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Cellular antibiotic pharmacology
Abstract:
Many perinatal pathogens are able to survive and in some cases replicate intracellularly. With the exception of viruses and toxoplasma, these pathogens principally infect phagocytic cells of the reticuloendothelial system. Such intracellular organisms, by evading the effects of antibiotics that act only extracellularly, may respond poorly to conventional therapy. Of currently available antibiotics, rifampin, chloramphenicol and trimethoprim are the most active intracellularly. Other antibiotics are either taken up by cells but appear to be inactive intracellularly (lincomycin) or are excluded from cells (penicillins, cephalosporins, aminoglycosides). The clinical role of antibiotics that are active intracellularly is not clear; anecdotal human experience and limited controlled animal experience suggests that they may be useful in the treatment of some infections. Because of the decreased microbicidal activity of newborn phagocytes, intracellular activity of antibiotics may be of greater importance than in older patients. Further study is needed to answer these questions. Methods of enhancing intracellular activity of antibiotics are available should this property prove to be desirable.
Insights
Many perinatal pathogens survive inside host cells, evading standard antibiotic treatments. Intracellularly active antibiotics like rifampin may offer better therapeutic options, especially for neonates, but require further research.
Area of Science:
- Microbiology
- Pharmacology
- Neonatal Medicine
Background:
- Perinatal pathogens frequently exhibit intracellular survival and replication.
- Intracellular pathogens evade extracellularly acting antibiotics, leading to treatment challenges.
- Phagocytic cells of the reticuloendothelial system are primary targets for many intracellular perinatal pathogens.
Purpose of the Study:
- To review the activity of antibiotics against intracellular pathogens.
- To highlight the importance of intracellular antibiotic activity in perinatal infections.
- To discuss the potential clinical utility and future research directions for intracellular antibiotics.
Main Methods:
- Literature review of antibiotic intracellular activity.
- Analysis of antibiotic uptake and efficacy within host cells.
- Evaluation of existing clinical and animal data on intracellular antibiotic use.
Main Results:
- Rifampin, chloramphenicol, and trimethoprim demonstrate significant intracellular activity.
- Penicillins, cephalosporins, and aminoglycosides are largely excluded from cells or inactive intracellularly.
- Newborn phagocytes have reduced microbicidal activity, increasing the importance of intracellular antibiotic efficacy.
Conclusions:
- Antibiotics with intracellular activity may be crucial for treating certain perinatal infections.
- Further clinical and animal studies are needed to define the role of intracellular antibiotics.
- Strategies to enhance antibiotic intracellular activity exist and warrant investigation.