sodium-dodecyl-sulfate and Endocarditis--Bacterial

Strains of coagulase-negative staphylococci were tested for in vivo resistance in a rabbit model of prophylaxis of endocarditis. Regimens of nafcillin, cefazolin, cefamandole, and vancomycin were compared for efficacy in the prevention of infection caused by two methicillin-resistant strains and a susceptible strain. For the two resistant strains, vancomycin was the most effective drug tested. All regimens were effective against the susceptible strain. The two strains for which prophylaxis with beta-lactam antibiotics failed produced a beta-lactam antibiotic-inducible penicillin-binding protein (PBP) that comigrated in sodium dodecyl sulfate-polyacrylamide gels with the low-affinity PBP 2a that is associated with methicillin resistance in strains of Staphylococcus aureus. Like PBP 2a, this PBP had low binding affinity for beta-lactam antibiotics. Peptide maps after either V8 protease or chymotrypsin digestion of radiolabeled PBP 2a or silver-stained preparations were virtually identical to one another and to maps of PBP 2a from a heterogeneous and a homogeneous strain of S. aureus. Methicillin resistance in coagulase-negative staphylococci and therapeutic failure with beta-lactam antibiotics in vivo is associated with production of PBP 2a, which appears to be highly conserved structurally among different species of staphylococci.

Topics: Animals; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactams; Carrier Proteins; Coagulase; Electrophoresis, Polyacrylamide Gel; Endocarditis, Bacterial; Hexosyltransferases; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Penicillin-Binding Proteins; Peptide Mapping; Peptidyl Transferases; Rabbits; Sodium Dodecyl Sulfate; Spectrometry, Fluorescence; Staphylococcus

The effectiveness of a water-soluble C-12 alkyl sulfate (T6) (U.S. Patent No. 4,323,358) in retarding bioprosthetic calcification was evaluated in 23 porcine-valved conduits (13 T6-treated conduits and 10 controls) implanted in young sheep between the right ventricle and the pulmonary trunk. The grafts were divided into three groups according to the period of function: Group I, less than 2 months; Group II, 2 to 4 months; and Group III, 5 to 7 months. In Group I (four T6 and four controls), endocarditis occurred in five cases. In Group II (three T6 and three controls), four conduits showed severe fibrous peel ingrowth. In Group III (six T6 and three controls), fibrous peel was the main feature in four conduits and calcium deposits occurred in the porcine aortic wall in all cases, with cusp involvement in two; in both T6-treated and control conduits, chemical analysis showed a much lower calcium content of the cusps (8.45 +/- 80 versus 2.95 +/- 1.52 mg/gm dry weight, respectively) than that reported in other animal or human explants. The grade of calcification in control and T6-treated conduits was equal on x-ray analysis, and no differences in calcification patterns were noted on electron microscopy. This experimental model shows a low degree of cusp calcification and no significant differences between T6-treated and control conduits. Peel formation markedly interferes with performance of the porcine-valved conduit. The results of this analysis indicate that valved conduits are not the optimum model for evaluating calcium-retardant agents in biological valves.

Topics: Animals; Aortic Diseases; Bioprosthesis; Calcinosis; Endocarditis, Bacterial; Heart Valve Prosthesis; Sheep; Sodium Dodecyl Sulfate; Sulfuric Acid Esters; Sulfuric Acids; Surface-Active Agents; Swine; Time Factors