zithromax and Streptococcal-Infections

Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020.. To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis.. We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020.. Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events.. Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.. We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence).  Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 tri

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Ampicillin; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Child; Child, Preschool; Clindamycin; Humans; Infant; Macrolides; Middle Aged; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Streptococcal Infections; Streptococcus pyogenes; Sulfonamides; Young Adult

Psoriasis is a chronic skin disease that affects approximately two per cent of the general population. Plaque psoriasis is the most common form: it usually appears as raised, red patches of inflamed skin, covered with silvery white scales. The patches often occur in a symmetrical pattern. Guttate psoriasis is a particular form of psoriasis with widespread, small erythematosquamous lesions. Streptococcal infection is suspected to be a triggering factor for the onset of guttate psoriasis, and flare-up of chronic plaque psoriasis. The previous Cochrane Review on this topic was published in 2000; it required an update because antistreptococcal treatment continues to be used to treat psoriasis, especially for the acute form of guttate psoriasis.. To assess the effects of antistreptococcal interventions for guttate and chronic plaque psoriasis.. We searched Cochrane Skin Specialised Register, Cochrane Register of Studies Online, CENTRAL, MEDLINE, Embase, LILACS, and five trials registers (January 2019). We checked the reference lists of included and excluded studies and searched conference proceedings from the American Academy of Dermatology, Society for Investigative Dermatology, and European Academy of Dermatology and Venereology.. We considered randomised controlled trials (RCTs) assessing antistreptococcal interventions (tonsillectomy or systemic antibiotic treatment) in people with clinically diagnosed acute guttate and chronic plaque psoriasis compared with placebo, no intervention, or each other.. We used standard methodological procedures expected by Cochrane. Primary outcome measures were: 1) time-to-resolution; achieving clear or almost clear skin (Physician Global Assessment (PGA) 0 or 1 or Psoriasis Area and Severity Index (PASI) 90 or 100); 2) proportion of participants with adverse effects and severe adverse effects. Secondary outcomes were: 1) proportion of participants achieving clear or almost clear skin; 2) proportion of participants achieving PASI 75 or PGA 1 to 2; 3) risk of having at least one relapse at long-term follow-up. Short-term assessment was defined as within eight weeks of the start of treatment; long-term was at least one year after the start of treatment.. We included five trials (162 randomised participants); three were conducted in a hospital dermatology department. One study declared funding by a pharmaceutical company. Participants' ages ranged from 12 to 77 years; only two participants were younger than 15 years. Mean PASI score at baseline varied from 5.7 (i.e. mild) to 23 (i.e. severe) in four studies. Twenty-three of 162 participants had streptococcus-positive throat swab culture. We did not perform a meta-analysis due to heterogeneity of participants' characteristics and interventions.None of the trials measured our efficacy primary outcome, time-to-resolution, or the secondary outcome, risk of having at least one relapse at long-term follow-up.We rated the quality of the results as very low-quality evidence, due to high risk of bias (absence of blinding of participants and caregivers, and high risk of outcome reporting bias) and imprecision (single study data with a low number of events). Hence, we are very uncertain about the results presented.Guttate psoriasisOne three-armed trial (N = 43) assessed penicillin (50,000 international units (IU)/kg/day in three doses) versus erythromycin (250 mg four times per day) versus no treatment (treatment for 14 days, with six-week follow-up from start of treatment). Adverse events and the proportion of participants achieving clear or almost clear skin were not measured.One trial (N = 20) assessed penicillin (1.6 MU (million units) intramuscularly once a day) versus no treatment (six weeks of treatment, with eight-week follow-up from start of treatment). At six-week (short-term) follow-up, no adverse events were observed in either group, and there was no statistically significant difference between the two groups in the proportion of participants with clear or almost clear skin (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.68 to 5.85).One trial (N = 20) assessed rifampicin (300 mg twice daily) versus placebo (14-day treatment duration; six-week follow-up from start of treatment); none of the review outcomes were measured.These trials did not measure the proportion of participants achieving PASI 75 or PGA 1 to 2.Chronic plaque psoriasisOne trial (N = 50) assessed long-term azithromycin treatment (500 mg daily dose) versus vitamin C. Adverse events were reported in the azithromycin group (10 out of 30 had nausea and mild abdominal upset), but not in the vitamin C group. The proportion of participants who achieved clear or almost clear skin was not measu. We found only five trials (N = 162), which assessed the effects of five comparisons (systemic antibiotic treatment (penicillin, azithromycin) or tonsillectomy). Two comparisons (erythromycin compared to no treatment, and rifampicin compared to placebo) did not measure any of the outcomes of interest. There was very low-quality evidence for the outcomes that were measured, Therefore, we are uncertain of both the efficacy and safety of antistreptococcal interventions for guttate and chronic plaque psoriasis.The included trials were at unclear or high risk of bias and involved only a small number of unrepresentative participants, with limited measurement of our outcomes of interest. The studies did not allow investigation into the influence of Streptococcal infection, and a key intervention (amoxicillin) was not assessed.Further trials assessing the efficacy and tolerance of penicillin V or amoxicillin are needed in children and young adults with guttate psoriasis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Ascorbic Acid; Azithromycin; Child; Erythromycin; Humans; Middle Aged; Penicillin V; Psoriasis; Randomized Controlled Trials as Topic; Rifampin; Streptococcal Infections; Tonsillectomy; Vitamins

The standard duration of treatment for children with acute group A beta hemolytic streptococcus (GABHS) pharyngitis with oral penicillin is 10 days. Shorter duration antibiotics may have comparable efficacy.. To summarize the evidence regarding the efficacy of two to six days of newer oral antibiotics (short duration) compared to 10 days of oral penicillin (standard duration) in treating children with acute GABHS pharyngitis.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 3) which contains the Cochrane Acute Respiratory Infections Group's Specialized Register, MEDLINE (January 1966 to March week 3, 2012) and EMBASE (January 1990 to April 2012).. Randomized controlled trials (RCTs) comparing short duration oral antibiotics to standard duration oral penicillin in children aged 1 to 18 years with acute GABHS pharyngitis.. Two review authors scanned the titles and abstracts of retrieved citations and applied the inclusion criteria. We retrieved included studies in full, and extracted data. Two review authors independently assessed trial quality.. We included 20 studies with 13,102 cases of acute GABHS pharyngitis. The updated search did not identify any new eligible studies; the majority of studies were at high risk of bias. However, the majority of the results were consistent. Compared to standard duration treatment, the short duration treatment studies had shorter periods of fever (mean difference (MD) -0.30 days, 95% confidence interval (CI) -0.45 to -0.14) and throat soreness (MD -0.50 days, 95% CI -0.78 to -0.22); lower risk of early clinical treatment failure (odds ratio (OR) 0.80, 95% CI 0.67 to 0.94); no significant difference in early bacteriological treatment failure (OR 1.08, 95% CI 0.97 to 1.20) or late clinical recurrence (OR 0.95, 95% CI 0.83 to 1.08). However, the overall risk of late bacteriological recurrence was worse in the short duration treatment studies (OR 1.31, 95% CI 1.16 to 1.48), although no significant differences were found when studies of low dose azithromycin (10 mg/kg) were eliminated (OR 1.06, 95% CI 0.92 to 1.22). Three studies reported long duration complications. Out of 8135 cases of acute GABHS pharyngitis, only six cases in the short duration treatment versus eight in the standard duration treatment developed long-term complications in the form of glomerulonephritis and acute rheumatic fever, with no statistically significant difference (OR 0.53, 95% CI 0.17 to 1.64).. Three to six days of oral antibiotics had comparable efficacy compared to the standard duration 10-day course of oral penicillin in treating children with acute GABHS pharyngitis. . In areas where the prevalence of rheumatic heart disease is still high, our results must be interpreted with caution.

Topics: Acute Disease; Administration, Oral; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Administration Schedule; Humans; Infant; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Recurrence; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

The standard duration of treatment for acute group A beta hemolytic streptococcus (GABHS) pharyngitis with oral penicillin is 10 days. Shorter duration antibiotics may have comparable efficacy.. To summarize the evidence regarding the efficacy of two to six days of newer oral antibiotics (short duration) compared to 10 days of oral penicillin (standard duration) in treating children with acute GABHS pharyngitis.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 4), which contains the Acute Respiratory Infections Group's Specialized Register; the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (1966 to October 2007); OLDMEDLINE (1950 to December 1965); and EMBASE (January 1990 to November 2007).. Randomized controlled trials (RCTs) comparing short duration oral antibiotics to standard duration oral penicillin in children aged 1 to 18 years with acute GABHS pharyngitis.. Two review authors scanned the titles and abstracts of retrieved citations and applied the inclusion criteria. We retrieved included studies in full and extracted data. Two review authors independently assessed trial quality.. Twenty studies were included with 13,102 cases of acute GABHS pharyngitis. Compared to standard duration treatment, the short duration treatment had shorter periods of fever (mean difference (MD) -0.30 days, 95% CI -0.45 to -0.14) and throat soreness (MD -0.50 days, 95% CI -0.78 to -0.22); lower risk of early clinical treatment failure (OR 0.80, 95% CI 0.67 to 0.94); no significant difference in early bacteriological treatment failure (OR 1.08, 95% CI 0.97 to 1.20), or late clinical recurrence (OR 0.95, 95% CI 0.83 to 1.08). However, the overall risk of late bacteriological recurrence was worse in the short duration treatment (OR 1.31, 95% CI 1.16 to 1.48), although no significant differences were found when studies of low dose azithromycin (10mg/kg) were eliminated (OR 1.06, 95% CI 0.92 to 1.22). Three studies reported long duration complications with no statistically significant difference (OR 0.53, 95% CI 0.17 to 1.64).. Three to six days of oral antibiotics had comparable efficacy compared to the standard duration 10 day oral penicillin in treating children with acute GABHS pharyngitis. In countries with low rates of rheumatic fever, it appears safe and efficacious to treat children with acute GABHS pharyngitis with short duration antibiotics. In areas where the prevalence of rheumatic heart disease is still high, our results must be interpreted with caution.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child; Drug Administration Schedule; Humans; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

Acute rheumatic fever and rheumatic chronic valvular heart disease is an important preventable cause of morbidity and mortality in suburban and rural India. Its diagnosis is based on clinical criteria. These criteria need verification and revision in the Indian context. Furthermore, there are glaring differences in management protocols available in literature. These facts prompted Indian Academy of Pediatrics to review the management of rheumatic fever.. Management of Rheumatic fever was reviewed and recommendation was formulated at national consultative meeting on 20th May 2007 at New Delhi.. To formulate uniform guidelines on management of acute rheumatic fever and rheumatic heart disease in the Indian context. Guidelines were formulated for the management of streptococcal pharyngitis, acute rheumatic fever and its cardiac complication as well as secondary prophylaxis for recurrent episodes.. (1) Streptococcal eradication with appropriate antibiotics (Benzathine penicillin single dose or penicillin V oral or azithromycin). (2) Diagnosis of rheumatic fever based on Jones criteria. (3) Control inflammatory process with aspirin with or without steroids (total duration of treatment of 12 weeks). (4) Treatment of chorea according to severity (therapy to continue for 2-3 weeks after clinical improvement). (5) Protocol for managing cardiac complication like valvular heart disease, congestive heart failure and atrial fibrillation. (6) Secondary prophylaxis with benzathine penicillin and management of anaphylaxis.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Humans; Penicillin G Benzathine; Pharyngitis; Rheumatic Fever; Rheumatic Heart Disease; Streptococcal Infections

Azithromycin has become a frequent choice for the treatment of group A streptococcal (GAS) tonsillopharyngitis. In this study, our objective was to determine the optimal dose of azithromycin for treatment of GAS tonsillopharyngitis in children and adults by analyzing trials that used different dose regimens.. We performed a meta-analysis of randomized, controlled trials that involved bacteriological confirmation of GAS tonsillopharyngitis, random assignment to receive either azithromycin or a 10-day comparator antibiotic, and assessment of bacteriological eradication by throat culture after therapy. The primary outcomes of interest were bacteriological and clinical cure rates.. Nineteen trials involving 4626 patients were included in the analysis. One trial used 10-day course of 2 different comparator antibiotics, and 2 trials compared 2 dose regimens of azithromycin with a 10-day course of comparator antibiotic; all other trials compared 1 dose regimen of azithromycin with a single 10-day course of comparator antibiotic. In children, azithromycin administered at 60 mg/kg per course was superior to the 10-day courses of comparators (P < .00001), with bacterial failure occurring 5 times more often in patients receiving the 10-day courses of antibiotics. Azithromycin administered at 30 mg/kg per course was inferior to the 10-day courses of comparators (P = .02), with bacterial failure occurring 3 times more frequently in patients receiving azithromycin. Three-day regimens were inferior to 5-day regimens (P = .002). In adults, no studies compared dosages by weight. Three-day regimens of 500 mg/day showed a trend favoring azithromycin over the 10-day courses of comparators (P = .14); 5-day regimens were inferior to 3-day regimens (P = .006). Clinical cure rates were significantly different for the different azithromycin regimens, with differences that resembled those for bacterial cure rate.. This analysis suggests that azithromycin administered at a dosage of 60 mg/kg in children or administered for 3 days at a dosage of 500 mg/day in adults is more effective than other treatment regimens in producing eradication and clinical cure of GAS tonsillopharyngitis.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child; Humans; Pharyngitis; Randomized Controlled Trials as Topic; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

Pharyngitis is one of the most common infectious diseases affecting children. Group A streptococci are the leading bacterial cause of pharyngitis in children and adults. Because inappropriate antibiotic treatment for pharyngitis is becoming a major issue, only true group A beta-hemolytic streptococcus (GABHS) infections, proven by rapid antigen test or culture, should be treated with antibiotics. GABHS pharyngitis is often a mild and self-limiting infection in the absence of antimicrobial therapy. However, antimicrobial treatment must be administered to eradicate the pathogen from the throat, limit the spread of the infection and prevent possible progression to rheumatic fever, suppurative disease or toxin-mediated complications. Penicillin V for 10 days is the standard therapy and is effective in the management of GABHS pharyngitis. However, there are drawbacks to penicillin V therapy, including the length of the dosing regimen, which are leading to decreasing penicillin prescription rates in many countries. In addition bacteriologic treatment failures have been documented in up to 35% of GABHS patients treated with penicillin V, particularly in children <6 years old. A number of mechanisms may be responsible for these failures, but poor compliance with the standard 10-day penicillin treatment is likely to be a major factor. There is growing evidence to suggest that children with GABHS pharyngitis can be effectively treated with non-penicillin V antibiotics, which have the advantage of simpler and shorter dosing regimens compared with penicillin V. Among the antibiotics that have been tested clinically, azithromycin is the most widely studied. A total dose of 60 mg/kg azithromycin, given either as 12 mg/kg once daily for 5 days or 20 mg/kg once daily for 3 days, provides the best rate of GABHS eradication. Thus a total dose of 60 mg/kg azithromycin given during 3 or 5 days constitutes an alternative treatment to standard penicillin therapy in cases of penicillin hypersensitivity, when patient nonadherence to a 10-day penicillin regimen is suspected or for patients who fail therapy with a beta-lactam.

Topics: Azithromycin; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Follow-Up Studies; Humans; Infant; Male; Microbial Sensitivity Tests; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive-compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing-remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of post-streptococcal OCD and tic disorders. The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea. The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen. The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.

Topics: Antibiotic Prophylaxis; Autoimmune Diseases; Azithromycin; Basal Ganglia; Child; Child, Preschool; Chorea; Double-Blind Method; Forecasting; Frontal Lobe; Humans; Immunoglobulins, Intravenous; Infant; Models, Neurological; Neurons; Obsessive-Compulsive Disorder; Penicillins; Plasma Exchange; Randomized Controlled Trials as Topic; Research; Rheumatic Fever; Streptococcal Infections; Streptococcus pyogenes; Tic Disorders

The objective of this review is to examine the use of short-course antibacterial therapy of group A beta-hemolytic streptococcal (GABHS) pharyngotonsillitis, compared with traditional 10-day therapy. In preparing this paper we reviewed the medical literature of studies comparing 10 days of penicillin with shorter courses of antibacterial therapy. Short-course therapy of 6 days of amoxicillin, 4 to 5 days of cephalosporins, and 5 days of azithromycin was found to be as, or more effective than traditional 10-day penicillin therapy. The benefits of short-course therapy include superior compliance and adherence, lower incidence of adverse effects, less effect on the bacterial flora, improved patient and parent satisfaction, and lower drug costs. In conclusion, short courses of amoxicillin, cephalosporins, and macrolides provide superior or equal efficacy to a 10-day course of penicillin therapy in the treatment of GABHS pharyngotonsillitis.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Child; Humans; Penicillins; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

An orally administered antimicrobial regimen for the treatment of pharyngitis caused by group A beta-hemolytic streptococci that could be given once daily and for less than 10 days would be convenient and might improve compliance, decrease cost, and result in fewer side effects compared with a regimen given multiple times daily for 10 days. Previous attempts to administer oral penicillin once daily or for less than 10 days were not successful. Several cephalosporins and azithromycin have been reported to be effective when administered once daily or for less than 10 days. However, large, comprehensive studies have not been performed. In addition, the spectra of these cephalosporins and azithromycin are much broader than that of penicillin, and, even when they are administered for short courses, they are more expensive. Therefore, these novel regimens cannot be endorsed and should not supplant penicillin as the agent of choice. In contrast, once-daily amoxicillin therapy appears to be effective, is inexpensive, and has a narrower spectrum of antimicrobial activity; if these findings are confirmed by additional investigations, it could become an alternative regimen for the treatment of pharyngitis caused by group A beta-hemolytic streptococci.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Child; Humans; Penicillins; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Time Factors

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

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

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

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

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 most frequent bacterial cause of pharyngitis/tonsillitis, a common infection in children, is group A beta-hemolytic streptococci. Prevention of acute rheumatic fever is the principal goal of treatment, although antibiotic therapy may also relieve the signs and symptoms of infection, shorten the infective period and prevent suppurative complications. Penicillin is the drug of choice. Alternatives are required, however, for patients allergic to penicillin and may be needed if the rate of bacteriologic failure with penicillin observed during the past decade continues. Erythromycin is generally effective in this infection, but its use, especially in children, is complicated by the need for multiple daily doses, a lengthy treatment period and a high rate of gastrointestinal side effects. The newer macrolides clarithromycin and azithromycin offer lower rates of gastrointestinal complaints and more convenient dosing. Clarithromycin is recommended for twice daily and azithromycin for once daily administration. Because of its prolonged tissue half-life, the recommended duration of azithromycin therapy is 5 days, compared with 10 days for penicillin, erythromycin and clarithromycin. Newer macrolides are rational alternatives to erythromycin for streptococcal pharyngitis/tonsillitis in penicillin-allergic patients.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Clarithromycin; Erythromycin; Humans; Penicillins; Pharyngitis; Streptococcal Infections; Tonsillitis

Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most frequently isolated pathogens in patients with acute otitis media (AOM). Other potential causative pathogens include Streptococcus pyogenes in older children and Chlamydia pneumoniae in younger children. The recent emergence of penicillin-resistant S. pneumoniae and the increasing frequency of beta-lactamase-producing strains of M. catarrhalis and H. influenzae are creating concerns regarding the use of amoxicillin as traditional first line empiric therapy for AOM in younger children. Both the in vitro antibiotic activity against these more resistant causative pathogens and the antibiotic concentrations achieved in middle ear fluid must be considered when selecting antibiotics for treatment of refractory AOM. The newer macrolides, azithromycin and clarithromycin, provide reasonable in vitro coverage against penicillin-resistant S. pneumoniae and beta-lactamase-producing H. influenzae, although azithromycin is more active against the latter. Both drugs also achieve notably higher, sustained concentrations in middle ear fluid than do beta-lactam antibiotics. Thus the newer macrolides represent important new rational alternatives for the management of AOM.

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactam Resistance; Child; Child, Preschool; Clarithromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Lactams; Moraxella catarrhalis; Neisseriaceae Infections; Otitis Media; Penicillin Resistance; Penicillins; Streptococcal Infections; Streptococcus pneumoniae

The exact aetiology of pityriasis lichenoides chronica (PLC) remains unknown. While phototherapy is the most investigated therapeutic modality, azithromycin has been used scarcely. The aim of this study is to evaluate the therapeutic efficacy of azithromycin in the treatment of PLC compared to NB-UVB and evaluating the presence of streptococcal infection as a possible etiological factor in PLC patients. The study was designed as a randomised controlled trial. Twenty-four patients with PLC were randomly allocated into either azithromycin (n = 13, standard dose every 10 days) or NB-UVB (n = 11, thrice weekly) groups. End of study (EOS) was either complete clearance of lesions or a maximum of 8 weeks. Therapeutic efficacy was defined as percent reduction in lesions and was calculated for the rash as a whole, erythematous papules alone, and hypopigmented lesions alone and graded into complete, very-good, good, poor or no response. Anti-streptolysin O titre (ASOT), anti-deoxyribonuclease B titre (anti-DNaseB) and throat culture were evaluated at day 0. No significant difference existed between both groups as regards therapeutic efficacy. At EOS, NB-UVB achieved significantly more percent reduction in the extent of hypopigmented lesions and consequently in the rash as a whole (p = 0.001, p = 0.034, respectively). The extent of the rash as a whole was significantly less in the NB-UVB at EOS (p = 0.029, respectively). The effect of NB-UVB on hypopigmented lesions appeared early at week 4 of treatment. Only two patients, one from each group, relapsed during the 3 month follow-up. Evidence of recent streptococcal infection was present in 79% of the cases, mainly in the form of elevated ASOT (94.7%). It was significantly more encountered in young children (< 13 years) (p = 0.03) and was associated with more extent of erythematous papules and consequently with more extent of the rash as a whole (p = 0.05 and p = 0.01, respectively). It did not affect outcome of therapy at EOS. Azithromycin did not show more favorable response in patients with recent streptococcal infection. Therapeutic efficacy of azithromycin is comparable to NB-UVB in treatment of PLC; however, NB-UVB is superior in management of hypopigmented lesions. It is highly suggested that PLC could be a post streptococcal immune mediated disorder.Registration number: ClinicalTrials.gov, NCT03831269.

Topics: Antibodies; Azithromycin; Child; Child, Preschool; Exanthema; Humans; Pityriasis Lichenoides; Streptococcal Infections; Treatment Outcome; Ultraviolet Therapy

To evaluate the clinical efficacy of azithromycin, cefaclor, and amoxicillin in treatment of pediatric tonsillitis, a total of 256 children with Group A β-hemolytic streptococcus (GAS) tonsillitis were randomly divided into 3 groups. Only patients assessed with streptococcus-positive tonsillitis, considered to be compliant with treatment and complete clinical and microbiological evaluations at the end of therapy (day 14) and follow-up (day 30) were included in the efficacy analysis. Our study demonstrated that 96.4% of patients in the azithromycin group, 92.4% of patients in the cefaclor group, and 91.0% of patients in the amoxicillin group were recorded as clinical success at the end of therapy. Bacteriological eradication rates of the 3 groups at the end of therapy were 94.0%, 89.9%, and 88.5%, respectively. A pathogen recurrence rate was evaluated as 2.6%, 7.0%, and 5.9% at the follow-up. Treatment-stimulated adverse events occurred in 2.4% of patients in the azithromycin group, 11.3% in the cefaclor group, and 11.4% in the amoxicillin group. In summary, azithromycin showed an effective tendency for the treatment of pediatric tonsillitis with lower occurrence rate of adverse reactions, although there is no statistical significance for the clinical and bacteriological eradication efficacy between these 3 groups.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefaclor; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Male; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

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

Neonatal deaths, estimated at approximately 4 million annually, now account for almost 40% of global mortality in children aged under-five. Bacterial sepsis is a leading cause of neonatal mortality. Assuming the mother is the main source for bacterial transmission to newborns, the primary objective of the trial is to determine the impact of one oral dose of azithromycin, given to women in labour, on the newborn's bacterial carriage in the nasopharynx. Secondary objectives include the impact of the intervention on bacterial colonization in the baby and the mother during the first month of life.. This is a Phase III, double -blind, placebo controlled randomized clinical trial in which 830 women in labour were randomized to either a single dose of 2 g oral azithromycin or placebo (ratio 1:1). The trial included pregnant women in labour aged 18 to 45 years attending study health centres in the Western Gambia. A post-natal check of the mother and baby was conducted at the health centre by study clinicians before discharge and 8-10 days after delivery. Home follow up visits were conducted daily during the first week and then weekly until week 8 after delivery. Vaginal swabs and breast milk samples were collected from the mothers, and the pathogens Streptococcus pneumoniae, Group B Streptococcus (GBS) and Staphylococcus aureus were isolated from the study samples. For bacterial isolates, susceptibility pattern to azithromycin was determined using disk diffusion and E-test. Eye swabs were collected from newborns with eye discharge during the follow up period, and Chlamydial infection was assessed using molecular methods.. This is a proof-of-concept study to assess the impact of antibiotic preventive treatment of women during labour on bacterial infections in the newborn. If the trial confirms this hypothesis, the next step will be to assess the impact of this intervention on neonatal sepsis. The proposed intervention should be easily implementable in developing countries.. ClinicalTrials.gov Identifier--NCT01800942--First received: February 26, 2013.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Delivery, Obstetric; Double-Blind Method; Female; Gambia; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Microbial Sensitivity Tests; Middle Aged; Milk, Human; Nose; Pregnancy; Pregnancy Complications, Infectious; Staphylococcus aureus; Streptococcal Infections; Streptococcus agalactiae; Streptococcus pneumoniae; Vagina; Young Adult

Group A streptococcal (GAS) tonsillopharyngitis is one of the few conditions for which antibiotics are advocated among common upper respiratory infections. Although a 3-day course of azithromycin is attracting attention as a treatment of choice for the condition, it is not clear if the efficacy of the treatment is comparable with that of treatment with cephalosporins. A prospective, randomized, comparative multicenter study was conducted to compare the efficacy of azithromycin (AZM) given once daily for 3 days with that of cefcapene-pivoxyl (CFPN-PI) divided into three daily doses for 5 days. 88 patients (male: 38, mean age: 16.5) were treated with AZM and 69 (male: 34, mean age: 16.9) with CFPN-PI. The symptoms of all but 5 (2 for AZM and 3 for CFPN-PI) of the patients were resolved by the 8th day of the treatment. By the 4th day of the treatment, criteria for clinical efficacy were fulfilled in 71 (80.7%) subjects who were treated with AZM and in 48 (67.6%) of those treated with CFPN-PI (p = 0.07). The same figures on the 8th day of the treatment were 86 (97.7%) and 68 (95.8%), respectively (p = 0.66), confirming there was no significant difference in clinical efficacy between the two treatments. Mild adverse reactions were reported by two patients treated with AZM and by none treated with CFPN-PI. The clinical efficacy of a 3-day course with AZM was comparable with that of a 5-day course of CFPN-PI for GAS tonsillopharyngitis.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Chi-Square Distribution; Drug Administration Schedule; Female; Humans; Male; Microbial Sensitivity Tests; Pharyngitis; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome; Young Adult

Long-term administration of azithromycin (AZM) in children with cystic fibrosis (CF) has improved outcomes. However, the doses and schedule of administration are not very well studied in children with CF.. A randomized controlled trial was conducted to compare the effect of two doses of azithromycin (5mg/kg/day and 15mg/kg/day) on FEV(1) and pulmonary exacerbations in children with cystic fibrosis. Enrolled children were randomly allocated to receive daily azithromycin (5mg/kg/day or 15mg/kg/day) for 6months. Clinical assessment and FEV(1) measurement were performed monthly.. 56 children (28 in high dose group and 28 in low dose group) were enrolled. 47 (24 and 23 children in low and high dose groups) completed 12months of follow up. There was no difference in clinical scores, FEV(1), pulmonary exacerbation rates between two groups at baseline, 6months and at 12months. Per protocol analysis revealed that pulmonary exacerbation increased after discontinuing AZM and there was significantly more increase after 12months of enrolment in children getting high dose azithromycin. There was no improvement in FEV(1) in either group at the end of treatment period. Children tolerated daily low as well as high dose AZM well for 6months. There was no significant side effect of azithromycin.. In this randomized controlled trial, we did not find differences in the effect of 2 doses (5mg/kg/day or 15mg/kg/day) of AZM on change in percentage predicted FEV(1), clinical scores, Pseudomonas colonization rates, pulmonary exacerbations and need for antibiotics. There was increase in exacerbations after stopping azithromycin in both the groups. Our results also suggest that the decrease in the incidence of LRTI persists only till 6months after discontinuing azithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Body Weight; Candidiasis; Child; Child, Preschool; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Interleukin-8; Male; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Spirometry; Sputum; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pneumoniae; Treatment Outcome

To determine the proportion of subjects with oropharyngeal streptococci resistant to either levofloxacin or azithromycin prior to and during antibacterial exposure, and to follow temporal changes in the proportion of resistant and susceptible isolates through 6 weeks post-exposure. This randomized, open-label, single-center study is registered with ClinicalTrials.gov (identifier: NCT00821782).. A total of 143 healthy volunteers (levofloxacin, n = 71; azithromycin, n = 72) without antibacterial exposure in the previous 90 days received either levofloxacin 750 mg once daily for 5 days or azithromycin 500 mg once daily on day 1 and 250 mg once daily on days 2 through 5. Oropharyngeal cultures were obtained pre-exposure, at day 5, and at 2, 4, and 6 weeks post-dosing. Bacterial strains were identified and the minimum inhibitory concentrations for levofloxacin and azithromycin were determined.. At study entry 117 streptococci were isolated from 72 subjects randomized to azithromycin and 53 (45.3%) were azithromycin-resistant. None of the 121 streptococci isolated from 71 subjects randomized to.levofloxacin were colonized by a levofloxacin-resistant microorganism prior to dosing. At the end of dosing, the number of subjects with resistant streptococci (S. mitis, S. salivarius, S. sanguis, or alpha streptococcus species [spp.]) increased in azithromycin-exposed subjects and resistant isolates remained through 6 weeks post-dosing. In contrast, a small number of levofloxacin-resistant streptococci were observed at the end of dosing but decreased by week 2 post-dosing and continued to decrease through the 6-week evaluation period (p < 0.001 azithromycin vs. levofloxacin for S. mitis, S. salivarius, S. sanguis and alpha streptococcus spp. at week 6). Limitations of this study included the fact that, since previous antibiotic use was self-reported, genetic typing was not done. The results of this study may not be completely generalizable, because subjects in this study received study drug under directly-observed conditions, thus ensuring compliance.. Both antibacterial agents were well tolerated. Levofloxacin 750 mg administered for 5 days was associated with less microbial resistance than that observed with azithromycin in healthy subjects.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Microbial Viability; Ofloxacin; Oropharynx; Streptococcaceae; Streptococcal Infections; Young Adult

The azithromycin immediate-release formulation (AZ-IR) provides effective treatment for group A beta-haemolytic streptococcal pharyngitis in adults. Single-dose therapy with a novel azithromycin extended-release (AZ-ER) formulation could reduce treatment failure and eliminate non-compliance contributing to antimicrobial resistance. A randomized, double-blind, double-dummy, multicentre trial was conducted comparing AZ-ER (single oral 2-g dose) with AZ-IR (3 days, 500 mg once daily) for the treatment of group A beta-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents (n = 598). The primary endpoint was bacteriological eradication at test -of-cure (TOC; day 24-28) in the bacteriological per-protocol population (n = 420). Bacteriological eradication was achieved in 85.4% (175/205) and 81.4% (175/215) of subjects in the AZ-ER and AZ-IR groups, respectively (95% CI -3.1-11.1). Clinical cure at TOC occurred in 99.0% of subjects in the AZ-ER group and in 96.7% in the AZ-IR group. At long-term follow-up, bacteriological recurrence was observed in 5.5% (9/163) and 7.7% (12/156), respectively. Both treatments were well tolerated; and most adverse events (AEs) were mild to moderate in intensity. The most frequent treatment-related AE was diarrhoea, or loose stools, in 11% of both treatment groups. AZ-ER-treated and AZ-IR-treated subjects had AE burdens (AE days/patient-year) of 7.6 days and 9.2 days, respectively. A similar trend in favour of AZ-ER was noted for treatment-related diarrhoea burden (1.9 days vs. 2.5 days). A single 2-g dose of AZ-ER is as effective and well tolerated as 3 days of AZ-IR (500 mg once daily) for treating group A beta-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome; Young Adult

High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM.. To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM.. This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study).. The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001).. In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Moraxellaceae Infections; Otitis Media; Patient Compliance; Pneumococcal Infections; Streptococcal Infections; Streptococcus pyogenes

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) describes a subgroup of children with obsessive-compulsive disorder and/or tic disorder that experience symptom exacerbations following streptococcal infections. We hypothesized that the prevention of streptococcal infections among children in the PANDAS subgroup would decrease neuropsychiatric symptom exacerbations.. Twenty-three subjects with PANDAS were enrolled in a double blind, randomized controlled trial. Antibiotic prophylaxis with penicillin or azithromycin was administered for 12 months. Rates of streptococcal infections and neuropsychiatric symptom exacerbations were compared between the study year and the baseline year prior to entry.. Significant decreases in streptococcal infections during the study year were found with a mean of .1 (.3 SD) per subject, compared to the baseline year with 1.9 (1.2 SD) in the penicillin group and 2.4 (1.1 SD) in the azithromycin group [p<.01]. Significant decreases in neuropsychiatric exacerbations during the study year were also found with a mean of .5 (.5 SD) per subject in the penicillin group and .8 (.6 SD) in the azithromycin group, compared to the baseline year with 2.0 (.9 SD) in the penicillin group and 1.8 (.6 SD) in the azithromycin group [p<.01].. Penicillin and azithromycin prophylaxis were found to be effective in decreasing streptococcal infections and neuropsychiatric symptom exacerbations among children in the PANDAS subgroup.

Topics: Antibiotic Prophylaxis; Azithromycin; Child; Child, Preschool; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Obsessive-Compulsive Disorder; Penicillins; Psychiatric Status Rating Scales; Retrospective Studies; Streptococcal Infections; Treatment Outcome

To determine if macrolide resistant Streptococcus pneumoniae will be a major concern in areas that receive annual mass azithromycin distributions for trachoma.. A cross sectional survey was conducted of nasopharyngeal S pneumoniae isolates for susceptibility to azithromycin 1 year after administering a single dose of azithromycin to treat trachoma in a village in Nepal.. S pneumoniae was isolated from 50 (86%) of 57 nasopharyngeal cultures and no resistance to azithromycin was detected.. The authors were unable to demonstrate that mass azithromycin therapy for trachoma produced macrolide resistant S pneumoniae that persists until the next scheduled annual treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Nepal; Prevalence; Rural Health; Streptococcal Infections; Streptococcus pneumoniae; Trachoma

Topics: Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Cefixime; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Nasopharynx; Pharyngitis; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

In this multicenter, investigator-blind trial, we compared the efficacy and safety of azithromycin and cefadroxil for the treatment of uncomplicated skin and skin structure infections (SSSIs). A total of 296 patients were randomized to receive either azithromycin (500 mg on day 1, followed by 250 mg once a day on days 2 to 5) or cefadroxil (500 mg twice a day for 10 days). Outpatients, ranging in age from 18 to 75 years, with acute uncomplicated SSSIs were enrolled in the study. Clinical and bacteriologic response was assessed between days 10 and 13 (primary end point) and between days 28 and 32. In a modified intent-to-treat analysis, clinical success rates assessed between days 10 and 13 were 97% (111/114) for azithromycin and 96% (101/105) for cefadroxil (P = .717). For azithromycin and cefadroxil, corresponding rates of bacteriologic eradication for Staphylococcus aureus were 94% (64/68) and 86% (60/70), respectively, and for Streptococcus pyogenes, 80% (4/5) and 100% (6/6), respectively. Clinical success rates assessed between days 28 and 32 were 100% (82/82) for azithromycin compared with 90% (75/83) for cefadroxil (P = .007). Corresponding rates of eradication for S aureus were 100% (59/59) versus 89% (56/63), respectively; and for S pyogenes, 100% (4/4) versus 83% (5/6), respectively. The incidence of treatment-related adverse events was similar in the 2 treatment groups. However, 5 of the 139 patients (4%) in the cefadroxil group discontinued therapy because of treatment-related adverse events compared with none of the 152 patients in the azithromycin group (P = .02). Five-day therapy with azithromycin was as effective as 10-day therapy with cefadroxil for treating uncomplicated SSSIs.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Cefadroxil; Female; Follow-Up Studies; Humans; Male; Middle Aged; Severity of Illness Index; Single-Blind Method; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Time Factors; Treatment Outcome; United States

To compare a 3-day azithromycin vs. a 10-day penicillin V regimen for treatment of acute group A streptococcal (GAS) pharyngitis in children and to determine whether viral infection and/or pharyngeal GAS carriage in patients and adult contacts affect clinical and bacteriologic efficacy.. This multicenter, randomized, comparative, open label study compared 3-day, once daily 10 mg/kg azithromycin oral suspension with a 10-day regimen of 100,000 IU/kg/day penicillin V oral suspension in three divided doses in children with acute GAS pharyngitis. Clinical and bacteriologic efficacy and tolerability of the antibiotics were evaluated. Recurrence of symptoms and infection was monitored for 6 months.. In total, 292 children (age range, 2 to 12 years) received at least one dose of study medication. Clinical success (cure/improvement) with either antibiotic was similar at the end of therapy (Day 14; azithromycin, 95%; penicillin V, 97%) and at Day 28 (azithromycin, 94%; penicillin V, 95%). Bacteriologic eradication was significantly less with azithromycin than with penicillin V at Day 14 (azithromycin, 38%; penicillin V, 81%; P < 0.001) and at Day 28 (azithromycin, 31%; penicillin V, 68%; P < 0.001). There was no associated increase in GAS-related sequelae. The lower incidence of bacteriologic eradication with azithromycin was not the result of possible concomitant viral infections in the patients, GAS carriage in one parent/guardian or any reduced susceptibility in pretreatment GAS isolates. Both antibiotics were equally well-tolerated.. Treatment with 3-day, once daily 10 mg/kg azithromycin for GAS pharyngitis is associated with similar high levels of clinical efficacy, but lower levels of bacteriologic eradication, than with 10-day 100,000 IU/kg/day penicillin V.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Infant; Male; Penicillin V; Penicillins; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

Three-day, 10 mg/kg/day azithromycin (AZM) studies in pediatric acute group A streptococcal tonsillopharyngitis have shown contradictory bacteriologic results. This study investigates the efficacy and tolerability of two dosages of 3-day azithromycin (20 mg/kg/day and 10 mg/kg/day) compared with 10-day penicillin V.. This was a prospective, comparative, randomized, multicenter trial. Children were scheduled to return for visits at 14 days (main end point) and 1 month after the onset of treatment for clinical and bacteriologic assessment. Molecular tools were used to compare pre- and posttreatment group A beta-hemolytic Streptococcus (GABHS) isolates.. Between November, 1997, and July, 1998, 501 patients (169 AZM 10 mg, 165 AZM 20 mg, 167 penicillin V) between 2 and 12 years old were enrolled; 500 were assessable for safety, 469 for intent to treat analysis and 420 for efficacy in the per protocol analysis. Before treatment 25 (7.9%) of 315 GABHS stains isolated from patients receiving AZM were resistant to this compound. On Day 14 pretreatment GABHS were eradicated from 78 (57.8%) of the 135 children receiving the AZM 10 mg regimen, 131 (94.2%) of the 139 receiving AZM 20 mg and 123 (84.2%) of the 146 taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 40.5% (n = 30) of the children receiving AZM 10 mg, 14.8% (n = 18) of children taking AZM 20 mg and 13.2% (n = 15) of those treated with penicillin V. AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day microbiologically on Day 14 (P = 0.0001) and Day 30 (P = 0.0001) and clinically on Day 14 (P = 0.0035). AZM 20 mg/kg/day was statistically equivalent both microbiologically and clinically to standard therapy with penicillin V at all endpoints. The incidence of treatment-related adverse events was similar in the two azithromycin groups [AZM 10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)] but significantly higher than those observed in the penicillin V group [5 of 166 (3%); P < 0.0001]. Most treatment-related adverse events were gastrointestinal and of mild-to-moderate severity. Fourteen patients withdrew from the trial because of adverse events (1 in the penicillin V group, 7 in the AZM 10 mg group and 6 in the AZM 20 mg group).. This is the first study to demonstrate a daily dose-dependent difference in microbiologic efficacy of a regimen; 3-day AZM 20 mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day for pediatric GABHS tonsillopharyngitis.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infant; Male; Penicillin V; Penicillins; Pharyngitis; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

Invasive group A streptococcal (GAS) infections are a cause of serious morbidity and high mortality. There is a need for a simple, effective antimicrobial regimen that could be used to prevent invasive GAS disease in high risk situations. To assess azithromycin as a chemoprophylactic agent, we evaluated its efficacy for eradication of oropharyngeal (OP) GAS and its impact on the nasopharyngeal (NP) colonization rate of macrolide-resistant Streptococcus pneumoniae.. We obtained OP and NP swabs for GAS and pneumococcus culture, respectively, from 300 schoolmates of a child with an invasive GAS infection. GAS culture-positive students were treated with daily azithromycin (12 mg/kg/day) for 5 days. We obtained follow-up OP and NP swabs at 9 (Day 17) and 24 (Day 32) days post-treatment from those students identified as GAS carriers on Day 0 and determined macrolide susceptibility of GAS and pneumococcal isolates.. Of the 300 students swabbed 152 (50%) carried GAS in their oropharynx. On Day 17, efficacy of azithromycin for GAS eradication was 95% (140 of 147) for all students. NP colonization rates for pneumococci decreased from 46% (67 of 146) to 12% (17 of 144; P < 0.001) by Day 17 and to 20% (27 of 137; P < 0.001) by Day 32. The prevalence of erythromycin-resistant pneumococcal isolates increased from 2% (3 of 146) to 4% (6 of 144) by Day 17 and to 8% (11 of 137; P = 0.04) by Day 32.. Azithromycin is an effective short course regimen for eradication of oropharyngeal GAS. However, azithromycin selected for macrolide-resistant strains of pneumococci. These findings highlight the importance of determining the appropriate circumstances for antimicrobial prophylaxis to prevent invasive GAS infections.

Topics: Anti-Bacterial Agents; Azithromycin; Carrier State; Chi-Square Distribution; Child; Colony Count, Microbial; Confidence Intervals; Drug Administration Schedule; Drug Resistance, Microbial; Female; Humans; Male; Nasopharynx; Oropharynx; Pneumococcal Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes; Treatment Outcome

To compare the safety and efficacy of a short course (5 days) of ceftibuten vs. azithromycin for 3 days for treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis in children.. A multicenter, open label, prospective, randomized trial in which patients > or =3 to < or =16 years of age with proven GABHS pharyngitis were randomized to receive either once daily ceftibuten for 5 days or azithromycin for 3 days. Patients were evaluated for clinical outcomes and/or for adverse events at days 6 to 8, 13 to 15 and 33 to 35 posttherapy. Microbiologic assessments (pharyngeal cultures) were conducted at baseline and at each follow-up visit.. A total of 132 patients in the ceftibuten arm and 116 in the azithromycin arm were enrolled in the safety analysis, whereas 126 and 101, respectively, were enrolled for ceftibuten and azithromycin efficacy evaluation. Clinical success (cure or marked amelioration) at days 6 to 8 was recorded in 98 and 94% in the 2 groups, respectively. In the bacteriologic efficacy analysis at 6 to 8 days, the GABHS strain was eradicated in 76% of the patients treated with ceftibuten and in 76% of those receiving azithromycin. At 33 to 35 days, 84% of the patients in the ceftibuten arm and 71% in the azithromycin arm were GABHS-negative, and bacteriologic relapse was observed in 4 and 7% of the ceftibuten and azithromycin cases, respectively. Both treatments were well-tolerated by all patients.. Ceftibuten and azithromycin allow simple treatment schedules (i.e. once daily administration, short duration of treatment). The somewhat higher eradication rate recorded after ceftibuten administration is consistent with the overall superior bactericidal activity of beta-lactams compared with macrolides vs. GABHS in vitro.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Ceftibuten; Cephalosporins; Child; Child, Preschool; Female; Humans; Male; Pharyngitis; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

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

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

An open, comparative multicenter study was performed to evaluate the efficacy and safety of azithromycin (10 mg/kg) given once daily for three days in comparison with cefaclor (30 mg/kg) divided into three daily doses and given for a period of ten days. One hundred and twenty-two children aged 1-12 years with clinical symptoms of group A beta-hemolytic streptococcal tonsillopharyngitis and a positive throat culture were randomly allocated to the treatment groups. Overall, the clinical success (cure or improvement) of both regimens was identical in the evaluable patients (86.3%, 44 of 51 patients in either treatment group). In contrast, bacterial eradication after completion of treatment was lower with azithromycin than with cefaclor. Possible reasons for this discrepancy between clinical success and eradication rates could be antibiotic resistance, pre-disease carriage or insufficient dosage. Both agents were well tolerated; only mild or moderate side effects most frequently involving the gastrointestinal tract, were recorded in either therapy group.

Topics: Anti-Bacterial Agents; Azithromycin; Cefaclor; Cephalosporins; Child; Female; Humans; Male; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

For many years alternatives to penicillin have been studied for the management of pediatric group A beta-hemolytic Streptococcus (GABHS) pharyngitis. As a result of its pharmacokinetic profile azithromycin is unique among these alternative antimicrobials in allowing once daily dosing and shorter duration of treatment. However, the optimum dose (e.g. 10 or 12 mg/kg/day) and duration (e.g. 3 or 5 days) of azithromycin therapy have not been defined yet.. An open, comparative multicenter study was conducted in 343 children with clinical symptoms of GABHS pharyngitis and a positive culture to evaluate the efficacy and safety of azithromycin (10 mg/kg) once daily for 3 days compared with penicillin V three times daily for 10 days.. Among the evaluable patients bacteriologic eradication documented at follow-up visits was inferior with azithromycin when compared with penicillin V therapy: at Days 9 to 20 (mean, 12 days), negative cultures in 65% (99 of 152 patients) vs. 82% (128 of 126 patients) (P < 0.001); and at Days 17 to 57 (mean, 25 days), in 55% vs. 80% (P < 0.001). Overall clinical success (cure or improvement) was achieved in 93% (149 of 160 patients) of azithromycin-treated and in 89% (143 of 160 patients) of penicillin-treated patients (P > 0.50). There was no correlation between bacteriologic response and clinical outcome, as assessed shortly after completion of therapy or during 6-month follow-up. Both treatments were well-tolerated.. In the present study on GABHS pharyngitis in children, a once daily (10-mg/kg), 3-day oral regimen of azithromycin was as clinically effective and as safe as traditional penicillin but appeared inferior in eliminating GABHS from the throat.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Infant; Male; Penicillin V; Penicillins; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes

The efficacy and safety of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis/tonsillitis in paediatric patients were compared in a double-blind, double-dummy prospective study. A total of 489 children (age range, 2-13 years) were randomized to receive treatment with penicillin V (125-250 mg 4 x daily for 10 days) or azithromycin in an oral suspension (10 or 20 mg/kg 1 x daily for 3 days). Only patients with baseline cultures positive for Streptococcus pyogenes and complete clinical and microbiological assessments at the end of the therapy and follow-up one month later were included in the efficacy analysis. A satisfactory clinical response (cure or improvement) was recorded in 99% of the 10 mg/kg azithromycin group, 100% of the 20 mg/kg azithromycin group, and 97% of the penicillin V group at the end of therapy (day 12-14). At the follow-up evaluation (day 28-30), relapse rates in patients cured or improved at the end of therapy were 6%, 5%, and 2%, respectively. Bacteriological eradication rates at the end of therapy were 98% in both azithromycin groups and 92% in patients who received penicillin V (p = 0.011); pathogen recurrence was recorded at follow-up in 4% of the 20 mg/kg azithromycin group and in 6% of both the 10 mg/kg azithromycin and penicillin V groups. Treatment-related adverse events, the majority of mild to moderate severity, occurred in 13% of patients in the 20 mg/kg azithromycin group, 9% in the 10 mg/kg azithromycin group, and 5% in the penicillin V group. Azithromycin in a dosage of 10 or 20 mg/kg/day one daily for three days was as safe and effective as penicillin V administered four times daily in the treatment of paediatric patients with acute pharyngitis/tonsillitis.

Topics: Administration, Oral; Adolescent; Analysis of Variance; Anti-Bacterial Agents; Azithromycin; Chi-Square Distribution; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Penicillin V; Penicillins; Pharyngitis; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Clindamycin; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Streptococcal Infections; Streptococcus pyogenes

To compare three traditional measures of compliance with antibiotic therapy (parent report diary, preregimen and postregimen bottle-weight difference, and urine bioassay for antibiotic activity), with a deuterium oxide tracer measure of compliance.. Clinical trial in which all four compliance measures were used for subjects participating in a comparison of the efficacy of azithromycin and penicillin in treating group A beta-hemolytic streptococcal infection. Subjects were 41 children, aged 3 to 15 years (average age, 7.9 years), in a suburban pediatric private practice, who had positive rapid streptococcal antigen test results.. Of the 41 subjects, 20 children were randomly assigned to receive azithromycin and 21 to receive penicillin. Compliance was uniformly high by all four measures. Parent diaries indicated that all doses were administered. Urine bioassays were obtained for 40 subjects, and all showed antibiotic activity. Differences in bottle weights were obtained for 27 subjects and showed that 142% of the prescribed medication was missing from the bottles at the end of the regimen. The deuterium oxide measure was obtained for 40 subjects and showed that 107% of the prescribed azithromycin and 92% of the prescribed penicillin were ingested. The correlation coefficient between measured and expected deuterium enrichment was 0.89. There was no significant correlation between the bottle-weight measure and the deuterium oxide tracer.. The bottle-weight measure overestimates compliance; the deuterium oxide tracer is feasible for use in an office setting and produces a high correlation between the expected urinary enrichment and the measured enrichment. Increased use of this quantitative and direct measure would improve the accuracy of compliance measurement in trials of pediatric liquid medications.

Topics: Adolescent; Azithromycin; Child; Child, Preschool; Deuterium; Deuterium Oxide; Drug Packaging; Erythromycin; Female; Humans; Male; Parents; Patient Compliance; Penicillin V; Pharyngitis; Regression Analysis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Water

An open, randomized, multicentre study was undertaken to compare a three-day regimen of azithromycin with a seven-day course of dicloxacillin or flucloxacillin in the treatment of 118 children (aged 2-12 years) with clinically diagnosed acute skin and skin-structure infections. Sixty patients received a single daily dose of azithromycin of 10 mg/kg for three days, whilst 58 received a cloxacillin ester: either dicloxacillin (n = 49) at a daily dose of 12.5-25 mg/kg (depending on severity of infection); or flucloxacillin (n = 9) at 250-2000 mg/day (depending on age). Both cloxacillin esters were administered in four divided doses for seven days. Clinical, safety and, where possible, bacteriological assessments were made before therapy and after 3 to 5 and 7 to 10 days of treatment. A successful clinical response (cure and improvement) was recorded in 57 of 59 (97%) of evaluable azithromycin patients, and in 57 of 58 (98%) of cloxacillin ester patients. Eradication of the key pathogens was 31 of 34 (91%) and 34 of 35 (97%) for Staphylococcus aureus, and 5 of 5 and 4 of 4 for Streptococcus pyogenes in the azithromycin and cloxacillin ester groups, respectively. Both medications were well tolerated, with mild to moderate side-effects (abdominal pain and vomiting) occurring in two patients in each group, and laboratory abnormalities (elevated eosinophil count) in one patient in each group. There were no withdrawals from therapy. The results of this study suggest that azithromycin is as effective and as well tolerated as a cloxacillin ester antibiotic in the treatment of children with acute skin and skin-structure infections.

Topics: Azithromycin; Child; Child, Preschool; Dicloxacillin; Drug Administration Schedule; Erythromycin; Floxacillin; Humans; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes

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

Of 96 children (aged 2-12 years) with either acute pharyngitis or acute tonsillitis, 49 received a single daily dose of azithromycin 10 mg/kg (maximum 500 mg) for three days, and 47 received penicillin V at a dose of 125 mg or 250 mg qid (depending on body weight) for ten days. Clinical assessments and laboratory safety tests were performed during and after therapy. Before enrollment, all patients were screened for group A beta-haemolytic streptococci (GABHS) with a rapid test, and a throat swab was taken for confirmatory culture. The presence of GABHS at baseline was confirmed in 41 azithromycin- and 44 penicillin V-treated patients. Cure or improvement was seen in 98% and 100% of azithromycin- and penicillin V-treated patients, respectively. At day 11, bacterial eradication was achieved in 39/41 (95%) azithromycin-treated patients, 38 (93%) of whom were considered clinically cured, while one patient (2%) relapsed. In the penicillin V group, 42/44 (95%) had GABHS eradicated, with 41 (93%) clinically cured and three patients (7%) improved. The remaining two patients in each group were clinically cured despite persistence of Streptococcus pyogenes. At follow-up evaluation (day 30), re-occurrence was observed in 5/37 (14%) and 3/40 (8%) of azithromycin- and penicillin V-treated patients, respectively; all patients were asymptomatic. Both drugs were well-tolerated with only two patients in the azithromycin group complaining of side effects. Treatment related laboratory test abnormalities were observed in 6/47 (13%) and 4/45 (9%) azithromycin- and penicillin V-treated patients, respectively, but none was judged to be clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Azithromycin; Child; Child, Preschool; Erythromycin; Female; Humans; Male; Penicillin V; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

In this open study, 93 children (aged 2-12 years) with a clinical diagnosis of pharyngitis or tonsillitis caused by Streptococcus pyogenes (culture and/or ELISA test positive) were given azithromycin, as a single daily dose of 10 mg/kg (maximum 500 mg) for three days (n = 46); or erythromycin ethylsuccinate, 30-50 mg/kg daily given in three divided doses, for ten days (n = 47). Forty-four of 46 azithromycin patients, and 46 of 47 erythromycin patients, had S. pyogenes isolated at baseline and were included in the clinical and bacteriological analyses. At the end of treatment (day 10-12), 38 (86%) of the 44 azithromycin patients were considered cured, four (9%) improved, one (2%) failed and one relapsed. In the erythromycin group, 30 of 46 (65%) were considered cured, 15 (33%) improved and one (2%) failed. Eradication of S. pyogenes was achieved in 40 of 44 (91%) and 45 of 46 (98%) azithromycin and erythromycin patients, respectively. Re-occurrence of S. pyogenes, assessed 28-32 days after start of treatment, occurred in five of 37 (14%) azithromycin patients (three with clinical symptoms) and five of 39 (13%) erythromycin patients (four with clinical signs). There were no statistically significant differences in clinical or bacteriological efficacy between the two groups. Both drugs were well-tolerated, with side-effects (mainly gastrointestinal) reported in five of 46 (11%) azithromycin patients and in six of 47 (13%) erythromycin patients, one of whom withdrew from treatment. No laboratory abnormalities were observed in the azithromycin patients, but were recorded in two of 43 (5%) erythromycin patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Azithromycin; Child; Child, Preschool; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

The safety and efficacy of azithromycin was compared with that of penicillin V in a multicenter study of the treatment of streptococcal pharyngitis in outpatients. Patients were randomized in a 2:1 ratio to either azithromycin 500 mg once on day 1 followed by 250 mg once daily for 4 days, or penicillin V (V-Cillin K) 250 mg every 6 hours for 10 days. Two hundred and forty-two patients from 29 centers were evaluable at the 11th day after enrollment. Five of 229 (2.2%) azithromycin-treated patients were not evaluable because their enrollment isolates of group A beta-hemolytic streptococci (GABHS) were resistant to the drug. In both treatment groups, 99% of patients were clinically cured or improved. Eradication of GABHS occurred in 91% of azithromycin-treated patients compared with 96% of penicillin-treated patients (p = 0.21). Of the patients who had a recurrence of GABHS, clinical evidence of infection occurred in 3 of 13 (23%) patients who had been treated with azithromycin and in 7 of 10 (70%) patients treated with penicillin. Adverse events, generally mild to moderate gastrointestinal complaints, were significantly more common in the azithromycin-treated patients (16.6%) than in penicillin-treated patients (1.7%) (p less than 0.001). Discontinuation because of side effects occurred with similar frequency in both groups. Azithromycin appears to be a safe and effective alternative treatment for streptococcal pharyngitis in adult outpatients.

Topics: Abdominal Pain; Adult; Azithromycin; Erythromycin; Female; Humans; Male; Penicillin V; Pharyngitis; Streptococcal Infections

Seventy-eight patients participated in this multicenter, third-party-blinded study comparing a single daily dose of azithromycin for 5 days (500 mg on day 1 followed by 250 mg/day for days 2-5) with amoxicillin (500 mg three times daily) for 10 days in the treatment of acute bacterial maxillary sinusitis. A total of 38 evaluable patients contributed to the efficacy analysis. The overall clinical response rate was 100% for both antibiotics. The clinical cure rate, as determined by the investigator, was 73.9% for azithromycin and 73.3% for amoxicillin; improvement was seen in 26.1% and 26.7% of patients, respectively. The bacteriologic cure rate in these 38 patients was 100% in both groups. Both antibiotics were well tolerated; side effects were reported by 4.9% of patients in the azithromycin group compared with 8.1% in the amoxicillin group. Most of these side effects were gastrointestinal disturbances that were reported by four of five (three amoxicillin, one azithromycin) patients experiencing side effects. All side effects were mild, and in both groups only minor abnormalities in laboratory data were detected. No patient discontinued the study because of treatment-related side effects. In this study, a 5-day course (one dose per day) of azithromycin proved to have efficacy, safety, and tolerability that was equal to a 10-day course (three doses per day) of amoxicillin in the treatment of acute bacterial sinusitis.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin; Azithromycin; Erythromycin; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Maxillary Sinusitis; Middle Aged; Staphylococcal Infections; Streptococcal Infections

This was a randomized, third-party-blinded, multicenter study that compared once-daily azithromycin (500 mg on day 1, followed by 250 mg on days 2-5) to cefaclor (500 mg three times daily for 10 days) in the treatment of patients with acute bronchitis or pneumonia. A total of 546 patients were entered into the study and 272 patients were evaluable for efficacy analysis. Of these, 249 (176 azithromycin, 73 cefaclor) had bronchitis and 23 (15 azithromycin, 8 cefaclor) had pneumonia. The combined clinical cure and improvement rate, as determined by the investigator, was 96% for azithromycin and 94% for cefaclor, with 88% bacteriologic eradication in both treatment groups. The elimination of Haemophilus influenzae was significantly better with azithromycin (94.5%) than with cefaclor (61.1%) (p less than 0.001; Fisher's exact two-tail test). The two antibiotics were well tolerated during this study; the incidence of side effects reported was similar for azithromycin and cefaclor. Approximately two thirds of the side effects were mild. Only minor abnormalities in the screening laboratory tests were noted. This study shows that a 5-day course of once-daily azithromycin is as effective as a 10-day three times daily course of cefaclor in the treatment of patients with acute lower respiratory tract infections.

Topics: Azithromycin; Bronchitis; Cefaclor; Erythromycin; Haemophilus Infections; Humans; Klebsiella Infections; Moraxella catarrhalis; Neisseriaceae Infections; Pneumonia; Prospective Studies; Sputum; Staphylococcal Infections; Streptococcal Infections

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

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

Antimicrobial prophylaxis is widely recommended for pregnant women who have preterm premature rupture of the membranes. Erythromycin prophylaxis was used during an initial period (control) and then changed to intravenous amoxicillin for 48 h, followed by 5 days of oral amoxicillin along with a single dose of azithromycin (case). Healthcare records were reviewed retrospectively. The primary outcome was latency (between membrane rupture and delivery) and the secondary outcomes were mode of delivery, maternal high dependency unit (HDU) admission, and several laboratory parameters. There were 78 women in the case group (amoxicillin and azithromycin) and controls were selected on a 1:1 ratio. There was no statistically significant difference between cases and controls with respect to group B Streptococcus or

Topics: Adult; Amoxicillin; Antibiotic Prophylaxis; Azithromycin; Delivery, Obstetric; Erythromycin; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Streptococcal Infections; Streptococcus agalactiae; Time Factors; Treatment Outcome

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

Topics: Acute Disease; Anti-Bacterial Agents; Autoimmune Diseases; Azithromycin; Behavior Therapy; Child; Diagnosis, Differential; Humans; Male; Obsessive-Compulsive Disorder; Penicillins; Streptococcal Infections

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacteremia; Biomarkers; Ceftriaxone; Diagnosis, Differential; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Male; Oseltamivir; Pneumonia, Bacterial; Streptococcal Infections; Streptococcus

The early shortage of novel coronavirus disease (COVID-19) tests in the United States led many hospitals to first screen for common respiratory pathogens, and only if this screen was negative to proceed with COVID-19 testing. We report a case of a 56-year-old woman with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coinfection with group A

Topics: Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; Ceftriaxone; Chicago; Chronic Pain; Coinfection; Coronavirus Infections; COVID-19; Extracorporeal Membrane Oxygenation; Female; Humans; Hydroxychloroquine; Hypertension; Lung; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Streptococcal Infections; Streptococcus pyogenes; Tomography, X-Ray Computed; Treatment Outcome

In 2016, we detected an outbreak of group A Streptococcus (GAS) invasive infections among the estimated 1000 persons experiencing homelessness (PEH) in Anchorage, Alaska. We characterized the outbreak and implemented a mass antibiotic intervention at homeless service facilities.. We identified cases through the Alaska GAS laboratory-based surveillance system. We conducted emm typing, antimicrobial susceptibility testing, and whole-genome sequencing on all invasive isolates and compared medical record data of patients infected with emm26.3 and other emm types. In February 2017, we offered PEH at 6 facilities in Anchorage a single dose of 1 g of azithromycin. We collected oropharyngeal and nonintact skin swabs on a subset of participants concurrent with the intervention and 4 weeks afterward.. From July 2016 through April 2017, we detected 42 invasive emm26.3 cases in Anchorage, 35 of which were in PEH. The emm26.3 isolates differed on average by only 2 single-nucleotide polymorphisms. Compared to other emm types, infection with emm26.3 was associated with cellulitis (odds ratio [OR], 2.5; P = .04) and necrotizing fasciitis (OR, 4.4; P = .02). We dispensed antibiotics to 391 PEH. Colonization with emm26.3 decreased from 4% of 277 at baseline to 1% of 287 at follow-up (P = .05). Invasive GAS incidence decreased from 1.5 cases per 1000 PEH/week in the 6 weeks prior to the intervention to 0.2 cases per 1000 PEH/week in the 6 weeks after (P = .01).. In an invasive GAS outbreak in PEH in Anchorage, mass antibiotic administration was temporally associated with reduced invasive disease cases and colonization prevalence.

Topics: Adolescent; Adult; Alaska; Anti-Bacterial Agents; Azithromycin; Bacterial Outer Membrane Proteins; Disease Outbreaks; Epidemiological Monitoring; Fasciitis, Necrotizing; Female; Humans; Ill-Housed Persons; Incidence; Male; Mass Drug Administration; Medical Records; Middle Aged; Polymorphism, Single Nucleotide; Prevalence; Streptococcal Infections; Streptococcus pyogenes; Whole Genome Sequencing; Young Adult

We identified risk factors for any emm type group A streptococcal (GAS) colonization while investigating an invasive emm26.3 GAS outbreak among people experiencing homelessness in Alaska. Risk factors included upper extremity skin breakdown, sleeping outdoors, sharing blankets, and infrequent tooth brushing. Our results may help guide control efforts in future outbreaks.

Topics: Adolescent; Adult; Alaska; Anti-Bacterial Agents; Azithromycin; Disease Outbreaks; Female; Genotype; Humans; Ill-Housed Persons; Male; Middle Aged; Risk Factors; Skin; Streptococcal Infections; Streptococcus pyogenes; Surveys and Questionnaires; Young Adult

Streptococcus pyogenes, or group A streptococcus (GAS), is the main etiological agent of bacterial tonsillopharyngitis and a common cause of a wide variety of other mild to severe infections.. Objectives of the present study was to determine and evaluate the distribution of genetic mechanisms associated with certain phenotypes of macrolide resistance in Bulgarian GAS isolated during the years of 2013-2016.. All GAS strains were screened for the macrolide resistance genes erm(A), erm(B) and mef(A), using multiplex polymerase chain reaction (PCR). The minimal inhibitory concentrations (MICs) of erythromycin, azithromycin, clarithromycin, clindamycin were determined by E-tests.. Almost 23% of GAS isolates obtained in 2013-2014 and near 40% of them in 2015-2016 contained various elements of resistance. The predominant gene was mef(A), which encodes an efflux pump (M-phenotype), identified in 57.84% of the macrolide-resistant strains. The next frequently prevalent mechanism was a combination of mef(A) and erm(B) in 22.55%, which determined high-level inducible or constitutive resistance to macrolides, lincosamides and streptogramins (iMLSB or cMLSB). The highest MIC value (>256mg/L) was detected in association with erm(B) (p<0.05). The MIC range was observed to be much higher in the isolates with combinations of resistance genes vs. those with mef genes alone (p<0.05).. The data about the distribution and prevalence of macrolide resistance mechanisms obtained in this study can help in the treatment of persistent and recurrent GAS infections and in the correct choice of empiric therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Proteins; Bulgaria; Child; Child, Preschool; Clarithromycin; Clindamycin; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Infant; Macrolides; Male; Membrane Proteins; Methyltransferases; Microbial Sensitivity Tests; Middle Aged; Multiplex Polymerase Chain Reaction; Streptococcal Infections; Streptococcus pyogenes; Young Adult

Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation.. TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end.. GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005).. Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Azithromycin; Cell Line; Cytokines; Drug Therapy, Combination; Female; Mice; Sepsis; Streptococcal Infections

The frequency and mechanisms of resistance to macrolides in Streptococcus.pyogenes isolated within 3 periods: 2011-2012 (246 strains), 2013-2014 (273 strains) and from January to November of 2015 (120 strains) were studied. The strains of S.pyogenes (639) were isolated from 17107 nasopharyngeal, vaginal and middle ear discharge smears of children on their visits to physiciants or hospitalization at somatic hospital departments. The susceptibility was tested by the disk diffusion method and E-test strips. Identification of the mechanisms of resistance to macrolides and lincosamides included phenotypic and molecular genetic methods. PCR was used to determine ermB and mef genes in 23 erythromycin resistant isolates. As compared to 2011-2012, resistance of S.pyogenes to macrolides increased from 5 to 16% in 2015 and that to clindamycin from 2 to 10%. Among 23 erythromycin resistant strains 6 (26.1%) belonged to the M phenotype, 3 (13.0%) belonged to the iMLS(b) phenotype and 14 (60.9%) belonged to the cMLS(b) pheno-type. The results of detecting the macrolide resistance genes in S.pyogenes showed that only 26.1% of the isolates expressed the mefA gene. The predominant share (65.2%) of the erythromycin resistant isolates possesed the ermB gene as a determinant and in 4.3% of the isolates the ermB gene was associatied with the mefgene. No resistance genes were detected 1 isolate. Therefore, the main mech- anism that determined resistance of S.pyogenes to macrolides was methylation of ribosomes mediated by the ermB gene.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Child; Clarithromycin; Clindamycin; Drug Resistance, Multiple, Bacterial; Ear, Middle; Erythromycin; Female; Gene Expression; Genotype; Humans; Male; Membrane Proteins; Methylation; Microbial Sensitivity Tests; Nasopharynx; Phenotype; Ribosomes; Streptococcal Infections; Streptococcus pyogenes; Vagina

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; Bacteremia; Drug Therapy, Combination; Endophthalmitis; Female; Humans; Hypercholesterolemia; Hypertension; Middle Aged; Patient Transfer; Penicillin G; Risk Factors; Streptococcal Infections; Streptococcus pneumoniae; Treatment Outcome; Vancomycin; Vitrectomy

Resistant pathogens are an increasing threat affecting millions of people globally. More complicated patients are presented with pathogens harboring new resistance mechanisms, while the pipeline of new antimicrobials hardly proposes solutions. In such a scenario, more severely ill patients remain with no adequate treatment to offer. In addition, massive misuse of antimicrobials, including excessive length of treatment or wrong dosage, also contributes to increasing the rate of pathogens resistance to antimicrobials. Isolation of Streptococcus pyogenes (Group A Streptococcus-GAS) is the main indication for antibiotic treatment to patients diagnosed with acute tonsillitis. Hence, GAS resistance to antibiotics requires periodic monitoring.. To assess susceptibility rates of GAS to penicillin, macrolides, clindamycin, and tetracycline in northern Israel and to compare the findings to the high antimicrobial susceptibility of GAS isolates reported in the same region in 2004 and to other geographical areas.. Throat samples from 300 outpatients were collected and cultured at the regional laboratory of Emek Medical Center during September to October 2011.. In 300 samples, the susceptibility rates of GAS to penicillin, erythromycin, azithromycin, clindamycin, and tetracycline in northern Israel still remain very high.. Continuous control of antimicrobials usage and periodic surveillance of susceptibility rates, together with educational programs and appropriate and targeted treatment protocols, are essential and highly recommended to keep these high susceptibility rates for as long as possible.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Clindamycin; Drug Resistance, Bacterial; Epidemiological Monitoring; Erythromycin; Female; Humans; Israel; Male; Microbial Sensitivity Tests; Penicillins; Streptococcal Infections; Streptococcus pyogenes; Tetracycline; Tonsillitis; Young Adult

A series of novel alkylides, possessing 3-O-arylalkyl group instead of 3-O-cladinose, were designed, synthesized and evaluated for in vitro antibacterial activities. The increased potency clearly ranked by the order of 3-O-(3-aryl-2-propargyl), 3-O-(3-aryl-E-prop-2-enyl), 3-O-(3-aryl-propyl), and 3-O-(3-aryl-Z-prop-1-enyl) groups. Some alkylides, exemplified by 7a, 10a, 21, 22, 26, 27 and 33, showed improved activities against inducible MLS(B) resistance and efflux resistance compared to the second-generation macrolides. Among them, 26 possessed comparable activities against erythromycin-susceptible Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes (MICs of 0.016-0.5 μg/mL). Moreover, 26 displayed dramatically enhanced potency against both efflux resistant and inducibly MLS(B) resistant strains (MICs of 0.125-0.5 μg/mL) resistant to clarithromycin and azithromycin (MICs of 1- >254 μg/mL), independent of methicillin-susceptible and methicillin-resistant phenotypes.

Topics: Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Multiple, Bacterial; Humans; Macrolides; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Streptococcus pneumoniae; Streptococcus pyogenes; Structure-Activity Relationship

Streptococcus pyogenes or group A streptococcus (GAS) is responsible for serious invasive infections with a risk of secondary infection in patients with more contact than in the general population. Regardless of clustering, few intrafamilial invasive infections have been reported despite a recent increase in the incidence of invasive GAS disease. We report the cases of two brothers, one a boy of 8.5 years with toxic shock syndrome with no bacteria identified and the second, 1 week later, his 14.5-year-old brother in hospital for sepsis due to GAS. The occurrence of a confirmed case of invasive GAS and a probable case within such a short period met the definition of clustered cases. Both brothers showed no risk factors for invasive disease and no gateway including skin was found. Antibiotic therapy was initiated in the family as recommended by the French Higher Council of Public Hygiene.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacteremia; Ceftriaxone; Chemoprevention; Child; Clindamycin; Cluster Analysis; Drug Therapy, Combination; Emergencies; Family; Humans; Male; Risk Factors; Severity of Illness Index; Shock, Septic; Siblings; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

Group A streptococci (GAS) are responsible for up to 30% of cases of pharyngitis in children, and such children do not benefit from treatment with antibiotics. During the last decade, increased resistance to macrolides has emerged as a critical issue in the treatment of GAS pharyngitis. The objective of this study was to determine the antimicrobial resistance of group A beta haemolytic Streptococcus isolated from outpatient children. From 2002 to 2006, 96 GAS strains were obtained from the pharynx of outpatients having symptoms of acute pharyngitis. Antibiotic resistance was determined by disc susceptibility tests according to CLSI standards. The presence of ermA, ermB and mefA was established by the amplification of streptococcal DNA with specific primers. Antimicrobial susceptibility tests revealed that all the strains tested were sensitive to vancomycin, linezolid, penicillin and ceftriaxone. Simultaneously, high levels of resistance to macrolides were evident; 78% of the isolates were resistant to clindamycin and erythromycin. No significant change in the yearly or seasonal incidence of resistance was observed. We describe high antimicrobial resistance of GAS to macrolides in outpatient children (78%), which can be explained by the frequent use of macrolides in the treatment of such individuals. Therefore, macrolides should not be the first drug of choice.

Topics: Azithromycin; Bacterial Proteins; Child; Child, Preschool; Clindamycin; Drug Resistance, Bacterial; Erythromycin; Genes, Bacterial; Humans; Latvia; Macrolides; Membrane Proteins; Methyltransferases; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes

A series of new 4'',11-di-O-arylalkylcarbamoyl azithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. Some derivatives exhibited greatly improved activity against erythromycin-resistant bacteria. Among them, compounds 5f and 5k were found to have potent activity against erythromycin-resistant Streptococcus pneumoniae whose resistance was encoded by the erm or mef gene.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Chemistry, Pharmaceutical; Drug Design; Drug Resistance, Multiple, Bacterial; Macrolides; Membrane Proteins; Methyltransferases; Microbial Sensitivity Tests; Models, Chemical; Streptococcal Infections; Streptococcus pneumoniae

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

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

4''-Carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin were designed, synthesized and evaluated. The 4''-carbamate analogs retained excellent activity against erythromycin-susceptible Staphylococcus pneumoniae and showed improved activity against erythromycin-resistant Staphylococcus pneumoniae. Compared with 4''-carbamate analogs, 11,12-cyclic carbonate-4''-carbamate analogs exhibited improved activity against erythromycin-resistant Staphylococcus pneumoniae encoded by the mef gene or the erm and mef genes, and 11,4''-di-O-arylalkylcarbamoyl analogs showed greatly improved activity (0.25-0.5 microg/mL) against erythromycin-resistant Staphylococcus pneumoniae encoded by the erm gene. Among them, the novel series of 11,4''-di-O-arylalkylcarbamoyl analogs 7a-k exhibited potent and balanced activity against susceptible and resistant bacteria. In particular, compounds 7f and 7k were the most effective against susceptible bacteria and resistant bacteria encoded by the erm gene or the mef gene.

Topics: Anti-Bacterial Agents; Azithromycin; Carbamates; Carbonates; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus pneumoniae

Although long-term use of azithromycin has shown a significant clinical improvement for patients with cystic fibrosis (CF), its long-term effect on the susceptibility of commensal flora within CF airways has not yet been examined. We therefore suggest that long-term use of azithromycin increases macrolide resistance in commensal streptococci.. Erythromycin susceptibility in naturally colonizing viridans group streptococci (VGS) was characterized, as well as macrolide resistance gene determinants through sequence analysis, in pneumococci (n = 15) and VGS [n = 84; i.e. Streptococcus salivarius (n = 30), Streptococcus mitis (n = 17), Streptococcus sanguinis (n = 11), Streptococcus oralis (n = 10), Streptococcus parasanguinis (n = 6), Streptococcus gordonii (n = 3), Streptococcus infantis (n = 3), Streptococcus cristatus (n = 2), Streptococcus anginosus (n = 1) and Streptococcus australis (n = 1)] isolated from sputum from 24 adult CF patients, who were on oral azithromycin therapy for at least the previous 7 months.. Almost three-quarters of isolates (74; 74.7%) were resistant to erythromycin, whilst a further 15 (15.2%) had reduced susceptibility, leaving only 10 (10.1%) isolates susceptible to erythromycin. The majority (89.8%) were not susceptible to erythromycin, as demonstrated by possession of the erm(B) gene in 25/99 (25.3%), the mef(A) gene in 1/99 (1.0%), the mef(E) gene in 75/99 (75.8%) and both erm(B) and mef(E) genes simultaneously in 11/99 (11.1%). These results indicate that genotypic resistance for macrolides is common in VGS in adult CF patients, with efflux being over three times more frequent.. Long-term treatment with azithromycin in CF patients may reduce antibiotic susceptibility in commensal VGS, where these organisms may potentially act as a reservoir of macrolide resistance determinants for newly acquired and antibiotic-susceptible pathogens.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Cystic Fibrosis; DNA, Bacterial; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; Membrane Proteins; Methyltransferases; Microbial Sensitivity Tests; Molecular Sequence Data; Sequence Analysis, DNA; Streptococcal Infections; Streptococcus

Many studies have shown a correlation between higher consumption of long-acting macrolides and the development of resistance of S. pyogenes but, to our knowledge, no studies have reported the disappearance of S. pyogenes macrolide resistance. We evaluated the possible relationship between the rational use of long-acting macrolide consumption and the disappearance of S. pyogenes erythromycin resistance in an area of northeastern Italy, the district of Pordenone (approximately 300,000 inhabitants). The emerging use of new long-acting macrolides, especially since 1993, has caused a great increase in total macrolide consumption (expressed as defined daily doses per 1,000 inhabitants per day; DDDs), followed by a steady increase in the percentage of S. pyogenes resistant to erythromycin (from 4% in 1994 to 56.3% in 2000). Subsequently, from 2000 to 2007, the maintenance of steady-high DDDs of clarithromycin but low DDDs of azithromycin resulted in a sharp decrease in the percentage of S. pyogenes resistance to erythromycin (from 33.3% in 2001 to 0.2% in 2008). Disappearance of S. pyogenes erythromycin resistance in the last few years, compared with data of long-acting macrolide consumption from 2000 to 2007, suggests that S. pyogenes resistance to erythromycin is more likely associated with the specific type of compound used rather than with total consumption of long-acting macrolides.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Delayed-Action Preparations; Drug Resistance, Multiple, Bacterial; Drug Utilization; Erythromycin; Humans; Italy; Macrolides; Streptococcal Infections; Streptococcus pyogenes

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Humans; India; Penicillin G Benzathine; Pharyngitis; Practice Guidelines as Topic; Rheumatic Fever; Rheumatic Heart Disease; Streptococcal Infections

This study compared the in vitro activity of telithromycin with that of azithromycin against 438 Streptococcus pyogenes and 198 Streptococcus pneumoniae, isolated over the period 2005-2007 from specimens of different human origin obtained in three Piemonte Region's hospitals.. The determination of antimicrobial activity was evaluated by the microdilution broth method and the erythromycin-resistant (Ery-R) phenotypes by the triple-disc test. Exactly 78.8% of S. pyogenes and 69.2% of S. pneumoniae were erythromycin-susceptible (Ery-S). Concerning S. pyogenes, telithromycin was active against M and inducible MLS(B), subtype-C, phenotypes but not against constitutive MLS(B) strains. Telithromycin acted well against all S. pneumoniae, irrespective of their mechanism of macrolide-resistance. On the contrary, the Ery-R isolates, both S. pyogenes and S. pneumoniae, were resistant to azithromycin.. Our results indicate that macrolide resistance in streptococci still persist in northwest Italy (21.2% of S. pyogenes and 308% of S. pneumoniae) and that telithromycin is confirmed as being extremely active even against recent clinical Ery-R streptococcal isolates.. The present study emphasizes that an active surveillance of the phenotype distribution and antibacterial resistance in streptococci is essential in guiding the effective use of empirical treatment option for streptococcal infections, also at regional level.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Bacterial; Erythromycin; Humans; Italy; Ketolides; Microbial Sensitivity Tests; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

Topics: Anti-Bacterial Agents; Azithromycin; Bacteremia; Bacterial Proteins; Drug Resistance, Bacterial; Exotoxins; Humans; Macrolides; Membrane Proteins; Microbial Sensitivity Tests; Prevalence; Streptococcal Infections; Streptococcus pyogenes; Virulence

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Bacterial; Humans; Macrolides; Streptococcal Infections; Streptococcus

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Bacterial; Humans; Pharyngeal Diseases; Randomized Controlled Trials as Topic; Streptococcal Infections

This study shows a significant association between the number of macrolide prescriptions reimbursed by the Italian National Health Service and resistance of Streptococcus pyogenes to erythromycin in children from a region in northern Italy with high prevalence of erythromycin resistance. Recent prescription of a macrolide (especially azithromycin) is a predictor of erythromycin resistance, as well as a possible risk factor for resistance at a community level.

Topics: Adolescent; Azithromycin; Child; Child, Preschool; Drug Resistance, Bacterial; Erythromycin; Humans; Infant; Italy; Macrolides; Microbial Sensitivity Tests; State Medicine; Streptococcal Infections; Streptococcus pyogenes

From 2002 to 2003, a total of 381 consecutive S. pyogenes isolates were obtained from throat swabs (n = 337) and samples of pus (n = 31), sputum (n=10) and blood (n = 3) at Hacettepe University Hospital. The susceptibility of the isolates to erythromycin was tested by the agar dilution method. Erythromycin resistant strains were then tested for their MICs to azithromycin, clindamycin, and penicillin, their phenotype of resistance to macrolides-lincosamides-streptogramin B (MLSB) and for the presence of macrolide resistance genes. The rate of resistance to erythromycin was 6.8%. Constitutive (cMLSB), inducible (iMLSB), and M phenotypes of resistance were detected in 7.7, 30.8, and 57.7% of resistant strains, respectively. One strain had both cMLSB and iMLSB phenotypes. All M phenotypes carried the mefA gene, all iMLSB phenotype carried the ermTR gene, 1 isolate with cMLSB phenotype harboured the ermB gene, and 1 isolate with cMLSB phenotype carried both the ermB and mefA genes. One strain which showed cMLSB and iMLSB phenotypes harboured the ermB gene.

Topics: Azithromycin; Clindamycin; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; Microbial Sensitivity Tests; Penicillins; Streptococcal Infections; Streptococcus pyogenes; Turkey

Group B streptococcus (GBS) is a leading cause of serious neonatal infection. Neonatal morbidity and mortality can be reduced by appropriate prenatal screening and intrapartum chemoprophylaxis.. A 20-year-old primigravida was treated with oral antibiotics at 35 weeks for a recurrent urinary tract infection. Her GBS screen following the antibiotic treatment showed a negative culture. The patient, therefore, did not receive intravenous antibiotics during her induction of labor for mild preeclampsia. The infant developed early onset neonatal GBS pneumonia and sepsis.. Oral antibiotics can cause a temporary negative culture in a GBS-colonized patient. Relying on a negative culture for management may not be appropriate in a patient treated with oral antibiotics. Additional studies are necessary to elucidate the effects of oral antibiotics on GBS.

Topics: Administration, Oral; Adult; Azithromycin; Bacteremia; Combined Modality Therapy; False Negative Reactions; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Risk Assessment; Streptococcal Infections; Streptococcus agalactiae; Treatment Outcome; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Autoimmune Diseases of the Nervous System; Azithromycin; Child; Humans; Mental Disorders; Penicillins; Randomized Controlled Trials as Topic; Research Design; Sample Size; Streptococcal Infections

Topics: Anti-Bacterial Agents; Autoimmune Diseases of the Nervous System; Azithromycin; Child; Humans; Mental Disorders; Penicillins; Randomized Controlled Trials as Topic; Research Design; Sample Size; Streptococcal Infections

From January 1993 to December 2002, 28 patients with nutritionally variant streptococci (NVS) infections were treated at a university hospital in Taiwan. Twelve (43%) of these patients had various underlying malignancies, and 7 (25%) had underlying valvular heart diseases. Nine patients (32%) had infective endocarditis, and 9 (32%) had primary bacteremia. The deaths of 7 patients (25%) were directly related to NVS infection. Among the 28 isolates recovered from these patients, 50% were not susceptible to penicillin, 33% were not susceptible to cefotaxime, and 93% were not susceptible to azithromycin.

Topics: Adolescent; Adult; Aged; Azithromycin; beta-Lactam Resistance; Cefotaxime; Child; Drug Resistance, Bacterial; Female; Hospitals, University; Humans; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Streptococcal Infections; Streptococcus; Taiwan

In the present study, the minimal inhibitory concentration (MIC) of azithromycin and roxithromycin for 200 Streptococcus pyogenes isolates from outpatients with tonsillopharyngitis were determined using Etest. All but one (99.5%) of the isolates were sensitive to both antibiotics; the MIC of the resistant isolate being 12 mg/l to azithromycin and 32 mg/l to roxithromycin. In this region, macrolides remain the drug of choice for the treatment of patients with S. pyogenes tonsillitis who present allergy to penicillin. The routine testing of susceptibility of S. pyogenes to macrolides in northern Israel is not justified.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Humans; Israel; Microbial Sensitivity Tests; Penicillins; Pharyngitis; Roxithromycin; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

A total of 341 clinical isolates of Streptococcus pyogenes from Vienna, Austria and three Hungarian cities were tested for susceptibility to four macrolides and 12 other antibiotics. All isolates were fully susceptible to penicillin and the other beta-lactams tested. A high level of tetracycline resistance was found in Austria (26.7%) and in Hungary (30.5%). The rate of resistance to erythromycin, clarithromycin and azithromycin was 4.7% in Vienna and 3.7% in the Hungarian communities. In both countries, the MIC(90) values of erythromycin and clarithromycin were 0.12 mg/L and the MIC(90) of josamycin was 0.5mg/L. The M phenotype of resistance conferred by the mefA genes was predominant (n = 9) among the macrolide-resistant isolates (n = 14).

Topics: Anti-Bacterial Agents; Austria; Azithromycin; Bacterial Proteins; beta-Lactams; Clarithromycin; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Hungary; Josamycin; Macrolides; Membrane Proteins; Microbial Sensitivity Tests; Pharyngitis; Pharynx; Skin; Streptococcal Infections; Streptococcus pyogenes; Tetracycline Resistance; Tonsillitis; Vagina

A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Area Under Curve; Drug Resistance, Multiple, Bacterial; Erythromycin; Haemophilus influenzae; Macrolides; Mice; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Streptococcal Infections; Streptococcus pneumoniae; Structure-Activity Relationship

We evaluated the activities of clarithromycin and azithromycin against 19 isolates of Streptococcus pneumoniae using a neutropenic lung infection model. The isolates included five susceptible isolates (clarithromycin and azithromycin MICs, /=64 micro g/ml). Infected mice were administered either saline (control), clarithromycin (4, 40, or 200 mg/kg of body weight twice daily or 200 mg/kg once daily), or azithromycin (4, 40, or 200 mg/kg once daily or 40 mg/kg twice daily) by oral gavage for 72 h. Mortality was assessed at regular intervals for 10 days, and survival in each group was compared to that of untreated controls. Animals infected with susceptible isolates demonstrated significant improvement in survival compared to the controls following treatment with either agent at doses of >/=40 mg/kg. In contrast, none of the regimens improved the survival of animals infected with isolates exhibiting high-level macrolide resistance. Among mice infected with strains expressing low-level resistance, significant improvement in survival compared to the controls was noted among isolates treated with clarithromycin at 40 (seven of nine isolates) and 200 (nine of nine isolates) mg/kg twice a day and with azithromycin at 40 (one of nine isolates) and 200 (three of nine isolates) mg/kg once a day. Animals infected with isolates of S. pneumoniae exhibiting low-level, mefA-mediated macrolide resistance responded to treatment with clarithromycin at rates similar to those observed among mice infected with fully susceptible isolates.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Clarithromycin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Half-Life; Humans; Lung Diseases; Mice; Microbial Sensitivity Tests; Serotyping; Streptococcal Infections; Streptococcus pneumoniae

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

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

To study the emergence of macrolide resistance in throat flora following treatment with clarithromycin or azithromycin.. Throat samples were collected before and after treatment and plated as a lawn on Columbia blood agar with an erythromycin E test strip. Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin and azithromycin were determined against isolates of distinct morphology with erythromycin E test MIC results equal to or greater than 2 mg/L. Polymerase chain reaction techniques were used to determine the genetic mechanisms of resistance.. There were 749 resistant isolates of which 474 (63%) were streptococci. Only a quarter of the patients had no resistant streptococci before treatment started. There were increases in the numbers of resistant isolates and in the number of patients carrying a resistant flora during and after treatment. The most common genes identified were mefA/E in isolates with low-level resistance and ermA/M in isolates with high-level resistance.. There is a pool of streptococci carrying genes associated with macrolide resistance in the normal respiratory flora of generally healthy adults. Differences between the patients treated with clarithromycin and those treated with azithromycin were difficult to assess because of the large number of patients in each group with macrolide-resistant streptococci before treatment. Although there were some differences these were not statistically significant.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Bacterial; Erythromycin; Humans; Microbial Sensitivity Tests; Pharynx; Polymerase Chain Reaction; Streptococcal Infections; Streptococcus

Topics: Anti-Bacterial Agents; Azithromycin; Cephalosporins; Humans; Penicillin Resistance; Pharyngitis; Streptococcal Infections

We compared recommended doses of 2 oral macrolide antibiotics (10 days of clarithromycin, 5 days of azithromycin) for eradicating group A streptococci from the throats of individuals aged > or = 12 years with symptomatic pharyngitis and a positive throat culture. Patients received either clarithromycin (250 mg b.i.d. for 10 days [n=260]) or azythromycin (500 mg on day 1, followed by 250 mg q.d. for 4 days [n=265]). Follow-up throat cultures were obtained both at 13--19 days and at 28--38 days. We evaluated 392 patients (median age, 26 years; clarithromycin, 194 patients; azyithromycin, 198 patients). Ten days of clarithromycin therapy was more effective than 5 days of azithromycin therapy in eradicating the organism (91% [176/194] vs. 82% [162/198]; P=.012). More than 97% of all streptococcal isolates were macrolide-sensitive. Whether these bacteriologic eradication rates were the result of the 2 macrolides compared or were due to differences in duration of therapy could not be determined, but the statistically significant difference in eradication of group A streptococci does raise additional questions about shortened courses of macrolide therapy for this common infection.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Clarithromycin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Microbial; Humans; Male; Microbial Sensitivity Tests; Military Personnel; Streptococcal Infections; Streptococcus

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

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

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Aortic Valve; Azithromycin; Endocarditis, Bacterial; Female; Rabbits; Staphylococcal Infections; Streptococcal Infections

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Humans; Otitis Media; Pneumonia, Bacterial; Soft Tissue Infections; Streptococcal Infections; Streptococcus pyogenes; Whooping Cough

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Microbial; Drug Tolerance; Humans; Infant; Microbial Sensitivity Tests; Penicillin V; Penicillins; Pharyngitis; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

Topics: Anti-Bacterial Agents; Azithromycin; Clinical Trials as Topic; Drug Administration Schedule; Follow-Up Studies; Humans; Penicillin V; Penicillins; Pharyngitis; Prognosis; Streptococcal Infections

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

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

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

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

We compared the activities of azithromycin, erythromycin, and penicillin G in a mouse model of systemic infection and septic arthritis induced by type IV group B streptococci (GBS). The in vitro and in vivo efficacy data for these drugs were analyzed relative to the pharmacokinetics of the drugs in sera, joints, and kidneys. Adult CD-1 mice were infected intravenously with 10(7) CFU of type IV GBS. Intraperitoneal drug administration was initiated with different dose regimens at different times after infection. A single dose of azithromycin (100 mg/kg) strongly reduced the incidence of articular lesions with respect to that with erythromycin or penicillin G. Treatment with azithromycin (three intraperitoneal administrations of 50 mg/kg at 12-h intervals) resulted in the complete prevention of arthritis. In contrast, erythromycin was poorly effective and penicillin G was effective only if inoculated 30 min after infection and at high doses (400,000 or 600,000 IU/kg). Furthermore, azithromycin was able to cure about 70% of the mice when administered 7, 8, and 9 days after GBS infection. Azithromycin was much more active than erythromycin and penicillin G with respect to bacterial killing in the joints and kidneys. In fact, cultures from these tissues were always negative no matter what treatment schedule was employed. The pharmacokinetics of azithromycin account for its superior in vivo efficacy against type IV GBS. A longer half-life and higher levels of this drug in serum and tissues with respect to those for erythromycin or penicillin G were achieved. The high affinity of azithromycin for the joints strongly supports its potential value for therapy of septic arthritis, which is a severe and frequent clinical manifestation of GBS infection.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Infectious; Azithromycin; Chronic Disease; Erythromycin; Female; Joints; Kidney; Male; Mice; Microbial Sensitivity Tests; Penicillin G; Penicillins; Streptococcal Infections; Streptococcus agalactiae

High throughput chemical file screening with an enzymatic assay to detect inhibitors of the ErmC methyltransferase enzyme from macrolide-lincosamide-streptogramin B (MLSB) resistant pathogenic bacteria identified low molecular weight compounds that had IC50S (50% inhibitory concentration) in the nMolar to microMolar range. These same inhibitors were assessed in vitro for their capacity to inhibit the liver enzyme, cathechol-O-methyltransferase and the prokaryotic enzyme, EcoRI methylase. Selective inhibitors of the ErmC methyltransferase were tested in tertiary assays to determine their minimal inhibitory concentrations (MICs), as single agents and in combination with the macrolide, azithromycin, against strains of pathogenic bacteria expressing MLSB-resistance. Compounds that were active in vitro, alone or in combination with azithromycin, against strains of macrolide-resistant pathogens were tested in a mouse model of infection using an MLSB-resistant strain of Staphylococcus aureus or a macrolide-susceptible strain of Streptococcus pyogenes.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Enzyme Inhibitors; Lincosamides; Macrolides; Methyltransferases; Mice; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes; Virginiamycin

Some recently introduced macrolides have several clinical advantages over erythromycin. Azithrommcin, a prototype of these new macrolides could be a good alternative for the treatment of streptococcal pharyngitis, even over penicillin, whose failure rate can be as high as 30%. The aim of this study was to evaluate the in vitro susceptibility of 120 strains of S pyogenes isolated between 1990 and 1992 (40 per year), from diverse infections (specially tonsillitis). We determined Minimal Inhibitory Concentrations (MIC) of azithromycin, clarithromycin, roxithromycin, erythromycin and penicillin using the agar dilution method and the Minimal Bactericidal Concentration (MBC) by tube dilution for azythromycin and erythromycin. The MIC 90 for the new macrolides ranged from 0.03 to 0.12 microgram/ml, and was 0.03 microgram/ml for erythromycin and penicillin (not different). All strains were susceptible to all antibiotics and the date of isolation did not influence susceptibility. The MBC for azithromycin was 0.12 microgram/ml (identical to its MIC), which demonstrates the bactericidal effect of this antibiotic. It is concluded that this in vitro data supports the potential role of these new macrolides in the treatment of streptococcal infections.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Microbial; Erythromycin; In Vitro Techniques; Microbial Sensitivity Tests; Penicillins; Roxithromycin; Streptococcal Infections; Streptococcus pyogenes; Time Factors

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.

Topics: Administration, Oral; Adolescent; Azithromycin; Child; Child, Preschool; Erythromycin; Female; Half-Life; Humans; Male; Pharyngitis; Streptococcal Infections; Suspensions

Since serious sequelae may follow streptococcal infections, eradication is viewed as necessary for successful therapy. Studies were therefore conducted to compare the effectiveness of azithromycin with other macrolide antibiotics and amoxycillin to eliminate these organisms in experimental localized infections. In a Streptococcus pneumoniae lung infection induced by transtracheal challenge, the pathogen was not recovered after therapy with azithromycin (ED50 7.9 mg/kg), while clarithromycin was not effective (ED50 > 100 mg/kg). However, in a S. pneumoniae middle ear infection, azithromycin and clarithromycin were effective (ED50 2.9 and 6.3 mg/kg, respectively) in eradicating the pathogen from this closed space infection. Against a localized Streptococcus pyogenes infection (implanted inoculated disc), azithromycin effectively eradicated the pathogen, while clarithromycin, roxithromycin and erythromycin did not. Eradication of a viridans streptococcus or Streptococcus gordonii (formerly Streptococcus sanguis) from heart tissue in experimental bacterial endocarditis was also evaluated. Azithromycin given prophylactically or therapeutically was efficacious in eliminating the viridans streptococcus and S. gordonii in the bacterial endocarditis model of infection; erythromycin was only marginally effective in the same studies. All studies provided evidence of the bactericidal action of azithromycin in vivo and demonstrated the ability of the compound to eradicate streptococcal pathogens in localized infections.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Disease Models, Animal; Endocarditis, Bacterial; Erythromycin; Female; Gerbillinae; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Otitis Media; Pneumococcal Infections; Pneumonia; Rats; Roxithromycin; Streptococcal Infections; Streptococcus pyogenes