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PubMed2001

Azithromycin monthly pulse vs daily doxycycline in the treatment of acne vulgaris.

Acne vulgaris is a common skin disease seen primarily in adolescent and young adults. As the treatment involves long term therapy with antibiotics, an agent with a long half life can be very useful in increasing the compliance. To evaluate the role of a monthly dose of azithromycin and compare it with daily doxycycline, we conducted this randomized comparative study. Sixty patients with moderate to severe acne were randomly assigned to two treatment groups, A & B. Patients in group A received 100 mg doxycycline daily in addition to topical 0.05% tretinoin cream, whereas patients in group B were given 500 mg azithromycin once a day for four days per month along with 0.05% topical tretinoin for a total of 12 weeks. Of the 60 patients, 22 in group A and 28 in group B were evaluated. The monthly dose of azithromycin was found to be as effective as daily doxycycline on a pure protocol basis and statistically significantly better than doxycycline by intention to treat analysis.

Acne Vulgaris↗
PubMed2004

Acne treated successfully with azithromycin.

AIM: To study the efficacy, safety, and compliance of 500 mg azithromycin thrice weekly for 12 weeks in acne vulgaris. METHODS: An open-label, noncomparative study was carried out for 12 weeks at the outpatient clinics of Aga Khan University Hospital, Abassi Shaheed Hospital, and Burhani Community Hospital in Karachi, Pakistan. Thirty-five adolescent and postadolescent patients with moderate to severe papulopustular acne vulgaris were enrolled. All patients completed the study. Azithromycin, 500 mg orally thrice weekly for 12 weeks, was used. After the baseline visit, patients were scheduled to return at four-weekly intervals for 12 weeks. Efficacy was gauged by the percentage clearance of papulopustular acne lesions. Safety assessments included the monitoring of adverse events, and compliance was checked at the four-weekly regular visits up to 12 weeks. RESULTS: Twenty-nine patients (82.9%) showed remarkable improvement in the first 4 weeks with 60% reduction of their inflammatory papulopustular lesions. Maximum clearance (80%) was observed at 12 weeks. Residual postinflammatory pigmentation and pitted and linear scarring represented the aftermath of the relapsing pattern of acne. Six patients (17.1%) showed slow clearance with eruptions of new lesions. Adverse events, such as heartburn and nausea, were reported by four patients (11.4%). All patients completed the 12-week study period. CONCLUSION: Azithromycin, 500 mg thrice weekly for 12 weeks, is a safe and effective treatment of acne vulgaris with excellent patient compliance.

Acne Vulgaris↗
PubMed2006

Macrolide and azithromycin use are linked to increased macrolide resistance in Streptococcus pneumoniae.

The connection between regional rates of antimicrobial resistance in Streptococcus pneumoniae and regional antimicrobial use in Finland was investigated. During the 6-year study period of 1997 to 2002, a total of 31,609 S. pneumoniae isolates were tested for penicillin resistance and a total of 23,769 isolates were tested for macrolide resistance in 18 central hospital districts in Finland. The regional macrolide resistance rates were compared with the local use of (i) all macrolides pooled and (ii) azithromycin. The penicillin resistance levels were compared with the consumption data for (i) penicillins, (ii) cephalosporins, (iii) all beta-lactams pooled, and (iv) all macrolides pooled. A statistically significant association between macrolide resistance and total use of macrolides and the use of azithromycin was found. Moreover, total use of beta-lactams and total use of cephalosporins were significantly connected to low-level penicillin resistance. A statistically significant association between penicillin-nonsusceptible isolates and penicillin or total macrolide consumption was not found. In conclusion, total macrolide use and azithromycin use are associated with increased macrolide resistance, and beta-lactam use and cephalosporin use are connected to increased low-level penicillin resistance in S. pneumoniae. Unnecessary prescribing of macrolides and cephalosporins should be avoided.

Anti-Bacterial Agents↗
PubMed1988

In vitro activities of azithromycin (CP 62,993), clarithromycin (A-56268; TE-031), erythromycin, roxithromycin, and clindamycin.

The in vitro activity of azithromycin (CP 62,993 or XZ-450) against Haemophilus influenzae was greater than that of three other macrolides. However, azithromycin was four- to eightfold less active than erythromycin against the gram-positive cocci and against Listeria monocytogenes. Erythromycin and azithromycin were similar in their activity against Legionella pneumophila, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis.

Azithromycin↗
PubMed1988

Activities of amikacin, roxithromycin, and azithromycin alone or in combination with tumor necrosis factor against Mycobacterium avium complex.

The effect of amikacin and two new macrolides (roxithromycin and azithromycin) used either alone or in combination with recombinant tumor necrosis factor (TNF) to inhibit or kill Mycobacterium avium complex in human macrophages was examined in vitro. Macrophage monolayers infected with M. avium complex (strain 101, serotype 1) were treated with antibiotics or TNF by using three different protocols: (i) antibiotics or TNF was added to the monolayers immediately after infection and washed out after 24 h, (ii) antibiotics or TNF was replenished daily for 4 dys, or (iii) infected macrophage monolayers were treated with antibiotics plus TNF for 4 consecutive days. The number of viable intracellular bacteria was determined after 2 and 4 days of treatment by lysing cultured macrophages. Treatment for 24 h resulted in an inhibition of growth, as determined by macrophage lysis at day 4, for all three antimicrobial drugs and killing of 22% of intracellular bacteria after treatment with TNF. After treating the monolayers with amikacin, roxithromycin, or azithromycin for 4 consecutive days and replenishing the drug concentration daily, we observed 18 +/- 6, 20 +/- 4, and 22 +/- 1% killing, respectively. TNF (100 U/ml) was added daily to the monolayers, which resulted in 54 +/- 5% killing after 4 days. Combinations of antibiotics with TNF were associated with 62 +/- 3% killing with TNF-azithromycin, 73 +/- 6% killing with TNF-roxithromycin, and 56 +/- 4% killing of intracellular M. avium complex with TNF-amikacin after 4 days. The mycobactericidal effect was enhanced (91 +/- 4% killing by roxithromycinamikacin). Combinations of antimicrobial agents with immunomodulators like TNF may be useful for treatment of M. avium complex infection.

Amikacin↗
PubMed1991

In vitro activity of azithromycin against clinical isolates of Legionella species.

The activities of azithromycin, erythromycin, and ciprofloxacin against 21 Legionella isolates were measured by an agar dilution method and in macrophages. The MICs for 90% of strains tested were 2.0, 1.0, and 0.5 micrograms/ml for azithromycin, erythromycin, and ciprofloxacin, respectively. Azithromycin and ciprofloxacin were both bactericidal in the macrophage system, but erythromycin was bacteriostatic.

Animals↗
PubMed1993

Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine.

Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections.

Animals↗
PubMed1994

Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin.

Following intravaginal inoculation of progesterone-treated outbred mice with Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered in vaginal swabs for 21 days but all animals were culture negative after 28 days. Serum antibody titers were elevated and remained high for at least 70 days. Between 28 and 70 days, upper tract infection (inflammation and distension of the uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and hydrosalpinx) was seen in > 80% of the animals. Mice were dosed orally, commencing at 7 days after infection, with minocycline, doxycycline, or amoxicillin-clavulanate. Further groups received azithromycin either as a single high dose or as lower once-daily doses. In addition, minocycline and amoxicillin-clavulanate were administered at 24 h after infection, and this early treatment prevented elevation of antibody titers whereas delayed therapy did not. Vaginal swabs from mice in all treatment regimens were culture negative except for 25% of mice receiving either early amoxicillin-clavulanate or low-dose azithromycin, which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae. Numbers of fertile mice in the early treatment regimens and their litter sizes were similar to those of noninfected controls, although 25% of amoxicillin-clavulanate-treated mice had unilateral hydrosalpinges. In comparison, 88% of untreated mice developed hydrosalpinges and only 25% conceived. Delayed dosing did not affect the outcome of amoxicillin-clavulanate therapy but did diminish the protective efficacy of minocycline such that 50% of treated mice had either unilateral hydrosalpinges or ovarian abscesses. Doxycycline and azithromycin were highly effective in restoring fertility. This model makes possible the study of both short- and long-term outcomes of chlamydial infection.

Amoxicillin↗
PubMed1995

Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin on respiratory tract pathogens.

Pharmacodynamic parameters have become increasingly important for the determination of the optimal dosing schedules of antibiotics. In this study, the postantibiotic effects (PAEs), the postantibiotic sub-MIC effects (PA SMEs), and the sub-MIC effects (SMEs) of roxithromycin, clarithromycin, and azithromycin on reference strains of Streptococcus pyogenes group A, Streptococcus pneumoniae, and Haemophilus influenzae were investigated. The PAE was induced by 2x MICs (S. pneumoniae) or 10x MICs of the different drugs for 2 h, and the antibiotics were eliminated by washing and dilution. The PA SMEs were studied by addition of 0.1, 0.2, and 0.3x MICs during the postantibiotic phase of the bacteria, and the SMEs were studied by exposition of the bacteria to the drugs at the sub-MICs only. Growth curves were followed by viable counts for 24 h. The SMEs were generally very short. A PAE of 2.9 to 8 h was noted for all antibiotics against all strains. Clarithromycin induced a statistically significantly shorter PAE on S. pneumoniae than did roxithromycin and azithromycin and did so also against H. influenzae in comparison with azithromycin. The PA SMEs were long and varied at 0.3x MIC between 6.4 19.6 h. This pronounced suppression of regrowth of bacteria which are first treated with a suprainhibitory concentration of antibiotics and then reexposed to sub-MIC levels indicates that long dosing intervals for macrolides and azalides can be allowed.

Azithromycin↗
PubMed1997

Susceptibility of penicillin-susceptible and -resistant pneumococci to dirithromycin compared with susceptibilities to erythromycin, azithromycin, clarithromycin, roxithromycin, and clindamycin.

Agar dilution with incubation in air and CO2 was used to determine the MICs of erythromycin, dirithromycin, azithromycin, clarithromycin, roxithromycin, and clindamycin for 79 penicillin-susceptible, 72 penicillin-intermediate, and 74 penicillin-resistant pneumococci (158 erythromycin-susceptible and 67 erythromycin-resistant pneumococci). MICs obtained in air were usually 1 to 3 dilutions lower than those obtained in CO2. In air, the respective MICs at which 50% (MIC50s) and 90% (MIC90s) of penicillin-susceptible, -intermediate, and -resistant strains are inhibited were as follows: erythromycin, 0.016 and 0.5, 0.03 and > 64, and 2 and > 64 microg/ml; dirithromycin, 0.03 and 0.5, 0.06 and > 64, and 8 and > 64 microg/ml; azithromycin, 0.03 and 0.5, 0.06 and > 64, and 2 and > 64 microg/ml; clarithromycin, 0.016 and 0.06, 0.03 and > 64, and 2 and > 64 microg/ml; roxithromycin, 0.06 and 2, 0.06 and > 64, and 2 and > 64 microg/ml; and clindamycin, 0.03 and 0.06, 0.06 and > 64, and 0.06 and > 64 microg/ml. The MICs of erythromycin, azithromycin, and dirithromycin were very similar; however, clarithromycin MICs were generally 1 to 2 dilutions lower and roxithromycin MICs were 1 to 2 dilutions higher than those of the other compounds tested. Strains resistant to one macrolide were resistant to all macrolides; however, not all macrolide-resistant strains were resistant to clindamycin, and 32 macrolide-resistant (MICs, > or = 28 microg/ml), clindamycin-susceptible (MICs, < or = 0.25 microg/ml) strains were encountered. Time-kill testing of six strains showed similar killing kinetics for all compounds, with 99.9% killing of all strains observed with the compounds only at or above the MIC after 24 h.

Aminoglycosides↗
PubMed1999

Azithromycin activities against Orientia tsutsugamushi strains isolated in cases of scrub typhus in Northern Thailand.

Azithromycin was given to mice and humans infected with strains of Orientia tsutsugamushi from northern Thailand, where drug-resistant scrub typhus occurs. Azithromycin and doxycycline yielded comparable mouse survival rates (73 and 79%, respectively; P > 0.5). Symptoms, signs, and fever in two pregnant women abated rapidly with azithromycin. Prospective human trials are needed.

Adult↗
PubMed1999

Azithromycin as treatment for disseminated Mycobacterium avium complex in AIDS patients.

This multicenter, randomized, dose-ranging study was performed to determine the safety and efficacy of two different doses of azithromycin for treating disseminated Mycobacterium avium complex (MAC) in patients with AIDS. Eighty-eight AIDS patients with symptoms and blood cultures consistent with disseminated MAC were treated with 600 or 1,200 mg of azithromycin daily for 6 weeks; 62 patients completed the entire 6 weeks of study. Of note, this study was done prior to the time when combination antiretroviral or anti-MAC regimens were the standard of care. Over the 6-week study period, symptomatic improvement was noted in both dose groups. Microbiological responses were comparable, with mean decreases of 1. 5 and 2.0 log CFU/ml in the high- and low-dose groups, respectively. Sterilization of blood cultures occurred in 54% of samples; patients with lower baseline colony counts were more likely to achieve culture negativity. Resistance developed in one patient. Gastrointestinal symptoms were the most common side effects and were more frequent in patients receiving 1,200 mg. Azithromycin is a useful alternative treatment for disseminated MAC infection in AIDS patients. Symptomatic improvement correlates with measurable decreases in mycobacterial load.

AIDS-Related Opportunistic Infections↗
PubMed1999

Efficacy of doxycycline, azithromycin, or trovafloxacin for treatment of experimental Rocky Mountain spotted fever in dogs.

Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration.

Animals↗
PubMed2000

Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children.

A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae.

Acute Disease↗
PubMed2000

Single-oral-dose azithromycin prophylaxis against experimental streptococcal or staphylococcal aortic valve endocarditis.

Azithromycin and ampicillin protected 94 and 72% of animals challenged with Streptococcus oralis, respectively (P = 0.177), while azithromycin and vancomycin protected 59 and 94% of the methicillin-resistant Staphylococcus aureus (MRSA)-challenged animals, respectively (P = 0.018). Azithromycin is effective in preventing experimental streptococcal endocarditis, but against MRSA it is less effective than vancomycin.

Administration, Oral↗
PubMed2002

Effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on Chlamydia pneumoniae in a continuous-infection Model.

Persistent infections with Chlamydia pneumoniae have been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1beta, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.

Anti-Bacterial Agents↗
PubMed2002

Distribution of azithromycin in plasma and tonsil tissue after repeated oral administration of 10 or 20 milligrams per kilogram in pediatric patients.

Azithromycin concentrations in the tonsils of 56 pediatric patients, treated with 10 or 20 mg of the drug per kg of body weight for 3 days, were compared. Azithromycin levels in plasma and tonsil samples were determined up to 8.5 days after the last dose. The 20-mg/kg regimen resulted in an improved tonsillar distribution of azithromycin, suggesting the achievement of enhanced therapeutic concentrations at infective sites of the upper respiratory tract.

Administration, Oral↗