Chemotherapy. 1996 May-Jun;42(3):186-91.
The influence of azithromycin [Zithromax] on the biofilm formation of Pseudomonas aeruginosa in vitro.

Ichimiya T, Takeoka K, Hiramatsu K, Hirai K, Yamasaki T, Nasu M.

Second Department of Internal Medicine, Oita Medical University, Japan.

The influence of azithromycin [Zithromax] on biofilm formation by Pseudomonas aeruginosa, a cause of refractory chronic respiratory tract infection, was investigated. Alginic acid produced by a mucoid strain of P. aeruginosa was quantified by high-performance liquid chromatography from colonies growing on an agar medium. Polysaccharides in the biofilm formed on silicon chips by a nonmucoid strain were determined by a tryptophan reaction. The effect of azithromycin [Zithromax] was examined at concentrations below the minimum inhibitory concentration (sub-MIC) for each strain. Azithromycin [Zithromax] significantly inhibited the production of alginic acid from the mucoid strain at > or = 1/256 MIC, and the production of exopolysaccharides from the nonmucoid strain at > or = 1/16 MIC. The inhibition of biofilm formation by azithromycin [Zithromax] was also observed by scanning electron microscopy. These findings suggest that azithromycin [Zithromax] inhibits biofilm formation by P. aeruginosa at concentrations well below the MIC.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8983885&dopt=Abstract Zithromax azithromycin




Eur J Clin Microbiol Infect Dis. 1997 Jan;16(1):13-6.
Synergistic effect of azithromycin [Zithromax] on the phagocytic killing of Staphylococcus aureus by human polymorphonuclear leukocytes.

Herrera-Insua I, Perez P, Ramos C, Martinez P, Gomez-Lus ML, Prieto J.

Departamento de Microbiologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.

Many macrolides have been shown to affect the interaction between bacteria and various immune defense mechanisms, such as chemotaxis, accumulation, and bioactivity within phagocytic cells. The interaction of azithromycin [Zithromax] with human polymorphonuclear leukocytes (PMNs) was studied in vitro and compared with the interactions between other macrolides and PMNs. The opsonophagocytic killing of Staphylococcus aureus was synergistically enhanced by azithromycin [Zithromax] at concentrations below and above the minimal inhibitory concentration, with a reduction of up to 2.82 log10 cfu/ml with 2 mg/ml of azithromycin. Other macrolides were effective only at subinhibitory concentrations. The beneficial azithromycin-leukocyte interaction may explain azithromycin's efficacy against intracellular pathogens.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9063667&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1997 Apr;39(4):493-8.
Effect of combination therapy of rifampicin and azithromycin [Zithromax] on TNF levels during a rat model of chronic osteomyelitis.

Littlewood-Evans AJ, Hattenberger M, Zak O, O'Reilly T.

Pharma Research, Ciba-Geigy AG, Basle, Switzerland.

The purpose of the present study was to evaluate the combination of azithromycin [Zithromax] and rifampicin on experimental chronic osteomyelitis due to Staphylococcus aureus. Alterations in bone bacterial titre, activity of tumour necrosis factor (TNF), a cytokine implicated in inflammation-induced bone pathology, and histopathological changes during infection and following antibiotic treatment were evaluated. Rats were infected with S. aureus by direct tibial inoculation and then randomized 56 days after infection to receive saline treatment or a combination of azithromycin [Zithromax] and rifampicin (50 mg/kg po and 25 mg/kg sc respectively) once daily for 21 days. The combination of azithromycin [Zithromax] and rifampicin was successful as determined by dramatic reduction in bone bacterial counts (approximately log 4 cfu), but regrowth of the organisms occurred suggesting that the duration of treatment was insufficient. TNF alpha mRNA and TNF activity were constantly elevated by approximately 20- and >200-fold, respectively, and remained elevated irrespective of antimicrobial treatment. Bone histology revealed extensive increase in bone turnover in both the infected and antibiotic treated bones with no difference being observed between the groups. This suggests that, in infected bone, the elevated TNF levels observed may be directly related to the bone pathology and both remain largely unchanged despite potent antibiotic therapy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9145822&dopt=Abstract Zithromax azithromycin




Sex Transm Dis. 1997 May;24(5):257-60.
Comparison of E-test with agar dilution methods in testing susceptibility of N. gonorrhoeae to azithromycin.

Yasin RM, Suan KA, Meng CY.

Bacteriology Division, Institute for Medical Research, Kuala Lumpur, Malaysia.

BACKGROUND AND OBJECTIVES: The antimicrobial susceptibility pattern of Neisseria gonorrhoeae varies from one country to another and may also change with time. To monitor these variations and changes, it is desirable to have a method that is simple and reproducible. This study was undertaken to determine the in vitro susceptibility of N. gonorrhoeae to azithromycin [Zithromax] and to assess the reliability of results obtained using E-test methodology for determination of the minimum inhibitory concentration (MIC) of azithromycin. STUDY DESIGN: The MICs for 135 clinical isolates of N. gonorrhoeae were determined by a modified Kirby-Bauer method recommended by the National Committee for Clinical Laboratory Standards against penicillin, cefuroxime, ceftriaxone, norfloxacin, tetracycline, kanamycin, spectinomycin, and azithromycin. The MIC of azithromycin [Zithromax] was determined by both the E-test and agar dilution method. All tests were done simultaneously. RESULTS: The MIC of azithromycin [Zithromax] to all 135 isolates ranged from 0.078 to 0.25 microgram/ml with the agar dilution method and from 0.016 to 0.50 microgram/ml with the E-test. The MIC50 and MIC90 of azithromycin [Zithromax] were 0.064 microgram/ml and 0.125 microgram/ml, respectively, by the agar dilution method, whereas they are slightly higher by the E-test method. Seventy-six of the isolates were beta-lactamase producers and 69 were high-level tetracycline-resistant N. gonorrhoeae. There was no difference in the MIC50 and MIC90 of azithromycin [Zithromax] in these groups of isolates. The percentage agreement within the acceptable +/-1 log2 dilution difference between MICs obtained by E-test and those obtained by the agar dilution method was 97.8%. CONCLUSIONS: Azithromycin [Zithromax] has a very good in vitro antigonococcal activity, and the E-test is a reliable method to determine the MIC of azithromycin [Zithromax] against N. gonorrhoeae.

PIP: A single dose of a new antibiotic, azithromycin, has been shown to be effective in the treatment of uncomplicated Neisseria gonorrhoeae. A clinical study was conducted to assess the in vitro susceptibility of N gonorrhoeae to azithromycin [Zithromax] and compare the reliability of results obtained using the new E-test methodology for determination of the minimum inhibitory concentration (MIC) of antibiotic with those obtained through the standard agar dilution method. 135 clinical isolates of N gonorrhoeae were obtained from patients attending hospital-based sexually transmitted disease clinics in five geographic locations in Malaysia. 76 of the isolates were penicillinase-producing N gonorrhoeae and 69 were high-level tetracycline-resistant N gonorrhoeae. All isolates were susceptible to azithromycin [Zithromax] based on the susceptible MIC breakpoint of 2.0 mcg/ml. The MICs ranged from 0.0078-0.25 mcg/ml by agar dilution method and from 0.016-0.50 mcg/ml by E-test. Agreement between these two methods was 97.8%. The single-dose regime and good antigonococcal and antichlamydial activity of azithromycin [Zithromax] make this antibiotic a suitable treatment choice. Moreover, the findings of this study suggest that the simpler, faster E-test is as reliable as the agar dilution method. Given the tendency of the antimicrobial susceptibility pattern of N gonorrhoeae to change rapidly, it is important to monitor MICs to detect the emergence of resistance.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9153733&dopt=Abstract Zithromax azithromycin

abbott.com

The National Committee for Clinical Laboratory Standards (NCCLS) methods for susceptibility testing of Haemophilus influenzae in Haemophilus test medium allow a pH range of 7.2 to 7.4. However, it is known that bacteria may appear to be less susceptible to macrolides at lower pHs. Forty-four strains of H. influenzae were tested for their susceptibilities to clarithromycin and azithromycin [Zithromax] by the disk diffusion and broth microdilution methods. The isolates appeared to be less susceptible at pH 7.2 than at pH 7.4 by both methods. Clarithromycin was less active at pH 7.2 against 43% of the isolates by the disk diffusion method and against 52% of the isolates by the broth microdilution method. Similarly, azithromycin [Zithromax] was less active at pH 7.2 against 41 and 45% of the isolates by the disk diffusion and broth microdilution methods, respectively. Forty-two isolates were classified as clarithromycin susceptible and all isolates were classified as azithromycin [Zithromax] susceptible by the disk diffusion method, regardless of the medium pH. However, only 21 isolates were clarithromycin susceptible at pH 7.2 and 34 isolates were susceptible at pH 7.4 by the broth microdilution method, even though quality control results indicated valid testing at both pHs. This study indicated that the results of tests of the susceptibility of H. influenzae with clarithromycin and azithromycin [Zithromax] are highly dependent on the pH of the medium. Test results and their interpretations varied even when the medium pH was within the NCCLS-approved range and, coupled with the current NCCLS breakpoint of 8 microg/ml in the case of clarithromycin, may explain some of the observed discordances between the disk diffusion and broth microdilution methods.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9163435&dopt=Abstract Zithromax azithromycin




Int J Clin Pharmacol Res. 1996;16(4-5):103-7.
Azithromycin [Zithromax] in the treatment of pneumonias caused by Chlamydia spp: a retrospective study.

Kuzman I, Oreskovic K, Schonwald S, Culig J.

University Hospital of Infectious Diseases Dr. Fran Mihaljevic, Zagreb.

A retrospective study was undertaken in order to compare the efficacy and safety of azithromycin [Zithromax] and doxycycline in the treatment of pneumonias caused by Chlamydia spp. Patients with radiologically confirmed pneumonia and positive complement fixation test for chlamydial infection who were hospitalized in the University Hospital of Infectious Diseases, Zagreb during the years 1989-1992 were reviewed. Among them, 83 were treated with azithromycin, given in a total dose of 1.5 g over 5 days (500 mg once daily at day 1 followed by 250 mg at days 2-5, 60 patients) or 3 days (500 mg once daily, 23 patients). Twenty-two patients were treated with doxycycline (100 mg b.i.d. for 10 days). Treatment groups were comparable with respect to age, sex, and severity of signs and symptoms of illness. All the patients were cured. There were no differences in duration of fever after treatment initiation between patients treated with azithromycin [Zithromax] (whether pretreated with beta-lactam antibiotics or not) and doxycycline (p > 0.05). In addition, 3- and 5-day azithromycin [Zithromax] courses were equally effective (p > 0.05). Both drugs were well tolerated, and only two patients treated with azithromycin [Zithromax] reported nausea. It may be concluded that in the treatment of pneumonias caused by Chlamydia spp. azithromycin [Zithromax] is as effective and well tolerated as doxycycline.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9172008&dopt=Abstract Zithromax azithromycin




Int J STD AIDS. 1997 May;8(5):299-302.
Azithromycin [Zithromax] and erythromycin resistant Neisseria gonorrhoeae following treatment with azithromycin.

Young H, Moyes A, McMillan A.

Department of Medical Microbiology, Edinburgh University Medical School, UK.

A pre-treatment and a 3-week post-treatment isolate of Neisseria gonorrhoeae from a 13-year-old boy treated with azithromycin [Zithromax] in a single 1 g oral dose were characterized microbiologically. Both isolates were of the same serovar/auxotype (1B6/non-requiring) and had similar antibiograms apart from erythromycin and azithromycin: the pre- and post-treatment MICs (minimum inhibitory concentrations) were: 1 mg/L and 32 mg/L to erythromycin and 0.125 mg/L and 3 mg/L to azithromycin. The finding that both isolates were 1B6/NR, had similar antibiograms (other than azithromycin [Zithromax] and erythromycin), and no other 1B6/NR isolates were resistant to erythromycin supports the view that macrolide resistance developed following treatment. A high overall level of azithromycin [Zithromax] susceptibility was confirmed by testing 67 clinical isolates: MIC90 0.5 mg/L (range 0.023-0.75 mg/L). We conclude that the long half-life of azithromycin [Zithromax] which is beneficial in treating chlamydial infection may result in increased selective pressure for resistance in gonococci. This report also highlights the importance of antibiotic susceptibility surveillance of gonococci and stresses the need for appropriate treatment of gonococcal infection, particularly when it is prescribed outwith departments of genitourinary medicine.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9175650&dopt=Abstract Zithromax azithromycin