zithromax and Skin-Diseases--Infectious

Azithromycin is an azalide antimicrobial agent. Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit. Although slightly less potent than erythromycin against gram-positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram-negative bacilli, including Haemophilus influenzae. Absorption is approximately 37% after a 500-mg oral dose. The large volume of distribution (23 L/kg) and low peak serum level (0.4 micrograms/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation. Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination. Drug elimination is biphasic, with a terminal half-life of up to 5 days. Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases. Many used a 5-day course of 250 mg once daily, supplemented with a 250-mg dose on the first day of therapy. Selected trials in sexually transmitted diseases examined single 1-g doses. Promising results also were obtained with oral daily doses of 500 mg in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis. Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported. Gastrointestinal tolerance is better than that of erythromycin. Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.

Topics: Azithromycin; Drug Interactions; Erythromycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Respiratory Tract Infections; Sexually Transmitted Diseases; Skin Diseases, Infectious

Azithromycin (Zithromax) and clarithromycin (Biaxin Filmtabs) are new macrolide antibiotics with several advantages over erythromycin. Azithromycin has an expanded spectrum against gram-negative bacilli. Clarithromycin is more active than erythromycin against gram-positive cocci; combination with its 14-hydroxy metabolite enhances its antimicrobial activity. These new agents penetrate well into tissues and concentrate in macrophages and polymorphonuclear leukocytes. They offer improved bioavailability and an extended half-life. The high tissue-to-serum level and extended elimination half-life of azithromycin allow for once-daily dosing and short-course therapy. Clarithromycin and 14-hydroxyclarithromycin maintain high serum levels and tissue-to-serum concentrations. Both of these new agents have been effective in streptococcal pharyngitis, acute sinusitis, acute lower respiratory tract infections, skin and soft-tissue infections, and sexually transmitted diseases. A single dose of azithromycin is effective for genital chlamydial infections. Adverse reactions to these agents have usually been mild and have not included serious organ toxicity. In clinical trials, the rate of premature discontinuation of therapy has been less than observed with erythromycin. Azithromycin and clarithromycin should be used according to the current guidelines of the Food and Drug Administration; their future role will be determined by ongoing laboratory and clinical evaluations.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Clinical Protocols; Clinical Trials as Topic; Drug Resistance, Microbial; Erythromycin; Humans; Respiratory Tract Infections; Sexually Transmitted Diseases; Skin Diseases, Infectious; Therapeutic Equivalency

Azithromycin and clarithromycin are erythromycin analogues that have recently been approved by the FDA. These drugs inhibit protein synthesis in susceptible organisms by binding to the 50S ribosomal subunit. Alteration in this binding site confers simultaneous resistance to all macrolide antibiotics. Clarithromycin is several-fold more active in vitro than erythromycin against gram-positive organisms, while azithromycin is 2- to 4-fold less potent. Azithromycin has excellent in vitro activity against H influenzae (MIC90 0.5 microgram/ml), whereas clarithromycin, although less active against H influenzae (MIC90 4.0 micrograms/ml) by standard in vitro testing, is metabolized into an active compound with twice the in vitro activity of the parent drug. Both azithromycin and clarithromycin are equivalent to standard oral therapies against respiratory tract and soft tissue infections caused by susceptible organisms, including S aureus, S pneumoniae, S pyogenes, H influenzae, and M catarrhalis. Clarithromycin is more active in vitro against the atypical respiratory pathogens (e.g., Legionella), although insufficient in vivo data are available to demonstrate a clinical difference between azithromycin and clarithromycin. Superior pharmacodynamic properties separate the new macrolides from the prototype, erythromycin. Azithromycin has a large volume of distribution, and, although serum concentrations remain low, it concentrates readily within tissues, demonstrating a tissue half-life of approximately three days. These properties allow novel dosing schemes for azithromycin, because a five-day course will provide therapeutic tissue concentrations for at least ten days. Clarithromycin has a longer serum half-life and better tissue penetration than erythromycin, allowing twice-a-day dosing for most common infections. Azithromycin pharmacokinetics permit a five-day, single daily dose regimen for respiratory tract and soft tissue infections, and a single 1 g dose of azithromycin effectively treats C trachomatis genital infections; these more convenient dosing schedules improve patient compliance. Azithromycin and clarithromycin also are active against some unexpected pathogens (e.g., B burgdorferi, T gondii, M avium complex, and M leprae). Clarithromycin, thus far, appears the most active against atypical mycobacteria, giving new hope to what has become a difficult group of infections to treat. Gastrointestinal distress, a well known and major obstacle to patient complia

Topics: Azithromycin; Bacterial Infections; Clarithromycin; Erythromycin; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Mycobacterium Infections, Nontuberculous; Respiratory Tract Infections; Sexually Transmitted Diseases; Skin Diseases, Infectious

Clarithromycin and azithromycin are new semisynthetic macrolide antibiotics structurally related to erythromycin. They are well absorbed and widely distributed, with excellent cellular and tissue penetration. Both have a broader spectrum of activity and fewer gastrointestinal side effects than erythromycin. Currently, clarithromycin and azithromycin are approved by the U.S. Food and Drug Administration for respiratory tract infections and skin infections, but they may also have use in mycobacterial and Toxoplasma infections in patients with acquired immunodeficiency syndrome.

Topics: Azithromycin; Clarithromycin; Erythromycin; Humans; Respiratory Tract Infections; Skin Diseases, Infectious

Tolerability of azithromycin oral suspension, 10 mg/kg once daily for 3 days, was assessed in paediatric patients (< or = 18 years) with respiratory or skin and soft-tissue infections. Of 2425 patients evaluated, 1213 received azithromycin and 1212 received standard regimens of amoxycillin/clavulanic acid, cefaclor, cefixime, ceftriaxone, clarithromycin, erythromycin, or penicillin V. The incidence of treatment-related adverse events was significantly lower in patients receiving azithromycin than comparators (7.9 vs. 11.5%, P=0.003), while discontinuation rates were similar (1.0 and 1.1%, respectively). Significantly fewer gastrointestinal events were recorded for azithromycin than comparators (6.5 vs. 9.9%, P=0.002), and their duration was significantly shorter (mean 2.3 vs. 5.0 days, P=0.0001). Azithromycin paediatric oral suspension is well tolerated and associated with significantly fewer adverse events than comparators.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Community-Acquired Infections; Female; Humans; Infant; Infant, Newborn; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Skin Diseases, Infectious; Soft Tissue Infections

The efficacy of a newly developed macrolide antibiotic, azithromycin, for infections in the field of surgery, was investigated clinically by means of collaborative studies conducted in 17 major institutes and their affiliated hospitals throughout Japan. The following results were obtained. Clinical assessment: Azithromycin was administered at a dose of 250 mg or 500 mg once a day for 3 days. Clinical efficacy was evaluated in 170 patients. These subjects consisted of 81 with superficial purulent diseases, 12 with mastitis, 25 with periproctal abscess, 42 with superficial secondary infection due to trauma, burn and operative wound, 5 with cholecystitis or cholangitis, and 5 with other infections. The clinical efficacy rate was 96.3% (78/81) for superficial purulent diseases, 83.3% (10/12) for mastitis, 84.0%(21/25) for periproctal abscess, and 76.2%(32/42) for superficial secondary infection due to trauma, burn and operative wound. The overall clinical efficacy rate was 88.8%(151/170) respectively. The bacteriological eradication rate was 87.9%(116/132) for gram-positive bacteria, 85.0%(34/40) for gram-negative bacteria, and 100%(63/63) for anaerobic strains of casual bacteria, which were isolated from 140 patients. The overall bacteriological eradication rate was 90.6%(213/235) respectively. Adverse effects were observed in 6 of 170 patients in whom they were evaluated. They consisted of gastrointestinal symptoms in 5 patients and exanthema in 1. Abnormal changes in clinical laboratory test values were observed in 5 patients, and consisted of eosinophilia in 1, elevations of S-GOT and S-GPT in 1, elevations of S-GOT, S-GPT and gamma-GTP in 1, elevation of S-GPT in 1, and elevations of AL-P and gamma-GTP in 1. These results suggest that azithromycin is very useful for surgical infections in the field of surgery.

Topics: Abscess; Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Mastitis; Middle Aged; Rectal Diseases; Skin Diseases, Infectious; Suppuration; Surgical Wound Infection; Treatment Outcome

An open, multicentre study was carried out in 200 paediatric patients between 6 months and 12 years of age with skin and/or soft tissue infections (mild-to-moderate dermatological conditions and abscesses) to compare the efficacy and safety of azithromycin and cefaclor oral suspensions. Patients were randomly assigned to receive either azithromycin (10 mg/kg once daily for 3 days) or cefaclor (20 mg/kg/day in three divided doses for 10 days). The clinical efficacy of both treatments was comparable: 92/98 (94%) of the evaluable azithromycin patients were cured or improved as were 93/98 (95%) of those treated with cefaclor. Before treatment, 74 pathogens were isolated from 60 of the azithromycin- and 80 pathogens from 66 of the cefaclor-treated patients. In the azithromycin group, 70/74 (95%) pathogens were eradicated, as were 79/80 (99%) pathogens in the cefaclor group. All 200 patients were evaluable for safety analyses. Both drugs were well tolerated, with a low incidence of side-effects: 3/100 (3%) in the azithromycin group and 2/100 (2%) in the cefaclor group. No patient in either treatment group withdrew from the study because of adverse events. In conclusion, azithromycin is as effective and as well tolerated as cefaclor in the treatment of children with skin and/or soft tissue infections.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Cefaclor; Cephalosporins; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Male; Skin Diseases, Infectious; Soft Tissue Infections

This randomized, third-party-blinded study compared short-course therapy of once-daily azithromycin (500 mg on day 1, followed by 250 mg/day on days 2-5) with cephalexin (500 mg twice daily for 10 days) in the treatment of patients with skin and skin structure infections. At 25 centers, a total of 361 patients were entered into the study and 148 were evaluable for efficacy. The main causative pathogens, Staphylococcus aureus and Streptococcus pyogenes, were responsible for approximately two thirds of the infections in the two treatment groups. Clinical cure and improvement rates for the two treatments were comparable; 99% with azithromycin and 96% with cephalexin. On completion of therapy, both treatments had eradicated approximately 98% of pathogens. In general, both agents were well-tolerated. The results of this study show that a 5-day course of once-daily treatment with azithromycin is as effective as a 10-day course of twice-daily treatment with cephalexin in the management of skin and skin structure infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Cephalexin; Drug Administration Schedule; Erythromycin; Humans; Middle Aged; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections

The toleration and safety profile of the azalide antibiotic, azithromycin, has been assessed in 3,995 patients aged 2-94 (mean, 36) years, comprising 1,644 females and 2,351 males. Patients with infections of the respiratory tract or skin/skin structure received 1.5 g azithromycin over 5 days; patients with urethritis/cervicitis caused by Chlamydia were treated with 1 g as a single dose. Assessments of side effects and laboratory safety test abnormalities were made pretreatment and approximately 7-14 and 30 days after the start of therapy. Twelve standard antibiotics have been used for comparison. Overall, side effects were recorded in 12.0% of patients, significantly less (p less than 0.05) than with comparative drugs (14.2%). The most common side effects were diarrhea (3.6%), abdominal pain (2.5%), and other gastrointestinal symptoms. Ninety-three percent of side effects were classed as mild or moderate, and only 0.7% of patients withdrew from treatment, significantly less (p less than 0.001) than with comparative agents (2.6%). The frequency of side effects was not affected by patient age. Azithromycin had no marked or consistent effect on laboratory safety parameters. Treatment-related laboratory abnormalities were rare, the most common being transient increases of ALT and AST in 1.7% and 1.5% of patients, respectively. Specific tests revealed no neurologic, audiometric, or ophthalmologic abnormalities, or evidence of phospholipidosis. There were no pharmacokinetic interactions observed with theophylline, warfarin, cimetidine, carbamazepine, or methylprednisolone, but coadministration with food altered the absorption of the drug. Coadministration with antacids decreased the peak serum concentration of azithromycin, but did not affect its overall absorption. Azithromycin was well tolerated in the presence of a wide variety of concurrent illnesses and medications.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Carbamazepine; Child; Child, Preschool; Cimetidine; Contraindications; Drug Evaluation; Drug Interactions; Eating; Erythromycin; Female; Humans; Male; Methylprednisolone; Middle Aged; Respiratory Tract Infections; Skin Diseases, Infectious; Theophylline; Urethritis; Uterine Cervicitis

In this double-blind, randomised trial conducted in 22 centres in the USA, azithromycin given over five days, as a once-a-day regimen, (500 mg on day 1, 250 mg on days 2-5) was compared with cephalexin (500 mg b.i.d.) given for ten days in the treatment of patients with skin and skin structure infections. A total of 366 patients entered the study and 179 of these were eligible for the efficacy analysis. The overall clinical response to azithromycin was 94.0%, compared with 95.8% for cephalexin. The clinical cure rates were 53.0% for azithromycin and 59.4% for cephalexin; the respective improvement rates were 41.0% and 36.5%. Distribution of response (cured, improved, failed) was similar in each group (p = 0.37). The bacteriological eradication rate for azithromycin-treated patients was 94.2% and for cephalexin-treated patients was 90.3% (p = 0.34). Clinical and bacteriological response was similar in each group for all primary diagnoses. The two antibiotics were well tolerated, the overall incidence of side effects being 13.7% with approximately 60% due to gastrointestinal disturbances. In all but one case (cephalexin) the severity of the reported side effects was mild or moderate. Six patients withdrew from the study due to treatment-related events; five had been treated with azithromycin and one with cephalexin. In summary, a five-day, once-daily regimen of azithromycin was as effective as a ten-day, twice-daily regimen of cephalexin in the treatment of patients with skin and skin structure infections.

Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Cellulitis; Cephalexin; Double-Blind Method; Drug Administration Schedule; Erythromycin; Female; Humans; Impetigo; Male; Middle Aged; Skin Diseases, Infectious; Wound Infection

Two open, randomized, single centre studies have investigated the efficacy and safety of azithromycin (CP-62,993) in the treatment of infections by azithromycin-sensitive pathogens: (A) acute bacterial infections of skin or soft tissue (compared with erythromycin; n = 82); and (B) urethritis and/or cervicitis caused by Neisseria gonorrhoeae and/or Chlamydia trachomatis (compared with doxycycline; n = 108). In study A, azithromycin was administered to 42 patients for five days at a dosage of 250 mg bd on day 1 and 250 mg once daily on days 2-5; erythromycin was given to 40 patients for seven days at a dosage of 500 mg every 6 h. In study B, azithromycin was administered either as a single 1 g dose or as a single 500 mg dose on day 1 and 250 mg once daily on days 2 and 3; doxycycline was given at a dose of 100 mg every 12 h for seven days. In study A, 68 patients were clinically assessed: clinical cure or improvement in patients receiving azithromycin or erythromycin was achieved in 86% and 82%, respectively. The principal causative pathogen was Staphylococcus aureus; there was eradication of 15/25 pathogens (60%) with azithromycin and 13/23 (57%) with erythromycin. In study B, 94 and 93 patients were clinically assessed at weeks 1 and 2, respectively: clinical cure was achieved with all treatment regimens at week 1; at week 2 there was reappearance of symptoms in one patient with a mixed infection who had received 3-day azithromycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Doxycycline; Erythromycin; Female; Gonorrhea; Humans; Male; Middle Aged; Neisseria gonorrhoeae; Skin Diseases, Infectious; Staphylococcus; Streptococcus; Urethritis; Uterine Cervicitis

If the demonstration of the interest to treat beta-haemolytic streptococcal pharyngitis is not to be done, the recommended antibiotics, most of the time, display the drawback of a treatment with one to three intakes daily for 10 days. The azithromycin, with its numerous properties, allows for the required treatment duration, to decrease the intakes number, thus facilitating the compliance. Its in vitro activity is very good on streptococci with a MIC90 of 0.06 mg/l. Its in vivo activity in animal, with experimental Streptococcus pyogenes infection models is identical to the amoxicillin activity, and better than those of other tested macrolides. One of the major characteristics of azithromycin in man is its most peculiar pharmacokinetic with an extended half life and very high tonsillar concentrations, for at least 10 days after the administration of the product at the 1.5 g dose regimen over 3 days. In streptococcal acute tonsillitis clinical studies, with a 1.5 g dose regimen over 5 days, clinical results and bacterial eradication are identical to those obtained in the Penicillin V groups. This administration facility should greatly improve the treatment compliance and lower the risks of a prematurely discontinued treatment.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Disease Models, Animal; Fasciitis, Necrotizing; Female; Humans; Male; Mice; Penicillins; Skin Diseases, Infectious; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis