Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

2012

Helen C. Steel,  Annette J. Theron,  Riana Cockeran,  Ronald Anderson,  and Charles Feldman 

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ABSTRACT

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

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NIH - Mediatotors of Inflammation

Role of procalcitonin in guiding antibiotic therapy.

Dec 2012

Fazili T, Endy T, Javaid W, Maskey M.

Abstract

Purpose The role of procalcitonin in guiding antibiotic therapy is reviewed. Summary Procalcitonin is a prohormone for calcitonin, which is secreted by the parafollicular cells of the thyroid gland. The biological activity of procalcitonin is significantly different from calcitonin and is believed to be part of the complex inflammatory cascade of the immune system. Procalcitonin has been shown to be elevated in bacterial infections but not in viral infections or other inflammatory conditions. The first published study that suggested that procalcitonin levels increased in the presence of bacterial infection was conducted in France in the early 1990s. Numerous studies have been conducted using procalcitonin-guided therapy to reduce antibiotic use. These studies were performed in one of three clinical settings: outpatient primary care (two multicenter, noninferiority studies of patients with upper- and lower-respiratory-tract infections), emergency room and inpatient (five studies in patients with chronic obstructive pulmonary disease, exacerbation, bronchitis, or community-acquired pneumonia), and the intensive care unit (ICU) (two studies in medical ICU patients and two in postoperative ICU patients with infection or sepsis). Based on the findings of these studies, a cutoff value of 0.25 μg/L in non-ICU patients or of 0.5 μg/L in ICU patients seems appropriate for making a decision about the initiation and discontinuation of antibiotic therapy. In patients with a significantly elevated baseline procalcitonin level, a subsequent drop of >80% appears to be reasonable for discontinuing antibiotics. Conclusion Published evidence supports the use of procalcitonin as a biomarker of bacterial infection that can be used to reduce antibiotic exposure.

PubMed