To study the penetration of antibiotics into peritoneal tissue fluid, a subcutaneous tissue capsule model was modified by implanting multiple, perforated spherical capsules in the peritoneal cavity ofrabbits. Capsules became vascularized, encased in connective tissue, and filled with fluid having a mean protein concentration of 3.6 g/100 ml. Capsular fluid was obtained by percutaneous needle aspiration and assayed for antibiotic by the disk plate bioassay technique. Cephalosporins were administered intramuscularly at a dose of30 mg/kg. Mean peak concentrations of cephaloridine and cefazolin were significantly higher than cephalothin and cephapirin in capsular fluids, but the percent penetration (ratio of capsular mean peak to serum mean peak) ranged from 8.7 to 16.9% and was not significantly different among the cephalosporins. At 24 h the capsular concentration of cefazolin was significantly greater than for the other cephalosporins (P < 0.001). Lower rabbit serum protein binding observed at high in vivo concentrations may have enabled cefazolin to penetrate capsular fluid, but in vitro protein binding studies did not confirm a decrease in serum protein binding at high concentrations within the clinical range. Kanamycin and amikacin showed comparable capsular fluid peak concentrations as did gentamicin and tobramycin. The percent penetration ranged from 15.2 to 34.5% for the aminoglycosides. The only statistical difference was that amikacin penetration was significantly higher than that for tobramycin. Mean capsular concentrations of amikacin, cefazolin, and cephaloridine compared most favorably with the minimum inhibitory concentration of gram-negative bacilli at the dosages used in this study.
A series of 27 strains of six species of Brucella was tested for susceptibility in vitro to a representative cross section of antibiotics in current use. The activity against each species was plotted, with the cumulative per cent of strains inhibited indicated for each concentration. As a class, the tetracycline antibiotics were the most effective. Erythromycin, gentamicin, streptomycin, and kanamycin, as well as rifampin, were quite active. The penicillin-cephalosporin group, with the exception of ampicillin, was comparatively ineffective, as were the polypeptides and the miscellaneous group of chloramphenicol, lincomycin, cycloserine, and sulfadiazine. Species differences were noticeable, with some strains of B. canis being considerably more resistant to streptomycin and the tetracyclines than B. suis and B. abortus. B. melitensis, B. ovis, and B. neotomae were intermediate in antibiotic susceptibility.
During the past year we have compared several techniques for testing human sera for Brucella agglutinins. These have included a tube dilution method, the rapid slide method (Huddleson) and a rapid slide or screening test designed by Castaneda (1). In addition, a blocking test and a modification of the indirect Coombs test were investigated. High speed centrifugation of Brucellaserum mixtures was also used to increase the titer of Brucella agglutinins.Several unsuccessful attempts also were made to adapt the Middlebrook-Dubos (2) hemagglutination method to the detection of antibodies against Brucella. In addition, paper chromatograms were made in attempts to differentiate specific from non-specific Brucella agglutinins by the method of Hess and Roepke (3).Sera from 104 adults were studied. Of these subjects, 27 had brucellosis proved by culture, 28 had presumptive evidence of brucellosis, and 49 had no evidence of infection with Brucella and were classed as "normal" controls.
METHODSVenous blood was obtained aseptically and allowed to clot in a sterile glass tube in a refrigerator. The serum was separated within a few hours. It was not heatinactivated but was tested immediately or stored in a deep-freeze cabinet at O°C. until tested.Tube dilution agglutination method. The agglutinin titer was determined by a modification of the method of Fitch, Donham, Bishop, and Boyd (4). The serum was diluted two-fold serially from 1: 10 to 1: 2,560 with 0.85 per cent saline solution. Brucella abortus antigen (0.5 ml.) was added to 0.5 ml. of saline (control) and 0.5 ml. of each dilution of the serum in separate tubes.' The
The in vitro activity of various antibiotics against
Pseudomonas pseudomallei
was studied. The tetracyclines were the most active, followed by gentamicin, kanamycin, novobiocin, chloramphenicol, rifampin, cycloserine, erythromycin, and ampicillin.
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