Tokai J Exp Clin Med. 1997 Sep;22(3):99-102.
Comparison of in vitro activity of azithromycin [Zithromax] and ampicillin against 31 isolates of Streptococcus milleri.

Kaneko A, Sasaki J.

Department of Oral Surgery, Tokai University School of Medicine, Kanagawa, Japan.

Antibacterial action of azithromycin [Zithromax] against 31 strains of dental infection-derived Streptococcus milleri and tissue transfer of the agent were compared with ampicillin, the drug of first choice for dental infections. Concentrations required to inhibit 50% of isolates(MIC50) and Concentrations required to kill 50% of isolates(MBC50) were 0.10 and 0.2 microgram/ml, respectively, for azithromycin. The antibacterial action of azithromycin [Zithromax] was 4 times more potent in than ampicillin. The MBC90 for azithromycin [Zithromax] was 0.39 microgram/ml, for amplicill 3.13 micrograms/ml. Bactericidally, azithromycin [Zithromax] was 8 times more active than ampicillin. The peak value of concentrations (Cmax) of azithromycin [Zithromax] was 0.45 microgram/ml, about 1/10 that of ampicillin. The half-life of azithromycin [Zithromax] was 10 hours, about 5 times longer than that of ampicillin. The contact time of MIC90 concentrations for azithromycin [Zithromax] was 12 hours, distinctly longer than the 8 hours calculated for ampicillin. Azithromycin [Zithromax] showed excellent tissue transfer concentrations: the gingival transfer concentration following oral administration of 500 mg/day ranged from 0.7-23.5 micrograms/ml.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9618830&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1998 Jul;42(1):75-82.
Gastric mucosal distribution and clinical efficacy of azithromycin [Zithromax] in patients with Helicobacter pylori related gastritis.

Blandizzi C, Malizia T, Gherardi G, Costa F, Marchi S, Marveggio C, Natale G, Senesi S, Bellini M, Maltinti G, Campa M, Tacca MD.

Dipartimento di Oncologia, Universita di Pisa, Italy.

The gastric mucosal distribution of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients with duodenal ulcer and Helicobacter pylori-related gastritis. The time course of ulcer healing, H. pylori infection, and gastritis activity was also evaluated. Twenty patients (median age 50 years) received the following treatment for 1 month: three cycles of azithromycin [Zithromax] (500 mg/day for 3 consecutive days) on days 1-3, 11-13 and 21-23 plus omeprazole (40 mg/day) for 30 consecutive days. Endoscopic biopsy specimens of gastric mucosa and blood samples were collected on days 0, 4, 7, 10, 20 and 30. An additional follow-up endoscopy was carried out on day 60. H. pylori infection was determined by both histology and rapid urease test. Azithromycin [Zithromax] concentrations in both plasma and gastric mucosa were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the reference organism. Azithromycin [Zithromax] concentrations in plasma ranged between 0.17 mg/L (95% CI: 0.08-0.26; n = 5) and 0.32 mg/L (95% CI: 0.21-0.43; n = 5) throughout the treatment period. In addition, azithromycin [Zithromax] concentrations in gastric mucosa were significantly higher than plasma concentrations at all times examined and ranged from 18.5 mg/kg (95% CI: 15-20; n = 20) to 24.6 mg/kg (95% CI: 16.8-32.4; n = 5), Indicating that the drug was highly retained in the target tissue. Accordingly, the ratio of azithromycin [Zithromax] mucosal level to plasma concentration varied between 77.9 (95% CI: 56.5-99.3; n = 5) and 112.7 (95% CI: 100.2-125.2; n = 5). At the end of treatment (day 30) H. pylori was no longer detected in 16 of 20 patients (80%), and this finding was consistent with a marked decrease in the grading of gastritis activity. At the follow-up endoscopy (day 60) the infection was eradicated in only four patients (20%). These data indicate a favourable distribution of azithromycin [Zithromax] into gastric mucosa of patients with H. pylori infection and suggest that this new macrolide antibiotic represents a valuable option for treatment regimens against H. pylori. However, the low eradication rate achieved with azithromycin [Zithromax] plus omeprazole is a source of concern and requires further investigation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9700531&dopt=Abstract Zithromax azithromycin




AIDS. 1998 Aug 20;12(12):1503-12.
Preventing Mycobacterium avium complex in patients who are using protease inhibitors: a cost-effectiveness analysis.

Bayoumi AM, Redelmeier DA.

Department of Medicine, University of Toronto, Canada.

BACKGROUND: Practice guidelines recommending Mycobacterium avium complex (MAC) prophylaxis for patients with HIV disease were based on clinical trials in which individuals did not receive protease inhibitors. OBJECTIVE: To estimate the cost-effectiveness of strategies for MAC prophylaxis in patients whose treatment regimen includes protease inhibitors. DESIGN: Decision analysis with Markov modelling of the natural history of advanced HIV disease. Five strategies were evaluated: no prophylaxis, azithromycin, rifabutin, clarithromycin and a combination of azithromycin [Zithromax] plus rifabutin. MAIN OUTCOME MEASURES: Survival, quality of life, quality-adjusted survival, health care costs and marginal cost-effectiveness ratios. RESULTS: Compared with no prophylaxis, rifabutin increased life expectancy from 78 to 80 months, increased quality-adjusted life expectancy from 50 to 52 quality-adjusted months and increased health care costs from $233000 to $239800. Ignoring time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $44300 per life year. Adjusting for time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $41500 per quality-adjusted life year (QALY). In comparison with rifabutin, azithromycin [Zithromax] was associated with increased survival, increased costs and an incremental cost-effectiveness ratio of $54300 per QALY. In sensitivity analyses, prophylaxis remained economically attractive unless the lifetime chance of being diagnosed with MAC was less than 20%, the rate of CD4 count decline was less than 10 x 10(6) cells/l per year, or the CD4 count was greater than 50 x 10(6) cells/l. CONCLUSION: MAC prophylaxis increases quality-adjusted survival at a reasonable cost, even in patients using protease inhibitors. When not contraindicated, starting azithromycin [Zithromax] or rifabutin when the patient's CD4 count is between 50 and 75 x 10(6) cells/l is the most cost-effective strategy. The main determinants of cost-effectiveness are CD4 count, viral load, place of residence and patient preference.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9727572&dopt=Abstract Zithromax azithromycin




J Infect Dis. 1998 Sep;178(3):900-3.
Combination drug therapy for cryptosporidiosis in AIDS.

Smith NH, Cron S, Valdez LM, Chappell CL, White AC Jr.

Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

Aside from effective antiretroviral therapy, there is no consistently effective antiparasitic therapy for cryptosporidiosis in AIDS. The purpose of this study was to assess safety, efficacy, and durability of combination therapy with paromomycin and azithromycin [Zithromax] for chronic cryptosporidiosis. Patients with AIDS, chronic cryptosporidiosis, and < 100 CD4 cells/microL were treated with open-label paromomycin (1.0 g twice a day) plus azithromycin [Zithromax] (600 mg once a day) for 4 weeks, followed by paromomycin alone for 8 weeks. In 11 patients, median stool frequency decreased from 6.5/day (baseline) to 4.9/day (week 4) and 3.0/day (week 12). Median reductions in 24-h oocyst excretion were 84%, 95%, and >99% at 2, 4, and 12 weeks, respectively. None of the responses were attributable to antiretrovirals. Of 5 survivors at 12-30 months of follow-up, 3 remain asymptomatic off medications, and 2 have chronic, mild diarrhea. Treatment of cryptosporidiosis with azithromycin [Zithromax] and paromomycin was associated with significant reduction in oocyst excretion and some clinical improvement.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9728569&dopt=Abstract Zithromax azithromycin

bbott.com

The dynamics of clarithromycin and azithromycin [Zithromax] efficacy against pulmonary Haemophilus influenzae infection in rats were evaluated. Efficacy was measured by reduction in pulmonary H. influenzae burden on days 3 and 7 postinoculation. Clarithromycin therapy was effective on day 3 or 7 of therapy, while azithromycin [Zithromax] was effective on day 7 but not on day 3 of therapy. Both macrolides produced marked efficacy against all six strains of H. influenzae tested, including four strains for which MICs were above the susceptible breakpoint (8 microgram/ml) concentration of clarithromycin. The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both blood and tissue, while azithromycin [Zithromax] was concentrated primarily in tissue. During pulmonary infection in rats, H. influenzae was found in both intracellular locations and an extracellular location in the lung. Blood concentrations of clarithromycin and azithromycin [Zithromax] approximated human pharmacokinetics, and the blood concentrations for either macrolide rarely exceeded MICs for H. influenzae. At dosages producing blood concentrations similar to values achieved clinically, clarithromycin produced efficacy on day 3 of therapy, while both clarithromycin and azithromycin [Zithromax] were equally effective on day 7. The different dynamics of clarithromycin and azithromycin [Zithromax] suggest that length of therapy should be considered as a key parameter in evaluations of drug efficacy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9736568&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1998 Nov;42(11):2914-8.
In vitro selection of resistance to four beta-lactams and azithromycin [Zithromax] in Streptococcus pneumoniae.

Pankuch GA, Jueneman SA, Davies TA, Jacobs MR, Appelbaum PC.

Department of Pathology (Clinical Microbiology), Hershey Medical Center, Hershey, Pennsylvania 17033, USA.

Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin [Zithromax] among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin [Zithromax] MICs, 0.125 to 4 microg/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing in medium with amoxicillin (with or without clavulanate) lead to an increased MIC, with the MIC rising from 0.008 to 0.125 microg/ml. Five of the six penicillin-susceptible strains showed increased azithromycin [Zithromax] MICs (0.5 to >256.0 microg/ml) after 17 to 45 subcultures. Subculturing in medium with cefaclor did not affect the cefaclor MICs of three strains but and led to increased cefaclor MICs (from 0.5 to 2.0 to 4.0 microg/ml) for three of the six strains, with MICs of other beta-lactams rising 1 to 3 twofold dilutions. Subculturing in cefuroxime led to increased cefuroxime MICs (from 0.03 to 0.06 microg/ml to 0.125 to 0.5 microg/ml) for all six strains without significantly altering the MICs of other beta-lactams, except for one strain, which developed an increased cefaclor MIC. Subculturing in azithromycin [Zithromax] did not affect beta-lactam MICs. Subculturing of the four strains with decreased penicillin susceptibility in amoxicillin (with or without clavulanate) or cefuroxime did not select for beta-lactam resistance. Subculturing of one strain in cefaclor led to an increase in MIC from 0.5 to 2.0 microg/ml after 19 passages. In contrast to strains that were initially azithromycin [Zithromax] susceptible, which required >10 subcultures for resistance selection, three of four strains with azithromycin [Zithromax] MICs of 0.125 to 4.0 microg/ml showed increased MICs after 7 to 13 passages, with the MICs increasing to 16 to 32 microg/ml. All azithromycin-resistant strains were clarithromycin resistant. With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin [Zithromax] contained ermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9797225&dopt=Abstract Zithromax azithromycin




Ophthalmic Res. 1999;31(1):47-52.
Pharmacokinetics of azithromycinin rabbit lacrimal glands and conjunctiv a.

Karcioglu ZA, Ahmed WS, Raines D, El-Yazigi A.

King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

PURPOSE AND BACKGROUND: To measure azithromycin [Zithromax] levels in rabbit lacrimal and Harder glands, conjunctiva and plasma after a single oral dose of 20 mg/kg. Drug levels in lacrimal gland tissue are significant in trachoma because the gland may be involved in the disease process and it is the source of tears by which the drug is carried to the external eye. METHODS: Lacrimal and Harder glands, conjunctiva and plasma were collected from New Zealand white female rabbits at 24, 48, 72, 96 and 144 h following a single oral dose of azithromycin [Zithromax] (20 mg/kg). Azithromycin [Zithromax] levels in tissue and plasma were measured using high-performance liquid chromatography (HPLC) electrochemical detection. RESULTS: Azithromycin [Zithromax] levels peaked within the first 24 h in all tissues and plasma assayed. The highest concentration was in the lacrimal gland (6.2 microg/g, SD +/- 0.8), followed by Harder gland (4.4 microg/g, SD +/- 0.8), conjunctiva (0. 9 microg/g, SD +/- 0.5) and plasma (0.06 microg/g, SD +/- 0.03). These concentrations reached their lowest measured levels at 120 and 144 h. CONCLUSION: Azithromycin [Zithromax] levels measured throughout the 144 h after dosing were consistently above the minimum inhibitory range (MIC) for Chlamydia trachomatis (0.03-0.25 microg/ml) in the lacrimal glands, while the conjunctiva maintained a concentration above the MIC for 96 h and stayed within MIC levels for 144 h.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9831822&dopt=Abstract Zithromax azithromycin