Thirty bacterial species were tested for their ability to stimulate to increased DNA synthesis in human blood lymphocytes. A definite stimulation was obtained with eighteen bacterial species. For three of these species ten different strains of each were tested, and all increased DNA synthesis. The maximum response was after 3--4 days of culture, suggesting a mitogenic effect. This was confirmed by the induction of polyclonal antibody production shown by a plague assay, which was positive for nine of eleven species tested. Most bacterial species increased the DNA synthesis in B-lymphocyte-enriched and unseparated lymphocytes but had negligible activity on T-lymphocyte-enriched cultures. Among bacteria with a mitogenic effect and ability to induce polyclonal antibody production are Staphylococcus aureus strain Cowan I with a high content of protein A and many common human pathogens such as Haemophilus influenzae, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Streptococcus group A and Streptococcus pneumoniae.
The effects on the mitogenic response of human T lymphocytes were studied for 20 different antibiotics. No apparent inhibitory effect could be detected for penicillins, cephalosporins, aminoglycosides, chloramphenicol, sulfamethoxazole, trimethoprim, nalidixic acid, and 5-fluorocytosine. There were effects at high concentrations with erythromycin, clindamycin, and rifampin, and these antibiotics could also be shown to depress the mitogenic response of B lymphocytes. With fusidic acid, nitrofurantoin, and doxycycline there was an inhibiting effect at low concentrations on the mitogenic responses of B and T lymphocytes and on in vitro antibody production. Protein synthesis in unstimulated lymphocytes was also inhibited. Some antibiotics thus may impair the function of human lymphocytes in vitro.Antibiotics, such as actinomycin D and doxorubicin, are used as immunosuppressive agents, and some antibiotics used in the treatment of bacterial and fungal infections have also been shown to depress granulocyte and lymphocyte functions in vitro (7, 11-13, 15, 19, 20-22, 25-27) and the immune response in humans and experimental animals (2, 3,8,16,21,23).The in vitro effects of a wide range of antibiotics on granulocyte chemotaxis and lymphocyte function were recently reported from our laboratory (11, 12). The aim of the present study was to extend the investigations on the in vitro functions of human B and T lymphocytes in the presence of commonly used antibiotics. MATERIALS AND METHODS Antibiotics
It was previously found that Arcanobacterium haemolyticum, which can cause tonsillitis with exanthema, is not eradicated from the pharynx by administration of phenoxymethylpenicillin, despite minimum inhibitory concentration values of 0.015-1.0 micrograms/ml. Therefore, recent clinical isolates were studied for penicillin tolerance by using a disk diffusion screening test and a pour plate assay. Macrobroth dilution minimum inhibitory and bactericidal concentrations and antibiotic kill kinetics were determined for 4 isolates. Tolerance was present in 38 of 40 clinical isolates with the disk diffusion assay. With the pour plate assay all 40 isolates were tolerant, 34 of them highly tolerant. The presence of the tolerant phenotype was confirmed by macrobroth dilution assays. It is concluded that A. haemolyticum is often penicillin-tolerant, suggesting that phenoxymethylpenicillin administration would be ineffective in eradicating A. haemolyticum from the pharynx.
The effects of three different dressings - two occlusive and one non-occlusive - on the bacterial flora of excised wounds in rats were studied. The number of colony forming units per gram of granulation tissue were significantly lower 4, 8 and 12 days postoperatively in wounds treated with a zinc medicated occlusive dressing compared with wounds treated with non-zinc medicated occlusive hydrocolloid dressing or wet-to-dry non-occlusive gauze dressing. The minimum inhibitory concentration (MIC) of zinc sulphate was determined on different strains of bacteria isolated from the wounds of rats and on strains isolated from humans. The most susceptible species isolated from both rat wounds and humans were Streptococcus sp., STaphylococcus aureus and Escherichia coli; whereas, Proteus and Enterococcus sp. had higher MIC-values. In vitro, the hydrocolloid dressing disclosed no antibacterial effects. If the practitioner prefers an occlusive dressing we believe, due to our animal and in vitro experiments, that the zinc medicated occlusive dressing will reduce the risk of wound infection in man.
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