BACKGROUND: 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 2021.
OBJECTIVES: 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.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023.
SELECTION CRITERIA: 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.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures recommended by Cochrane. We assessed the risk of bias in the 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 reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.
MAIN 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). Based on an analysis of evaluable participants, 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). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. 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 trial, 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial, 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial, 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials, 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better at preventing serious but rare complications.
AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high.
ANTECEDENTES: La duración estándar del tratamiento de la faringoamigdalitis aguda por estreptococo beta hemolítico grupo A (EBHGA) en niños con penicilina oral es de 10 días. Los tratamientos acortados pueden tener una eficacia comparable.
OBJETIVOS: Resumir la evidencia acerca de la eficacia de tratamientos de dos a seis días de duración con nuevos antibióticos orales (duración abreviada) en comparación con los 10 días de penicilina oral (duración estándar) en el tratamiento de la faringitis aguda por EBHGA en niños.
ESTRATEGIA DE BÚSQUEDA: Se realizó la búsqueda en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL)( 2012, número 3), que contiene el Registro Especializado del Grupo Cochrane de Infecciones Respiratorias Agudas (Cochrane Acute Respiratory Infections Group’s Specialized Register), MEDLINE (desde enero de 1966 hasta marzo, semana 3, 2012) y EMBASE (desde enero de 1990 hasta abril de 2012).
CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) que compararan tratamientos antibióticos orales abreviados con el tratamiento de duración estándar con penicilina oral en niños de 1 a 18 años con faringitis aguda por EBHGA.
OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos de los autores de la revisión examinaron los títulos y resúmenes de las citas recuperadas y aplicaron los criterios de inclusión. Se recuperaron los estudios incluidos en su totalidad y se extrajeron los datos. Dos autores de la revisión evaluaron de forma independiente la calidad de los ensayos.
RESULTADOS PRINCIPALES: Se incluyeron 20 estudios con 13.102 casos de faringitis aguda por EBHGA. La búsqueda actualizada no identificó nuevos estudios elegibles. La mayoría de los estudios tenían un alto riesgo de sesgo, sin embargo, la mayoría de los resultados fueron consistentes. En comparación con el tratamiento de duración estándar, los tratamientos abreviados tuvieron períodos más cortos de fiebre (diferencia de medias (DM) -0,30 días; intervalo de confianza (IC) del 95%: -0,45 a -0,14) y de odinofagia (DM -0,50 días; IC 95%: -0,78 a -0,22); menor riesgo de fracaso clínico precoz del tratamiento (odds ratio (OR) 0,80; IC 95%: 0,67 a 0,94); no mostraron diferencias significativas en el fracaso bacteriológico precoz del tratamiento (OR 1,08; IC 95%: 0,97 a 1,20) o en la recurrencia clínica tardía (OR 0,95; IC 95%: 0,83 a 1,08). Sin embargo, el riesgo global de recurrencia bacteriológica tardía fue mayor en los estudios de tratamiento abreviado (OR 1,31; IC 95%: 1,16 a 1,48), aunque no se encontraron diferencias significativas al eliminar los estudios con azitromicina a dosis bajas (10 mg/kg) (OR 1,06; IC 95%: 0,92 a 1,22). Tres estudios reportaron complicaciones a largo plazo. De 8.135 casos de faringitis aguda por EBHGA, sólo seis casos del tratamiento abreviado versus ocho del tratamiento de duración estándar, desarrollaron complicaciones a largo plazo en forma de glomerulonefritis post-estreptocócica y fiebre reumática aguda, pero esta diferencia no fue estadísticamente significativa (OR 0,53; IC 95%: 0,17 a 1,64).
CONCLUSIONES DE LOS AUTORES: El tratamiento antibiótico oral abreviado de tres a seis días de duración tuvo una eficacia comparable con la duración estándar de 10 días de penicilina oral en el tratamiento de la faringitis aguda por EBHGA en niños. En zonas donde la prevalencia de la cardiopatía reumática sigue siendo alta, estos resultados deben ser interpretados con cautela.
OBJETIVO: Evaluar la eficacia y la seguridad de corta duración el tratamiento con antibióticos del grupo A beta-hemolítico estreptococos (GAS) faringoamigdalitis.
MÉTODOS: Se realizó un meta-análisis de ensayos controlados aleatorios (ECA) recuperados de PubMed y en el Registro Cochrane Central de Ensayos Controlados utilizando una estrategia de búsqueda estructurada. La última fecha fue accedida la base de datos fue en noviembre 14, 2007. Se incluyeron los ECA que los pacientes que participan de cualquier edad con faringoamigdalitis GAS, la comparación de corta duración (<o = 7 días) vs largo del curso (por lo menos 2 días más largo que corto, por supuesto) el tratamiento con los mismos antibióticos. El análisis primario en comparación de 5 a 7 días con 10 días de tratamiento, utilizando un modelo de efectos aleatorios.
RESULTADOS: Once ECA que comparaban corta duración versus largo ciclo de tratamiento (5 con la penicilina V, 4 con cefalosporinas orales, 1 con ceftriaxona intramuscular, y 1 con clindamicina, 6 de los 11 fueron abiertos) fueron incluidos. En el análisis primario, las tasas de erradicación microbiológica de GAS fueron inferiores para los de corta duración versus largo ciclo de tratamiento (8 ECA, 1607 pacientes, odds ratio [OR] = 0,49, IC del 95% intervalo de confianza [IC]: 0.32-0.74). Esta asociación se observó con el tratamiento de penicilina V (3 ECA, los pacientes de 500, o bien, 0.36, IC 95% 0.13-0.99, la), pero no fue significativa con el tratamiento con cefalosporinas (4 ECA, 1.018 pacientes, o bien, 0.62, IC 95%, 0,38 de 1,03). La erradicación microbiológica fue menos probable con el tratamiento acortado en los ensayos que afecta principalmente a niños y adolescentes (menores de 18 años) (6 ECA, 1258 pacientes, o bien, 0.63, IC 95% 0.40-0.98, las). El éxito clínico fue inferior en los pacientes que recibieron tratamiento acortado (5 ECA, 1.217 pacientes, o bien, 0.49, IC 95% 0.25-0.96, las). Los eventos adversos no difirió entre los grupos comparados. Las asociaciones anteriores fueron consistentes en el análisis de la participación de todos los ECA incluidos.
CONCLUSIÓN: La corta duración del tratamiento de la faringoamigdalitis GAS, en particular con la penicilina V, se asocia con inferiores tasas de erradicación bacteriológica.
En Un meta-análisis estrellas de 5 ENSAYOS Aleatorios Controlados estafadores Adultos 1030, la erradicación de probability bacteriológico En El Tratamiento del Grupo A-beta hemolítico estreptococos (GAS) faringoamigdalitis Con 5 Días de cefalosporinas de Selección (cefpodoxima, cefuroxima, cefotiam, y cefdinir) sin FUE inferior a 10 Días de Penicilina (odds ratio, 1,46; 95% Intervalo de confianza, 0.96-2.22, p = 0,08).
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 2021.
OBJECTIVES:
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.
SEARCH METHODS:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023.
SELECTION CRITERIA:
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.
DATA COLLECTION AND ANALYSIS:
Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures recommended by Cochrane. We assessed the risk of bias in the 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 reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.
MAIN 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). Based on an analysis of evaluable participants, 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). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. 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 trial, 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial, 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial, 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials, 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better at preventing serious but rare complications.
AUTHORS' CONCLUSIONS:
We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high.
