Antimicrob Agents Chemother. 1992 Jul;36(7):1412-7.
Activity and local delivery of azithromycin [Zithromax] in a mouse model of Haemophilus influenzae lung infection.

Vallee E, Azoulay-Dupuis E, Pocidalo JJ, Bergogne-Berezin E.

Institut National de la Sante et de la Recherche Medicale U 13, Paris, France.

We compared the activities of azithromycin [Zithromax] and erythromycin against Haemophilus influenzae in a mouse model of nonparenchymatous lower respiratory tract infection. In vitro and in vivo efficacy data for both drugs were analyzed relative to their pharmacokinetics in lungs and in vivo uptake by phagocytes. Aged C57BL/6 mice (mean age, 15.1 +/- 1.9 months) were infected intratracheally with 10(8) CFU of H. influenzae serotype b. Oral drug administration was initiated 4 h after infection by various dosage regimens. In terms of bacterial killing in the lung, azithromycin [Zithromax] was much more active than erythromycin (P less than 0.01). Its in vivo activity was also more durable after a single administration relative to the durability of three doses of erythromycin given at 6-h intervals. The MIC of azithromycin [Zithromax] was eightfold lower than that of erythromycin, and better penetration and a longer half-life in lung tissue were achieved after a single oral administration. Phagocytes delivered increased amounts of both drugs to the infected lungs, particularly at the site of infection (bronchoalveolar airspaces), and detectable levels of azithromycin [Zithromax] were maintained locally for long periods. The fact that the efficacy of azithromycin [Zithromax] coincided with the arrival of large numbers of polymorphonuclear leukocytes within the airspaces suggests that active extracellular concentrations were provided by the release of azithromycin [Zithromax] from these cells. This further supports the potential value of once-daily azithromycin [Zithromax] regimens for the treatment of lower respiratory tract infections in humans, provided that inhibitory concentrations against common pathogens such as H. influenzae are maintained for adequate periods of time.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1324644&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1992 Jul;36(7):1573-4.
In vitro activities of azithromycin, clarithromycin, L-ofloxacin, and other antibiotics against Chlamydia pneumoniae.

Hammerschlag MR, Qumei KK, Roblin PM.

Department of Pediatrics and Medicine, State University of New York, Brooklyn 11203.

The in vitro susceptibilities of 11 strains of Chlamydia pneumoniae to azithromycin, clarithromycin, erythromycin, L-oflaxacin, and doxycycline were determined. Clarithromycin was the most active agent tested, with an MIC for 90% of strains and minimal chlamydiacidal concentration for 90% of strains of 0.03 microns/ml. The activity of azithromycin [Zithromax] was similar to those of erythromycin and doxycycline, with MICs for 90% of strains of 0.125 to 0.25 microns/ml. However, the prolonged half-life and enhanced tissue penetration of azithromycin [Zithromax] should allow for less frequent dosing and shorter duration of therapy than with erythromycin or clarithromycin. L-Ofloxacin had activity similar to that of ofloxacin, with MICs of 0.125 to 0.5 micron/ml. From the results of this in vitro study, azithromycin [Zithromax] and clarithromycin appear to be effective antibiotics that may have a role in the treatment of infections due to C. pneumoniae.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1324650&dopt=Abstract Zithromax azithromycin




J Chromatogr. 1992 May 8;576(2):358-62.
Equivalence of a high-performance liquid chromatographic assay and a bioassay of azithromycin [Zithromax] in human serum samples.

Riedel KD, Wildfeuer A, Laufen H, Zimmermann T.

Department of Research and Development, Pfizer/Mack, Illertissen, Germany.

Two sensitive methods for the determination of the azalide antibiotic azithromycin [Zithromax] in human serum were compared. High-performance liquid chromatography (HPLC) and a microbiological assay were simultaneously applied to 768 serum samples obtained in a clinical study. There was excellent agreement between the azithromycin [Zithromax] concentrations measured by HPLC and by the bioassay. The correlation coefficient for the two methods was r2 = 0.96. The precision and the sensitivity of the methods were found to be very similar.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1328265&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1992 Jun;36(6):1241-3.
In vitro activity of azithromycin [Zithromax] compared with that of erythromycin against Actinobacillus actinomycetemcomitans.

Pajukanta R, Asikainen S, Saarela M, Alaluusua S, Jousimies-Somer H.

Department of Periodontology, University of Helsinki, Finland.

The in vitro susceptibility of Actinobacillus actinomycetemcomitans to azithromycin, a new macrolide antibiotic of a new class known as azalides, was compared with that of erythromycin by the agar dilution method on Mueller-Hinton Haemophilus test medium. Eighty-two A. actinomycetemcomitans strains, 79 recent clinical isolates obtained from 40 periodontally healthy or diseased subjects, and 3 type strains were included in the study. Erythromycin showed poor in vitro activity against A. actinomycetemcomitans. Azithromycin, however, was highly effective against A. actinomycetemcomitans: all strains were inhibited at 2.0 micrograms/ml. Azithromycin [Zithromax] exhibited the best in vitro activity against the serotype a subpopulation of A. actinomycetemcomitans: 100% of the strains were inhibited at 1.0 micrograms/ml. The lowest MICs were, however, recorded by serotype b strains. Since azithromycin [Zithromax] has favorable pharmacokinetic properties, including excellent distribution into tissues, it could be expected to pass into gingival crevicular fluid at levels sufficient to inhibit A. actinomycetemcomitans in vivo. Therefore, it is a good candidate for future clinical trials in A. actinomycetemcomitans-associated periodontitis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1329617&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1992 Jun;36(6):1302-9.
In vitro and in vivo intraleukocytic accumulation of azithromycin [Zithromax] (CP-62, 993) and its influence on ex vivo leukocyte chemiluminescence.

Bonnet M, Van der Auwera P.

Service de Medecine, Institut Jules Bordet, Universite Libre de Bruxelles, Belgium.

The accumulation of azithromycin [Zithromax] in phagocytic cells was studied both in vitro by using a radiolabelled drug and a bioassay and in vivo for 12 volunteers receiving 1.5 g (total dose) orally within 3 days. In vitro, neutrophils and unfractionated blood leukocytes accumulated azithromycin [Zithromax] up to 160-fold the extracellular concentration within 1 h at 37 degrees C but less than 3-fold at 4 degrees C. Dead cells accumulated up to 30-fold azithromycin, whereas NaF-treated cells accumulated up to 60-fold arithromycin. The mean efflux from preloaded cells was at most 31.0% +/- 10.6% (standard error of the mean) of the cell-associated concentration within 4 h of incubation at 37 degrees C in drug-free buffer. In vivo, the azithromycin [Zithromax] concentration was 45.2 +/- 6.1 mg/liter of intracellular fluid at 2 h after the third dose and 36.6 +/- 8.3 mg/liter at 1 week thereafter. The corresponding concentrations in serum were 0.2 +/- 0.1 (2 h) and less than 0.05 (1 week). The luminol-enhanced chemiluminescence response induced by phorbol myristate acetate, opsonized zymosan, and two opsonized strains of Haemophilus influenzae (a type b capsulated strain and a noncapsulated strain) was also studied ex vivo by using the blood leukocytes from the 12 test volunteers and 4 control volunteers at 2 and 6 h after the third oral dose of azithromycin [Zithromax] and at 2, 4, and 7 days thereafter. Azithromycin [Zithromax] did not influence this response despite high levels of cellular accumulation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1329619&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1992 Aug;36(8):1611-3.
Activity of azithromycin [Zithromax] against Mycobacterium avium infection in beige mice.

Cynamon MH, Klemens SP.

Veterans Affairs Medical Center, Syracuse, New York.

The comparative activities of azithromycin [Zithromax] and clarithromycin and the activities of azithromycin [Zithromax] alone and in combination with other antimycobacterial agents were evaluated in the beige mouse model of disseminated Mycobacterium avium complex infection. Azithromycin [Zithromax] was similar in activity to clarithromycin. Azithromycin [Zithromax] plus clofazimine plus ethambutol reduced the number of splenic organisms more than azithromycin [Zithromax] alone, while the combination was less active than azithromycin [Zithromax] alone for bacteria in lungs. Rifabutin had activity similar to that of azithromycin [Zithromax] for organisms in spleens and lungs. Rifabutin plus azithromycin [Zithromax] was more active than either agent alone for organisms in spleens, but the combination's activity was not significantly different from that of rifabutin for organisms in lungs. The activity of azithromycin [Zithromax] against several M. avium complex isolates was evaluated. The reduction of viable cell counts in spleens ranged from 1.7 to 0.8 log units. For the three isolates studied, there was little correlation between the in vitro MIC and the in vivo activity.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1329622&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1992 Jul;30(1):27-37.
Comparative in-vitro activity of azithromycin, macrolides (erythromycin, clarithromycin and spiramycin) and streptogramin RP 59500 against oral organisms.

Williams JD, Maskell JP, Shain H, Chrysos G, Sefton AM, Fraser HY, Hardie JM.

Department of Medical Microbiology, London Hospital Medical College, UK.

The in-vitro activities of azithromycin, clarithromycin, spiramycin and RP 59500 were compared with erythromycin against a wide range of oral organisms which have been implicated in oral infections and/or endocarditis (clindamycin was included for oral streptococci). All compounds tested showed good activity against many of these organisms, although some variation was observed with different species. Clarithromycin was the most active of the antibiotics tested against Gram-positive anaerobes, including Actinomyces spp., Propionibacterium spp., Lactobacillus spp. and Bifidobacterium dentium. Azithromycin [Zithromax] was slightly less active than erythromycin against these species. In general, RP 59500 had higher MICs than the macrolides, other than spiramycin, against these organisms, but was superior in activity against Peptostreptococcus spp., inhibiting all isolates at 2 mg/L. Azithromycin [Zithromax] was, in general, the most active antibiotic tested against the Gram-negative anaerobes: Fusobacterium spp., Bacteroides spp., Wolinella spp., Actinobacillus actinomycetemcomitans, Selenomonas spp. and Mitsuokella multiacida, including those isolates which were insusceptible to erythromycin. Clarithromycin showed similar activity to erythromycin against most Gram-negative species, but was superior against Capnocytophaga ochraceus and Eikenella corrodens. RP 59500 was less active than the macrolides against most Gram-negative anaerobes, but was superior to erythromycin and clarithromycin against Fusobacterium spp. and Leptotrichia buccalis, some strains of which were moderately resistant to erythromycin. The macrolides and clindamycin were about equally active against the oral streptococci, whereas RP 59500 showed lower inhibitory activity. The in-vitro results suggest that azithromycin [Zithromax] and clarithromycin may be of value in the treatment of dental sepsis and the prophylaxis of endocarditis. RP 59500 showed useful activity against Gram-positive anaerobes and, because of its bactericidal activity against oral streptococci, may also prove to have a role in these areas.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1331019&dopt=Abstract Zithromax azithromycin