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Publications (4)25.98 Total impact

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    T H Steinberg · W L Hand
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    ABSTRACT: Phagocytosis stimulated a substantial increase in clindamycin uptake and a smaller increase in rifampin accumulation by polymorphonuclear leukocytes. The effect of this increased antibiotic uptake on intraphagocytic bactericidal activity was evaluated. Although zymosan stimulated antibiotic uptake by polymorphonuclear leukocytes, neither zymosan nor formyl-methionyl-leucyl-phenylalanine enhanced the ability of clindamycin or rifampin to kill ingested staphylococci. Properties other than antibiotic uptake are important in determining intraphagocytic bactericidal activity.
    Preview · Article · May 1987 · Antimicrobial Agents and Chemotherapy
  • W L Hand · R W Corwin · T H Steinberg · G D Grossman
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    ABSTRACT: To provide additional criteria for therapy of pulmonary infections caused by facultative intracellular bacteria, we studied the uptake of 12 antibiotics by alveolar macrophages (AM) obtained from healthy, young volunteers by bronchoalveolar lavage. These human AM were incubated with radiolabeled antibiotics for periods as long as 2 h. Entry of antimicrobials into the cells was determined by means of a velocity-gradient centrifugation technique. Antibiotic uptake was expressed as the ratio of the cellular to the extracellular drug concentration (C/E). Penicillin G, cefamandole, and gentamicin were taken up poorly by human AM (C/E = 0.5 to 0.8). Isoniazid achieved a cellular concentration similar to the extracellular level of the drug (C/E = 0.9). Chloramphenicol, rifampin, tetracycline, and lincomycin, drugs that are lipid-soluble, were concentrated several-fold by AM (C/E = 2 to 5). The remaining antibiotics tested, clindamycin, erythromycin, erythromycin propionate, and ethambutol, were markedly concentrated by AM (C/E = 9 to 23). Accumulation of clindamycin (C/E = 23) was a rapid, active, energy-requiring process, which appeared to be dependent upon mitochondrial oxidative metabolism. The ability of the tested antimicrobial agents to enter human AM correlates well with the efficacy of these drugs in treatment of certain intracellular pulmonary infections.
    No preview · Article · Jul 1984 · The American review of respiratory disease
  • Thomas H. Steinberg · W. Lee Hand
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    ABSTRACT: The ability of antibiotics to enter phagocytes during infection with facultative intracellular organisms was investigated using an in vitro model. Human polymorphonuclear leukocytes (PMNLs) were incubated with ingestible particles or phorbol myristate acetate (PMA), after which radiolabeled antibiotics were added to the cell suspension. Antibiotic uptake, determined by a velocity-gradient centrifugation technique, was expressed as the cellular:extracellular (C/E) antibiotic concentration ratio. Phagocytosis or PMA exposure enhanced PMNL clindamycin uptake (for example, C/E ratio of 12 for control vs 30 after zymosan). Entry of penicillin was unaffected and erythromycin uptake was slightly decreased after phagocytosis. Because clindamycin uptake by phagocytes is mediated by the nucleoside transport system, adenosine uptake after phagocytosis was studied. Adenosine uptake was stimulated by phagocytosis, and this increase was inhibited by clindamycin. Thus, clindamycin uptake, mediated by the nucleoside transport system, was augmented by phagocytosis. This marked stimulation of a membrane transport system by phagocytosis has not been previously described.
    No preview · Article · Apr 1984 · The Journal of Infectious Diseases
  • W L Hand · N L King-Thompson · T H Steinberg
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    ABSTRACT: Optimal therapy of infections due to organisms capable of surviving within phagocytes would include use of antimicrobials that penetrate phagocytic cells and inactivate intracellular organisms. To establish those characteristics of drug and cell that mediate the antibiotic-phagocyte interaction, we have studied the uptake of radiolabelled antibiotics by rabbit alveolar macrophages (AM), human AM from smokers and non-smokers, and human polymorphonuclear leukocytes (PMN). Relative entries of drug groups into the three types of phagocytic cells were similar. Penicillin G and cephalosporin antibiotics were taken up poorly by phagocytes. Lipid-soluble antibiotics, such as rifampicin and chloramphenicol, were concentrated several-fold (2-5) by phagocytes. Ethambutol, erythromycin and clindamycin were concentrated many-fold (5-50) by phagocytic cells. Human AM of smokers accumulated certain antibiotics more avidly than AM of non-smokers. Clindamycin entry into phagocytes was shown to be an active, energy-requiring process, mediated by the nucleoside transport system. Ingestion of microbial particles by PMN stimulated transport of both clindamycin and nucleoside (adenosine) into the cell.
    No preview · Article · Nov 1983 · Journal of Antimicrobial Chemotherapy