Evaluation of the efficacy, safety and toleration of azithromycin vs. penicillin V in the treatment of acute streptococcal pharyngitis in children: results of a multicenter, open comparative study

Schaad, Urs B.; Heynen, G

doi:10.1097/00006454-199609000-00011

Cited by 55 publications

(20 citation statements)

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“…In our work, the number of GAS isolates (7 of 135) that developed resistance to macrolides after low-dose azithromycin treatment was strikingly high (8). This phenomenon was not observed in three recent clinical trials of azythromycin treatment in patients with tonsillopharyngitis (4,16,18). In two studies (4, 18) the susceptibilities of the posttreatment isolates were not reported.…”

Section: Discussioncontrasting

confidence: 44%

Emergence of Group A Streptococcus Strains with Different Mechanisms of Macrolide Resistance

Bingen

Leclercq

Fitoussi

et al. 2002

Antimicrob Agents Chemother

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The mechanisms of resistance to macrolides in seven group A streptococcal (Streptococcus pyogenes) isolates that were the cause of pharyngitis in children who were unsuccessfully treated with azithromycin (10 mg/kg of body weight/day for 3 days) were evaluated. All posttreatment strains were found to be genetically related to the pretreatment isolates by random amplified polymorphism DNA analysis and pulsed-field gel electrophoresis. Two isolates had acquired either a mef(A) or an erm(B) gene, responsible for macrolide efflux and ribosomal modification, respectively. Three isolates displayed mutations in the gene encoding the L4 ribosomal protein that is part of the exit tunnel within the 50S subunit of the bacterial ribosome. In the two remaining posttreatment strains, the mechanisms of macrolide resistance could not be elucidated.The recommended treatment for group A Streptococcus (GAS) pharyngitis, a 10-day course of penicillin, was established 50 years ago and remains the "gold standard."However, for patients hypersensitive to ␤-lactam antibiotics and in whom therapy with these drugs fails, macrolides are often the recommended substitute. Azithromycin is an azalide antibiotic chemically related to erythromycin and has a long half-life and excellent tissue penetration. Short-course azithromycin therapy has been reported to be effective for the eradication of oropharyngeal GAS (14).In a prospective, comparative, randomized, multicenter trial that was conducted between November 1997 and July 1998 and that involved 350 children with GAS pharyngitis, we observed better eradication rates on days 14 and 30 after a 3-day course of therapy with azithromycin at 20 mg/kg of body weight/day than after a 3-day course of therapy with azithromycin at 10 mg/kg/day. In the per protocol analysis, the failure rates on day 14 were 57 of 135 (42.2%) in the 10-mg/kg treatment arm and 8 of 139 (5.8%) in the 20-mg/kg treatment arm (8). Furthermore, analysis of bacterial isolates by random amplified polymorphic DNA (RAPD) analysis revealed seven cases of bacteriological treatment failure: azithromycin MICs for genetically related pre-and posttreatment GAS strains increased after treatment with this antimicrobial at 10 mg/kg/day for 3 days. In contrast, azithromycin MICs were not increased for any of the strains from any of the patients with treatment failure in the group treated with azithromycin at 20 mg/kg/day (8). The known mechanisms of macrolide resistance in streptococci are modification of the ribosomal target by a methylase encoded by erm genes (13, 20) and a macrolide-specific efflux mechanism encoded by the mef(A) gene (7). Mutation of the ribosomal target of macrolides is a rare resistance mechanism in streptococci and has been reported in only a few clinical pneumococcal isolates (21).In the study described here we investigated the mechanisms of macrolide resistance among the GAS strains that were the cause of bacteriological treatment failures in the group treated with azithromycin at 10 mg/kg/day. MATERIALS AND METHODS...

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Section: Discussioncontrasting

confidence: 44%

Emergence of Group A Streptococcus Strains with Different Mechanisms of Macrolide Resistance

Bingen

Leclercq

Fitoussi

et al. 2002

Antimicrob Agents Chemother

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“…First, it is not known if the dose of AZM in this study is optimum. The dose of AZM used in this study, 10 mg/kg for children, may be insufficient [18], although both 10 or 20 mg/kg/day for 3 days has been shown to be equally safe and effective [9]. Another study indicated that 10 mg/kg was associated with a higher bacteriological relapse and an increased risk of bacteria gaining resistance in comparison with 20 mg/kg [13].…”

Section: Discussionmentioning

confidence: 80%

“…Furthermore, a longer treatment period may increase the risk of carriage of resistant S. pneumoniae strains [17]. A 3-day course of AZM, another alternative to penicillin, has been shown to have efficacy comparable with that of a 10-day course of penicillin V [18]. In this context, the importance of our study lies in comparison of the efficacy of the alternative treatments, a newer cephalosporin and AZM.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, the importance of our study lies in comparison of the efficacy of the alternative treatments, a newer cephalosporin and AZM. Furthermore, the clinical efficacy of AZM for GAS tonsillopharyngitis has only been evaluated after 10-17 days of enrollment [9,18]. Our study, where it was judged on the 4th and 8th days of the enrollment, added short-term clinical efficacy of AZM.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of short-term clinical efficacy of 3-day therapy with azithromycin in comparison with 5-day cefcapene-pivoxyl for acute streptococcal tonsillopharyngitis in primary care

Koga

Rikimaru

Tokunaga

et al. 2011

Journal of Infection and Chemotherapy

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“…The use of macrolides in the treatment of pharyngitis has been studied in several clinical trials [32,38,39,41,45,47,50,52,54]. These trials showed that in a 10-day treatment, erythromycin and cefprozil produced clinical response rates of 91% and 95%, respectively [45].…”

Section: Clinical Trialsmentioning

confidence: 99%

The use of macrolides in treatment of upper respiratory tract infections

Wierzbowski¹,

Hoban²,

Hisanaga³

et al. 2006

Curr Allergy Asthma Rep

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Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to beta-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to beta-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in both S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found to be responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species, producing an efflux pump (mef), and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.

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Evaluation of the efficacy, safety and toleration of azithromycin vs. penicillin V in the treatment of acute streptococcal pharyngitis in children: results of a multicenter, open comparative study

Abstract: 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.

Cited by 55 publications

References 15 publications

Emergence of Group A Streptococcus Strains with Different Mechanisms of Macrolide Resistance

Emergence of Group A Streptococcus Strains with Different Mechanisms of Macrolide Resistance

Evaluation of short-term clinical efficacy of 3-day therapy with azithromycin in comparison with 5-day cefcapene-pivoxyl for acute streptococcal tonsillopharyngitis in primary care

The use of macrolides in treatment of upper respiratory tract infections

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