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 [Zithromax] 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 [Zithromax] 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 [Zithromax] 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.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11157684&dopt=Abstract Zithromax azithromycin




Int J Antimicrob Agents. 1999 Feb;11(2):121-32.
Effect of clarithromycin and azithromycin [Zithromax] 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 [Zithromax] 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 [Zithromax] alter cytokine production in human monocytes and thus possess immunomodulatory activity.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10221415&dopt=Abstract Zithromax azithromycin




Int J Antimicrob Agents. 2000 Sep;16(1):37-43.
Comparison of azithromycin [Zithromax] 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 [Zithromax] 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 [Zithromax] 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 [Zithromax] (two 600-mg tablets), blood samples were collected over 6 days and intracellular azithromycin [Zithromax] 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 [Zithromax] 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 [Zithromax] by white blood cells both in healthy volunteers and in AIDS patients.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11185411&dopt=Abstract Zithromax azithromycin




Bull World Health Organ. 2001;79(1):8-14. Epub 2003 Nov 05.
Pilot study of the use of community volunteers to distribute azithromycin [Zithromax] for trachoma control in Ghana.

Solomon AW, Akudibillah J, Abugri P, Hagan M, Foster A, Bailey RL, Mabey DC.

Clinical Research Unit, London School of Hygiene and Tropical Medicine, England.

OBJECTIVE: To assess the skills of community health volunteers in diagnosing active trachoma and distributing azithromycin [Zithromax] in the Northern Region of Ghana. METHODS: Six community health volunteers from Daboya were trained to diagnose trachoma and to treat the disease using azithromycin. They were also informed of the drug's possible side-effects. Under supervision, each volunteer then examined, and if necessary treated, 15 households. The dose of azithromycin [Zithromax] was determined by weight; height was also measured. Tablets were given in preference to suspension when possible. RESULTS: The volunteers' diagnostic sensitivity for active trachoma was 63%; their specificity was 96%. At the household level, their "decision to treat" was correct in 83% of households. In 344 treatment episodes, volunteers planned a dose of azithromycin [Zithromax] outside the range 15-30 mg/kg on only seven occasions (2.0% of all planned treatments). The volunteers' drug management skills were good, the response of the community was excellent, and adverse reactions were infrequent. Diagnosis of active trachoma, record-keeping skills, and knowledge of side-effects were found to need greater emphasis in any future education programme. Most people aged four years or older were able to swallow tablets. For those taking tablets, the correlation between the data gathered for height and weight shows that calculating azithromycin [Zithromax] doses by height is a valid alternative to calculating it by weight. CONCLUSION: Trained community health volunteers have a potential role in identifying active trachoma and distributing azithromycin. To simplify training and logistics, it may be better to base dosage schedules on height rather than weight for those taking tablets, which included most people aged four years or more in the population studied.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11217675&dopt=Abstract Zithromax azithromycin

hotmail.com

BACKGROUND: Treatment of malaria represents a problem as antimalarial drugs are relatively few, and because of the increasing widespread resistance of Plasmodium falciparum to most of these drugs. A partial efficacy of azithromycin [Zithromax] against Pl. falciparum hepatic stage and against trophozoytes in the erythrocytic stages of the disease has been demonstrated. No data concerning the activity against gametocytes are available, and primaquine stands as the only therapy against Pl. falciparum gametocytes. Primaquine causes haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, so primaquine therapy is usually avoided. A better tolerated therapy against gametocytes would be useful to reduce malaria transmission. We present the results of a study concerning the efficacy of azithromycin [Zithromax] in the treatment of P. falciparum gametocytes. METHODS: A prospective study was performed: 4 patients with Pl. falciparum gametocytes (3 children, 1 adult) were treated with azithromycin [Zithromax] for concomitant bacterial infections; in the meantime two children with gametocytes were taken as control. Azithromycin [Zithromax] was administered as recommended. RESULTS: Gametocytes were detectable in children thick blood smears after 8, 5 and 6 days respectively after the beginning of azithromycin [Zithromax] therapy, while they were undetectable in the adult thick blood smear 5 days after the beginning of the therapy. The gametocytes spontaneously disappeared in the two controls 4 to 6 days after the beginning of observation. CONCLUSIONS: These data suggest that azithromycin [Zithromax] seems ineffective against Pl. falciparum gametocytes. Further studies are needed in order to determine whether azithromycin [Zithromax] treated gametocytes are infective to mosquitoes or not, and to confirm this first observation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11218625&dopt=Abstract Zithromax azithromycin

facm.ucl.ac.be

Listeria monocytogenes, a facultative intracellular pathogen, readily enters cells and multiplies in the cytosol after escaping from phagosomal vacuoles. Macrophages exposed to gamma interferon, one of the main cellular host defenses against Listeria, become nonpermissive for bacterial growth while containing Listeria in the phagosomes. Using the human myelomonocytic cell line THP-1, we show that the combination of L-monomethyl arginine and catalase restores bacterial growth without affecting the phagosomal containment of Listeria. A previous report (B. Scorneaux, Y. Ouadrhiri, G. Anzalone, and P. M. Tulkens, Antimicrob. Agents Chemother. 40:1225-1230, 1996) showed that intracellular Listeria was almost equally sensitive to ampicillin, azithromycin, and sparfloxacin in control cells but became insensitive to ampicillin and more sensitive to azithromycin [Zithromax] and sparfloxacin in gamma interferon-treated cells. We show here that these modulations of antibiotic activity are largely counteracted by L-monomethyl arginine and catalase. In parallel, we show that gamma interferon enhances the cellular accumulation of azithromycin [Zithromax] and sparfloxacin, an effect which is not reversed by addition of L-monomethyl arginine and catalase and which therefore cannot account for the increased activity of these antibiotics in gamma interferon-treated cells. We conclude that (i) the control exerted by gamma interferon on intracellular multiplication of Listeria in THP-1 macrophages is dependent on the production of nitric oxide and hydrogen peroxide; (ii) intracellular Listeria may become insensitive to ampicillin in macrophages exposed to gamma interferon because the increase in reactive oxygen and nitrogen intermediates already controls bacterial growth; and (iii) azithromycin [Zithromax] and still more sparfloxacin cooperate efficiently with gamma interferon, one of the main cellular host defenses in Listeria infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10223943&dopt=Abstract Zithromax azithromycin

iupui.edu

BACKGROUND: Multidrug-resistant strains of Streptococcus pneumoniae are increasingly common worldwide, but the clinical significance of their resistance to the macrolide antibiotics is controversial. Applying pharmacokinetic and pharmacodynamic principles can assist in the selection of appropriate antimicrobial therapy. OBJECTIVES: The purpose of this study was to determine the in vitro activity of penicillin, azithromycin, clarithromycin, and clindamycin against clinical isolates of S. pneumoniae and to evaluate the pharmacodynamics of azithromycin [Zithromax] and clarithromycin based on serum and epithelial lining fluid (ELF) concentrations. METHODS: The minimum inhibitory concentrations (MICs) of penicillin, azithromycin, clarithromycin, and clindamycin were determined for 307 isolates of S. pneumoniae using broth microdilution. Using serum and ELF concentrations after standard dosing, we calculated the proportion of isolates against which it would be possible to obtain a ratio of azithromycin [Zithromax] area under the curve to MIC > or =25 and clarithromycin concentrations that exceeded the MIC for > or =40% of the dosing interval. RESULTS: Overall, 19.5%, 25.4%, 25.1%, and 7.2% of the 307 pneumococcal isolates were resistant to penicillin, azithromycin, clarithromycin, and clindamycin, respectively. However, 71.7% of penicillin-resistant strains were also resistant to azithromycin [Zithromax] and clarithromycin. Based on serum concentrations, clarithromycin achieved its pharmacodynamic target in 76.9% of isolates, compared with 59.9% for azithromycin. Based on ELF concentrations, clarithromycin achieved its pharmacodynamic target in 93.5% of isolates, compared with 74.6% for azithromycin. Based on ELF concentrations, clarithromycin achieved its pharmacodynamic target in 86.7% of penicillin-resistant isolates, compared with 28.3% for azithromycin. CONCLUSIONS: On the basis of serum and ELF concentrations, clarithromycin achieved pharmacodynamic targets against a greater proportion of S. pneumoniae isolates than did azithromycin. Clinical studies are needed to determine the efficacy of these agents against pneumococci that demonstrate in vitro resistance using current susceptibility breakpoints.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11318076&dopt=Abstract Zithromax azithromycin