Alternative and/or Integrative Therapies for Pneumonia Under
Purpose of review: Increasing antimicrobial resistance among common respiratory bacteria has created challenges in selecting appropriate therapy for pneumonia. Fortunately, the analysis of genome sequences has allowed us to find novel, nontraditional targets that are involved in disease pathogenesis or in adaptation and growth in infection sites. The advantage of the nonclassical targets is that targeting these sites could ablate infection without inducing resistance. Interfering with bacterial adhesion, inhibiting, neutralizing and clearing endotoxin, and administering cytokines as immunoadjuvants are the most promising alternative or integrative treatments for pneumonia that are under development.
Recent findings: Interference with bacterial adhesion is possible using inhibitors of sortase or inactivators of the srtA gene against gram-positive bacteria, inhibitors of the periplasmic chaperone or those of usher function against gram-negative bacteria, novel polysaccharides that are present on echinoderm surfaces, antiadhesin vaccines, or the passive administration of antiadhesin antibodies. Inhibition, neutralization, and clearance of endotoxin possibly interferes in the lipid A biosynthetic pathway or using lipid A analogues with reduced or lack of ability to activate the major endotoxin receptors or proteins such as recombinant Limulus antilipopolysaccharide factor, bactericidal/permeability increasing protein, or lipopolysaccharide binding protein. Tumor necrosis factor 70-80, an adenoviral vector that encodes murine tumor necrosis factor α, and recombinant interferon gamma seem to be the most promising cytokines for use as immunoadjuvants for the treatment of pneumonia.
Summary: Ideally, potential treatment of life-threatening bacterial pneumonia will combine immunoadjuvant and conventional antibiotic therapy. Compounds capable of stimulating early host defense and microbial clearance, but not the later phases of inflammatory tissue injury associated with sepsis, may be advantageous.
Increasing antimicrobial resistance among common respiratory bacteria has created challenges in selecting the appropriate therapy for pneumonia, which is a major infection control problem because of its reported frequency, associated high fatality rate, and attendant costs, mainly for hospitalized patients.
To overcome infections caused by resistant strains, new classes of antimicrobial compounds must be developed. A major challenge is to discover novel molecules that kill all microbes, including persistent organisms, using a new, target-based approach that is based on the sequence of bacterial genomes.
Also, nontraditional targets such as those involved in disease pathogenesis and those involved in adaptation and growth in infection sites can be found through the analysis of genome sequences. Targeting these sites could ablate infection without inducing resistance because this action may not result in the same degree of selective pressure that encourages resistance.
Interfering with bacterial adhesion, inhibiting, neutralizing and clearing endotoxin, and administering cytokines as immunoadjuvants are the most promising nontraditional alternative or integrative treatments for pneumonia that are under development.
Purpose of review: Increasing antimicrobial resistance among common respiratory bacteria has created challenges in selecting appropriate therapy for pneumonia. Fortunately, the analysis of genome sequences has allowed us to find novel, nontraditional targets that are involved in disease pathogenesis or in adaptation and growth in infection sites. The advantage of the nonclassical targets is that targeting these sites could ablate infection without inducing resistance. Interfering with bacterial adhesion, inhibiting, neutralizing and clearing endotoxin, and administering cytokines as immunoadjuvants are the most promising alternative or integrative treatments for pneumonia that are under development.
Recent findings: Interference with bacterial adhesion is possible using inhibitors of sortase or inactivators of the srtA gene against gram-positive bacteria, inhibitors of the periplasmic chaperone or those of usher function against gram-negative bacteria, novel polysaccharides that are present on echinoderm surfaces, antiadhesin vaccines, or the passive administration of antiadhesin antibodies. Inhibition, neutralization, and clearance of endotoxin possibly interferes in the lipid A biosynthetic pathway or using lipid A analogues with reduced or lack of ability to activate the major endotoxin receptors or proteins such as recombinant Limulus antilipopolysaccharide factor, bactericidal/permeability increasing protein, or lipopolysaccharide binding protein. Tumor necrosis factor 70-80, an adenoviral vector that encodes murine tumor necrosis factor α, and recombinant interferon gamma seem to be the most promising cytokines for use as immunoadjuvants for the treatment of pneumonia.
Summary: Ideally, potential treatment of life-threatening bacterial pneumonia will combine immunoadjuvant and conventional antibiotic therapy. Compounds capable of stimulating early host defense and microbial clearance, but not the later phases of inflammatory tissue injury associated with sepsis, may be advantageous.
Increasing antimicrobial resistance among common respiratory bacteria has created challenges in selecting the appropriate therapy for pneumonia, which is a major infection control problem because of its reported frequency, associated high fatality rate, and attendant costs, mainly for hospitalized patients.
To overcome infections caused by resistant strains, new classes of antimicrobial compounds must be developed. A major challenge is to discover novel molecules that kill all microbes, including persistent organisms, using a new, target-based approach that is based on the sequence of bacterial genomes.
Also, nontraditional targets such as those involved in disease pathogenesis and those involved in adaptation and growth in infection sites can be found through the analysis of genome sequences. Targeting these sites could ablate infection without inducing resistance because this action may not result in the same degree of selective pressure that encourages resistance.
Interfering with bacterial adhesion, inhibiting, neutralizing and clearing endotoxin, and administering cytokines as immunoadjuvants are the most promising nontraditional alternative or integrative treatments for pneumonia that are under development.
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