Bicyclomycin, a new antibiotic. I1I. In vitro and in vivo antimicrobial activity. J. Antibiot. (Tokyo) 25:582-593. 7. Regoes, J., 0. Zak, R. Solf, W. A. Vischer, and E. G. ...
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, JUIY 1984, 0066-4804/84/070035-04$02.00/0 Copyright C 1984, American Society for Microbiology
Vol. 26, No. 1
p. 35-38
Duodeno-Pancreatic Secretions Enhance Bactericidal Activity of Antimicrobial Drugs H. METT,l* K. GYR,2 0. ZAK,' AND K. VOSBECK' Research Department, Pharmaceuticals Division, Ciba-Geigy, Ltd., CH4002 Basel,' and Division of Gastro-Enterology, Cantonal Hospital Basel, CH4031 Basel,2 Switzerland Received 23 November 1983/Accepted 5 April 1984
We have studied the action of various antimicrobial agents in microbiological media and in human duodenopancreatic secretions. In the latter medium, clioquinol exhibited a rapid bactericidal effect on both growing and stationary bacteria at concentrations near its MIC. However, it was merely bacteriostatic in microbiological media, even at high concentrations. Phanquinone, chlorquinaldol, and, to a lesser extent, also chloramphenicol and trimethoprim likewise displayed enhanced bactericidal activity in duodeno-pancreatic secretions, but various other antibacterial agents did not. These findings suggest that duodeno-pancreatic secretions contain a factor augmenting the antibacterial activity of a number of drugs.
Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) is an antimicrobial agent used to treat protozoal and bacterial infections of the intestinal tract (2, 9). In the usual microbiological media, its activity against gram-negative bacteria is relatively weak (7, 8). We have, therefore, studied its action under more physiological conditions, i.e., in human duodenopancreatic secretions, which represent the natural environment for drugs used in therapy of enteric infections, and found its activity to be greatly enhanced. Similar observations were made with several other antibiotics, indicating the presence in duodeno-pancreatic secretions of an activity that augments the bactericidal activity of certain antimicrobial
duodeno-pancreatic secretions or in minimal medium M9 (10) supplemented with 4 g of glucose per liter and 50 mg of histidine per liter. Supplement C (Difco Laboratories; 0.3% [vol/vol]) was added to the media where indicated. Supplement C is an additive composed of yeast concentrate and hematin, which is required to allow growth of certain bacterial strains in minimal media. In some experiments, bacteria were grown in brain heart infusion (BHI; Difco) broth or on BHI agar plates, or one of the proteins-fetuin (a glycoprotein from fetal calf serum), ovalbumin, or bovine serum albumin-was added to the medium (see Table 2). The proteins were from Sigma Chemical Co., St. Louis, Mo.
agents.
MIC. Clioquinol was dissolved in dimethyl sulfoxide and diluted 100-fold into the first of the dilution tubes. MICs were determined by serial two-fold dilution of the antibiotic in medium (0.5 ml each), inoculation with 105 CFU/ml, and incubation for 20 h at 37°C. Viable bacteria were then quantitated by plating on BHI agar. Since aqueous solutions containing more than 10 ,ug of clioquinol per ml remained visibly turbid, the MIC was defined as the lowest concentration preventing bacterial growth (108 CFU/ml). MBC was defined as the lowest concentration reducing the viability at least 1,000-fold (
