Drugs online research references
Circulation. 2001 Jan 23;103(3):351-6.
Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment.
Gieffers J, Fullgraf H, Jahn J, Klinger M, Dalhoff K, Katus HA, Solbach W, Maass M.
Institute of Medical Microbiology and Hygiene, Medical University of Lubeck, Lubeck, Germany.
BACKGROUND: Recovery of the intracellular bacterium Chlamydia pneumoniae from atherosclerotic plaques has initiated large studies on antimicrobial therapy in coronary artery disease. The basic concept that antibiotic therapy may eliminate and prevent vascular infection was evaluated in vitro and in vivo by examining the antibiotic susceptibility of C pneumoniae in circulating human monocytes, which are thought to transport chlamydiae from the respiratory tract to the vascular wall. METHODS AND RESULTS: Blood monocytes (CD14+) from 2 healthy volunteers were obtained before and after oral treatment with azithromycin or rifampin and then inoculated with a vascular C pneumoniae strain and continuously cultured in the presence of the respective antibiotic. Progress of infection and chlamydial viability was assessed by immunogold-labeling and detection of C pneumoniae-specific mRNA transcripts. Circulating monocytes from patients undergoing treatment with experimental azithromycin for coronary artery disease were examined for C pneumoniae infection by cell culture. Antibiotics did not inhibit chlamydial growth within monocytes. Electron microscopy showed development of chlamydial inclusion bodies. Reverse transcription-polymerase chain reaction demonstrated continuous synthesis of chlamydial mRNA for 10 days without lysis of the monocytes. The in vivo presence of viable pathogen not eliminated by azithromycin was shown by cultural recovery of C pneumoniae from the circulating monocytes of 2 patients with coronary artery disease. CONCLUSIONS: C pneumoniae uses monocytes as a transport system for systemic dissemination and enters a persistent state not covered by an otherwise effective antichlamydial treatment. Prevention of vascular infection by antichlamydial treatment may be problematic: circulating monocytes carrying a pathogen with reduced antimicrobial susceptibility might initiate reinfection or promote atherosclerosis by the release of proinflammatory mediators.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11157684&dopt=Abstract
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Int J Antimicrob Agents. 1999 Feb;11(2):121-32.
Effect of clarithromycin and azithromycin on production of cytokines by human monocytes.
Khan AA, Slifer TR, Araujo FG, Remington JS.
Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, CA 94301, USA.
We examined the in vitro effect of clarithromycin and azithromycin on cytokine production by LPS and Pansorbin stimulated human monocytes. At concentrations that are physiologically achievable, both antibiotics affected in vitro production of IL-1alpha, IL-1beta, IL-6, IL-10, GM-CSF and TNF-alpha to varying degrees. Of those individuals in whom a significant increase or decrease in cytokine production was noted, clarithromycin treatment resulted in a significant suppression of production of each cytokine in 71% and a significant increase in 29% of the individuals. Similar results were noted with azithromycin. The results with IL-6 and TNF-alpha in the clarithromycin studies were most striking. A significant decrease was noted in 60% of individuals for IL-6 and 86% for TNF-alpha. For azithromycin, the most interesting results were for IL-1alpha (decrease in 100% of individuals) and for TNF-alpha (decrease in 100% of individuals). These results show that both clarithromycin and azithromycin alter cytokine production in human monocytes and thus possess immunomodulatory activity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10221415&dopt=Abstract
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Int J Antimicrob Agents. 2000 Sep;16(1):37-43.
Comparison of azithromycin leukocyte disposition in healthy volunteers and volunteers with AIDS.
McNabb J, Owens RC, Xuan D, Quintiliani R, Nightingale CH, Nicolau DP.
Department of Pharmacy Research, Hartford Hospital, CT 06102, USA.
Azithromycin, has been proved to be effective in the treatment and prophylaxis of a wide variety of infections. While the penetration of azithromycin into a number of types of mammalian cells has been well characterized, the influence of HIV infection on the intracellular disposition of this agent has not been studied. We therefore studied the disposition of azithromycin in polymorphonuclear (PMN) and mononuclear (MONO) leukocytes from six healthy volunteers and six volunteers with AIDS. After oral administration of a single 1200-mg dose of azithromycin (two 600-mg tablets), blood samples were collected over 6 days and intracellular azithromycin concentrations in MONOs and PMNs were measured. Analysis of the intracellular pharmacokinetics revealed an apparent difference in the MONO and PMN profile; this profile was similar for both groups. Intracellular concentrations of azithromycin remained high throughout the study period. Furthermore, no statistically significant differences in the intracellular area under the curve (11309+/-2543 vs. 16650+/-6254 for PMN; 14180+/-3802 vs. 21211+/-10001 for MONO) were observed between the healthy and AIDS populations, respectively. Our data confirm the extensive uptake of azithromycin by white blood cells both in healthy volunteers and in AIDS patients.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11185411&dopt=Abstract
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