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PubMed1999

[Tissue penetration properties of macrolide antibiotics--comparative tissue distribution of erythromycin-stearate, clarithromycin, roxithromycin and azithromycin in rats].

The ability of antibiotics to penetrate the target organs is an important factor for the clinical effects and side effects in the treatment of infection. In the present study, the comparative tissue distribution of 4 kinds of macrolide antibiotics was determined in rats. After oral administration of 20 mg/kg, roxithromycin (RXM) had the highest plasma concentration, and clarithromycin (CAM) has the second highest. The Cmax of RXM and CAM were 2.7 and 1.0 micrograms/ml, respectively. On the other hand, both levels of erythromycin-stearate (EM-S) and azithromycin (AZM) were extremely low, with a Cmax of 0.1 microgram/ml. Concentration of the 4 compounds were measurable in the liver, kidney, spleen, lung and heart. The concentration in all tissues for each compound were significantly higher than those in the plasma. AZM had the most sustained and the highest tissue levels. The distribution patterns of RXM and AZM were almost similar to the case of EM-S, in that the highest tissue concentration was observed in the liver, followed in descending order by concentration in the kidney, spleen, lung and heart. On the other hand, CAM had the highest concentration in the lung, and was moderated in the liver. Major clinical indications are infections of the respiratory tracts, and commonly reported side-effects are hepatotoxity. Therefore, it is worth noting that the lung levels of CAM were significantly higher than in the liver, as the separation of clinical effects and side-effects.

Animals↗
PubMed2000

Azithromycin eruption in infectious mononucleosis: a proposed mechanism of interaction.

The penicillin family of antibiotics may induce drug eruptions when prescribed to patients with infectious mononucleosis. Very similar phenomena have also been cited with other antibiotic families. We report the first case of a cutaneous reaction in a patient with infectious mononucleosis treated with azithromycin. We propose an immune-based hypothesis to explain the transient sensitivity resulting in this secondary cutaneous eruption.

Adult↗
PubMed2000

[Pharmacokinetic effects of antibiotics on the development of bacterial resistance particularly in reference to azithromycin].

Antibiotics reduce the mortality from infectious diseases but not the prevalence of these diseases. Use, and often abuse, of antimicrobial agents encourages the evolution of bacteria toward resistance, often resulting in therapeutic failure. There are two factors which influence potential utility of a drug in a specific clinical situation. The first is the measure of potency of the antibiotic for the pathogen in question (minimal inhibitory concentration [MIC], minimal bactericidal concentration [MBC]). The second is whichever relationship between the concentration-time profile and potency of the antibiotic linked most robustly to clinical outcome (time above MIC or MBC [T > MIC or T > MBC]; Peak/MIC or MBC; area under the curve [AUC]/MIC or AUC/MBC). Herein the effects of pharmacokinetics of antimicrobials on the evolution of antimicrobial resistance with particular reference to azithromycin are considered.

Aminoglycosides↗
PubMed2000

Fluoroquinolone-resistance in Neisseria gonorrhoeae, Hawaii, 1999, and decreased susceptibility to azithromycin in N. gonorrhoeae, Missouri, 1999.

In 1999, 360,076 cases of gonorrhea were reported in the United States (1). Gonorrhea is a major cause of pelvic inflammatory disease, often leading to ectopic pregnancy and infertility, and it can facilitate human immunodeficiency virus (HIV) transmission (2). During the 1980s, resistance to penicillin and tetracycline among gonococcal isolates became widespread; as a result, CDC recommended that other antimicrobial agents be used to treat gonorrhea. This report summarizes investigations of an increase in fluoroquinolone-resistant Neisseria gonorrhoeae in Hawaii and of a cluster of N. gonorrhoeae infections with decreased susceptibility to azithromycin in Missouri.

Anti-Bacterial Agents↗
PubMed2000

Bleeding complication during coumarin therapy due to amiodarone and azithromycin.

A patient with mechanical heart valves developed bleeding, after the introduction of amiodarone and azithromycin. Though the anticoagulant effect could be neutralized, the patient succumbed to heart failure. Any new drug prescribed to patients on anticoagulant must be assessed for its potential for interaction and warrants frequent prothrombin time testing.

Amiodarone↗
PubMed2002

[A case of immotile-dyskinetic cilia syndrome responding to clenbuterol hydrochloride and azithromycin].

In this case, a 30-year-old man had been treated for chronic sinusitis and bronchiectasis since 2000, and presented at our outpatient clinic in May 2001 with chief complaints of massive yellow sputum expectoration and dyspnea. After he was admitted by our hospital, Pseudomonas aeruginosa bacteria were isolated at the rate of 10(8)/ml from his sputum culture. In electron-microscopic observation, the cilia of the bronchial epithelium were found to lack dynein arms. Semen examination revealed decreased sperm motility. Thus, the following diagnosis was made: diffuse bronchiectasis associated with the immotile-dyskinetic cilia syndrome, complicated with a P. aeruginosa infection. After the airway infection was ameliorated, 40 mg/day of clenbuterol hydrochloride was administered in combination with 250 mg of azithromycin, which was given twice a week, and which led to a markedly decreased frequency of exacerbation of airway infection. Moreover, chest CT scanning and respiratory function testing also indicated improvements. It was hypothesized that the decreased cilia motility due to P. aeruginosa-produced pyocyanin would be ameliorated with a b2 stimulant, and the inhibitory effect of a macrolide on the P. aeruginosa biofilm and production of pyocyanin would also be involved in the improvement of this case.

Adult↗
PubMed2003

An outbreak of pneumococcal pneumonia among military personnel at high risk: control by low-dose azithromycin postexposure chemoprophylaxis.

In the winter of 1998-1999 an outbreak of pneumococcal pneumonia occurred among Ranger students undergoing high-intensity training. Thirty pneumonia cases (attack rate = 12.6%) were identified among a group of 239 students. Eighteen students were hospitalized; Streptococcus pneumoniae-positive cultures were detected in 11 (61.1%) of these 18 hospitalized cases. Pneumococci were also identified in throat swabs of 30 (13.6%) of 221 nonhospitalized students surveyed. Serum antipneumolysin seroconversions were detected in 30 (18.3%) of 164 students tested. An association between development of serum antipneumolysin antibody and pneumococcal pharyngeal carriage/colonization was found. Of 30 seroconverters, eight (26.7%) had S. pneumoniae-positive cultures compared with only 17 (12.7%) of 134 nonseroconverters (relative risks = 2.02, 95% confidence interval = 1.02-4.02, p = 0.05). The outbreak was controlled by administrating lowdose, oral azithromycin prophylaxis (250 mg weekly for 2 weeks) and was associated with a 69% reduction in pneumococcal carriage and a 94% reduction in pneumonia rates.

Adult↗
PubMed2000

[Pharmacokinetics and tissue distribution of azithromycin in humans].

Azithromycin(AZM) is a new macrolides antibiotic developed by Pfizer Inc. of the US. It has a 15-membered ring structure obtainable by introducing methyl-substituted nitrogen into a 14-membered ring lactone of erythromycin(EM). An effective drug concentration is sustained long owning to its superiority in tissue distribution and long half life(T1/2). AZM is also demonstrated to be twice to three times more powerful than the existing macrolides owning to its reinforced antimicrobial activity against Gram-negative microorganisms including influenza virus. AZM is already used in clinical practice in foreign countries and its excellent clinical performance has been demonstrated by the data. As for the domestic basic and clinical studies of AZM, Phase I study was initiated in 1991 following completion of nonclinical studies, and general clinical studies, a dose-setting study and Phase III controlled studies were conducted between 1992 and 1994. Usefulness of AZM is substantiated by the data from those studies.

Anti-Bacterial Agents↗
PubMed2000

[Azithromycin in the field of dermatology].

Azithromycin (AZM) is a new macrolides antibiotic that has a 15-membered ring structure obtained by introducing methyl-substituted nitrogen into a 14-membered ring lactone of erythromycin(EM). This article reviewed and summarized the clinical studies in the treatment of skin and skin structure infections conducted in Japan and abroad of AZM.

Anti-Bacterial Agents↗
PubMed2002

Azithromycin-induced rash in infectious mononucleosis.

Antibiotic-induced skin eruption in the setting of infectious mononucleosis is a common and well-documented clinical scenario. The skin lesions are non-specific and the mechanisms causing them are unclear. Several reports have described this entity with different antibiotic classes, mainly penicillins. Only 1 case of azithromycin-induced skin eruption has previously been described in this setting. Herein, we report the second case.

Adult↗
PubMed1992

The new macrolactones: clarithromycin (Biaxin) and azithromycin (Zithromax).

Clarithromycin and azithromycin are new macrolactone antibiotics which offer several advantages over erythromycin such as increased bioavailability secondary to better acid stability, excellent tissue and intracellular distribution, extended half-lives allowing for once-daily or twice-daily dosing, lower gastrointestinal intolerance, and greater microbiological activity against selected organisms (eg, H. influenzae). These new agents are significantly more expensive than erythromycin.

Azithromycin↗
PubMed2003

[Azithromycin (Sumamed) administration in empiric treatment of nosocomial pneumonia in upper digestive tract cancer patients].

Septic complications are the most frequent and potentially lethal complications among patients treated for tumours. Respiratory tract infection, including pneumonia, is third most frequent of all infections occurring among patients undergoing surgical treatment. Of great clinical and pharmaeconomical importance is rational therapy with antibiotics, which lowers the risk of septic complications and sometimes even saves patients' lives. Azithromycin proved to be effective cure for environmental pneumonia. There has been presented a preliminary research on effectiveness of azithromicin in the treatment of septic pneumonia among patients treated for upper digestive tract cancers.

Aged↗
PubMed2004

[The use of azithromycin in prophylaxis of respiratory infections occurred in the organized collectives, clinical sequelae].

The influence of azithromycin prophylaxis on clinical course of extra-hospitalpneumonia (EP) and efficiency of empirical antibiotic therapy was studied. During 5 months EP was diagnosed in 2 groups (prophylaxis and control) in 8.6% (47/548) and 20.2% (137/678) subjects respectively. Mild EP was diagnosed in all cases. No significant differences in EP clinical course between the groups were noted. The empirical therapy using benzylpenicillin was considered as effective in 90.5% [95% CI=84.3-94.9%] and in 89.4% [95% CI=76.9-96.5%] cases in the control group and group of prophylaxis respectively (P=0.84).

Adolescent↗
PubMed1990

[Activity of azithromycin and roxithromycin alone or in combination against Mycobacterium avium and Mycobacterium xenopi].

The effect of two new macrolides, azithromycin and roxithromycin used either alone or in combination with amikacin rifabutine and 1.25 (HO)2 vitamin D3 was examined in vitro. Macrophage monolayers infected with M. avium complex or M. xenopi were treated with antibiotics or 1.25 (OH)2 vitamin D3 by using different protocols: antibiotics or 1.25 (OH)2 vitamin D3 was added to the macrophage monolayers immediately after infection and released by washing out after 24 h; antibiotics or 1.25 (OH)2 vitamin D3 was replenished daily for 4 days; or infected macrophage monolayers were treated with antibiotics plus vitamin D3 for 4 consecutive days. Treatment for 24 h resulted in an inhibition of growth. After treating the macrophage monolayers with the four antibiotics alone or in combination for 4 consecutive days intracellular killing of mycobacteria was observed and the combinations were significantly more lethal than antibiotics alone. The mycobactericidal effect was enhanced when vitamin D3 was added to the culture.

Azithromycin↗
PubMed1990

[Azithromycin versus josamycin: treatment of 89 cases of acute pneumonia].

In an open, multicenter randomized clinical trial on patients with acute pneumonia, 5-day therapy using a new oral macrolide antibiotic, azithromycin (Az), was compared with standard 10-day therapy using another macrolide, josamycin (J). Eighty-nine patients were treated (46 Az, 43 J); both groups were comparable, except in terms of the sex ratios. The causative agent was determined in 31 cases; streptococcal pneumonia was the most common diagnosis (48%). Cure rates were 93% for J and 80% for Az (p greater than 0.30), as judged by a fall in body temperature and an improvement in clinical condition and in radiographic findings. Among 6 failures, there were 4 cases of empyema (1 J, 3 Az). Of 6 deaths, 2 were pneumonia-dependent (1 J and 1 Az, Haemophilus and Streptococcus pneumoniae, respectively). We conclude that 5-day Az is as effective as 10-day J and that such short-course therapy is an advantage in the treatment of pneumonia caused by macrolide susceptible pathogens.

Adult↗
PubMed1988

In vitro activity of azithromycin (CP-62,993), a novel macrolide, against enteric pathogens.

Azithromycin (CP-62,993 [9-deoxy-9A-methyl-9A-aza-9A-homoerythromycin]) is a novel macrolide antimicrobial. In this study the in vitro activity of CP-62,993 has been determined against selected enteropathogens, including Clostridium difficile, and compared with that of erythromycin. MICs were determined using an agar incorporation technique in Mueller-Hinton medium, containing saponin-lysed horse blood at a final concentration of 10% v/v, with an inoculum of 10(4) cfu. CP-62,993 was considerably more active than erythromycin against Salmonella typhi (MIC90 4 and greater than 32 mg/l, respectively), S. enteritidis (MIC90 4 and greater than 32 mg/l), Shigella flexneri (MIC90 2 and 32 mg/l), Sh. dysenteriae (MIC90 2 and 32 mg/l), Sh. sonnei (MIC90 4 and 32 mg/l), Campylobacter jejuni (MIC90 0.12 and 1 mg/l), Vibrio cholerae (MIC90 0.25 and 8 mg/l), V. parahaemolyticus (MIC90 0.5 and 8 mg/l), Yersinia enterocolitica (MIC90 4 and greater than 32 mg/l), Escherichia coli-ETEC (MIC90 4 and 32 mg/l), E. coli-EIEC (MIC90 4 and greater than 32 mg/l), Plesiomonas shigelloides (MIC90 1 and 8 mg/l) and Aeromonas hydrophila (MIC90 4 and 32 mg/l). CP-62,993 (MIC90 2 mg/l) was slightly less active than erythromycin (MIC90 1 mg/l) against isolates of C. difficile. The results suggest a potential clinical role for CP-62,993 in the treatment of enteric infections where antimicrobial therapy is indicated.

Azithromycin↗
PubMed1995

[Comparative clinical study of azithromycin with tosufloxacin tosilate in the treatment of acute odontogenic infection].

To objectively assess azithromycin (AZM) for its clinical efficacy, safety and usefulness in the treatment of acute odontogenic infections (periodontitis, pericoronitis and osteitis of the jaw), a double-blind, randomized, multi-center trial was conducted in which tosufloxacin tosilate (TFLX) was used as the control drug. AZM was administered to 90 patients at a once-daily 500 mg dose for 3 days, while TFLX was given to 90 patients at a 150 mg t.i.d. dose for 7 days. 1. The clinical efficacy rates calculated according to evaluation at an endpoint set on the 3rd day of treatment by a committee of experts were 85.9% (73/85) in the AZM group and 78.9% (71/90) in the TFLX group. No statistically significant difference between the treatment groups was detected, and clinical equivalence was verified (p = 0.002). 2. The clinical efficacy rates according to evaluations made by investigators at the end-of-tail point was 87.1% (74/85) in the AZM group and 73.3% (66/90) in the TFLX group. The efficacy rate in the AZM group was higher than that in the TFLX group, and the difference was statistically significant (p = 0.006). 3. The bacteriological elimination rate in the AZM group was 97.5% (39/40) and that in the TFLX group was 85.7% (30/35), but the difference was deemed statistically not significant. 4. Adverse reactions were observed in 11 of 88 cases (12.5%) in the AZM group and 5 of 90 cases (5.6%) in the TFLX group. Six of 85 cases (7.1%) in the AZM group and 5 of 85 cases (5.9%) in the TFLX group showed laboratory abnormalities. However, neither adverse reactions nor laboratory abnormalities showed any differences in statistical significance between the treatment groups. 5. The safety rates, expressed as percentages of cases with no adverse events and no laboratory abnormalities, was 84.1% (74/88) in the AZM group and 90.0% (81/90) in the TFLX group. The difference between the two groups was found to be statistically insignificant. 6. The usefulness rates, the ratio of cases rated as either "Very useful" or "Useful", was 83.9% (73/87) in the AZM group, and it was statistically higher (p = 0.025) than 72.2% (65/90) obtained for TFLX group. Judging from the above results, it has been concluded that AZM is as useful as TFLX in the treatment of acute dental infections.

Adolescent↗
PubMed1995

[Effects of azithromycin on fecal flora of healthy adult volunteers].

New macrolide antibiotic, azithromycin (AZM), was administered to six healthy male volunteers and its effects on their intestinal microflora were investigated. Each volunteer was given 500 mg of AZM orally, once a day for 3 consecutive days. Stool samples were obtained from them prior to the medication and 1, 7, 14 and 28 days after the third day the medication. A slight decrease in the total aerobic bacterial count was observed. Also, several species of anaerobic bacteria showed slight decreases through the 14th day post medication. Individual variances were observed, however. A marked decrease in the number of Bifidobacterium was found for each of the volunteers. Clostridium difficile was detected from one of the volunteers on the 28th day post medication without diarrhea related symptoms.

Adult↗