Arzneimittelforschung. 1993 Apr;43(4):484-6.
Uptake and subcellular distribution of azithromycin [Zithromax] in human phagocytic cells. Demonstration of the antibiotic in neutrophil polymorphonuclear leucocytes and monocytes by autoradiography and electron microscopy.

Wildfeuer A, Reisert I, Laufen H.

Department of Pathology, University of Ulm, Fed. Rep. of Germany.

Azithromycin [Zithromax] (CAS 83905-01-5), a new azalide antibiotic, reached high concentrations in alveolar macrophages obtained from patients. Uptake of [14C] azithromycin [Zithromax] by macrophages resulted in an intracellular/extracellular concentration ratio of approximately 634 after 90 min incubation. Electron microscopic autoradiography provided visual evidence for the marked uptake and localization of [3H] azithromycin [Zithromax] in human neutrophils and monocytes isolated from healthy volunteers. Quantitative analysis of the autoradiographs showed the distribution of azithromycin [Zithromax] over the various compartments of the phagocytic cells.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8388213&dopt=Abstract Zithromax azithromycin




Eur J Clin Microbiol Infect Dis. 1993 Feb;12(2):131-3.
Effect of pH variation on the susceptibility of Helicobacter pylori to three macrolide antimicrobial agents and temafloxacin.

Malanoski GJ, Eliopoulos GM, Ferraro MJ, Moellering RC Jr.

Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts 02215.

The in vitro susceptibility of 27 clinical isolates of Helicobacter pylori to erythromycin, clarithromycin, azithromycin [Zithromax] and temafloxacin under various pH conditions was evaluated. Clarithromycin (MIC90 0.03 micrograms/ml) was found to be significantly more active than either erythromycin (MIC90 0.125 micrograms/ml) or azithromycin [Zithromax] (MIC90 0.25 micrograms/ml) at a neutral pH. Lowering the pH to 5.75 resulted in a loss in efficacy from 8- to 32-fold for all three macrolides studied. The MIC90 of clarithromycin (0.5 micrograms/ml) remained lower than those of azithromycin [Zithromax] (2 micrograms/ml) and erythromycin (4 micrograms/ml). No synergism or antagonism was observed with combinations of clarithromycin and temafloxacin at either the neutral or lower pH values.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8388791&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 May;37(5):1015-24.
Preincubation of Haemophilus influenzae with subinhibitory concentrations of macrolides: influence on human neutrophil chemiluminescence.

Bonnet M, Van der Auwera P.

Service de Medecine, Institut Jules Bordet, Centre des Tumeurs de l'Universite Libre de Bruxelles, Belgium.

Preincubation of Haemophilus influenzae with antibiotics may influence opsonophagocytosis as studied by chemiluminescence. Two strains of H. influenzae (strain 1 [type b] and strain 2 [uncapsulated]) were pretreated with erythromycin, roxithromycin, clarithromycin, and azithromycin [Zithromax] for 1 h in Haemophilus test medium (the last 25 min was either without serum or with 10% fresh serum or 10% decomplemented serum). Human neutrophils were stimulated with a pretreated or control inoculum at four different bacterium/neutrophil ratios and tested for luminol chemiluminescence with an LKB luminometer. The results were normalized for bacterium/neutrophil ratio and compared by the two-sided Wilcoxon test. Pretreatment of bacteria with one-half of the MICs of erythromycin, clarithromycin, and roxithromycin produced nonsignificant (P > 0.05) increases in the chemiluminescence response (means of 23% for strain 1 and 4% for strain 2). Pretreatment with azithromycin [Zithromax] at one-half of the MIC produced an increase in the chemiluminescence response induced by serum-opsonized strain 1 (320% +/- 36% [mean +/- standard error of the mean]) and strain 2 (107% +/- 20%) (P < 0.05). This increase was concentration dependent: for strain 1, 60% +/- 18% at one-fourth of the MIC to 440% +/- 41% at the MIC; for strain 2, 10% +/- 5% at one-fourth of the MIC to 300% +/- 20% at the MIC. For strain 1, the maximal increase with azithromycin [Zithromax] pretreatment (at the MIC) required opsonization with fresh serum. Opsonization with decomplemented serum was associated with a 53% +/- 21% increase; this increase was 28% +/- 3% in the absence of serum. For strain 2, azithromycin [Zithromax] reduced the lag phase of the chemiluminescence response induced by the absence of serum but did not alter the chemiluminescence response in the presence of decomplemented serum. A significant contribution of soluble factors in the enhanced response observed with bacteria preincubated with azithromycin [Zithromax] was excluded. The increase of the chemiluminescence response with azithromycin [Zithromax] pretreatment was probably due to improvement in complement-dependent opsonization for strain 1 and to improvement in both serum-independent and serum-dependent opsonization for strain 2.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8390808&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 May;37(5):1203-5.
In vitro activity of azithromycin [Zithromax] against bacterial enteric pathogens.

Gordillo ME, Singh KV, Murray BE.

Department of Internal Medicine, University of Texas Medical School, Houston 77030.

The in vitro activity of azithromycin [Zithromax] against enteric bacterial pathogens was determined by agar dilution. Azithromycin [Zithromax] was highly active against Campylobacter spp. (MIC for 90% of strains tested [MIC90] = 0.125 micrograms/ml) and against enterotoxigenic, enterohemorrhagic, enteroinvasive, and enteropathogenic Escherichia coli (MIC90 = 2 micrograms/ml), Shigella spp. (MIC90 = 1 micrograms/ml), and Salmonella spp. (MIC90 = 4 micrograms/ml), including Salmonella typhi (MIC90 = 1 microgram/ml). On the basis of the in vitro activity of the drug against these organisms, clinical studies of azithromycin [Zithromax] in enteric diseases should be considered; the high intracellular concentrations achieved by azithromycin [Zithromax] may be particularly relevant for organisms like S. typhi, Campylobacter spp., and Shigella spp. which typically invade cells as part of their infectious process.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8390813&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 May;31(5):681-8.
Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin [Zithromax] and other macrolide antibiotics.

Molinari G, Guzman CA, Pesce A, Schito GC.

Institute of Microbiology, University of Genoa, Italy.

The ability of three macrolide antibiotics (erythromycin, clarithromycin and azithromycin) to inhibit the expression of several pathogenicity traits of Pseudomonas aeruginosa at concentrations that do not affect the rate of growth of this microorganism was investigated. Sub-MICs of azithromycin [Zithromax] manifested the broadest spectrum of action and strongly suppressed the synthesis of elastase, proteases, lecithinase and DNase. Clarithromycin and erythromycin were far less effective. Gelatinase was reduced almost to the same level by the three antibiotics, while haemolysins and lipase were only marginally affected. Loss of motility was a strain and drug-dependent event, but all the macrolides tested shared the ability to induce this effect. However, only azithromycin [Zithromax] totally suppressed synthesis of pyocyanin in all isolates. These results indicate that newer macrolides and especially axithromycin are endowed with a remarkable ability to inhibit in vitro the expression of a number of physiological processes that are considered more essential than replication in the pathogenesis of P. aeruginosa. Since erythromycin sub-MICs have already been shown to exert beneficial effects in clinical practice, our data, pointing to a much higher potency of azithromycin, suggest its use in future studies.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8392997&dopt=Abstract Zithromax azithromycin




Am J Trop Med Hyg. 1993 Jul;49(1):101-5.
Antimalarial activity of azithromycin [Zithromax] and erythromycin against Plasmodium berghei.

Gingras BA, Jensen JB.

Department of Microbiology, Michigan State University, East Lansing.

Several antibiotics that inhibit protein synthesis on 70S ribosomes, including the macrolide erythromycin, and the azalides azithromycin [Zithromax] (ZITHROMAX) and CP-63,956, demonstrated antimalarial activity against two strains of Plasmodium berghei. In a four-day in vivo test, the azalides were 25-fold more potent than erythromycin against the chloroquine-sensitive P. berghei N strain, and displayed additive effects with chloroquine. This effect was not observed with the erythromycin-chloroquine combination. Against the chloroquine-resistant P. berghei MSU/RC strain, the azalides were 60-fold more potent than erythromycin. Additive effects were observed with azalide-chloroquine combinations against this strain, but these results were not significantly different from the erythromycin-chloroquine combination.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8394660&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jun;31 Suppl E:1-4.
In-vitro concentration of azithromycin [Zithromax] in human phagocytic cells.

Panteix G, Guillaumond B, Harf R, Desbos A, Sapin V, Leclercq M, Perrin-Fayolle M.

Institut Pasteur de Lyon, France.

The in-vitro intraphagocytic uptake and retention of azithromycin [Zithromax] in both human polymorphonuclear leucocytes (PMN) and alveolar macrophages was measured by an improved high-performance liquid chromatography (HPLC) method that was approximately three-fold more sensitive than previous methods. Azithromycin [Zithromax] was accumulated in PMN and alveolar macrophages (about 300-fold), with maximum uptake being obtained after incubation for 60 min. Azithromycin [Zithromax] was eliminated only partially from the cells during the washing process, and was released slowly during re-incubation of phagocytic cells in antibiotic-free medium. This intracellular retention distinguishes azithromycin [Zithromax] from most of the macrolides and quinolones which, in spite of high I/E ratios, are released rapidly from cells.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396080&dopt=Abstract Zithromax azithromycin