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PubMed1989

In vitro and in vivo uptake of azithromycin (CP-62,993) by phagocytic cells: possible mechanism of delivery and release at sites of infection.

Azithromycin, a novel azalide antibiotic, concentrated in human and mouse polymorphonuclear leukocytes (PMNs), murine peritoneal macrophages, and mouse and rat alveolar macrophages, attaining intracellular concentrations up to 226 times the external concentration in vitro. In murine peritoneal macrophages, azithromycin achieved concentration gradients (internal to external) up to 26 times higher than erythromycin. The cellular uptake of azithromycin was dependent on temperature, viability, and pH and was decreased by 2,4-dinitrophenol. Azithromycin did not decrease phagocyte-mediated bactericidal activity or affect PMN or macrophage oxidative burst activity (H2O2 release or Nitro Blue Tetrazolium reduction, respectively). Azithromycin remained in cells for several hours, even after extracellular drug was removed. However, its release was significantly enhanced by phagocytosis of Staphylococcus aureus (82 versus 23% by 1.5 h). In vivo, 0.05 micrograms of azithromycin was found in peritoneal fluids of mice 20 h after oral treatment with a dose of 50 mg/kg. Following caseinate-induced PMN infiltration, there was a sixfold increase in peritoneal cavity azithromycin to 0.32 micrograms, most of which was intracellular. Therefore, the uptake, transport, and later release of azithromycin by these cells demonstrate that phagocytes may deliver active drug to sites of infection.

Animals↗
PubMed1992

Double-blind randomized study comparing the efficacies and safeties of a short (3-day) course of azithromycin and a 5-day course of amoxicillin in patients with acute exacerbations of chronic bronchitis.

The efficacies and safeties of a three-dose regimen of azithromycin (500 mg once daily for 3 days) and a 15-dose regimen of amoxicillin (500 mg three times daily for 5 days) were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. A total of 92% of patients suffered a type 1 exacerbation. Treatment success, defined as cure or major improvement, was achieved in all patients in the azithromycin group by day 5, compared with 23 (92%) of 25 patients in the amoxicillin group. On day 12, these data were 24 of 25 (96%) in the azithromycin group and 20 of 25 (80%) in the amoxicillin group (results were not significantly different). Several pathogens were isolated (MIC ranges [micrograms per milliliter] in parentheses): Haemophilus influenzae or Haemophilus parainfluenzae was isolated 23 times (azithromycin, less than or equal to 0.06 to 32; amoxicillin, 0.12 to 2); Streptococcus pneumoniae was isolated from 11 patients (azithromcyin, less than or equal to 0.06 greater than 256; amoxicillin, less than or equal to 0.06 to 0.25); Moraxella (Branhamella) catarrhalis was isolated from eight patients (azithromycin, less than or equal to 0.06; amoxicillin, less than or equal to 0.06 to 16); and other members of the family Enterobacteriaceae were isolated from eight patients. One patient treated with azithromycin had Legionella pneumophila pneumonia, and another in that group had a significant rise in titer of antibody against influenza A virus. One patient treated with amoxicillin also had a significant rise in titer of antibody against influenza A virus. Microbiological response rates were comparable. One patient who received azithromycin developed abnormal liver function. Two patients treated with amoxicillin developed abnormal liver functions, one developed exanthema, and one treatment was stopped because of nausea. It is concluded that a three-dose (3-day) regimen of azithromycin is as effective clinically and microbiologically as a 15-dose (5-day) regimen of amoxicillin in the treatment of acute exacerbations of chronic bronchitis.

Aged↗
PubMed1993

Uptake of azithromycin by human monocytes and enhanced intracellular antibacterial activity against Staphylococcus aureus.

The uptake of azithromycin by human monocytes and the intracellular antibacterial activity of azithromycin against Staphylococcus aureus were investigated. With an extracellular pH of 6.9, the maximum intracellular concentration of azithromycin in monocytes was about six times the extracellular concentration. The half-life for diffusion was 44 min. The results support the view that no active transport is involved in the intracellular accumulation of azithromycin. In cell-free medium, the maximum effect of azithromycin on S. aureus was bacteriostasis, which was achieved at a concentration of 5 mg/liter. In contrast, concentrations greater than 1.5 mg of azithromycin per liter were bactericidal for S. aureus ingested by monocytes. The difference in maximum growth inhibition on S. aureus for the two conditions was 0.1.68 h-1 (95% confidence interval, 0.128 to 0.208). The concentration of the drug that achieved 50% of the maximum effect was 0.434 mg/liter for both conditions. The enhancement of the effect on S. aureus ingested by monocytes suggests that the intracellular environment in human monocytes favors the antibacterial action of azithromycin. Enhancement of the antibacterial activity of azithromycin was not observed with granulocytes.

Azithromycin↗
PubMed1994

Efficacy of azithromycin as a causal prophylactic agent against murine malaria.

The efficacy of the newly marketed azalide azithromycin was compared with that of the clinical agent doxycycline in a murine model of sporozoite-induced malaria. Drug was administered once; Plasmodium yoelii sporozoites were administered 2 h later; survival at day 60 was determined. For parenterally administered drug, 160 mg of azithromycin or doxycycline per kg of body weight was 100% effective; 40 mg of azithromycin per kg was 80% effective, but 40 mg of doxycycline per kg was 40% effective. Orally administered azithromycin was somewhat less effective than parenterally administered drug, consistent with the 37% clinical oral bioavailability of this agent. For orally administered azithromycin, 160 mg/kg was 100% effective and 40 mg/kg was 40% effective. The efficacy of azithromycin in comparison with that of doxycycline and the known prolonged levels of azithromycin in the livers of humans suggest that azithromycin has potential as a clinical causal prophylactic agent for malaria.

Animals↗
PubMed2002

Experimental acute otitis media due to nontypeable Haemophilus influenzae: comparison of high and low azithromycin doses with placebo.

Treatment of acute otitis media (AOM) with azithromycin 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 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 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 concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin 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 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 at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin (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.

Acute Disease↗
PubMed2002

Assessment of azithromycin in combination with other antimalarial drugs against Plasmodium falciparum in vitro.

Initial field malaria prophylaxis trials with azithromycin revealed insufficient efficacy against falciparum malaria to develop azithromycin 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 was tested in combination with chloroquine against 10 representative Plasmodium falciparum isolates. Azithromycin 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 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 combination should be evaluated for malaria prophylaxis and that a quinine-azithromycin combination should be evaluated for malaria treatment in areas of drug resistance.

Animals↗
PubMed2005

Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane.

The aim of the present study was to elucidate the effect of the macrolide antibiotic azithromycin on Pseudomonas aeruginosa. We studied the susceptibility to azithromycin in P. aeruginosa PAO1 using a killing assay. PAO1 cells at the exponential growth phase were resistant to azithromycin. In contrast, PAO1 cells at the stationary growth phase were sensitive to azithromycin. The divalent cations Mg2+ and Ca2+ inhibited this activity, suggesting that the action of azithromycin is mediated by interaction with the outer membranes of the cells, since the divalent cations exist between adjacent lipopolysaccharides (LPSs) and stabilize the outer membrane. The divalent cation chelator EDTA behaved in a manner resembling that of azithromycin; EDTA killed more PAO1 in the stationary growth phase than in the exponential growth phase. A 1-N-phenylnaphthylamine assay showed that azithromycin interacted with the outer membrane of P. aeruginosa PAO1 and increased its permeability while Mg2+ and Ca2+ antagonized this action. Our results indicate that azithromycin directly interacts with the outer membrane of P. aeruginosa PAO1 by displacement of divalent cations from their binding sites on LPS. This action explains, at least in part, the effectiveness of sub-MICs of macrolide antibiotics in pseudomonal chronic airway infection.

Anti-Bacterial Agents↗
PubMed2006

Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome.

RATIONALE: Bronchiolitis obliterans syndrome (BOS) remains the leading cause of death after lung transplantation. Treatment is difficult, although azithromycin has recently been shown to improve FEV(1). The exact mechanism of action is unclear. HYPOTHESES: (1) Azithromycin reduces airway neutrophilia and interleukin (IL)-8 and (2) airway neutrophilia predicts the improvement in FEV(1). METHODS: Fourteen lung transplant patients with BOS (between BOS 0-p and BOS 3) were treated with azithromycin, in addition to their current immunosuppressive treatment. Before and 3 mo after azithromycin was introduced, bronchoscopy with bronchoalveolar lavage (BAL) was performed for cell differentiation and to measure IL-8 and IL-17 mRNA ratios. RESULTS: The FEV(1) increased from 2.36 (+/- 0.82 L) to 2.67 L (+/- 0.85 L; p = 0.007), whereas the percentage of BAL neutrophilia decreased from 35.1 (+/- 35.7%) to 5.7% (+/- 6.5%; p = 0.0024). There were six responders to azithromycin (with an FEV(1) increase of > 10%) and eight nonresponders. Using categorical univariate linear regression analysis, the main significant differences in characteristics between responders and nonresponders were the initial BAL neutrophilia (p < 0.0001), IL-8 mRNA ratio (p = 0.0009), and the postoperative day at which azithromycin was started (p = 0.036). There was a significant correlation between the initial percentage of BAL neutrophilia and the changes in FEV(1) after 3 mo (r = 0.79, p = 0.0019). CONCLUSION: Azithromycin significantly reduces airway neutrophilia and IL-8 mRNA in patients with BOS. Responders have a significantly higher BAL neutrophilia and IL-8 compared with nonresponders and had commenced treatment earlier after transplantation. BAL neutrophilia can be used as a predictor for the FEV(1) response to azithromycin.

Adult↗
PubMed2005

Effects of azithromycin on clinical isolates of Pseudomonas aeruginosa from cystic fibrosis patients.

There is considerable interest in the use of azithromycin for the treatment of lung disease in patients with cystic fibrosis (CF). Although its mechanism of action as an inhibitor of bacterial protein synthesis has been well-established, it is less clear how azithromycin ameliorates the lung disease associated with Pseudomonas aeruginosa, which is considered to be resistant to the drug. We tested the effects of azithromycin on clinical isolates (CIs) from CF patients and compared them with laboratory reference strains to establish how this drug might interfere with the production of bacterial virulence factors that are relevant to the pathogenesis of airway disease in CF patients. Azithromycin inhibited P aeruginosa PAO1 protein synthesis by 80%, inhibiting bacterial growth and the expression of immunostimulatory exoproducts such as pyocyanin, as well as the gene products necessary for biofilm formation. In contrast, the effects of azithromycin on CIs of P aeruginosa were much more variable, due in large part to their slow growth and limited exoproduct expression. Culture supernatants for two of three clinical strains induced appreciable CXCL8 expression from cultured epithelial cells. Azithromycin treatment of the organisms inhibited 65 to 70% of this induction; azithromycin had no direct effect on the ability of either normal cells or CF epithelial cells to produce CXCL8. Azithromycin does decrease the P aeruginosa synthesis of immunostimulatory exoproducts and is likely to be most effective against planktonic, actively growing bacteria. This effect is less predictable against CIs than the prototypic strain PAO1.

Anti-Bacterial Agents↗
PubMed2004

Determination of the lack of a drug interaction between azithromycin and warfarin.

STUDY OBJECTIVE: To determine the effect on the international normalized ratio (INR) of adding azithromycin to patients receiving stable dosages of warfarin. DESIGN: Retrospective chart review. SETTING: Outpatient clinic. PATIENTS: Ambulatory patients receiving warfarin and azithromycin concurrently who had a documented therapeutic INR value before the start of azithromycin therapy (pre-INR) and a documented INR value within 30 days after the start of azithromycin therapy (post-INR). MEASUREMENTS AND MAIN RESULTS: Patients given felodipine during long-term warfarin therapy formed a comparative control group. Patient demographics were similar in both treatment groups. Mean age of the azithromycin group (17 patients) was 59 +/- 13 years and of the control group (20 patients) 65 +/- 12 years. All 17 patients in the azithromycin group and 16 of the controls were women. Mean change from pre-INR to post-INR in the azithromycin and control groups, respectively, was 0.14 +/- 0.64 (pre-INR 2.46, post-INR 2.61) and 0.19 +/- 0.54 (pre-INR 2.46, post-INR 2.66) (p = 0.74). A post hoc power analysis based on a pooled standard deviation of 0.60 revealed that the study had 68% power to detect a 0.5 change in the INR value. CONCLUSION: No interaction between azithromycin and warfarin was observed in ambulatory patients with therapeutic baseline INR values.

Aged↗
PubMed1996

Azithromycin. A review of its pharmacological properties and use as 3-day therapy in respiratory tract infections.

The azalide antibacterial agent azithromycin is a semisynthetic acid-stable erythromycin derivative with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. The drug is noted for its activity against some Gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae. Azithromycin has similar activity to other macrolides against Streptococcus pneumoniae and Moraxella catarrhalis, and is active against atypical pathogens such as Legionella pneumophila, Chlamydia pneumoniae and Mycoplasma pneumoniae. Once-daily administration of azithromycin is made possible by the long elimination half-life of the drug from tissue. Azithromycin is rapidly and highly concentrated in a number of cell types after absorption, including leucocytes, monocytes and macrophages. It undergoes extensive distribution into tissue, from where it is subsequently eliminated slowly. A 3-day oral regimen of once-daily azithromycin has been shown to be as effective as 5- to 10-day courses of other more frequently administered antibacterial agents [such as erythromycin, amoxicillin-clavulanic acid and phenoxymethylpenicillin (penicillin V)] in patients with acute exacerbations of chronic bronchitis, pneumonia, sinusitis, pharyngitis, tonsillitis and otitis media. Adverse effects of azithromycin are mainly gastrointestinal in nature and occur less frequently than with erythromycin. Azithromycin is likely to prove most useful as a 3-day regimen in the empirical management of respiratory tract infections in the community. Its ease of administration and 3-day duration of therapy, together with its good gastrointestinal tolerability, should optimise patient compliance (the highest level of which is achieved with once-daily regimens). Azithromycin is also likely to be useful in the hospital setting, particularly for outpatients and for those unable to tolerate erythromycin.

Anti-Bacterial Agents↗
PubMed2005

Once-daily azithromycin for 3 days compared with clarithromycin for 10 days for acute exacerbation of chronic bronchitis: a multicenter, double-blind, randomized study.

STUDY OBJECTIVES: To compare the efficacy and safety of oral azithromycin 500 mg once daily for 3 days with those of oral clarithromycin 500 mg twice daily for 10 days. DESIGN: Randomized, double-blind, double-dummy, multicenter study. SETTING: Seventy-six study centers in eight countries (Argentina, Brazil, Canada, Chile, Costa Rica, India, South Africa, and USA). PATIENTS: Three hundred and twenty-two adult outpatients with acute exacerbation of chronic bronchitis (AECB) as documented by increased cough or sputum production, worsening dyspnea, and purulent sputum production. INTERVENTIONS: Randomization 1 : 1 to azithromycin 500 mg once daily for 3 days or clarithromycin 500 mg twice daily for 10 days. RESULTS: The primary efficacy endpoint was clinical response at day 21-24, or test of cure (TOC) visit in the modified intent-to-treat (MITT) analysis (n = 318 patients). The TOC clinical cure rates in the MITT population were equivalent in the two treatment groups at 85% with azithromycin and 82% with clarithromycin (95% CI -5.9%, 12.0%). Clinical success rates on day 10-12 were also equivalent at 93% with azithromycin and 94% with clarithromycin (95% CI -7.9%, 4.4%). Clinical cure rates at TOC by pathogen were equivalent for the two treatment groups for Haemophilus influenzae (azithromycin, 85.7%; clarithromycin, 87.5%), Moraxella catarrhalis (91.7% and 80.0%, respectively) and Streptococcus pneumoniae (90.6% and 77.8%, respectively). Bacteriologic success rates were also equivalent between the azithromycin and clarithromycin treatment groups at TOC for S. pneumoniae (90.6% and 85.2%, respectively), H. influenzae (71.4% and 81.3%, respectively) and M. catarrhalis (100% and 86.7%, respectively). The overall incidence of treatment-related adverse events was similar in the azithromycin and clarithromycin groups (20.9% and 26.8%, respectively), with the most common being abdominal pain (6.3% and 6.1%, respectively), diarrhea (4.4% and 5.5%, respectively), and nausea (4.4% and 3.7%, respectively). CONCLUSIONS: Three-day treatment with azithromycin 500 mg once daily is equivalent to a 10-day treatment with clarithromycin 500 mg twice daily in adult patients with AECB.

Acute Disease↗
PubMed2000

Operational comparison of single-dose azithromycin and topical tetracycline for trachoma.

PURPOSE: World Health Organization guidelines for antibiotic treatment of trachoma currently include a 6-week course of tetracycline eye ointment twice daily or a single dose of oral azithromycin. Previous trials have shown similar efficacy of these two alternatives when administration of the ointment was carefully supervised. It is believed, however, that azithromycin may be a more effective treatment in practice, and the purpose of this study was to test that hypothesis. METHODS: A masked randomized controlled trial was conducted to compare azithromycin and tetracycline under practical operational conditions-i.e., without supervision of the administration of the ointment. Three hundred fourteen children aged 6 months to 10 years with clinically active trachoma were recruited and individually randomized to receive one of the two treatments. Follow-up visits were conducted at 10 weeks and 6 months. The outcome was resolution of disease (clinical "cure"). RESULTS: Children allocated to azithromycin were significantly more likely to have resolved disease than those allocated to tetracycline, both at 10 weeks (68% versus 51%; cure rate ratio, 1.31; 95% confidence interval [CI], 1.08-1.59; P = 0.007) and at 6 months (88% versus 73%; cure rate ratio, 1.19; 95% CI, 1.06-1.34; P = 0.004). Azithromycin was particularly effective for intense inflammation (P = 0.023, Fisher's exact test). CONCLUSIONS: Single-dose oral azithromycin was a more effective treatment for active trachoma than tetracycline ointment as applied by caregivers. The high cure rate achieved with tetracycline in this study in the absence of supervision and the significantly higher costs of azithromycin, suggest that in the absence of donation programs, switching routine treatment from tetracycline to azithromycin would not be a good use of resources.

Administration, Topical↗
PubMed2006

[Levofloxacin-azithromycin combined triple therapy for Helicobacter pylori eradication].

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of levofloxacin- azithromycin combined triple therapy for H. pylori eradication. METHODS: 1) First-line eradication: A total of 78 H. pylori-positive patients were enrolled. Seventeen military men in Armed Forces Capital Hospital were treated with 7 days of levofloxacin-azithromycin combined triple therapy (omeprazole 20 mg bid, levofloxacin 500 mg od, and azithromycin 500 mg od), and 61 patients in Kangbuk Samsung Hospital were treated with standard PPI-based triple therapy (omeprazole 20 mg bid, amoxicillin 1.0 g bid, and clarithromycin 500 mg bid) for 7 days. 2) Second-line eradication: A consecutive series of 59 patients who failed H. pylori eradication with standard PPI-based triple therapy in Kangbuk Samsung Hospital were randomized to two groups. Thirty patients were retreated with 7 days of bismuth-based quadruple therapy (omeprazole 20 mg bid, bismuth 120 mg qid, metronidazole 500 mg tid, and tetracycline 500 mg qid), and remaining 29 patients were retreated with levofloxacin-azithromycin combined triple therapy. Patient's compliance and tolerability were evaluated at the end of treatment. The status of H. pylori infection was assessed 8 weeks later then. The successful eradication of H. pylori was defined as negative results from histology and CLO test, or 13C-urea breath test. RESULTS: First-line eradication rate of levofloxacin-azithromycin triple therapy was lower than that of standard PPI-based triple therapy, but there was no statistically significant difference (70.6% vs. 80.3%, p=0.390). Second-line eradication rate of levofloxacin-azithromycin combined triple therapy was significantly lower than that of bismuth-based quadruple therapy (ITT/PP 65.5%/73.1% vs. 90%/90%, p<0.0001). The compliances of all patients were more than 85%. Two of patients with levofloxacin-azithromycin combined triple therapy complained self-limiting side effects (mild dizziness; mild insomnia with general weakness). CONCLUSIONS: Levofloxacin-azithromycin combined triple therapy should not be recommended as the first-line or second-line H. pylori eradication regimen in Korea.

Adult↗
PubMed1994

Distribution of orally administered azithromycin in various blood compartments.

The concentrations of azithromycin in whole blood, plasma, erythrocytes and polymorphonuclear leucocytes (PMNLs) were measured in 6 healthy volunteers following the last administration of a three-day regimen of 500 mg once daily. Marked enrichment of azithromycin was observed in PMNLs; the drug concentration amounted to 119 +/- 31 (SD) mg/l 6 hours after the administration. Twelve days thereafter 42 +/- 10 mg/l azithromycin was still measured in the PMNLs, although the drug was no longer demonstrable in plasma (< 0.02 mg/l). The elimination of azithromycin from the PMNLs (half-life 210 +/- 69 hours) was clearly slower than the elimination from plasma (half-life 93 +/- 70 hours). The maximal concentrations of azithromycin in plasma (0.64 +/- 0.27 mg/l) and erythrocytes (0.17 +/- 0.06 mg/l) were much lower and occurred earlier (tmax = 3 hours) than those observed in the PMNLs. The enrichment factor for azithromycin in PMNLs relative to plasma came to 177 +/- 92 at 3 hours or 1814 +/- 706 at 120 hours after the last administration. In a parallel in vitro study, the effect of accumulation of azithromycin in PMNLs on the intracellular survival of ingested staphylococci was investigated. At subinhibitory extracellular concentrations of azithromycin as low as 0.03 mg/l (MIC = 1 mg/l), a significant reduction in bacterial viability was observed, thus demonstrating antibacterial activity of the intracellularly enriched antibiotic.

Administration, Oral↗
PubMed1995

[Azithromycin, pharmacodynamic evaluation in animal models].

Several experimental models have been used in order to evaluate the in vivo efficacy of azithromycin against numerous human pathogenic bacteria and parasites, including comparison between azithromycin and other antibiotics belonging or not to the macrolide family. Using the experimental models, three major objectives can be distinguished: the comparative studies of the efficacy dose 50 (ED50) of azithromycin compared to other orally given antibiotics, the azithromycin efficacy in animal infected with intracellular multiplying micro-organisms, and the demonstration of the specific azithromycin accumulation in tissues in direct relationship with the local recruitment of phagocytic cells at the infectious foci. The ED50 of azithromycin has been compared with those of erythromycin or cefaclor in varying acute murine infections. Evidence was given of a similar efficacy for the three tested antibiotics. Nevertheless a marked advantage for azithromycin was observed in experimental local infections and with infections due to Gram-negative bacteria (Haemophilus influenzae, Branhamella catarrhalis). The second objective was to confirm in vivo the preferential efficacy of azithromycin in models using intracellular multiplying microorganisms, due to its great capacity to accumulate inside of professional phagocytes. Several models have been used, such as those performed with Listeria monocytogenes, Legionella pneumophila, S. typhimurium, Brucella melitensis, M. avium and C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Azithromycin monotherapy for patients hospitalized with community-acquired pneumonia: a 31/2-year experience from a veterans affairs hospital.

BACKGROUND: Current American Thoracic Society (ATS) community-acquired pneumonia treatment guidelines recommend azithromycin monotherapy for a limited subset of hospitalized patients. We evaluated the effectiveness of azithromycin monotherapy in a more generalized population of patients hospitalized with mild-to-moderate community-acquired pneumonia. METHODS: We reviewed medical records from a Veterans Affairs facility for patients admitted with community-acquired pneumonia between December 1, 1997, and June 30, 2001, comparing those receiving azithromycin monotherapy, other ATS-recommended antibiotics, and non-ATS-recommended antibiotics. We excluded patients with immunosuppression, metastatic cancer, or hospital-acquired pneumonia. Outcome measures included times to stability, meeting criteria for change to oral therapy, and eligibility for discharge; length of stay; intensive care unit transfer; and mortality. Outcomes were adjusted for pneumonia severity, skilled nursing facility status, and processes of care. RESULTS: A total of 442 patients were eligible for the study (221 in the azithromycin monotherapy group, 129 in the ATS group, and 92 in the non-ATS group). Times to clinical stability and to fulfilling early switch criteria were not statistically significantly different among the 3 groups. Mean time to fulfilling early discharge criteria was 2.48 days for patients receiving azithromycin monotherapy vs 2.84 days for those receiving ATS antibiotics (P =.008) and 2.58 days for those receiving non-ATS antibiotics (P =.64). Overall mean length of stay was shorter in the azithromycin monotherapy group (4.35 days) vs the ATS (5.73 days) (P =.002) and non-ATS (6.21 days) (P<.001) groups. Mortality, intensive care unit transfer, and readmission rates were similar across the groups. CONCLUSION: Azithromycin monotherapy is equally as efficacious as other ATS-recommended regimens for treating hospitalized patients with mild-to-moderate community-acquired pneumonia.

Aged↗
PubMed2006

Single-dose azithromycin prevents trichiasis recurrence following surgery: randomized trial in Ethiopia.

BACKGROUND: Trichiasis recurrence following surgery is a serious problem for trachoma programs. OBJECTIVE: To determine if postoperative treatment with azithromycin compared with topical tetracycline reduces recurrence up to 1 year, and if azithromycin treatment of household members provides additional benefit compared with treating only the surgical patient. DESIGN: A randomized, single-masked, clinical trial was conducted in Ethiopia. A total of 1452 patients with trichiasis were randomized 1:1:1 to the following 3 arms: single-dose (1 g) oral azithromycin alone, single-dose azithromycin for household members (20 mg/kg up to 1 g) plus the patient, or topical tetracycline (twice per day for 6 weeks). MAIN OUTCOME MEASURES: Trichiasis recurrence within 1 year following surgery. RESULTS: The combined azithromycin groups had significantly fewer recurrences, 6.9 of 100 person-years overall, compared with topical tetracycline, 10.3 of 100 person-years (P = .047). There was no additional reduction in the arm that also treated household members, 8.1 of 100 person-years, compared with treating the surgical patients alone, 5.8 of 100 person-years (P = .19). CONCLUSIONS: In trachoma-endemic areas, a single dose of azithromycin reduced postoperative trichiasis recurrence rates by one third compared with topical tetracycline. Application to Clinical Practice In countries where azithromycin is part of the Trachoma Control Program, patients with trachomatous trichiasis should be treated postoperatively to prevent recurrence.

Administration, Oral↗