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PubMed2002

Comparative intracellular (THP-1 macrophage) and extracellular activities of beta-lactams, azithromycin, gentamicin, and fluoroquinolones against Listeria monocytogenes at clinically relevant concentrations.

The activities of ampicillin, meropenem, azithromycin, gentamicin, ciprofloxacin, and moxifloxacin against intracellular hemolysin-positive Listeria monocytogenes were measured in human THP-1 macrophages and were compared with the extracellular activities observed in broth. All extracellular concentrations were adjusted to explore ranges that are clinically achievable in human serum upon conventional therapy. In broth, ampicillin, meropenem, and azithromycin were only bacteriostatic, whereas gentamicin, ciprofloxacin, and moxifloxacin were strongly bactericidal in a concentration-dependent manner. In cells, ampicillin, meropenem, azithromycin, and ciprofloxacin were slightly bactericidal (0.3- to 0.8-log CFU reductions), moxifloxacin was strongly bactericidal (2.1-log CFU reduction), and gentamicin was virtually inactive. The difference in the efficacies of moxifloxacin and ciprofloxacin in cells did not result from a difference in levels of accumulation in cells (6.96 +/- 1.05 versus 7.75 +/- 1.03) and was only partially explainable by the difference in the MICs (0.58 +/- 0.04 versus 1.40 +/- 0.17 mg/liter). Further analysis showed that intracellular moxifloxacin expressed only approximately 1/7 of the activity demonstrated against extracellular bacteria and ciprofloxacin expressed only 1/15 of the activity demonstrated against extracellular bacteria. Gentamicin did not increase the intracellular activities of the other antibiotics tested. The data suggest (i) that moxifloxacin could be of potential interest for eradication of the intracellular forms of L. monocytogenes, (ii) that the cellular accumulation of an antibiotic is not the only determinant of its intracellular activity (for fluoroquinolones, it is actually a self-defeating process as far as activity is concerned), and (iii) that pharmacodynamics (activity-to-concentration relationships) need to be considered for the establishment of efficacy against intracellular bacteria, just as they are for the establishment of efficacy against extracellular infections.

Anti-Bacterial Agents↗
PubMed2004

Activities of two novel macrolides, GW 773546 and GW 708408, compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin against Haemophilus influenzae.

The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW 773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x 10(-9) to 2.2 x 10(-6) with GW 773546, 1.5 x 10(-9) to 6.0 x 10(-4) with GW 708408, and 7.1 x 10(-9) to 3.8 x 10(-4) with telithromycin, whereas the frequencies were 1.3 x 10(-9) to 6.0 x 10(-4) with erythromycin and azithromycin and 2.0 x 10(-9) to 2.0 x 10(-3) with clarithromycin. Alterations in the L22 protein (which were predominant) and the L4 protein were present in mutants selected by the single-step selection process. The postantibiotic effects of GW 773546, GW 708408, and telithromycin for seven H. influenzae strains were 6.6 h (range, 5.2 to 8.8 h), 4.7 h (range, 2.6 to 6.9 h), and 6.4 h (range, 3.8 to 9.7 h), respectively. The results of in vitro studies obtained with both novel macrolides were similar to those obtained with telithromycin and better than those obtained with older macrolides.

Anti-Bacterial Agents↗
PubMed2004

Azithromycin inhibits MUC5AC production induced by the Pseudomonas aeruginosa autoinducer N-(3-Oxododecanoyl) homoserine lactone in NCI-H292 Cells.

The features of chronic airway diseases, including chronic bronchitis, cystic fibrosis, bronchiectasis, and diffuse panbronchiolitis, include chronic bacterial infection and airway obstruction by mucus. Pseudomonas aeruginosa is one of the most common pathogens in chronic lung infection, and quorum-sensing systems contribute to the pathogenesis of this disease. The quorum-sensing signal molecule [N-(3-oxododecanoyl) homoserine lactone (3O-C(12)-HSL)] not only regulates bacterial virulence but also is associated with the immune response. In this study, we investigated whether 3O-C(12)-HSL could stimulate the production of a major mucin core protein, MUC5AC. The effect of a macrolide on MUC5AC production was also studied. 3O-C(12)-HSL induced NCI-H292 cells to express MUC5AC at both the mRNA and the protein levels in time- and dose-dependent manners. A 15-membered macrolide, azithromycin, inhibited MUC5AC production that was activated by 3O-C(12)-HSL. 3O-C(12)-HSL induced extracellular signal-regulated kinase (ERK) 1/2 and I-kappa B phosphorylation in cells, and this induction was suppressed by azithromycin. 3O-C(12)-HSL-induced MUC5AC production was blocked by the ERK pathway inhibitor PD98059. Our findings suggest that the P. aeruginosa autoinducer 3O-C(12)-HSL contributes to excessive mucin production in chronic bacterial infection. Azithromycin seems to reduce this mucin production by interfering with intracellular signal transduction.

4-Butyrolactone↗
PubMed2005

Absolute bioavailability and intracellular pharmacokinetics of azithromycin in patients with cystic fibrosis.

Chronic pulmonary infections with Pseudomonas aeruginosa are the primary cause of morbidity and mortality in patients with cystic fibrosis (CF). The macrolide antibiotics exhibit immunomodulatory and antivirulence activity. Clinical trials with azithromycin in CF have demonstrated significant improvements in pulmonary function and decreased hospitalizations. The purpose of this study was to compare the pharmacokinetics (PK) of azithromycin in patients with CF and controls. The study was conducted as an open-label, parallel, two-period crossover study involving 12 healthy volunteers and 12 patients with CF. Period 1 examined the serum PK following a single oral and intravenous dose, while period 2 examined the intracellular PK following multiple-dose oral administration. CF subjects differed significantly from controls based on weight (53.1 versus 71.0 kg; P < 0.01) and body mass index (19.7 versus 23.2; P < 0.01), respectively. Ninety-two percent of CF patients were pancreatic insufficient and were receiving pancreatic enzymes. The rate (time to reach maximum serum drug concentration, 3.0 versus 3.0 h; P = 0.78) and extent of absorption (absolute bioavailability, 34.2 versus 42.8%; P = 0.37) were similar in patients with CF and controls, respectively. Distribution to the tissues (rate of drug transfer from the central to the peripheral compartment, 1.22 versus 0.759 h(-1); P = 0.03) and elimination (rate of elimination from the central compartment, 0.693 versus 0.492 h(-1); P < 0.01) were more rapid in the healthy volunteers than in the CF subjects, respectively. Mononuclear cell concentrations (15.2 +/- 6.0 mg/liter) far exceeded the maximum serum drug concentration ( approximately 50-fold), demonstrating significant intracellular accumulation. These results indicate no alteration in dosage of azithromycin is necessary in patients with CF taking pancreatic enzymes.

Adult↗
PubMed2001

Influence of variations in test methods on susceptibility of Haemophilus influenzae to ampicillin, azithromycin, clarithromycin, and telithromycin.

The National Committee for Clinical Laboratory Standards standard broth microdilution method for testing the susceptibility of Haemophilus influenzae to ampicillin, azithromycin, clarithromycin, and telithromycin was evaluated by altering one variable at a time. Variables that were tested included age of colony for inoculum preparation, inoculum density, test medium, incubation atmosphere, and incubation time. For the macrolide, azalide, and ketolide agents, incubation in 5 to 7% CO(2) most significantly affected the MICs, producing nearly twofold increases for clarithromycin and telithromycin and a greater than threefold increase for azithromycin. For ampicillin, a 10-fold increase in inoculum density increased the geometric mean MICs for beta-lactamase-negative strains from 1. 50 to 2.45 microg/ml. In addition, 206 H. influenzae strains were tested for their susceptibilities to the same drugs by the broth microdilution tests in two media, as well as by agar dilution tests, disk diffusion tests, and Etests, on six different agar media. The three standard methods with Haemophilus test medium (HTM) compared favorably with each other except for a high minor discrepancy rate (27%) by the disk diffusion test with ampicillin and clarithromycin. Agar dilution test MICs on the five comparative media were generally higher than those on HTM agar but were only rarely more than one twofold concentration higher. Etest MICs of azithromycin and telithromycin were more than twofold higher than agar dilution and broth microdilution MICs on HTM; ampicillin Etest MICs were nearly twofold lower. The use of media other than HTM agar appears to have a minimal effect on susceptibility test results for the ketolide, azalide, or macrolide drugs that we tested against H. influenzae.

Ampicillin↗
PubMed1992

A double blind study of single dose azithromycin and doxycycline in the treatment of chlamydial urethritis in males.

OBJECTIVE: To compare the efficacy and safety of azithromycin and doxycycline in the treatment of males with uncomplicated urethritis caused by chlamydia trachomatis. DESIGN: A multicentre, double-blind, randomised treatment study. SUBJECTS: 130 male outpatients with clinical signs and symptoms of urethritis. SETTING: STD clinics at four Norwegian University Hospitals. METHODS: Patients were randomly allocated to 1000 mg azithromycin as single dose or doxycycline 100 mg twice daily for 7 days. Clinical, bacteriological and safety assessments were made at entry and after 1 and 2 weeks. Safety data were also repeated after 4 weeks. RESULTS: Demographic data were similar in both groups. At the week 1 assessment bacteriological eradication was achieved in 44 of 44 evaluable azithromycintreated patients and in 42 of 42 in the doxycycline group. At the week 2 assessment the corresponding figures were 35 of 35 and 34 of 34 respectively. CONCLUSION: Azithromycin 1000 mg single dose was as effective as doxycycline 100 mg twice daily for 7 days in male patients with chlamydial urethritis.

Adolescent↗
PubMed2005

Comparative randomized pilot study of azithromycin and doxycycline efficacy and tolerability in the treatment of prostate infection caused by Ureaplasma urealyticum.

A total of 1,442 patients with symptoms of chronic prostatitis were examined over a 4-year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases Dr. Fran Mihaljević, Zagreb, Croatia. The inclusion criteria for chronic prostatitis caused by Ureaplasma urealyticum were the presence of clinical symptoms, presence of U. urealyticum in expressed prostatic secretion (EPS) or voided urine collected immediately after prostatic massage (VB(3)), absence of U. urealyticum in urethral swabs and absence of other possible pathogens of chronic prostatitis in EPS or VB(3). A total of 63 patients with prostate infection caused by U. urealyticum were available for this pilot study. The patients were randomized according to a computer randomization list to receive a total dose of 4.5 g of azithromycin given as a 3-day therapy of 1 x 500 mg weekly for 3 weeks or doxycyline 100 mg b.i.d. for 21 days. Patients' sexual partners were treated at the same time. Clinical efficacy and tolerability of the administered drug as well as possible adverse events were evaluated during, at the end and 4-6 weeks after completion of therapy. Bacteriological efficacy was evaluated 4-6 weeks after completion of therapy. Treatment groups did not differ regarding age, distribution of urethral, prostatic, sexual and other symptoms, or digitorectal prostatic examination. Five patients treated with doxycycline had nausea. In the group of patients with prostate infection caused by U. urealyticum, the eradication rate was not significantly different with regard to the administered azithromycin (25/32) or doxycycline (23/31). Clinical cure did not significantly differ with regard to the administered azithromycin (22/32) or doxycycline (21/31).

Adult↗
PubMed1992

Influence of azithromycin and other macrolides on the intracellular killing of Staphylococcus aureus by human polymorphonuclear leucocytes of healthy donors and a patient with Chédiak-Higashi syndrome.

A mixture of human blood phagocytes from healthy donors and opsonized staphylococci was incubated in vitro for 30 min. After that time all the bacteria were phagocytosed. The test tubes were further incubated for 2, 4 and 24 h with or without addition of a macrolide (erythromycin, azithromycin, clarithromycin, roxithromycin) and the effect of these drugs on the survival of intracellular staphylococci (Staphylococcus aureus ATCC 25923) was measured. The minimal effective concentration of the antibiotic which killed 80-90% of the bacteria after a 4-hour incubation was 0.1 mg/l for erythromycin, azithromycin and clarithromycin and 1.2 mg/l for roxithromycin. The percentage of surviving bacteria after 2 and 4 h incubation was not significantly different between these macrolides at the minimal effective concentration. Increasing the concentration of each antibiotic above the minimal effective concentration did not alter the killing rate of intracellular staphylococci. The bacterial activity of polymorphonuclear leucocytes (PMNL) from a patient with Chédiak-Higashi syndrome was less in comparison to PMNL from healthy donors, but was improved in vitro by the addition of erythromycin or azithromycin.

Anti-Bacterial Agents↗
PubMedDate not supplied

Therapeutic effects of roxithromycin and azithromycin in experimental murine brucellosis.

Mice infected with Brucella melitensis were treated with azithromycin or roxithromycin at a dose of 50 mg/kg/day i.p. alone and in combination with streptomycin 75 mg/kg/day for 14 days. Streptomycin at this dose was previously documented to be ineffective against murine brucellosis. Azithromycin- and azithromycin/streptomycin-treated animals demonstrated a significantly better cure rate than controls. Therapy failure was observed in all mice treated with roxithromycin 50 mg/kg/day i.p. alone or in combination with streptomycin 75 mg/kg/day. Our findings demonstrate that azithromycin cures experimental murine brucellosis and may be an effective alternative in the therapy of human brucellosis.

Animals↗
PubMedDate not supplied

Effect of subinhibitory concentrations of ceftazidime, ciprofloxacin, and azithromycin on the hemagglutination and adherence of uropathogenic Escherichia coli strains.

The effect of subinhibitory concentrations (sub-MICs) of ceftazidime, ciprofloxacin, and azithromycin on the hemagglutination (HA) and adherence ability of 29 P-fimbriated Escherichia coli strains to the buffalo green monkey kidney (BGMK) cell line was investigated. Comparisons were made between the values of HA titer before and those after exposure of strains to 1/2, 1/4, 1/8, 1/16 and 1/32 MIC of antibiotics, as well as between the number of bacteria attached to the BGMK cells before and the number after their exposure to the same concentrations of antibiotics. Azithromycin at concentrations of 1/2 and 1/4 MIC damaged the HA capacity of the studied strains, while ceftazidime at concentrations of 1/2, 1/4, 1/8 and 1/16 MIC and ciprofloxacin at concentrations of 1/2 and 1/4 MIC increased the HA capacity of P-fimbriated E. coli. All three antibiotics decreased the adhesive capacity of E. coli to the BGMK cells. Comparing the number of adhered bacteria before and after exposure to sub-MICs of antibiotics, statistically significant differences were determined (p < 0.01) after exposure of the strains to all the concentrations of ceftazidime used after exposure to 1/2, 1/4, 1/8 and 1/16 MIC of ciprofloxacin, and after exposure to 1/2, 1/4 and 1/8 MIC of azithromycin. Filaments formed by sub-MICs of ceftazidime and ciprofloxacin in a static experimental system caused HA, but in an experimental system imitating in vivo conditions, the strains adhered poorly to the cells.

Anti-Bacterial Agents↗
PubMedDate not supplied

A linear model for the pharmacokinetics of azithromycin in healthy volunteers.

The pharmacokinetic profile of azithromycin, after oral ingestion of 500 mg, was determined in 10 healthy volunteers. Statistical and biochemical reason seemed to indicate a zero-order absorption of the drug. The disposition of azithromycin was described by a two-compartment model (plasma compartment and extravascular compartment) with elimination from the plasma compartment. The absorption process ends abruptly after a time T = 2.3 +/- 0.49 h, from the administration. The transfer rate constant from the plasma compartment to the extravascular compartment (k12 = 0.12 +/- 0.04 h-1) and the mean residence time of the drug in the extravascular compartment (MRT2 = 43.53 +/- 13.80 h) indicate a rapid and extensive distribution of azithromycin from the serum into the extravascular fluids. The results confirmed the efficacy of a single daily dose of 500 mg per os for clinical use.

Administration, Oral↗
PubMedDate not supplied

Azithromycin: an interim analysis.

Azithromycin, a novel azalide antibiotic structurally related to erythromycin, has been shown by in vitro studies to have similar activity to erythromycin against Gram-positive pathogens but additionally to have increased activity against some Gram-negative bacteria, notably Haemophilus influenzae. Azithromycin achieves excellent concentrations in tissues, polymorphonuclear leucocytes and alveolar macrophages, and has a prolonged tissue elimination half-life. These properties suggest that short-course, once-daily treatment regimens will be appropriate for a variety of bacterial infections, including those of the respiratory tract, skin and soft tissues. The results of a series of clinical trials using such a regimen are reviewed. It is concluded that azithromycin is clinically and bacteriologically effective in these indications and is well tolerated when compared with regimens using standard antibiotics.

Azithromycin↗
PubMedDate not supplied

The treatment of non-gonococcal urethritis with single dose oral azithromycin.

In an uncontrolled study, the efficacy of azithromycin in the treatment of non-gonococcal urethritis was assessed in 41 male patients aged between 20 and 40 years with a mean age of 27 +/- 5 years. Clinical and microbiological diagnosis confirmed that 28 men were found positive for Chlamydia trachomatis, 10 for Ureaplasma urealyticum and three for both C. trachomatis and U. urealyticum. All patients received 1 g azithromycin orally (four 250 mg capsules). The length of time between the treatment and following visits were 7-10 days and 14-21 days for second and third visits, respectively. Complete eradication was achieved in 27 out of 41 patients. Of the remaining 14, six were found positive for C. trachomatis and were excluded as they did not return for the follow-up visit, one patient did not achieve complete eradication, one patient infected with both C. trachomatis and U. urealyticum failed to achieve complete eradication, and six patients infected with U. urealyticum failed to be completely cured. No adverse effects were reported in any patient. Single dose administration of 1 g azithromycin appears to be an effective and well-tolerated treatment for chlamydial urethritis and an advantage in terms of patient compliance.

Administration, Oral↗
PubMedDate not supplied

Comparison of the efficacy, safety and tolerability of azithromycin and co-amoxiclav in the treatment of acute periapical abscesses.

The activity, safety and tolerability of the azalide azithromycin were compared with those of co-amoxiclav in the treatment of acute periapical abscesses in adults in an open, randomized, multicentre comparative study. Patients of either sex, recruited from 106 dental practices in Belgium, were aged between 18 and 75 years and had acute periapical abscesses not requiring drainage, confirmed by radiology. Azithromycin was administered as a 500-mg tablet orally once daily for 3 days (n = 150) and co-amoxiclav as a 625-mg capsule three times daily, for 5-10 days (n = 153). Both before and after treatment, masticatory pain, percussion pain, headache, and oedema and redness of soft tissue were graded on a four-point scale. Overall clinical success (cure plus improvement) was seen in 131/144 (91%) evaluable patients receiving azithromycin and in 142/148 (96%) receiving co-amoxiclav (difference not significant). There was no significant difference between the two groups in the incidence or severity of adverse events or in the number of discontinuations because of adverse events.

Adolescent↗
PubMed1992

The new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin.

OBJECTIVE: To review the chemistry, antimicrobial spectrum, pharmacokinetics, clinical trials, adverse effects, and drug interactions of four new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin. DATA SOURCES: Information was obtained from comparative clinical trials, abstracts, conference proceedings, and review articles. Indexing terms included azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, and macrolide antibiotics. STUDY SELECTION: Emphasis was placed on comparative clinical trials involving the new macrolide antibiotics. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed by sample size, macrolide dosage regimen, and therapeutic response. DATA SYNTHESIS: The erythromycins have gained widespread use in treating a variety of infections. Although they are effective, limitations include the need to administer four times a day and the intolerable adverse gastrointestinal effects. Four of the more extensively studied agents, azithromycin, clarithromycin, dirithromycin, and roxithromycin, are currently being studied in patients. Based on the studies to date, the newer macrolides may offer several advantages over erythromycin, including: (1) greater antimicrobial activity against certain organisms; (2) longer elimination half-life, thus allowing less frequent administration; and (3) lower incidence of adverse gastrointestinal effects. CONCLUSIONS: The new macrolide antibiotics appear to offer an improvement over erythromycin. Definitive conclusions about the role of these drugs should await completion of ongoing clinical studies.

Anti-Bacterial Agents↗
PubMedDate not supplied

Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin.

OBJECTIVE: To describe two cases of rhabdomyolysis in patients taking lovastatin that were precipitated by the use of the newer macrolide antibiotics clarithromycin and azithromycin. CASE SUMMARIES: In each case, the patients were treated over 5 years with lovastatin and developed rhabdomyolysis that coincided with the completion of a prescribed regimen of a newer macrolide antibiotic. Following intravenous hydration and administration of bicarbonate, the patients' condition resolved without permanent' sequelae. DISCUSSION: Rhabdomyolysis is a clinical syndrome resulting from the destruction of skeletal muscle that may progress to renal failure Several drugs have been associated with rhabdomyolysis, including lovastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor. Erythromycin is a macrolide antibiotic that may increase the risk of lovastatin-induced rhabdomyolysis. To our knowledge, these cases are the first published reports of lovastatin-induced rhabdomyolysis associated with azithromycin and clarithromycin. CONCLUSIONS: The risk of drug-induced rhabdomyolysis due to the potential interaction between lovastatin and azithromycin or clarithromycin should be considered before the concomitant use of these agents.

Aged↗
PubMed1997

Toleration of intravenous azithromycin.

OBJECTIVE: To study the toleration of various infusate concentrations of single intravenous doses of azithromycin. DESIGN: Randomized, double-blind, two-treatment, two-period, crossover. SETTING: Clinical pharmacology unit. PARTICIPANTS: Twenty-four healthy men aged 19-41 years. STUDY DESIGN: All subjects were initially randomized to receive single 1-hour intravenous infusions of azithromycin 1 g at infusate concentrations of 1, 2, or 5 mg/mL (n = 6 each) compared with placebo (n = 6). Subjects who were randomized to receive 1 mg/mL concentrations were subsequently administered 5 mg/mL concentrations at least 2 weeks later, those given 2 mg/mL were crossed over to 4 mg/mL, and those in the 5-mg/mL group were crossed over to 1 mg/mL concentrations. MAIN OUTCOME MEASURES: Subjects recorded intravenous infusion toleration using visual analog scales ranging from 0 (no signs or symptoms) to 10 (poor toleration) for erythema, pain, swelling, and tenderness. Vascular Doppler recordings were obtained during and after infusion cephalad to the infusion site. RESULTS: Infusion site reactions increased in incidence and severity with infusion concentrations of 4 and 5 mg/mL; the most frequent reactions were tenderness and erythema. There were no apparent trends in Doppler readings. CONCLUSIONS: Single doses of azithromycin 1 g at infusate concentrations up to 2 mg/mL were well tolerated when administered over 1 hour to healthy men.

Adult↗
PubMed1996

Influence of subinhibitory concentrations of ceftazidime, ciprofloxacin and azithromycin on the morphology and adherence of P-fimbriated escherichia coli.

The influence of subinhibitory concentrations (1/2, 1/4, 1/8, 1/16 and 1/32 x MIC) of ceftazidime, ciprofloxacin and azithromycin on the morphology and adherence of 29 wild-type P-fimbriated strains of Escherichia coli was studied. Bacterial adherence to the Buffalo green monkey (BGM) cell line was tested before and after treatment with antibiotics and detected by means of an immunofluorescence staining. Significant dose dependent reduction of bacterial adherence was observed, which correlated with the alterations in bacterial cell morphology. After exposure of strains to sub-MICs of antibiotics, normal shapes, spherical forms and filaments were noted. The greatest filamentation and the greatest loss of adherence ability occurred at 1/2 x MIC of ceftazidime. Treatment with sub-MICs of ciprofloxacin resulted in shorter filaments, while filamentation did not occur after bacterial exposure to sub-MICs of azithromycin. Azithromycin was least damaging to the adherence ability of E. coli and at a concentration of 1/2 x MIC caused globoid cell formation.

Animals↗