Ann Intern Med. 1996 Feb 15;124(4):389-99.
Doxycycline compared with azithromycin [Zithromax] for treating women with genital Chlamydia trachomatis infections: an incremental cost-effectiveness analysis.

Magid D, Douglas JM Jr, Schwartz JS.

Robert Wood Johnson Clinical Scholars Program, University of Washington, Seattle, USA.

OBJECTIVE: To compare the economic consequences of doxycycline therapy with those of azithromycin [Zithromax] therapy for women with uncomplicated cervical chlamydial infections. DESIGN: Decision analysis in which the health outcomes, costs, and cost-effectiveness of two provider-administered treatment strategies for women with uncomplicated cervical chlamydial infections were compared: 1) initial therapy with doxycycline, 100 mg orally twice daily for 7 days (estimated cost, $5.51) and 2) initial therapy with azithromycin, 1 g orally administered as a single dose (estimated cost, $18.75). RESULTS: Under baseline assumptions, the azithromycin [Zithromax] strategy incurred fewer major and minor complications and was less expensive overall than the doxycycline strategy despite a higher initial cost for acquiring antibiotic agents. In univariate sensitivity analyses, the azithromycin [Zithromax] strategy prevented more major complications but was more expensive than the doxycycline strategy when doxycycline effectiveness was greater than 0.93. In a multivariate sensitivity analysis combining 11 parameter estimates selected so that the cost-effectiveness of the doxycycline strategy would be maximized relative to that of the azithromycin [Zithromax] strategy, the azithromycin [Zithromax] strategy resulted in fewer complications but was more costly. The incremental cost-effectiveness was $521 per additional major complication prevented. However, if the difference in the cost of azithromycin [Zithromax] and doxycycline decreased to $9.80, the azithromycin [Zithromax] strategy was less expensive and more effective, even under these extreme conditions. CONCLUSIONS: On the basis of the best available data as derived from the literature and experts, the azithromycin [Zithromax] strategy was more cost-effective than the doxycycline strategy for women with uncomplicated cervical chlamydial infections. Despite the dominance of the azithromycin [Zithromax] strategy over the doxycycline strategy, the adoption of the azithromycin [Zithromax] strategy may be limited by the practical financial constraints of our currently fragmented health care system, in which the costs and benefits of preventing chlamydia sequelae are often incurred by different components of the system.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8554247&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1995 Nov;39(11):2406-10.
In vitro effectiveness of azithromycin [Zithromax] against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus.

Strickman D, Sheer T, Salata K, Hershey J, Dasch G, Kelly D, Kuschner R.

Department of Rickettsial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.

In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin [Zithromax] against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi. The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry. Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 micrograms/ml for doxycycline and 8 micrograms/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-4 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin. Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug. Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 microgram/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin [Zithromax] was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 microgram/ml to levels below that achieved by 0.25 microgram of doxycycline per ml. Azithromycin [Zithromax] was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found. When tested in an in vitro assay system, azithromycin [Zithromax] was more effective than doxycycline against doxycycline-susceptible and -resistant strains of R. tsutsugamushi.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8585717&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1995 Oct;36(4):641-6.
Efficacy of azithromycin [Zithromax] and rifabutin in preventing infection by Mycobacterium avium complex in beige mice.

Bermudez LE, Petrofsky M, Inderlied CB, Young LS.

Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115, USA.

We investigated the potential of the azalide, azithromycin, and rifabutin in preventing disseminated infection due to Mycobacterium avium complex (MAC) in beige mice. Azithromycin [Zithromax] 200 mg/kg, rifabutin (30 mg/kg or 60 mg/kg) were administered by gavage 6 days before mice were challenged orally with 10(8) cfu MAC and daily for 10 days thereafter during which time the mice were again challenged with the same inoculum on alternate days (days +1, +3, +5, +7, and +9). Sixty-four days later, the presence of bacteria in the blood and the number of viable bacteria in liver, spleen and appendix were estimated. Treatment with azithromycin [Zithromax] and 60 mg/kg/day rifabutin but not 30 mg/kg/day, significantly decreased the incidence of bacteraemia and the number of bacteria in the appendix. The administration of azithromycin [Zithromax] resulted in significantly fewer MAC in the liver and spleen but not in the appendix whereas the converse was true of 60 mg/kg rifabutin. Our results indicate that both azithromycin [Zithromax] and rifabutin can prevent MAC disseminated infection, but that the azalide is more effective than the rifamycin in reducing the burden of infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8591938&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1995 Oct;36(4):647-56.
Comparative activity of azithromycin [Zithromax] and doxycycline against Brucella spp. infection in mice.

Domingo S, Gastearena I, Vitas AI, Lopez-Goni I, Dios-Vieitez C, Diaz R, Gamazo C.

Dpto. de Microbiologia, Clinica Universitaria de Navarra, Pamplona, Spain.

The activities of a short therapeutic regimen with azithromycin [Zithromax] and the classic treatment doxycycline with streptomycin were compared and evaluated in mice infected with Brucella melitensis. In a chronic model, starting therapy 31 days after challenge, azithromycin [Zithromax] (10 days, 50 mg/kg/day) significantly reduced the infection (2.9 logs, day 48 post-infection). The effectiveness of doxycycline (21 days, 50 mg/kg/12 hourly) was greater than azithromycin [Zithromax] (4.1 logs of reduction, day 48 post-infection), and when doxycycline was administered for a period of 45 days, all the animals were bacteriologically cured from day 78. The combination with streptomycin (14 days, 10 mg/kg/day) did not improve the effect of any of the regimens. In an acute model infection, treatments with doxycycline or doxycycline-streptomycin, for a period of 3 days, starting 1 day after lethal challenge, were able to protect all the mice. In contrast, only 50% of the mice treated with azithromycin [Zithromax] survived the challenge. In conclusion, although a short oral treatment with azithromycin [Zithromax] was able to reduce the infection significantly, it was not able to cure the animals as effectively as the classic regimen with doxycycline administered for a longer period of time.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8591939&dopt=Abstract Zithromax azithromycin

uthscsa.edu

OBJECTIVE: To determine the activity of clarithromycin, its metabolite (14-hydroxyclarithromycin), and azithromycin [Zithromax] against Haemophilus influenzae and Staphylococcus aureus using time-kill methodology and to evaluate the susceptibility of the organisms following exposure to various concentrations of the azalide macrolides. DATA SOURCES AND METHODS: Clinical isolates of H. influenzae and S. aureus were obtained from the Clinical Microbiology Laboratory at University Hospital, San Antonio, Texas. Susceptibility testing was performed according to National Committee for Clinical Laboratory Standards guidelines. 14-Hydroxyclarithromycin was added to clarithromycin solutions used for H. influenzae. Time-kill studies were performed using antimicrobial concentrations of 0.25-8x minimum inhibitory concentration (MIC) and an initial inoculum of approximately 10(5) CFU/mL. Samples were plated onto solid agar at 0, 4, 8, 12, and 24 hours. At 0, 12, and 24 hours, samples were then plated onto solid agar incorporated with antibiotic. After incubating plates at 35 degrees C for 24 hours, colony counts were determined. RESULTS: The MICs of clarithromycin and clarithromycin plus 14-hydroxyclarithromycin for H. influenzae were 4 and 2 microg/mL, respectively. For S. aureus, the MIC of clarithromycin was 0.25 microg/mL, and the MIC of azithromycin [Zithromax] for both organisms was 1 microg/mL. H. influenzae developed resistance to both macrolides within 12 hours when exposed to sub-MICs of clarithromycin plus 14-hydroxyclarithromycin. However, when exposed to concentrations less than or equal to the MIC of azithromycin, resistance was not conferred to clarithromycin. S. aureus, on the other hand, became resistant to azithromycin [Zithromax] and less susceptible to clarithromycin following exposure to sub-MICs of either macrolide. CONCLUSIONS: Clarithromycin and azithromycin [Zithromax] elicited a concentration-independent bacteriostatic effect against H. influenzae and S. aureus at concentrations at least two times the MIC. In addition, concentrations maintained above the MIC prevented changes in the susceptibility of H. influenzae and S. aureus to both macrolides.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10630825&dopt=Abstract Zithromax azithromycin




Am J Gastroenterol. 1996 Feb;91(2):264-7.
Azithromycin [Zithromax] for the cure of Helicobacter pylori infection.

Di Mario F, Dal Bo N, Grassi SA, Rugge M, Cassaro M, Donisi PM, Vianello F, Kusstatscher S, Salandin S, Grasso GA, Ferrana M, Battaglia G.

Instituto di Medicina Interna, Cattedra Malattie Apparato Digerente, Universita degli Studi di Padova, Italy.

OBJECTIVES: Azithromycin, a new antibiotic chemically related to erythromycin, has been proposed for the cure of Helicobacter pylori, achieving high gastric tissue levels (above the MIC for H. pylori) after oral administration. The aim of the study was to establish whether azithromycin [Zithromax] plus metronidazole in association with either omeprazole or bismuth subcitrate is useful in curing H. pylori infection of the stomach. PATIENTS AND METHODS: The study involved 132 dispeptic patients who proved to be H. pylori infected by antral and corpus histology (Giemsa, modified) and rapid urease test (CLOtest); the Sydney system was used to classify the gastritis. Sixty-three patients received bismuth subcitrate 120 mg q.i.d. for 14 days plus azithromycin [Zithromax] 500 mg o.d. for the first 3 days plus metronidazole 250 mg q.i.d. for the first 7 days; 69 patients received omeprazole 40 mg for 14 days plus azithromycin [Zithromax] 500 mg o.d. for the first 3 days plus metronidazole 250 mg q.i.d. for the first 7 days. Patients were well matched for common clinical variables. Cure of H. pylori infection was assessed by the same methods 2 months after completion of treatment. RESULTS: Eleven patients dropped out of the study, only one reporting side effects (nausea, vomiting, and epigastric pain). Cumulative "per protocol" cure rate was 66.1% (CI 95%, 58.5-75.3%). There was no statistically significant difference between the two treatment groups: 58.9% (CI 95% 48.4-74.6%) versus 72.3% (CI 95%, 60.7-82.5%). Intention to treat does not substantially modify results. Few side effects were recorded. Cured patients showed a significant reduction in the activity of gastritis. CONCLUSION: Azithromycin, combined with omeprazole and metronidazole, the cure rate of H. pylori was about 70%. The cure of H. pylori infection improves the activity of gastritis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8607490&dopt=Abstract Zithromax azithromycin




Int J STD AIDS. 1996;7 Suppl 1:34-7.
Azithromycin [Zithromax] in the prophylaxis of opportunistic infections in AIDS.

McCutchan JA.

UCSD Treatment Center, Department of Medicine, San Diego, California, USA.

Prevention of opportunistic infections contributes to improved quality of life and survival in individuals with acquired immunodeficiency syndrome (AIDS). Agents which are more effective and convenient, less costly, and better tolerated are needed for multiple organism primary prophylaxis. Azithromycin, azalide with high and prolonged intracellular levels, promise to provide to protection against Mycobacterium avium complex (MAC) disease in those with advanced AIDS when given weekly. A large trail comparing rifabutin (300 mg daily), a currently approved primary prophylactic agent for MAC, with azithromycin [Zithromax] (1200 mg weekly) has been completed and is under analysis. If weekly azithromycin [Zithromax] provides equivalent or better protection from disseminated MAC, the cost effectiveness and convenience of MAC prophylaxis may be improved.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8652726&dopt=Abstract Zithromax azithromycin