zithromax and Bacterial-Infections

Recurrent bacterial infection causes frequent bronchiectasis (BE) exacerbations. The effectiveness and safety of long-term administration of macrolides in BE remain controversial, especially in children who require minimal treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide use in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) which elucidated long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged < 18 years. The primary outcome was frequency of acute exacerbation; secondary outcomes included changes in pulmonary function, sputum scores, and adverse events including bacterial resistance. We included four RCTs. Long-term macrolide treatment showed a significant decrease in the frequency of exacerbation (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.10-0.87), mean number of exacerbations per patient (mean difference, - 1.40; 95% CI, - 2.26 to - 0.54), and sputum purulence score (mean difference, - 0.78; 95% CI, - 1.32 to - 0.24). However, long-term macrolide treatment was accompanied by an increased carriage of azithromycin-resistant bacteria (OR, 7.13). Long-term macrolide administration prevents exacerbation of BE in children; however, there are risks of increasing antibiotic resistance. Benefits and risks should be weighed and determined on a patient-by-patient basis.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchiectasis; Child; Disease Progression; Drug Resistance, Bacterial; Humans; Macrolides; Odds Ratio; Protein Synthesis Inhibitors; Quality of Life; Randomized Controlled Trials as Topic; Risk; Treatment Outcome

Topics: Anti-Bacterial Agents; Antiviral Agents; Azithromycin; Bacterial Infections; COVID-19 Drug Treatment; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; SARS-CoV-2

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

As bacterial infections provoke exacerbations, COPD patients may benefit from prophylactic antibiotics. However, evidence regarding their overall benefit-risk profile is conflicting.. To update previous evidence and systematically evaluate the beneficial effects and side effects of prophylactic antibiotics in stable COPD patients.. Several databases were searched up to 26 April 2017 for randomized controlled trials (RCTs) on prophylactic antibiotics in stable COPD patients. The primary outcomes were exacerbations and quality of life. Duration and schedule of antibiotics were considered in subgroup analyses.. Twelve RCTs involving 3683 patients were included. Prophylactic antibiotics significantly reduced the frequency of exacerbations [risk ratio (RR) 0.74, 95% CI 0.60-0.92] and the number of patients with one or more exacerbations (RR 0.82, 95% CI 0.74-0.90). Erythromycin and azithromycin appeared the most effective, with the number needed to treat ranging from four to seven. Quality of life was also significantly improved by prophylactic antibiotics (mean difference -1.55, 95% CI -2.59 to -0.51). Time to first exacerbation was prolonged in six studies, with one conflicting result. Neither the rate of hospitalization nor the rate of adverse events was significantly changed. Furthermore, no significant changes were observed in lung function, bacterial load and airway inflammation. However, antibiotic-resistant isolates were significantly increased (OR 4.49, 95% CI 2.48-8.12).. Prophylactic antibiotics were effective in preventing COPD exacerbations and improving quality of life among stable patients with moderate to severe COPD. The choice of prophylactic antibiotics should be analysed and considered case by case, especially for long and continuous use.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Disease Progression; Erythromycin; Hospitalization; Humans; Outcome Assessment, Health Care; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic

Diarrhoea is one of the most commonly occurring diseases. This article presents a review of the current state of the treatment of acute infectious diarrhoea, as well as of the most important pathogens. The general principles of the therapy of diarrhoea are exemplified, followed by a description of the targeted antimicrobial therapy of the most important bacterial gastrointestinal infections, including salmonellosis, shigellosis and Campylobacter infections, as well as infections with pathogenic Escherichia coli strains, yersiniosis and cholera. Diarrhoea caused by toxigenic Clostridium difficile strains has increased in incidence and in severity. These infections will therefore be described in detail, including important new aspects of treatment. Symptomatic therapy is still the most important component of the treatment of infectious diarrhoea. However, empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhoea, underlying immune deficiency, advanced age or significant comorbidities. Increasing resistance, in particular against fluoroquinolones, must be taken into consideration. Therapy with motility inhibitors is not recommended for Shiga toxin-producing Escherichia coli (STEC) infections, Clostridium difficile infections (CDI), and severe colitis. The macrocyclic antibiotic fidaxomicin can reduce the rate of recurrent disease in CDI. Furthermore, evidence for the benefits of faecal microbiota transplantation as a treatment option for multiple recurrences of CDI is increasing. In conclusion, the treatment of acute diarrhoea is still primarily supportive. General empirical antibiotic therapy for acute diarrhoea is not evidence-based.

Topics: Acute Disease; Aminoglycosides; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Campylobacter Infections; Cholera; Ciprofloxacin; Diarrhea; Dysbiosis; Dysentery, Bacillary; Enterocolitis, Pseudomembranous; Escherichia coli Infections; Fidaxomicin; Gastroenteritis; Humans; Rifamycins; Rifaximin; Salmonella Infections; Shiga-Toxigenic Escherichia coli; Yersinia Infections

In chronic persistent asthma and severe acute exacerbations of bronchial asthma, infectious agents are the predominant triggers that drive disease and airway pathobiology. In acute exacerbations of bronchial asthma (AEBA) including near fatal and fatal asthma, viral agents, particularly human rhinovirus-C, respiratory syncytial virus and influenza A appear to be the more prevalent and recurring threats. Both viral, and to a lesser extent bacterial agents, can play a role, and co-infection may also be present and worsen prognosis in hospitalized patients, placing a portion at risk for critical asthma syndrome. During severe acute exacerbations, infectious agents must be treated empirically, but the initial treatment regimens can vary and viral coverage may also vary based on seasonality and patient age. Early treatment with ceftriaxone and azithromycin, along with oseltamivir in winter months, should be initiated with all cases of severe exacerbations where infection is suspected, and definitely in critical asthma syndrome until infection is excluded by appropriate diagnostic testing. In this manuscript we will outline the impact of the major viral agents on severe asthma including the data from the 2009 H1N1 influenza pandemic. The role of bacterial infections in acute exacerbations of asthma will also be reviewed as well as the benefit of empiric antibiotics and the role of macrolides in both acute and chronic asthma.

Topics: Animals; Asthma; Azithromycin; Bacterial Infections; Ceftriaxone; Coinfection; Critical Illness; Disease Progression; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Oseltamivir; Seasons; Syndrome

Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm. Accumulating effectively in cells, particularly phagocytes, it is delivered in high concentrations to sites of infection, as reflected in rapid plasma clearance and extensive tissue distribution. Azithromycin is indicated for respiratory, urogenital, dermal and other bacterial infections, and exerts immunomodulatory effects in chronic inflammatory disorders, including diffuse panbronchiolitis, post-transplant bronchiolitis and rosacea. Modulation of host responses facilitates its long-term therapeutic benefit in cystic fibrosis, non-cystic fibrosis bronchiectasis, exacerbations of chronic obstructive pulmonary disease (COPD) and non-eosinophilic asthma. Initial, stimulatory effects of azithromycin on immune and epithelial cells, involving interactions with phospholipids and Erk1/2, are followed by later modulation of transcription factors AP-1, NFκB, inflammatory cytokine and mucin release. Delayed inhibitory effects on cell function and high lysosomal accumulation accompany disruption of protein and intracellular lipid transport, regulation of surface receptor expression, of macrophage phenotype and autophagy. These later changes underlie many immunomodulatory effects of azithromycin, contributing to resolution of acute infections and reduction of exacerbations in chronic airway diseases. A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis. Other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial. Long-term administration of azithromycin must be balanced against the potential for increased bacterial resistance. Azithromycin has a very good record of safety, but recent reports indicate rare cases of cardiac torsades des pointes in patients at risk.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Cytokines; Drug Resistance, Bacterial; Epithelial Cells; Humans; Immunomodulation; Intracellular Signaling Peptides and Proteins; Lysosomes; Macrolides; Phagocytes; Phospholipids; Transcription Factors

Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis.. To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012.. Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose.. Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review.. Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon and not obviously associated with azithromycin, although a once-weekly high dose regimen was associated with more frequent gastrointestinal adverse events. Treatment with azithromycin was associated with reduced identification of Staphylococcus aureus on respiratory culture, but also a significant increase in macrolide resistance.. This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained. Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Cystic Fibrosis; Disease Progression; Humans; Macrolides; Outcome Assessment, Health Care; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic

Periodontal disease as a biofilm infectious disease is considered. Periodontal disease-associated bacteria formed biofilm in periodontal pockets or on the surface of cementum. Planktonic bacteria from biofilm invade into periodontal tissues and lead to inflammation and destruction of tissues directly and indirectly by eliciting the host defense mechanism. Supragingival dental plaques (biofilm) are easily removed by professional mechanical tooth cleaning, while subgingival dental plaques and bacteria invading into periodontal tissues are difficult to remove. Therefore, the development of a method for periodontal disease based on the concept that regards periodontal disease as a biofilm infectious disease is needed. Hereby, I report the effect of antibiotics on an in vitro biofilm model of periodontal disease and the systemic administration of azithromycin for early-onset (aggressive) periodontitis like a treatment resistant periodontitis.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Biofilms; Chronic Periodontitis; Female; Humans

Erythromycins have been part of our armamentarium against selected bacterial infections since they were discovered in 1952 and approved by the Food and Drug Administration (FDA) in 1964. In 1991, two newer, long-acting erythromycin analogues, azythromycin (brand name: Zithromax) and clarithromycin (brand name: Biaxin) were approved by the FDA. They were joined a few years later by a third long-acting form, dirithromycin (brand name: Dynabac).

Topics: Ambulatory Care; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Delayed-Action Preparations; Erythromycin; Humans; Tooth Diseases

The advanced macrolides, azithromycin and clarithromycin, and the ketolide, telithromycin, are structural analogs of erythromycin. They have several distinct advantages when compared with erythromycin, including enhanced spectrum of activity, more favorable pharmacokinetics and pharmacodynamics, once-daily administration, and improved tolerability. Clarithromycin and azithromycin are used extensively for the treatment of respiratory tract infections, sexually transmitted diseases, and Helicobacter pylori-associated peptic ulcer disease. Telithromycin is approved for the treatment of community-acquired pneumonia. Severe hepatotoxicity has been reported with the use of telithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Humans; Ketolides; Macrolides; Minocycline; Tetracyclines; Tigecycline

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

The advanced macrolides, azithromycin and clarithromycin, and the ketolide telithromycin are structural analogues of erythromycin. They have several distinct advantages when compared with erythromycin including enhanced spectrum of activity, more favorable pharmacokinetics and pharmacodynamics, once daily administration, and improved tolerability. This article reviews the pharmacokinetics, antimicrobial activity, clinical use, and adverse effects of these antimicrobial agents.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Humans; Ketolides; Macrolides

Azithromycin has recently replaced clindamycin oral suspension for prop hylaxis of infective endocarditis (IE) in children. It is also currently recommended by the American Heart Association as an alternative to penicillin, along with clindamycin for prophylaxis of infective endocarditis in adults. The objectives of this paper were to firstly, review the current literature on the efficacy of azithromycin as a suitable prophylactic agent in the prevention of infective endocarditis; and secondly, to review its pharmacological properties as a suitable therapeutic agent in the management of odontogenic infections.. A review of the literature.. The available evidence from animal models on infective endocarditis supports the efficacy of this drug as a prophylactic agent against oral streptococci. The pharmacological properties of this agent would make it a very promising therapeutic adjunct in the management of odontogenic infections. At present there are only a small number of studies available with valuable data on the efficacy of this relatively new drug. Further investigations comparing this compound with other commonly used adjuncts would be of great benefit.

Topics: Adolescent; Adult; Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Child; Child, Preschool; Dental Care; Dental Care for Chronically Ill; Endocarditis, Bacterial; Humans; Middle Aged; Mouth Diseases; Tooth Diseases

In this study, we evaluated the efficacy of azithromycin in otolaryngologic infections and tissue penetration. Azithromycin is a new macrolide developed by Pfizer Pharmaceuticals. Azithromycin maintained sustained high tissue levels compared with serum levels following small doses administered over a short period of time. Furthermore, excellent efficacy was achieved with the 3 day regimen of azithromycin, comparable to 10 day regimens of other antibiotics. In summary, azithromycin was demonstrated to be a highly useful antibiotic in infections of ear, nose, and throat.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clinical Trials as Topic; Humans; Male; Middle Aged; Otorhinolaryngologic Diseases; Tissue Distribution; Treatment Outcome

Azithromycin has adequate tissue levels for 7 days with a 3 day treatment regimen. The antibacterial activity is excellent. In dental infections, recurrence of infection happens when antibiotics cause a temporary improvement in symptoms but the etiologic agent is not eradicated. Azithromycin produces a "focused" cure and is an appropriate antibiotic for these infections. For this reason, the antibiotic was approved.

Topics: Anti-Infective Agents; Azithromycin; Bacteria; Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Naphthyridines; Periodontal Diseases; Treatment Outcome

Azithromycin and clarithromycin are two relatively new macrolide antimicrobial agents. Although azithromycin and clarithromycin are structural analogues of erythromycin, they offer distinct advantages in comparison. This article reviews the pharmacokinetics, antimicrobial activity, clinical use, and adverse affects of these antimicrobial agents.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Drug Resistance, Microbial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans

Over 7 million cases of traveler's diarrhea, defined as the passage of > or = 3 unformed stools in a 24-h period, occur each year among visitors to developing countries. Bacterial enteric pathogens are the most common etiologic agents isolated. Preliminary clinical results for patients with diarrhea predominantly caused by Campylobacter species have shown that azithromycin may be an effective alternative to fluoroquinolones for the treatment of traveler's diarrhea.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Campylobacter Infections; Diarrhea; Fluoroquinolones; Humans; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

The global challenge of optimally treating bacterial infections is continuously evolving. Azithromycin, the first azalide antibiotic, presents pharmacokinetics and pharmacodynamics that allow for a simple dosing regimen with minimal side effects. Current azithromycin uses include a variety of community-acquired respiratory tract, skin and soft tissue, and sexually transmitted disease infections. Azithromycin has also demonstrated substantial activity against atypical organisms such as Mycobacterium avium complex (MAC) and Chlamydia trachomatis. Due to a never-ending need for new antibiotic therapies, several other potential indications for azithromycin are being researched. This article will present various current research associated with azithromycin's potential use for malaria, trachoma, coronary artery disease (CAD), Pseudomonas aeruginosa infections, erythema migrans, short-term therapy for respiratory infections, typhoid, cryptosporidiosis, pelvic inflammatory disease, acne, Mediterranean spotted fever and MAC. As bacterial and parasite resistance patterns fluctuate globally, azithromycin may be an alternative therapy for the previously mentioned indications, which will also enhance patient compliance and therefore effectively eradicate infection worldwide.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clinical Trials as Topic; Humans; Malaria

The macrolides are a well established group of antibacterials frequently used in general practice. The most frequently used macrolides in paediatric patients are erythromycin, a naturally occurring compound, and clarithromycin and azithromycin, recently developed macrolides. Overall adverse effect rates of 7 to 26% for erythromycin, 14 to 26% for clarithromycin, and 6 to 27% for azithromycin have been described in children. Adverse gastrointestinal effects, including nausea, vomiting, diarrhoea and abdominal cramps, are the most common problems in children. Allergic reactions, hepatotoxicity, ototoxicity and adverse effects involving the central and peripheral nervous systems have also been observed in children. Stevens-Johnson, Schonlein-Henoch and Churg-Strauss syndromes have been rarely described in children. Treatment-related laboratory abnormalities have been recorded in 2 to 4% of erythromycin- and in 0 to 1% of both clarithromycin- and azithromycin-treated children. Elevation in liver function tests was the most common abnormality cited. Increased macrolide use in children in recent years has resulted in a growing potential for drug interactions between them and other pharmacologically active agents via the inhibition of cytochrome P450 (CYP) microsomal enzymes. Drug interactions with theophylline, cyclosporin, carbamazepine, terfenadine and warfarin limit erythromycin use. Clarithromycin is a weak inducer of CYP and exhibits fewer drug-drug interactions than erythromycin. However, its use with theophylline, carbamazepine and terfenadine is contraindicated. In contrast, no significant interactions have been reported with azithromycin to date. Macrolides have been proven to be well tolerated in the treatment of upper and lower respiratory tract infections, skin and soft tissue infections, and also in less frequent infections occurring in paediatric patients. In addition, clarithromycin and azithromycin have shown good tolerability profiles in immunocompromised paediatric patients. In conclusion, macrolides antibacterials have proven to be well tolerated in paediatric patients. Although the incidence of adverse effects is similar with the use of erythromycin and the newer macrolides, drug interactions occur significantly less when clarithromycin or azithromycin are administered.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Clarithromycin; Drug Hypersensitivity; Drug Interactions; Erythromycin; Humans; Liver Function Tests

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

Erythromycin, the prototypical macrolide, has been widely used since the 1950s in the management of pediatric infections. Erythromycin is the drug of choice for infants and children with Legionnaire's disease, pertussis, diphtheria, lower respiratory tract infections caused by Mycoplasma pneumoniae, Chlamydia pneumoniae and Chlamydia trachomatis and enteritis caused by Campylobacter jejuni. It is also indicated for treatment of syphilis; for streptococcal, staphylococcal and pneumococcal infections; genital infections caused by Ureaplasma urealyticum; and for the prevention of rheumatic fever and endocarditis in patients who are allergic to beta-lactam antibiotics. The new macrolides azithromycin and clarithromycin are also active against Borrelia burgdorferi, Helicobacter pylori, Mycobacterium avium-intracellulare complex, Cryptosporidium spp. and Toxoplasma gondii. Erythromycin is associated with a low risk of serious side effects, although gastric distress occurs in a significant proportion of patients. Drug interactions with theophylline, carbamazepine, warfarin, cyclosporine, terfenadine and digoxin limit erythromycin use. The newer macrolides azithromycin and clarithromycin are more stable, better absorbed and better tolerated than erythromycin. Azithromycin is more active than erythromycin against Haemophilus influenzae. Excellent tissue and intracellular penetration may contribute to their clinical efficacy. In children both azithromycin and clarithromycin are indicated for acute otitis media caused by Streptococcus pneumoniae, H. influenzae and Moraxella catarrhalis and for pharyngitis/tonsillitis caused by Streptococcus pyogenes. (As of December, 1996, azithromycin for oral suspension was approved for community-acquired pneumonia in children caused by C. pneumoniae, H. influenzae, M. pneumoniae and S. pneumoniae.) Claritromycin is also indicated for acute maxillary sinusitis, uncomplicated skin and skin structure infections, pneumonia and disseminated mycobacterial infections. Azithromycin and clarithromycin are associated with a lower incidence of gastrointestinal side effects, a low rate of drug discontinuation caused by side effects and a low potential for interaction with other drugs.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clarithromycin; Drug Interactions; Erythromycin; Haemophilus Infections; Haemophilus influenzae; History, 20th Century; Humans; Infant; Infant, Newborn; Microscopy, Electron; Phagocytes; Phagocytosis

Requirements for the antimicrobial activity of an antibiotic are: (1) binding of the drug to a specific site in the bacteria; (2) occupation of a critical number of binding sites; and (3) persistence at these binding sites for a sufficient time. With concentration-dependent antibiotics the ratio of the peak serum drug concentration to the MIC of a pathogen is the primary determinant of bacterial killing; with concentration-independent antibiotics it is the length of time serum concentration remains above the MIC, rather than the peak level. The pharmacokinetics of the new macrolides azithromycin and clarithromycin differ notably from those of conventional antibiotics in a more rapid and extensive distribution to body tissues. Because of these unique tissue pharmacokinetics, the pharmacodynamic models that apply to other classes of antibiotics may not explain the antimicrobial activity and clinical efficacy of azithromycin and clarithromycin.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clarithromycin; Ear, Middle; Haemophilus Infections; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Streptococcal Infections; Tissue Distribution

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clarithromycin; Community-Acquired Infections; Helicobacter Infections; Humans; Malaria; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial

One of the chemical features that distinguishes the 15-membered ring azalide azithromycin from the 14-membered ring macrolide compound erythromycin is the former's increased stability at acid pH. Azithromycin also differs pharmacokinetically from erythromycin, an important feature being azithromycin's ability to achieve high tissue concentrations, with the agent being delivered to the sites of infection by direct uptake and by targeted delivery via phagocytes. High tissue concentrations are maintained for prolonged periods because of azithromycin's long half-life, leading to once-daily dosing for 3 or 5 days. Notable microbiological features of azithromycin are in-vitro activity against many pyogenic bacteria (e.g. Neisseria gonorrhoeae and Moraxella catarrhalis), as well as organisms against which beta-lactam antibiotics are usually ineffective (e.g. Legionella and Chlamydia spp.), organisms that are resistant to benzylpenicillin and erythromycin (e.g. Haemophilus influenzae) and organisms for which satisfactory therapy is limited (e.g. Toxoplasma gondii and the Mycobacterium avium-intracellulare complex). These properties of azithromycin suggest that it might be a useful agent for the treatment of a wide range of bacterial infections.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Humans

Azithromycin and clarithromycin are alternatives to conventional macrolides in the routine treatment of many dermatologic, upper respiratory, and lower respiratory tract infections. In this role as alternative therapy, they are better tolerated, less toxic, and more convenient to take, although at a greater cost to the patient. This dosing convenience is an important consideration for the clinician; as shown by Nelson, patient compliance ranges from 95% with once-daily dosing to 58% with four-times-a-day dosing. Thus, less frequent dosing with both drugs as well as the shorter course of therapy possible with azithromycin may be therapeutically advantageous. In addition to their role as alternatives to conventional macrolide therapy, azithromycin and clarithromycin extend the spectrum of macrolides and offer new therapeutic options for H. influenzae, MAC in AIDS, MOTT, and leprosy. Finally, experimental therapy may extend their use for additional opportunistic infections, such as toxoplasmosis and cryptosporidiosis.

Topics: Azithromycin; Bacterial Infections; Clarithromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests

Topics: Adult; Azithromycin; Bacterial Infections; Child; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Microbial Sensitivity Tests

Topics: Animals; Azithromycin; Bacterial Infections; Biological Availability; Clarithromycin; Drug Interactions; Half-Life; Humans; Microbial Sensitivity Tests; Tissue Distribution

Topics: Administration, Oral; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Cefixime; Cefotaxime; Cefpodoxime Proxetil; Cefprozil; Ceftibuten; Ceftizoxime; Cefuroxime; Cephalosporins; Child; Clarithromycin; Fluoroquinolones; Humans

Topics: Animals; Azithromycin; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Erythromycin; Humans; Microbial Sensitivity Tests

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

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of clarithromycin and azithromycin are described. Clarithromycin and azithromycin are new macrolide antibiotics that are similar in structure to erythromycin. Compared with erythromycin, clarithromycin demonstrates increased activity against Staphylococcus aureus, streptococci, Legionella pneumophila, Moraxella catarrhalis, and Chlamydia trachomatis. Clarithromycin also has in vitro activity against Mycobacterium avium complex (MAC) and Toxoplasma gondii. Azithromycin has increased gram-negative activity compared with erythromycin, including activity against Haemophilus influenzae, while maintaining activity against gram-positive organisms. Azithromycin also has activity against sexually transmitted organisms including Chlamydia trachomatis. The pharmacokinetic profiles of clarithromycin and azithromycin are characterized by good oral bioavailability, excellent tissue penetration and persistence, and long elimination half-lives, which allow for once-daily or twice-daily dosing. Initial data show that clarithromycin and azithromycin are effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures. Azithromycin has been shown to be effective for the treatment of sexually transmitted diseases caused by Chlamydia trachomatis. Clarithromycin and azithromycin have been used to treat MAC and Toxoplasma infections in patients with the acquired immunodeficiency syndrome. The most frequently reported adverse effects for both agents have been nausea, diarrhea, and abdominal pain. Oral formulations of clarithromycin and azithromycin have recently been approved by the FDA. Clarithromycin and azithromycin are new macrolide antibiotics that have potential advantages over erythromycin; however, the role of these agents will be better defined as results of more ongoing trials become available for evaluation.

Topics: Azithromycin; Bacterial Infections; Clarithromycin; Drug Interactions; Drug Labeling; Drug Resistance, Microbial; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria

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

To discuss the chemistry, mechanism of action, spectrum of activity, pharmacokinetics, clinical trials, adverse-effect profile, drug interactions, and dosage guidelines of azithromycin, the first azalide antibiotic.. Pertinent literature published between 1988 and the present was identified via a MEDLINE search. Of 77 articles retrieved, 37 have been referenced.. Azithromycin is a new agent, and as such, limited data regarding this drug are available in the literature. We evaluated all pharmacokinetic, microbiologic, and basic science articles pertaining to azithromycin, and reviewed the clinical efficacy trials that we believed were of good quality for each indication for which azithromycin has received approval to date. Comparative clinical trials involving large numbers of patients, clinical outcome assessments, and recommendations for azithromycin use are included.. Azithromycin is a macrolide derivative and the first of the 15-membered ring azalide class of antimicrobials. Although its mechanism of action and susceptibility to resistance are similar to those of the macrolide antibiotics, azithromycin's extended spectrum of activity includes gram-positive and gram-negative organisms, as well as atypical pathogens. Azithromycin is stable at gastric pH and has an absolute bioavailability of approximately 37 percent following oral administration. Although its serum concentrations are typically low, the drug concentrates to a high degree in tissue. Azithromycin is cleared primarily by the biliary and fecal routes; its serum half-life is in excess of 60 hours. Several clinical trials have proven that a 5-day course of azithromycin administered once a day is equally efficacious to a 7- to 14-day course of other commonly used oral antimicrobials, administered two to four times a day, for the treatment of upper and lower respiratory tract and skin and skin-structure infections. Urethritis and cervicitis caused by chlamydia are treated with a single 1-g dose. Trials have shown azithromycin's adverse-effect profile to be equal or even superior to that of other agents, with only 0.7 percent of patients discontinuing therapy versus 2.6 percent for comparable drugs.. Azithromycin represents a significant improvement in the treatment of selected community-acquired infections. Although this agent may revolutionize the treatment of sexually transmitted diseases caused by chlamydia, it also should impact the management of respiratory tract and skin and skin-structure infections. Because of its unique pharmacokinetics and excellent adverse-effect profile, patient compliance should be greatly enhanced compared with other commonly used oral antimicrobials. Azithromycin's primary role in the near future will be in the community setting. Although its use in the hospital may be limited, this drug will be a convenient therapeutic option to have on hand in the emergency room and outpatient clinic. Azithromycin may also be used in the future to treat opportunistic infections in immunocompromised patients.

Topics: Azithromycin; Bacterial Infections; Clinical Trials as Topic; Drug Costs; Drug Interactions; Drug Resistance, Microbial; Erythromycin; Humans; Intestinal Absorption

Macrolides are the primary drugs of choice for a number of clinically significant infections in children. The clinical aspects of newer macrolides such as roxithromycin, clarithromycin, dirithromycin, flurithromycin, miocamycin, rokitamycin, azithromycin and RP 59500 are discussed in different pediatric infections including streptococcal infections (e.g. pharyngitis, otitis, pneumonia, skin infections), staphylococcus soft tissue infections, mycoplasma pneumonia, chlamydial infections as well as legionellosis and campylobacter enteritis. Also, incidences of adverse events in pediatric patients receiving different macrolides are indicated as well as the dosages in children. The advantages of newer macrolides are: lower dosages, b.i.d. or once daily dosage regimens, good intracellular and tissue penetration, better activity against gram-negative microorganisms (some) and a low rate of adverse reactions.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Erythromycin; Humans; Infant; Virginiamycin

High and prolonged tissue levels accompanied by low serum concentrations are a feature of azithromycin, an azalide antibiotic. It has a broad spectrum of activity against gram-positive and gram-negative microorganisms and several intracellular pathogens. A number of animal models of localised infection have been developed which demonstrate that the efficacy of azithromycin correlates with its extravascular pharmacokinetics and not with blood levels. In many instances, because of high tissue bioavailability, azithromycin has better in vivo efficacy than comparative agents, despite a similar or higher minimum inhibitory concentration. Additionally, the extravascular kinetics of azithromycin are associated with bactericidal activity against pathogens such as Staphylococcus aureus, Streptococcus pneumoniae and Escherichia coli. Intracellular pathogens are susceptible to azithromycin and it is believed that the agent penetrates and remains within host cells infected by organisms including Mycobacterium avium, Legionella pneumophila and Borrelia burgdorferi. This paper reviews the in vivo efficacy of azithromycin and standard agents in animal models of infection, especially those involving intracellular pathogens.

Topics: Animals; Azithromycin; Bacterial Infections; Disease Models, Animal; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Mice; Phagocytes; Tissue Distribution

To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women.. We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate.. From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection.. A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings.. ClinicalTrials.gov, NCT03248297.. Merck for Mothers Investigator Studies Program grant.

Topics: Abscess; Administration, Oral; Adult; Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Cameroon; Cesarean Section; Chorioamnionitis; Double-Blind Method; Endometritis; Female; Humans; Infant, Newborn; Infection Control; Labor, Obstetric; Peripartum Period; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Treatment Outcome; Wound Infection

Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients. A major concern with prolonged treatment with antibiotics is the development of bacterial resistance. In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients.. This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period. In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period.. There was no increased risk for acquisition of macrolide resistance genes in the azithromycin group compared to the placebo group in COPD patients. However, loss of the macrolide resistance gene ermB was increased overtime in the placebo treated group compared to the azithromycin group (n = 5 for the placebo group versus n = 0 for the azithromycin group at 12 months; p = 0.012). The change in relative abundance of the three macrolide-resistance genes showed that all but one (ermF) increased during treatment with azithromycin.. The acquisition rate of macrolide resistance genes in COPD patients treated with azithromycin maintenance therapy was limited, but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo. This study was part of the COLUMBUS trial ( Clinicaltrials.gov , NCT00985244 ).

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Macrolides; Male; Middle Aged; Prevalence; Pulmonary Disease, Chronic Obstructive

Macrolides are among the most widely prescribed antibiotics worldwide. However, their impact on the gut's bacterial microbiota remains uncertain. We characterised the intestinal microbiota in 6-11 month-old infants in India who received a 3-day course of azithromycin or placebo during a randomised trial of oral poliovirus vaccine immunogenicity (CTRI/2014/05/004588). In 60 infants per study arm, we sequenced the V4 region of the bacterial 16S rRNA gene in stool samples collected before and 12 days after finishing treatment. We also tested for the presence of common bacterial, viral, and eukaryotic enteropathogens in the same samples using real-time PCR in a Taqman array card (TAC) format. Azithromycin induced a modest decline in microbiota richness and a shift in taxonomic composition driven by a reduction in the relative abundance of Proteobacteria and Verrucomicrobia (specifically Akkermansia muciniphila). The former phylum includes pathogenic strains of Escherichia coli and Campylobacter spp. that declined in prevalence based on the TAC assay. These findings differ from previous observations among older children and adults in Europe and North America, suggesting that the effects of azithromycin on the bacterial microbiota may be specific to the age and geographic setting of its recipients.

Topics: Age Factors; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Biodiversity; Female; Gastroenteritis; Gastrointestinal Microbiome; Humans; India; Infant; Infant, Newborn; Male; Metagenome; Metagenomics; Public Health Surveillance; Time Factors

We have recently completed a proof-of-concept trial showing that bacterial colonization decreased in women and newborns after the administration of azithromycin during labor. Here, we aim to assess the effect of the intervention on maternal and neonatal clinical infections.. This was a double-blind, placebo-controlled randomized trial. Gambian women in labor were given either an oral dose of azithromycin (2 g) or placebo. Follow-up was conducted for 8 weeks after delivery.. From April 2013 to April 2014, we recruited 829 mothers and their 830 newborns. Sixteen infants died during the follow-up period (8 per arm). No maternal deaths or serious adverse events related to the intervention were reported. Maternal infections were lower in the azithromycin group (3.6% vs 9.2%; relative risk [RR], 0.40; 95% confidence interval [CI], 0.22-0.71; P = .002), as was the prevalence of mastitis (1.4% vs 5.1%; RR, 0.29; 95% CI, 0.12-0.70; P = .005) and fever (1.9% vs 5.8%; RR, 0.33; 95% CI, 0.15-0.74; P = .006). Among newborns, the overall prevalence of infections was also lower in the azithromycin group (18.1% vs 23.8%; RR, 0.76; 95% CI, 0.58-0.99; P = .052) and there was a marked difference in prevalence of skin infections (3.1% vs 6.4%; RR, 0.49; 95% CI, 0.25-0.93; P = .034).. Azithromycin given to women in labor decreases infections in both women and newborns during the puerperal period. Larger studies designed to evaluate the effect of the intervention on severe morbidity and mortality are warranted.

Topics: Administration, Oral; Azithromycin; Bacterial Infections; Carrier State; Developing Countries; Double-Blind Method; Female; Fever of Unknown Origin; Gambia; Humans; Infant, Newborn; Infant, Newborn, Diseases; Mastitis; Pneumococcal Infections; Pregnancy; Puerperal Infection; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus agalactiae

Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa. Asymptomatic bacterial colonization is an intermediate step towards sepsis. We conducted a phase III, double-blind, placebo-controlled randomized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus, GBS or S. pneumoniae in the newborn at day 6 postpartum. Study participants were recruited in a health facility in western Gambia. They were followed for 8 weeks and samples were collected during the first 4 weeks. Between April 2013 and April 2014 we recruited 829 women who delivered 843 babies, including 13 stillbirths. Sixteen babies died during the follow-up period. No maternal deaths were observed. No serious adverse events related to the intervention were reported. According to the intent-to-treat analysis, prevalence of nasopharyngeal carriage of the bacteria of interest in the newborns at day 6 was lower in the intervention arm (28.3% versus 65.1% prevalence ratio 0.43; 95% CI 0.36-0.52, p <0.001). At the same time-point, prevalence of any bacteria in the mother was also lower in the azithromycin group (nasopharynx, 9.3% versus 40.0%, p <0.001; breast milk, 7.9% versus 21.6%, p <0.001; and the vaginal tract, 13.2% versus 24.2%, p <0.001). Differences between arms lasted for at least 4 weeks. Oral azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and may lower the risk of neonatal sepsis. Trial registrationClinicalTrials.gov Identifier NCT01800942.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Carrier State; Double-Blind Method; Female; Gambia; Humans; Infant; Infant, Newborn; Male; Middle Aged; Nasopharynx; Placebos; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Treatment Outcome; Young Adult

Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use.. To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit.. The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids.. Azithromycin 500 mg daily or matched placebo for 3 days.. The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of -0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score.. Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, -0.166; 95% CI, -0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score.. In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics.. clinicaltrials.gov Identifier: NCT01444469.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Bacterial Infections; Disease Progression; Double-Blind Method; Emergency Medical Services; Female; Humans; Male; Middle Aged; Quality of Life; Treatment Outcome; United Kingdom

Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus at delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery of S. pneumoniae (SPAZ, 7.2% [30/418], versus SPCQ, 19.3% [84/436]; P<0.001) and H. influenzae (2.9% [12/418] versus 6.0% [26/436], P=0.028), but not S. aureus, was significantly reduced among women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small but increased in the SPAZ group (13.3% [4/30], versus SPCQ, 2.2% [2/91]; P=0.033). The proportions of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine were similar (SPAZ, 10.3% [3/29], versus SPCQ, 17.6% [16/91]; P=0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage of S. pneumoniae and H. influenzae observed in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistant S. pneumoniae and other pathogenic bacteria in both mothers and infants and assess the clinical significance of their circulation.

Topics: Adolescent; Adult; Antibiotic Prophylaxis; Antimalarials; Azithromycin; Bacterial Infections; Carrier State; Cross-Sectional Studies; Drug Combinations; Drug Resistance, Bacterial; Female; Haemophilus influenzae; Humans; Malaria; Microbial Sensitivity Tests; Nasopharynx; Papua New Guinea; Pregnancy; Pyrimethamine; Serotyping; Staphylococcus aureus; Streptococcus pneumoniae; Sulfadoxine; Young Adult

Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.

Topics: Anti-Bacterial Agents; Australia; Azithromycin; Bacteria; Bacterial Infections; Bronchiectasis; Carrier State; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Infant; Macrolides; Male; Nasopharynx; New Zealand; Pacific Islands; Placebos; Population Groups

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

Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindness, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs.. We examined associations between clinical signs of TF and ocular colonization with four pathogens commonly found in the nasopharnyx, three years after the initiation of mass azithromycin distribution. Children aged 0 to 5 years were randomly selected from 16 Gambian communities. Both eyes of each child were examined and graded for trachoma according to the World Health Organization (WHO) simplified system. Two swabs were taken from the right eye: one swab was processed for polymerase chain reaction (PCR) using the Amplicor test for detection of C. trachomatis DNA and the second swab was processed by routine bacteriology to assay for the presence of viable Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Prevalence of TF was 6.2% (96/1538) while prevalence of ocular C. trachomatis infection was 1.0% (16/1538). After adjustment, increased odds of TF were observed in the presence of C. trachomatis (OR = 10.4, 95%CI 1.32-81.2, p = 0.03), S. pneumoniae (OR = 2.14, 95%CI 1.03-4.44, p = 0.04) and H. influenzae (OR = 4.72, 95% CI 1.53-14.5, p = 0.01).. Clinical signs of TF can persist in communities even when ocular C. trachomatis infection has been controlled through mass azithromycin distribution. In these settings, TF may be associated with ocular colonization with bacteria commonly carried in the nasopharnyx. This may affect the interpretation of impact surveys and the determinations of thresholds for discontinuing mass drug administration.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Carrier State; Child, Preschool; Cross-Sectional Studies; Eye Infections, Bacterial; Female; Gambia; Humans; Infant; Infant, Newborn; Male; Prevalence

Azithromycin or doxycycline is recommended for nongonococcal urethritis (NGU); recent evidence suggests their efficacy has declined. We compared azithromycin and doxycycline in men with NGU, hypothesizing that azithromycin was more effective than doxycycline.. From January 2007 to July 2011, English-speaking males ≥16 years, attending a sexually transmitted diseases clinic in Seattle, Washington, with NGU (visible urethral discharge or ≥5 polymorphonuclear leukocytes per high-power field [PMNs/HPF]) were eligible for this double-blind, parallel-group superiority trial. Participants received active azithromycin (1 g) + placebo doxycycline or active doxycycline (100 mg twice daily for 7 days) + placebo azithromycin. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Ureaplasma urealyticum biovar 2 (UU-2), and Trichomonas vaginalis (TV) using nucleic acid amplification tests. Clinical cure (<5 PMNs/HPF with or without urethral symptoms and absence of discharge) and microbiologic cure (negative tests for CT, MG, and/or UU-2) were determined after 3 weeks.. Of 606 men, 304 were randomized to azithromycin and 302 to doxycycline; CT, MG, TV, and UU-2 were detected in 24%, 13%, 2%, and 23%, respectively. In modified intent-to-treat analyses, 172 of 216 (80%; 95% confidence interval [CI], 74%-85%) receiving azithromycin and 157 of 206 (76%; 95% CI, 70%-82%) receiving doxycycline experienced clinical cure (P = .40). In pathogen-specific analyses, clinical cure did not differ by arm, nor did microbiologic cure differ for CT (86% vs 90%, P = .56), MG (40% vs 30%, P = .41), or UU-2 (75% vs 70%, P = .50). No unexpected adverse events occurred.. Clinical and microbiologic cure rates for NGU were somewhat low and there was no significant difference between azithromycin and doxycycline. Mycoplasma genitalium treatment failure was extremely common. Clinical Trials Registration.NCT00358462.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Double-Blind Method; Doxycycline; Humans; Male; Middle Aged; Placebos; Treatment Outcome; Trichomonas Infections; Urethritis; Urine; Washington; Young Adult

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

Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.. We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.. A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04).. Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Drug Resistance, Bacterial; Female; Humans; Macrolides; Male; Middle Aged; Nasopharynx; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

To examine study entry microbiology in patients stratified by disease severity in a clinical trial in acute bacterial exacerbation of chronic bronchitis (ABECB).. Patients were assigned to differing antibiotic therapies based on stratification by disease severity using parameters including forced expiratory volume in 1 second (FEV(1)) as a percentage of predicted value, number of exacerbations during the previous 12 months, and defined co-morbidities. All patients were required to have sputum Gram stain and culture at study entry.. There was no statistically significant difference in overall microbiology between patients with less severe and more severe clinical presentations. Typical ABECB pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) were found in 46.2% (147/318) of patients with less severe presentations and 41.9% (143/341) of patients with more severe presentations. Gram-negative organisms and Staphylococcus aureus were also found in both groups. Pneumococcal susceptibilities to the three antibiotics utilized in the trial revealed marked resistance to azithromycin. Limitations of this analysis include that the clinical trial was designed to examine clinical outcomes rather than microbiology, and that we do not correlate study entry microbiology with clinical outcomes.. Stratification of patients by disease severity did not reveal a statistically significant difference in overall microbiological profile. Gram-negative organisms and S. aureus were recovered even from patients with less severe clinical presentations. Pneumococcal resistance varied with the agent tested. These findings may have implications for the selection of appropriate antibiotic therapy.

Topics: Acute Disease; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis, Chronic; Double-Blind Method; Drug Resistance, Bacterial; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Ofloxacin; Severity of Illness Index; Sputum

The purpose of this study was to explore whether endometrial microbial colonization and plasma cell endometritis are risk factors for adverse pregnancy outcomes, and whether these outcomes are influenced by interactions between interconceptional antibiotics and the micro-flora.. Subgroup analyses of data from a double-blind, randomized, placebo-controlled trial of a course of metronidazole plus azithromycin given every 4 months to women with a prior preterm delivery to prevent recurrent preterm delivery. Endometrial cultures and histology were obtained at randomization and repeated 2 weeks after the first treatment. Fifty-nine on antibiotics versus 65 on placebo had pregnancy outcomes. Prevalence of adverse pregnancy outcomes (pregnancy loss or preterm birth < 37 weeks) was stratified by treatment group and endometrial characteristics. Subgroups were assessed and screened for potential interaction (P values for significance set a priori at < .01), prior to formal statistical testing for interaction (P values < .05).. The prevalence of adverse pregnancy outcome was 62.7% in the presence of endometrial microbial colonization at baseline (any microbe) and 50% in the absence of colonization (RR = 1.25; 99% CI 0.42-3.7). Prevalence of adverse pregnancy outcomes was 61.9% with plasma cell endometritis, and 70.8% without; RR = 0.87 (0.50-1.5). There was a nonsignificant reduction in adverse pregnancy outcome in the absence of Gardnerella vaginalis or gram-negative rods with RR (95% CI) = 0.60 (0.3-1.2) and 0.66 (0.4-1.2), respectively. In the presence of these microbes, antibiotics appeared to increase adverse outcomes: RR = 1.5 (1.1-2.0) and 1.5 (1.1-2.1), respectively. This reversal of impact represents a crossover interaction.. Neither baseline endometrial microbial colonization nor plasma cell endometritis were risk factors for adverse pregnancy outcome. However, colonization with specific microbes interacted with antibiotics to increase adverse outcomes.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Double-Blind Method; Endometritis; Endometrium; Female; Humans; Metronidazole; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth

Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin.. A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years.. Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles.. We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Atovaquone; Azithromycin; Bacterial Infections; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Infant, Newborn; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Azithromycin; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the efficacy and safety of a single 2.0-g dose of a novel azithromycin microsphere formulation with that of 10 days of levofloxacin, 500 mg/d, when used to treat adults with uncomplicated acute bacterial maxillary sinusitis (ABS).. An international, multicenter, randomized, double-blind, double-dummy trial. Eligible outpatients > or =18 years of age with clinical and radiographic evidence of ABS underwent maxillary sinus aspiration before randomization. Primary endpoint was clinical efficacy at the test-of-cure visit (day 17-24).. Clinical success rates were 94.5% (242/256) in azithromycin-microspheres-treated patients and 92.8% (233/251) in the levofloxacin group. In patients with documented Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, clinical cure rates were 97.3% (36/37), 96.3% (26/27), and 100% (8/8), respectively, for the azithromycin group and 92.3% (36/39), 100% (30/30), and 90.9% (10/11), respectively, for the levofloxacin group.. Single-dose azithromycin microspheres provided clinical and bacteriologic efficacy and safety comparable to 10 days of levofloxacin.. A novel microsphere formulation of azithromycin given as a single dose was safe and effective for the treatment of ABS.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Chemistry, Pharmaceutical; Confidence Intervals; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; International Cooperation; Levofloxacin; Male; Maxillary Sinusitis; Microspheres; Middle Aged; Ofloxacin; Probability; Risk Assessment; Severity of Illness Index; Treatment Outcome

To compare the safety and efficacy of oral azithromycin and levofloxacin in the treatment of outpatients with acute bacterial exacerbations of chronic bronchitis (ABECB).. Randomized, double-blinded, double-dummy, multicenter trial with 1:1 treatment allocation.. Outpatient treatment setting.. Two hundred thirty-five male or female outpatients between the ages of 35 and 75 years who had received a clinical diagnosis of ABECB.. Blinded treatment with either oral azithromycin, 500 mg on day 1 and 250 mg per day for days 2 to 5, or, oral levofloxacin, 500 mg q24h for 7 days.. Both treatments were well-tolerated, with the majority of adverse events being GI in nature. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 89% of patients receiving azithromycin and in 92% of patients receiving levofloxacin by day 4 of therapy. At day 24, the posttherapy visit, favorable responses were approximately 82% and 86%, respectively, for patients in the two treatment groups. The bacterial eradication rates of respiratory pathogens were 96% for azithromycin and 85% for levofloxacin.. Despite increasing concerns over macrolide resistance and a higher incidence of Gram-negative pathogens, a standard 5-day course of oral azithromycin was clinically and bacteriologically equivalent to a 7-day course of oral levofloxacin in the treatment of patients with ABECB.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Bronchitis, Chronic; Double-Blind Method; Female; Humans; Levofloxacin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Ofloxacin

53 patients with planned antibiotic therapy for the treatment of acute exacerbation of chronic bronchitis as an example of a severe bacterial infection requiring antibiotics were included in a prospective, multicentre, double-blind, placebo-controlled study. The chronic bronchitis was staged by forced expiratory volume of the 1st second (FEV(1)) measured in the infection-free interval prior to the current episode and had to be between 35 and 75% for the predicted value. Patients were randomly assigned to receive newer macrolide antibiotics plus either Esberitox N or placebo. Antibiotic therapy was administered according to generally accepted guidelines and Esberitox N or placebo was given for 28 days. The baseline-adjusted means for FEV(1) (%) on day 10 were 68.7 points for the Esberitox N group and 59.2 points for the placebo group (p = 0.0303). For FEV(1) the difference between the two treatment groups was 267 ml (p = 0.0499). The time to half maximal improvement was 5.7 days in the Esberitox N group compared to 12.8 days in the placebo group. The treatment was well tolerated; no serious adverse events were documented. In conclusion, comedication of antibiotics with Esberitox N in subjects with acute exacerbation of chronic bronchitis seems to be of benefit for the patient. Apparently, therapy with Esberitox N leads to a faster recovery from this severe bacterial infection, possibly via preventing an impairment of the host's immune system which might otherwise occur as a consequence of aggressive antimicrobial therapeutics.

Topics: Adjuvants, Immunologic; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis, Chronic; Chronic Disease; Clarithromycin; Double-Blind Method; Drug Therapy, Combination; Humans; Lung Diseases, Obstructive; Pilot Projects; Plant Extracts; Roxithromycin; Time Factors

Prior use of antibiotics is associated with carriage of resistant bacteria. Colonization by Streptococcus pneumoniae, Haemophilus influenzae, nonpneumococcal alpha-hemolytic streptococci (NPAHS), and Staphylococcus aureus was evaluated in children receiving antibiotic therapy for acute otitis media and in untreated, healthy control subjects. Children were randomly assigned to receive either amoxicillin/clavulanate (90 mg/kg per day) or azithromycin. Swabs were obtained before initiating therapy and again 2 weeks and 2 months after initiating therapy. We also obtained swabs from control subjects at the time of enrollment and 2 weeks and 2 months after enrollment. The decrease in the rate of carriage of S. pneumoniae and H. influenzae at 2 weeks was significant only in the amoxicillin/clavulanate group (P<.001 and P=.005, respectively). The rate of nasopharyngeal colonization with NPAHS among treated patients increased from 23% to 39% at 2 months (P=.01). This increase was similar for both treatment groups. These results suggest that the competitive balance between organisms is altered by antibiotic therapy.

Topics: Acute Disease; Amoxicillin; Azithromycin; Bacterial Infections; Child, Preschool; Clavulanic Acid; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Male; Nasopharyngeal Diseases; Otitis Media; Serotyping; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae

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

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to azithromycin for the treatment of patients with acute exacerbations of chronic bronchitis (AECB) of suspected bacterial origin. Between October 1998 and April 1999, 567 patients with AECB were enrolled at 37 centers across the United States and Canada of which 280 (49%) had acute bacterial exacerbation of chronic bronchitis (i.e. pretherapy pathogen). Patients were randomized to either oral moxifloxacin 400 mg administered once daily for 5 days or azithromycin for 5 days (500 mg qd x 1, then 250 mg qd x 4). For the purpose of study blinding, all patients received encapsulated tablets. The main outcome measure was clinical response at the test-of-cure visit (14-21 days post-therapy). Secondary measures included bacteriologic response and a time-course of bacteriological eradication (one center only). Three patient populations were analysed for efficacy: clinically-valid, microbiologically-valid (i.e. those with a pretherapy pathogen), and intent-to-treat (i.e. received at least one dose of study drug). For the efficacy-valid group, clinical response at the test-of-cure visit was 88% for patients in each treatment group. In 237 microbiologically-valid patients, corresponding clinical resolution rates were 88% for 5-day moxifloxacin vs. 86% for 5-day azithromycin. Bacteriological eradication rates at the end of therapy were 95% for 5-day moxifloxacin and 94% for the azithromycin group. Corresponding eradication rates at the test-of-cure visit were 89% and 86%, respectively. Of note, eradication rates at test-of-cure for Haem. philos influenzae and H. parainfluenzae for moxifloxacin were 97% and 88% compared to 83% and 62% respectively for azithromycin. Among 567 intent-to-treat patients (283 moxifloxacin and 284 azithromycin), drug-related events were reported for 22% and 17%, respectively. Diarrhea and nausea were the most common drug-related events reported in each treatment group. Moxifloxacin 400 mg once daily for 5 days was found to be clinically and bacteriologically equivalent to 5-day azithromycin for the treatment of AECB of proven bacterial etiology. Given its excellent in-vitro activity, especially against antibiotic-resistant respiratory pathogens, and its acceptable safety profile, moxifloxacin should be considered an effective alternative therapy for patients wi

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Bacterial Infections; Bronchitis; Chronic Disease; Double-Blind Method; Female; Fluoroquinolones; Humans; Male; Middle Aged; Moxifloxacin; Multicenter Studies as Topic; Prospective Studies; Quinolines

Despite the advances in therapy, chronic obstructive pulmonary disease (COPD) requires frequent hospital admissions due to acute exacerbations. We carried out a prospective randomized study of two groups of patients with COPD, one (n = 54) treated with azithromycin (500 mg/day) for three days every 21 days during the winter months, and a control group (n = 40) without treatment. A statistically significant reduction in the number of acute infectious episodes (187) and hospital admissions (22) was observed in the treated group versus the control group (249 and 45, respectively). A short prophylactic treatment course with azithromycin is a good alternative in the management of patients with severe, advanced COPD, and could lead to an improvement in social and healthcare costs

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Female; Hospitalization; Humans; Lung Diseases, Obstructive; Male; Prospective Studies; Statistics as Topic

We compared the clinical and microbiological efficacy of dirithromycin with that of azithromycin in outpatients with acute bacterial exacerbations of chronic bronchitis who could be graded into stage III according to Ball's system of stratification. A total of 80 patients was studied. Of these, 40 were treated with dirithromycin as a once-daily dose of 500 mg for 5 days, and 40 with azithromycin as a once-daily dose of 500 mg for 3 days. At post-therapy, treatment success (cure or improvement) was achieved in 36 out of 40 (90%) patients receiving dirithromycin compared with 37 out of 40 (92.5%) in the azithromycin group. At the late post-therapy visit, 34 out of 36 (94.4%) dirithromycin-treated patients were cured as were 33 of 37 (89.2%) azithromycin-treated patients. A small proportion of patients treated with dirithromycin (10%) or with azithromycin (12.5%) suffered mild side effects. Gastrointestinal disorders, including abdominal cramps, nausea, or diarrhea, were common adverse effects. The main pathogens isolated before treatment were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Eradication rates at the end of treatment were 90% (36 out of 40) for the dirithromycin group and 92.5% (37 out of 40) for the azithromycin group. Persistence of H. influenzae isolates was found in 3 out of 11 (27.3%) patients treated with dirithromycin and in 2 out of 9 (22.2%) who had received azithromycin. At the late post-therapy visit, eradication occurred in 34 out of 36 (94.4%) strains in the dirithromycin group and in 33 out of 37 (89.2%) in the azithromycin group. We conclude that dirithromycin and azithromycin appear to be equally effective in the treatment of acute bacterial exacerbations of chronic bronchitis.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Drug Costs; Erythromycin; Female; Haemophilus influenzae; Humans; Macrolides; Male; Middle Aged; Moraxella catarrhalis; Streptococcus pneumoniae; Treatment Outcome

A randomized study of a 3-day course of azithromycin therapy (500 mg once daily) vs. a 10-day course of co-amoxiclav therapy (625 mg thrice daily) in patients with acute sinusitis was performed with an account of the GCP criteria. One hundred patients in 2 groups each of 50 persons were enrolled. The estimates of the patient body temperature, headache, pain on palpation in the area of the accessory nasal sinuses, nasal cavity stuffing, nasal discharge nature and the nose mucous membrane appearance were recorded prior to the treatment, in 72 hours and on the 10th-12th and 26th-30th days of the treatment. The microbiological analysis of the punctate from the accessory nasal sinuses was undertaken before the antibiotic therapy and 72 hours after its start. The economic analysis included the cost of the antibiotic therapy course, hospitalization term, medical manipulations and laboratory tests as well as the cost/efficacy index. The frequency of the relapses within 6 months after the cure was estimated in the two groups compared. In 72 hours and on the 10th-12th days after the treatment start the efficacy of azithromycin was significantly higher than that of co-amoxiclav. The cure was stated in 41 (82 per cent) and 26 (52 per cent) patients on the 10th-12th days, in 6 (12 per cent) and 21 (42 per cent) patients the improvement was stated and the fail was stated in 3 (6 per cent) and 2 (4 per cent) patients respectively. The efficacy of the drugs on the 26th-30th days after the treatment start did not differ. The isolates of Staphylococcus aureus and Streptococcus pyogenes were the main pathogens. The bacteriologic eradication was recorded in 29 (90.6 per cent) patients treated with azithromycin and only in 18 (69.2 per cent) patients treated with co-amoxiclav. Adverse reactions and relapses of the disease within 6 months after the cure were more frequent in the patients treated with co-amoxiclav. The cost of the azithromycin therapy was significantly lower. It was shown that the shortened course of the azithromycin therapy provided earlier cure of the patients with acute sinusitis, better tolerance of the drug, less frequent adverse reactions, lower cost as compared to the use of co-amoxiclav and no relapses.

Topics: Acute Disease; Adolescent; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Costs and Cost Analysis; Drug Therapy, Combination; Female; Humans; Male; Sinusitis; Time Factors

Azithromycin (AZM) preparations in fine granules and capsules were evaluated in 36 pediatric patients with various infections. In patients with pneumonia caused by Moraxella catarrhalis, Haemophilus influenzae or Mycoplasma pneumoniae, bronchitis, pharyngitis, scarlet fever, whooping cough, or campylobacter enteritis, AZM was found effective in 94.4% (34/36). As for the bacteriological efficacy of AZM, all of 12 strains identified were found eradicated by the treatment. Plasma T 1/2(24 approximately 48 hrs.) of AZM in fine granules, given two patients at 10 mg/kg body weight once daily for 3 days, were 41.5 and 51.4 hours, while AUC0 approximately infinity was 7.45 and 13.44 mg.hr/ml. The rates of AZM recovered in the urine samples from two pediatrics patients in the first 81 hours of treatment, when it is given in fine granules at 10 mg/kg body weight once daily for 3 days, were 6.27% and 11.0%. Data from 43 patients were included for drug safety evaluation. Neither adverse reactions nor abnormal laboratory changes were observed. In conclusion, AZM was found useful in treatment of pediatric infections.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Capsules; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form w

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Capsules; Child; Child, Preschool; Dosage Forms; Drug Resistance, Microbial; Female; Humans; Infant; Male

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 (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

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

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Double-Blind Method; Female; Fluoroquinolones; Humans; Japan; Jaw; Male; Middle Aged; Naphthyridines; Osteitis; Pericoronitis; Periodontitis

In the treatment of diffuse panbronchiolitis, azithromycin (AZM), a new macrolide antibiotic with 15-membered lactone ring, was studied for its efficacy and safety. AZM, 250 mg, was intermittently administered to a total of 60 patients twice a weeks, for 3 months as a rule, and its efficacy was clinically evaluated in 52 patients and the safety in 55. The rate of efficacy was 84.6% (44/52). Clinical findings 12 weeks after the start of administration showed a decrease in sputum volume in 30 of 46 patients and amelioration of dyspnea on exertion in 23 of 46 patients, and no worsening of symptoms was observed in the patients. Vital capacity (4/22), FEV1.0 (6/21), cold agglutination reaction (22/28), and CRP (16/36) were also improved. The rate of eradication of organisms isolated from the sputum except for indigenous organisms was 39.5% (15/38); 4 of the 22 strains of Pseudomonas aeruginosa were eradicated. Adverse reactions were observed in 4 of the 55 patients (7.3%), 1 patient each with rash, itching, diarrhea, and a gastric symptom (heavy feeling in the stomach). 4 of the 54 patients (7.4%) exhibited abnormal changes in clinical laboratory test values values. These were an increase in eosinophil count in 2, elevation of GOT in 1, and elevation of Al-P in 1. These adverse reactions and abnormal changes in laboratory tests were mild or moderate. Therefore, long-term intermittent administration of AZM, twice a week, is expected to have the same effect in the treatment of diffuse panbronchiolitis as long-term small-dose administration of 14-membered macrolides such as erythromycin and clarithromycin, whose effects have already been established.

Topics: Adolescent; Adult; Aged; Azithromycin; Bacterial Infections; Bronchiolitis; Drug Administration Schedule; Female; Humans; Japan; Male; Middle Aged

An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Bacterial Infections; Bronchitis; Chronic Disease; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Sputum

A total of 51 patients with acute exacerbation of chronic bronchitis and pneumonia were enrolled: 27 treated with azithromycin (500 mg once a day for 3 days), and 24 with roxithromycin (150 mg every 12 hours for 7 days). The two regimens were equally effective, with clinical cure in 80% and 72% of patients respectively. Bacteriological eradication on day 19-23 was obtained in 7/11 cases (64%) and in 6/13 cases (46%) in the two groups, respectively. No side effects occurred in patients treated with azithromycin, while they occurred in the roxithromycin group (2 vomiting and 1 gastritis). Clinical and bacteriological efficacy, excellent tolerability, simplified dosage (single daily dose) and short-course (3 days) therapeutic regimen make azithromycin, in our experience, efficacious for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Bronchitis; Chronic Disease; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia; Prospective Studies; Roxithromycin; Treatment Outcome

Sixty patients with acute odontogenic infections were randomly allocated to oral treatment with azithromycin 500 mg/day once-daily for three days (n = 30) or spiramycin 3,000,000 units three-times daily for seven days (n = 30). Baseline and post-treatment oral specimens were collected from patients to test for pathogenic bacteria. Aerobic bacteria were tested using the Kirby-Bauer disc diffusion method, and anaerobic bacteria with a broth microdilution method, for their susceptibility to azithromycin and spiramycin. A greater incidence of resistance was found in the spiramycin group than in the azithromycin group. The bacteriological assessment showed that the normal balance of microflora was re-established in 67% of patients treated with azithromycin vs 53% in the group treated with spiramycin. Clinical cure was higher in the azithromycin treatment group (97%) compared with the spiramycin group (73%). These results indicate that three-day azithromycin, possibly because of its unusual pharmacokinetics, is more effective than seven-day spiramycin in the treatment of odontogenic infections.

Topics: Azithromycin; Bacterial Infections; Erythromycin; Female; Humans; Male; Mouth Diseases; Spiramycin; Tooth Diseases

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 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

In this randomised, double-blind study carried out in 28 centres, azithromycin (500 mg single dose on day 1, followed by 250 mg once-daily on days 2-5) was compared with cefaclor (500 mg t.i.d. for 10 days) in the treatment of acute bacterial pneumonia. A total of 119 patients entered the study, and of these 71 were evaluable and included in the efficacy analysis. The overall satisfactory clinical response was 97.3% for azithromycin patients and 100% for cefaclor patients. The clinical cure rates of azithromycin and cefaclor were 46.9% and 41.0%, respectively; improvement was seen in an additional 46.9% of azithromycin-treated patients and in 59.0% of the cefaclor group. The bacteriological eradication rates were 80.4% and 92.6%, respectively. These rates of clinical and bacteriological efficacy, were not statistically different. Both antibiotics were well tolerated during the study; only two patients (one on each study drug) discontinued medication due to adverse events. The overall incidence of side effects was 18.9% (10 of 53 patients) for azithromycin- and 12.1% (eight of 66 patients) for cefaclor-treated patients. Gastrointestinal disturbances were the most commonly reported side effects (nine of 10 azithromycin-treated patients and six of eight cefaclor-treated patients). In addition, two cefaclor patients reported headache. All azithromycin side effects were mild or moderate in severity, but there were two severe occurrences in the cefaclor group (1 nausea, 1 vomiting) the later leading to discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Cefaclor; Double-Blind Method; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia

Bacterial infection causes lung inflammation and recruitment of several inflammatory factors that may result in acute lung injury (ALI). During bacterial infection, reactive oxygen species (ROS) and other signaling pathways are activated, which intensify inflammation and increase ALI-related mortality and morbidity. To improve the ALI therapy outcome, it is imperative clinically to manage bacterial infection and excessive inflammation simultaneously. Herein, a synergistic nanoplatform (AZI+IBF@NPs) constituted of ROS-responsive polymers (PFTU), and antibiotic (azithromycin, AZI) and anti-inflammatory drug (ibuprofen, IBF) was developed to enable an antioxidative effect, eliminate bacteria, and modulate the inflammatory milieu in ALI. The ROS-responsive NPs (PFTU NPs) loaded with dual-drugs (AZI and IBF) scavenged excessive ROS efficiently both in vitro and in vivo. The AZI+IBF@NPs eradicated Pseudomonas aeruginosa (PA) bacterial strain successfully. To imitate the entry of bacterial-derived compounds in body, a lipopolysaccharide (LPS) model was adopted. The administration of AZI+IBF@NPs via the tail veins dramatically reduced the number of neutrophils, significantly reduced cell apoptosis and total protein concentration in vivo. Furthermore, nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3) and Interleukin-1 beta (IL-1β) expressions were most effectively inhibited by the AZI+IBF@NPs. These findings present a novel nanoplatform for the effective treatment of ALI.

Topics: Acute Lung Injury; Azithromycin; Bacterial Infections; Humans; Ibuprofen; Inflammation; Nanoparticles; Polymers; Reactive Oxygen Species

Protracted bacterial bronchitis (PBB) causes chronic wet cough for which seasonal azithromycin is increasingly used to reduce exacerbations. We investigated the impact of seasonal azithromycin on antimicrobial resistance and the nasopharyngeal microbiome. In an observational cohort study, 50 children with PBB were enrolled over two consecutive winters; 25/50 at study entry were designated on clinical grounds to take azithromycin over the winter months and 25/50 were not. Serial nasopharyngeal swabs were collected during the study period (12-20 months) and cultured bacterial isolates were assessed for antimicrobial susceptibility. 16S rRNA-based sequencing was performed on a subset of samples. Irrespective of azithromycin usage, high levels of azithromycin resistance were found; 73% of bacteria from swabs in the azithromycin group vs. 69% in the comparison group. Resistance was predominantly driven by azithromycin-resistant

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Bronchitis, Chronic; Child; Chronic Disease; Cough; Drug Resistance, Bacterial; Erythromycin; Humans; Microbiota; RNA, Ribosomal, 16S; Seasons; Streptococcus pneumoniae

There are reports of high rates of antibiotic prescribing among hospitalized patients with COVID-19 around the world. To date, however, there are few reports of prescribing in relation to COVID-19 in Pakistan. Herein, we describe a point prevalence survey of antibiotic prescribing amongst patients hospitalized with suspected or proven COVID-19 in Pakistan. A Point Prevalence Survey (PPS) was undertaken in seven tertiary care health facilities in Punjab Provence, Pakistan. Baseline information about antimicrobial use according to the World Health Organization (WHO) standardized methodology was collected on a single day between 5

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Ceftriaxone; Coinfection; COVID-19; COVID-19 Drug Treatment; Drug Prescriptions; Female; Humans; Male; Meropenem; Pakistan; Prevalence

Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton-McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bacteria; Bacterial Infections; Cells, Cultured; Humans; Macrolides; Mice, Inbred BALB C; Models, Molecular; Oxidation-Reduction; Pneumonia

More evidence is needed to support recommendations for medical management of acute radiation syndrome (ARS) and associated infections resulting from a radiological/nuclear event. While current guidelines recommend the administration of antibiotics to chemotherapy patients with febrile neutropenia, the clinical benefit is unclear for acute radiation injury patients. A well-characterized nonhuman primate (NHP) model of hematopoietic ARS was developed that incorporates supportive care postirradiation. This model evaluated the efficacy of myeloid growth factors within 24 to 48 h after total body irradiation (TBI). However, in this model, NHPs continued to develop life-threatening bacterial infections, even when granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was administered in combination with antibiotic monotherapy. In this study, we evaluated the efficacy of combination antibiotic therapies administered to NHPs following 7.4-Gy TBI to understand the occurrence of bacterial infection in NHPs with hematopoietic ARS. We compared enrofloxacin-linezolid, enrofloxacin-cefepime, and enrofloxacin-ertapenem to enrofloxacin monotherapy. The primary endpoint was 60-day postirradiation mortality, with secondary endpoints of overall survival time, incidence of bacterial infection, and bacteriologic culture with antimicrobial susceptibility testing. We observed that enrofloxacin-ertapenem significantly increased survival compared to enrofloxacin monotherapy. Bacteria isolated from nonsurviving macaques with systemic bacterial infections exhibited uniform resistance to enrofloxacin and variable resistance to beta-lactam antibiotics, linezolid, gentamicin, and azithromycin. Multidrug antibiotic resistance was observed in

Topics: Acute Radiation Syndrome; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Cefepime; Enrofloxacin; Ertapenem; Gentamicins; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Linezolid; Radiation Dosage

Inappropriate antibiotic prescriptions contributed to a global issue of antimicrobial resistance. This study aimed to assess the prevalence of bacterial pathogens and antimicrobial resistance isolated from maxillofacial infections (MIs). Two hundred and twenty-two patients with different MIs were included in this study. Swab samples were taken from the site of infections. Samples were cultured, and isolated bacteria were identified using various biochemical tests. Antimicrobial resistance patterns of isolates were assessed by the disk diffusion method. The mean age of the patients was 50.8 years. The male-to-female ratio was 127/95 (P<0.05). Smoking and alcohol consumption were found in 60.36% and 37.38% of patients, respectively. Most patients had a ≤1-week infection duration (P<0.05). Abscess lesion was the most predominant infection type (P<0.05). The prevalence of aerobic bacteria among abscess, pus localization, and deep facial infections was 59.33%, 64.28%, and 46.66%, respectively. The prevalence of anaerobic bacteria among abscess, pus localization, and deep facial infections was 40.66%, 23.80%, and 53.33%, respectively.

Topics: Abscess; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacteria; Bacterial Infections; Ceftriaxone; Drug Resistance, Bacterial; Female; Gentamicins; Humans; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Surgery, Oral; Tetracyclines

In the study, new polymeric micelles loaded with azithromycin were prepared to enhance azithromycin's solubility and evaluate its in vitro/in vivo antibacterial activity against Staphylococcus aureus. Amphiphilic α-Linolenic acid-methoxy poly (ethylene glycol) polymer (MPEG-LNA) was synthesized through DCC-DMAP esterification procedure. Through thin-film hydration method, optimized azithromycin-loaded micelles (AZI-M) were prepared with 87.15% of encapsulation efficiency and 11.07% of drug loading capacity when the ratio of LNA to MPEG was 4. Azithromycin's water-solubility was obviously enhanced due to its loading into the polymeric micelles. The azithromycin-loaded micelles were characterized in terms of x-ray diffraction, Fourier transform infrared spectroscopy, in vitro release, and in vitro/in vivo antibacterial experiments. Although the drug-loaded micelles provided a slow and continuous azithromycin's release in comparison with free azithromycin, in vitro antibacterial activity results confirmed that its effect on the inhibition of bacterial growth and biofilm formation was similar to free azithromycin. It is more interesting that the azithromycin-loaded micelles achieved good in vivo antibacterial therapeutic effect like QiXian® (azithromycin lactobionate injection) in mouse model of intraperitoneal infection. AZI-M can be considered as a potential candidate for in vivo antibiotic therapy of Staphylococcus aureus infections.

Topics: alpha-Linolenic Acid; Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Drug Carriers; Mice; Micelles; Polyesters; Polyethylene Glycols; Polymers

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child Mortality; Child, Preschool; Female; Humans; Male; Mass Drug Administration

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

The dissemination of COVID-19 around the globe has been followed by an increased consumption of antibiotics. This is related to the concern for bacterial superinfection in COVID-19 patients. The identification of bacterial pathogens is challenging in low and middle income countries (LMIC), as there are no readily-available and cost-effective clinical or biological markers that can effectively discriminate between bacterial and viral infections. Fortunately, faced with the threat of COVID-19 spread, there has been a growing awareness of the importance of antimicrobial stewardship programs, as well as infection prevention and control measures that could help reduce the microbial load and hence circulation of pathogens, with a reduction in dissemination of antimicrobial resistance. These measures should be improved particularly in developing countries. Studies need to be conducted to evaluate the worldwide evolution of antimicrobial resistance during the COVID-19 pandemic, because pathogens do not respect borders. This issue takes on even greater importance in developing countries, where data on resistance patterns are scarce, conditions for infectious pathogen transmission are optimal, and treatment resources are suboptimal.

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Bacterial Infections; COVID-19; Developing Countries; Drug Resistance, Bacterial; Humans; Pandemics; SARS-CoV-2; Superinfection

This is a review of the macrolide and ketolide field focusing on differentiating the pharmacodynamics and especially the toxicology of the macrolides and ketolides. We emphasize the diversity in pharmacodynamics and toxicity of the macrolides and ketolides, resulting from even small structural changes, which makes it important to consider the various different compounds separately, not necessarily as a class. The ketolide, telithromycin, was developed because of rising bacterial macrolide resistance but was withdrawn postapproval after visual disturbances, syncope, myasthenia gravis, and hepatotoxicity were noted. These diverse adverse effects could be attributed to inhibition of nicotinic acetylcholine receptors. Solithromycin, a later generation ketolide, was effective in treating bacterial pneumonia, but it was not approved by the U.S. Food and Drug Administration owing, in part, to its structural similarity to telithromycin. This Miniperspective describes that structurally similar macrolides/ketolides have clearly mechanistically distinct effects. Understanding these effects could help in developing and securing regulatory approval of a new macrolide/ketolide that is active against macrolide-resistant pathogenic bacteria.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Drug-Related Side Effects and Adverse Reactions; Humans; Ketolides; Macrolides

The COVID-19 pandemic has dramatically challenged care for cancer patients, especially those with active treatment who represent a vulnerable population for SARS-CoV-2 infection. Aggressive lymphoid neoplasms, such as diffuse large B cell lymphoma and high-grade B cell lymphoma, need to be treated without delay in order to get the best disease outcome. Because of that, our clinical practice was changed to minimise the risk of SARS-CoV-2 infection while continuing haematological treatment. In this report, we analyse the management of front-line therapy in 18 patients during the COVID-19 outbreak, as well as the results of the implemented measures in their outcome.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Azithromycin; Bacterial Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Cyclophosphamide; Doxorubicin; Febrile Neutropenia; Female; Granulocyte Colony-Stimulating Factor; Humans; Hydroxychloroquine; Infection Control; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Pandemics; Plasmablastic Lymphoma; Prednisone; Rituximab; SARS-CoV-2; Spain; Superinfection; Vincristine

In addition to their antibiotic activities, azithromycin (AZM) exhibits anti-inflammatory effects in various respiratory diseases. One of the potent anti-inflammatory mechanisms is through inhibition of CD4+ helper T (Th) cell effector function. However, their impact on specific Th subset is obscure. Herein, we demonstrate the cellular basis of phenotypic and functional alterations associated with Th subsets following AZM treatment

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Cell Differentiation; Cell Movement; Cells, Cultured; Healthy Volunteers; Humans; Interferon-gamma; Interleukin-4; Receptors, Antigen, T-Cell; Receptors, CCR4; Receptors, CXCR3; T-Lymphocyte Subsets; Th1 Cells

Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects.. The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections.. Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic. The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Biocompatible Materials; Biofilms; Cervix Uteri; Chlamydia trachomatis; Drug Liberation; Escherichia coli; Female; HeLa Cells; Humans; Liposomes; Microbial Sensitivity Tests; Particle Size; Plankton; Swine; Vagina

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child Mortality; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Mass Drug Administration

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

Topics: Africa South of the Sahara; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child Mortality; Humans; Mass Drug Administration

To examine whether short-term use of azithromycin increases the risk of sensorineural hearing loss (SNHL) in adults with uncomplicated infections.. A retrospective cohort study using Medicaid claims data, 1999 to 2010.. Adults (18-64 years old) who had continuous enrollment in Medicaid for the 12 months (baseline) before the date of first dispensation (index date) of oral azithromycin or amoxicillin ± clavulanate for uncomplicated infections.. We operationalized sensorineural hearing loss (SNHL) by a charge for audiometry and followed by a diagnosis of SNHL within 30 days.. We adjusted for the baseline covariates through propensity score matching. Adults were followed for up to 120 days after the index date. The hazard of SNHL in azithromycin-exposed adults was compared with those who had amoxicillin ± clavulanate using a Cox proportional hazard model. We performed several sensitivity analyses by varying the follow-up time, SNHL definition, adjusting for cumulative antibiotic use, and switching exposure status during the follow-up period.. A total of 493,774 patients entered the study cohort. The unadjusted incidence rates of SNHL were 38 and 41 cases per 10,000 patient-years following exposure to azithromycin and amoxicillin ± clavulanate, respectively. The adjusted (matched) hazard ratio (HR) of SNHL for azithromycin versus amoxicillin ± clavulanate was 0.91 (95% confidence interval [CI], 0.77-1.07). The sensitivity analyses findings were consistent with the primary analysis.. Azithromycin short-term use was not associated with an increased risk of SNHL in comparison to amoxicillin ± clavulanate.

Topics: Adolescent; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Audiometry; Azithromycin; Bacterial Infections; Female; Hearing Loss, Sensorineural; Humans; Incidence; Male; Medicaid; Middle Aged; Retrospective Studies; United States; Young Adult

Patients with more severe chronic obstructive pulmonary disease frequently experience exacerbations and it is estimated that up to 50% of these exacerbations are associated with bacterial infections. The mainstay treatment for these infection-related exacerbations constitutes the administration of glucocorticoids, alone or in combination with antibiotics. A recent line of evidence demonstrates that many hormones including the steroid beclomethasone can also directly affect bacterial growth, virulence, and antibiotic resistance. The effect of these regimens on the release of potentially virulent and toxic membrane vesicles (MVs) is at present unclear. In this study, we determined the effect of several pharmacological agents on MVs release by and bacterial growth of common respiratory pathogens. We found that neither the release of MVs nor the bacterial growth was affected by the glucocorticoids budesonide and fluticasone. The macrolide antibiotic azithromycin only inhibited the growth of Moraxella catarrhalis but no effects were observed on bacterial MV release at a concentration that is achieved locally in the epithelial lining on administration. The macrophage pro-inflammatory response to MVs was significantly reduced after treatment with budesonide and fluticasone but not by azithromycin treatment. Our findings suggest that these glucocorticoids may have a positive effect on infection-related inflammation although the bacterial growth and MV release remained unaffected.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Beclomethasone; Budesonide; Cell Line; Cell-Derived Microparticles; Fluticasone; Glucocorticoids; Humans; Inflammation; Macrophages

Solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced activity against macrolide-resistant bacteria due to interaction with three ribosomal sites) and the first fluoroketolide, was tested against a 2014 collection of 6,115 isolates, including Streptococcus pneumoniae (1,713 isolates), Haemophilus influenzae (1,308), Moraxella catarrhalis (577), Staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by reference broth microdilution methods. The geographic samples included 2,748 isolates from the United States, 2,536 from Europe, 386 from Latin America, and 445 from the Asia-Pacific region. Solithromycin was observed to be very active against S. pneumoniae (MIC50/90, 0.008/0.12 μg/ml), demonstrating 2-fold greater activity than telithromycin (MIC50/90, 0.015/0.25 μg/ml) and 16- to >256-fold greater activity than azithromycin (MIC50/90, 0.12/>32 μg/ml), with all strains being inhibited at a solithromycin MIC of ≤1 μg/ml. Against H. influenzae, solithromycin showed potency identical to that of telithromycin (MIC50/90, 1/2 μg/ml), and both of these compounds were 2-fold less active than azithromycin (MIC50/90, 0.5/1 μg/ml). All but one of the M. catarrhalis isolates were inhibited by solithromycin at ≤0.25 μg/ml. Solithromycin inhibited 85.3% of S. aureus isolates at ≤1 μg/ml, and its activity was lower against methicillin-resistant (MIC50/90, 0.06/>32 μg/ml) than against methicillin-susceptible (MIC50/90, 0.06/0.06 μg/ml) isolates. Little variation in solithromycin activity was observed by geographic region for the species tested. Solithromycin was very active against beta-hemolytic streptococci (MIC50/90, 0.015/0.03 μg/ml), and all isolates were inhibited at MIC values of ≤0.5 μg/ml. In conclusion, solithromycin demonstrated potent activity against global and contemporary (2014) pathogens that represent the major causes of community-acquired bacterial pneumonia. These data support the continued clinical development of solithromycin for the treatment of this important indication.

Topics: Anti-Bacterial Agents; Asia; Azithromycin; Bacterial Infections; Community-Acquired Infections; Epidemiological Monitoring; Europe; Haemophilus influenzae; Humans; International Cooperation; Ketolides; Latin America; Macrolides; Microbial Sensitivity Tests; Moraxella catarrhalis; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae; Triazoles; United States

Management of common infections and optimal use of antimicrobial agents are presented, highlighting new evidence from the medical literature that enlightens practice. Primary therapy of staphylococcal skin abscesses is drainage. Patients who have a large abscess (>5 cm), cellulitis or mixed abscess-cellulitis likely would benefit from additional antibiotic therapy. When choosing an antibiotic for outpatient management, the patient, pathogen and in vitro drug susceptibility as well as tolerability, bioavailability and safety characteristics of antibiotics should be considered. Management of recurrent staphylococcal skin and soft tissue infections is vexing. Focus is best placed on reducing density of the organism on the patient's skin and in the environment, and optimizing a healthy skin barrier. With attention to adherence and optimal dosing, acute uncomplicated osteomyelitis can be managed with early transition from parenteral to oral therapy and with a 3-4 week total course of therapy. Doxycycline should be prescribed when indicated for a child of any age. Its use is not associated with dental staining. Azithromycin should be prescribed for infants when indicated, whilst being alert to an associated ≥2-fold excess risk of pyloric stenosis with use under 6 weeks of age. Beyond the neonatal period, acyclovir is more safely dosed by body surface area (not to exceed 500 mg/m(2)/dose) than by weight. In addition to the concern of antimicrobial resistance, unnecessary use of antibiotics should be avoided because of potential later metabolic effects, thought to be due to perturbation of the host's microbiome.

Topics: Abscess; Anti-Bacterial Agents; Antiviral Agents; Azithromycin; Bacterial Infections; Cellulitis; Child; Child, Preschool; Disease Management; Doxycycline; Drainage; Female; Humans; Infant; Male; Osteomyelitis; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Virus Diseases

Topics: Anti-Bacterial Agents; Arrhythmias, Cardiac; Azithromycin; Bacterial Infections; Death, Sudden, Cardiac; Heart Rate; Humans

Polyacrylamide hydrogel has in the last decade gained popularity as an injectable filler for facial augmentation due to its features of non-toxicity, biocompatibility, safety profile, and immediate effect. However, as all types of injections carry the risk of infection and since the polyacrylamide hydrogel is a non-degradable implant, the possibility of bacterial biofilm formation exists. Theoretically, the risk of infection and subsequent biofilm formation can be avoided by using prophylactic antibiotic treatment prior to the time of injection.. This retrospective study of outcomes following polyacrylamide hydrogel injections includes 657 subjects from one centre, which had facial injections from 2001 and 2011. Until 2007 prophylactic antibiotics were not given prior to treatment, but in September 2007 a single oral dose of azithromycin (Zitromax) and moxifloxacin (Avelox) was introduced as prophylactic antibiotics. A total of 496 subjects were injected before 2007 without antibiotic prophylactic treatment, and 161 subjects received these two antibiotics prior to treatment from September 2007.. The prophylactic antibiotics (azithromycin and moxifloxacin) significantly reduced the incidence of clinical signs of inflammation/infections from 7 to 2% (P=0.03).. Even though the incidence of inflammation/infections following injection of polyacrylamide hydrogel is relatively low, it may be reduced further by using prophylactic antibiotic treatment. Based on our experience, we recommend prophylactic antibiotics to patients who have facial augmentation with polyacrylamide hydrogel in order to avoid infection and risk of biofilm formation due to contamination during injection with naturally occurring micro flora from skin and lips.

Topics: Acrylic Resins; Adolescent; Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bacterial Infections; Biofilms; Cosmetic Techniques; Face; Female; Fluoroquinolones; Humans; Incidence; Inflammation; Injections; Male; Middle Aged; Moxifloxacin; Retrospective Studies; Young Adult

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

Exceptional therapeutic effects of macrolides in treating various infections and inflammatory conditions can be significantly contributed to their unique pharmacokinetic properties. Macrolides accumulate in cells and tissues, with concentrations usually 10 to more than 100 times higher of those measured in plasma. Intracellular distribution of macrolides has so far been examined using extensive subcellular fractionation techniques, radiolabeled compounds and conventional pharmacokinetic methods. In this study we evaluated four fluorescently labeled macrolides on their applicability to monitor azithromycin distribution in vitro and in vivo. 9-Deoxo-9a-{3-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]propyl}-9a-aza-9a-homoerythromycin A (9a-NBD-azithromycin) was selected as a compound with most similar cellular pharmacokinetics to azithromycin. 9a-NBD-azithromycin demonstrated antimicrobial properties comparable to azithromycin, displayed the same biological activity profile in LPS-stimulated J774A.1 murine macrophage cells and, even though it accumulated in cells almost 50% more than azithromycin, it showed same rate of retention. Identical to azithromycin, 9a-NBD-azithromycin was localized in lysosomes of J774A.1 cells. Two hours after 9a-NBD-azithromycin was administered intraperitonally to mice, a strong fluorescent signal was located in kidneys and liver and slightly weaker in the spleen. In kidneys, the signal was concentrated in tubuli, and glomeruli were negative. Patchy florescence in hepatocytes supports lysosomal cellular localization. Weaker staining of white pulp compared to red pulp of spleen is in agreement with lower accumulation of azithromycin in lymphocytes compared to other cell types present. We conclude that 9a-NBD-azithromycin can be used as a fluorescent analog of azithromycin to visualize its distribution in in vitro systems, and is also suitable for in vivo studies.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Cell Line; Cell Line, Tumor; Cell Survival; Fluorescent Dyes; Humans; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Structure-Activity Relationship; Tissue Distribution

A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N'-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N'-(β-cyanoethyl)-N'-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N'-(β-cyanoethyl)-N'-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3). Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Models, Molecular; Pneumococcal Infections; Streptococcus pneumoniae; Thiourea; Urea

We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week(-1)) with ciprofloxacin at the rate of 750 mg day(-1) for 4 weeks rather than at 500 mg day(-1) for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Chronic Disease; Ciprofloxacin; Cohort Studies; Drug Therapy, Combination; Fluoroquinolones; Humans; Macrolides; Male; Prostatitis; Retrospective Studies

Four macrolides-6-O-methyl-8a-aza-8a-homoerythromycin, clarithromycin, azithromycin and azithromycin 11,12-cyclic carbonate, have been selected for the construction of a series of new quinolone derivatives. The quinolone moiety is connected to the macrolide scaffold via a diaminoaklyl 4''-O-propionyl ester chain of varying length. At the terminus the linker is attached via one of the nitrogen atoms in the linker at C(6) or C(7) of the quinolone. Many of compounds described, particularly clarithromycin derivative 37, and azithromycin derivatives 48 and 55, exhibited excellent antibacterial activity against a wide range of clinically relevant macrolide-resistant organisms, with profiles superior to that of telithromycin, an enhanced spectrum ketolide.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; Microbial Sensitivity Tests; Propionates

Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP) is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking.. In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay.. SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens.. These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.

Topics: Anti-Bacterial Agents; Antimalarials; Azithromycin; Bacterial Infections; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Mefloquine; Microbial Sensitivity Tests; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Sulfadoxine

Almost one million people die of severe malaria every year. In recent years, artemisinin-based combination therapies have become the backbone of the treatment of uncomplicated falciparum malaria and have helped to reduce the burden of malaria in large parts of the malaria-endemic world. However, the treatment of severe malaria, the clinical syndrome responsible for most malaria-associated deaths, remains largely unaffected by this development. Invasive bacterial infections and misdiagnosis of bacterial infections as severe malaria are well recognized phenomena, but recent data indicate that their prevalence and clinical importance might be far greater than previously anticipated. Therefore, there could be good reasons to routinely combine antimalarials, such as artemisinins or quinine, with broad spectrum antibiotics with antimalarial activity in standardized combination therapies for the parenteral treatment of severe falciparum malaria.

Topics: Anti-Bacterial Agents; Antimalarials; Azithromycin; Bacterial Infections; Child, Preschool; Clindamycin; Doxycycline; Drug Combinations; Humans; Infant; Malaria, Falciparum; Tropical Climate

The need to limit unnecessary antibiotic treatments and recent studies with unusual antibiotics in pediatrics (fluoroquinolones) or in digestive tract infections (azithromycin) have led to update the treatment of acute gastro-enteritis. In 2007, the European Society for Pediatric Infectious Diseases and the European Society for Gastroenterology Hepatology and Nutrition have issued guidelines. The proven shigellosis as well as the strong suspicion have to be treated promptly with antibiotics, mainly azithromycin. There is no argument to treat moderate salmonella gastroenteritis or carriage. However, the severe cases and those occurring in high risk patient must be treated (ciprofloxacin or ceftriaxone). It is recommended to treat diarrhoea due to Campylobacter jejuni in case of early diagnosis. The presumptive antibiotic treatment should be limited but can not be dismissed, in invasive cases gastro-enteritis, especially in traveller children.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Campylobacter Infections; Campylobacter jejuni; Ceftriaxone; Child; Ciprofloxacin; Diarrhea; Dysentery, Bacillary; Escherichia coli Infections; Gastroenteritis; Humans; Salmonella 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: Adenoviridae Infections; Administration, Topical; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clinical Trials, Phase I as Topic; Conjunctivitis; Corneal Ulcer; Dexamethasone; Diagnostic Techniques, Ophthalmological; Drug Combinations; Drug Delivery Systems; Eye Diseases; Glucocorticoids; Humans; Phenytoin; Sclera; United States; United States Food and Drug Administration

Acute pancreatitis is an important cause of morbidity and mortality, mainly due to sepsis. The aim of this study was to determine the incidence of infectious complications and their impact on mortality in patients hospitalized for acute pancreatitis.. Patients admitted for acute pancreatitis were retrospectively included within a period between 1995 and 2000. Incidence of abdominal and extra-abdominal sepsis and specific care were specifically analyzed. Risk factors for death were evaluated by uni- and multivariated analysis.. Two hundreds and twelve consecutive patients (128 males, median age 54 years) were included. Mortality was 10.8%. At least one infectious episode was collected in 25% of the patients with an abdominal sepsis (26.8%), bacteriemia (24.4%), respiratory (24.4%) and urinary tracts (19.5%) infections. Infection was polymicrobial in 37.5%. An antibiotic prophylaxis was administered in 10.8%, more often in patients with severe pancreatitis. It did not alter mortality or incidence of infections but significantly delayed occurrence of sepsis. Mortality of patients treated with more than one line of antibiotics was higher. However in this study infectious complications were not an independent factor for mortality.. Infections are frequent and polymicrobial but are not an independent prognostic factor during acute pancreatitis.

Topics: Acute Disease; Adult; Age Factors; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; APACHE; Azithromycin; Bacterial Infections; Ceftriaxone; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Humans; Incidence; Male; Middle Aged; Pancreatitis; Prognosis; Retrospective Studies; Risk Factors; Sepsis; Time Factors

We performed a comparative analysis of microbiological and clinical responses to combination therapy in 104 symptomatic patients showing evidence of infection by traditional uropathogens (TU) or by unusual pathogens (UP) at the prostatic level. Eighty-two pathogens out of a total of 104 isolated microorganisms were eradicated at the end of a 6-week course of combination therapy with ciprofloxacin, azithromycin, alfuzosin and a S. repens extract. The TU and UP groups showed eradication rates of 75.5% and 82.3%, and clinical success rates of 78.8% and 85.7%, respectively. Thus, a similar response to therapy was observed in patients infected by TU or by UP. Intergroup differences were not significantly different, with the exception of higher scores relative to the impact of the disease on quality of life in TU-patients. Long-term improvement of signs and symptoms of prostatitis indicates that combination therapy is beneficial for symptomatic patients showing evidence of infection by unusual pathogens at the prostatic level. Our data support the hypothesis that organisms other than the traditionally recognized uropathogens may play a role in the onset of prostatitis.

Topics: Adrenergic alpha-Antagonists; Adult; Androgen Antagonists; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Ciprofloxacin; Drug Therapy, Combination; Humans; Male; Middle Aged; Plant Extracts; Prostatitis; Quinazolines; Serenoa; Treatment Outcome

Despite widespread azithromycin use, no audit has targeted this drug to date. Azithromycin was audited in primary military clinics between July 1, 2003 and December 31, 2003 (period 1). Consumption (defined daily doses/1000 visits) and economic expenditure of penicillin V, amoxicillin, erythromycin, and azithromycin were evaluated. An educational intervention was performed (dissemination of local guideline regarding indications for azithromycin use) and its impact was assessed between July 1, 2004 and December 31, 2004 (period 2). During periods 1 and 2, 105 and 31 patients were prescribed azithromycin. Azithromycin was appropriately chosen in 5.7% vs. 70.9% of cases (p < 0.0001), but unnecessary in 90.5% vs. 16.2 (p < 0.0001). Azithromycin prescription during period 1 resulted in extrapolated excess expenditure of 420,000 New Israeli shekels/year (1 U.S. dollar = 4.5 New Israeli shekels). There was an attributable decrease of 82.1% in azithromycin consumption (adjusted attributable cost reduction 38.1%), but an increase in amoxicillin consumption (20.2%). Intervention decreased azithromycin consumption and expenditure but its effect was offset by increased consumption of other agents, mainly amoxicillin. Interventions in primary care settings should target prescribing behavior through a multifaceted approach to increase efficacy while preventing a trade-off effect.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Benchmarking; Cross-Sectional Studies; Drug Prescriptions; Educational Measurement; Female; Hospitals, Military; Humans; Israel; Male; Medical Audit; Military Medicine; Military Personnel

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

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Biological Availability; Humans; Microbial Sensitivity Tests

Topics: Acute Disease; Azithromycin; Bacterial Infections; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Maxillary Sinusitis; Microspheres; Ofloxacin; Randomized Controlled Trials as Topic; Rhinitis; Risk Assessment; Severity of Illness Index; Treatment Outcome

Traditional approaches to antimicrobial management of acute bacterial rhinosinusitis (ABRS) focus on courses of therapy of at least 10 days duration. The rationale for this length of therapy originated from studies in tonsillopharyngitis. Short-course antibiotic therapy for ABRS with 3-5 days of azithromycin has proved equally effective. Potential added benefits of short-course therapy include improved compliance, fewer adverse events as well as reduced risk of treatment failure, bacterial resistance and cost. Single-dose therapy is now possible with a novel microsphere formulation of azithromycin, which permits administration of a higher 2.0 g oral dose. This has proved as effective and well tolerated as 10 days levofioxacin 500 mg/day in patients with uncomplicated ABRS. High single-dose therapy has the potential to maximize adherence to prescribed therapy and thus to help in the battle to control rising antibiotic resistance among respiratory pathogens.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Microspheres; Middle Aged; Ofloxacin; Rhinitis; Sinusitis; Time Factors; Treatment Outcome

The antibacterial susceptibility of Chlamydia trachomatis in 138 patients with chronic prostatitis (CP) and clinical failures after antibacterial treatment with azithromycin (AZI) were investigated. Azithromycin was not found to be top-of-the-line drug in the follow-up treatment, showing only average results in vitro. The investigation of the susceptibility of chlamydia to antibiotics in causes of chronic prostatitis is highly recommended.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Humans; Male; Microbial Sensitivity Tests; Prostatitis

Acute otitis media (AOM) is one of the most common diseases of childhood. Knowledge, of which bacteria are the most common pathogens in AOM and their susceptibilities towards antibiotics, is essential for the reasonable empiric treatment. With rapidly increasing frequencies of antibiotic resistance surveillance of the common etiologic pathogens has become pertinent. The purpose of this paper is to present the bacteriological findings and antibiotic susceptibilities, in cultures from nasopharyngeal swabs, in Danish children with AOM.. Children aged up to 10 years who had AOM diagnosed in general practice in Denmark were swabbed in nasopharynx, cultures were incubated and susceptibility testing was performed as tablet diffusion and minimal inhibitory concentrations (MICs) were determined by E-test.. We included 331 patients, in 257 bacteria were found, which could be classified as commonly ear pathogenic. The most frequent bacteria found was Streptococcus pneumoniae followed by Haemophilus influenzae and Moraxella catarrhalis. Ninety-six percent of the tested S. pneumoniae were susceptible towards penicillin and 99% towards erythromycin. Eighty-nine percent of the H. influenzae were susceptible to ampicillin and all tested M. catarrhalis were susceptible towards erythromycin. In more than 30% of H. influenzae MIC of phenoxymethylpenicillin were above the level that could be achieved in middle ear fluid.. Antimicrobial resistance is still infrequent in pathogens that might cause AOM in children in Denmark; this is probably due to minimal use of antibiotics as well as the use of phenoxymethylpenicillin as primary drug for treatment of AOM. Phenoxymethylpenicillin and azithromycin are not efficient for treating the majority of infections due to H. influenzae.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Denmark; Drug Utilization; Female; Humans; Infant; Male; Nasopharynx; Otitis Media, Suppurative; Penicillin V

The present study was conducted to determine the in vitro activity of amoxicillin-clavulanic acid compared to that of four newer antimicrobial agents (ampicillin, azithromycin, cefuroxime and trimethoprim-sulfamethoxazole). All of the agents were tested against 21232 recent clinical isolates encompassing 37 species submitted from 16 European countries between 1997 and 1999. After 20 years of clinical use, amoxicillin-clavulanic acid continues to retain much of its initial activity against targeted gram-positive organisms, selected gram-negative organisms and major respiratory pathogens.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Cefuroxime; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

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 effect of 2,3 modifications on the antibacterial activity of ketolides was evaluated by introducing substituents in position 2 and converting the C-1, C-2, C-3 beta-keto-ester into stable 2,3 enol-ether or 2,3 anhydro derivatives. Introduction of a fluorine in C-2 is beneficial with regard to the overall antibacterial spectrum whereas the enol-ether and 2,3 unsaturated compounds, as well as the bulky gem dimethyl or 2-chloro derivatives, are less active particularly against erythromycin resistant strains. A 2-fluoro ketolide derivative demonstrates good antibacterial activity and in vivo efficacy against multi-resistant Streptococcus pneumoniae. Compared to azithromycin against Haemophilus influenzae, this compound is equivalent in vitro and slightly more active in vivo. These results demonstrate that within the ketolide class, to retain good antibacterial activity, position 2 needs to remain tetrahedral and tolerates only very small substituents such as fluorine.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Macrolides; Mice; Structure-Activity Relationship

To evaluate the palatability of antimicrobial agents effective against beta-lactamase-producing bacteria in American children.. In a taste test of 4 antimicrobial agents, azithromycin (cherry flavored), cefprozil (bubble gum flavored), cefixime (strawberry flavored), and amoxicillin-clavulanic acid (banana flavored) were compared.. An urban inner-city primary care clinic.. A volunteer sample of 30 healthy children (aged 5-8 years).. Palatability was determined using a single-blind taste test of 4 flavored antimicrobial agents. The 4 antimicrobial agents used were azithromycin, cefprozil, cefixime, and amoxicillin-clavulanic acid.. After each antimicrobial test dose, subjects rated the taste on a 10-cm visual analog scale incorporating a facial hedonic scale. Preference assessments for the best-tasting and worst-tasting agent were also conducted.. Of the 20 children who expressed a preference, significantly more children (9 [45%], P<.05) selected the cefixime preparation as the best-tasting formulation compared with the other preparations. The cefixime preparation was also significantly the least likely to be selected as the worst-tasting preparation (2 [10%], P<.05). There were no significant differences between the other 3 preparations with respect to being selected as either the best or worst tasting. The mean (+/- SD) visual analog scale score for cefixime was highest (8.53 [2.49]) compared with the scores for azithromycin (6.78 [3.45]), cefprozil (6.26 [4.04]), and amoxicillin-clavulanic acid (6.24 [4.01]).. The cefixime preparation was most commonly rated as best tasting by children.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Cefixime; Cefprozil; Cephalosporins; Child; Child, Preschool; Female; Flavoring Agents; Humans; Male; Pain Measurement; Patient Acceptance of Health Care; Taste; Urban Population

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

The comparative activity of telithromycin (HMR 3647) against 419 human anaerobic isolates was determined by the agar dilution method. At concentrations of

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria, Anaerobic; Bacterial Infections; Clarithromycin; Humans; Ketolides; Macrolides; Microbial Sensitivity Tests; Roxithromycin

The activity of erythromycin, azithromycin and clarithromycin against 112 anaerobes was tested by the Oxyrase agar dilution MIC method at pH 7.2 without supplemental CO2 and by an agar dilution MIC method in CO2 with media adjusted to pH 8.0. MICs (mg/L) of erythromycin, azithromycin and clarithomycin against Bacteroides fragilis ATCC 25285 and Bacteroides thetaiotaomicron ATCC 29741 were similar by the two methods. MICs for 94 clinical isolates tested by the two methods were within two dilutions of each other. Eighteen additional isolates required CO2, and did not grow in Oxyrase. With the exception of fusobacteria, with which azithromycin yielded the lowest MICs, clarithromycin had the lowest MICs with both methods. These results show that the pH effect of incubation in CO2 can be avoided by using the Oxyrase method, or by incubating in CO2 with pH adjusted to 8.0. The latter method has the advantage of allowing testing of strains requiring CO2.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria, Anaerobic; Bacterial Infections; Carbon Dioxide; Clarithromycin; Colony Count, Microbial; Culture Media; Drug Resistance, Microbial; Drug Resistance, Multiple; Erythromycin; Gram-Negative Bacteria; Humans; Hydrogen-Ion Concentration; Microbial Sensitivity Tests; Oxygenases

The activity of trovafloxacin and five other oral agents against 250 aerobic and 137 anaerobic strains isolated from human and animal bite wounds was determined by an agar dilution method. Trovafloxacin was active against all aerobic and fastidious facultative isolates at < or = 0.5 mg/L and all anaerobes at < or = 2 mg/L (Bacteroides tectum, Porphyromonas salivosa and Prevotella heparinolytica, < or = 0.25 mg/L; Porphyromonas spp., < or = 0.5 mg/L; Prevotella spp. and peptostreptococci, < or = 2.0 mg/L), except Fusobacterium nucleatum and other fusobacteria (MIC90 < or = 4 mg/L). Levofloxacin was generally one to two dilutions more active than ofloxacin, while ciprofloxacin was active against aerobes (MIC < or = 1 mg/L) but less active against anaerobic strains (MIC90 < or = 16 mg/L).

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Bites and Stings; Bites, Human; Ciprofloxacin; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Resistance, Multiple; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Species Specificity; Wound Infection

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Humans; Virus Diseases

Azithromycin reaches high concentrations in phagocytic and other host cells, suggesting that they may transport this agent to specific sites of infection. Models of localized infection (Haemophilus influenzae middle ear infection in gerbils, Streptococcus pyogenes implanted contaminated paper disc and Streptococcus pneumoniae pneumonia in mice) that induced severe inflammatory response after challenge were used to explore this hypothesis. Animals were given a single 100 or 50 mg/kg po dose of azithromycin at various times from 2 to 120 h following introduction of a pathogen or sterile medium. When azithromycin was given during a period of little or no inflammation, there was marginal difference between concentrations found in infected or non-infected sites (bulla, disc, lung). However, when the compound was given during a period of inflammation, considerably higher drug concentrations were found in infected sites than in non-infected sites at 5-24 h after dosing (0.38-0.44 mg/c compared with 0.07-0.14 mg/L of bulla wash; 1.01-1.75 micrograms compared with < or = 0.01-0.03 microgram at the disc site; 1.72-5.28 mg/kg compared with 0.7-1.53 mg/kg of lung). When the observation periods were extended to include 48, 56 or 96 h after dosing, the ratio of azithromycin infection site concentration: serum concentration steadily increased with time in all model systems (middle ear, implanted disc and pneumonia), reflecting the maintenance of concentrations at the sites of infection, while serum concentrations declined. Bioassay of cell pellets and supernatants, obtained from pooled bulla washes of gerbils treated with azithromycin during a period of inflammation, revealed that cellular components accounted for about 75% of the azithromycin detected. These data show that increased azithromycin concentrations occur at sites of localized infection. This correlates with the presence of inflammation and is associated with the cellular components of the inflammatory response. Therefore, phagocytes may be important vehicles for delivering azithromycin to and sustaining azithromycin concentrations at sites of infection.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Blister; Female; Gerbillinae; Haemophilus Infections; Haemophilus influenzae; Lung; Male; Mice; Otitis Media; Phagocytes; Pneumococcal Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

Azithromycin (AZM), a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 days to pediatric patients with bacterial infections and the therapeutic efficacy of AZM was investigated. 1. A total of 12 patients with the following diseases was evaluated: pharyngitis in two, tonsillitis in four, bronchitis in one, Mycoplasma pneumonia in one, scarlet fever in two and enteritis in two. The drug was rated "excellent" in eight cases and "good" in four. 2. Eleven strains were isolated from patients: five strains of Streptococcus pyogenes, four strains of Haemophilus influenzae, and two strains of Haemophilus parainfluenzae. Isolated bacteria were eradicated in eight strains and persisting in one, resulting in 88.9% in eradication rate. No follow-up examinations in post-treatment were performed in two cases. 3. No adverse reaction was reported, while one case of eosinophilia was noted as an abnormal laboratory test value. 4. As far as compliance is concerned, patients claimed that the formulation of the drug is "easy to take" or "ordinary". With the results presented as above, we have concluded that AZM is a useful antibiotic in pediatric patients with bacterial infections.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Capsules; Child; Child, Preschool; Drug Resistance, Microbial; Female; Haemophilus influenzae; Humans; Infant; Male; Pharyngitis; Pneumonia, Mycoplasma; Streptococcus pyogenes; Tonsillitis

Azithromycin (AZM) was orally administered to 12 pediatric patients with the following bacterial infections: pharyngitis in four cases, tonsillitis in one, pharyngo-bronchitis in two, and mycoplasmal pneumonia in five. In eleven of the twelve cases (91.7%) was the drug found effective. Neither abnormal clinical findings nor abnormal laboratory test results changes were observed. Eleven of the twelve pediatric patients claimed that the formulation of the drug is easy to take. The above results suggest that AZM is a useful antibiotic drug in the treatment of pediatric patients with bacterial infections.

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

Fine granules or capsules of azithromycin (AZM) were given to 32 pediatric patients for the treatment of the following diseases: pharyngitis in three cases; tonsillitis in one; bronchitis in six; pneumonia in six; mycoplasmal pneumonia in 14; pertussis and enteritis in one, each. Effectiveness of AZM was evaluated in 30 cases and the drug was rated "excellent" in 18 patients, "good" in 11 and "fair" in one, resulting in a total efficacy rate of 96.7%. Three strains of bacteria were isolated from 3 patients as the causative organisms including: Streptococcus pneumoniae, Haemophilus influenzae and Haemophilus parainfluenzae, from three different patients, respectively. One patient complained of mild diarrhea, another patient mild urticaria. Abnormal laboratory test results were reported as follows: one patient showed a slight decrease in leukocyte count, three patients showed slight increases in eosinophils, and one patient had slight elevations in GOT and GPT. The above results suggest that AZM is a useful antibiotic drug in the treatment of pediatric patients with various bacterial infections.

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

The Third International Conference on the Macrolides, Azalides, and Streptogramins was held in Lisbon, Portugal. Conferees were given news on the latest advances in the development of innovative antibiotics belonging to these increasingly important groups of drugs, and learned of their expanding clinical indications. The following areas were emphasized at the conference: multiresistant gram-positive bacteremias in patients with serious underlying infections, azithromycin's effectiveness against acute community-acquired pneumonia, results of clarithromycin plus ethambutol in HIV-infected patients with MAC bacteremia, duodenal ulcers associated with Helicobacter pylori infections, and use of roxithromycin against AIDS-related cryptosporidium diarrhea.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacteremia; Bacterial Infections; Clarithromycin; Clofazimine; Cryptosporidiosis; Drug Therapy, Combination; Duodenal Ulcer; Ethambutol; Humans; Microbial Sensitivity Tests; Mycobacterium avium-intracellulare Infection; Pneumonia; Smoking; Virginiamycin

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Humans

L-701,677, L-708,299 and L-708,365 are novel azalide derivatives of erythromycin that exhibit improved acid stability over erythromycin, azithromycin and clarithromycin. The half-life in aqueous solution at pH = 2.1 of these compounds ranged from 0.3 hour for erythromycin to 16.2 hours for L-708,299. The rank order of half-life in acid solution from most to least stable was L-708,299 > L-701,677 > L-708,365 > azithromycin = clarithromycin > erythromycin. In a disseminated Streptococcus pyogenes mouse infection model, azithromycin and L-708,365 were slightly more efficacious than clarithromycin, L-701,677 and L-708,299; all 5 compounds being more active than erythromycin. In a Klebsiella pneumoniae pulmonary challenge mouse model, azithromycin, L-701,677, L-708,299 and L-708,365 were all equal in efficacy and at least four-fold more active than clarithromycin and erythromycin. Clarithromycin, L-708,365 and interestingly erythromycin, showed greater bacterial clearance than azithromycin, L-701,677 and L-708,299 in a localized infection model that measured clearance of Staphylococcus aureus from mouse thigh tissues. Our results indicate that L-701,677, L-708,299 and L-708,365 exhibit improved acid stability and were at least equally efficacious as presently marketed macrolide/azalide antibiotics.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Drug Evaluation, Preclinical; Drug Stability; Erythromycin; Female; Half-Life; Klebsiella Infections; Macrolides; Mice; Mice, Inbred DBA; Molecular Structure; Staphylococcal Infections; Streptococcal Infections

The susceptibility of 201 anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin was tested by agar dilution and E test methods by using a commercially available plate and dish system (OxyDish) to provide anaerobic conditions. Plates were incubated for 48 h. MICs for 50% of strains tested and MICs for 90% of strains tested by agar dilution and E test methods corresponded within 1 doubling dilution for all compounds. When all antibiotics were considered together, agar and E test MICs were within 1 and 2 doubling dilutions of each other in 84 to 91% and > 99% of cases, respectively.

Topics: Agar; Azithromycin; Bacteria, Anaerobic; Bacterial Infections; Clarithromycin; Drug Resistance, Microbial; Erythromycin; Evaluation Studies as Topic; Humans; Microbial Sensitivity Tests; Oxygenases; Roxithromycin

Topics: Azithromycin; Bacterial Infections; Child; Drug Administration Schedule; Humans

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Cefixime; Cefotaxime; Cefuroxime; Clarithromycin; Fluoroquinolones; Humans; Pneumonia

Topics: Azithromycin; Bacterial Infections; Clarithromycin; Drug Costs; Erythromycin; Humans

Topics: Animals; Azithromycin; Bacterial Infections; Clarithromycin; Erythromycin; Humans

Topics: Azithromycin; Bacterial Infections; Clarithromycin; Erythromycin; Humans; United States; United States Food and Drug Administration

Topics: Azithromycin; Bacterial Infections; Clarithromycin; Clinical Trials as Topic; Erythromycin; Humans; Microbial Sensitivity Tests

Azithromycin (CAS 83905-01-5) disks with the selected loading (10, 15, 20 micrograms) were used for determination of the most suitable azithromycin disk concentration. Estimation was carried out by means of the regression line related to the zone size inhibition. Testing was performed on a variety of freshly isolated gram-positive, gram-negative and anaerobic bacteria derived from various specimens collected from patients. Using the disk diffusion method with 10 micrograms of azithromycin per disk in total 431 gram-positive, 875 gram-negative bacterial strains and 59 anaerobic bacteria were analysed. It was concluded that azithromycin disk containing 10 micrograms is sufficient for determination of bacterial sensitivity.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Bacteria, Anaerobic; Bacterial Infections; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Drug Resistance, Microbial; Erythromycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans

Topics: Azithromycin; Bacterial Infections; Erythromycin; Humans

Topics: Acetylcysteine; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Congresses as Topic; Daptomycin; Disaccharides; Drug Evaluation; Erythromycin; Glycopeptides; Humans; New York City; Peptides; Rifamycins

Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.

Topics: Azithromycin; Bacterial Infections; Bronchi; Bronchoalveolar Lavage Fluid; Cell Count; Epithelium; Erythromycin; Female; Humans; Lung Diseases; Macrophages; Male; Sputum

Infection models were used to clarify the roles of serum and extravascular concentrations in the in-vivo efficacy observed with azithromycin. In-vivo experiments were designed to give serum concentrations well below the MIC and tissue levels generally above the MIC at time of challenge and during the course of infection. The efficacy of azithromycin against a Salmonella enteritidis oral challenge (a tissue-associated infection model) in mice correlated directly with azithromycin liver levels, but not serum concentrations. The significance of extravascular pharmacokinetics was observed in a comparative study of azithromycin and ciprofloxacin against the salmonella challenge. Ciprofloxacin has a greater than 100-fold in-vitro potency advantage over azithromycin against this organism, but azithromycin (5 mg/kg) produced a greater reduction in cfu than ciprofloxacin (100 mg/kg) at the primary site of infection (liver). In another model, extravascular fluid levels, measured by bioassay of implanted paper discs, were compared with plasma levels in relation to control of a localized Staphylococcus aureus infection in rats. Extravascular fluid levels of azithromycin were greater than the MIC of the strain used for five days after a 100 mg/kg dose, while erythromycin levels were less than 20% of the MIC at 30 h after a 200 mg/kg dose. Serum concentrations of both compounds were less than 20% of the MIC at the time of challenge. The antibiotic levels at the site of infection correlated with the reduction of Staph. aureus cfu (99% with azithromycin compared with controls, P less than 0.01; 0% with erythromycin) recovered from inoculated discs. The significance of extravascular concentrations of azithromycin was further supported in other models of localized infections induced with Escherichia coli or a mixture of Staph. aureus and Bacteroides fragilis.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bacteroides fragilis; Ciprofloxacin; Disease Models, Animal; Erythromycin; Escherichia coli; Female; Liver; Male; Mice; Rats; Salmonella enteritidis; Staphylococcus aureus

Azithromycin (CP-62,993), a new acid-stable 15-membered-ring macrolide, was well absorbed following oral administration in mice, rats, dogs, and cynomolgus monkeys. This compound exhibited a uniformly long elimination half-life and was distributed exceptionally well into all tissues. This extravascular penetration of azithromycin was demonstrated by tissue/plasma area-under-the-curve ratios ranging from 13.6 to 137 compared with ratios for erythromycin of 3.1 to 11.6. The significance of these pharmacokinetic advantages of azithromycin over erythromycin was shown through efficacy in a series of animal infection models. Azithromycin was orally effective in treating middle ear infections induced in gerbils by transbulla challenges with amoxicillin-resistant Haemophilus influenzae or susceptible Streptococcus pneumoniae; erythromycin failed and cefaclor was only marginally active against the H. influenzae challenge. Azithromycin was equivalent to cefaclor and erythromycin against Streptococcus pneumoniae. In mouse models, the new macrolide was 10-fold more potent than erythromycin and four other antibiotics against an anaerobic infection produced by Fusobacterium necrophorum. Similarly, azithromycin was effective against established tissue infections induced by Salmonella enteritidis (liver and spleen) and Staphylococcus aureus (thigh muscle); erythromycin failed against both infections. The oral and subcutaneous activities of azithromycin, erythromycin, and cefaclor were similar against acute systemic infections produced by Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, or S. aureus, whereas azithromycin was more potent than erythromycin and cefaclor against the intracellular pathogen Listeria monocytogenes. The pharmacokinetic advantage of azithromycin over erythromycin in half-life was clearly demonstrated in prophylactic treatment of an acute mouse model of S. aureus infection. These properties of azithromycin strongly support the further evaluation of this new macrolide for use in community-acquired infections of skin or soft tissue and respiratory diseases.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Disease Models, Animal; Erythromycin; Female; Gerbillinae; Half-Life; Haplorhini; Male; Rats; Species Specificity; Tissue Distribution