoid like forms (CLF) of Helicobacter pylori. Enzyme activity and antigenicity. Zentralbl Bakteriol. 1993 Sep;280(1-2):259–272. doi: 10.1016/s0934-8840(11)80964-3. [DOI] [PubMed] [Google Scholar]
  25. Nilsson L., Sörén L., Rådberg G. Frequencies of variants resistant to different aminoglycosides in Pseudomonas aeruginosa. J Antimicrob Chemother. 1987 Aug;20(2):255–259. doi: 10.1093/jac/20.2.255. [DOI] [PubMed] [Google Scholar]
  26. Svensson E., Hanberger H., Nilsson L. E. Pharmacodynamic effects of antibiotics and antibiotic combinations on growing and nongrowing Staphylococcus epidermidis cells. Antimicrob Agents Chemother. 1997 Jan;41(1):107–111. doi: 10.1128/aac.41.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sörberg M., Nilsson M., Hanberger H., Nilsson L. E. Morphologic conversion of Helicobacter pylori from bacillary to coccoid form. Eur J Clin Microbiol Infect Dis. 1996 Mar;15(3):216–219. doi: 10.1007/BF01591357. [DOI] [PubMed] [Google Scholar]
  28. Sörén L., Nilsson M., Nilsson L. E. Quantitation of antibiotic effects on bacteria by bioluminescence, viable counting and quantal analysis. J Antimicrob Chemother. 1995 May;35(5):669–674. doi: 10.1093/jac/35.5.669. [DOI] [PubMed] [Google Scholar]
  29. Thore A., Anséhn S., Lundin A., Bergman S. Detection of bacteriuria by luciferase assay of adenosine triphosphate. J Clin Microbiol. 1975 Jan;1(1):1–8. doi: 10.1128/jcm.1.1.1-8.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. West A. P., Millar M. R., Tompkins D. S. Survival of Helicobacter pylori in water and saline. J Clin Pathol. 1990 Jul;43(7):609–609. doi: 10.1136/jcp.43.7.609-b. [DOI] [PMC free article] [PubMed] [Google Scholar]

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