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Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Sep;40(9):2099–2105. doi: 10.1128/aac.40.9.2099

Antimicrobial activity of human pancreatic juice and its interaction with antibiotics.

E B Minelli 1, A Benini 1, C Bassi 1, H Abbas 1, M Falconi 1, F Locatelli 1, R de Marco 1, P Pederzoli 1
PMCID: PMC163480  PMID: 8878588

Abstract

Pancreatic juice (PJ) should be a factor of variability in the antimicrobial activity of antibiotics eliminated by the pancreas during pancreatic infections. We studied its effects on the activity of antimicrobial drugs with different mechanisms of action. Samples of pure PJ were collected from 16 patients with stabilized external pancreatic fistulas. The antimicrobial activity of the juice at different concentrations (from 1.25 to 100%) alone and in combination with mezlocillin, imipenem, ceftriaxone, gentamicin, ofloxacin, and ciprofloxacin was studied by a microbiological method (continuous turbidimetric recording of bacterial growth). The human PJ showed dose-dependent antimicrobial activity that increased directly with the concentration. The activity of the antibiotics at bactericidal concentrations were not modified by the PJ, while the combination with subinhibitory concentrations produced the following variable and different effects: (i) additivity with mezlocillin, ceftriaxone, gentamicin, and ciprofloxacin and autonomy (no interaction) with imipenem and ofloxacin against Providencia rettgeri and (ii) additivity with ceftriaxone, ofloxacin, gentamicin, imipenem, and mezlocillin and autonomy with ciprofloxacin against Escherichia coli. In the presence of PJ, fluoroquinolones showed constant positive effects, while beta-lactams showed more variable antimicrobial activity. Antibiotic concentrations and PJ pharmacodynamics are the main factors determining the final effect of the interaction in vitro. These results may be useful in choosing antibiotics for the treatment of pancreatic infections when they are supplemented with the pharmacokinetic data for each drug.

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Selected References

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  1. Barriere S. L., Ely E., Kapusnik J. E., Gambertoglio J. G. Analysis of a new method for assessing activity of combinations of antimicrobials: area under the bactericidal activity curve. J Antimicrob Chemother. 1985 Jul;16(1):49–59. doi: 10.1093/jac/16.1.49. [DOI] [PubMed] [Google Scholar]
  2. Bassi C., Fontana R., Vesentini S., Cavallini G., Marchiori L., Falconi M., Corrà S., Pederzoli P. Antibacterial and mezlocillin-enhancing activity of pure human pancreatic fluid. Int J Pancreatol. 1991 Nov-Dec;10(3-4):293–297. doi: 10.1007/BF02924168. [DOI] [PubMed] [Google Scholar]
  3. Bassi C., Pederzoli P., Vesentini S., Falconi M., Bonora A., Abbas H., Benini A., Bertazzoni E. M. Behavior of antibiotics during human necrotizing pancreatitis. Antimicrob Agents Chemother. 1994 Apr;38(4):830–836. doi: 10.1128/aac.38.4.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradley E. L., 3rd Antibiotics in acute pancreatitis. Current status and future directions. Am J Surg. 1989 Nov;158(5):472–478. doi: 10.1016/0002-9610(89)90290-0. [DOI] [PubMed] [Google Scholar]
  5. Büchler M., Malfertheiner P., Friess H., Bittner R., Vanek E., Schlegel P., Beger H. G. The penetration of antibiotics into human pancreas. Infection. 1989 Jan-Feb;17(1):20–25. doi: 10.1007/BF01643494. [DOI] [PubMed] [Google Scholar]
  6. Büchler M., Malfertheiner P., Friess H., Isenmann R., Vanek E., Grimm H., Schlegel P., Friess T., Beger H. G. Human pancreatic tissue concentration of bactericidal antibiotics. Gastroenterology. 1992 Dec;103(6):1902–1908. doi: 10.1016/0016-5085(92)91450-i. [DOI] [PubMed] [Google Scholar]
  7. Clissold S. P., Todd P. A., Campoli-Richards D. M. Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1987 Mar;33(3):183–241. doi: 10.2165/00003495-198733030-00001. [DOI] [PubMed] [Google Scholar]
  8. Li R. C., Nix D. E., Schentag J. J. New turbidimetric assay for quantitation of viable bacterial densities. Antimicrob Agents Chemother. 1993 Feb;37(2):371–374. doi: 10.1128/aac.37.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mett H., Gyr K., Zak O., Vosbeck K. Duodeno-pancreatic secretions enhance bactericidal activity of antimicrobial drugs. Antimicrob Agents Chemother. 1984 Jul;26(1):35–38. doi: 10.1128/aac.26.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miglioli P. A., Bertazzoni-Minelli E., Berti T. Enhancement of antibiotic antibacterial activity by experimental pleural exudates. Drugs Exp Clin Res. 1987;13(3):161–166. [PubMed] [Google Scholar]
  11. Minelli Bertazzoni E., Panzetta G. Antibacterial interaction of cefuroxime and serum from uraemic patients. J Antimicrob Chemother. 1986 Sep;18(3):365–373. doi: 10.1093/jac/18.3.365. [DOI] [PubMed] [Google Scholar]
  12. Norrby S. R., Alestig K., Ferber F., Huber J. L., Jones K. H., Kahan F. M., Meisinger M. A., Rogers J. D. Pharmacokinetics and tolerance of N-formimidoyl thienamycin (MK0787) in humans. Antimicrob Agents Chemother. 1983 Feb;23(2):293–299. doi: 10.1128/aac.23.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Olsson-Liljequist B., Hoffman B. M. In-vitro activity of clarithromycin combined with its 14-hydroxy metabolite A-62671 against Haemophilus influenzae. J Antimicrob Chemother. 1991 Feb;27 (Suppl A):11–17. doi: 10.1093/jac/27.suppl_a.11. [DOI] [PubMed] [Google Scholar]
  14. Pederzoli P., Bassi C., Vesentini S., Campedelli A. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet. 1993 May;176(5):480–483. [PubMed] [Google Scholar]
  15. Pederzoli P., Falconi M., Bassi C., Vesentini S., Orcalli F., Scaglione F., Solbiati M., Messori A., Martini N. Ciprofloxacin penetration in pancreatic juice. Chemotherapy. 1987;33(6):397–401. doi: 10.1159/000238527. [DOI] [PubMed] [Google Scholar]
  16. Pederzoli P., Orcalli F., Falconi M., Bozzini L., Martini N. Penetration of mezlocillin into pancreatic juice. J Antimicrob Chemother. 1986 Mar;17(3):397–397. doi: 10.1093/jac/17.3.397. [DOI] [PubMed] [Google Scholar]
  17. Prichard M. N., Shipman C., Jr A three-dimensional model to analyze drug-drug interactions. Antiviral Res. 1990 Oct-Nov;14(4-5):181–205. doi: 10.1016/0166-3542(90)90001-n. [DOI] [PubMed] [Google Scholar]
  18. Rubinstein E., Mark Z., Haspel J., Ben-Ari G., Dreznik Z., Mirelman D., Tadmor A. Antibacterial activity of the pancreatic fluid. Gastroenterology. 1985 Apr;88(4):927–932. doi: 10.1016/s0016-5085(85)80009-3. [DOI] [PubMed] [Google Scholar]
  19. Stern C. M. Bactericidal glycopeptide in human amniotic fluid. J Antimicrob Chemother. 1981 Jul;8(1):3–4. doi: 10.1093/jac/8.1.3. [DOI] [PubMed] [Google Scholar]
  20. Tanaka N., Iseki M., Miyoshi T., Aoki H., Imanaka H. Mechanism of action of bicyclomycin. J Antibiot (Tokyo) 1976 Feb;29(2):155–168. doi: 10.7164/antibiotics.29.155. [DOI] [PubMed] [Google Scholar]
  21. Taylor P. W. Bactericidal and bacteriolytic activity of serum against gram-negative bacteria. Microbiol Rev. 1983 Mar;47(1):46–83. doi: 10.1128/mr.47.1.46-83.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tisdale J. E., Pasko M. T., Mylotte J. M. Antipseudomonal activity of simulated infusions of gentamicin alone or with piperacillin assessed by serum bactericidal rate and area under the killing curve. Antimicrob Agents Chemother. 1989 Sep;33(9):1500–1505. doi: 10.1128/aac.33.9.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Todd P. A., Faulds D. Ofloxacin. A reappraisal of its antimicrobial activity, pharmacology and therapeutic use. Drugs. 1991 Nov;42(5):825–876. doi: 10.2165/00003495-199142050-00008. [DOI] [PubMed] [Google Scholar]

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