J Vet Pharmacol Ther. 2002 Apr;25(2):99-104.
Pharmacokinetics of azithromycin [Zithromax] in foals after i.v. and oral dose and disposition into phagocytes.

Davis JL, Gardner SY, Jones SL, Schwabenton BA, Papich MG.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.

The properties of azithromycin [Zithromax] suggest that it may be an alternative to erythromycin for treatment of Rhodococcus equi pneumonia in foals. To investigate this possibility, the disposition of azithromycin [Zithromax] in plasma, polymorphonuclear leukocytes (PMN), and alveolar cells was examined after a single administration in foals. Azithromycin [Zithromax] suspension was administered orally (p.o.) at a dose of 10 mg/kg to five healthy 2-3-month-old foals. Two weeks later, azithromycin [Zithromax] for injection was administered by intravenous (i.v.) infusion at a dose of 5 mg/kg to the same foals. Plasma samples were collected after p.o. and i.v. administration. Peripheral blood PMN and bronchoalveolar lavage fluid and alveolar cells were collected after p.o. administration. Azithromycin [Zithromax] concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC) with coulometric electrochemical detection. Azithromycin [Zithromax] p.o. absorption was variable with a mean systemic availability of 39% (+/-20%). The plasma half-life was 16 and 18.3 h after i.v. and p.o. administration, respectively. Azithromycin [Zithromax] had a very large volume of distribution (V(d)) of 11.6 L/kg [V(d(ss))] and 12.4 L/kg [V(d(area))]. The large V(d) can be attributed to high tissue and intracellular concentrations, exhibited by the high concentration of azithromycin [Zithromax] in PMN and alveolar cells. The PMN half-life was 49.2 h. Dosage of 10 mg/kg of azithromycin [Zithromax] p.o. once daily for foals with R. equi pneumonia is recommended for further study.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12000529&dopt=Abstract Zithromax azithromycin

etsu.esu

Azithromycin [Zithromax] is an important antibiotic for the treatment of several different Gram-positive and Gram-negative bacterial infections. Erythromycin and clarithromycin are less useful antibiotics against Gram-negative infections. This difference in inhibitory activity was explored by comparing the effects of azithromycin [Zithromax] and erythromycin on cellular functions in Haemophilus influenzae cells. Effects of both antibiotics on translation, cell viability, and growth rates have been measured. An IC(50) of 0.4 microg/ml was found for the effects of azithromycin [Zithromax] on each of these processes. For erythromycin, an IC(50) of 1.5 microg/ml was observed, indicating a fourfold lower sensitivity of the organisms to this compound. The features of a second target for macrolide antibiotic inhibition in H. influenzae cells have also been examined. Inhibition of the synthesis of the large 50S ribosomal subunit was measured. Subunit formation was prevented in a concentration dependent fashion, with azithromycin [Zithromax] showing a ninefold greater effect on this process compared with erythromycin. Synthesis of the 30S ribosomal subunit was not effected. Pulse and chase labeling kinetics confirmed the slower synthesis rate of the 50S particle in the presence of each antibiotic. The results are discussed in terms of the stronger effect of azithromycin [Zithromax] on ribosome biosynthesis in this organism.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12000992&dopt=Abstract Zithromax azithromycin

virginia.edu

Polymorphonuclear leukocytes (PMNL) concentrate, transport, and release certain antimicrobial agents as they move in a chemotactic gradient. Antipyretic agents are frequently used in febrile patients receiving antimicrobial agents. Thus, the influence of ibuprofen, acetaminophen, and acetylsalicylic acid on uptake, transport, and release of azithromycin [Zithromax] and moxifloxacin was studied. Uptake of the antimicrobial agents by human PMNL and the effect of the antipyretics were quantitated by bioassay of released antimicrobial agent. Transport and release were determined in chemotactic plates overlaid with sentinel bacteria that could detect transported and released antimicrobial agent. None of the antipyretics altered PMNL directed or non-directed movement. Uptake of azithromycin [Zithromax] was significantly inhibited by acetylsalicylic acid but not by the other antipyretics. All of the antipyretic agents studied at therapeutic levels inhibited transport and release of both azithromycin [Zithromax] and moxifloxacin. Administration of any of these antipyretic agents with antimicrobial agents that are transported and released by PMNL could compromise the efficacy of therapy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12001049&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 2002 May;49(5):857-61.
Intracellular activity of ABT-773 and other antimicrobial agents against Legionella pneumophila.

Jung R, Danziger LH, Pendland SL.

Department of Pharmacy Practice, University of Colorado Health Science Center, Denver, CO, USA.

The intracellular activity of ABT-773 against Legionella pneumophila was compared with azithromycin [Zithromax] and ciprofloxacin using HL-60 cells. Against L. pneumophila ATCC 33152 and three clinical isolates the MICs (mg/L) were ABT-773 0.015, ciprofloxacin 0.03 and azithromycin [Zithromax] 0.03. At 48 h, the mean percentage inhibition was as follows: 28.5 +/- 5.9% and 32.6 +/- 4.6% at 8 x and 16 x MIC of ABT-773; 38.1 +/- 8.6% and 48.2 +/- 7.0% at 8 x and 16 x MIC of ciprofloxacin; and 26.3 +/- 9.9% and 28.5 +/- 9.9% at 8 x and 16 x MIC of azithromycin. In this study, all three agents were highly active, with ABT-773 demonstrating similar activity to azithromycin [Zithromax] against L. pneumophila.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12003984&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2002 Jul;46(7):2194-9.
Experimental acute otitis media due to nontypeable Haemophilus influenzae: comparison of high and low azithromycin [Zithromax] doses with placebo.

Babl FE, Pelton SI, Li Z.

Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Treatment of acute otitis media (AOM) with azithromycin [Zithromax] results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes. We sought to determine the effect of azithromycin [Zithromax] at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM. In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin [Zithromax] per kg of body weight per day for 5 days. Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy. Azithromycin [Zithromax] concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin [Zithromax] at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI. A 30-mg/kg dose of azithromycin [Zithromax] daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin [Zithromax] at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin [Zithromax] (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12069974&dopt=Abstract Zithromax azithromycin

na.amedd.army.mil

Initial field malaria prophylaxis trials with azithromycin [Zithromax] revealed insufficient efficacy against falciparum malaria to develop azithromycin [Zithromax] as a single agent. The objective of this in vitro study was to determine the best drug combination(s) to evaluate for future malaria treatment and prophylaxis field trials. In vitro, azithromycin [Zithromax] was tested in combination with chloroquine against 10 representative Plasmodium falciparum isolates. Azithromycin [Zithromax] was also assessed in combination with eight additional antimalarial agents against two or three multidrug-resistant P. falciparum isolates. Parasite susceptibility testing was carried out with a modification of the semiautomated microdilution technique. The incubation period was extended from the usual 48 h to 68 h. Fifty percent inhibitory concentrations (IC(50)s) were calculated for each drug alone and for drugs in fixed combinations of their respective IC(50)s (1:1, 3:1, 1:3, 4:1, 1:4, and 5:1). These data were used to calculate fractional inhibitory concentrations and isobolograms. Chloroquine-azithromycin [Zithromax] studies revealed a range of activity from additive to synergistic interactions for the eight chloroquine-resistant isolates tested, while an additive response was seen for the two chloroquine-sensitive isolates. Quinine, tafenoquine, and primaquine were additive to synergistic with azithromycin, while dihydroartemisinin was additive with a trend toward antagonism. The remaining interactions appeared to be additive. These results suggest that a chloroquine-azithromycin [Zithromax] combination should be evaluated for malaria prophylaxis and that a quinine-azithromycin [Zithromax] combination should be evaluated for malaria treatment in areas of drug resistance.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12121927&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2002 Sep;46(9):2956-62.
In vitro selection of resistance in Haemophilus influenzae by amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin.

Clark C, Bozdogan B, Peric M, Dewasse B, Jacobs MR, Appelbaum PC.

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033, USA.

Abilities of amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin to select resistant mutants of Haemophilus influenzae were tested by multistep and single-step methodologies. For multistep studies, 10 random strains were tested: 5 of these were beta-lactamase positive. After 50 daily subcultures in amoxicillin-clavulanate, MICs did not increase more than fourfold. However, cefprozil MICs increased eightfold for one strain. Clarithromycin and azithromycin [Zithromax] gave a >4-fold increase in 8 and 10 strains after 14 to 46 and 20 to 50 days, respectively. Mutants selected by clarithromycin and azithromycin [Zithromax] were associated with mutations in 23S rRNA and ribosomal proteins L4 and L22. Three mutants selected by clarithromycin or azithromycin [Zithromax] had alterations in ribosomal protein L4, while five had alterations in ribosomal protein L22. Two mutants selected by azithromycin [Zithromax] had mutations in the gene encoding 23S rRNA: one at position 2058 and the other at position 2059 (Escherichia coli numbering), with replacement of A by G. One clone selected by clarithromycin became hypersusceptible to macrolides. In single-step studies azithromycin [Zithromax] and clarithromycin had the highest mutation rates, while amoxicillin-clavulanate had the lowest. All resistant clones were identical to parents as observed by pulsed-field gel electrophoresis. The MICs of azithromycin [Zithromax] for azithromycin-resistant clones were 16 to >128 micro g/ml, and those of clarithromycin for clarithromycin-resistant clones were 32 to >128 micro g/ml in multistep studies. For strains selected by azithromycin, the MICs of clarithromycin were high and vice versa. After 50 daily subcultures in the presence of drugs, MICs of amoxicillin-clavulanate and cefpodoxime against H. influenzae did not rise more than fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs rose to variable degrees.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12183253&dopt=Abstract Zithromax azithromycin