iuk3.ukl.uni-freiburg.de

We investigated the antimicrobial efficacy of clinically meaningful, low concentrations of azithromycin [Zithromax] against intracellular growth of two clinical isolates of Legionella pneumophila. The mature monocytic cell line Mono Mac 6 was used as a model to investigate the effects of antimicrobial agents on L. pneumophila. Extracellular susceptibility was determined by microdilution susceptibility testing in BYEalpha broth after 48 h of incubation. Mono Mac 6 cells infected with L. pneumophila were incubated with various concentrations of azithromycin. After 2 days of incubation, intracellular bacteria were released from the phagocytes and plated on to BCYEalpha agar. Addition of the intracellular-acting antibiotics azithromycin [Zithromax] or ciprofloxacin at their MICs (0.5 and 0. 015 mg/L, respectively) resulted in a significant decrease in cfu, of up to approximately 1 log(10) after 48 h of incubation. In contrast, incubation of intraphagocytic L. pneumophila in the presence of antibiotics without intracellular activity (ceftizoxime, imipenem or amoxycillin-clavulanic acid) did not have any effect. Azithromycin [Zithromax] inhibited intracellular replication at concentrations as low as 0.125 mg/L, approximately one-quarter of the extracellular MIC. The Mono Mac 6 cell line is a useful infection model for investigating the intracellular activity of antimicrobial agents in vitro. In accordance with clinical data and animal experiments, azithromycin [Zithromax] and ciprofloxacin inhibited the intraphagocytic replication of L. pneumophila. In particular, azithromycin [Zithromax] killed ingested legionellae in vitro at concentrations below the peak serum concentrations and below the MIC.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10980164&dopt=Abstract Zithromax azithromycin




Pharmacotherapy. 2000 Sep;20(9):1055-9.
Retrospective evaluation of a potential interaction between azithromycine and warfarin in patients stabilized on warfarin.

Beckey NP, Parra D, Colon A.

Department of Veterans Affairs Medical Center, West Palm Beach, Florida 33410, USA.

STUDY OBJECTIVE: To investigate a potential interaction between azithromycin [Zithromax] and warfarin. DESIGN: Retrospective case-control study. SETTING: Veterans Affairs medical center. PATIENTS: Fifty-two patients stable on anticoagulation therapy. INTERVENTION: Patients who received a prescription for azithromycin [Zithromax] and warfarin at any time since the hospital was opened, June 1, 1995, to July 22, 1999, were identified through a computerized report generated from the pharmacy prescription package. MEASUREMENTS AND MAIN RESULTS: Patients having a stable international normalized ratio (INR; defined as a therapeutic INR +/- 0.2) for at least two consecutive visits before receiving an azithromycin [Zithromax] prescription were reviewed. Changes in INR from before and after addition of azithromycin [Zithromax] were compared with changes in a control group. Controls were identified from a computer-generated report of patients who received a prescription for terazosin and warfarin at any time since the hospital was opened to July 22, 1999 (terazosin was chosen as it has no known interaction with warfarin). These patients also had a stable INR for at least two consecutive visits before receiving the terazosin prescription. In patients with INRs on record within 14 days after starting azithromycin [Zithromax] or terazosin (9 patients/group), the average change in INR was 0.18 +/- 0.48 in the azithromycin [Zithromax] group and 0.07 +/- 0.49 in the terazosin group (p=0.60). For patients with an INR on record within 30 days after starting azithromycin [Zithromax] or terazosin (26 patients/group), the average change in INR was 0.25 +/- 0.67 in the azithromycin [Zithromax] group and 0.05 +/- 0.55 in the terazosin group (p=0.18). CONCLUSION: An interaction between azithromycin [Zithromax] and warfarin was not observed in this retrospective review of patients with a stable INR receiving the combination.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10999497&dopt=Abstract Zithromax azithromycin




Akush Ginekol (Sofiia). 1998;37(3):58-62.
[A new therapeutic approach in the treatment of genital chlamydial infections. Azithromycin [Zithromax] (Sumamed)]

[Article in Bulgarian]

Borisov I.

Azithromycin [Zithromax] is a member of a new class of macrolides called azalydes. Although azithromycin [Zithromax] resembles erythromycine there are significant differences in antibacterial activity and pharmacokinetic profile. Azithromycin [Zithromax] is taken up by cells and the intracellular concentrations are significantly higher than serum concentrations. After a single oral dose of Ig, azithromycin [Zithromax] has a long lasting effect--the tissue concentrations in the uterine and cervical tissues are kept above the minimal inhibitory concentration for Chlamydia trachomatis for more than 10 days. In order to achieve the maximal bioavailability and avoid side effects (gastrointestinal discomfort), azithromycin [Zithromax] should be taken apart from meals (one hour before or two hours after meals). Azithromycin [Zithromax] has no hepatotoxic potential and the possibility for drug interactions is not apparent. It is also recommended for use in pregnant women--FDA category B. A single oral dose of Ig azithromycin [Zithromax] is the reasonable choice for the treatment of uncomplicated genital chlamydial infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10204275&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 2000 Dec;46(6):909-15.
In vitro development of resistance to ceftriaxone, cefprozil and azithromycin [Zithromax] in Streptococcus pneumoniae.

Nagai K, Davies TA, Dewasse BE, Pankuch GA, Jacobs MR, Appelbaum PC.

Department of Pathology (Clinical Microbiology), Hershey Medical Center, 500 University Drive, Hershey, PA 170331, USA.

Approval of ceftriaxone for the treatment of otitis media has led to fear of selection of resistant mutants owing to widespread use. To test this, we examined the ability of sequential subcultures in sub-MICs of ceftriaxone, cefprozil and azithromycin [Zithromax] to select resistant mutants in 12 pneumococci. Daily subculturing was performed 50 times or until mutants with raised ceftriaxone, cefprozil or azithromycin [Zithromax] MICs were selected. Of eight ceftriaxone-susceptible parents, ceftriaxone did not select for any resistant mutants, while cefprozil selected for four mutants (MICs 2-4 mg/L after 21-50 subcultures). Among four ceftriaxone-resistant parents, subculturing in ceftriaxone selected for one stable mutant with raised ceftriaxone MIC (>16 mg/L after 21 subcultures) and subculturing in cefprozil selected for one mutant with raised cefprozil MIC (64 mg/L after 44 subcultures). Mutations were observed in pbp2x and pbp1a. Among six azithromycin-susceptible parents, subculturing in azithromycin [Zithromax] selected for five resistant mutants (MIC 0.5-32 mg/L after 10-42 passages) and among six azithromycin-resistant strains, subculturing selected for mutants with raised azithromycin [Zithromax] MICs in all six strains (MIC 16-32 mg/L after 4-18 passages). All azithromycin-resistant mutants derived from azithromycinsusceptible parents had mutations in domain V of 23S rRNA while all azithromycin-resistant parents and derived mutants had mefE. Single-step mutation rates among the 12 strains at the MIC ranged from 1.5 x 10(-6) to <6.2 x 10(-10) for ceftriaxone, >1.3 x 10(-5) to 8.9 x 10(-8) for cefprozil and >1.1 x 10(-6) to 6.7 x 10(-10) for azithromycin. Multi-step and single-step testing showed that ceftriaxone selected for resistant mutants less often than cefprozil and azithromycin.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11102409&dopt=Abstract Zithromax azithromycin




J Infect Dis. 2001 Jan 15;183(2):232-238. Epub 2000 Dec 13.
Effect of azithromycin [Zithromax] on murine arteriosclerosis exacerbated by Chlamydia pneumoniae.

Rothstein NM, Quinn TC, Madico G, Gaydos CA, Lowenstein CJ.

Division of Cardiology, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Chlamydia pneumoniae infection can exacerbate atherosclerosis in animals. To test the hypothesis that antibiotic therapy inhibits the atherogenic effects of C. pneumoniae infection, 10-week-old apolipoprotein E (ApoE) null mice were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin [Zithromax] or placebo, and were killed at 20 weeks of age. Infection did not affect the size of the aortic lesion, and antibiotic treatment had no effect. Another group of mice, 12-week-old ApoE mice, were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin [Zithromax] or placebo, and were killed at 26 weeks of age. C. pneumoniae infection increased the size of the lesion in infected mice, but azithromycin [Zithromax] did not reduce the size of the aortic lesion in infected mice. Therefore, immediate therapy of acute infection may be necessary to prevent the proatherogenic effects of C. pneumoniae infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11120929&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2001 Jan;45(1):217-22.
Activity of moxifloxacin by itself and in combination with ethambutol, rifabutin, and azithromycin [Zithromax] in vitro and in vivo against Mycobacterium avium.

Bermudez LE, Inderlied CB, Kolonoski P, Petrofsky M, Aralar P, Wu M, Young LS.

Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, California, USA.

Moxifloxacin activity against Mycobacterium avium complex (MAC) was evaluated in vitro against 25 strains. The MIC was determined to range from 0.125 to 2.0 microg/ml. In addition, U937 macrophage monolayers infected with MAC strain 101 (serovar 1) were treated with moxifloxacin (0.25 to 8 microg/ml) daily, and the number of intracellular bacteria was quantitated after 4 days. Moxifloxacin showed inhibitory activity at 0.5 microg/ml and higher. To assess the activity of moxifloxacin containing regimens in vivo, we infected C57BL bg(+)/bg(+) mice with 3 x 10(7) MAC strain 101 bacteria intravenously. One week later treatment was begun with the following: (i) moxifloxacin (50 mg/kg/day or 100 mg/kg/day), ethambutol (100 mg/kg/day), or a combination of moxifloxacin and ethambutol; or (ii) moxifloxacin (100 mg/kg/day), azithromycin [Zithromax] (200 mg/kg/day), or rifabutin (40 mg/kg/day) as oral monotherapy; or (iii) all permutations of two-drug therapy or all three drugs in combination. All groups contained at least 14 animals, and the control group received the drug vehicle. After 4 weeks, quantitative blood cultures were obtained and the number of bacteria in liver and spleen was quantitated. Moxifloxacin, ethambutol, and azithromycin [Zithromax] were active as single agents in liver, spleen, and blood. Rifabutin showed inhibitory activity only in the blood. Two-drug combinations containing azithromycin [Zithromax] were no more active than azithromycin [Zithromax] alone. Similarly, the three-drug combination was not more active than azithromycin [Zithromax] alone in the spleen. Rifabutin did not add to the activity of any other single agent or two-drug combination. Moxifloxacin at both concentrations in combination with ethambutol was significantly more active than each drug alone.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11120969&dopt=Abstract Zithromax azithromycin

popcsi.unian.it

The in vitro anti-cryptosporidial activity of buforin II alone and in combination with azithromycin [Zithromax] and minocycline was investigated. Buforin II showed moderate activity, which increased with increasing concentration to 55.7% suppression of growth at 20 microM. Moreover, its activity was enhanced when it was combined with either azithromycin [Zithromax] or minocycline with >90% parasite reduction at the highest concentration tested. Buforin II may be active in inhibiting Cryptosporidium parvum growth in vitro upon combination with either azithromycin [Zithromax] or minocycline.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11152438&dopt=Abstract Zithromax azithromycin