Arzneimittelforschung. 1989 Jul;39(7):755-8.
Interaction of azithromycin [Zithromax] and human phagocytic cells. Uptake of the antibiotic and the effect on the survival of ingested bacteria in phagocytes.

Wildfeuer A, Laufen H, Muller-Wening D, Haferkamp O.

Department of Pathology, University of Ulm/Donau, Zusmarshausen, Fed. Rep. of Germany.

14C-labeled azithromycin, a new macrolide antibiotic, was accumulated by various phagocytic cells isolated from volunteers or patients. The concentration of the antibiotic in monocytes, polymorphonuclear leucocytes (PMNLs), and alveolar macrophages was greater than that in the surrounding medium by a factor of between 200 and 668. Azithromycin [Zithromax] penetrated somewhat more rapidly into PMNLs and monocytes than into alveolar macrophages. On the other hand the final concentration in the alveolar macrophages was greater by a factor of about 3 than that in the other two phagocytic cells. Staphylococcus aureus, Legionella pneumophila and Haemophilus influenzae previously taken up by the phagocytes were rapidly inactivated by low (0.031-0.5 micrograms/ml) concentrations of the antibiotic, which in the presence of the cells were subinhibitory. There is thus a clear synergism between azithromycin [Zithromax] and the phagocytic cells which leads to increased intracellular killing of the bacteria.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2551303&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1987 Dec;31(12):1948-54.
Pharmacokinetic and in vivo studies with azithromycin [Zithromax] (CP-62,993), a new macrolide with an extended half-life and excellent tissue distribution.

Girard AE, Girard D, English AR, Gootz TD, Cimochowski CR, Faiella JA, Haskell SL, Retsema JA.

Central Research Division, Pfizer Inc., Groton, Connecticut 06340.

Azithromycin [Zithromax] (CP-62,993), a new acid-stable 15-membered-ring macrolide, was well absorbed following oral administration in mice, rats, dogs, and cynomolgus monkeys. This compound exhibited a uniformly long elimination half-life and was distributed exceptionally well into all tissues. This extravascular penetration of azithromycin [Zithromax] was demonstrated by tissue/plasma area-under-the-curve ratios ranging from 13.6 to 137 compared with ratios for erythromycin of 3.1 to 11.6. The significance of these pharmacokinetic advantages of azithromycin [Zithromax] over erythromycin was shown through efficacy in a series of animal infection models. Azithromycin [Zithromax] was orally effective in treating middle ear infections induced in gerbils by transbulla challenges with amoxicillin-resistant Haemophilus influenzae or susceptible Streptococcus pneumoniae; erythromycin failed and cefaclor was only marginally active against the H. influenzae challenge. Azithromycin [Zithromax] was equivalent to cefaclor and erythromycin against Streptococcus pneumoniae. In mouse models, the new macrolide was 10-fold more potent than erythromycin and four other antibiotics against an anaerobic infection produced by Fusobacterium necrophorum. Similarly, azithromycin [Zithromax] was effective against established tissue infections induced by Salmonella enteritidis (liver and spleen) and Staphylococcus aureus (thigh muscle); erythromycin failed against both infections. The oral and subcutaneous activities of azithromycin, erythromycin, and cefaclor were similar against acute systemic infections produced by Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, or S. aureus, whereas azithromycin [Zithromax] was more potent than erythromycin and cefaclor against the intracellular pathogen Listeria monocytogenes. The pharmacokinetic advantage of azithromycin [Zithromax] over erythromycin in half-life was clearly demonstrated in prophylactic treatment of an acute mouse model of S. aureus infection. These properties of azithromycin [Zithromax] strongly support the further evaluation of this new macrolide for use in community-acquired infections of skin or soft tissue and respiratory diseases.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2830841&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1988 Apr;32(4):524-9.
In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin [Zithromax] [CP-62,993], and A-56268) on Toxoplasma gondii.

Chang HR, Pechere JC.

Department of Microbiology, Faculte de Medecine de Geneve, Centre Medical Universitaire, Switzerland.

The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with [3H]uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin [Zithromax] (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin [Zithromax] and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2837140&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1988 May;32(5):752-4.
In vitro activities of azithromycin [Zithromax] (CP 62,993), clarithromycin (A-56268; TE-031), erythromycin, roxithromycin, and clindamycin.

Barry AL, Jones RN, Thornsberry C.

Clinical Microbiology Institute, Tualatin, Oregon 97062.

The in vitro activity of azithromycin [Zithromax] (CP 62,993 or XZ-450) against Haemophilus influenzae was greater than that of three other macrolides. However, azithromycin [Zithromax] was four- to eightfold less active than erythromycin against the gram-positive cocci and against Listeria monocytogenes. Erythromycin and azithromycin [Zithromax] were similar in their activity against Legionella pneumophila, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2840016&dopt=Abstract Zithromax azithromycin




Eur J Clin Microbiol Infect Dis. 1988 Aug;7(4):541-4.
Comparative in vitro activity of the new oral macrolide azithromycin.

Neu HC, Chin NX, Saha G, Labthavikul P.

Department of Medicine, College of Physicians & Surgeons, Columbia University, New York, New York 10032.

The in vitro activity of the new oral macrolide azithromycin [Zithromax] was compared with that of erythromycin against gram-positive and gram-negative aerobic and anaerobic bacteria. Ninety percent of hemolytic streptococci groups A and B, and Streptococcus pneumoniae were inhibited by 0.5 microgram/ml. Activity of azithromycin [Zithromax] was similar to that of erythromycin; erythromycin-resistant staphylococci and streptococci were not inhibited. Azithromycin [Zithromax] was more active than erythromycin against Haemophilus influenzae (MIC90 1 microgram/ml) and Neisseria gonorrhoeae. It inhibited Campylobacter spp. and Pasteurella multocida, and had an MIC50 of 8 micrograms/ml for Escherichia coli, Salmonella spp., Shigella spp. and Yersinia enterocolitica compared to an erythromycin value of greater than 64 micrograms/ml.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2846300&dopt=Abstract Zithromax azithromycin




Agents Actions. 1988 Aug;25(1-2):124-31.
Comparative studies on the effects of erythromycin A and azithromycin [Zithromax] upon extracellular release of lysosomal enzymes in inflammatory processes.

Carevic O, Djokic S.

Institute of Public Health, Zagreb, Yugoslavia.

In the present studies the in vivo and in vitro effects of erythromycin A and azithromycin, a new type of macrolide (Fig. 2.), were investigated upon extracellular release of lysosomal enzymes, beta-glucuronidase (beta-Gluc) and beta-N-acetylglucosaminidase (beta-Glm) by using two experimental model systems: in vivo-adjuvant-induced arthritis in rats and in vitro- human polymorphonuclear leucocytes (PMNL) exposed to bovine serum albumin/anti-bovine serum albumin (BSA/anti-BSA), immune complex. Administrations of erythromycin A or azithromycin [Zithromax] at doses of 5, 10 and 15 mg/kg into rats one day prior and 2, 4, 6, 8 and 10 days after a single subplantar injection of Freund's complete adjuvant significantly (p less than 0.01) inhibited extracellular release of lysosomal enzymes tested in the synovial fluid of injected left hind paw. These effects were dose-dependent. Further, erythromycin A and azithromycin [Zithromax] at concentrations of 10(-7) M, 10(-6) M and 10(-5) M significantly (p less than 0.01) reduced excocytosis of both lysosomal enzymes, beta-Gluc and beta-Glm from human PMNL initiated by BSA/anti-BSA in a dose-related fashion. However, azithromycin [Zithromax] was by far more effective (p less than 0.01) in decreasing extracellular release of beta-Gluc and beta-Glm either in the in vivo or in vitro experiments in comparison with erythromycin A. Appropriate control experiments excluded the possibilities that erythromycin A or azithromycin [Zithromax] interfered with activities of lysosomal enzymes or with test reagents. Also, in no instances was there enhanced release of a cytoplasmic enzyme LDH.(ABSTRACT TRUNCATED AT 250 WORDS)

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2847507&dopt=Abstract Zithromax azithromycin




Minerva Pediatr. 1995 Jun;47(6):249-60.
[Efficacy and tolerance of azithromycin [Zithromax] in respiratory tract infections in children]

[Article in Italian]

Toscano MA, Marzullo E, Minneci MS, Salmeri M, Chinnici V, Emanuele A, Gulino A, Malafarina D, Mannino G, Marletta V, et al.

Istituto di Microbiologia, Universita degli Studi, Catania.

This study was carried out to determine the clinical efficacy and the clinical safety of azithromycin [Zithromax] in a group of children with acute respiratory tract infections. The study involved 82 children treated with a single daily 10 mg/kg dose of azithromycin [Zithromax] for three consecutive days. 7 days later, the overall clinical response was 100% (cure and improvement): bacteriological cure was achieved in 97.5% of the patients treated. Recurrences were never observed. Side effects not requiring interruption of therapy were observed in 3 patients (3.6%). The side effects were gastrointestinal disturbances. In conclusion azithromycin [Zithromax] showed a remarkably clinical efficacy for treatment of acute respiratory infections in children. Tolerability and therapeutic compliance were excellent.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7476752&dopt=Abstract Zithromax azithromycin