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Intracellular penetration and antimicrobial activity of antibiotics. 1983

R F Jacobs, and C B Wilson

Delayed response or recurrence of clinical infections may, in part, be due to the inability of certain antibiotics to penetrate human polymorphonuclear leukocytes (PMN) and exert intracellular antibacterial activity. We determined the penetration of PMN by certain hydrophilic and certain lipophilic antibiotics, and assessed their activity against intracellular Haemophilus influenzae, type b or Staphylococcus aureus. We found that penicillin G was excluded from human PMN while chloramphenicol was concentrated within these cells; chloramphenicol killed significantly more intracellular H. influenzae than did penicillin or ampicillin. Clindamycin and trimethoprim penetrated into normal and chronic granulomatous disease (CGD) PMN equally and were at least transiently concentrated in the cells. Clindamycin and the combinations trimethoprim/sulphamethoxazole and trimethoprim/rifampicin were most effective in killing intracellular Staph. aureus in vitro; these antibiotics reduced the bacterial density in CGD PMN to values comparable to those in normal PMN. The mechanism by which clindamycin and rifampicin killed intracellular Staph. aureus appeared to be due to direct antimicrobial activity. Antibiotics that penetrate into phagocytes may be more effective in infections due to pathogens capable of intracellular survival.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D006105 Granulomatous Disease, Chronic A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern. Autosomal Recessive Chronic Granulomatous Disease,Chronic Granulomatous Disease,Chronic Granulomatous Disease, Atypical,Chronic Granulomatous Disease, X-Linked,Cytochrome B-Negative Granulomatous Disease, Chronic, X-Linked,Cytochrome B-Positive Granulomatous Disease, Chronic, X-Linked,Granulomatous Disease, Chronic, X-Linked,Granulomatous Disease, Chronic, X-Linked, Variant,X-Linked Chronic Granulomatous Disease,Chronic Granulomatous Disease, X Linked,Chronic Granulomatous Diseases,Granulomatous Diseases, Chronic,X Linked Chronic Granulomatous Disease
D006193 Haemophilus influenzae A species of HAEMOPHILUS found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. Bacterium influenzae,Coccobacillus pfeifferi,Haemophilus meningitidis,Hemophilus influenzae,Influenza-bacillus,Mycobacterium influenzae
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001419 Bacteria One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive. Eubacteria
D013211 Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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