zithromax and Respiratory-Tract-Infections

Acute wheezing episodes are frequent in young children and are associated with high morbidity and healthcare utilization. The role of respiratory viruses in triggering acute wheezing is well known. There is also accumulating evidence that airway bacteria, either alone or as part of bacteria-virus interaction, are important determinants of acute asthma exacerbations. Targeting airway bacteria with antibiotics to reduce the severity of acute wheezing episodes and prevent recurrent wheezing among preschool children has been recently evaluated in three randomized, double-blind, placebo-controlled trials. The results of these studies are controversial. An interventional approach with azithromycin in young children during acute wheezing episodes cannot be generically incorporated into clinical practice, due to the potential consequences of widespread use of antibiotics in such a common clinical setting. This intervention may be reserved for children with really severe, recurrent wheezing episodes. Future research should focus on risk factors that facilitate acquisition of bacterial airway infection in young children and better understanding how virus and bacteria interact with each other during wheezing attacks. Identifying objective biomarkers that may direct the treatment to specific groups of children may represent a significant step forward in the clinical approach of acute wheezing.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child, Preschool; Clinical Trials as Topic; Dysbiosis; Humans; Inflammation; Microbial Interactions; Microbiota; Patient Selection; Recurrence; Respiratory Sounds; Respiratory Tract Infections; Severity of Illness Index; Virus Diseases

In health, the glucose concentration of airway surface liquid (ASL) is 0.4 mM, about 12 times lower than the blood glucose concentration. Airway glucose homeostasis comprises a set of processes that actively maintain low ASL glucose concentration against the transepithelial gradient. Tight junctions between airway epithelial cells restrict paracellular glucose movement. Epithelial cellular glucose transport and metabolism removes glucose from ASL. Low ASL glucose concentrations make an important contribution to airway defense against infection, limiting bacterial growth by restricting nutrient availability. Both airway inflammation, which increases glucose permeability of tight junctions, and hyperglycemia, which increases the transepithelial glucose gradient, increase ASL glucose concentrations, with the greatest effect seen where they coexist. Elevated ASL glucose drives proliferation of bacteria able to use glucose as a carbon source, including Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacteria. Clinically, this appears to be important in driving exacerbations of chronic lung disease, especially in patients with comorbid diabetes mellitus. Drugs can restore airway glucose homeostasis by reducing the permeability of tight junctions (eg, metformin), increasing epithelial cell glucose transport (eg, β-agonists, insulin), and/or by lowering blood glucose (eg, dapagliflozin). In cell culture and animal models these reduce ASL glucose concentrations and limit bacterial growth, preventing infection. Observational studies in humans indicate that airway glucose homeostasis-modifying drugs could prevent chronic lung disease exacerbations if tested in randomized trials.

Topics: Adrenergic beta-Agonists; Animals; Azithromycin; Glucocorticoids; Glucose; Humans; Hypoglycemic Agents; Lung Diseases; PPAR gamma; Respiratory Mucosa; Respiratory Tract Infections; Tight Junctions; Vitamin D

Mycobacterium abscessus is an emerging mycobacteria that is responsible for lung diseases and healthcare-associated extrapulmonary infections. Recent findings support its taxonomic status as a single species comprising 3 subspecies designated abscessus, bolletii and massiliense. We performed a review of English-language publications investigating all three of these subspecies. Areas covered: Worldwide, human infections are often attributable to environmental contamination, although the isolation of M. abscessus in this reservoir is very rare. Basic research has demonstrated an association between virulence and cell wall components and cording, and genome analysis has identified gene transfer from other bacteria. The bacteriological diagnosis of M. abscessus is based on innovative tools combining molecular biology and mass spectrometry. Genotypic and phenotypic susceptibility testing are required to predict the success of macrolide (clarithromycin or azithromycin)-based therapeutic regimens. Genotyping methods are helpful to assess relapse and cross-transmission and to search for a common source. Treatment is not standardised, and outcomes are often unsatisfactory. Expert commentary: M. abscessus is still an open field in terms of clinical and bacteriological research. Further knowledge of its ecology and transmission routes, as well as host-pathogen interactions, is required. Because the number of human cases is increasing, it is also necessary to identify more active treatments and perform clinical trials to assess standard effective regimens.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cystic Fibrosis; Humans; Mycobacterium; Mycobacterium Infections; Prevalence; Respiratory Tract Infections; Treatment Outcome; Virulence

Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die from acute respiratory tract infections annually. Among these, pneumonia represents the most frequent cause of mortality, hospitalisation and medical consultation. Azithromycin is a macrolide antibiotic, structurally modified from erythromycin and noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae).. To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication.. We searched CENTRAL (2014, Issue 10), MEDLINE (January 1966 to October week 4, 2014) and EMBASE (January 1974 to November 2014).. Randomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis.. The review authors independently assessed all potential studies identified from the searches for methodological quality. We extracted and analysed relevant data separately. We resolved discrepancies through discussion. We initially pooled all types of acute LRTI in the meta-analyses. We investigated the heterogeneity of results using the forest plot and Chi(2) test. We also used the index of the I(2) statistic to measure inconsistent results among trials. We conducted subgroup and sensitivity analyses.. We included 16 trials involving 2648 participants. We were able to analyse 15 of the trials with 2496 participants. The pooled analysis of all the trials showed that there was no significant difference in the incidence of clinical failure on about days 10 to 14 between the two groups (risk ratio (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). A subgroup analysis in trials with acute bronchitis participants showed significantly lower clinical failure in the azithromycin group compared to amoxycillin or amoxyclav (RR random-effects 0.63; 95% CI 0.45 to 0.88). A sensitivity analysis showed a non-significant reduction in clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00).. There is unclear evidence that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxycillin or amoxyclav. However, most studies were of unclear methodological quality and had small sample sizes; future trials of high methodological quality and adequate sizes are needed.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchitis; Drug Therapy, Combination; Humans; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Failure

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with adverse outcomes and thus prevention of exacerbations is crucial. New data attest that long-term macrolide therapy decreases the risk of COPD exacerbations. We review the key studies that analyzed the effect of long-term use of macrolide antibiotics on the prevention of exacerbations, focusing on the higher quality evidence. Health-related quality of life, sputum bacteriology and development of resistance, inflammatory markers, lung function, cost-benefit analysis, and lung function in relation to long-term macrolide therapy are also discussed.. Two well designed, randomized, placebo-controlled trials report that select patients treated for 1 year with erythromycin or azithromycin, in addition to usual care, have prolonged time to and lower frequency of COPD exacerbations. There are more hearing decrements and higher prevalence of macrolide-resistant bacteria among the patients treated with macrolide therapy.. Prevention of COPD exacerbations is paramount given the adverse consequences on quality of life, lung function, and survival. Macrolide therapy for 1 year, in addition to usual therapy, decreases the risk of COPD exacerbations but carries the risk of hearing decrements and development of macrolide-resistant bacteria.

Topics: Anti-Bacterial Agents; Azithromycin; Cost-Benefit Analysis; Disease Progression; Drug Administration Schedule; Drug Resistance, Bacterial; Erythromycin; Humans; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sputum; Time Factors; Treatment Outcome

Mycobacterium abscessus is the most common rapidly growing mycobacterium that causes lung disease. This review describes recently published literature regarding M. abscessus taxonomy, environmental niche, diagnosis, management and outcome in pulmonary disease in adults and adolescents with cystic fibrosis.. The classification of M. abscessus subsp. abscessus, M. abscessus subsp. massiliense and M. abscessus subsp. bolletii is useful clinically because of the discovery of the erm(41) gene, which is responsible for macrolide resistance in M. abscessus. Macrolide susceptibility is key for successful treatment of M. abscessus subsp. massiliense. The poor outcome and eradication of M. abscessus subsp. abscessus remains both a diagnostic and treatment challenge in approximately 80% of isolates that are macrolide resistant. Molecular studies, such as genotyping, may allow prediction of disease progression. Overall, there is a dearth of new literature surrounding M. abscessus.. New studies differentiating M. abscessus subsp. abscessus and M. abscessus subsp. massiliense based on the erm(41) gene demonstrate the latter to have a better prognosis and improved treatment outcomes. M. abscessus subsp. abscessus remains a formidable pathogen in diagnosis and treatment.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Cystic Fibrosis; DNA-Binding Proteins; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Genotype; Humans; Molecular Diagnostic Techniques; Molecular Sequence Data; Mycobacterium Infections, Nontuberculous; Polymorphism, Single Nucleotide; Respiratory Tract Infections; Sequence Analysis, DNA; Transcription Factors; Treatment Outcome

Antibiotics have significant role in the treatment of respiratory diseases. The main aim of their use is to treat infection, but anti-inflammatory properties of macrolides are also beneficial in selected diseases. The role of antibiotics in the therapy of asthma exacerbation can be neglected and should be limited to exceptional situations of bacterial infections which are very rare. During last few years the role of atypical infections in asthma inception, induction of exacerbation and modification of chronic course of disease has been discussed. Antibiotics play significant role in cystic fibrosis therapy. They are especially recommended during exacerbation, when new pathogens are revealed and in chronic Pseudomonas aeruginosa infection. This paper includes the principal rules of antibiotics therapy in patients with cystic fibrosis. The role of azithromycin in antiinflammatory therapy in this group of patients is also presented.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Asthma; Azithromycin; Child; Cystic Fibrosis; Humans; Respiratory Tract Infections

Topics: Acute Disease; Administration, Oral; Azithromycin; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dosage Forms; Drug Delivery Systems; Drug Interactions; Drug Resistance, Bacterial; Haemophilus influenzae; Humans; Microspheres; Patient Satisfaction; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Streptococcus pneumoniae

Lower respiratory tract infections are serious health problem in pediatric population. The prevalence of infections is the highest in the youngest group and typical bacteria is the most common cause of diseases in this group. The role of atypical pathogens is on the rise in older patients. The choice of therapy depends on ethiology The article is focused on the role of azithromycin showing the benefits of such therapy.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Humans; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Azithromycin; Cerebral Palsy; Child; Chronic Disease; Humans; Male; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die of acute respiratory tract infections annually. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Azithromycin is a new macrolide antibiotic, structurally modified from erythromycin and noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae).. To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007 Issue 2), MEDLINE (January 1966 to July 2007), and EMBASE (January 1974 to July 2007).. Randomized and quasi-randomized controlled trials, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic bronchitis were studied.. The criteria for assessing study quality were generation of allocation sequence, concealment of treatment allocation, blinding, and completeness of the trial. All types of acute LRTI were initially pooled in the meta-analyses. The heterogeneity of results was investigated by the forest plot and Chi-square test. Index of I-square (I(2)) was also used to measure inconsistent results among trials. Subgroup and sensitivity analyses were conducted.. Fifteen trials were analysed. The pooled analysis of all trials showed that there was no significant difference in the incidence of clinical failure on about day 10 to 14 between the two groups (relative risk (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). Sensitivity analysis showed a reduction of clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00).. There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav. Future trials of high methodological quality are needed.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchitis; Drug Therapy, Combination; Humans; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Failure

Cystic fibrosis is the most common incurable hereditary disease in the US. Persistent respiratory infection is the leading cause of morbidity and mortality in cystic fibrosis patients.. This study aimed to review the literature on economic and quality of life outcomes and treatment compliance associated with antibiotic therapies for cystic fibrosis patients.. A systematic literature review was conducted using keyword searches of the MEDLINE database and selected conference abstracts. The review covered studies published between January 1990 and May 2007.. Evidence suggests that inhaled tobramycin, a key chronic suppressive therapy, can reduce other healthcare costs. The main determinants of the cost of care include disease severity and respiratory infection. Costs vary widely by country. There is evidence that inhaled tobramycin and oral azithromycin improve quality of life and that treatment setting and patient convenience may also impact on quality of life. Antibiotic treatment compliance varied significantly and depended on the method of measurement, with more subjective measures tending to be higher. This review concludes by offering directions for future research.

Topics: Anti-Bacterial Agents; Azithromycin; Cystic Fibrosis; Health Care Costs; Humans; Patient Compliance; Quality of Life; Respiratory Tract Infections; Severity of Illness Index; Tobramycin

Few adequately designed clinical trials have addressed optimal treatment duration in lower respiratory tract infections. Drugs possessing favourable pharmacokinetic and pharmacodynamic profiles may obtain early bacterial eradication allowing shorter treatment duration. This may be associated with a number of advantages including reduced resistance induction, increased compliance, lesser adverse events, and cost containment. Recently, a novel 2.0 g single dose of azithromycin microspheres has been compared with 7-day levofloxacin 500 mg or extended release clarithromycin in over 400 patients with community-acquired pneumonia. Clinical cure and bacteriological eradication rates, hospitalizations, and deaths were similar between azithromycin and comparators. Azithromycin 2.0 g microspheres proved as effective as 7 days of levofloxacin 500 mg in acute exacerbation of chronic bronchitis patients across all degrees of obstruction severity. In both settings Azithromycin microspheres obtained clinical cure in most patients harbouring macrolide-resistant Streptococcus pneumoniae strains. The drug was well tolerated in clinical studies and in healthy volunteers with modest and transitory adverse events. An undoubted advantage of single-dose azithromycin administration is the facility in ensuring that patients complete their prescribed course of therapy. A further advantage of single-dose therapy is the potential for use as directly-observed therapy, which may be useful in specific clinical conditions.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Azithromycin; Capsules; Clinical Trials as Topic; Drug Carriers; Humans; Microspheres; Respiratory Tract Infections; Staphylococcal Infections

Mycobacterium abscessus is the most pathogenic and chemotherapy-resistant rapid-growing mycobacterium. It is commonly associated with contaminated traumatic skin wounds and with post-surgical soft tissue infections. It is also one of the mycobacteria that are most often isolated from cystic fibrosis patients. It is essential to differentiate this species from the formerly indistinct "M. chelonae-complex", as chemotherapy is especially difficult in M. abscessussenso strictu. Clarithromycin or azithromycin are the only regular oral antimycobacterial agents with an effect on M. abscessus, and should preferably be supplemented with other drugs since long-term monotherapy may cause resistance. Amikacin is a major parenteral drug against M. abscessus that should also be given in combination with another drug. The recently introduced drug tigecycline may prove to be an important addition to chemotherapy, but has yet to be fully clinically evaluated as an antimycobacterial agent. Surgery can be curative, or at least helpful, in the healing of M. abscessus infection, and if conducted, it should include the removal of all foreign or necrotic material. There is increasing awareness of M. abscessus as an emerging pathogen.

Topics: Administration, Oral; Amikacin; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cystic Fibrosis; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Mycobacterium; Mycobacterium Infections; Respiratory Tract Infections; Skin; Soft Tissue Infections; Species Specificity; Surgical Wound Infection; Tigecycline; Tuberculosis, Cutaneous; Wounds and Injuries

Laboratory surveillance data suggest that macrolide resistance among Streptococcus pneumoniae has increased dramatically over the past 15 years. This review examines the specifics of macrolide resistance and the clinical relevance of in vitro susceptibility testing in light of the pharmacokinetics and pharmacodynamics of azithromycin and clarithromycin. These drugs concentrate extensively within respiratory tissue and have other positive characteristics not reflected by in vitro susceptibility testing. In general, clarithromycin is the most potent macrolide and the one most likely to maintain clinical efficacy against the low-level resistance associated with most macrolide-resistant pneumococci in the USA. These findings suggest that susceptibility data may underestimate clinical utility and that clarithromycin still has a place in the empiric treatment of respiratory infections.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Ketolides; Macrolides; Microbial Sensitivity Tests; Respiratory Tract Infections; Risk Factors; Streptococcus pneumoniae

It has been recognized for more than 20 years that the macrolides have immunomodulatory effects that are beneficial for those suffering from chronic pulmonary inflammatory syndromes, such as diffuse panbronchiolitis, cystic fibrosis, asthma and bronchiectasis. The macrolides have consistently been associated with decreased length of stay and mortality when used alone or in combination with beta-lactam antibiotics. This effect can be demonstrated against combinations consisting of beta-lactams and other antibiotics active against 'atypical chest pathogens' when treating community-acquired pneumonia (CAP) in hospitalized patients. As such, it appears that the macrolides' effects in CAP patients are more than just antibacterial in nature. AIMS OF THIS REVIEW: This review aims: to give the reader information on the background areas described, as well as related areas; to review the CAP benefits with macrolides and how they may be related to the immunomodulatory properties they demonstrate, albeit in a shorter period of time than previously demonstrated with chronic pulmonary disorders; to use ex vivo data to support these extrapolations.. A literature search using Medline was conducted from 1966 onwards, searching for articles with relevant key words such as macrolide, diffuse panbronchiolitis, community-acquired pneumonia, biofilm, immunomodulation, cystic fibrosis, erythromycin, clarithromycin, roxithromycin and azithromycin, bronchiectasis and asthma. When appropriate, additional references were found from the bibliographies of identified papers of interest. Any relevant scientific conference proceedings or medical texts were checked when necessary.. (1) Research into macrolide immunomodulation for chronic pulmonary disorders demonstrates consistent positive effects, although of types other than seen with diffuse panbronchiolitis. These effects, together with their inhibitory activity on biofilms, have the potential to make them a useful option. (2) The benefits for CAP are consistent, and higher when a macrolide is given with another atypical agent than if the other atypical agent is given alone, suggesting a non-antibacterial benefit. (3) Recent research of the immunomodulatory properties of azithromycin imply that azithromycin may have a previously unknown short-term biphasic effect on inflammation modulation: enhancement of host defence mechanisms shortly after initial administration followed by curtailment of local infection/inflammation in the following period. (4) Additional in vivo research is needed prior to developing any firm conclusions.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Chronic Disease; Clarithromycin; Community-Acquired Infections; Erythromycin; Humans; Inflammation; Macrolides; Respiratory Tract Infections

Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated resistance of Streptococcus pneumoniae and Streptococcus pyogenes to macrolide antibiotics among patients with community-acquired respiratory tract infections.. MEDLINE and EMBASE databases were searched and experts were consulted to identify published and unpublished literature reporting macrolide resistance rates. Identified studies were evaluated by two independent reviewers; those meeting a priori specified criteria (resistance by patient condition and strain, resistance thresholds, 1997-2003 isolates) were included. Data from included studies were abstracted by two independent reviewers using a standard review form. Discrepancies in abstracted data were resolved by the study investigator.. Random-effects meta-analysis was performed for outcomes present in at least four studies overall and for specified subgroups. We identified 3849 studies and performed detailed review on 407; of these 29, published between 1998-2003, met the inclusion criteria. Mean resistance of S. pneumoniae isolates to azithromycin was 27.2% [95% confidence interval (CI) 24.6-29.7]; mean resistance to erythromycin was statistically equivalent (30.4%; 95% CI 28.1-32.7). Resistance of S. pyogenes to erythromycin (30.0%; CI 18.6-41.5) was similar to that of S. pneumoniae. Too few studies of clarithromycin were included to allow evaluation of resistance. In subgroup analyses, substantial variation in resistance to erythromycin was seen by geographic area.. Reported macrolide resistance of S. pneumoniae varies substantially and may be a significant issue in certain regions. Use of meta-analysis to aggregate individual studies enabled determination of robust values for macrolide resistance. This information is useful for clinical and policy decision makers in developing appropriate antibiotic strategies.

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; Microbial Sensitivity Tests; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes

Azithromycin is a macrolide antibiotic that has been structurally modified from erythromycin with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. This allows once-daily administration for 3-5 days of treatment compared with traditional multi dosing 7-10-day treatment regimens. It has been successfully employed in lower respiratory tract infections. Recent data indicate that azithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of azithromycin in lower respiratory tract infections analysing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and cystic fibrosis both in adults and children. In addition, pharmacokinetic and pharmacodynamic properties of the drug are also considered.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bronchitis, Chronic; Child; Community-Acquired Infections; Cystic Fibrosis; Drug Administration Schedule; Drug Resistance, Bacterial; Haemophilus influenzae; Humans; Multicenter Studies as Topic; Pneumonia, Bacterial; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Streptococcus pneumoniae

The rationale for the use of high-dose, short-course azithromycin treatment regimens is based on the pharmacokinetic properties of azithromycin. Its long elimination half-life (approximately 60 h) and antibacterial potency make short-course (1-day) regimens feasible. Azithromycin is concentrated within phagocytic cells, which deliver it in a targeted manner to sites of infection. In vitro and in vivo models demonstrate that azithromycin is taken up, transported and released at the sites of infection by polymorphonuclear neutrophils and macrophages. Uptake is not saturable, so delivery of the total azithromycin therapeutic regimen as a single dose of azithromycin microspheres should lead to increased uptake and delivery of the drug to sites of infection. By achieving higher drug concentrations at the site of infection, a single, high dose of azithromycin microspheres should maximize efficacy. The new microsphere formulation allows for 'front loading' of the dose to achieve the highest drug levels early in the course of infection while maintaining favorable tolerability.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Half-Life; Humans; Microspheres; Phagocytes; Respiratory Tract Infections

The rationale for the use of single dose and shorter course azithromycin treatment regimens is based on the pharmacokinetic properties of azithromycin. The drug has a long elimination half-life (>50 h), which enables short course 1- or 3-day dose regimens to be clinically effective. Azithromycin is concentrated within phagocytic cells and tissues and it achieves targeted delivery by these cells to sites of infection. In vitro and in vivo models have demonstrated that azithromycin is taken up, transported and released at the sites of infection by phagocytic cells such as polymorphonuclear neutrophils and macrophages. Uptake is not saturable; therefore delivery of the total dose of azithromycin as a 1- or 3-day regimen should lead to increased uptake and delivery of the drug to sites of infection.

Topics: Azithromycin; Biological Availability; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Maximum Tolerated Dose; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Risk Assessment; Treatment Outcome

Oral azithromycin suspension has been prescribed to >80 million patients. Children find the color and taste of the oral suspension of azithromycin agreeable, and the drug is well-tolerated. On average 9% of patients have treatment-related adverse events, which are most frequently gastrointestinal complaints. The side effects are mild to moderate and very seldom necessitate withdrawal of the treatment. In addition to the conventional 3-day 10-mg/kg/day regimen and the 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5 regimens, single dose 30 mg/kg and 3-day 20-mg/kg/day regimens are well-tolerated, although these new dosages are associated with more adverse effects.

Topics: Administration, Oral; Adolescent; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Male; Maximum Tolerated Dose; Otitis Media; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Outcome

Topics: Acute Disease; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Pharyngitis; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Severity of Illness Index; Treatment Outcome

To describe the pharmacology, efficacy, and safety data of the use of single-dose azithromycin for respiratory tract infections in children and adults.. A MEDLINE search (1990-September 2003) was performed to identify all pertinent studies and review articles. When appropriate information was not available in the literature, data were obtained from the product manufacturers or abstracts from international conferences.. All available studies were reviewed to provide pharmacokinetic, pharmacodynamic, efficacy, and safety data on use of single-dose azithromycin for respiratory tract infections.. Several studies have demonstrated that shorter regimens of azithromycin (1500 mg over 3 day vs 5 day or single dose vs 3 day) provide higher serum exposures compared with the longer regimens. This makes it possible to give the same dose over a shorter period of time and achieve the same efficacy with the potential for enhanced adherence. Single-dose azithromycin 30 mg/kg was approved in 2003 for treatment of acute otitis media (AOM) in children. Studies have demonstrated that, when administering azithromycin as a single dose, its efficacy and safety are comparable to that of other standard regimens for AOM. Single-dose regimens for treatment of respiratory tract infections in adults have not been studied widely, with only 2 studies being conducted for treatment of community-acquired pneumonia and one study for treatment of tonsillitis; all demonstrated at least equal efficacy with the single-dose regimen compared with comparators given for longer periods of time.. Available data regarding single-dose azithromycin are promising. Although use of this regimen in children is warranted based on studies to date, additional large-scale trials are needed prior to mainstream use of the regimen in adults.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Community-Acquired Infections; Humans; Otitis Media; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Safety

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Biological Availability; Child; Clarithromycin; Clinical Trials as Topic; Half-Life; Humans; Intestinal Absorption; Macrolides; Respiratory Tract Infections; Skin Diseases, Bacterial

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; History, 20th Century; Humans; Japan; Lung Neoplasms; Respiratory Tract Infections

Azithromycin is the sole member of the macrolide sub-class, the azalides. Due to its altered chemical structure, azithromycin is characterized by a broader spectrum of activity, lower incidence of adverse events and drug interactions and a pharmacokinetic profile, that is in contrast to existing macrolides. Because of its high and prolonged cellular and tissue concentrations, patients are able to complete a course of azithromycin within a shorter timeframe as compared to other antibiotics. Azithromycin is widely used in the treatment of adult and pediatric respiratory tract infections. Continued research into azithromycin's utility has resulted in indication development for several devastating infections such as trachoma. Large-scale studies of its activity against Chlamydia pneumoniae related atherosclerosis are underway.

Topics: Adult; Anti-Bacterial Agents; Arteriosclerosis; Azithromycin; Bacteria; Child; Chlamydia Infections; Chlamydophila pneumoniae; Drug Resistance, Microbial; Humans; Respiratory Tract Infections; Trachoma

The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced-generation' macrolides compared with erythromycin, the first macrolide used clinically as an antibiotic. Their pharmacokinetics are characterized by a combination of low serum concentrations, high tissue concentrations and, in the case of azithromycin, an extended tissue elimination half-life. Azithromycin is particularly noted for high and prolonged concentrations at the site of infection. This allows once-daily dosing for 3 days in the treatment of respiratory tract infections, in contrast to longer dosage periods required for erythromycin, clarithromycin, roxithromycin and agents belonging to other classes of antibiotics. The spectrum of activity of the advanced-generation macrolides comprises Gram-positive, atypical and upper respiratory anaerobic pathogens. Azithromycin and the active metabolite of clarithromycin also demonstrate activity against community-acquired Gram-negative organisms, such as Haemophilus influenzae. Advanced-generation macrolides, and in particular azithromycin, are highly concentrated within polymorphonuclear leucocytes, which gravitate by chemotactic mechanisms to sites of infection. Following phagocytosis of the pathogens at the infection site, they are exposed to very high, and sometimes cidal, intracellular concentrations of antibacterial agent. Pharmacodynamic models and susceptibility breakpoints derived from studies with other classes of drugs, such as the beta-lactams and aminoglycosides, do not adequately explain the clinical utility of antibacterial agents that achieve high intracellular concentrations. In the case of azithromycin, attention should focus on tissue pharmacokinetic and pharmacodynamic concepts.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Drug Design; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections; Tissue Distribution

We carried out a meta-analysis of randomized controlled trials comparing 3-5 days of azithromycin with other antibiotics that are typically given in longer courses for the treatment of upper respiratory tract infections. For acute otitis media (19 comparisons including 3421 patients), acute sinusitis (11 comparisons including 1742 patients) and acute pharyngitis (16 comparisons including 2447 patients), azithromycin had similar clinical failure rates to the other antibiotics [random effects odds ratios 1.12, 95% confidence interval (CI) 0.81-1.54; 0.91, 95% CI 0.60-1.39; and 1.07, 95% CI 0.59-1.94, respectively]. The difference in clinical failures was <0.5%, and no 95% CIs exceeded 2.0%. There was no heterogeneity between studies. Subtle differences between comparators could have been due to chance. There were no significant differences in bacteriological outcomes. Azithromycin was discontinued because of adverse events in only 37 of 4870 (0.8%) patients. Short courses of azithromycin are as effective as longer courses of other antibiotics for upper respiratory tract infections. Convenience of dosing should be balanced against the increased cost of this regimen for the treatment of these common infections, where often no antibiotic may be indicated at all.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Chi-Square Distribution; Confidence Intervals; Humans; Odds Ratio; Otitis Media; Pharyngitis; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sinusitis

We carried out a meta-analysis of randomized controlled trials of azithromycin compared with other antibiotics in the treatment of lower respiratory tract infections, including acute bronchitis (five comparisons including 1372 patients), acute exacerbations of chronic bronchitis (13 comparisons including 1342 patients) and community-acquired pneumonia (18 comparisons with 1664 patients). For the first two indications, azithromycin did not offer any statistically significant reduction in clinical failures [random effects odds ratios 0.84, 95% confidence interval (CI) 0.54-1.31 and 0.64, 95% CI 0.31-1.32, respectively] and absolute risk differences were small. For community-acquired pneumonia, azithromycin significantly reduced clinical failures by about one-third (random effects odds ratio 0.63, 95% CI 0.41-0.95). The absolute incremental benefit was approximately one clinical failure prevented per 50 treated patients with community-acquired pneumonia. There was no significant heterogeneity for different comparators and for bacterial versus atypical pneumonias. Azithromycin was discontinued because of adverse events in only 23 of 3487 patients (0.7%). Although results should be interpreted cautiously as most trials were open-label and susceptible to bias, the meta-analysis indicates that, compared with antibiotics with traditional pharmacokinetics that require more prolonged courses, azithromycin offers no significant advantage for bronchitis, but may be more effective in community-acquired pneumonia.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchitis; Chi-Square Distribution; Chronic Disease; Community-Acquired Infections; Confidence Intervals; Humans; Odds Ratio; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Azithromycin(AZM), an azalide macrolide with a 15-membered ring, is superior in cell/tissue penetration. Sustained pulmonary tissue concentrations are maintained which are higher than various MICs for major respiratory pathogens. Much research and clinical investigation has been done to evaluate the clinical efficacy of azithromycin abroad. In Japan, an optimal dose-finding pneumonia study was started in January, 1993, and a controlled comparative pneumonia study with clarithromycin was started in December of the same year. Patient compliance was excellent with the 3-day once daily regimen of AZM(500 mg). Azithromycin has been demonstrated to be highly clinically useful based on high efficacy (including the elderly population) and an established safety profile.

Topics: Anti-Bacterial Agents; Azithromycin; Clinical Trials as Topic; Humans; Patient Compliance; Respiratory Tract Infections; Treatment Outcome

An extended elimination half-life and good tissue penetration enable oral azithromycin to attain high and prolonged concentrations in infected tissues, yielding high antibacterial activity in vivo. It has been suggested, however, that prolonged subinhibitory concentrations of azithromycin from 2 to 4 weeks after therapy may lead to the emergence of azithromycin resistance in vivo, compared with other macrolide antibiotics. Data from two types of in vitro susceptibility studies, an animal tissue infection model, and a clinical pediatric study demonstrate that prolonged tissue concentrations of azithromycin are unlikely to lead to the emergence of resistance in the clinical setting. Further, data from in vitro susceptibility studies indicate that resistance to macrolides, and azithromycin in particular, is significantly over-estimated for bacterial strains incubated in the presence of CO2.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Carbon Dioxide; Child; Clinical Trials as Topic; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections; Streptococcus

The macrolide class of antibiotics is well established and often recommended for use in the treatment of community-acquired respiratory tract infection (RTI). The newer agents clarithromycin and azithromycin are frequently prescribed as first- or second-line therapy, and have been considered as superior to erythromycin in microbiological activity and clinical efficacy. In-vitro data show that clarithromycin and azithromycin have good activity (MIC < or = 0.5 microg/ml) against certain RTI pathogens. However the activity of both compounds is intrinsically low against Haemophilus influenzae whilst several other important RTI pathogens - notably Streptococcus pneumoniae and Streptococcus pyogenes - exhibit a high prevalence of resistance to them. In many countries, the prevalence of resistance to clarithromycin and azithromycin is still rising with cross resistance with erythromycin. Maximum serum concentrations of clarithromycin and azithromycin are lower than the MIC90s for these agents against H. influenzae and S. pneumoniae. Concentrations in tissues have been reported to be much higher than those in serum. However, the high concentrations observed in tissues are largely a reflection of high concentrations inside cells. Concentrations of clarithromycin and azithromycin in extracellular tissue fluids, where Haemophilus and streptococci are located, are in equilibrium with concentrations in the serum, and remain low. It has been suggested that phagocytes deliver azithromycin to infection sites in a targeted fashion, but the evidence in support of this hypothesis is weak. Recent clinical experience with clarithromycin and azithromycin is consistent with preclinical results, and suggests that these agents have limited efficacy against certain respiratory infections. Clarithromycin and azithromycin are the first choice treatment of atypical infections caused by intracellular pathogens. For community-acquired RTIs, where H. influenzae and S. pneumoniae are present, they may no longer be an appropriate choice for first-line therapy. Indeed, in areas where levels of drug resistant S. pneumoniae are high, their use may be questionable as second-line therapy.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Community-Acquired Infections; Drug Resistance, Microbial; Global Health; Humans; Respiratory Tract Infections

Azithromycin is an azalide antimicrobial agent active in vitro against major pathogens responsible for infections of the respiratory tract, skin and soft tissues in children. Pathogens that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp., Streptococcus pyogenes and Streptococcus agalactiae. Azithromycin is also generally active against erythromycin- and penicillin-susceptible Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus. Azithromycin is administered once daily, achieves clinically relevant concentrations at sites of infection, is slowly eliminated from the body and has few drug interactions. In children, azithromycin is usually given as either a 3-day course of 10 mg/kg/day or a 5-day course with 10 mg/kg on the first day, followed by 5 mg/kg/day for a further 4 days. These standard regimens were as effective as amoxicillin/clavulanic acid, clarithromycin, cefaclor and amoxicillin in the treatment of children with otitis media. Azithromycin was also as effective as either phenoxymethylpenicillin (penicillin V), erythromycin, clarithromycin or cefaclor against streptococcal pharyngitis or tonsillitis in children, but appears to result in more recurrence of infection than phenoxymethylpenicillin in this indication, necessitating a dosage of 12 mg/kg/day for 5 days. Community-acquired pneumonia, bronchitis and other respiratory tract infections in children responded as well to azithromycin as to amoxicillin/clavulanic acid, cefaclor, erythromycin or josamycin. Azithromycin was similar or superior to ceftibuten in mixed general practice populations of patients. However, symptoms of lower respiratory tract infections resolved more rapidly with azithromycin than with erythromycin, josamycin or cefaclor. Skin and soft tissue infections responded as well to azithromycin as to cefaclor, dicloxacillin or flucloxacillin, and oral azithromycin was as effective as ocular tetracycline in treating trachoma. Although not as well tolerated as phenoxymethylpenicillin in the treatment of streptococcal pharyngitis, azithromycin is at least as well tolerated as most other agents used to treat respiratory tract and other infections in children and was better tolerated than amoxicillin/clavulanic acid. Adverse events that do occur are mostly gastrointestinal and tend to be mild. Azithromycin is an effective and well tolerated alternative to first-line agents in the treatment of respiratory tract, skin and soft tissue infections in children, offerring the convenience of a short, once-daily regimen.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Drug Tolerance; Humans; Infant; Otitis Media; Pharyngitis; Respiratory Tract Infections; Streptococcal Infections; Tonsillitis

In vitro susceptibility testing has demonstrated good activity of the azalide azithromycin and the macrolide clarithromycin against Gram-positive and -negative pathogens as well as atypical organisms involved in the etiology of upper and lower respiratory tract infections. One difference between these drugs in terms of their antimicrobial spectrum is the activity of azithromycin against Haemophilus influenzae. This organism is 2 to 8 times more susceptible in vitro to azithromycin than to clarithromycin or to erythromycin, the prototypical macrolide antibiotic. A principal concern in the management of respiratory tract infections today is the emergence of penicillin-resistant strains of Streptococcus pneumoniae. Both azithromycin and clarithromycin are active against penicillin-susceptible S. pneumoniae, although the activity of azithromycin is somewhat less than that of erythromycin and clarithromycin. Results of susceptibility testing of resistant organisms have varied among centers; in some areas all of the intermediately and some of the highly penicillin-resistant S. pneumoniae isolates are susceptible to the newer macrolides, whereas in other areas they are not. High tissue antibiotic concentrations achieved with these drugs may contribute to their effectiveness against some of the resistant S. pneumoniae isolates.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Clarithromycin; Ear, Middle; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Penicillin Resistance; Respiratory Tract Infections; Streptococcal Infections; Streptococcus pneumoniae

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.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Interactions; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections

To review the clinical microbiology and therapeutic use of dirithromycin, emphasizing comparative data between dirithromycin and the standard macrolide erythromycin, as well as clarithromycin and azithromycin.. A MEDLINE search of English-language literature during the years 1966-1996, and an extensive review of journals were conducted to prepare this article.. The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open and controlled studies. Controlled single- or double-blind studies were evaluated to assess the efficacy of dirithromycin in the treatment of various upper and lower respiratory tract infections, as well as skin and soft tissue infections.. The spectrum of activity of dirithromycin is similar to that of erythromycin, clarithromycin, or azithromycin, with some notable exceptions. Dirithromycin was more active in vitro against Campylobacter jejuni and Borrelia burgdorferi than was erythromycin or clarithromycin, but in general demonstrated less activity than erythromycin, clarithromycin, or azithromycin against a majority of microorganisms. The pharmacokinetic profile of dirithromycin offers the advantages of once-daily dosing and high and prolonged tissue concentrations; dosing adjustments are not needed in the elderly or in patients with renal or mild hepatic impairment. Clinical efficacy and bacteriologic eradication rates with dirithromycin and erythromycin are comparable for the treatment of respiratory and skin and soft tissue infections due to susceptible pathogens. Dirithromycin appears to have adverse effect profiles similar to those of the other macrolides, with reported problems most often related to the gastrointestinal tract. Dirithromycin does not seem to cause clinically important interactions with drugs such as theophylline, oral contraceptives, cyclosporine, or terfenadine.. Dirithromycin offers some attractive pharmacokinetic properties. The long elimination half-life of dirithromycin allows once-daily dosing and higher and more prolonged tissue concentrations than are achievable with erythromycin. The spectrum of activity, adverse effect profile, clinical efficacy, and bacteriologic eradication rate of dirithromycin may be similar to those of erythromycin. No significant drug interactions with dirithromycin have been reported. Based on available data, dirithromycin may not offer any unique clinical advantage over clarithromycin or azithromycin. Future clinical trials may reveal a special role for dirithromycin in patient care.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria, Anaerobic; Clarithromycin; Drug Interactions; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Macrolides; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Azithromycin; Child; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections

Azithromycin and clarithromycin are structural analogues of erythromycin that have similar mechanisms of action. The newer macrolides have several distinct advantages over erythromycin, including improved oral bioavailability; longer half-life, allowing once or twice daily administration; higher tissue concentrations; and fewer gastrointestinal adverse effects. Clarithromycin and azithromycin also have enhanced antimicrobial activity. The clinical efficacy of the newer macrolides has been similar to erythromycin for the treatment of upper and lower respiratory tract and skin and soft tissue infections. New therapeutic roles include the use of azithromycin for C. trachomatis infections and the inclusion of clarithromycin or azithromycin as part of therapeutic regimens for disseminated MAC infections in HIV-infected patients. Further clinical trials are needed to determine the optimal roles for and uses of these new macrolides.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Microbial; Humans; Respiratory Tract Infections

Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the abov

Topics: Animals; Azithromycin; Bacterial Infections; Biological Availability; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Intestinal Absorption; Microbial Sensitivity Tests; Respiratory Tract Infections; Sexually Transmitted Diseases; Tissue Distribution

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

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.

Topics: Azithromycin; Clarithromycin; Drug Interactions; Erythromycin; Humans; Respiratory Tract Infections

Azithromycin is a new azalide antimicrobial agent which has a broad spectrum of activity against common lower respiratory tract pathogens including pneumococci, staphylococci, Legionella species, Mycoplasma and Chlamydia species. In particular, it is more active against Haemophilus influenzae than other macrolides. In comparison to other new macrolides, azithromycin achieves higher tissue and intracellular concentrations and these concentrations are sustained for several days after dosing due to a long elimination half-life. The efficacy of azithromycin against lower respiratory tract infections has been proven in several clinical studies. Once-daily dosing with azithromycin, over a 3- or 5- day period was as effective as a 10-day course of other commonly used antibiotics such as amoxycillin/clavulanic acid, erythromycin or cefaclor in lower respiratory tract infections. Azithromycin short-course therapy may offer an advantage in terms of patient compliance and the duration of treatment.

Topics: Animals; Azithromycin; Erythromycin; Humans; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin.. We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 days were eligible for enrolment. Participants with a procalcitonin concentration of 0·25 ng/mL or less were randomly assigned (1:1), in blocks of four with stratification by site, to receive over-encapsulated oral azithromycin 250 mg or matching placebo (two capsules on day 1 followed by one capsule daily for 4 days). Participants, non-study clinical providers, investigators, and study coordinators were masked to treatment allocation. The primary outcome was efficacy of azithromycin versus placebo in terms of clinical improvement at day 5 in the intention-to-treat population. The non-inferiority margin was -12·5%. Solicited adverse events (abdominal pain, vomiting, diarrhoea, allergic reaction, or yeast infections) were recorded as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT03341273.. Between Dec 8, 2017, and March 9, 2020, 691 patients were assessed for eligibility and 499 were enrolled and randomly assigned to receive azithromycin (n=249) or placebo (n=250). Clinical improvement at day 5 was observed in 148 (63%, 95% CI 54 to 71) of 238 participants with full data in the placebo group and 155 (69%, 61 to 77) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis (between-group difference -6%, 95% CI -15 to 2). The 95% CI for the difference did not meet the non-inferiority margin. Solicited adverse events and the severity of solicited adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (47 [23%, 95% CI 18 to 29] of 204 participants) compared with placebo (35 [16%, 12 to 21] of 221; between-group difference -7% [95% CI -15 to 0]; p=0·066).. Placebo was not non-inferior to azithromycin in terms of clinical improvement at day 5 in adults with lower respiratory tract infection and a low procalcitonin concentration. After accounting for both the rates of clinical improvement and solicited adverse events at day 5, it is unclear whether antibiotics are indicated for patients with lower respiratory tract infection and a low procalcitonin concentration.. National Institute of Allergy and Infectious Diseases, bioMérieux.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Humans; Procalcitonin; Respiratory Tract Infections; Treatment Outcome

Recurrent enteric infections and micronutrient deficiencies, including deficiencies in the tryptophan-kynurenine-niacin pathway, have been associated with environmental enteric dysfunction, potentially contributing to poor child growth and development. We are conducting a randomized, placebo-controlled, 2 × 2 factorial interventional trial in a rural population in Haydom, Tanzania, to determine the effect of 1) antimicrobials (azithromycin and nitazoxanide) and/or 2) nicotinamide, a niacin vitamer, on attained length at 18 months. Mother/infant dyads were enrolled within 14 days of the infant's birth from September 2017 to September 2018, with the follow-up to be completed in February 2020. Here, we describe the baseline characteristics of the study cohort, risk factors for low enrollment weight, and neonatal adverse events (AEs). Risk factors for a low enrollment weight included being a firstborn child (-0.54 difference in weight-for-age

Topics: Adult; Azithromycin; Body Weight; Child Health; Child Nutrition Disorders; Child, Preschool; Cohort Studies; Early Medical Intervention; Female; Humans; Infant; Infant, Newborn; Male; Mothers; Neonatal Sepsis; Niacinamide; Nitro Compounds; Poverty; Respiratory Tract Infections; Rural Population; Seasons; Surveys and Questionnaires; Tanzania; Thiazoles; Young Adult

HIV-associated chronic lung disease (HCLD) in children is associated with small airways disease, is common despite antiretroviral therapy (ART), and is associated with substantial morbidity. Azithromycin has antibiotic and immunomodulatory activity and may be effective in treating HCLD through reducing respiratory tract infections and inflammation.. To determine whether prophylactic azithromycin is effective in preventing worsening of lung function and in reducing acute respiratory exacerbations (AREs) in children with HCLD taking ART.. This double-blind, placebo-controlled, randomized clinical trial (BREATHE) was conducted between 2016 and 2019, including 12 months of follow-up, at outpatient HIV clinics in 2 public sector hospitals in Malawi and Zimbabwe. Participants were randomized 1:1 to intervention or placebo, and participants and study personnel were blinded to treatment allocation. Participants included children aged 6 to 19 years with perinatally acquired HIV and HCLD (defined as forced expiratory volume in 1 second [FEV1] z score < -1) who were taking ART for 6 months or longer. Data analysis was performed from September 2019 to April 2020.. Once-weekly oral azithromycin with weight-based dosing, for 48 weeks.. All outcomes were prespecified. The primary outcome was the mean difference in FEV1 z score using intention-to-treat analysis for participants seen at end line. Secondary outcomes included AREs, all-cause hospitalizations, mortality, and weight-for-age z score.. A total of 347 individuals (median [interquartile range] age, 15.3 [12.7-17.7] years; 177 boys [51.0%]) were randomized, 174 to the azithromycin group and 173 to the placebo group; 162 participants in the azithromycin group and 146 placebo group participants had a primary outcome available and were analyzed. The mean difference in FEV1 z score was 0.06 (95% CI, -0.10 to 0.21; P = .48) higher in the azithromycin group than in the placebo group, a nonsignificant difference. The rate of AREs was 12.1 events per 100 person-years in the azithromycin group and 24.7 events per 100 person-years in the placebo groups (hazard ratio, 0.50; 95% CI, 0.27 to 0.93; P = .03). The hospitalization rate was 1.3 events per 100 person-years in the azithromycin group and 7.1 events per 100 person-years in the placebo groups, but the difference was not significant (hazard ratio, 0.24; 95% CI, 0.06 to 1.07; P = .06). Three deaths occurred, all in the placebo group. The mean weight-for-age z score was 0.03 (95% CI, -0.08 to 0.14; P = .56) higher in the azithromycin group than in the placebo group, although the difference was not significant. There were no drug-related severe adverse events.. In this randomized clinical trial specifically addressing childhood HCLD, once-weekly azithromycin did not improve lung function or growth but was associated with reduced AREs; the number of hospitalizations was also lower in the azithromycin group but the difference was not significant. Future research should identify patient groups who would benefit most from this intervention and optimum treatment length, to maximize benefits while reducing the risk of antimicrobial resistance.. ClinicalTrials.gov Identifier: NCT02426112.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Drug Dosage Calculations; Female; HIV Infections; Hospitalization; Humans; Male; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Treatment Outcome

Intermittent preventive treatment in pregnancy (IPTp) with azithromycin and monthly sulfadoxine-pyrimethamine increased the mean child weight, mid-upper arm and head circumference at four weeks of age in a rural low-income setting. Now we assess for how long these gains were sustained during 0-5 years of age.. We enrolled 1320 pregnant Malawian women in a randomized trial and treated them with two doses of sulfadoxine-pyrimethamine (control) or monthly sulfadoxine-pyrimethamine as IPTp against malaria, or monthly sulfadoxine-pyrimethamine and two doses of azithromycin (AZI-SP) as IPTp against malaria and reproductive tract infections. Child weight, mid-upper arm circumference, head circumference and weight-for-height Z-score were recorded at one, six, 12, 24, 36, 48, and 60 months.. Throughout follow-up, the mean child weight was approximately 100 g higher (difference in means 0.12 kg, 95% CI 0.04-0.20, P = 0.003 at one month; 0.19 kg, 95% CI 0.05-0.33, P = 0.007, at six months), mean head circumference 2 mm larger (0.3 cm, 95% CI 0.1 to 0.5, P = 0.004 at one month) and the cumulative incidence of underweight by five years of age was lower (hazard ratio 0.74, 95% CI 0.60 to 0.90, P = 0.002) in the AZI-SP group than in the control group. The 2 mm difference in the mean mid-upper arm circumference at one month (0.2 cm, 95% CI 0.0 to 0.3, P = 0.007) disappeared after three years of age. There was no difference in mean weight-for-height Z-score at any time point.. In Malawi, IPTp with azithromycin and monthly sulfadoxine-pyrimethamine has a modest, 3-5-year positive impact on child weight, mid-upper arm circumference and head circumference, but not on weight-for-height Z-score.

Topics: Adult; Anti-Bacterial Agents; Antimalarials; Arm; Azithromycin; Birth Weight; Child; Child, Preschool; Drug Combinations; Female; Follow-Up Studies; Head; Humans; Incidence; Infant; Infant, Newborn; Malaria; Malawi; Male; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pyrimethamine; Respiratory Tract Infections; Sulfadoxine

Clinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD. Maintenance therapy, with the macrolide antibiotic azithromycin, is currently widely used in chronic respiratory diseases including PCD. In addition to its antibacterial properties, azithromycin is considered to have beneficial anti-inflammatory and anti-quorum-sensing properties. The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory exacerbations in PCD. The secondary objectives are to evaluate the efficacy of azithromycin on lung function, ventilation inhomogeneity, hearing impairment, and symptoms (respiratory, sinus, ears and hearing) measured on a PCD-specific health-related quality of life instrument, and to assess the safety of azithromycin maintenance therapy in PCD.. The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months. Subjects with a confirmed diagnosis of PCD, age 7-50 years, are eligible for inclusion. Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria are exclusion criteria. The planned number of subjects to be included is 125. The trial has been approved by the Research Ethics Committees of the participating institutions.. We present a study protocol of an ongoing RCT, evaluating for the first time, the efficacy and safety of a pharmacotherapeutic treatment for patients with PCD. The RCT evaluates azithromycin maintenance therapy, a drug already commonly prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment, and the patients' perception of disease severity and necessity of additional management and treatment during trial participation.. EudraCT 2013-004664-58 (date of registration: 2014-04-08).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Disease Progression; Double-Blind Method; Europe; Female; Humans; Kartagener Syndrome; Male; Middle Aged; Quality of Life; Regression Analysis; Research Design; Respiratory Tract Infections; Spirometry; Treatment Outcome; Vital Capacity; Young Adult

Recent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response. Macrolides have anti-inflammatory properties, including the ability to downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections, and may reduce virus-related exacerbations. In this study, we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade.. A randomised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3-6 months during two respiratory syncytial virus (RSV) seasons (2015-2016 and 2016-2017). We expect a reduction of at least 20% in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group. Standard frequentist and Bayesian analyses will be performed using an intent-to-treat approach.. We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidenced by a reduction in the total number of days with unscheduled face-to-face provider encounters.. This research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014. On completion, the results will be published.. NCT02544984.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chronic Disease; Clinical Protocols; Double-Blind Method; Female; Humans; Infant; Lung Diseases; Macrolides; Male; Pre-Exposure Prophylaxis; Quality of Life; Respiratory Tract Infections; Texas; Treatment Outcome

The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg(0.75), 1.88 liters · kg, 1.79 liters/h · kg(0.75), and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼ 4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating Ureaplasma spp. from the preterm respiratory tract.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; Bronchopulmonary Dysplasia; Cytokines; Humans; Infant; Infant, Newborn; Infant, Premature; Inflammation; Microbial Sensitivity Tests; Nonlinear Dynamics; Respiratory Tract Infections; Treatment Outcome; Ureaplasma; Ureaplasma Infections

A cluster-randomized trial demonstrated that mass oral azithromycin distribution reduced childhood mortality 49.6% (Trachoma Amelioration in Northern Amhara [TANA]). The relative risk of childhood mortality was then estimated using two approaches: an expert survey and a Bayesian analysis. The survey asked public health experts to estimate the true effect of mass azithromycin distribution on childhood mortality. The Bayesian estimation used the TANA study's results and prior estimates of the efficacy of other effective population-level interventions. The experts believed mass azithromycin reduces childhood mortality (relative risk = 0.83, 95% credible intervals [CrI] = 0.70-1.00). The Bayesian analysis estimated a relative risk of 0.71 (95% CrI = 0.39-0.93). Both estimates suggest that azithromycin may have a true mortality benefit, though of a smaller magnitude than found in the single available trial. Prior information about nonantibiotic, population-level interventions may have informed the expert's opinions. Additional trials are needed to confirm a mortality benefit from mass azithromycin.

Topics: Administration, Oral; Africa South of the Sahara; Anti-Bacterial Agents; Azithromycin; Bayes Theorem; Child, Preschool; Cluster Analysis; Diarrhea; Humans; Infant; Malaria; Respiratory Tract Infections; Surveys and Questionnaires; Trachoma; Treatment Outcome

The aim of this study was to describe clinical effectiveness of azithromycin in the management of lower respiratory tract infections in daily clinical practice, to examine duration of symptoms after therapy initiation, and to record any possible adverse effects of azithromycin treatment. A total of 153 patients were included in the analysis of the effectiveness of azithromycin: 94 patients with community acquired pneumonia (CAP) and 59 with acute exacerbation of chronic bronchitis (AECB). Clinical effectiveness was assessed as improvement, cure or failure after three-day treatment with azithromycin. The assessment was based on a calculation of clinical score for each diagnosis before treatment and on days 4, 10 and 28 after treatment initiation. Clinical effectiveness of azithromycin was 93.6% in CAP group and 94.9% in AECB group. Azithromycin led to relief of symptoms within three days in 88.6% of CAP patients and 77.2% of AECB patients. Overall, 15 adverse events were reported in 14 (9.1%) patients. The most common adverse events were abdominal pain, diarrhea and vomiting, each reported in four (2.6%) patients. Accordingly, azithromycin was found to have high clinical effectiveness and a small number of adverse events in the treatment of lower respiratory tract infections. ISRCTN38391551.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Respiratory Tract Infections; Treatment Outcome; Young Adult

Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed.. To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes.. A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment.. Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child's signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period.. The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures.. A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed.. Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy.. clinicaltrials.gov Identifier: NCT01272635.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Disease Progression; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Recurrence; Respiratory Tract Infections; Secondary Prevention

Current definitions of pulmonary exacerbation (PE) in cystic fibrosis are based on studies in participants with significant lung disease and may not reflect the spectrum of findings observed in younger patients with early lung disease.. We used data from a recent trial assessing the efficacy of azithromycin in children to study signs and symptoms associated with PEs and related changes in lung function and weight.. While increased cough was present in all PEs, acute weight loss and reduction in oxygen saturation were not observed. Changes in lung function did not differ between subjects who did experience a PE and those who were exacerbation-free.. Cough was the predominant symptom in CF patients with early lung disease experiencing a PE. There was no significant difference in mean 6-month change in lung function or weight among subjects with one or more exacerbations and those without an exacerbation.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Cough; Cystic Fibrosis; Disease Progression; Double-Blind Method; Female; Humans; Lung; Lung Diseases; Male; Middle Aged; Respiratory Function Tests; Respiratory Tract Infections

Chloroquine-azithromycin is being evaluated as combination therapy for malaria. It may provide added benefit in treating or preventing bacterial infections that occur in children with malaria.. We aim to evaluate the effect of treating clinical malaria with chloroquine-azithromycin on the incidence of respiratory-tract and gastrointestinal-tract infections compared to treatment with chloroquine monotherapy.. We compared the incidence density and time to first events of respiratory-tract and gastrointestinal-tract infections among children assigned to receive chloroquine-azithromycin or chloroquine for all symptomatic malaria episodes over the course of 1 year in a randomized longitudinal trial in Blantyre, Malawi.. The incidence density ratios of total respiratory-tract infections and gastrointestinal-tract infections comparing chloroquine-azithromycin to chloroquine monotherapy were 0.67 (95% confidence interval [CI], .48, .94) and 0.74 (95% CI, .55, .99), respectively. The time to first lower-respiratory-tract and gastrointestinal-tract infections were significantly longer in the chloroquine-azithromycin arm compared to the chloroquine arm (P = .04 and P = .02, respectively).. Children treated routinely with chloroquine-azithromycin had fewer respiratory and gastrointestinal-tract infections than those treated with chloroquine alone. This antimalarial combination has the potential to reduce the burden of bacterial infections among children in malaria-endemic countries.

Topics: Antimalarials; Azithromycin; Child, Preschool; Chloroquine; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Incidence; Longitudinal Studies; Malaria; Malawi; Male; Respiratory Tract Infections; Risk

Macrolide antibiotics have been shown beneficial in cystic fibrosis (CF) and diffuse panbronchiolitis, and earlier findings also suggest a benefit in non-CF bronchiectasis.. To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis.. The BAT (Bronchiectasis and Long-term Azithromycin Treatment) study, a randomized, double-blind, placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherlands among 83 outpatients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year.. Azithromycin (250 mg daily) or placebo for 12 months.. Number of infectious exacerbations during 12 months of treatment. Secondary end points included lung function, sputum bacteriology, inflammatory markers, adverse effects, symptom scores, and quality of life.. Forty-three participants (52%) received azithromycin and 40 (48%) received placebo and were included in the modified intention-to-treat analysis. At end of study, the median number of exacerbations in the azithromycin group was 0 (interquartile range [IQR], 0-1), compared with 2 (IQR, 1-3) in the placebo group (P < .001). Thirty-two (80%) placebo-treated vs 20 (46%) azithromycin-treated individuals had at least 1 exacerbation (hazard ratio, 0.29 [95% CI, 0.16-0.51]). In a mixed-model analysis, change in forced expiratory volume in the first second of expiration (percent of predicted) over time differed between groups (F1,78.8 = 4.085, P = .047), with an increase of 1.03% per 3 months in the azithromycin group and a decrease of 0.10% per 3 months in the placebo group. Gastrointestinal adverse effects occurred in 40% of patients in the azithromycin group and in 5% in the placebo group (relative risk, 7.44 [95% CI, 0.97-56.88] for abdominal pain and 8.36 [95% CI, 1.10-63.15] for diarrhea) but without need for discontinuation of study treatment. A macrolide resistance rate of 88% was noted in azithromycin-treated individuals, compared with 26% in the placebo group.. Among adults with non-CF bronchiectasis, the daily use of azithromycin for 12 months compared with placebo resulted in a lower rate of infectious exacerbations. This could result in better quality of life and might influence survival, although effects on antibiotic resistance need to be considered.. clinicaltrials.gov Identifier: NCT00415350.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Biomarkers; Bronchiectasis; Double-Blind Method; Drug Resistance, Bacterial; Female; Humans; Inflammation; Lung; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Respiratory Tract Infections; Sputum

To describe clinical effectiveness of azithromycin in the management of respiratory tract infections in children up to 12 years of age; to examine duration of symptoms after commencement of therapy and to mark adverse events possibly caused by treatment with azithromycin.. The overall ITT population included 156 children (65 with acute pharyngitis/tonsillitis (AP), 32 with acute otitis media (AOM), and 59 with lower respiratory tract infections (LRTI)). Clinical effectiveness was based on results of improvement and cure after 3 day's treatment with azithromycin, calculating the clinical score for each diagnosis before treatment, at the 4th day (end of the therapy) and at the 12th or 28th day (end of the study). To better estimate patients' (parents') satisfaction with treatment, a diary was provided for each child and parents recorded the days when a child felt relief of symptoms.. In this study azithromycin led to relief of symptoms after 3 days in 89.1% of patients. Antibiotics had been prescribed within 1 year prior to inclusion in 74.4% of patients and 29.5% had previously been treated with macrolides. Clinical effectiveness in the intention-to-treat (ITT) population was 94.8% and there were 5.2% failures. Overall, 18 (11.5%) patients reported 25 adverse events (AEs) and nine AEs were characterized as possibly, probably or definitely related to azithromycin. The most common adverse events were diarrhea in nine (5.8%) cases, vomiting in six (3.8%) and abdominal pain reported in four (2.6 %) patients.. Results of this study show that azithromycin in the treatment of children with respiratory tract infections has high clinical effectiveness and a small number of adverse events. However, major limitations of the study are its design as a non-comparative, observational, postmarketing study and that the etiology of infections was not confirmed. Despite this, it can be concluded that azithromycin is a reliable antibiotic treatment for children's respiratory tract infections, giving fast resolution of symptoms with few adverse events in patients with presumed bacterial infections.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Male; Respiratory Tract Infections; Treatment Outcome

We evaluated the effect of a single mass distribution of azithromycin for trachoma on the risk of acute lower respiratory infection (ALRI) during a 6-month period among young children living in 8 communities in rural Tanzania.. In 8 communities, a cohort of randomly selected children (n = 1036) was followed for incidence of ALRI episodes. Mass treatment for trachoma using a single dose of oral azithromycin was provided in 4 of the 8 communities where trachoma prevalence was .10%. All children were followed with biweekly surveillance at home for 6 months. Incidence of ALRI episodes was calculated for 0 to 1 month, 1 to 3 months, and 3 to 6 months posttreatment and in comparable time points in the nontreated villages.. In the multivariate analysis, living in a MDA village was associated with a 38% (rate ratio 5 0.62, 95% confidence interval [CI] = 0.43-0.91) decreased risk of ALRI in the 0- to 1-month follow-up period as compared with those in the untreated communities after adjusting for covariates and clustering. There were no significant differences in ALRI incidence by exposure status in the 1- to 3-month (rate ratio = 0.91, 95% CI = 0.69-1.20) and in the 3- to 6-month (rate ratio = 1.00, 95% CI = 0.76-1.30) follow-up periods.. Mass distribution of a single dose of oral azithromycin for trachoma is associated with a significant short-term reduction in ALRI morbidity among young children.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Cohort Studies; Drug Therapy; Female; Humans; Incidence; Infant; Male; Prospective Studies; Respiratory Tract Infections; Trachoma

Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment.. The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment.. We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms.. http://www.clinicaltrials.gov NCT00985244.

Topics: Anti-Bacterial Agents; Azithromycin; Disease Progression; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Humans; Lung; Netherlands; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Research Design; Respiratory Tract Infections; Time Factors; Treatment Outcome

it is known that the efficacy of azithromycin, in animal infection models, is best correlated with AUC/MIC. The pharmacokinetic-pharmacodynamic (PK-PD) relationship for azithromycin, however, has not been previously confirmed with clinical data. The objectives of this PK-PD analysis were to characterize exposure-response relationships for the efficacy and safety of azithromycin extended release (ER) in Japanese patients, and to evaluate the effects of potential covariates on the prediction of response.. sparse serum azithromycin concentration, MIC, efficacy and safety data were collected from three Japanese Phase 3 studies of a 2 g single dose of azithromycin-ER for respiratory tract infections. These sparse concentration data were combined with data from eight Phase 1 PK studies in Japanese and Western populations, to develop a robust population PK model using a non-linear mixed effects approach. The exposure-response relationships for efficacy and safety were evaluated using logistic regression.. a two-compartment model with first-order absorption and first-order elimination with a lag time adequately described the PK of azithromycin-ER, without any significant ethnic differences in AUC. The percentage of bacteriological and clinical success in patients with AUC/MIC  >  5 (95.8% and 100%, respectively) was much higher than in those with AUC/MIC  ≤  5 (60.0% and 83.3%, respectively).. as expected, the probabilities of success in the clinical and bacteriological responses were positively associated with AUC/MIC, but not with AUC. For the exposure-safety relationship, the incidence of treatment-related diarrhoea was inversely associated with azithromycin exposure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asian People; Azithromycin; Bacteria; Bacterial Infections; Diarrhea; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Respiratory Tract Infections; Serum; Young Adult

Respiratory tract infection is a serious complication associated with bronchoscopic biopsy. This study attempted to examine its incidence and determine an efficacious therapy for preventing such infections.. Nine hundred and thirty patients who underwent bronchoscopic biopsy in Osaka City University Hospital outpatient clinic were enrolled in the study. All patients were randomly assigned to receive a 3-day course of azithromycin (500 mg/day), cefcapene pivoxil hydrochloride (300 mg/day) or no antibiotics. The primary outcome was the incidence of respiratory tract infection after bronchoscopic biopsy among the three groups.. In the no-treatment group, nine of the 310 patients (2.9%) had respiratory tract infection after bronchoscopic biopsy. All patients with infection had abnormal bronchoscopic findings. Of the patients with respiratory tract infection, 60% were in the no-treatment group, 26.7% in the cefcapene group and 13.3% in the azithromycin group. Although not statistically significant, the incidence in the azithromycin group (0.7%) was lower than in the no-treatment group (P = 0.06). Among the patients with abnormal bronchoscopic findings, the incidence in the azithromycin group was significantly lower than that in the no-treatment group (3.0% vs. 14.8%; P = 0.02). Moreover, maximum C-reactive protein values also appeared to be lower in the azithromycin group than in the no-treatment group and the cefcapene group.. A 3-day course of azithromycin administration is well tolerated and effective in preventing infection post bronchoscopy.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Biopsy; Bronchoscopy; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Staphylococcal Infections; Treatment Outcome

The aim of this study of 352 patients, 1-14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences.. The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates.. Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria.. Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.

Topics: Adolescent; Ambulatory Care Facilities; Azithromycin; Child; Child, Preschool; Chlamydophila Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Probability; Recurrence; Reference Values; Respiratory Tract Infections; Risk Assessment; Severity of Illness Index; Single-Blind Method; Treatment Outcome

Epidemics of community-acquired pneumonia (CAP) are a frequent cause of morbidity among Russian military trainees. We evaluated azithromycin prophylaxis against CAP. In 2001-2002, incoming military trainees were randomized to 1 of 3 trial arms by training group: azithromycin, 500 mg per week for 8 weeks (R1); azithromycin, 1500 mg once at enrollment (R2); or no therapy (R3). During the 22 weeks of training, CAP was diagnosed in 20.2% of 678 subjects in the R3 group, 8.6% of 508 subjects in the R1 group, and 10.3% of 507 subjects in the R2 group. Throat carriage cultures revealed that the proportion of Streptococcus pneumoniae isolates with resistance to macrolides correspondingly increased during the study, from 0% (all) to 40% (R1) and 22.6% (R2) by week 20. Azithromycin prophylaxis is effective against CAP in a healthy population of young men at transient high risk of disease; however, azithromycin use must be tempered with the possible concomitant risk of selection for resistant endemic pathogens.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Community-Acquired Infections; Humans; Male; Military Personnel; Prospective Studies; Respiratory Tract Infections; Risk Factors; Soft Tissue Infections

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).

Topics: Adolescent; Adult; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Bronchopneumonia; Humans; Male; Military Personnel; Respiratory Tract Infections

The efficacy and safety of azithromycin prophylaxis of community-acquired pneumonia (CAP) in young adults in a military training centre of the Ministry of Defence of the Russian Federation located in the Central European Region of Russia were studied. Two prophylactic regimens with azithromycin vs. the control were evaluated: azithromycin, 500 mg/w for 8 weeks (R1), azithromycin, 1500 mg once upon the enrolment (R2) and no drugs (R3). Nasopharyngeal carriage of Streptococcuspneumoniae and its susceptibility to antibacterials were estimated thrice: before the exposure, after the exposure within the 9th week and after the exposure within the 20th week. The MLS(B) phenotype was suspected when the isolates were resistant to erythromycin and clindamycin. During the observation period of 22 weeks CAP was diagnosed in 20.2% of 678 subjects in group R3, 8.6% of 508 subjects in group R1 (Risk Ratio =0.4, 95% Cl = 0.3-0.6) and 10.3% of 507 subjects in group R2 (Risk Ratio = 0.5, 95% Cl = 0.4-0.7). The S.pneumoniae carriage rate at visit 0 was 34-35%, within the 9th week it was 75, 66 and 50% (p<0.05) in groups R1, R2 and R3 respectively, and within the 20th week it was 69, 57 and 36% in the same groups (p<0.05). At visit 0 no macrolide resistance was detected in any of the 40 isolates tested. The background level of intermediate penicillin resistance was revealed in 0-14% of the isolates. Dramatic growth of macrolide resistance was observed within the 9th week in group R1 (95.7%, 44 resistant strains, Azithro+Clinda resistance in 37% of them) and in group R2 (89.5%, 34 resistant strains, Azithro+Clinda resistance in 11.9% of them). By the 20th week the resistance rate decreased up to 40 % (16 resistant strains, Azithro+Clinda resistance in 10% of them) in group R1 and up to 22.6% (7 resistant strains, Azithro+Clinda resistance in 5.4% of them) in group R2. As for penicillin resistance, no unfavourable shifts were detected. The study demonstrated the effectiveness of the azithromycin prophylaxis of CAP in healthy young men at high transient risk of the disease, as well as the possible risk for selection of resistant endemic pathogens.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Carrier State; Clindamycin; Community-Acquired Infections; Drug Resistance, Bacterial; Erythromycin; Humans; Microbial Sensitivity Tests; Military Personnel; Nasopharyngeal Diseases; Penicillins; Pneumococcal Infections; Respiratory Tract Infections; Russia; Streptococcus pneumoniae

Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance. During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin. No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001). There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio [OR], 0.41; 95% confidence interval [CI], 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment. The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given.

Topics: Anti-Bacterial Agents; Azithromycin; Blindness; Child; Child, Preschool; Chlamydia trachomatis; Drug Resistance, Bacterial; Female; Gastrointestinal Diseases; Humans; Infant; Male; Nepal; Respiratory Tract Infections; Streptococcus pneumoniae; Trachoma

Acute respiratory tract infection (ARTI) is the commonest reason for which antibiotics are prescribed, despite the fact that ARTI is mostly of viral origin. The effectiveness of antibiotics in these illnesses is, at best, questionable. Jordan is a developing country where bacterial infections are thought to be more common than in developed countries and initially viral illnesses are frequently superimposed by bacterial infections. The present study represents an attempt to assess whether routine antibiotic treatment of ARTI has any beneficial effect on the course of the illness. The study was conducted in northern Jordan between 1 June and December 14, 2000. Patients > or =8 y of age visiting either of 2 health centers and diagnosed by the physician with ARTI above the level of the bronchioles were assigned on an alternating basis to receive either azithromycin or placebo. Patients were assessed at their initial visit and were subsequently followed up after 3 d, 1 week and 2 weeks. A total of 185 patients were included in the study. Patients administered azithromycin or placebo did similarly in terms of the proportions improved or cured and the duration of illness. We conclude that routine use of antibiotics (azithromycin) in ARTI is unlikely to alter the course of the illness.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Female; Humans; Male; Middle Aged; Patient Compliance; Respiratory Tract Infections; Treatment Outcome

To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Infant; Male; Respiratory Tract Infections; Treatment Outcome

Military Special Forces trainees undergo intense psychological and physical stressors that often lead to respiratory infection. During 1998-2000, 477 Navy Special Forces trainees were enrolled in a double-blind trial of oral azithromycin (1 g given weekly) plus a placebo injection, compared with benzathine penicillin G (1.2 million U) plus azithromycin placebo tablets. Among the 464 subjects with complete data, 44 developed acute respiratory infection (20 with pneumonia) during the 2 weeks of most intense training; of these subjects, 12 (27.3%) had evidence of Chlamydia pneumoniae infection and 7 (15.9%) had evidence of Mycoplasma pneumoniae infection. Trainees who received azithromycin were less likely than were trainees who received benzathine penicillin G to develop acute respiratory infection (risk ratio, 0.50; 95% confidence interval [CI], 0.28-0.92) and less likely at the end of training to report episodes of breathing difficulty (odds ratio [OR], 0.59; 95% CI, 0.34-1.01) or sore throat (OR, 0.66; 95% CI, 0.41-1.05). Compared with benzathine penicillin G prophylaxis, weekly oral azithromycin was superior in preventing respiratory infection in this population at transient high risk.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Double-Blind Method; Humans; Male; Military Personnel; Mycoplasma pneumoniae; Penicillin G Benzathine; Penicillins; Pneumonia, Mycoplasma; Respiratory Tract Infections; Treatment Outcome

The aim of the present study was to assess the hypothesis that, when present in nasopharyngeal secretions, Streptococcus pneumoniae. Haemophilus influenzae, and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection. Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled. Participants were randomly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days. The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis in their nasopharyngeal secretions was assessed. Of 265 patients enrolled, 132 received placebo and 133 azithromycin. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients (29%). In this predefined subgroup of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 occurred in 73% of those treated with azithromycin compared with 47% of those who received placebo (P=0.007). The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group. Respiratory complications requiring antibiotic treatment occurred in 19% of patients in the placebo group and in 3% of the azithromycin group (P=0.025). In the remaining 188 patients without Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 was similar in both groups (69% in the placebo group vs. 64% in the azithromycin group [P=0.75]). Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis is present in nasopharyngeal secretions. This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Azithromycin; Common Cold; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Haemophilus influenzae; Humans; Male; Middle Aged; Moraxella catarrhalis; Nasopharynx; Reference Values; Respiratory Tract Infections; Sinusitis; Streptococcus pneumoniae; Treatment Outcome

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

Our aim was to study a new form of azithromycin (500 mg tablets) in order to evaluate the tolerability and the influence of the ingestion of food on tolerability, the efficacy and treatment compliance in a large number of patients with respiratory tract infections. We carried out an open, non-comparative, multicenter, observational and prospective pharmacovigilance study of 3223 outpatients with respiratory tract infections randomly assigned to receive a daily dose of azithromycin for three months taken either during or outside meals. Patients were evaluated during an initial visit and two later ones in order to record the adverse events and establish the clinical efficacy. The diagnostics were as follows: pharyngotonsillitis (1200), acute otitis media (394), acute bronchitis (1134), exacerbation of chronic bronchitis (436), and community-acquired pneumonia (53). The overall therapeutic efficacy was satisfactory (cure or improvement) in 96% to 97% at the second visit and in 93% to 94% in the third (pharyngotonsillitis, 93%; acute otitis media, 91%; acute bronchitis, 94%; exacerbation of chronic bronchitis, 94%; and community-acquired pneumonia, 96%). A total of 170 adverse events were reported in 141 patients (4.4%); 12 were severe yet not related to the study medication. Eighty-eight patients showed adverse events presumed to be related to azithromycin; most were in the digestive tract. No differences in tolerability were observed in relation to food intake. Treatment compliance was high (97%). The elevated clinical efficacy, adequate compliance and the excellent tolerability profile of azithromycin tablets make them a safe and effective alternative in the treatment of respiratory tract infections.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Middle Aged; Product Surveillance, Postmarketing; Respiratory Tract Infections; Sex Characteristics

A prospective assessment of the pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae before and after an azithromycin chemoprophylaxis intervention clinical trial in a cohort of US Marine Corps trainees. In addition, the minimum inhibitory concentrations (MICs) for all streptococcal isolates, for azithromycin, penicillin, erythromycin and cefotaxime are reported.. Between November 1994 and March 1995, 1108 asymptomatic male US Marine Corps trainees, located in Southern California, were randomly assigned to one of three intervention groups: (1) weekly oral azithromycin, 500 mg (n = 362); (2) 1.2 MU benzathine penicillin G, intramuscularly once (n = 374); or (3) no chemoprophylaxis (n = 372). Subjects provided both a pre- and post-training pharyngeal culture and microbial analysis was conducted to determine the colonization status of each study subject.. The pretraining colonization prevalence was 1.2% for S. pneumoniae and 2.4% for S. pyogenes. There was no statistical difference in pretraining prevalence between the three treatment groups for either organism. Post-training pharyngeal cultures revealed an overall prevalence of 1.1% with no difference between treatment arms. However, the overall post-training prevalence of S. pyogenes colonization increased to 4.8%, with the azithromycin group having significant evidence of protection (0.7%) in comparison with the no-treatment group (8.2%). The Etest method demonstrated no significant difference in the MIC50, MIC90, and MIC ranges between pre- and post-training isolates for any of the tested drugs.. The use of azithromycin as a chemoprophylactic agent to reduce the colonization and subsequent infection of streptococcal respiratory disease among healthy adult male military recruits may be beneficial.

Topics: Anti-Bacterial Agents; Azithromycin; Cohort Studies; Humans; Male; Microbial Sensitivity Tests; Penicillins; Pharynx; Pneumococcal Infections; Prevalence; Prospective Studies; Respiratory Tract Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.

Topics: Administration, Oral; Adult; Azithromycin; Humans; Male; Penicillin G Benzathine; Pharynx; Respiratory Tract Infections; Streptococcus

Lower respiratory tract infection (LRTI) is one of the major health problems in developing countries such as Indonesia. According to the National Household Health Survey conducted by the Ministry of Health in 1992, LRTIs still rank fourth as the main cause of death in Indonesia. The problem of LRTIs could be simply managed as long as the causative organism can be identified and the proper antibiotic known. In some occasions, it is not quite so easy to identify the causative micro-organism, especially in lower tract infections. There are several methods of obtaining specimens from LRTIs for cultures. The easiest, most simple way is to collect expectorated sputum. Unfortunately, because of the high rate of contamination by upper respiratory tract flora, this method is not reliable. Recognizing the difficulties with routine expectorated sputum cultures, two alternative approaches have been suggested. One approach is to bypass potential expectorated sputum 'contaminants' in the oropharynx by transtracheal aspiration or transthoracic aspiration. The second approach is to modify the usual technique of processing expectorated sputum by either washing techniques or by quantitative cultures. Azithromycin and clarithromycin are chemically related to macrolide erithromycin. Both antibiotics retain the traditional macrolide spectrum of activity against gram-positive and atypical pneumonia pathogens, while demonstrating improved activity against gram-negative bacteria. The American Thoracic Society (ATS) recommended the use of macrolide for outpatients with community-acquired pneumonia, without comorbidity and 60 years of age or younger. A total of 34 outpatients with acute LRTIs were open-comparative, randomly allocated to treatment with the new macrolide in Persahabatan Hospital, Jakarta, 1996. The purposes of this study were: (i) to identify the causative micro-organisms; and (ii) to evaluate the clinical efficacy of the new macrolide in these infections. Azithromycin 500 mg was given orally once a day for 3 days and was administered 1 h before or 2 h after every meal. Clarithromycin 500 mg was given orally every 12 h for 10 days. The diagnosis of the patients were: 16 with pneumonia, 10 with acute bronchitis and 8 with acute exacerbation of chronic bronchitis. In this study of 34 patients, the sputum specimens were washed with N acetylcysteine before culture and we could only detect micro-organisms in one patient. Before treatment, we found 47 strains in 33 (97.05

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Bronchitis; Clarithromycin; Female; Humans; Klebsiella pneumoniae; Male; Pneumonia; Respiratory Tract Infections; Specimen Handling; Sputum; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae

A total of 371 children, aged 6 months to 12 years, with acute otitis media, acute sinusitis, streptococcal tonsillitis/pharyngitis, or pneumonia were included in an open, multicenter study. Among them, 192 children were randomized to receive azithromycin for 3 days (10 mg/kg daily), and 179 for 5 days (10 mg/kg on day 1 and 5 mg/kg on days 2-5). The overall clinical cure rate was 95.7% and 96.1%, and bacteriological eradication rate 90.1% and 94.2% in the 3-day and 5-day groups, respectively. Side effects, mostly mild gastrointestinal disturbances, were observed in 5.3% of children from the 3-day, and 6.7% from the 5-day group. Only in one child (0.3%) was therapy discontinued due to vomiting. The results of this study demonstrate that 3-day and 5-day azithromycin courses have comparable efficacy and tolerability in children with respiratory infections.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteriological Techniques; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Infant; Male; Respiratory Tract Infections; Treatment Outcome

Azithromycin and cefaclor were compared for the treatment of acute otitis media, streptococcal pharyngitis/tonsillitis, or sinusitis in an open multicentre study conducted in 530 adults. At the end of therapy (day 11-15), 228/245 (93%) patients treated with azithromycin 500 mg once daily for 3 days and 233/241 (97%) treated with cefaclor 250 mg given three times daily for 10 days were considered to have responded satisfactorily (cured or improved). In bacteriologically evaluable patients with pharyngitis/ tonsillitis, Streptococcus pyogenes was eradicated in 116/117 (99%) azithromycin- and in 115/119 (97%) cefaclor-treated patients at day 11-15; one patient in each group had become reinfected after initial eradication of the pathogen. When followed up on day 25-30, S. pyogenes infection had recurred in 5/105 (5%) azithromycin and 4/108 (3%) cefaclor patients who had responded satisfactorily at day 11-15, and whose baseline pathogen had been eradicated. Of these patients, two in the azithromycin and one in the cefaclor group also relapsed clinically; the others remained asymptomatic. Patients tolerated both treatments well; treatment-related adverse events were recorded in 11% of the 267 azithromycin- and 10% of the 263 cefaclor-treated patients assessed for safety. One azithromycin patient and five cefaclor patients withdrew because of adverse events. The results of the study show that a 3-day regimen of azithromycin, given once daily, is as effective and well tolerated as a multiple-daily, 10-day cefaclor regimen for the treatment of upper respiratory tract infections in adults.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Cefaclor; Cephalosporins; Female; Humans; Male; Middle Aged; Respiratory Tract Infections

An open, multicentre study was undertaken in order to evaluate the efficacies and safety profiles of azithromycin and roxithromycin in 440 adults with acute otitis media, sinusitis or acute beta-haemiolytic streptococcal pharyngitis/tonsillitis. Treatment with 500 mg azithromycin, administered orally once daily for 3 days, produced a satisfactory clinical outcome (cure or improvement) in 51/52 (98%) patients with otitis media, 91/91 (100%) patients with pharyngitis/tonsillitis and 64/68 (94%) patients with sinusitis. Treatment with 150 mg roxithromycin, given orally twice daily for 10 days, produced satisfactory clinical responses in 54/55 (98%), 91/92 (99%) and 69/73 (94%) patients with otitis media, pharyngitis/tonsillitis and sinusitis respectively. Of the 17 azithromycin-treated patients with sinusitis who were clinically and bacteriologically evaluable, Staphylococcus aureus persisted in two and Streptococcus pneumoniae in one. S. aureus also persisted in 1/12 clinically and bacteriologically-evaluable patient treated with roxithromycin. Of the 58 and 64 patients with pharyngitis/tonsillitis treated with azithromycin and roxithromycin, respectively, who were clinically and bacteriologically evaluable, Streptococcus pyogenes persisted at the end of treatment in 7/58 (12%) in the azithromycin group and in 13/64 (20%) in the roxithromycin group. At follow-up, there was no evidence of S. pyogenes reinfection in patients treated with azithromycin. Three episodes of reinfection occurred in the roxithromycin treatment group. Also, three patients showed evidence of clinical relapse at follow-up, although no pathogens were isolated. Azithromycin was associated with a lower incidence of adverse events. No azithromycin-treated patient was withdrawn prematurely because of a treatment-related event. Three roxithromycin-treated patients were withdrawn from treatment because of severe headache, thyroiditis or fatigue. In conclusion, for adults with acute upper respiratory tract infections, a 3-day course of once-daily azithromycin was found to be as effective and as well tolerated as a 10-day course of twice-daily roxithromycin.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Middle Aged; Recurrence; Respiratory Tract Infections; Roxithromycin

A 3-day regimen of azithromycin (500 mg once daily) and a 10-day regimen of co-amoxiclav (625 mg three times daily) were compared in a double-blind study of 67 patients with acute infectious exacerbations of chronic bronchitis (AIECBs, n = 54), acute bronchitis (n = 7), or pneumonia (n = 6). In patients treated with azithromycin, satisfactory clinical responses (cure or improvement) were seen in 24/28 (86%) patients with AIECBs, 2/4 (50%) with acute bronchitis and 2/2 (100%) with pneumonia. Responses were satisfactory in 24/26 (92%), 4/4 (100%) and 4/4 (100%) patients, respectively, receiving co-amoxiclav. Streptococcus pneumoniae and Haemophilus influenzae were the commonest pathogens isolated at baseline. At the end of treatment, baseline pathogens were eradicated in 9/10 microbiologically-assessable patients treated with azithromycin and in 10/10 treated with co-amoxiclav. Adverse events related or possibly related to treatment occurred in five patients in each treatment group; the majority of these events affected the gastrointestinal system. One patient in each treatment group discontinued therapy because of adverse events. The study, therefore, demonstrates that 500 mg azithromycin administered once daily for 3 days is as efficacious and well tolerated as co-amoxiclav given three times daily for 10 days in the domiciliary treatment of adults with acute lower respiratory tract infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Clavulanic Acids; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Respiratory Tract Infections

Clinical and bacteriological efficacy and tolerability of azithromycin (500 mg once daily for 3 days) and those of a 10-day regimen of co-amoxiclav (37 mg three times daily) were evaluated in a large-scale, double-blind comparative study of 369 patients (> or = 18 years old) with acute lower respiratory tract infections. After treatment, 165/173 (95%) azithromycin- and 166/173 (96%) co-amoxiclav-treated patients had responded satisfactorily (cure or improvement). Baseline pathogens (mainly Streptococcus pneumoniae and Haemophilus influenzae) were eradicated in 82/82 (100%) azithromycin- and 73/74 (99%) co-amoxiclav-treated patients who were bacteriologically assessable. Adverse events, which were predominantly of mild to moderate severity and mostly affected the gastrointestinal system, were recorded in 13/186 (7%) azithromycin- and 19/183 (10%) co-amoxiclav-treated patients. Only two (1%) azithromycin-treated patients discontinued treatment due to adverse events compared with eight (4%) who received co-amoxiclav. The results show that azithromycin at a dose of 500 mg once daily for 3 days is an effective and safe alternative to a 10-day, three-times-daily course of co-amoxiclav in the treatment of lower respiratory tract infections in adults.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Clavulanic Acids; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Treatment Outcome

In an open, multicentre study, the clinical and bacteriological efficacy, safety and tolerance of azithromycin and roxithromycin were compared in a total of 204 adults with acute lower respiratory tract infections (LRTIs) [acute bronchitis, acute infectious exacerbations of chronic bronchitis (AIECBs), or pneumonia]. Following treatment with 500 mg/day azithromycin administered orally once daily for 3 days, a satisfactory clinical response of cure or improvement was recorded in 91/99 (91.9%) evaluable patients at the post-therapy evaluation (day 10-14). Of the 94 evaluable patients treated with roxithromycin (150 mg given orally twice daily for 10 days), 82 (87.2%) were classified as cured or improved at post-therapy. The main pathogens isolated before treatment were Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus species, Haemophilus influenzae and Moraxella catarrhalis. In the 46 azithromycin-treated patients evaluated both clinically and bacteriologically, 92.0% of pathogens were eradicated; H. influenzae persisted in one azithromycin-treated patient with acute bronchitis who was classed as clinically improved. In the roxithromycin group, 81.1% of the pathogens were eradicated in 35 patients; S. aureus persisted in one clinically cured patient with acute bronchitis, and H. influenzae persisted in one patient with AIECB and one with pneumonia, and Haemophilus species in one with AIECB, who were all classified as clinically improved. Azithromycin was well tolerated with a lower incidence of adverse events than that recorded in the roxithromycin treatment group. Treatment was not discontinued due to adverse events in any of the azithromycin-treated patients, whereas two roxithromycin-treated patients were withdrawn from treatment due to vomiting and/or dyspepsia.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Roxithromycin; Treatment Outcome

Azithromycin (AZM) was studied for its clinical efficacy in pediatric infections. The study on AZM was carried out in 43 patients whose diagnoses were given as follows: pharyngitis in five cases, tonsillitis in one, bronchitis in four, pneumonia in four, Mycoplasma pneumonia in 14, scarlet fever in nine, impetigo in four, pyodermia in one and Campylobacter enteritis in one. The patients received AZM once daily at 1.6 approximately 20.0 mg/kg body weight for three to five days. Effectiveness of AZM was evaluated in 39 cases and the drug was rated "excellent" in 15, "good" in 19, "fair" in one, "poor" in four, resulting in an efficacy rate of 87.2%. Twenty bacterial isolates were identified as causative isolates in 19 patients: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Campylobacter jejuni and Mycoplasma pneumoniae. AZM eradicated 16 isolates but four persisted after therapy. One patient complained of loose stool, while two patients were found with decreases in white blood cell counts, and seven showed increases in eosinophils. However, no serious case of adverse event was reported.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Capsules; Child; Child, Preschool; Drug Resistance, Microbial; Female; Haemophilus influenzae; Humans; Impetigo; Infant; Male; Respiratory Tract Infections; Streptococcus pyogenes

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluation in the pediatric patients. Antibacterial activity of AZM against 43 clinical isolates: AZM exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold higher activity against Gram-negative bacteria than erythromycin or clarithromycin. Plasma or urine samples were collected from eight patients receiving the drug in fine granular form, and two patients receiving it in capsules for the determination of drug levels. The elimination half-lives of AZM after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3 micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The cumulative excretion rates up to 120 hours after the start of treatment were 8.24 and 13.84% for fine granules, and 3.83% for capsules. AZM was administered to 123 patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference to the standard dose of 10 mg/kg. The drug was used to treat patients with pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia, chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI. The effectiveness of AZM was evaluated in 109 cases. The drug was rated "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an efficacy rate of 94.5%. Furthermore, AZM eradicated 43 of 46 (93.5%) bacteria that had been identified before the treatment. Three patients complained of side effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes were reported as follows: decreased leukocyte (3 cases), increased eosinophil (5), increased platelet (2), increased eosinophil and platelet, elevated GPT (1), and elevated GOT and GPT (1). The abnormalities, however, were mild enough to raise no clinically significant problems. In conclusion, AZM in once daily regimen was effective and safe in treatment of pediatric infections.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Capsules; Child; Child, Preschool; Female; Humans; Infant; Male; Respiratory Tract Infections; Staphylococcus aureus; Streptococcus pyogenes

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluations. 1. Antibacterial activities. MIC profile of AZM was as follows: 0.78 approximately 1.56 micrograms/ml against Staphylococcus aureus, < or = 0.025 approximately 0.10 microgram/ml against Streptococcus pyogenes, 0.10 approximately 0.39 and 6.25 micrograms/ml against Streptococcus pneumoniae, < or = 0.025 approximately 0.39 microgram/ml against Moraxella(Branhamella) catarrhalis, 0.39 approximately 3.13 micrograms/ml against Haemophilus influenzae, and 0.20 approximately 6.25 micrograms/ml against Haemophilus parainfluenzae. 2. Absorption and excretion. The elimination half-life of AZM after its administration at 10 mg/kg/day for three days was 28.1 approximately 46.1 hours. The cumulative urinary excretion rate in the first 120 hours after start of treatment was 4.01 approximately 8.47%. 3. Clinical evaluation. AZM was given to 76 pediatric patients to treat following infections: pharyngitis in seven, tonsillitis in 11, bronchitis in 11, pneumonia in 19, Mycoplasma pneumonia in eight, scarlet fever in 13, infective enteritis in one, SSTI in four, and otitis media in two. Effectiveness of AZM was assessed in 75 patients and the drug was rated "excellent" or "good" in 71 resulting in an efficacy rate of 94.7%, 87.0% of the 46 cases indicated that AZM had eradicated bacteria identified before the treatment. One patient complained of moderate diarrhea which disappeared after treatment of anti-diarrheic. Abnormal laboratory changes were reported in 12 patients in the following: decreased leukocytes in eight, increased eosinophils in two, increased platelet count in one, and increased GPT in one. All cases of abnormality was deemed mild in severity and clinically insignificant.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Capsules; Child; Child, Preschool; Female; Half-Life; Humans; Infant; Male; Pharyngitis; Pneumonia, Bacterial; Respiratory Tract Infections; Tonsillitis

Azithromycin (AZM), 10% fine granules or 100 mg capsules, were given orally to 27 children with various pediatric infections. The results of the study are shown below. 1. Pharmacokinetic investigation. We studied plasma and urinary concentrations after 100 mg AZM capsules were given. One patient received 8.3 mg/kg of AZM once a day for 3 days, and AZM concentration in plasma was 0.033 microgram/ml 48 hours after the final dosing. Doses of 8.3 and 12.5 mg/kg body weight of AZM were respectively given to two patients once daily for 3 days. As a result, AZM concentrations in urine during a period between 96 and 120 hours post-dosing were 1.67 and 4.53 micrograms/ml, respectively, and urinary excretion rate in 120 hours after the first dosing was 10.54% in the patient that was given 12.5 mg/kg. 2. Clinical investigation. Clinical efficacies were examined in 24 patients. Excellent results were obtained in 7 patients, good results in 14 patients, hence the clinical efficacy rate was 87.5%. Bacteriologically, Haemophilus influenzae strains isolates from 2 patients were eradicated in 1 and decreased in the other. Safety was evaluated in 26 patients. An adverse reaction was observed in 1 patient (urticaria). Abnormal laboratory test results were observed in 2 patients, decreased WBC in 1 and elevation of eosinophils in the other. The above results suggest that AZM is a useful oral antibiotic for pediatric patients with infection with susceptible organisms.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Male; Pharyngitis; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Respiratory Tract Infections

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was administered at a standard dose of 10 mg/kg once daily for 3 days to pediatric patients with bacterial infections. AZM was studied for its pharmacokinetic and clinical evaluation. 1. AZM possessed potent activity against Gram-positive bacteria and Gram-negative bacteria that had been clinically isolated. 2. Plasma samples were collected from two patients diagnosed as having pneumonia or enteritis, and urine samples were collected from one patient diagnosed as having pneumonia for drug level determination. The drug concentrations in plasma were 0.095 and 0.204 microgram/ml just before the end of treatment, and 0.017 and 0.096 microgram/ml at 48 hours post-treatment. The drug concentrations in urine were 5.16 micrograms/ml and 5.63 micrograms/ml during a period between 24 and 48 hours and between 48 and 72 hours after the start of treatment, respectively. 3. The drug was found effective in 37 of 38 cases with various pediatric infections. AZM treatment eradicated bacteria in 17 of 30 strains (56.7%). 4. One patient complained of mild vomiting, while abnormal laboratory test results indicating mild eosinophilia were reported in four cases.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Capsules; Child; Child, Preschool; Enteritis; Female; Humans; Infant; Male; Pharyngitis; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Respiratory Tract Infections

Fine granule preparation of azithromycin (AZM), a new macrolide antibiotic, was given to treat various infections in pediatric patients. Efficacies of AZM in a total of 21 patients (tonsillitis in six, bronchitis in five, pneumonia in five, impetigo contagiosa in three, staphylococcal scalded skin syndrome in one and bacterial enterogastritis in one) were rated "excellent" in 11 patients and "good" in eight. The remaining two cases were not included in the evaluation. AZM eradicated all strains of infection-causative bacteria identified in the 21 patients: Staphylococcus aureus in two, Streptococcus pneumoniae in four, Moraxella (Branhamella) catarrhalis in four, Haemophilus influenzae in six, Haemophilus parainfluenzae in three and Mycoplasma pneumoniae in one. One patient complained of mild diarrhea, while two patients showed increases in eosinophils as abnormal laboratory changes.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Child, Preschool; Female; Humans; Infant; Male; Mycoplasma pneumoniae; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Respiratory Tract Infections; Staphylococcus aureus; Streptococcus pneumoniae; Tonsillitis

Azithromycin (AZM), an oral macrolide antibiotic drug, was studied for its efficacy and pharmacokinetics in the treatment of pediatric patients with respiratory tract infections. The results of the study are presented. Fifteen pediatric patients in an age range between 1 and 10 years were given 8.9 to 14.7 mg/ kg body weight of AZM once daily for 3 to 4 days. Pharmacokinetics of AZM in three patients were examined. AZM concentration in plasma was 0.037 microgram/ml at 72 hours after final dosing, while urine concentration was 10.9 micrograms/ml measured during a period between 72 and 96 hours post-dosing. Fourteen patient cases were included in analysis of drug efficacy for AZM. AZM was found "markedly effective" in all seven patients with pneumonia, and "effective" in all three patients with acute bronchitis, two patients with mycoplasmal pneumonia, and one patient with tonsillitis. In one patient with mycoplasmal bronchitis, AZM was found slightly effective. The efficacy rate was 92.9% (13/14). The study found one case of side effect, moderate diarrhea. No laboratory abnormality was documented. In conclusion, an antibiotic AZM was found useful in a treatment of pediatric respiratory tract infections.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Capsules; Child; Child, Preschool; Female; Humans; Infant; Male; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Respiratory Tract Infections

Azithromycin (AZM) is a new oral macrolide antibiotic drug. AZM either in 10% fine granules form or in 100 mg capsule form was studied for its pharmacokinetics and treatment efficacy in pediatric patients with various infections. 1. Pharmacokinetics. Plasma and urine samples were collected from four patients with pharyngitis and post-dosing drug levels were determined. The drug was given once daily at 10 mg/kg body weight for 3 days. The drug concentrations found in plasma at 96 hours after the first dosing (48 hours after the final dosing) lay in a range of 0.02 and 0.04 microgram/ml and in urine at 120 hours after the first dosing (72 hours after the final dosing) in a range between 3.2 and 7.7 micrograms/ml. AZM was found in two patients but no effect was observed on blood levels of theophylline determined between 48 and 96 hours after the first dosing in the treatment of underlying bronchial asthma. 2. Clinical study results. Clinical studies of AZM was carried out in 25 pediatric patients with bacterial infections that mainly affected the respiratory tract. The patients received either 10% fine granules at 10 or 20 mg/ kg body weight or 100 mg capsules at 10 mg/kg body weight once daily over 3 to 6 days. The drug was found markedly effective in six patients, moderately effective in thirteen patients, while the investigators could not assess the drug efficacy in six patients. Although no side effect was reported in the study, two patients experienced slight decrease in WBC.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Child; Child, Preschool; Female; Humans; Infant; Male; Pharyngitis; Pneumonia, Bacterial; Respiratory Tract Infections; Tonsillitis

Azithromycin (AZM) was studied for its concentrations in plasma and urine, efficacy and safety. 1. Plasma and urine samples were collected from one patient diagnosed as having Mycoplasma pneumonia for drug level determination. The drug was given once daily at 9.7 mg/kg body weight for three days. The drug concentrations in plasma was 0.149 microgram/ml in 12 hours after the start of the treatment, and 0.095 microgram/ml at the point of 24 hours after the end of the treatment. Urinary recovery rate up to 72 hours post-dosing was 6.39%. 2. The effectiveness of AZM was assessed in 19 patients with following diagnoses: pharyngitis in two patients, bronchitis in four, pneumonia in seven and Mycoplasma pneumonia in six. The drug was rated "excellent" in 11, "good" in seven, "poor" in one, resulting in an efficacy rate of 94.7%. 3. AZM eradicated two strains of Streptococcus pyogenes and Streptococcus pneumoniae identified in patients. 4. The AZM MIC's were 0.39 microgram/ml against Staphylococcus aureus, 0.20 microgram/ml against S. pneumoniae, < or = 0.0008 microgram/ml against Mycoplasma pneumoniae. 5. One patient complained of mild diarrhea, while another showed a slight increase in eosinophils, suggesting an abnormal laboratory change. In conclusion, AZM was found useful in treatment of pediatric infections.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Child; Child, Preschool; Female; Humans; Infant; Male; Pharyngitis; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Respiratory Tract Infections

Azithromycin was given to 55 cases of lower respiratory tract infections in the doses of 500 mg on day 1, followed by 250 mg on days 2-5. It produced bacteriological cure in 70.8% patients and clinical cure or improvement in 69.09% of patients. 4.27% of patients had throat colonisation with new organisms, of which 9.09% needed a second antibiotic. The drug was well tolerated and minor side effects were noted. Gastrointestinal disturbances (16.36%) headache and giddiness (14.55%), rash (3.64%) were the noted side effects. Reduction of platelet count by 50% occurred in 12.29% of the cases compared to 0.2% reported earlier. But this thrombocytopenia was clinically not significant, as it did not cause any symptoms.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Evaluation Studies as Topic; Female; Humans; India; Male; Respiratory Tract Infections; Treatment Outcome

The efficacies and safeties of a 3-day, 3-dose course of azithromycin (10 mg/kg of body weight per day) and a 10-day, 30-dose course of erythromycin (40 mg/kg/day) for the treatment of acute lower respiratory tract infections in children were compared in an open randomized multicenter study. Sixty-eight of 85 evaluable patients (80%) had radiologically proven pneumonia, and 20% had bronchitis. Treatment success defined as cure or major improvement was achieved in 42 of 45 (93%) azithromycin recipients versus 36 of 40 (90%) erythromycin recipients. Adverse events were reported in 12 of 45 and 6 of 40 of the patients treated with azithromycin and erythromycin, respectively, a difference which was not statistically significant. In conclusion, a 3-day course of azithromycin is as effective as a 10-day course of erythromycin in the treatment of community-acquired lower respiratory tract infections in children, with comparable safety and acceptability profiles. This shorter treatment course might have a beneficial effect on compliance, especially in the pediatric age group.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bronchitis; Child; Child, Preschool; Community-Acquired Infections; Erythromycin; Follow-Up Studies; Humans; Pneumonia; Prospective Studies; Respiratory Tract Infections

Azithromycin (AZM) in 10% fine granules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.5% received 3 day administration) to children with infectious diseases and the efficacy and the safety of AZM were investigated. In addition AZM concentrations were determined in blood samples from 18 patients and in urine samples from 17 patients to examine o pharmacokinetic characteristics of AZM. 1. Absorption and excretion: Cmax's in 16 patients who received 10 mg/kg and 2 patients who received 20 mg/kg were 0.29 +/- 0.24 micrograms/ml and 0.75 micrograms/ml, respectively, while T 1/2's were 42.0 +/- 11.8 hours for the former and 51.3 hours for the latter. AUC(0 to approximately infinity)'s were 10.72 +/- 5.00 micrograms x hr/ml in the former and 28.83 micrograms x hr/ml in the latter. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 10 mg/kg AZM in 14 patients, while it peaked at 24 to 48 hours in the patients who received 20 mg/kg. Urinary recovery rates in the first 120 hours after the start were 9.1 +/- 2.6% for 10 mg/kg and 10.8 +/- 3.4% for 20mg/kg. 2. Clinical efficacy: The study received 619 entries and 564 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate, combining both "Excellent" and "Good" cases was 94.3% in 246 cases where pathogens were identified, classified as Group A. The efficacy rate was 90.7% for the remaining 321 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 92.2%. For the 116 cases where the patients had failed to respond to previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 94.0%. 3. Adverse reactions and abnormal laboratory tests: Incidents of diarrhea, soft stool, skin rashes, or vomiting were found in 15 patients (2.5%) of 596 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 15 patients including 4 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 23 patients (5.6%), increase in eosinophils in 28 (7.1%), increase in platelet count in 2 (0.5%), decrease in platelet count in 1 (0.3%), elevation of GOT in 3 (0.8%), and elevation of GPT in

Topics: Absorption; Administration, Oral; Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Dosage Forms; Humans; Infant; Japan; Male; Patient Compliance; Respiratory Tract Infections

Azithromycin (AZM) in 100 mg capsules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.9% received 3 day administration) to children with infectious diseases and the efficacy and the safety of AZM were investigated. In addition, AZM concentrations were determined in blood samples from 9 patients and in urine samples from 12 patients to examine pharmacokinetic characteristics of AZM. 1. Absorption and excretion: Cmax was 0.45 +/- 0.28 micrograms/ml, T 1/2 was 52.7 +/- 20.2 hours, and AUC(0 approximately to infinity) was 12.09 +/- 4.93 micrograms.hr/ml in the 9 patients each of whom received 8.5 to 14.3 mg/kg AZM. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 8.5 to 14.7 mg/kg AZM in 12 patients and the average urinary recovery rate in 120 hours was 7.3 +/- 2.8%. 2. Clinical efficacy: The study received 139 entries and 119 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate combining both "Excellent" and "Good" cases, was 100% for 40 cases in which pathogens were identified, classified as Group A. The efficacy rate was 97.5% for the remaining 79 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 98.3%. For the 31 cases where the patients had failed to respond to the previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 93.5%. 3. Adverse reactions and abnormal laboratory tests: 8 incidents of diarrhea, skin rashes, urticaria, or vomiting were found in 7 patients (5.4%) of 130 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 7 patients including 2 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 10 patients (9.3%), an increase in eosinophils in 12 (11.4%), an increase in platelet count in 1 (1.0%), an elevation of GOT in 3 (3.1%), an elevation of GPT in 6 (6.2%), and an elevation of LDH in 1 (1.1%). The abnormalities were transient and did not require particular intervention. Moreover, none of the patients indicated clinical signs associated with the abnormal changes of laboratory tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Absorption; Administration, Oral; Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Capsules; Child; Child, Preschool; Female; Humans; Japan; Male; Patient Compliance; Respiratory Tract Infections

A multicenter open prospective comparative study was carried out during two years enrolling 60 patients with upper respiratory infections. Thirty were treated with single daily 500 mg doses of azithromycin for three days, and 30 received two daily doses of roxithromycin of 150 mg each for seven days. Both treatments were equally well tolerated, and there was no substantial difference concerning clinical recovery. However, azithromycin treatment was more practical and of shorter duration.

Topics: Acute Disease; Adolescent; Adult; Azithromycin; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Roxithromycin

The efficacy and safety of azithromycin and clarithromycin were compared in an open multicentre study involving 380 adult patients with acute otitis media, acute sinusitis, or acute streptococcal pharyngitis or tonsillitis. Patients were assigned randomly to receive azithromycin as a single dose of 500 mg daily for three days, or clarithromycin 250 mg bid for ten days. Overall clinical efficacy was found to be similar in each treatment group at day 10-14, with a satisfactory outcome (cured or improved) in 95% of azithromycin and 96% of clarithromycin patients. Bacteriological efficacy was also similar, with eradication of the pathogen in 94% and 95% of isolates, respectively, in the azithromycin and clarithromycin groups. In otitis media, a satisfactory clinical response was seen in 97% of patients in each treatment group. Azithromycin therapy resulted in a clinical response rate of 93% in sinusitis patients, with bacteriological eradication in 93% of patients. Two patients (who were cured clinically) had persistent pathogens. Similarly, clarithromycin achieved clinical response and bacteriological eradication in 95% and 92% of sinusitis patients, respectively. Pathogens persisted in two patients with clinical cure, and in one case of clinical failure. In pharyngitis or tonsillitis, Streptococcus pyogenes was eradicated successfully in 95% of patients in both groups, and the clinical success rates were 96% and 97% for azithromycin and clarithromycin, respectively. No case of clinical failure was associated with persistence of S. pyogenes infection. At the follow-up assessment of this diagnosis group, reinfection had occurred in three (8%) azithromycin patients and one (3%) clarithromycin patient, and all but one patient remained asymptomatic. Both drugs were well-tolerated, with 8.4% of patients on azithromycin and 7.4% on clarithromycin reporting adverse events, mainly gastrointestinal. It was concluded that a three-day course of azithromycin was as effective and well-tolerated as a ten-day course of clarithromycin in adults with acute upper respiratory tract infections.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Child; Clarithromycin; Drug Administration Schedule; Erythromycin; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Otitis Media; Pharyngitis; Respiratory Tract Infections; Sinusitis; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections. Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease. Nine patients had pneumonia and 19 purulent bronchitis. Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group. The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25). Microbiological response rates were comparable in the two groups. In 5% of patients, serological evidence for virus or atypical pathogens was found. Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09). Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin. It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections.

Topics: Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Bronchitis; Clavulanic Acids; Drug Administration Schedule; Drug Combinations; Erythromycin; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Single-Blind Method; Streptococcus pneumoniae

The efficacy and safety of azithromycin and clarithromycin in lower respiratory tract infection (LRTI) were compared in an open, multicentre study. Five hundred and ten adult patients with a diagnosis of LRTI, including acute bronchitis, acute infective exacerbations of chronic bronchitis (AIECB) or pneumonia were enrolled. The patients were randomly assigned to receive either azithromycin (n = 252) as a single daily dose of 500 mg for three days, or clarithromycin (n = 258) 250 mg twice daily for ten days. In AIECB patients, baseline comparisons of the two treatment groups showed that there were no differences in the number of previous episodes of infection or in the incidence of current or past smokers. The overall clinical efficacy was found to be similar in each treatment group on day 10 to 14, with a satisfactory response (cured or improved) in 94% of azithromycin- and 97% of clarithromycin-treated patients. At follow-up evaluation (day 18 to 22), 97% of azithromycin- and 100% of clarithromycin-treated patients who had improved at day 10 to 14, showed satisfactory outcomes. Bacteriological efficacy was similar in both treatment groups, with eradication of 100% vs 95% of isolates in the azithromycin and clarithromycin groups, respectively. In AIECB, 100% of pathogens were eradicated by azithromycin, although one patient was clinically assessed as failed. Clarithromycin eradicated 93% of pathogens in this group; all patients being assessed as cured or improved. Both drugs were well tolerated, with 9% and 6% of patients reporting adverse events with azithromycin and clarithromycin, respectively. These adverse events were largely gastrointestinal in origin. It was concluded that a three-day course of azithromycin is as effective and well tolerated as a ten-day course of clarithromycin in adults with acute LRTIs.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Bronchitis; Clarithromycin; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia; Respiratory Tract Infections

In this open study, a three-day regimen of azithromycin (single daily dose of 10 mg/kg) was compared with a ten-day regimen of amoxycillin paediatric suspension (30 mg/kg/day in three divided doses; children > 20 kg received 250 mg tid daily) in 154 children (aged 2-12 years) with a clinical diagnosis of acute otitis media (13 recurrent). Full clinical, bacteriological and laboratory safety assessments were performed during and after the study. Of the 77 azithromycin patients, 61 (79%) were considered cured, 15 (19%) improved and one (1%) failed, compared with 45 (58%) cured, 28 (36%) improved and four (5%) failed among the 77 amoxycillin patients. Excluding from analysis the 13 patients with recurrent otitis media, azithromycin was found to be significantly superior to amoxycillin (P = 0.003). The incidence of side-effects was low, with only two (3%) and three (4%) patients reporting adverse events with azithromycin and amoxycillin, respectively. These were gastrointestinal in nature and of mild or moderate severity, except for one case of severe diarrhoea in the amoxycillin group. No treatment-related abnormalities in the laboratory safety tests were observed, and no patients withdrew from therapy. A three-day regimen of azithromycin was therefore shown to be more effective than, and as well tolerated as, amoxycillin in the treatment of children with acute otitis media.

Topics: Acute Disease; Amoxicillin; Azithromycin; Bacterial Infections; Child; Child, Preschool; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Otitis Media; Respiratory Tract Infections

The efficacy and tolerability of azithromycin and erythromycin in the treatment of acute respiratory tract infections in children were compared in an open, multicenter, randomized trial. A total of 151 children, aged from 2 months to 14 years, suffering from upper airways infections (60), or lower respiratory tract infections (91), were randomized to be treated either with azithromycin, 10 mg/Kg/day per os once daily for 3 or 10 mg/Kg/day 1 and 5 mg/Kg/days 2-5 (77 patients) or with erythromycin, 50 mg/Kg/day thrice daily for at least 7 days (74 patients). The two treatment groups did not significantly differ as to sex, age, weight, type and severity of infection, and infecting pathogens. Clinical evaluation was performed prior to therapy, on treatment days 1, 3, 5 and 7, and on day 10. Microbiological and laboratory assessment were carried out at baseline and after the end of therapeutic course. Chest X-ray and serologic assays for Mycoplasma pneumoniae infection were obtained in patients suspected to have lower respiratory tract infections. At the end of therapy, clinical cure was achieved in 73 out of 77 patients (94.8%) in the azithromycin group, and in 60/72 evaluable subjects (83.3%) in the erythromycin group. A significantly more rapid remission of several illness-related signs and symptoms was observed in patients treated with azithromycin. A total of 75 bacterial pathogens were isolated at baseline microbiological examination; at the end of the therapeutic course bacteriological eradication was obtained in 34/34 cases (100%) treated with azithromycin, and in 40/41 children (97.5%) treated with erythromycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Azithromycin; Bacterial Infections; Child; Child, Preschool; Drug Administration Schedule; Erythromycin; Female; Humans; Infant; Male; Respiratory Tract Infections; Treatment Outcome

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

To define the factors associated with overprescription of antibiotics by general practitioners (GPs) for patients diagnosed with COVID-19 during the first wave of the pandemic.. Anonymised electronic prescribing records of 1370 GPs were analysed. Diagnosis and prescriptions were retrieved. The initiation rate by GP for 2020 was compared with 2017-2019. Prescribing habits of GPs who initiated antibiotics for > 10% of COVID-19 patients were compared with those who did not. Regional differences in prescribing habits of GPs who had consulted at least one COVID-19 patient were also analysed.. For the March-April 2020 period, GPs who initiated antibiotics for > 10% of COVID-19 patients had more consultations than those who did not. They also more frequently prescribed antibiotics for non-COVID-19 patients consulting with rhinitis and broad-spectrum antibiotics for treating cystitis. Finally, GPs in the Île-de-France region saw more COVID-19 patients and more frequently initiated antibiotics. General practitioners in southern France had a higher but non-significant ratio of azithromycin initiation rate over total antibiotic initiation rate.. This study identified a subset of GPs with overprescribing profiles for COVID-19 and other viral infections; they also tended to prescribe broad-spectrum antibiotics for a long duration. There were also regional differences concerning antibiotic initiation rates and the ratio of azithromycin prescribed. It will be necessary to evaluate the evolution of prescribing practices during subsequent waves.

Topics: Anti-Bacterial Agents; Azithromycin; COVID-19; COVID-19 Testing; Drug Prescriptions; Electronics; General Practitioners; Humans; Practice Patterns, Physicians'; Respiratory Tract Infections

Most antibiotic use occurs in ambulatory settings. No benchmarks exist for pediatric institutions to assess their outpatient antibiotic use and compare prescribing rates to peers. We aimed to share pediatric outpatient antibiotic use reports and benchmarking metrics nationally.. We invited institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient (SHARPS-OP) Collaborative to contribute quarterly aggregate reports on antibiotic use from January 2019 to June 2022. Outpatient settings included emergency departments (ED), urgent care centers (UCC), primary care clinics (PCC) and telehealth encounters. Benchmarking metrics included the percentage of: (1) all acute encounters resulting in antibiotic prescriptions; (2) acute respiratory infection (ARI) encounters resulting in antibiotic prescriptions; and among ARI encounters receiving antibiotics, (3) the percentage receiving amoxicillin ("Amoxicillin index"); and (4) the percentage receiving azithromycin ("Azithromycin index"). We collected rates of antibiotic prescriptions with durations ≤7 days and >10 days from institutions able to provide validated duration data.. Twenty-one institutions submitted aggregate reports. Percent ARI encounters receiving antibiotics were highest in the UCC (40.2%), and lowest in telehealth (19.1%). Amoxicillin index was highest for the ED (76.2%), and lowest for telehealth (55.8%), while the azithromycin index was similar for ED, UCC, and PCC (3.8%, 3.7%, and 5.0% respectively). Antibiotic duration of ≤7 days varied substantially (46.4% for ED, 27.8% UCC, 23.7% telehealth, and 16.4% PCC).. We developed a benchmarking platform for key pediatric outpatient antibiotic use metrics drawing data from multiple pediatric institutions nationally. These data may serve as a baseline measurement for future improvement work.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Benchmarking; Child; Humans; Inappropriate Prescribing; Outpatients; Practice Patterns, Physicians'; Respiratory Tract Infections

The coronavirus disease 2019 (COVID-19) pandemic may have impacted outpatient antibiotic prescribing in low- and middle-income countries such as Brazil. However, outpatient antibiotic prescribing in Brazil, particularly at the prescription level, is not well-described.. We used the IQVIA MIDAS database to characterize changes in prescribing rates of antibiotics commonly prescribed for respiratory infections (azithromycin, amoxicillin-clavulanate, levofloxacin/moxifloxacin, cephalexin, and ceftriaxone) among adults in Brazil overall and stratified by age and sex, comparing prepandemic (January 2019-March 2020) and pandemic periods (April 2020-December 2021) using uni- and multivariate Poisson regression models. The most common prescribing provider specialties for these antibiotics were also identified.. In the pandemic period compared to the prepandemic period, outpatient azithromycin prescribing rates increased across all age-sex groups (incidence rate ratio [IRR] range, 1.474-3.619), with the greatest increase observed in males aged 65-74 years; meanwhile, prescribing rates for amoxicillin-clavulanate and respiratory fluoroquinolones mostly decreased, and changes in cephalosporin prescribing rates varied across age-sex groups (IRR range, 0.134-1.910). For all antibiotics, the interaction of age and sex with the pandemic in multivariable models was an independent predictor of prescribing changes comparing the pandemic versus prepandemic periods. General practitioners and gynecologists accounted for the majority of increases in azithromycin and ceftriaxone prescribing during the pandemic period.. Substantial increases in outpatient prescribing rates for azithromycin and ceftriaxone were observed in Brazil during the pandemic with prescribing rates being disproportionally different by age and sex. General practitioners and gynecologists were the most common prescribers of azithromycin and ceftriaxone during the pandemic, identifying them as potential specialties for antimicrobial stewardship interventions.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Brazil; Ceftriaxone; COVID-19; Female; Humans; Male; Outpatients; Pandemics; Practice Patterns, Physicians'; Respiratory Tract Infections

Sufficient and diverse medical countermeasures against severe pathogenic infections, such as inhalation anthrax, are a critical need. Azithromycin and clarithromycin are antimicrobials commonly used for both upper and lower respiratory infections. They inhibit protein synthesis by blocking the formation of the 50S ribosomal subunit. To expand the armamentarium, these 2 antibiotics were evaluated in a postexposure prophylactic model of inhalation anthrax in cynomolgus macaques.. This prophylaxis study had 4 test arms: azithromycin, clarithromycin, a levofloxacin control, and a placebo. Beginning 24 hours after exposure to a target challenge dose of 200 lethal dose 50 (LD50) of Bacillus anthracis Ames spores, animals were treated orally until 30 days postchallenge and then observed until 75 days postchallenge.. The test group that received clarithromycin had a survival rate of 67%. The test group that received azithromycin had a survival rate of 50%, but the peak azithromycin plasma levels achieved were <30 ng/mL-much lower than the expected 410 ng/mL. The levofloxacin positive control had a survival rate of 50%; all of the negative controls succumbed to infection.. The efficacy of clarithromycin prophylaxis was statistically significant compared with placebo, while azithromycin prophylaxis was indistinguishable from placebo. Given the low plasma concentrations of azithromycin achieved in the study, it is not surprising that half the animals succumbed to anthrax during the dosing period; the animals that survived beyond the time during which placebo control animals succumbed survived to the end of the observation period.

Topics: Animals; Anthrax; Anti-Bacterial Agents; Azithromycin; Bacillus anthracis; Clarithromycin; Disease Models, Animal; Levofloxacin; Macaca fascicularis; Respiratory Tract Infections

The over prescription of antibiotics for acute respiratory infections is a major public health problem worldwide.. To evaluate the frequency of prescription of antibiotics for non-pneumonia acute respiratory infections in private outpatient clinics in individuals without chronic diseases or immunosuppression.. All medical records of adult consultants in a national network of private ambulatory medical centers during May 2018 whose primary diagnosis corresponded to acute respiratory infections not pneumonia (ICD10) were identified and retrospectively analyzed, excluding those with chronic respiratory conditions or states of immunosuppression.. Of the 38,072 consultants (aged 36 years, 63% women) who met this criterion, 54% (n = 20,499) received a prescription for at least one antibiotic. The diagnoses that most frequently received this prescription were acute bronchitis (28.7%), acute sinusitis (16.5%) and acute tonsillitis (16.2%). The most frequently prescribed antibiotic globally was azithromycin (37.4%), followed by amoxicillin (20.1%) and amoxicillin plus clavulanic acid (17.7%). Levofloxacin prescription reached 12.5% of total prescriptions.. An antibiotic was prescribed in more than half of the non-pneumonia outpatient acute respiratory infections. Azithromycin was the most prescribed antibiotic, while levofloxacin exceeded 10% of prescriptions. These results reinforce the need to implement an antibiotic prescription surveillance system at the outpatient level.

Topics: Acute Disease; Adult; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Drug Prescriptions; Female; Humans; Levofloxacin; Male; Outpatients; Practice Patterns, Physicians'; Respiratory Tract Infections; Retrospective Studies

Respiratory tract infections (RTIs) are a common cause of antibiotic usage in hospitalized pediatric patients. Inappropriate use of antibiotics may lead to the emergence of multidrug-resistant microorganisms and increased treatment costs.. This study was designed to assess antibiotic usage in hospitalized pediatric patients with RTIs.. Medical charts of the patients admitted to the pediatric ward (PW) and pediatric intensive care unit (PICU) of a tertiary respiratory center were reviewed. Patients' demographic and clinical data, including gender, age, weight, history of allergy, length of hospital stay, clinical diagnosis, and prescribed antibiotics (indication, dose, and frequency of administration) were collected. The appropriateness of antibiotic usage was evaluated in each patient according to international guidelines.. Two hundred seventy-nine hospitalized patients were included in the study. The most common reason for hospitalization was pneumonia (38%), followed by cystic fibrosis (20.1%) and bronchitis (5%). The most commonly used antimicrobial agents were ceftriaxone, azithromycin, and clindamycin which guideline adherence for their usage was 85.3%, 23.3%, and 47%; respectively. Inappropriate dose selection was the main reason for non-adherence to the guidelines. The adherence rate to RTIs' guidelines (considering all parameters for each patient) was 27.6%. Multivariate logistic regression analysis demonstrated CF and prescription of azithromycin are predictors of guideline non-adherence.. We found relatively low adherence to international guidelines in our center that could be related to restricted definitions of optimal antibiotic therapy. Despite most patients received logical antimicrobial therapy, actions should be taken into account to reach optimal antibiotic usage.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Guideline Adherence; Humans; Respiratory Tract Infections; Retrospective Studies

Topics: Adenoviridae; Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Cephalosporins; COVID-19; COVID-19 Drug Treatment; Fluoroquinolones; Humans; Hydroxychloroquine; Incidence; Influenza A virus; Influenza B virus; Influenza, Human; Italy; Macrolides; Pandemics; Penicillins; Physical Distancing; Prescription Drug Overuse; Quarantine; Respiratory Syncytial Viruses; Respiratory Tract Infections; SARS-CoV-2

Chronic Azithromycin (AZM) is a common treatment for lung infection. Among adults at risk of cardiac events, AZM use has been associated with cardiovascular harm. We assessed cardiovascular safety of AZM among children with CF, as a secondary analysis of a placebo-controlled, clinical trial, in which study drug was taken thrice-weekly for a planned 18 months. Safety assessments using electrocardiogram (ECG) occurred at study enrollment, and then after 3 weeks and 18 months of participation. Among 221 study participants with a median of 18 months follow-up, increased corrected QT interval (QTc) of ≥30 msec was rare, at 3.4 occurrences per 100 person-years; and incidence of QTc prolongation was no higher in the AZM arm than the placebo arm (1.8 versus 5.4 per 100 person-years). No persons experienced QTc intervals above 500 msec. Long-term chronic AZM use was not associated with increased QT prolongation.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Cystic Fibrosis; Double-Blind Method; Female; Humans; Long QT Syndrome; Male; Multicenter Studies as Topic; Pseudomonas Infections; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Cystic fibrosis (CF) patients are at risk of acquiring chronic Pseudomonas aeruginosa lung infections. The biofilm mode of growth of P. aeruginosa induces tolerance to antibiotics and the host response; accordingly, treatment failure occurs. Supplemental azithromycin has proven beneficial in CF owing to potential immunomodulatory mechanisms. Clinical studies have demonstrated a reduction in exacerbations in CF patients by avian IgY anti-Pseudomonas immunotherapy. We hypothesise that azithromycin pre-treatment could potentiate the observed anti-Pseudomonas effect of IgY opsonisation in vivo. Evaluation of phagocytic cell capacity was performed using in vitro exposure of azithromycin pre-treated human polymorphonuclear neutrophils to IgY opsonised P. aeruginosa PAO3. A murine lung infection model using nasal planktonic P. aeruginosa inoculation and successive evaluation 24 h post-infection was used to determine lung bacteriology and subsequent pulmonary inflammation. Combined azithromycin treatment and IgY opsonisation significantly increased bacterial killing compared with the two single-treated groups and controls. In vivo, significantly increased bacterial pulmonary elimination was revealed by combining azithromycin and IgY. A reduction in the inflammatory markers mobiliser granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 2 (MIP-2) and interleukin 1 beta (IL-1β) paralleled this effect. Combination of azithromycin and anti-Pseudomonas IgY potentiated the killing and pulmonary elimination of P. aeruginosa in vitro and in vivo. The augmented effect of combinatory treatment with azithromycin and IgY constitutes a potential clinical application for improving anti-Pseudomonas strategies.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Birds; Colony Count, Microbial; Cystic Fibrosis; Cytokines; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Immunoglobulins; Immunotherapy; Lung; Mice; Mice, Inbred BALB C; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Topics: Azithromycin; Bacterial Typing Techniques; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; High-Throughput Nucleotide Sequencing; Hospitals, Pediatric; Humans; Infant; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Myanmar; Phylogeny; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae; Tetracycline; Whole Genome Sequencing

Inappropriate use of antibiotics in the outpatient setting is a common problem, yet literature evaluating best practices for stewardship interventions in this setting is sparse.. To evaluate the impact of clinical decision support (CDS) order panels for azithromycin prescribing on the percentage of inappropriate azithromycin prescriptions in primary care clinics.. Single-center, retrospective analysis of azithromycin prescribing within nine primary care clinics. Pre-intervention and post-intervention data included azithromycin prescriptions from November 2016 to April 2017 and February 2019 to July 2019, respectively. Key exclusion criteria included prescriptions for the treatment of a sexually transmitted infection or for prophylaxis against Mycobacterium avium complex.. The azithromycin CDS panel was created to provide point-of-care information on appropriate use of azithromycin along with recommended alternatives based on indications. CDS panels were implemented on January 10, 2019.. The primary composite outcome was the change in the percentage of inappropriate azithromycin prescribing before and after implementation of CDS panels. The composite outcome included prescriptions with inappropriate indications for azithromycin, unnecessary prescriptions, inappropriate treatment durations, and/or inappropriate dose.. There were 306 and 263 prescriptions for azithromycin prescriptions included for analysis in the pre- and post-intervention periods, respectively. Inappropriate prescriptions decreased by 12.6% from the pre- to post-intervention period (81.4% vs. 68.8%; P < 0.001). In both the pre- and post-intervention period, bronchitis and unspecified upper respiratory tract infections (URI) were the two most common indications where azithromycin was prescribed inappropriately.. Implementation of CDS order panels resulted in a reduction in inappropriate azithromycin prescribing. However, additional improvement in azithromycin prescribing is needed especially for the indications of bronchitis and unspecified URI.

Topics: Anti-Bacterial Agents; Azithromycin; Decision Support Systems, Clinical; Humans; Inappropriate Prescribing; Practice Patterns, Physicians'; Primary Health Care; Respiratory Tract Infections; Retrospective Studies

Adenoviruses have been reported to affect a broad range of host species, tend to be species specific, and often affect the respiratory system. This report describes the isolation of an adenovirus from deep nasal swabs of two wild North American porcupines (

Topics: Adenoviridae; Adenoviridae Infections; Animals; Anti-Bacterial Agents; Azithromycin; Bronchodilator Agents; Enrofloxacin; Male; Porcupines; Respiratory Tract Infections; Terbutaline

Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infection. There may exist an association between C. pneumoniae, asthma, and production of immunoglobulin (Ig) E responses in vitro. Interleukin (IL-4) is required for IgE production.. We previously demonstrated that doxycycline suppresses C. pneumoniae-induced production of IgE and IL-4 responses in peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Whereas macrolides have anti-chlamydial activity, their effect on in vitro anti-inflammatory (IgE) and IL-4 responses to C. pneumoniae have not been studied.. PBMC from IgE- adult atopic subjects (N = 5) were infected +/- C. pneumoniae BAL69, +/- azithromycin (0.1, 1.0 ug/mL) for 10 days. IL-4 and IgE levels were determined in supernatants by ELISA. IL-4 and IgE were detected in supernatants of PBMC (day 10).. When azithromycin (0.1, 1.0 ug/ml) was added, IL-4 levels decreased. At low dose, IgE levels increased and at high dose, IgE levels decreased. When PBMC were infected with C. pneumoniae, both IL-4 and IgE levels decreased. Addition of azithromycin (0.1, 1.0 ug/mL) decreased IL-4 levels and had no effect on IgE levels.. These findings indicate that azithromycin decreases IL-4 responses but has a bimodal effect on IgE responses in PBMC from atopic patients in vitro.

Topics: Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; In Vitro Techniques; Interleukin-4; Leukocytes, Mononuclear; Male; Middle Aged; Respiratory Tract Infections; Young Adult

Long-term use of nebulized or oral antibiotics is common in the treatment of cystic fibrosis and non-cystic fibrosis bronchiectasis. To date, however, few studies have focused on the use of nebulized antibiotics in COPD patients. The aims of this study are: to establish whether a combination of nebulized colistin plus continuous cyclic azithromycin in severe COPD patients with chronic bronchial infection due to. A retrospective cohort was created for the analysis of patients with severe COPD and chronic bronchial infection due to. We analyzed 32 severe COPD patients who received nebulized colistin for at least three months (median 17 months [IQR 7-24]). All patients but one received combination therapy with continuous cyclic azithromycin (median 24 months [IQR 11-30]). A significant reduction in the number of ECOPD from baseline of 38.3% at two years of follow-up was observed, with a clear decrease in. In patients with severe COPD and chronic bronchial infection due to

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Bronchi; Colistin; Disease Progression; Drug Therapy, Combination; Female; Humans; Male; Nebulizers and Vaporizers; Pseudomonas Infections; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Retrospective Studies; Severity of Illness Index; Sputum; Time Factors; Treatment Outcome

A major contributor to fatalities in cystic fibrosis (CF) patients stems from infection with opportunistic bacterium Pseudomonas aeruginosa. As a result of the CF patient's vulnerability to bacterial infections, one of the main treatment focuses is antibiotic therapy. However, the highly adaptive nature of P. aeruginosa, in addition to the intrinsic resistance to many antibiotics exhibited by most Gram-negative bacteria, means that multi-drug-resistant (MDR) strains are increasingly prevalent. This makes the eradication of pseudomonal lung infections nearly impossible once the infection becomes chronic. New methods to treat pseudomonal infections are greatly needed in order to eradicate MDR bacteria found within the respiratory tract, and ultimately better the quality of life for CF patients. Herein, we describe a novel approach to combatting pseudomonal infections through the use of bis-2-aminoimidazole adjuvants that can potentiate the activity of a macrolide antibiotic commonly prescribed to CF patients as an anti-inflammatory agent. Our lead bis-2-AI exhibits a 1024-fold reduction in the minimum inhibitory concentration of azithromycin in vitro and displays activity in a Galleria mellonella model of infection.

Topics: Adjuvants, Pharmaceutic; Animals; Anti-Bacterial Agents; Azithromycin; Benzimidazoles; Cystic Fibrosis; Disease Models, Animal; Drug Repositioning; Larva; Microbial Sensitivity Tests; Moths; Pseudomonas aeruginosa; Respiratory Tract Infections

Ureaplasma spp. in the maternal genitourinary tract has come to attention as a cause of preterm labor, spontaneous abortion, chorioamnionitis and adverse outcomes. A few controversies, however, still remain, namely, whether it should be treated aggressively or not. The aim of this study was to evaluate the effect of maternal azithromycin (AZ) treatment for Ureaplasma colonization on neonatal morbidities including bronchopulmonary dysplasia (BPD).. A retrospective case-control study of preterm babies delivered at ≤30 weeks of gestational age (GA) from 2012 to 2016 was conducted. Infants whose mothers had confirmed Ureaplasma colonization and treatment with AZ (m-AZ, cases) were matched by GA to control subjects whose mothers did not have Ureaplasma colonization. A subgroup analysis (nUU(+), infants with neonatal respiratory Ureaplasma colonization; nUU(-), infants without colonization) was also performed.. Fifty-five control subjects were matched to 110 m-AZ subjects. The incidence of preterm premature rupture of membranes (P = 0.003) and of moderate-severe BPD (P = 0.010) was significantly higher in the m-AZ group. On subgroup analysis with post-hoc analysis (m-AZ + nUU(+) [I, n = 55] vs m-AZ + nUU(-) [II, n = 55] vs controls [n = 55]), the incidence of moderate-severe BPD was significantly different: 26% (I) vs 22% (II) vs 7% (controls), P = 0.033.. Maternal Ureaplasma colonization was associated with moderate-severe BPD despite the use of AZ treatment. In addition, if the neonatal respiratory tract was colonized, then moderate-severe BPD developed even with maternal AZ treatment. Hence, selective antenatal and postnatal treatment of Ureaplasma colonization would be needed to control BPD development.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchopulmonary Dysplasia; Case-Control Studies; Female; Female Urogenital Diseases; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Incidence; Infant, Newborn; Infant, Premature; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Tract Infections; Retrospective Studies; Ureaplasma; Ureaplasma Infections

Human rhinovirus (RV) is a common upper and lower respiratory pathogen in lung allograft recipients causing respiratory tract exacerbation and contributing towards allograft dysfunction and long-term lung decline. In this study, we tested the hypothesis that RV could infect both the small and large airways, resulting in significant inflammation.. Matched large and small airway epithelial cells (AEC) were obtained from five lung allograft recipients. Primary cultures were established, and monolayers were infected with RV1b over time with varying viral titre. Cell viability, receptor expression, viral copy number, apoptotic induction and inflammatory cytokine production were also assessed at each region. Finally, the effect of azithromycin on viral replication, induction of apoptosis and inflammation was investigated.. RV infection caused significant cytotoxicity in both large AEC (LAEC) and small AEC (SAEC), and induced a similar apoptotic response in both regions. There was a significant increase in receptor expression in the LAEC only post viral infection. Viral replication was elevated in both LAEC and SAEC, but was not significantly different. Prophylactic treatment of azithromycin reduced viral replication and dampened the production of inflammatory cytokines post-infection.. Our data illustrate that RV infection is capable of infecting upper and lower AEC, driving cell death and inflammation. Prophylactic treatment with azithromycin was found to mitigate some of the detrimental responses. Findings provide further support for the prophylactic prescription of azithromycin to minimize the impact of RV infection.

Topics: Alveolar Epithelial Cells; Anti-Bacterial Agents; Apoptosis; Azithromycin; Cell Survival; Cells, Cultured; Cytokines; Humans; Inflammation; Lung Transplantation; Picornaviridae Infections; Respiratory Tract Infections; Rhinovirus; Virus Replication

Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution.. The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated.. The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations.. We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Azithromycin; Drug Carriers; Drug Compounding; Drug Liberation; Dry Powder Inhalers; Humans; Leucine; Particle Size; Respiratory Tract Infections; Solubility

To determine antibiotic susceptibility of isolates of Streptococcus pneumoniae (n = 573) and Haemophilus influenzae (n = 345) collected in 2014-16 from Bulgaria, Romania, Serbia and Croatia.. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.. Among S. pneumoniae, susceptibility was generally lowest in Romania and Serbia and highest in Bulgaria. Rates of susceptibility to penicillin (CLSI oral or EUCAST) were 22.3% and 21.8% in Romania and Serbia respectively, 57% in Croatia and 86.6% in Bulgaria. Similarly, macrolide susceptibility using CLSI/EUCAST breakpoints was low in Romania and Serbia (∼28% and 34.5%, respectively), higher in Croatia (55.9%) and highest in Bulgaria (∼75%). Only fluoroquinolones were active against all isolates in all four countries. Susceptibility was higher and variability across countries less pronounced for H. influenzae. Susceptibility by CLSI criteria to amoxicillin/clavulanic acid, azithromycin, cefuroxime, ceftriaxone and fluoroquinolones was ≥98% in all countries. Ampicillin susceptibility ranged from 85.3% in Romania to 100% in Bulgaria. Much greater variability was seen across breakpoints. Susceptibility to azithromycin and cefuroxime using CLSI criteria was ≥98% in all four countries, but was 0%-1% by EUCAST criteria.. The variability in antimicrobial susceptibility using different breakpoints makes it difficult for clinicians to interpret antimicrobial resistance data, and efforts should be made to harmonize breakpoints. The variability found across the four neighbouring countries demonstrates the need to monitor and publish national and local resistance patterns. These findings provide information critical for the selection of appropriate antimicrobial agents for the treatment of S. pneumoniae and H. influenzae.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bulgaria; Child; Community-Acquired Infections; Croatia; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Haemophilus Infections; Haemophilus influenzae; Humans; Macrolides; Microbial Sensitivity Tests; Middle Aged; Pneumococcal Infections; Respiratory Tract Infections; Romania; Serbia; Streptococcus pneumoniae; Surveys and Questionnaires; Young Adult

According to clinical trials, azithromycin taken daily for 1 year, decreased exacerbations of chronic obstructive pulmonary disease (COPD).. Effectiveness evaluation of long-term azithromycin to reduce exacerbations in severe COPD patient on optimal therapy in real-life practice.. We conducted a retrospective observational study of severe COPD patients who were prescribed azithromycin (PA)(250 mg, at least 3 times weekly for at least 6 months). Comparison group included severe COPD patients not prescribed azithromycin (NPA). Data were extracted from clinical chart review.. Study included 126 PA and 69 NPA patients. They had severe airflow obstruction, mostly emphysema and one-third bronchiectasis. A predominant feature in the PA group was respiratory tract colonization with Pseudomonas aeruginosa. The mean number of exacerbations per patient per year in the PA group was 3.2 ± 2.1 before initiating azithromycin, and 2.3 ± 1.6 during following year on therapy (p < 0.001). Patients in the NPA group had 1.7 ± 1.3 and 2.5 ± 1.7 exacerbations during first and second follow-up year respectively (p < 0.001). Exacerbation changes from pre to post differed between groups (p < 0.001). Decrease in emergency visits and hospital admissions was significant in PA group. Exacerbation reductions and patient proportions having ≥2 exacerbations extended to the second year of treatment.. These data showed that long-term azithromycin reduces exacerbation numbers in severe COPD patients, and benefits persist beyond one year. Desirable effects are more likely to outweigh the risks and adverse events in patients colonized with Pseudomonas aeruginosa.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Drug Administration Schedule; Female; Hospitalization; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Retrospective Studies; Smoking; Sputum

Data are needed from outpatient settings to better inform antimicrobial stewardship. In this study, a random sample of outpatient antibiotic prescriptions by primary care providers (PCPs) at our health care system was reviewed and compared to consensus guidelines. Over 12 months, 3,880 acute antibiotic prescriptions were written by 76 PCPs caring for 40,734 patients (median panel, 600 patients; range, 33 to 1,547). PCPs ordered a median of 84 antibiotic prescriptions per 1,000 patients per year. Azithromycin (25.8%), amoxicillin-clavulanate (13.3%), doxycycline (12.4%), amoxicillin (11%), fluoroquinolones (11%), and trimethoprim-sulfamethoxazole (10.6%) were prescribed most commonly. Medical records corresponding to 300 prescriptions from 59 PCPs were analyzed in depth. The most common indications for these prescriptions were acute respiratory tract infection (28.3%), urinary tract infection (23%), skin and soft tissue infection (15.7%), and chronic obstructive pulmonary disease (COPD) exacerbation (6.3%). In 5.7% of cases, no reason for the prescription was listed. No antibiotic was indicated in 49.7% of cases. In 12.3% of cases, an antibiotic was indicated, but the prescribed agent was guideline discordant. In another 14% of cases, a guideline-concordant antibiotic was given for a guideline-discordant duration. Therefore, 76% of reviewed prescriptions were inappropriate. Ciprofloxacin and azithromycin were most likely to be prescribed inappropriately. A non-face-to-face encounter prompted 34% of prescriptions. The condition for which an antibiotic was prescribed was not listed in primary or secondary diagnosis codes in 54.5% of clinic visits. In conclusion, there is an enormous opportunity to reduce inappropriate outpatient antibiotic prescriptions.

Topics: Adult; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Delivery of Health Care; Doxycycline; Female; Fluoroquinolones; Humans; Inappropriate Prescribing; Male; Middle Aged; Physicians, Primary Care; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Retrospective Studies; Soft Tissue Infections; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Department of Veterans Affairs; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Respiratory Tract Infections; Time Factors

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Respiratory Tract Infections; Time Factors

Early target attainment is the key factor influencing the outcome of antimicrobial therapy. The objective of the present study was to evaluate the relationship between azithromycin concentrations during the first 24-48 h of therapy and the clinical outcome in order to optimize antimicrobial therapy.. All children with lower respiratory tract infections receiving intravenous azithromycin monotherapy were included. The relationship between azithromycin trough concentrations during the first 24-48 h and the effectiveness and safety was explored.. Data from 44 children [mean (SD) age = 5.25 (3.72) years] were available for final analysis. Children with trough concentrations >0.25 mg/L (n = 8) had a more significant improvement in antibacterial efficacy in terms of decreased C-reactive protein (P = 0.006) and the percentage of neutrophils (P = 0.043) compared with children with trough concentrations ≤0.25 mg/L (n = 36). No drug-related adverse events were shown to have a causal association with azithromycin therapy.. Our study showed the clinical benefits of early target attainment of azithromycin therapy. A target trough concentration of 0.25 mg/L in the first 24-48 h of hospitalization was required to ensure better antibacterial efficacy.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; C-Reactive Protein; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Humans; Leukocyte Count; Plasma; Respiratory Tract Infections; Time Factors; Treatment Outcome

Interventions to support decision-making can reduce inappropriate antibiotic use for acute respiratory infections (ARI), but they may not be sustainable. The objective of the study is to evaluate the long-term effectiveness of a clinical decision-support system (CDSS) interposed at the time of electronic (e-) prescriptions for selected antibiotics.. This is a retrospective, observational intervention study, conducted within a large, statewide Veterans Affairs health system. Participants are outpatients with an initial visit for ARI. A CDSS was deployed upon e-prescription of selected antibiotics during the study period. From 01/2004 to 05/2006 (pre-withdrawal period), the CDSS targeted azithromycin and the fluoroquinolone gatifloxacin. From 05/2006 to 12/2011 (post-withdrawal period), the CDSS was retained for azithromycin but withdrawn for the fluoroquinolone. A manual record review was conducted to determine concordance of antibiotic prescription with ARI treatment guidelines.. Of 1131 included ARI visits, 380 (33.6%) were guideline-concordant. For azithromycin, concordance did not change between the pre- and post-withdrawal periods, and adjusted odds of concordance was 8.8 for the full study period, compared to unrestricted antibiotics. For fluoroquinolones, guideline concordance decreased from 88.6% (39 of 44 visits) to 51.3% (59 of 115 visits), pre- vs. post-withdrawal periods (p < 0.005). The adjusted odds of concordance compared to "All Other Antibiotics" visits decreased from 24.4 (95% CI 9.0-66.3) pre-withdrawal to 5.5 (95% CI 3.5-8.8) post-withdrawal (p = .008). Concordance did not change between those same time periods for antibiotics that were never subjected to the intervention ("All Other Antibiotics").. A CDSS interposed at the time of e-prescription of selected antibiotics can shift their use toward ARI treatment guidelines, and this effect can be maintained over the long term as long as the CDSS remains in place. Removal of the CDSS after 3.5 years of implementation resulted in a rise in guideline-discordant antibiotic use.

Topics: Anti-Bacterial Agents; Azithromycin; Decision Support Systems, Clinical; Electronic Prescribing; Fluoroquinolones; Gatifloxacin; Humans; Maryland; Outpatients; Practice Patterns, Physicians'; Prescription Drug Overuse; Respiratory Tract Infections; Retrospective Studies

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Bronchiolitis; Bronchiolitis Obliterans; Haemophilus Infections; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections

We sought to better understand barriers to adherence to published guidelines for respiratory infections among community providers.. A case-based survey was developed and emailed to all members of the state pediatric society. Providers chose their preferred management for acute otitis media, acute bacterial sinusitis, and community-acquired pneumonia. An "answer key" and a follow-up questionnaire were distributed to assess reevaluation of current practices.. We received 173 completed surveys (15% response rate). While most responders followed guideline recommendations (6 of the 10 questions with ≥ 65% choosing recommended antibiotic), discrepancies existed in several cases. After receiving the answer key, respondents said they reviewed the guidelines (69%), adjusted their practice (26%), used cases for teaching (9%), and discussed guidelines with colleagues (21%).. The majority of respondents followed published guidelines, but there was a tendency to overuse azithromycin in certain cases. Future guidelines including case-based discussions may enhance adherence.

Topics: Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Child; Guideline Adherence; Health Care Surveys; Humans; Practice Patterns, Physicians'; Respiratory Tract Infections

Pulmonary antibiotic delivery is recommended as maintenance therapy for cystic fibrosis (CF) patients who experience chronic infections. However, abnormally thick and sticky mucus present in the respiratory tract of CF patients impairs mucus penetration and limits the efficacy of inhaled antibiotics. To overcome the obstacles of pulmonary antibiotic delivery, we have developed nanocomposite microparticles (nCmP) for the inhalation application of antibiotics in the form of dry powder aerosols.. Azithromycin-loaded and rapamycin-loaded polymeric nanoparticles (NP) were prepared via nanoprecipitation and nCmP were prepared by spray drying and the physicochemical characteristics were evaluated.. The nanoparticles were 200 nm in diameter both before loading into and after redispersion from nCmP. The NP exhibited smooth, spherical morphology and the nCmP were corrugated spheres about 1 μm in diameter. Both drugs were successfully encapsulated into the NP and were released in a sustained manner. The NP were successfully loaded into nCmP with favorable encapsulation efficacy. All materials were stable at manufacturing and storage conditions and nCmP were in an amorphous state after spray drying. nCmP demonstrated desirable aerosol dispersion characteristics, allowing them to deposit into the deep lung regions for effective drug delivery.. The described nCmP have the potential to overcome mucus-limited pulmonary delivery of antibiotics.

Topics: Azithromycin; Cystic Fibrosis; Drug Delivery Systems; Humans; Nanocomposites; Nanoparticles; Particle Size; Respiratory Tract Infections; Sirolimus; Treatment Outcome; X-Ray Diffraction

Topics: Azithromycin; Humans; Infant; Infections; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Respiratory Tract Infections; Secondary Prevention

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Respiratory Tract Infections; Secondary Prevention

Antibiotic overuse is driving the emergence of antibiotic resistance worldwide. Good data on prescribing behaviours of healthcare providers are needed to support antimicrobial stewardship initiatives. This study examined the differences in antibiotic prescribing rates of public and private primary care clinics in Malaysia.. We used data from the National Medical Care Survey (NMCS), a nationwide cluster sample of Malaysian public and private primary care clinics in 2014. NMCS contained demographic, diagnoses and prescribing from 129 public clinics and 416 private clinics. We identified all encounters who were prescribed antibiotic and analyse the prescribing rate, types of antibiotics, and diagnoses that resulted in antibiotic.. Five thousand eight hundred ten encounters were prescribed antibiotics; antibiotic prescribing rate was 21.1 % (public clinics 6.8 %, private clinics 30.8 %). Antibiotic prescribing was higher in private clinics where they contributed almost 87 % of antibiotics prescribed in primary care. Upper respiratory tract infection (URTI) was the most frequent diagnosis in patients receiving antibiotic therapy and accounted for 49.2 % of prescriptions. Of the patients diagnosed with URTI, 46.2 % received antibiotic treatment (public 16.8 %, private 57.7 %). Penicillins, cephalosporins and macrolides were the most commonly prescribed antibiotics and accounted for 30.7, 23.6 and 16.0 % of all antibiotics, respectively. More recently available broad-spectrum antibiotics such as azithromycin and quinolones were more frequently prescribed in private clinics.. Antibiotic prescribing rates are high in both public and private primary care settings in Malaysia, especially in the latter. This study provides evidence of excessive and inappropriate antibiotic prescribing for self-limiting conditions. These data highlights the needs for more concerted interventions targeting both prescribers and public. Improvement strategies should focus on reducing inappropriate prescribing.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Cross-Sectional Studies; Drug Prescriptions; Female; Health Personnel; Humans; Inappropriate Prescribing; Macrolides; Malaysia; Male; Middle Aged; Patients' Rooms; Penicillins; Practice Patterns, Physicians'; Private Practice; Quinolones; Respiratory Tract Infections

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.

Topics: Animals; Azithromycin; Cell Line; Epithelial Cells; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Macrophages, Alveolar; Mice; Respiratory Tract Infections

The Centers for Disease Control and Prevention has promoted the appropriate use of antibiotics since 1995 when it initiated the National Campaign for Appropriate Antibiotic Use in the Community. This study examined upper respiratory tract infections included in the campaign to determine the degree to which antibiotics were appropriately prescribed and subsequent admission rates in a veteran population. This study was a retrospective chart review conducted among outpatients with a diagnosis of a respiratory tract infection, including bronchitis, pharyngitis, sinusitis, or nonspecific upper respiratory tract infection, between January 2009 and December 2011. The study found that 595 (35.8%) patients were treated appropriately, and 1,067 (64.2%) patients received therapy considered inappropriate based on the Get Smart Campaign criteria. Overall the subsequent readmission rate was 1.5%. The majority (77.5%) of patients were prescribed an antibiotic. The most common antibiotics prescribed were azithromycin (39.0%), amoxicillin-clavulanate (13.2%), and moxifloxacin (7.5%). A multivariate regression analysis demonstrated significant predictors of appropriate treatment, including the presence of tonsillar exudates (odds ratio [OR], 0.6; confidence interval [CI], 0.3 to 0.9), fever (OR, 0.6; CI, 0.4 to 0.9), and lymphadenopathy (OR, 0.4; CI, 0.3 to 0.6), while penicillin allergy (OR, 2.9; CI, 1.7 to 4.7) and cough (OR, 1.6; CI, 1.1 to 2.2) were significant predictors for inappropriate treatment. Poor compliance with the Get Smart Campaign was found in outpatients for respiratory infections. Results from this study demonstrate the overprescribing of antibiotics, while providing a focused view of improper prescribing. This article provides evidence that current efforts are insufficient for curtailing inappropriate antibiotic use.

Topics: Ambulatory Care; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Centers for Disease Control and Prevention, U.S.; Drug Utilization; Female; Fluoroquinolones; Humans; Inappropriate Prescribing; Male; Middle Aged; Moxifloxacin; Multivariate Analysis; Outpatients; Practice Patterns, Physicians'; Respiratory Tract Infections; Retrospective Studies; United States

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Humans; Respiratory Tract Infections; Streptococcus pneumoniae

Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

Topics: Adult; Aged; Aged, 80 and over; Aneurysm, Infected; Aortic Aneurysm, Abdominal; Azithromycin; Critical Care; Female; Humans; Infusion Pumps; Infusions, Intravenous; Male; Middle Aged; Phlebitis; Respiratory Tract Infections; Retrospective Studies; Safety; Solvents

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Humans; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Respiratory Tract Infections; Secondary Prevention

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Respiratory Tract Infections; Secondary Prevention

Topics: Antimalarials; Azithromycin; Chloroquine; Female; Gastrointestinal Diseases; Humans; Malaria; Male; Respiratory Tract Infections

Community-acquired respiratory tract infections (CARTI) are commonly caused by Streptococcus pneumoniae (SPN) and empirically treated with azithromycin. This study assessed clinical cure rates in azithromycin-treated subjects with CARTI caused by azithromycin-susceptible (Azi-S) or azithromycin-resistant (Azi-R) SPN.. 1127 subjects with CARTI (402 acute otitis media, 309 community-acquired pneumonia, 255 acute bacterial exacerbations of chronic bronchitis and 161 acute bacterial sinusitis) in 13 Phase 3 clinical trials (1993-2007) had a confirmed pathogen, received azithromycin and were assessed for clinical cure/failure. 34.4% of subjects (388/1127) had a positive culture for SPN; 33.4% (376/1127) had Azi-S or Azi-R SPN.. 28.9% (112/388) of subjects with SPN had Azi-R SPN: 35.7% (40/112) were low-level Azi-R SPN (LLAR; MIC 2-8 mg/L), while 64.3% (72/112) were high-level Azi-R SPN (HLAR; MIC ≥16 mg/L). Among Azi-S and Azi-R SPN CARTI subjects, clinical cure rates were: 86.2% (324/376) overall; 89.4% (236/264) for subjects with Azi-S SPN; 78.6% (88/112) for subjects with Azi-R SPN (P = 0.003, versus Azi-S); 77.5% (31/40) for subjects with LLAR SPN (P < 0.001); and 79.2% (57/72) for subjects with HLAR SPN (P = 0.122).. Clinical cure rates in CARTI subjects treated with azithromycin were higher for Azi-S SPN (89.4%) versus Azi-R SPN (78.6%; P = 0.003). However, cure rates were not different for subjects infected with LLAR-SPN versus HLAR-SPN. At the observed prevalence of Azi-R SPN of 28.9%, an additional 3.1 clinical failures would be predicted, as a consequence of azithromycin resistance (LLAR and HLAR), per 100 subjects treated empirically with azithromycin.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Phenotype; Respiratory Tract Infections; Streptococcus pneumoniae; Treatment Outcome; Young Adult

Recent clinical trials indicate that the use of azithromycin is associated with the emergence of macrolide resistance. The objective of our study was to simultaneously characterize free target site concentrations and correlate them with the MIC90s of clinically relevant pathogens. Azithromycin (500 mg once daily [QD]) was administered orally to 6 healthy male volunteers for 3 days. The free concentrations in the interstitial space fluid (ISF) of muscle and subcutaneous fat tissue as well as the total concentrations in plasma and polymorphonuclear leukocytes (PMLs) were determined on days 1, 3, 5, and 10. All concentrations were modeled simultaneously in NONMEM 7.2 using a tissue distribution model that accounts for nonlinear protein binding and ionization state at physiological pH. The model performance and parameter estimates were evaluated via goodness-of-fit plots and nonparametric bootstrap analysis. The model we developed described the concentrations at all sampling sites reasonably well and showed that the overall pharmacokinetics of azithromycin is driven by the release of the drug from acidic cell/tissue compartments. The model-predicted unionized azithromycin (AZM) concentrations in the cytosol of PMLs (6.0 ± 1.2 ng/ml) were comparable to the measured ISF concentrations in the muscle (8.7 ± 2.9 ng/ml) and subcutis (4.1 ± 2.4 ng/ml) on day 10, whereas the total PML concentrations were >1,000-fold higher (14,217 ± 2,810 ng/ml). The total plasma and free ISF concentrations were insufficient to exceed the MIC90s of the skin pathogens at all times. Our results indicate that the slow release of azithromycin from low pH tissue/cell compartments is responsible for the long terminal half-life of the drug and thus the extended period of time during which free concentrations reside at subinhibitory concentrations.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Half-Life; Healthy Volunteers; Humans; Male; Microbial Sensitivity Tests; Respiratory Tract Infections

The benefits of the use of antibiotics in the mass treatment for active trachoma and other diseases have been documented, but the secondary effects arising from such a programme have not been fully elucidated. The purpose of this study was to investigate the potential secondary benefits arising from the use of azithromycin in mass treatment of active trachoma in an economically challenged Kenyan nomadic community.. Health information reports for January 2005 to December 2010 were reviewed to determine the annual trends of infectious diseases in the two districts, Narok and Transmara. The year 2007 was considered as the baseline for mass drug administration (MDA). Odds ratios (OR) were used to describe the association.. The mass distribution coverage in Narok was 83% in 2008, 74% in 2009 and 63% in 2010. The odds for malaria (OR = 1.13; 95% CI 1.12-1.14), diarrhoeal diseases (OR = 1.04; 95% CI 1.01-1.06), urinary tract infections (UTIs) (OR = 1.21; 95% CI 1.17-1.26), intestinal worms (OR, 4.98; 95% CI 4.68-5.3), and respiratory diseases other than pneumonia (OR, 1.15; 95% CI 1.13-1.16) were higher after three rounds of mass treatment, indicating a better outcome. Before the intervention, there was a reducing trend in the odds for respiratory diseases. In Transmara (control), there was an increase in odds for malaria, respiratory infections, UTIs and intestinal worms. The odds for diarrhoeal diseases, skin diseases and pneumonia decreased throughout the study period.. Mass distribution of azithromycin may have contributed to the decrease in the prevalence of the respiratory infections in Narok District.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Kenya; Respiratory Tract Infections; Trachoma; Treatment Outcome

Novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]- 8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 2a and 2b were designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Among these, compound 2a possessing (S)-configuration for the asymmetrical carbon on the pyrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens including gram-positive (Streptococcus pneumoniae and Staphylococcus aureus), gram-negative (Haemophilus influenzae and Moraxcella catarrhalis), and atypical strains (Chalmydia pneumoniae and Mycoplasma pneumoniae), as well as multidrug-resistant Streptococcus pneumoniae and quinolone-resistant and methicillin-resistant Staphylococcus aureus). Furthermore, compound 2a showed excellent in vivo activity against the experimental murine pneumonia model due to multidrug resistant Streptococcus pneumoniae (MDRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies.

Topics: Animals; Anti-Bacterial Agents; Drug Design; Fluoroquinolones; Haemophilus influenzae; Male; Mice; Microbial Sensitivity Tests; Quinolones; Rats; Respiratory Tract Infections; Spiro Compounds; Staphylococcus aureus; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchiectasis; Erythromycin; Female; Humans; Male; Respiratory Tract Infections

To investigate the etiology of community-acquired respiratory tract infections (CARTI) and the antimicrobial resistance of the major pathogens in primary hospitals in Shanghai.. Patients with CARTI were prospectively recruited from 30 primary hospitals from December 2007 to July 2010. Those who had used antimicrobials within previous 2 weeks were excluded from the study. The clinical information such as temperature, white blood cell (WBC) count and percentage of neutrophils was recorded, and throat swab or deep cough sputum was collected to isolate pathogens. The specimens were collected and couriered to the Zhongshan Hospital microbiology laboratory within 2 h for bacterial culture. The minimal inhibition concentrations (MIC) of penicillin G, amoxicillin, cephradine, cephalexin, cefadroxil, sulfamethoxazole/trimethoprim and azithromycin were determined using the agar dilution test.. Totally 806 qualified cases were enrolled in this study. Fever (T ≥ 38 °C) was present in 51.7% (n = 417) , and increased WBC count (>10×10(9)/L) was noted in 68.5% (n = 552 cases) of the patients. For bacterial culture, 184 strains were isolated from throat swabs of 688 patients with upper respiratory infection; the most frequently isolated bacteria were Haemophilus influenzae (44, 23.9%), Staphylococcus aureus (44, 23.9%) and Group G streptococcus (43, 23.0%). Thirty-three strains were isolated from 118 patients with lower respiratory infections, with Haemophilus influenza (21, 63.6%), Group G streptococcus (6,18.2%) and Streptococcus pneumoniae (3,9.1%) as the leading pathogens. All strains of Haemophilus influenzae were susceptible to azithromycin. The susceptibility rate of Streptococcus pneumoniae to penicillin was as high as 94.7%, while that to azithromycin was significantly decreased (21.1%). The MIC90 values of cephalexin, cefadroxil and ceftazidime for β-hemolytic streptococcus spp were ≤ 2 mg/L.. Upper respiratory infections were responsible for most cases of CARTI. The commonly used antimicrobials in primary hospitals kept a high susceptibility to the frequent pathogens for CARTI. However, Streptococcus pneumoniae showed a decreased susceptibility to macrolides, which should be used carefully as a single agent when treating CARTI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Child; Child, Preschool; China; Community-Acquired Infections; Drug Resistance, Bacterial; Female; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Population Surveillance; Prospective Studies; Respiratory Tract Infections; Staphylococcus aureus; Streptococcus pneumoniae; Young Adult

Mycobacterium abscessus is an emerging cause of respiratory disease and soft tissue infections. Whole genome sequencing and other molecular approaches are enhancing our understanding of outbreaks, antibiotic resistance mechanisms, and virulence properties, and of the phylogeny of the M. abscessus complex. Infection models are providing further insights into factors such as colony phenotype that impact host-pathogen interactions. This paper reviews recent developments in our understanding of genetic variation in M. abscessus and the potential relevance for disease and treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Clarithromycin; DNA, Bacterial; Drug Resistance, Bacterial; Female; Genetic Variation; Host-Pathogen Interactions; Humans; Lung; Male; Mycobacterium; Mycobacterium Infections, Nontuberculous; Phylogeny; Respiratory Tract Infections; Sequence Analysis, DNA; Soft Tissue Infections; Virulence

Utilizing a fully synthetic route to tetracycline analogues, the C-9 side-chain of the fluorocyclines was optimized for both antibacterial activity and oral efficacy. Compounds were identified that overcome both efflux (tet(K), tet(A)) and ribosomal protection (tet(M)) tetracycline-resistance mechanisms and are active against Gram-positive and Gram-negative organisms. A murine systemic infection model was used as an oral efficacy screen to rapidly identify compounds with oral bioavailability. Two compounds were identified that exhibit both oral bioavailability in rat and clinically relevant bacterial susceptibility profiles against major respiratory pathogens. One compound demonstrated oral efficacy in rodent lung infection models that was comparable to marketed antibacterial agents.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Biological Availability; Cyclophosphamide; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Lung; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Neutropenia; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections; Ribosomes; Sepsis; Stereoisomerism; Structure-Activity Relationship; Tetracycline Resistance; Tetracyclines

A novel series of acylides 4 were designed to overcome antibacterial resistance and evaluated for in vitro and in vivo activity. This series of acylides was designed from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. These compounds showed significantly potent antibacterial activity against not only Gram-positive pathogens, including macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens such as Haemophilus influenzae. These acylides also showed better activity against telithromycin resistant Streptococcus pneumoniae strains.

Topics: Anti-Bacterial Agents; Chemistry, Pharmaceutical; Clarithromycin; Drug Design; Drug Resistance, Bacterial; Haemophilus influenzae; Humans; Ketolides; Microbial Sensitivity Tests; Models, Chemical; Nitrogen; Respiratory Tract Infections; Streptococcus pneumoniae

Macrolide antibiotics are widely prescribed for the treatment of respiratory tract infections; however, the increasing prevalence of macrolide-resistant pathogens is a public health concern. Therefore, the development of new macrolide derivatives with activities against resistant pathogens is urgently needed. A series of novel 6-O-(heteroaryl-isoxazolyl)propynyl 2-fluoro ketolides has been synthesized from erythromycin A. These compounds have shown very promising in vitro and in vivo antibacterial activities against key respiratory pathogens including erythromycin-susceptible/resistant strains.

Topics: Anti-Bacterial Agents; Crystallography, X-Ray; Drug Resistance, Bacterial; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Halogenation; Humans; Ketolides; Microbial Sensitivity Tests; Models, Molecular; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus

Topics: Azithromycin; Clarithromycin; Female; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

The prognosis of patients with chronic respiratory tract infections, especially diffuse panbronchiolitis, is remarkably improved by long-term administration of low-dose macrolides. However, in some cases, patients are refractory to macrolide treatment and show a low or no response; therefore, new treatment strategies are required. Here we present a patient refractory to either single low-dose clarithromycin or azithromycin but responded remarkably to the combination usage of both macrolides.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Therapy, Combination; Female; Humans; Immunologic Factors; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Treatment Outcome

We have shown that clarithromycin (CAM), a macrolide antibiotic, more highly distributes from plasma to lung epithelium lining fluid (ELF), the infection site of pathogens, than azithromycin (AZM) and telithromycin (TEL). Transporter(s) expressed on lung epithelial cells may contribute to the distribution of the compiunds to the ELF. However, distribution mechanisms are not well known. In this study, their transport characteristics in Calu-3 cell monolayers as model lung epithelial cells were examined. The basolateral-to-apical transport of CAM through Calu-3 cell monolayers was greater than that of AZM and TEL. Although verapamil and cyclosporine A as MDR1 substrates completely inhibited the basolateral-to-apical transport, probenecid as MRP1 inhibitor did not show an effect. These results suggest that the antibiotics are transported from plasma to ELF by MDR1 of lung epithelial cells. In addition, their affinity and binding rate to MDR1 was examined by ATP activity assay. The affinity and binding rate of CAM was greater than those of AZM and TEL. These corresponded with the distributions from plasma to ELF as described above. The present study suggests that the more highly distribution of CAM from plasma to ELF is due to the high affinity and binding rate to MDR1 of lung epithelial cells.

Topics: Adenosine Triphosphatases; Algorithms; Animals; Anti-Bacterial Agents; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B, Member 1; Azithromycin; Biological Transport, Active; Cell Line; Clarithromycin; Epithelial Cells; Ketolides; Lung; Mice; Multidrug Resistance-Associated Proteins; Protein Binding; Respiratory Tract Infections

In the present study, the serotype distribution and antibiotic resistance of S. pneumoniae from pediatric patients with upper respiratory infections in Beijing, 2010 were described. 140 pneumococcal isolates were obtained, and the prevailing five serotypes were 19F (18.6%), 23F (9.3%), 14 (9.3%), 15 (9.3%), and 6A (7.1%). The vaccine coverage of PCV7, PCV10, and PCV13 were 43.6%, 43.6%, and 60.0%, respectively. According to the CLSI 2010 criteria, 99.3% of the S. pneumoniae isolates were susceptible to penicillin. The resistance rates to erythromycin and azithromycin were 96.4% and 97.1%, respectively. Meanwhile, 64.3% (90/140) of all pneumococcal isolates were multidrug-resistant S. pneumoniae (MDRSP). PCV13 covered 68.9% (62/90) of MDRSP strains, whereas it was 47.8% (43/90) for PCV7. ErmB was the dominant macrolide-resistance gene, whereas 30.4% pneumococcal isolates expressed both ermB and mefA. No isolate expressed ermTR. The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 6A and 19A, and the conjugate vaccines could prevent the spread of MDRSP. S. pneumoniae is still sensitive to penicillin. The resistance rate of S. pneumoniae to macrolides is high and ermB is the dominant macrolide-resistance gene in China, so continued surveillance of the antimicrobial susceptibility of S. pneumoniae may be necessary.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; China; Drug Resistance, Bacterial; Erythromycin; Genes, Bacterial; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Respiratory Tract Infections; Serotyping; Streptococcus pneumoniae

A nationwide multicenter susceptibility surveillance study (Susceptibility to the Antimicrobials Used in the Community in España [SAUCE] project), SAUCE-4, including 2,559 Streptococcus pneumoniae, 2,287 Streptococcus pyogenes, and 2,736 Haemophilus influenzae isolates was carried out from May 2006 to June 2007 in 34 Spanish hospitals. Then, the results from SAUCE-4 were compared to those from all three previous SAUCE studies carried out in 1996-1997, 1998-1999, and 2001-2002 to assess the temporal trends in resistance and the phenotypes of resistance over the 11-year period. In SAUCE-4, on the basis of the CLSI breakpoints, penicillin (parenteral, nonmeningitis breakpoint) and cefotaxime were the antimicrobials that were the most active against S. pneumoniae (99.8% and 99.6%, respectively). Only 0.9% of isolates had a penicillin MIC of > or = 2 microg/ml. In S. pyogenes, nonsusceptibility to erythromycin was observed in 19.4% of isolates. Among the H. influenzae isolates, a beta-lactamase-positive prevalence of 15.7% was found. A statistically significant temporal decreasing trend over the 11-year period was observed for nonsusceptibility (from 60.0% to 22.9%) and resistance (from 36.5% to 0.9%) to penicillin and for the proportion of erythromycin-resistant isolates of S. pneumoniae of the macrolide-lincosamide-streptogramin B (MLS(B)) phenotype (from 98.4% to 81.3%). A similar trend was observed for the prevalence of ampicillin resistance (from 37.6% to 16.1%), beta-lactamase production (from 25.7% to 15.7%), and beta-lactamase-negative ampicillin resistance (BLNAR) in H. influenzae (from 13.5% to 0.7%). Among erythromycin-resistant isolates of S. pyogenes, a significant increasing trend in the prevalence of MLS(B) was observed (from 7.0% to 35.5%). SAUCE-4 confirms a generalized decline in the resistance of the main respiratory pathogens to the antimicrobials as well as a shift in their resistance phenotypes.

Topics: Ampicillin; Anti-Bacterial Agents; Cefotaxime; Erythromycin; Haemophilus influenzae; Lincosamides; Macrolides; Microbial Sensitivity Tests; Penicillins; Respiratory Tract Infections; Spain; Streptococcus pneumoniae; Streptococcus pyogenes; Streptogramin B

The macrolide efflux mechanism of resistance, mef, was characterized in community-acquired respiratory tract infections with Streptococcus pyogenes. Fifty-four (4.6%) M phenotype isolates were screen tested as negative for mef(A). Of these 54 isolates, 5 (0.4%), 27 (2.3%), and 1 (0.1%) were considered to be mef(I) positive, a novel mosaic variant of mef, or a novel subclass of mef, respectively. This study shows (i) the definitive presence of mef(E) in S. pyogenes and its global distribution, (ii) the presence of a mosaic variant of mef composed of mef(A) and mef(E), (iii) the previously undescribed presence of mef(I) in S. pyogenes, and (iv) the presence of a novel subclass of mef in S. pyogenes.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Community-Acquired Infections; Drug Resistance, Bacterial; Global Health; Humans; Macrolides; Membrane Proteins; Microbial Sensitivity Tests; Molecular Sequence Data; Population Surveillance; Respiratory Tract Infections; Sequence Analysis, DNA; Streptococcal Infections; Streptococcus pyogenes

Fifty-three Mycoplasma pneumoniae strains were isolated from pediatric patients in Shanghai, China, from October 2005 to February 2008. Of 53 clinical isolates, 44 (83%) were resistant to erythromycin (MICs of >128 microg/ml for all 44 strains), azithromycin, and clarithromycin. All macrolide-resistant M. pneumoniae strains harbored an A-to-G transition mutation at position 2063 in 23S rRNA genes. Forty-five (85%) clinical isolates were classified into the P1 gene restriction fragment length polymorphism type I, and six (11%) were type II.

Topics: Adhesins, Bacterial; Anti-Bacterial Agents; Child; China; Drug Resistance, Bacterial; Genes, rRNA; Humans; Macrolides; Microbial Sensitivity Tests; Mutation; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Respiratory Tract Infections; RNA, Ribosomal, 23S; Sequence Analysis, DNA

Fifty clinical Mycoplasma pneumoniae strains were isolated from 370 children with respiratory tract infections. Four strains were susceptible to macrolides, while the other 46 (92%) were macrolide resistant. The molecular mechanism of resistance was shown to be associated with point mutations in 23S rRNA at positions 2063 and 2064.

Topics: Anti-Bacterial Agents; Child; China; Drug Resistance, Bacterial; Humans; Macrolides; Microbial Sensitivity Tests; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Point Mutation; Respiratory Tract Infections; RNA, Ribosomal, 23S

In an effort to find new antibiotics, a novel series of 14-membered macrolides with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains has been synthesized based on commercially available clarithromycin. Chemical transformation of hydroxy group at position C-3 afforded range of ketolides and acylides. Compared to telithromycin, compound 15a demonstrated improved in vitro activity against erythromycin-susceptible and -resistant strains.

Topics: Anti-Bacterial Agents; Chemistry, Pharmaceutical; Clarithromycin; Drug Design; Drug Resistance, Multiple, Bacterial; Erythromycin; Humans; Imidazoles; Ketolides; Macrolides; Microbial Sensitivity Tests; Models, Chemical; Respiratory Tract Infections; Staphylococcus aureus; Streptococcus pneumoniae; Sulfides; Sulfur

Acute urticaria is a common and disturbing disorder in children and has a versatile etiology.. To investigate the association of acute urticaria with Mycoplasma pneumoniae infection in hospitalized children.. Hospitalized children with acute urticaria from Taiwan who did not respond to antihistamine treatment and avoidance of food allergens were studied from February 1, 2006, to July 31, 2007. These patients with urticaria were compared with those who had other respiratory tract diseases and were classified into 2 groups: urticaria patients with and without M pneumoniae infection. The presence of M pneumoniae infection was determined by positive serologic findings.. Sixty-five patients with acute urticaria and 49 patients with other respiratory tract diseases were enrolled in this study. Patients with urticaria had significantly less febrile duration but significantly higher platelet and lymphocyte counts than those with other respiratory tract diseases. Of the 65 patients with urticaria, 21 (32%) showed serologic evidence of M pneumoniae infection. Patients with M pneumoniae-associated urticaria received azithromycin treatment and needed a shorter time for improvement (P = .01) and complete resolution (P = .04). The total IgE levels and the results of specific IgE tests were not significantly different between urticaria patients with and without M pneumoniae infection.. This study found that in Taiwan one-third of acute childhood urticaria leading to patient hospitalization was related to M pneumoniae infection. Therefore, children with urticaria who are not responding to antihistamine treatment and abstinence from food allergens should be encouraged to undergo serologic examinations for M pneumoniae to diagnose this antibiotic-responsive disorder.

Topics: Abdominal Pain; Alanine Transaminase; Allergens; Aspartate Aminotransferases; Azithromycin; Blood Cell Count; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Female; Fever; Humans; Immunoglobulin E; Length of Stay; Male; Pneumonia, Mycoplasma; Respiratory Tract Infections; Taiwan; Urticaria; Vomiting

We investigated the in vitro activity of AR-709, a novel diaminopyrimidine antibiotic currently in development for treatment of community-acquired upper and lower respiratory tract infections, against 151 Streptococcus pneumoniae strains from various European countries. AR-709 showed excellent activity against both drug-susceptible and multidrug-resistant pneumococci.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Europe; Humans; Microbial Sensitivity Tests; Pyrimidines; Respiratory Tract Infections; Streptococcus pneumoniae

Thirty-one cats showing clinical signs of upper respiratory tract disease with a presumed bacterial component based on clinical signs were administered either amoxycillin or azithromycin to determine which drug protocol was optimal for empirical use. A clinical score was determined and nasal and pharyngeal swabs were collected for bacterial culture, virus isolation and polymerase chain reaction prior to the start of therapy. Cats failing to respond to the initial antibiotic were then administered the other drug. There were no differences in clinical scores between the two groups at the start of therapy. Eleven of 31 cats improved after administration of the first antibiotic, 16 cats were switched to the alternate antibiotic, and four cats were removed from the study for additional supportive treatments. Eight of 27 cats failed to respond to either antibiotic. The chi2 test for outcomes revealed no differences in response to therapy for either antimicrobial.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Cat Diseases; Cats; Chi-Square Distribution; Drug Resistance, Bacterial; Female; Male; Random Allocation; Respiratory Tract Infections; Treatment Outcome

Haemophilus influenzae is one of the main aetiological agents of community-acquired respiratory tract infections. The primary aim of this study was to evaluate the antibacterial activity of telithromycin against H. influenzae clinical isolates showing different pattern of resistance in comparison with azithromycin and clarithromycin at 1/4 x, 1/2 x, 1 x, 2 x, 4 x minimum inhibitory concentration (MIC) and to peak concentrations in epithelial lining fluid (ELF). The secondary aim was to determine the influence of CO2 enriched atmosphere on bacterial susceptibility.. Telithromycin showed high activity against H. influenzae, including strains susceptible to beta-lactams (n = 200), beta-lactamase producer (n = 50) and beta-lactamase negative ampicillin resistant (BLNAR) (n = 10), with MIC from < or =0.03 to 4 mg/L, and MIC50/MIC90 of 1/2 mg/L with susceptibility rate of 100%, and minimum bactericidal concentrations (MBC) from 2 to 4-fold higher than the MIC. Azithromycin was the most active tested macrolide (range: 0.25 - 4 mg/L; MIC50/MIC90: 1/2 mg/L), comparable to telithromycin, while clarithromycin showed the highest MICs and MBCs (range: 0.25 - 8 mg/L; MIC50/MIC90: 2/8 mg/L). In time-kill studies, telithromycin showed a bactericidal activity at the higher concentrations (4 - 2 x MIC and ELF) against all the strains, being complete after 12 - 24 hours from drug exposition. At MIC concentrations, at ambient air, bactericidal activity of telithromycin and azithromycin was quite similar at 12 hours, and better than that of clarithromycin. Besides, telithromycin and clarithromycin at ELF concentrations were bactericidal after 12 hours of incubation for most strains, while 24 hours were needed to azithromycin to be bactericidal. Incubation in CO2 significantly influenced the MICs and MBCs, and only slightly the in vitro killing curves.. Telithromycin showed an in-vitro potency against H. influenzae comparable to azithromycin, with an in-vitro killing rate more rapid and superior to clarithromycin at 2X-MIC against beta-lactamase producers and BLNAR strains, and to azithromycin at ELF concentrations against beta-lactamase negative strains. Against all strains, MICs and MBCs were lower in the absence of CO2 for the tested antibiotics, showing an adverse effect of incubation in a CO2 environment. The in-vitro potency together with the tissue concentrations of the antimicrobial, should be considered in predicting efficacy.

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Carbon Dioxide; Clarithromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Ketolides; Microbial Sensitivity Tests; Respiratory Tract Infections; Time Factors

We evaluated the recent prevalence of antimicrobial-resistant Haemophilus influenzae isolated from the upper respiratory tracts (URT) of patients in Japan. Mutations in the ftsI gene, which encodes penicillin binding protein 3 (PBP3), and the clonal dissemination of the resistant strains were also investigated. A total of 264 H. influenzae isolates were collected from patients with URT infections. According to the criteria of the Clinical and Laboratory Standards Institute for the susceptibility of H. influenzae to ampicillin (AMP), the isolates were distributed as follows: 161 (61.0%) susceptible strains (MIC < or = 1 microg/ml), 37 (14.0%) intermediately resistant strains (MIC = 2 microg/ml), and 66 (25.0%) resistant strains (MIC > or = 4 microg/ml). According to PCR-based genotyping, 172 (65.1%) of the isolates had mutations in the ftsI gene and were negative for the beta-lactamase (bla) gene. These 172 isolates were thus defined as genetically beta-lactamase-negative ampicillin-resistant (gBLNAR) strains. The ftsI mutant group included 98 (37.1%) strains with group I/II mutations in the variable mutated region (group I/II gBLNAR) and 74 (28.0%) strains with group III mutations in the highly mutated region (group III gBLNAR). Eighty-seven (33.0%) of the isolates were genetically beta-lactamase-negative ampicillin-susceptible (gBLNAS) strains. The group III gBLNAR strains showed resistance to beta-lactams. Only five strains (1.9%) were positive for a bla gene encoding TEM-type beta-lactamase. The three clusters consisting of 16 strains found among the 61 BLNAR strains (MIC > or = 4 microg/ml and without the bla gene) showed identical or closely related DNA restriction fragment patterns. Those isolates were frequently identified among strains with a MIC to AMP of 16 microg/ml. The current study demonstrates the apparent dissemination and spread of a resistant clone of H. influenzae among medical centers in Japan. The gBLNAR strains show a remarkable prevalence among H. influenzae isolates, with the prevalence increasing with time. This fact should be taken into account when treating URT infections.

Topics: Adolescent; Adult; Ampicillin; Ampicillin Resistance; Anti-Bacterial Agents; beta-Lactamases; Child; Child, Preschool; Female; Gene Frequency; Genotype; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Japan; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Polymerase Chain Reaction; Respiratory Tract Infections

Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; beta-Lactams; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Geography; Haemophilus influenzae; Health Surveys; Humans; Moraxella catarrhalis; Penicillin Resistance; Respiratory Tract Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Biopsy; Bronchoscopy; Humans; Postoperative Complications; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Azithromycin; Bronchoscopy; Drug Resistance, Microbial; Humans; Postoperative Complications; Respiratory Tract Infections

Measures to alleviate the growing problem of macrolide resistance in Taiwan resulted in a decrease in macrolide consumption, from 0.629 defined daily doses/1000 inhabitants per day (DIDs) in 1999 to 0.301 DIDs in 2003 (a reduction of 52%). A linear relationship was observed between the decline in erythromycin consumption and the decline in erythromycin resistance in Streptococcus pyogenes (46% in 1999 vs. 17% in 2003; p < 0.001) and azithromycin resistance in Haemophilus influenzae (31% in 2000 vs. 0% in 2003; p < 0.001). However, the rate of erythromycin resistance in Streptococcus pneumoniae showed a continued increase, from 80.2% in 1999 to 92% in 2003.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Drug Resistance, Bacterial; Drug Utilization; Erythromycin; Evaluation Studies as Topic; Haemophilus influenzae; Health Policy; Hospitals, Teaching; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes; Taiwan

Stevens-Johnson syndrome mostly involves the skin and mucous membranes. The diagnosis is made when the characteristic rash appears 1 to 3 weeks after exposure to a known stimulus and cannot be explained by some other diagnosis. A 62-year-old woman was admitted for evaluation of toxo-allergic dermatitis and collagenosis. Ten days prior to admission she was taking a course of azithromycin for upper respiratory tract infection. After a few days she was feeling better but maculopapular, erythematous rash developed over her palms, accompanied by fever and chills as well as reddish discoloration around her eyes. Within the next few days the rash progressed to the feet. Routine hematologic, biochemical and immunologic studies did not confirm the diagnosis of inflammatory rheumatic disease. Corticosteroid therapy with methylprednisolone (1 mg/kg) for the presumed Stevens-Johnson syndrome was started and her condition improved in several days; she became afebrile and her skin lesions gradually disappeared. There is only one report, in a child, documenting the association of Stevens-Johnson syndrome with azithromycin, as in this patient.

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Middle Aged; Respiratory Tract Infections; Stevens-Johnson Syndrome

Long-term administration of macrolide antibiotics reduced the number of lymphocytes in bronchoalveolar lavage fluid in patients with chronic airway inflammatory disease. To evaluate the inflammatory activity of macrolides, their effect on apoptosis of activated lymphocytes isolated from human peripheral blood was compared with that of other antibiotics. Macrolides, including clarithromycin and azithromycin, at a final concentration of 100 microg/ml accelerated apoptosis of activated lymphocytes, while other antibiotics such as fosfomycin sodium, beta-lactams--ceftazidime, piperacillin sodium and biapenem, and a quinolone, ofloxacin, did not cause significant induction of apoptosis. Our results suggest that 14- or 15-membered ring macrolides are specifically involved in the augmentation of apoptosis of activated lymphocytes, and this may be of value therapeutically for chronic airway diseases.

Topics: Annexin A5; Anti-Bacterial Agents; Apoptosis; Azithromycin; Clarithromycin; Humans; Lymphocyte Activation; Lymphocytes; Macrolides; Propidium; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Randomized Controlled Trials as Topic; Recurrence; Respiratory Tract Infections; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Electrocardiography; Female; Humans; Middle Aged; Respiratory Tract Infections; Tachycardia, Ventricular

Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Azithromycin; Diarrhea; Drug Administration Schedule; Fatigue; Female; Humans; Jaundice; Liver; Respiratory Tract Infections

In our study the in vitro susceptibility of common pathogens that cause respiratory tract and abdominal wound infections was tested against two newer fluorquinolones (moxifloxacin and gatifloxacin) as well as levofloxacin and azithromycin.. 50 isolates each of methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and Haemophilus influenzae isolated from the respiratory tract and from wounds were tested for their susceptibility to moxifloxacin, gatifloxacin, levofloxacin and azithromycin.. Moxifloxacin proved to be the most active substance against the tested gram-positive pathogens. Gatifloxacin was the most active against P. aeruginosa. Moxifloxacin and gatifloxacin proved to be comparably active against the clinical isolates of E. coli and H. influenzae.. Moxifloxacin and gatifloxacin display excellent activity against respiratory pathogens as well as nosocomial pathogens causing abdominal wound infections. When treating infections caused by P. aeruginosa the earlier fluorquinolones such as ciprofloxacin or ofloxacin are the substances of choice.

Topics: Abdominal Injuries; Anti-Bacterial Agents; Aza Compounds; Azithromycin; Bacteria, Aerobic; Fluoroquinolones; Gatifloxacin; Humans; Levofloxacin; Methicillin Resistance; Microbial Sensitivity Tests; Moxifloxacin; Ofloxacin; Quinolines; Quinolones; Respiratory Tract Infections; Wound Infection

The in vitro abilities of telithromycin, azithromycin and clarithromycin to select for resistance were compared by testing isolates of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and beta-haemolytic streptococci.. Five strains each of beta-lactamase-positive and beta-lactamase-negative H. influenzae, beta-lactamase-positive and beta-lactamase-negative M. catarrhalis, S. pneumoniae, beta-haemolytic group A, group C and group G streptococci and three strains of beta-lactamase-negative ampicillin-resistant H. influenzae were evaluated. Development of resistance was determined by multi-step and single-step methodologies. For multi-step studies, MIC values were determined after five serial passages on antibiotic-gradient plates and after 10 serial passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of >/=4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on plates containing antibiotics at concentrations equal to the highest NCCLS breakpoints.. Azithromycin, clarithromycin and telithromycin gave a >/=4-fold increase in 20, 20 and 10 streptococcus strains, in 4, 5 and 0 H. influenzae strains and in 2, 7 and 4 M. catarrhalis strains, respectively. After 10 passages on antibiotic-free plates, 21/26 strains for azithromycin, 22/32 for clarithromycin and 1/14 for telithromycin maintained high MIC values. In single-step studies, the frequency of mutations was <10(-10) for H. influenzae and M. catarrhalis for telithromycin, azithromycin and clarithromycin. Telithromycin induced mutations at a lower rate than azithromycin and clarithromycin in streptococcal strains.. Telithromycin showed a very limited ability to select for resistance in respiratory pathogens compared with azithromycin and clarithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Bacterial; Gene Frequency; Haemophilus influenzae; Humans; Ketolides; Macrolides; Microbial Sensitivity Tests; Moraxella catarrhalis; Mutation; Respiratory Tract Infections; Streptococcus; Streptococcus pneumoniae

Unilateral lung agenesis is a rare congenital condition of unknown etiology. A 33-year-old nullipara with right lung agenesis and scoliosis was admitted to the hospital at 30 weeks of gestation because of oligohydramnios. At 32 weeks she was treated for an upper respiratory tract infection with azithromycin. She went into premature labor at 34 weeks and was delivered by Cesarean for breech presentation. Both mother and infant did well.

Topics: Adult; Azithromycin; Breech Presentation; Cesarean Section; Female; Humans; Lung; Obstetric Labor, Premature; Oligohydramnios; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Respiratory Tract Infections; Scoliosis

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Patient Compliance; Practice Patterns, Physicians'; Respiratory Tract Infections

Among respiratory tract isolates of Streptococcus pneumoniae from children, resistance to penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole (SXT) increases on an annual basis. Pediatric patients who do not respond to conventional therapy for respiratory tract infections someday may be treated with fluoroquinolones. In this study, MICs of beta-lactams, azithromycin, SXT, and levofloxacin were determined and interpreted by using NCCLS guidelines for isolates of S. pneumoniae (2,834 from children and 10,966 from adults), Haemophilus influenzae (629 from children and 2,281 from adults), and Moraxella catarrhalis (389 from children and 1,357 from adults) collected during the 2000-2001 and 2001-2002 respiratory illness seasons in the United States as part of the ongoing TRUST surveillance studies. Rates of resistance to penicillin, azithromycin, and SXT were > or = 7.5% higher among patients < or = 4 years old than among patients 5 to 10, 11 to 17, and > or = 18 years old in both the 2000-2001 and the 2001-2002 respiratory illness seasons. Levofloxacin resistance was detected in 2 of 2,834 isolates (0.07%) from patients <18 years old. Levofloxacin MICs of 0.25 to 1 micro g/ml accounted for 99.6, 99.5, 99.3, 99.7, 98.4, and 98.0% of isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old. Multidrug resistance was twice as common among patients < or = 4 years old (25.3%) as among patients 5 to 10 years old (13.7%), 11 to 17 years old (11.9%), 18 to 64 years old (12.1%), and > 64 years old (12.4%). The most common multidrug resistance phenotype in S. pneumoniae isolates for all age groups was resistance to penicillin, azithromycin, and SXT (70.3 to 76.6%). For H. influenzae and M. catarrhalis isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old, levofloxacin MICs at which 90% of the isolates were inhibited were 0.015 and 0.03 to 0.06 microg/ml, respectively, in the 2000-2001 and 2001-2002 respiratory illness seasons. In the 2000-2001 and 2001-2002 respiratory illness season surveillance studies in the United States, 99.9% of pediatric isolates of S. pneumoniae were susceptible to levofloxacin. If fluoroquinolones become a treatment option for pediatric patients, careful monitoring of fluoroquinolone susceptibilities will be increasingly important in future surveillance studies.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Lactams; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Moraxella catarrhalis; Ofloxacin; Pneumococcal Infections; Prospective Studies; Respiratory Tract Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Anti-Bacterial Agents; Attitude of Health Personnel; Azithromycin; Cross Infection; Drug Resistance, Multiple; Germany; Humans; Respiratory Tract Infections; Treatment Outcome

Drug acquisition cost is an important component in the analysis of economic and clinical outcomes in the treatment of respiratory tract infections (RTIs). However, bacterial resistance has emerged as a crucial variable that must also be considered. Drug-resistant infections result in more expensive drug therapy, longer hospital stays, and increased mortality. The high prevalence of community-acquired pneumonia (CAP), as well as the continuing growth in resistant pathogens, make RTIs an appropriate model for studying methods of cost-containment without sacrificing clinical outcome. The University of Kentucky Medical Center has developed a uniform CAP treatment pathway to minimize costs and maximize outcomes. First-line therapy in this model is doxycycline monotherapy, high-dose amoxicillin plus azithromycin, or levofloxacin monotherapy. One major future concern in selecting antibacterial agents for CAP is the spread of macrolide- and fluoroquinolone-resistant Streptococcus pneumoniae.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Doxycycline; Drug Resistance, Multiple, Bacterial; Humans; Kentucky; Levofloxacin; Ofloxacin; Pneumonia, Bacterial; Respiratory Tract Infections; Streptococcus pneumoniae; Treatment Outcome; United States

Aboriginal children living in remote Australia experience high rates of bacterial infection such as trachoma, otitis media and streptococcal skin infection, which often progress to associated chronic diseases in later life.. In February, 1995, single dose azithromycin was given to 130 Aboriginal children with trachoma and their contacts. The impact of this program on respiratory and skin group A Streptococcus pyogenes carriage and infection was also monitored.. Immediately before treatment 90% of children had skin sores, 38% of sores had pus and 74% of sores with pus had group A Streptococcus (GAS). Overall 57% of children had GAS skin infections. At 2 to 3 weeks and 2 and 6 months after treatment, this proportion was 10, 32 and 51%, respectively. For the upper respiratory tract GAS recovery rates were 8% before treatment and 0, 11 and 15% at the 2- to 3-week, 2-month and 6-month posttreatment visits, respectively. Multiple types occurred concurrently in individuals, particularly after treatment. Identical types were sometimes recovered simultaneously from the upper respiratory tract and skin, suggesting that the high rates of acute rheumatic fever in this population in the absence of high rates of detectable throat GAS carriage could be related to high rates of skin GAS infection.. There is an urgent need for education, adequate housing, scabies eradication and improved hygiene to reduce skin trauma and subsequent GAS infection in this population. Clinical trials are needed to determine how these measures can best be integrated with the trachoma eradication program to maximize health outcomes.

Topics: Adolescent; Anti-Bacterial Agents; Australia; Azithromycin; Child; Child Welfare; Child, Preschool; Drug Administration Schedule; Female; Humans; Hygiene; Infant; Infant, Newborn; Male; Native Hawaiian or Other Pacific Islander; Respiratory Tract Infections; Skin Diseases, Bacterial; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

Azithromycin (Zithromax), an erythromycin derivative that belongs to a subgroup of the macrolides known as azolides, has generally been considered to be a very safe medication. Hepatic side effects are uncommon but may include jaundice, fever, and right upper quadrant pain. Herein we describe a patient who developed azithromycin-induced cholestatic hepatitis that resolved upon discontinuation of the drug. Lack of other known causes for liver disease, the temporal relationship with this drug, and the typical changes of liver histology have established the diagnosis. Clinicians should be aware of this side effect of azithromycin, which is widely prescribed.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Biopsy, Needle; Cholestasis, Intrahepatic; Humans; Liver; Liver Function Tests; Male; Respiratory Tract Infections

Topics: Azithromycin; Bacterial Infections; Drug Administration Schedule; Humans; Respiratory Tract Infections; Treatment Outcome

Topics: Azithromycin; Bacterial Infections; Child; Drug Administration Schedule; Humans; Respiratory Tract Infections; Treatment Outcome

The comparative safety of azithromycin was assessed in adult patients (> or =12 years) with community-acquired respiratory tract infections. Of 3229 patients evaluated, 1616 received azithromycin 500 mg once daily for 3 days and 1613 received standard regimens of amoxycillin, amoxycillin/clavulanic acid, cefaclor, clarithromycin, or roxithromycin. A similar incidence of treatment-related adverse events occurred with azithromycin (10.3%) and comparators (11.5%). Significantly fewer patients were withdrawn from azithromycin than comparator treatment (0.4 versus 2.1%; P=0.0001). Most adverse events were mild/moderate in intensity and affected the gastrointestinal system. Azithromycin was as well tolerated as other antibiotics commonly used for bacterial infections in adults.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Digestive System; Female; Humans; Incidence; Male; Penicillins; Respiratory Tract Infections

A novel series of erythromycin derivatives has been discovered with potent activity against key respiratory pathogens, including those resistant to erythromycin. These compounds are characterized by having an aryl group tethered to the C-6 position of the erythronolide skeleton. Extensive structural modification of the C-6 moiety led to the discovery of several promising compounds with potent activity against both mef- and erm-mediated resistant Streptoccoccus pneumoniae. Preliminary mechanistic studies indicated that the new macrolides are potent protein synthesis inhibitors, which interact with methylated ribosomes isolated from resistant organisms. In experimental animal models, these compounds exhibited excellent in vivo efficacy and balanced pharmacokinetic profiles.

Topics: Animals; Anti-Bacterial Agents; Carbamates; Cell-Free System; Drug Resistance, Multiple; Erythromycin; Haemophilus influenzae; Ketolides; Lung; Mice; Models, Molecular; Protein Biosynthesis; Protein Synthesis Inhibitors; Rats; Respiratory Tract Infections; Ribosomes; Staphylococcus aureus; Streptococcus pneumoniae; Streptococcus pyogenes; Structure-Activity Relationship; Transcription, Genetic

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Bacterial; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Chlamydophila pneumoniae; Humans; Male; Military Personnel; Mycoplasma pneumoniae; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes

Topics: Adult; Age Factors; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Humans; Middle Aged; Patient Compliance; Penicillins; Placebos; Respiratory Tract Infections; Risk Factors; Time Factors; Tonsillitis

Topics: Animals; Anti-Bacterial Agents; Drug Design; Drug Resistance, Microbial; Haemophilus influenzae; Lung; Lung Diseases; Macrolides; Mice; Models, Molecular; Rats; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus; Structure-Activity Relationship

The clinical studies with azithromycin fine granules and capsules were conducted during the period from March 1993 to October 1994. Cmax's in 16 patients who received 10 mg/kg fine granules, were 0.29 +/- 0.24 microgram/ml, T1/2's were 42.0 +/- 11.8 hours, and AUC 0 approximately infinity's were 10.72 +/- 5.00 micrograms.hr/ml. The clinical results for azithromycin fine granule and capsules 10 mg/kg once daily for 3 days are as follows. The efficacy rate of fine granules, combining both "Excellent" and "Good", for pneumoniae where causative pathogenes were identified, was 95.3%, and for those which had failed to respond to previous chemotherapies, was 94.6%, respectively. The efficacy rate of capsules for 3 to 5 days was 100% in 40 cases where causative pathogenes were identified. Adverse reactions were found in 2.5%(fine granules) and in 5.4%(capsules) in cases eligible for evaluation. Abnormal changes in laboratory test were as follows: decrease of WBC by 5.6%(fine granules) and 9.3%(capsules) and increase in eosinophils by 7.1%(fine granules) and 11.4% (capsules). 59.8% of the patients claimed that the azithromycin 10% fine granules product was "easy to take". The result of a questionnaire on parents' demand on the improvement of antibiotics, showed that most concern was on the drug frequency(preferably once or twice daily) and the drug administering period(preferably short: 3 days). With regard to the efficacy, safety and compliance, it can be concluded that Azithromycin is one of the useful therapeutic regimens in the treatment of pediatric infections.

Topics: Azithromycin; Child; Child, Preschool; Dosage Forms; Humans; Infant; Patient Compliance; Respiratory Tract Infections; Retrospective Studies; Tissue Distribution; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Cost-Benefit Analysis; Humans; Pneumonia; Respiratory Tract Infections

During first 3 days after patient hospitalization with pneumonia or chronic obstruction pulmonary disease (COPD) pathogens in sputum were studied according NCCLS standards (for 1999 year). Among 93 pathogens isolated in pneumonia the most frequent were S. pneumoniae (41.9%), H. influenzae (21.5%). Among 232 pathogens isolated in COPD the most frequent were S. pneumoniae (35.5%), H. influenzae (16.8%). Other pathogens were staphylococci, moraxella, gram-negative bacteria. No penicillin-resistant S. pneumoniae, were isolated, the strains with moderate penicillin resistance were less than 3% in both groups. Among H. influenzae isolated from patients with pneumonia 25% were beta-lactamase producers, from COPD patients 21% strains produced beta-lactamase. Totally among all studied pathogens only 58% were sensitive to ampicillin in pneumonia groups and 48% in COPD groups, for azithromycin 70.7% and 71% respectively, for cefuroxime 84.5% and 85% respectively. Ampicillin efficacy for empirical treatment of community-acquired low respiratory tract infections was substantially less than that of modern antibiotics.

Topics: Ampicillin; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Cefuroxime; Cephalosporins; Chronic Disease; Community-Acquired Infections; Drug Resistance, Microbial; Haemophilus influenzae; Humans; Inpatients; Penicillins; Pneumonia, Bacterial; Respiratory Tract Infections; Streptococcus pneumoniae

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.

Topics: Amiodarone; Anticoagulants; Atrial Fibrillation; Azithromycin; Coumarins; Drug Interactions; Fatal Outcome; Female; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Middle Aged; Postoperative Complications; Respiratory Tract Infections

The impact of increased macrolide consumption on the resistance of common respiratory pathogens to erythromycin and azithromycin was evaluated. The study focused mainly on azithromycin. During the period from 1991 to 1996, a 3.5-fold increase in macrolide prescriptions for outpatients was observed in Slovenia. Compared to 1994, when no macrolide resistance was evident in Streptococcus pyogenes and noninvasive Streptococcus pneumoniae, a significant increase in macrolide resistance was observed in these two pathogens in 1997. Moraxella catarrhalis remained uniformly susceptible to macrolides. Close monitoring of macrolide resistance of common respiratory pathogens is thus necessary.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Prescriptions; Drug Resistance, Microbial; Drug Utilization; Erythromycin; Humans; Moraxella; Respiratory Tract Infections; Streptococcus

In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11, 12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLSB resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.

Topics: Animals; Anti-Bacterial Agents; Colony Count, Microbial; Crystallography, X-Ray; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Drug Resistance, Multiple; Enterococcus; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Ketolides; Macrolides; Male; Mice; Models, Molecular; Molecular Conformation; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus; Streptococcus; Streptococcus pneumoniae

Comparative antibacterial efficacies of erythromycin, clarithromycin, and azithromycin were examined against Streptococcus pneumoniae and Haemophilus influenzae, with amoxicillin-clavulanate used as the active control. In vitro, the macrolides at twice their MICs and at concentrations achieved in humans were bacteriostatic or reduced the numbers of viable S. pneumoniae slowly, whereas amoxicillin-clavulanate showed a rapid antibacterial effect. Against H. influenzae, erythromycin, clarithromycin, and clarithromycin plus 14-hydroxy clarithromycin at twice their MICs produced a slow reduction in bacterial numbers, whereas azithromycin was bactericidal. Azithromycin at the concentrations achieved in the serum of humans was bacteriostatic, whereas erythromycin and clarithromycin were ineffective. In experimental respiratory tract infections in rats, clarithromycin (equivalent to 250 mg twice daily [b.i.d.]) and amoxicillin-clavulanate (equivalent to 500 plus 125 mg b.i.d., respectively) were highly effective against S. pneumoniae, but azithromycin (equivalent to 500 and 250 mg once daily) was significantly less effective (P < 0.01). Against H. influenzae, clarithromycin treatment (equivalent to 250 or 500 mg b.i.d.) was similar to no treatment and was significantly less effective than amoxicillin-clavulanate treatment (P < 0.01). Azithromycin demonstrated significant in vivo activity (P < 0.05) but was significantly less effective than amoxicillin-clavulanate (P < 0.05). Overall, amoxicillin-clavulanate was effective in vitro and in vivo. Clarithromycin and erythromycin were ineffective in vitro and in vivo against H. influenzae, and azithromycin (at concentrations achieved in humans) showed unreliable activity against both pathogens. These results may have clinical implications for the utility of macrolides in the empiric therapy of respiratory tract infections.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Clarithromycin; Drug Therapy, Combination; Erythromycin; Haemophilus influenzae; Humans; Male; Microbial Sensitivity Tests; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections; Streptococcus pneumoniae; Time Factors

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Microbial; Erythromycin; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes; United States

Topics: Anti-Bacterial Agents; Azithromycin; Edema; Female; Humans; IgA Vasculitis; Infant; Purpura; Remission, Spontaneous; Respiratory Tract Infections; Skin; Vasculitis, Leukocytoclastic, Cutaneous

Azithromycin, the prototypical azalide antibiotic, has a wide spectrum of activity that is characterized by resistance to beta-lactamase-producing microbes and efficacy against Gram-positive and Gram-negative pathogens, including Haemophilus influenzae. Tissue-directed pharmacokinetics include tissue concentrations up to 100-fold higher than those in plasma and a tissue half-life of up to 4 days. Pharmacokinetics of azithromycin permits a reduction in dosage frequency and duration while maintaining efficacy comparable to that of conventional 7- to 10-day three or four times daily regimens. Dosage interval, duration of treatment, side effects and palatability can affect compliance and thus clinical outcome. Compliance among children is important in light of the high incidence of community-acquired infections such as otitis media and streptococcal pharyngitis.. To compare the flavor, taste acceptability and color preference of oral antibiotic suspensions given to children.. The taste and acceptability of the oral suspension form of azithromycin vs. cefixime, cefpodoxime proxetil, cefprozil, clarithromycin or loracarbef were rated by children during blinded taste tests and with acceptability/ preference questionnaires.. Analysis of the mean acceptability/ preference rating from 769 children demonstrated that the flavor of azithromycin was rated significantly higher than that of cefpodoxime (4.3 vs. 2.8), cefprozil (4.0 vs. 3.4) and clarithromycin (4.3 vs. 2.7) and was comparable to that of cefixime (4.0 vs. 4.2) and loracarbef (4.4 vs. 4.5). A greater percentage of children preferred the taste of azithromycin to that of cefpodoxime (90.0% vs. 5.2%), cefprozil (63.0% vs. 33.1%) and clarithromycin (89.0% vs. 11.0%). The taste of azithromycin was not preferred to that of cefixime (39.0% vs. 53.9%) or loracarbef (36% vs. 58.5%).. The efficacy and safety of azithromycin in otitis media and streptococcal pharyngitis, the simple dosing regimen and a highly palatable oral suspension formulation should increase compliance among pediatric patients and thereby improve clinical outcomes.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Patient Compliance; Respiratory Tract Infections; Suspensions; Taste

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Azithromycin; Bacteremia; Disease Models, Animal; Lung; Mice; Pneumonia, Pneumococcal; Respiratory Tract Infections; Tissue Distribution

This study was carried out to determine the clinical efficacy and the clinical safety of azithromycin in a group of children with acute respiratory tract infections. The study involved 82 children treated with a single daily 10 mg/kg dose of azithromycin for three consecutive days. 7 days later, the overall clinical response was 100% (cure and improvement): bacteriological cure was achieved in 97.5% of the patients treated. Recurrences were never observed. Side effects not requiring interruption of therapy were observed in 3 patients (3.6%). The side effects were gastrointestinal disturbances. In conclusion azithromycin showed a remarkably clinical efficacy for treatment of acute respiratory infections in children. Tolerability and therapeutic compliance were excellent.

Topics: Anti-Bacterial Agents; Azithromycin; Bordetella pertussis; Child; Child, Preschool; Drug Tolerance; Female; Haemophilus; Humans; Infant; Male; Moraxella catarrhalis; Mycoplasma pneumoniae; Respiratory Tract Infections; Retrospective Studies; Streptococcus; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Microbial; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections

Azithromycin activity in vivo has been studied in a group of children with acute respiratory tract infections in order to test the efficacy and tolerability of this antibiotic. The study involved 135 children treated with a single daily 10 mg/kg dose of azithromycin for three consecutive days. Ten days after this treatment 100% of children with otitis media, tracheobronchitis, or rhinosinusitis and 95.9% of children with pharyngo-tonsillitis were cured. Recurrences were never observed. Azithromycin proved remarkably effective for treatment of acute respiratory infections and otitis media in children. Tolerability and therapeutic compliance were excellent.

Topics: Acute Disease; Azithromycin; Bacteria; Bronchitis; Child; Child, Preschool; Evaluation Studies as Topic; Female; Humans; Infant; Male; Otitis Media; Pharyngitis; Respiratory Tract Infections; Rhinitis; Sinusitis; Tonsillitis; Tracheitis

Topics: Acute Disease; Adult; Azithromycin; Erythromycin; Humans; Male; Nephritis, Interstitial; Respiratory Tract Infections

We compared the activities of azithromycin and erythromycin against Haemophilus influenzae in a mouse model of nonparenchymatous lower respiratory tract infection. In vitro and in vivo efficacy data for both drugs were analyzed relative to their pharmacokinetics in lungs and in vivo uptake by phagocytes. Aged C57BL/6 mice (mean age, 15.1 +/- 1.9 months) were infected intratracheally with 10(8) CFU of H. influenzae serotype b. Oral drug administration was initiated 4 h after infection by various dosage regimens. In terms of bacterial killing in the lung, azithromycin was much more active than erythromycin (P less than 0.01). Its in vivo activity was also more durable after a single administration relative to the durability of three doses of erythromycin given at 6-h intervals. The MIC of azithromycin was eightfold lower than that of erythromycin, and better penetration and a longer half-life in lung tissue were achieved after a single oral administration. Phagocytes delivered increased amounts of both drugs to the infected lungs, particularly at the site of infection (bronchoalveolar airspaces), and detectable levels of azithromycin were maintained locally for long periods. The fact that the efficacy of azithromycin coincided with the arrival of large numbers of polymorphonuclear leukocytes within the airspaces suggests that active extracellular concentrations were provided by the release of azithromycin from these cells. This further supports the potential value of once-daily azithromycin regimens for the treatment of lower respiratory tract infections in humans, provided that inhibitory concentrations against common pathogens such as H. influenzae are maintained for adequate periods of time.

Topics: Administration, Oral; Animals; Azithromycin; Bronchoalveolar Lavage Fluid; Drug Evaluation, Preclinical; Erythromycin; Female; Haemophilus Infections; Haemophilus influenzae; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Models, Biological; Phagocytes; Respiratory Tract Infections