Antibióticos para el tratamiento del dolor de garganta en niños y adultos
Referencias
Referencias de los estudios incluidos en esta revisión
Referencias de los estudios excluidos de esta revisión
Referencias adicionales
Referencias de otras versiones publicadas de esta revisión
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Ir a:
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | 669 participants aged from less than 1 year to older than 50 years of age. Research was divided into 3 studies: ordinary tonsillitis, "phlegmonous" tonsillitis, and "ulcerative" tonsillitis. Patients were excluded if they had a complication of tonsillitis on admission or if they had received previous antibiotic treatment for the current sore throat. | |
| Interventions | Age‐adjusted intramuscular penicillin twice daily for 6 days or no treatment as a control condition | |
| Outcomes | Incidence of rheumatic fever, otitis media, quinsy, sinusitis, and symptoms of sore throat and headache | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Participants allocated to alternate conditions on alternate days. |
| Allocation concealment (selection bias) | High risk | No concealment of allocation |
| Blinding (performance bias and detection bias) | High risk | No blinding of participants or assessments |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Unclear risk | No antipyretics were administered to the control group. The use of antipyretics to participants in the treatment group was unstated. Funding source for the study was not stated. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 intervention arms (2 intervention and 1 control) conducted between 8 March 8 and 30 April 1949 | |
| Participants | 395 United States Air Force recruits (intervention: n = 119; control: n = 129) admitted to Wyoming base hospital with respiratory symptoms or fever with exudate of the tonsils or pharynx | |
| Interventions | Intervention 1: intramuscular penicillin over 4 days. The dosage was 300,000 units on admission, 300,000 units at 48 hours, and 600,000 units at 96 hours. Intervention 2: aureomycin (0.5 g) administered immediately, then 0.5 g every 4 hours for 24 hours and 0.25 g every 4 hours for the next 3 days Control: no treatment | |
| Outcomes | Symptoms of sore throat at day 3 and 1 week, fever at day 3 and 1 week, and headache at day 3. Incidence of rheumatic fever and otitis media | |
| Notes | This investigation was supported through the Commission on Acute Respiratory Diseases, Armed Forces Epidemiological Board, Office of The Surgeon GeneraI, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants randomised by Air Force serial number. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | High risk | No blinding of participants or study investigators |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Low risk | The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 4 intervention arms (3 intervention and 1 control) | |
| Participants | 349 adult males (intervention: n = 262; control: n = 87) admitted to US military hospital within 31 hours of onset of exudative pharyngitis and isolation of group A streptococcal from throat culture. Age of participants was not reported. | |
| Interventions | Intervention: 3 injections of intramuscular penicillin (600,000 units) administered at 3‐day intervals. Intervention arms consisted of a) immediate treatment, b) 3‐day treatment delay, and c) 5‐day treatment delay; control consisted of intramuscular saline injection administered on day 1 and day 5. | |
| Outcomes | Incidence of rheumatic fever within 1 month of study enrolment | |
| Notes | The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases and the Commission on Streptococcal Diseases, Armed Forces Epidemiological Board, and was supported by the Offices of The Surgeons General, Departments of the Army and Air Force, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation performed by shuffling a deck of cards. |
| Allocation concealment (selection bias) | High risk | No concealment of treatment |
| Blinding (performance bias and detection bias) | Unclear risk | Blinding is not mentioned; however, participants in the control group did receive a placebo saline injection. The schedule for saline injections differed from the schedule for those receiving penicillin. |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Low risk | The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | 121 young adult males, aged 18 to 21 years (intervention: n = 62; control: n = 59), recruited into United States Air Force. Patients were excluded from study if their temperature was below 99.3 °F, if they had sore throat for more than 72 hours prior to presentation, or if they had some other generalised illness. | |
| Interventions | Intervention: intramuscular penicillin twice daily for 4 days; control: no treatment | |
| Outcomes | Incidence of rheumatic fever and symptoms of sore throat and fever at day 3 | |
| Notes | Aspirin gargles were given 6‐hourly. Whether participants were permitted to swallow the aspirin was not documented. The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases and the Commission on Streptococcal Diseases, Armed Forces Epidemiological Board, and was supported by the Offices of The Surgeons General, Departments of the Army and Air Force, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants randomised by hospital bed number. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | High risk | No blinding of participants or study investigators |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Low risk | The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms; we included data from 2 of the treatment arms in the review | |
| Participants | 640 United States Air Force recruits (intervention n = 420; control n = 220) admitted to hospital with exudative tonsillitis or pharyngitis who tested positive for GABHS. Patients were excluded if they presented with a suppurative complication at the time of admission, had a family history of rheumatic fever, or exhibited a previous reaction to penicillin. Age of participants was not reported; however, they are described as "young adult males". | |
| Interventions | Intervention: intramuscular penicillin (900,000 units) administered on day 9, 11, and 13 after onset of illness; control: placebo. A third treatment arm (not included in this review) involved administration of sulphonamide. | |
| Outcomes | Incidence of rheumatic fever within 45 days | |
| Notes | The study was conducted in 2 "halves" which were combined for this review. The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases and the Commission on Streptococcal Diseases, Armed Forces Epidemiological Board, and was supported by the Offices of The Surgeons General, Departments of the Army and Air Force, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants were randomised by Air Force serial number. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | Unclear risk | Participants were blinded; however, there was no mention of investigator blinding. |
| Incomplete outcome data (attrition bias) | Unclear risk | Missing data were not explained. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Low risk | The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms (2 intervention and 1 control). Study was conducted between 4 January and 9 July 1953. | |
| Participants | 366 United States Air Force recruits (intervention 1: n = 129; intervention 2: n = 119; control: n = 89) admitted to hospital with exudative tonsillitis or pharyngitis. Patients were excluded if they had previously developed rheumatic fever, had previous penicillin reaction, or if they had a suppurative complication at the time of admission. Age of participants was not reported. However, they are described as "young adult males". | |
| Interventions | Intervention 1: intramuscular penicillin (1,200,000 units); intervention 2: intramuscular penicillin (600,000 units); control: placebo injection | |
| Outcomes | Incidence of rheumatic fever, otitis media, and acute glomerulonephritis | |
| Notes | Antipyretic use was not documented. The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases and the Commission on Streptococcal Diseases, Armed Forces Epidemiological Board, and was supported by the Offices of The Surgeons General, Departments of the Army and Air Force, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants randomised by Air Force serial number. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | Unclear risk | Participants were blinded to the treatment they received; however, investigators were not blinded. |
| Incomplete outcome data (attrition bias) | Low risk | No missing data |
| Selective reporting (reporting bias) | Low risk | Relevant outcomes are reported. |
| Other bias | Low risk | The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms; we included data from 2 treatment arms in the review. Participants were recruited between February 1954 and September 1955. | |
| Participants | Data included in this review correspond to 283 participants older than 2 years (intervention: n = 186; control: n = 97) presenting to general practice in the United Kingdom with acute infection of the throat or middle ear. Patients were excluded if their illness had already lasted longer than 48 hours. Of the 308 participants enrolled in the full study, 69 were aged 2 to 4 years; 120 were aged 5 to 9 years; and 119 were aged 10 or more years. | |
| Interventions | Intervention: age‐adjusted oral penicillin administered 4 times per day for 5 days; control: placebo (barium sulphate) administered solution for the same frequency and duration as the intervention. A third treatment arm (not included in this review) consisted of an oral sulfadimidine solution. | |
| Outcomes | Incidence of rheumatic fever, otitis media, and symptom of sore throat on the third day as reported by the participant or estimated by the participant's mother | |
| Notes | All groups received controlled doses of antipyretics twice daily for 3 days. Data from only 200 participants presenting with sore throat on day 1 included in sore throat analysis. Specific funding details for the study were not provided; however, the investigators acknowledge Glaxo Laboratories for supplying the 3 preparations used in the trial, and the Medical Department, Imperial Chemical (Pharmaceuticals) Limited, for providing sulfadimidine. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Participants randomised by random bottle dispensing. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators. |
| Blinding (performance bias and detection bias) | Low risk | Participants and investigators were blinded to the treatment. |
| Incomplete outcome data (attrition bias) | Low risk | Incomplete data were distributed evenly across treatment arms. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Unclear risk | Funding source not described. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted between 1990 and 1992 | |
| Participants | 239 patients (intervention: n = 121; control: n = 118) aged 4 to 60 years, presenting with sore throat to 37 general practices in the Netherlands, who were clinically suspected of GABHS. Patients were excluded if they had imminent quinsy, concomitant disease, allergy to penicillin, previous use of antimicrobials within the preceding 4 weeks, or sore throat for greater than 14 days. Intervention participant characteristics: mean age = 26.6 years, 36% male; control participant characteristics: mean age = 24.6 years; 42% male | |
| Interventions | Intervention: treatment with oral penicillin V (250 mg for ages 4 to 9, 500 mg for ages 10 and over; 3 times per day for 10 days); control: placebo oral tablets for identical duration and frequency | |
| Outcomes | Presence of sore throat and fever on day 3 (assessed by treating medical practitioner), incidence of quinsy | |
| Notes | Raw data would be required to include 1‐week symptoms in the meta‐analysis. Funding sources for the study were not provided in the published article. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated random sequence |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ participants and investigators were blind to the treatment received |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | Funding sources were not reported for the study. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 4 intervention arms. We included a subset of data from 2 of the intervention arms in the review. | |
| Participants | 109 adult patients (intervention: n = 57; control: n = 52) presenting with uncomplicated acute sore throat to primary healthcare centres in Spain for whom the choice to use antibiotics for treatment was in doubt. Only data from participants who reported sore throat at baseline were included in the review ‐ the full study cohort in the published article includes participants who did not have sore throat at baseline. | |
| Interventions | Intervention: treatment with immediate antibiotics; antibiotic type and dosage were selected by the treating medical practitioner. Control: no treatment. 2 additional intervention arms not included in this review involved delayed antibiotic prescriptions. | |
| Outcomes | Duration and severity of sore throat, headache and fever symptoms as recorded by participants in a daily diary. We included data on the presence of sore throat and fever at day 3 and 1 week, and headache at day 3 in the review. | |
| Notes | We contacted the authors to provide the subset of data included in the review. The study was sponsored through a governmental grant of the Instituto de Salud Carlos III, Spanish Ministry of Health (grant no. EC08/00095), which is co‐funded by the European Regional Development Fund (FEDER; “A way of making Europe”). | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation was performed using permutated block sizes of 4 which were stratified according to type of infection. |
| Allocation concealment (selection bias) | Low risk | A centralised electronic database was used to allocate participants to the study intervention arms. |
| Blinding (performance bias and detection bias) | High risk | No blinding of participants or healthcare professionals delivering the study |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | Antibiotic choice was by the treating physician. Individuals were only eligible for inclusion in the trial if the benefit of antibiotics for treating their illness was in doubt. The study was funded by a government grant. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted from January to December 1989 | |
| Participants | 173 participants aged 5 to 50 years (intervention: n = 82; control: n = 91), presenting to general practice in the Gent region of Belgium with acute sore throat who tested positive for GABHS. Participants were excluded if they: produced a GABHS‐negative throat swab, had a sore throat for greater than 5 days, had a previous history of acute rheumatic fever, had an allergy to beta‐lactam antibiotics, had received any antibiotics within the past 14 days, or were in any high‐risk situation as determined by the physician. Intervention participant characteristics: mean age = 23.18 years, 36.5% male; control participant characteristics: mean age = 24.08 years; 43% male | |
| Interventions | Intervention: oral penicillin tablets (phenoxymethylcillin 250 mg for adults, 125 mg for children aged up to 10 years) administered 3 times per day for 10 days Control: identical oral placebo tablets administered with the same frequency schedule as the intervention | |
| Outcomes | Symptom of sore throat at day 3 as assessed by the treating physician and at 1 week as self reported in a daily symptom diary. The daily symptom diary was completed by a subset of participants (131/173). | |
| Notes | Participants used antipyretics as required. Use of antipyretics and other symptom‐relieving methods was documented in the daily diary. Funding sources for the study were not provided in the published article. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not documented. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ participants and study investigators were blind to the treatment received |
| Incomplete outcome data (attrition bias) | Unclear risk | 8 participants (5 from the intervention group and 3 from the control group) who were initially randomised into the study dropped out and were not included in the analysis. Data for sore throat at 1 week were only available for a subset of the initial study cohort (131/173). |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | Funding sources for the study were not reported. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted between 24 January and 1 July 1949 | |
| Participants | 1602 United States Air Force recruits (intervention: n = 798; control: n = 804) admitted to hospital with exudative pharyngitis or tonsillitis. Age information was not provided; however, participants are described as "young, adult males". | |
| Interventions | Intervention: intramuscular penicillin (prior to 3 March 1949: 300,000 units of procaine penicillin G administered at time of admission and then repeated after 72 hours; after 3 March 1949: 300,000 units of procaine penicillin G administered at time of admission and then repeated after 48 hours followed by 600,000 units after 96 hours) Control: no treatment | |
| Outcomes | Incidence of rheumatic fever as diagnosed using a modification of the Jones classification | |
| Notes | The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases, Armed Forces Epidemiological Board, Office of the Surgeon General, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants randomised by Air Force serial number (odd versus even last digit) |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | Unclear risk | Single‐blind study ‐ assessment was conducted by physicians who were unaware of treatment condition. Participants were not blinded. |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | Antipyretic use was not stated. The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | 103 young, adult males recruited in the United States Air Force. Patients were excluded if they had no exudate on their tonsils or larynx, if they had a leukocyte count of less than 10,000, or if they had experienced symptoms of sore throat for more than 31 hours. | |
| Interventions | Intramuscular penicillin daily for 5 days, oral chlortetracycline (Aureomycin) or oral tetracycline (Terramycin) administered every 6 hours for 3 days or oral lactose placebo for 3 days as a control condition | |
| Outcomes | Incidence of acute rheumatic fever, otitis media, quinsy, and symptoms of sore throat and headache | |
| Notes | The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases and the Commission on Streptococcal Diseases, Armed Forces Epidemiological Board, and was supported by the Offices of The Surgeons General, Departments of the Army and Air Force, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants were randomly allocated to treatment groups by drawing a card from a deck. |
| Allocation concealment (selection bias) | Low risk | The study investigators were unaware to which treatment participants had been allocated. |
| Blinding (performance bias and detection bias) | Unclear risk | Single‐blind study ‐ assessment was conducted by physicians who were unaware of the treatment condition |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Low risk | No antipyretics were administered. The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted between September 1988 and November 1989 | |
| Participants | 229 children aged 4 to 14 years (intervention: n = 111; control: n = 118) presenting to paediatric clinics in Jordan who tested positive for GABHS. Patients were excluded if they had an allergy to penicillin, had received antibiotics in the previous 7 days, had an acute illness of any kind in preceding 7 days, GABHS infection in preceding month, or recurrent infection requiring treatment other than penicillin. Intervention participant characteristics: mean age = 7.79 years, 54% male; control participant characteristics: mean age = 8.26 years; 56% male | |
| Interventions | Intervention: immediate treatment with oral penicillin V (liquid suspension of 50,000 IU/kg/day) administered over 3 doses daily for 10 days; control: identical oral placebo for 2 days followed by oral penicillin for 8 days | |
| Outcomes | Symptoms of sore throat and headache on day 3 as assessed by the treating physician | |
| Notes | Examination of participants was performed on day 3 before administering penicillin to the control group. The study was supported by the Deanship of Research, Jordan University of Science and Technology, Grant 87/59, and by Biochemie GmbH. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not described. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ both participants and study investigators were blind to the treatment received |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | High risk | The funding source for the study included a biotechnology company. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 4 treatment arms recruiting participants between 23 February 23 and 14 November 1950. 3 intervention arms involved antibiotic treatment. | |
| Participants | 2044 United States Air Force recruits (intervention (3 arms combined): n = 1009; control: n = 1035) admitted to US hospitals with exudative lesions on their tonsils or pharynx. All participants were males aged 17 to 21 years. | |
| Interventions | Intervention arm 1: chlortetracycline (Aureomycin) (total 11 g) administered over 6 days of treatment Intervention arm 2: chlortetracycline (Aureomycin) (total 10.5 g) administered over 5 days of treatment Intervention arm 3: chlortetracycline (Aureomycin) (total 8 g) administered over 4 days of treatment Control: no treatment | |
| Outcomes | Incidence of rheumatic fever diagnosed using modified Jones classification. | |
| Notes | Individuals who would have been eligible for inclusion during intervention arm 1 and for part of intervention arm 3 were not recruited into the study due to being included in a separate study being conducted simultaneously. The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases and the Commission on Streptococcal Diseases, Armed Forces Epidemiological Board, and was supported by the Offices of The Surgeons General, Departments of the Army and Air Force, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation was performed using Air Force serial numbers. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | High risk | No blinding of participants or healthcare workers |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Low risk | The study was funded by a government department. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms (2 intervention and 1 control) conducted from October 1993 to May 1994 | |
| Participants | 154 participants aged 16 to 60 years (intervention: n = 100; control: n = 54) presenting to general practice in the United Kingdom with sore throat and for whom the GP would normally prescribe an antibiotic. Patients were excluded if they had received antibiotics in the previous 14 days, had a history of rheumatic fever or nephritis, or allergy to penicillin or cephalosporins. | |
| Interventions | Intervention arm 1: penicillin V (250 mg 4 times daily) for 5 days Intervention arm 2: cefixime (200 mg daily) for 5 days Control: placebo for 5 days (dosage frequency not reported) | |
| Outcomes | Incidence of quinsy as diagnosed by medical practitioner | |
| Notes | Symptom results recorded in participant diary (including sore throat and fever) were bundled into a composite "symptom score". We requested the raw data on sore throat and fever resolution from the authors but did not receive this information, hence it could not be included in the meta‐analyses for symptom reduction. The trial was terminated earlier than expected due to local concerns about necrotising fascitis associated with GABHS. The trial was funded by Lederle. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | A block randomisation scheme was used (performed in blocks of 6). |
| Allocation concealment (selection bias) | Low risk | Medical practitioners were blinded to allocation. |
| Blinding (performance bias and detection bias) | Low risk | Both participant and medical practitioners were blinded to the intervention received. |
| Incomplete outcome data (attrition bias) | Low risk | A high number of participants did not complete the symptom diaries; however, there is low risk of incomplete data for the outcome of quinsy, which is the only outcome included for the study in our review. |
| Selective reporting (reporting bias) | Unclear risk | Other relevant outcomes (e.g. the incidence of other complications) were not reported in the published article, and symptoms of sore throat and fever could not be separated from the published data. |
| Other bias | High risk | A high number of eligible patients who were very ill declined to participate or were deemed too ill by their practitioner, which may have influenced the outcomes. The study was funded by a pharmaceutical company. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted over 2 periods: January 1982 to March 1983 (Hawaii) and November 1983 to Jannuary 1984 (Washington state) | |
| Participants | 26 children (intervention: n = 15; control: n = 11) presenting to a paediatric clinic with sore throat in the United States (Hawaii and Washington state) who yielded GABHS‐positive throat swabs. Patients were excluded if: the duration of symptoms was greater than 72 hours; they had received oral antibiotics within the past 72 hours or intramuscular antibiotics within the past 30 days; they had history of penicillin allergy; they had a rash suggestive of scarlet fever; they had a concurrent infection that required antibiotics other than penicillin; or if they had severe illness requiring immediate penicillin treatment. Participant characteristics: intervention mean age = 9.3 years, males = 36%; control: mean age = 7.8 years, males = 47% | |
| Interventions | Intervention: oral penicillin V (250 mg) 3 times daily for 3 days Control: oral placebo with a similar look and taste for the same frequency and duration as the intervention | |
| Outcomes | Symptom of fever at day 3 as assessed by the medical practitioner | |
| Notes | Participants agreed not to use antipyretics during the course of the study. The funding source for the study was not reported in the published article. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Participants were randomised using a random numbers table. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ study investigators and participants were blind to the treatment received |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | The funding source for the study was not reported. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms (2 intervention and 1 control). Study duration was not stated. | |
| Participants | 95 children and adult patients (intervention: n = 42; control: n = 43) who presented to a general practice in Scotland complaining of sore throat. The participant group included children and adults; however, the age and sex distribution across treatment arms was not reported. | |
| Interventions | Intervention arm 1: oral sulfanilamide (0.5 g) Intervention arm 2: oral sulphatriad (0.5 g) Control: similar looking and tasting oral lactose placebo (0.5 g) The duration and frequency of medication for each treatment arm was not stated. | |
| Outcomes | Symptom of sore throat and fever at day 3 and 1 week; incidence of sinusitis and quinsy | |
| Notes | Antipyretic use was not documented. The research was supported by a grant from the (UK) Medical Research Council. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | The randomisation method changed during the trial; initially each participating GP was intended to prescribe the same medication to all participants for a full month; however, due to criticism of the methods this was changed to randomisation by numbering of bottles. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators responsible for participant recruitment. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind ‐ participants and study investigators were blinded to treatment received |
| Incomplete outcome data (attrition bias) | Low risk | 5 cases were lost to follow‐up and not included in the analysis. 4 of the cases involved loss of the treating card, so the treatment was not known; 1 case did not adhere to the treatment. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | Antipyretic use was not documented. |
| Study characteristics | ||
| Methods | Double‐blind, randomised, placebo‐controlled trial | |
| Participants | 1217 participants aged over 5 years presenting to 4 community‐based medical centres with complaints of fever or sore throat of less than 10 days duration | |
| Interventions | Participants were randomised to receive either amoxicillin or placebo for 7 days. | |
| Outcomes | Duration of sore throat and fever. Incidence of complications and adverse reactions | |
| Notes | Antipyretics were given if deemed necessary by the physician. The study was funded by the World Health Organization, Ministry of Public Health, Siriraj‐China Medical Board, and Inclen Inc. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated random sequence |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design |
| Incomplete outcome data (attrition bias) | Unclear risk | Some loss to follow‐up occurred. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Low risk | The study was funded by international and government grants and industry funding. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 intervention arms conducted between September 1994 and May 1996 | |
| Participants | 716 participants aged 4 years and over (intervention: n = 454; control: n = 216) presenting to 11 GPs in the UK with a sore throat. Patients were excluded if there were other explanations for sore throat (drugs, aphthous ulcers, candida, etc.), were very ill (in which case not giving antibiotics could be considered unethical), had a history of rheumatic fever, recurrent tonsillitis, or quinsy, or were pregnant. | |
| Interventions | Intervention 1: 10‐day prescription of penicillin V: 250 mg 4 times daily (125 mg for children under 5 years old) Intervention 2: antibiotic prescription offered after 3 days if symptoms were not resolving Control: no treatment | |
| Outcomes | Symptoms of sore throat at day 3 and 1 week as recorded in a daily symptom diary. Incidence of rheumatic fever, otitis media, quinsy, and sinusitis. Participants who did not return diaries were followed up over the phone. | |
| Notes | The study was supported by a Wessex National Health Service regional research and development fund. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomised envelopes were used to allocate participants to treatment arms. |
| Allocation concealment (selection bias) | Low risk | Treating GPs were unaware of the allocation sequence. |
| Blinding (performance bias and detection bias) | High risk | There was no blinding of participants or assessors. |
| Incomplete outcome data (attrition bias) | Low risk | Low attrition of participants (outcomes recorded for 94%) |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Low risk | The study was funded by a government grant. |
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | 82 young, adult males recruited into the United States Air Force (41 in treatment group, 41 in control group) | |
| Interventions | Intervention: oral sulphatriad, taken every 4 hours Control: identical oral lactose placebo, taken every 4 hours | |
| Outcomes | Symptom of sore throat | |
| Notes | Antipyretics were administered to 1 participant in the treatment group and 2 participants in the control group. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants were randomised by Air Force serial number. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ outcomes were determined blind, and participants were unaware of treatment received |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | The funding source for the study was not reported. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted from January 1982 to April 1985 | |
| Participants | 178 participants aged 4 to 29 years (intervention: n = 91; control: n = 97) presenting to primary care facilities in the United States with streptococcal pharyngitis. Results reported for participants with severe illness or positive GABHS throat swab, or both, only. Patients were excluded if they had taken antibiotics during previous 4 days, had symptoms for more than 4 days, or had an allergy to penicillin. | |
| Interventions | Intervention: 8 individual doses of penicillin (250 mg, 4 times daily for 4 days) Control: identical placebo taken for same duration and frequency as intervention | |
| Outcomes | Symptoms of sore throat and fever on day 3 as self reported by telephone interview | |
| Notes | Aspirin or paracetamol was provided to participants in age‐adjusted doses. The study was supported in part by a grant (AA‐3) from the Health Research and Services Foundation, an agency of the Allegheny County United Way. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The randomisation method was not stated. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to study investigators. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ both participants and investigators were blinded to treatment received |
| Incomplete outcome data (attrition bias) | Unclear risk | Results were only reported for participants who tested positive for GABHS or had severe illness, or both. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Low risk | The study was funded by a government grant. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted during the winter months of 1958 to 1959 | |
| Participants | 35 children aged 5 to 11 years (intervention: n = 17; control: n = 18) admitted to hospital in the United Staes with acute respiratory illness who tested positive for GABHS. 16 participants initially enrolled in the study were excluded from the analysis because they did not produce GABHS‐positive throat swabs, leaving 35 participants included in the study. Children with history of penicillin hypersensitivity were also excluded. Participant age and sex distribution were not reported; however, it was stated that they were comparable across the treatment arms. | |
| Interventions | Intervention: intramuscular penicillin G (300,000 units) for 48 hours Placebo: oral syrup placebo | |
| Outcomes | Symptoms of fever on day 3 | |
| Notes | No antipyretics were administered. The study was published more than 20 years after being conducted. The funding source for the study was not reported. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants randomised to conditions by hospital number allocation. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | Unclear risk | The study was single‐blind ‐ an oral placebo was used to blind participants, but study outcomes were not determined blind. |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | The funding source for the study was not reported. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted from January 1983 to December 1984 | |
| Participants | 186 adults aged 18 to 50 years (intervention: n = 93, control: n = 93) presenting to an ambulatory setting in Massachusetts, United States, with sore throat who tested negative for GABHS culture. Patients were excluded if the had been ill for more than 6 days, had a temperature exceeding 40 °C, current otitis media or pneumonia, symptoms of vaginitis or urinary tract infection, were pregnant or breastfeeding, had a history of rheumatic fever, had significant medical illness other than hypertension, had taken antibiotics within previous 10 days, had allergy to erythromycin, were illiterate in English, or were considered to potentially be non‐compliant. Intervention participant characteristics: mean age = 25 years; male = 39% Control participant characteristics: mean age = 26 years; male = 32% | |
| Interventions | Intervention: erythromycin (333 mg, 3 times daily) Control: placebo | |
| Outcomes | Symptom of sore throat on day 3 and at 1 week as self reported by participants in a daily symptom diary collected at a 3‐week follow‐up visit | |
| Notes | The study was supported by the Henry J. Kaiser Foundation and by a grant from the Upjohn Company. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation method not reported. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed to practitioners responsible for recruiting participants. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ participants and treating practitioners were blinded to the treatment received |
| Incomplete outcome data (attrition bias) | Unclear risk | It is not clear how many participants in each group kept diaries for the sore throat data. The study authors excluded GABHS‐positive participants (15 out of 212 initially randomised into treatment). |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | High risk | The study was funded in part by a pharmaceutical company. |
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | 1213 children aged 3 to 16 years (intervention: n = 605; control: n = 608) with uncomplicated acute respiratory illness who returned a positive GAS test. Suppurative complications occurring in participants in the control condition were treated with sulphonamides. Patients were excluded if they had a complication on admission. | |
| Interventions | Intervention: intramuscular penicillin (600,000 units) Control: no treatment | |
| Outcomes | Incidence of rheumatic fever | |
| Notes | The study was supported by grants from the American Heart Association, the United States Public Health Service (Grant H‐4164‐C2), and Wyeth Inc. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants were allocated to treatment according to their bed chart number. |
| Allocation concealment (selection bias) | High risk | No allocation concealment |
| Blinding (performance bias and detection bias) | High risk | There was no blinding of participants or treating medical personnel. |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Unclear risk | All relevant outcomes reported. |
| Other bias | High risk | Antipyretic use was not documented. The study was funded in part by a pharmaceutical company. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms (2 intervention and 1 control) | |
| Participants | Children aged 2 to 10 years (intervention; n = 129; control: n = 59) presenting with presumed viral respiratory infections in New Zealand. Children with positive Streptococcus throat swabs or clinically diagnosed with otitis media or pneumonia were excluded. | |
| Interventions | Intervention arm 1: oral amoxicillin (Amoxil) 3 times a day for 5 days Intervention arm 2: oral cotrimoxazole (trimethoprim 40 mg, sulfamethoxazole 200 mg, Bactrim, Roche) 3 times a day for 5 days Control: oral placebo 3 times a day for 5 days | |
| Outcomes | Incidence of acute otitis media and sinusitis and symptoms of sore throat and fever at 1 week | |
| Notes | The funding source for the study was not documented. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The method of randomisation to treatment arm was not documented. |
| Allocation concealment (selection bias) | Low risk | The allocation sequence was not revealed. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ participants and study investigators were blinded to the treatment received |
| Incomplete outcome data (attrition bias) | Unclear risk | A higher number of participants in the control arm were withdrawn during the study and not included in the analysis. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | Antipyretic use was not documented. The funding source for the study was not reported. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted between March 1949 and February 1950. The study was conducted in 3 separate phases which involved differing treatment dosage in each phase. Hence there were 6 separate treatment arms (3 intervention and 3 control). | |
| Participants | 1974 United States Air Force recruits (intervention: total n = 978; control: total n = 996) admitted to hospital with either exudative pharyngitis or tonsillitis. All participants were young, adult males (further age characteristics were not provided). | |
| Interventions | Intervention arm 1: intramuscular penicillin (120,000 units) in 3 doses over 96 hours Intervention arm 2: intramuscular penicillin (600,000 units) in 2 doses over 72 hours Intervention arm 3: intramuscular penicillin (600,000 units) in 1 dose Control (3 separate arms): no treatment | |
| Outcomes | Incidence of rheumatic fever within 2 months as diagnosed by study investigator | |
| Notes | Antipyretic use was not documented. The study was conducted under the sponsorship of the Commission on Acute Respiratory Diseases and the Commission on Streptococcal Diseases, Armed Forces Epidemiological Board, and was supported by the Offices of The Surgeons General, Departments of the Army and Air Force, Washington, DC. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Participants were randomised according to Air Force serial number. |
| Allocation concealment (selection bias) | Unclear risk | No mention of allocation concealment |
| Blinding (performance bias and detection bias) | Unclear risk | Single‐blind study design ‐ participants were not blinded to the treatment received, but study investigators were |
| Incomplete outcome data (attrition bias) | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | The study was government funded. Antipyretic use was not documented. |
| Study characteristics | ||
| Methods | Randomised controlled trial conducted from October 1978 to June 1989 | |
| Participants | Participants were aged over 10 years (intervention: n = 256; control: n = 272) presenting to 48 GPs in Avon, United Kingdom with sore throat. Patients were excluded if the GP thought the participant would demonstrate poor compliance or if they had previous reaction to penicillin or a previous episode of rheumatic fever or acute nephritis. Participant age and sex characteristics were not reported. | |
| Interventions | Intervention: oral penicillin V (250 mg) 4 times a day for 5 days Control: identical‐looking and ‐tasting oral lactose placebo 4 times a day for 5 days | |
| Outcomes | Symptoms of sore throat and fever at day 3 as reported by the participants in a study questionnaire | |
| Notes | The study was financially supported by the Scientific Foundation Board of the Royal College of General Practitioners. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Participants were randomised according to a predetermined random order. |
| Allocation concealment (selection bias) | Low risk | GPs were blinded to the allocation sequence. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ participants and treating GPs were blinded to the treatment received |
| Incomplete outcome data (attrition bias) | High risk | A large number of participants recruited into the study did not complete the study questionnaire (only 528 out of 745 questionnaires were returned), and analysis was only performed on those returned. Participants not returning questionnaires were more likely than those who did return questionnaires to be smokers, of a lower social class, and aged between 15 and 34 years. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Unclear risk | The study was government funded. Antipyretic use was not documented. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms (2 intervention and 1 control) conducted between 1994 and 1996 | |
| Participants | 561 participants aged 15 to 60 years (intervention: n = 358; control, n = 164) presenting to 43 general practices in the Netherlands with sore throat of less than 7 days duration. Participants exhibited at least 2 of 4 Centor criteria (history of fever, absence of cough, swollen and tender lymph nodes, tonsillar exudate). Patients were excluded for medical reasons (imminent quinsy, suspected scarlet fever, recurrent illness requiring antibiotics) and intolerance to penicillin. Intervention arm 1 participant characteristics: mean age = 28 years, male = 39% Intervention arm 2 participant characteristics: mean age = 28 years, male = 36% Control participant characteristics: mean age = 28 years, male = 39% | |
| Interventions | Intervention arm 1: penicillin V (500 mg, 3 times daily) for 7 days Intervention arm 2: penicillin V (500 mg, 3 times daily) for 3 days, followed by 4 days of placebo Control: placebo for 7 days (oral tablet taken 3 times daily) | |
| Outcomes | Symptoms of sore throat at day 3 and 1 week. Incidence of acute otitis media, acute sinusitis, quinsy, and acute glomerulonephritis | |
| Notes | We contacted the authors for data that could be used in the meta‐analysis, which they provided. This study was funded by Groene Land Achmea Health Insurances and the Stichting Gezondheidszorgonderzoek Ysselmond in Zwolle. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation was performed by computer‐generated random sequence. |
| Allocation concealment (selection bias) | Low risk | GPs were blinded to the allocation sequence. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ participants and treating GPs were blind to the treatment received |
| Incomplete outcome data (attrition bias) | Low risk | Intention‐to‐treat analysis was performed. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes were reported. |
| Other bias | Low risk | The study was supported by government grants. |
| Study characteristics | ||
| Methods | Randomised controlled trial with 3 treatment arms (2 intervention and 1 control) conducted between 1994 and 1996 | |
| Participants | 156 children (intervention n = 100; control: n = 56) aged 4 to 15 years presenting to 43 family practices in the Netherlands with sore throat. Inclusion criteria were sore throat of less than 7 days duration exhibiting at least 2 of 4 Centor criteria (history of fever, absence of cough, swollen and tender lymph nodes, tonsillar exudate). Children were excluded for medical reasons (imminent quinsy, suspected scarlet fever, recurrent illness requiring antibiotics) and intolerance to penicillin. Intervention arm 1 participant characteristics: mean age = 9.9 years, male = 44% | |
| Interventions | Intervention arm 1: penicillin V (250 mg, 3 times daily for children aged 4 to 10 years; 500 mg, 3 times daily for children aged 11 to 15 years) for 7 days Intervention arm 2: penicillin V (250 mg, 3 times daily for children aged 4 to 10 years; 500 mg, 3 times daily for children aged 11 to 15 years) for 3 days followed by 4 days of placebo Control: placebo for 7 days (oral tablet taken 3 times daily) | |
| Outcomes | Duration of symptoms of sore throat, occurrence of streptococcal sequelae | |
| Notes | We contacted the authors for data that could be used in the meta‐analysis, which they provided. This study was funded by Groene Land Achmea Health Insurances and the Stichting Gezondheidszorgonderzoek Ysselmond in Zwolle. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation performed by computer‐generated random sequence. |
| Allocation concealment (selection bias) | Low risk | GPs were blinded to allocation sequence. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind study design ‐ participants and treating physicians were blinded to the treatment received |
| Incomplete outcome data (attrition bias) | Low risk | Intention‐to‐treat analysis was performed. |
| Selective reporting (reporting bias) | Low risk | All relevant outcomes reported. |
| Other bias | Low risk | The study was supported by government grants. |
GABHS: group A beta haemolytic Streptococcus
GAS: group A streptococcal
GP: general practitioner
IU: international units
Characteristics of excluded studies [ordered by study ID]
Ir a:
| Study | Reason for exclusion |
| Participants were randomised to 2 general practitioners for subsequent treatment with different management protocols. | |
| Study used a Likert scale to measure severity and duration of symptoms. No raw scores were available for entry into meta‐analysis. | |
| Non‐randomised allocation to treatment groups. "Where an exceptionally severe case fell in the control group and it was felt unjustifiable to withhold specific treatment, the case was transferred to one of the other groups and the next case was placed in the control group." This bias was not quantified. | |
| Study compared sulphonamides with other antibiotics. No control condition was used. | |
| Study is another report of data previously published by Brumfitt 1957. | |
| Cough was the main patient complaint, not sore throat. | |
| Study compared 2 different regimens of penicillin. No placebo control group was used. | |
| Assessed 2 regimens of penicillin. No control group used. | |
| Study compared penicillin V with cefadroxil. No placebo control group was used. | |
| Study did not use a control condition. | |
| Participants not treated with antibiotics were given antipyretics. Participants receiving antibiotics received no antipyretics. No control condition | |
| No participant‐centred outcomes, except return visits for upper respiratory infections | |
| Illness was "cold or flu‐like illness", not exclusively acute pharyngitis. Soreness of throat was not an outcome measure. | |
| Participants were not randomly allocated to treatment groups and were not blinded to treatment. | |
| No intervention was provided to participants. Study tracked natural course of illness only. | |
| Study investigated the combination of Ingavirin (antiviral medication) with an antibacterial agent in adults with viral respiratory infections. No comparison of antibiotics alone against placebo | |
| Participant population highly selected (non‐pregnant, negative rapid strep test, negative throat culture, no other infection present, not allergic to erythromycin, aged older than 12), and participant‐centred outcomes not compatible with those in our meta‐analysis. | |
| Study examined effect of penicillin on haemolytic streptococci infections in rheumatic patients only, without randomisation to control condition. Infections that were not treated with penicillin for "various reasons" were treated as controls. These reasons were not provided. | |
| No data suitable for our meta‐analysis were described, although symptoms were recorded. We approached the author for these data, but received no reply. | |
| No data on suppurative or non‐suppurative complications | |
| Study observed the effect of sulfadiazine on prevention of rheumatic fever only. No control condition was used. | |
| Study was a controlled clinical trial without participant randomisation. | |
| Investigation of the effect of fusafungine on chronic conditions of follicular pharyngitis. Not relevant to this review | |
| All participants were treated with antibiotics, and there was no placebo group for assessing long‐term complications. The methodological design did include a delayed antibiotic group; however, outcomes were not reported in such a way that could be included in the review. | |
| No data on suppurative or non‐suppurative complications | |
| Primary complaint was hoarseness, not sore throat. No patient‐centred outcomes apart from hoarseness | |
| Participants presented for laryngitis and hoarseness, not pharyngitis. | |
| Study compared 7 versus 10 days of treatment with penicillin. No control group was used. | |
| Study was a clinical trial without a control condition. | |
| Study compared the efficacy of amoxicillin against penicillin, no control condition was used. | |
| Study compared penicillin with cephalosporins, no control group was used. | |
| No placebo control group was used. Study compared different antibiotic regimens. | |
| Antibiotics were not offered as an intervention. Study investigated the efficacy of mangosteen spray against placebo only. | |
| Primary complaint was not sore throat, but purulent nasopharyngitis instead. | |
| Study did not involve any control measures. Data provided only for participants not treated with antibiotics. |
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Symptom of sore throat on day 3 Show forest plot | 16 | 3730 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.60, 0.80] |
| Analysis 1.1  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 1: Symptom of sore throat on day 3 | ||||
| 1.2 Symptom of sore throat on day 3: early (pre‐1975) versus late studies (post‐1975) Show forest plot | 16 | 3730 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.60, 0.80] |
| Analysis 1.2  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 2: Symptom of sore throat on day 3: early (pre‐1975) versus late studies (post‐1975) | ||||
| 1.2.1 Symptom of sore throat on day 3: early (pre‐1975) studies | 6 | 1141 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.56, 0.69] |
| 1.2.2 Symptom of sore throat on day 3: late (post‐1975) studies | 10 | 2589 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.60, 0.88] |
| 1.3 Symptom of sore throat on day 3: blind versus unblinded studies Show forest plot | 16 | 3730 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.60, 0.80] |
| Analysis 1.3  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 3: Symptom of sore throat on day 3: blind versus unblinded studies | ||||
| 1.3.1 Symptom of sore throat on day 3: blinded studies | 12 | 2662 | Risk Ratio (M‐H, Random, 95% CI) | 0.65 [0.54, 0.78] |
| 1.3.2 Symptom of sore throat on day 3: unblinded studies | 4 | 1068 | Risk Ratio (M‐H, Random, 95% CI) | 0.81 [0.65, 1.01] |
| 1.4 Symptom of sore throat on day 3: antipyretics versus no antipyretics Show forest plot | 5 | 1137 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.48, 0.70] |
| Analysis 1.4  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 4: Symptom of sore throat on day 3: antipyretics versus no antipyretics | ||||
| 1.4.1 Symptom of sore throat on day 3: antipyretics administered | 3 | 455 | Risk Ratio (M‐H, Random, 95% CI) | 0.52 [0.33, 0.81] |
| 1.4.2 Symptom of sore throat on day 3: no antipyretics administered | 2 | 682 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.55, 0.70] |
| 1.5 Symptom of sore throat on day 3: GABHS‐positive throat swab, negative swab, untested/inseparable Show forest plot | 15 | 3600 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.59, 0.78] |
| Analysis 1.5  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 5: Symptom of sore throat on day 3: GABHS‐positive throat swab, negative swab, untested/inseparable | ||||
| 1.5.1 Symptom of sore throat on day 3: GABHS‐positive throat swab | 11 | 1839 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.48, 0.71] |
| 1.5.2 Symptom of sore throat on day 3: GABHS‐negative throat swab | 6 | 736 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.63, 0.97] |
| 1.5.3 Symptom of sore throat on day 3: untested for GABHS culture or combined, inseparable data | 3 | 1025 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.80, 1.00] |
| 1.6 Symptom of sore throat at 1 week (6 to 8 days) Show forest plot | 14 | 3083 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.34, 0.75] |
| Analysis 1.6  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 6: Symptom of sore throat at 1 week (6 to 8 days) | ||||
| 1.7 Symptom of sore throat at 1 week (6 to 8 days): early (pre‐1975) versus late (post‐1975) Show forest plot | 14 | 3083 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.34, 0.75] |
| Analysis 1.7  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 7: Symptom of sore throat at 1 week (6 to 8 days): early (pre‐1975) versus late (post‐1975) | ||||
| 1.7.1 Symptom of sore throat at 1 week (6 to 8 days): early (pre‐1975) studies | 6 | 1140 | Risk Ratio (M‐H, Random, 95% CI) | 0.14 [0.08, 0.27] |
| 1.7.2 Symptom of sore throat at 1 week (6 to 8 days): late (post‐1975) studies | 8 | 1943 | Risk Ratio (M‐H, Random, 95% CI) | 0.73 [0.55, 0.97] |
| 1.8 Symptom of sore throat at 1 week (6 to 8 days): blind versus unblinded studies Show forest plot | 14 | 3053 | Risk Ratio (M‐H, Random, 95% CI) | 0.57 [0.39, 0.82] |
| Analysis 1.8  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 8: Symptom of sore throat at 1 week (6 to 8 days): blind versus unblinded studies | ||||
| 1.8.1 Symptom of sore throat at 1 week (6 to 8 days): blinded studies | 9 | 1616 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.38, 1.03] |
| 1.8.2 Symptom of sore throat at 1 week (6 to 8 days): unblinded studies | 5 | 1437 | Risk Ratio (M‐H, Random, 95% CI) | 0.43 [0.20, 0.91] |
| 1.9 Symptom of sore throat at 1 week (6 to 8 days): GABHS‐positive throat swab, GABHS‐negative swab Show forest plot | 12 | 2524 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.29, 0.80] |
| Analysis 1.9  Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 9: Symptom of sore throat at 1 week (6 to 8 days): GABHS‐positive throat swab, GABHS‐negative swab | ||||
| 1.9.1 Symptom of sore throat at 1 week (6 to 8 days): GABHS‐positive throat swab | 7 | 1117 | Risk Ratio (M‐H, Random, 95% CI) | 0.29 [0.12, 0.70] |
| 1.9.2 Symptom of sore throat at 1 week (6 to 8 days): GABHS‐negative throat swab | 5 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 0.73 [0.50, 1.07] |
| 1.9.3 Symptom of sore throat at 1 week (6 to 8 days): GABHS untested | 3 | 866 | Risk Ratio (M‐H, Random, 95% CI) | 0.35 [0.03, 4.47] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Symptom of fever on day 3 Show forest plot | 8 | 1443 | Risk Ratio (M‐H, Random, 95% CI) | 0.75 [0.53, 1.07] |
| Analysis 2.1  Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 1: Symptom of fever on day 3 | ||||
| 2.2 Symptom of fever on day 3: blinded versus unblinded studies Show forest plot | 8 | 1443 | Risk Ratio (M‐H, Random, 95% CI) | 0.75 [0.53, 1.07] |
| Analysis 2.2  Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 2: Symptom of fever on day 3: blinded versus unblinded studies | ||||
| 2.2.1 Symptom of fever on day 3: blinded studies | 4 | 703 | Risk Ratio (M‐H, Random, 95% CI) | 0.82 [0.54, 1.23] |
| 2.2.2 Symptom of fever on day 3: unblinded studies | 4 | 740 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.43, 1.21] |
| 2.3 Symptom of fever on day 3: children compared with adults Show forest plot | 5 | 766 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.31, 1.26] |
| Analysis 2.3  Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 3: Symptom of fever on day 3: children compared with adults | ||||
| 2.3.1 Symptom of fever on day 3: children | 2 | 61 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.76, 2.13] |
| 2.3.2 Symptom of fever on day 3: adults | 3 | 705 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.21, 1.10] |
| 2.4 Symptom of fever at 1 week (6 to 8 days) Show forest plot | 4 | 886 | Risk Ratio (M‐H, Random, 95% CI) | 0.91 [0.55, 1.52] |
| Analysis 2.4  Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 4: Symptom of fever at 1 week (6 to 8 days) | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Symptom of headache on day 3 Show forest plot | 4 | 1020 | Risk Ratio (M‐H, Random, 95% CI) | 0.49 [0.34, 0.70] |
| Analysis 3.1  Comparison 3: Antibiotics versus control for the treatment of sore throat: symptoms of headache, Outcome 1: Symptom of headache on day 3 | ||||
| 3.2 Symptom of headache on day 3: blinded versus unblinded studies Show forest plot | 4 | 1020 | Risk Ratio (M‐H, Random, 95% CI) | 0.49 [0.34, 0.70] |
| Analysis 3.2  Comparison 3: Antibiotics versus control for the treatment of sore throat: symptoms of headache, Outcome 2: Symptom of headache on day 3: blinded versus unblinded studies | ||||
| 3.2.1 Symptom of headache on day 3: blinded studies | 2 | 436 | Risk Ratio (M‐H, Random, 95% CI) | 0.33 [0.09, 1.20] |
| 3.2.2 Symptom of headache on day 3: unblinded studies | 2 | 584 | Risk Ratio (M‐H, Random, 95% CI) | 0.57 [0.45, 0.72] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Incidence of acute rheumatic fever within 2 months. Rheumatic fever defined by clinical diagnosis Show forest plot | 17 | 12132 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.36 [0.26, 0.50] |
| Analysis 4.1  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 1: Incidence of acute rheumatic fever within 2 months. Rheumatic fever defined by clinical diagnosis | ||||
| 4.2 Incidence of acute rheumatic fever within 2 months. Penicillin versus placebo Show forest plot | 14 | 8407 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.26 [0.18, 0.40] |
| Analysis 4.2  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 2: Incidence of acute rheumatic fever within 2 months. Penicillin versus placebo | ||||
| 4.3 Incidence of acute rheumatic fever within 2 months: early (pre‐1975) versus late studies (post‐1975) Show forest plot | 15 | 9984 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.30 [0.20, 0.45] |
| Analysis 4.3  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 3: Incidence of acute rheumatic fever within 2 months: early (pre‐1975) versus late studies (post‐1975) | ||||
| 4.3.1 Incidence of acute rheumatic fever within 2 months: early (pre‐1975) studies | 10 | 7617 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.30 [0.20, 0.45] |
| 4.3.2 Incidence of acute rheumatic fever within 2 months: late (post‐1975) studies | 5 | 2367 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Not estimable |
| 4.4 Incidence of otitis media within 14 days. Otitis media defined by clinical diagnosis Show forest plot | 10 | 3646 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.21 [0.11, 0.40] |
| Analysis 4.4  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 4: Incidence of otitis media within 14 days. Otitis media defined by clinical diagnosis | ||||
| 4.5 Incidence of otitis media within 14 days: early (pre‐1975) versus late studies (post‐1975) Show forest plot | 10 | 3646 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.21 [0.11, 0.40] |
| Analysis 4.5  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 5: Incidence of otitis media within 14 days: early (pre‐1975) versus late studies (post‐1975) | ||||
| 4.5.1 Incidence of otitis media within 14 days: early (pre‐1975) studies | 5 | 1837 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.25 [0.12, 0.52] |
| 4.5.2 Incidence of otitis media within 14 days: late (post‐1975) studies | 5 | 1809 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.05 [0.01, 0.31] |
| 4.6 Incidence of sinusitis within 14 days. Sinusitis defined by clinical diagnosis Show forest plot | 7 | 2270 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.46 [0.10, 2.05] |
| Analysis 4.6  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 6: Incidence of sinusitis within 14 days. Sinusitis defined by clinical diagnosis | ||||
| 4.7 Incidence of quinsy within 2 months. Quinsy defined by clinical diagnosis Show forest plot | 7 | 2367 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.16 [0.07, 0.35] |
| Analysis 4.7  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 7: Incidence of quinsy within 2 months. Quinsy defined by clinical diagnosis | ||||
| 4.8 Incidence of acute glomerulonephritis within 1 month. Acute glomerulonephritis defined by clinical diagnosis Show forest plot | 10 | 5147 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.07 [0.00, 1.32] |
| Analysis 4.8  Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 8: Incidence of acute glomerulonephritis within 1 month. Acute glomerulonephritis defined by clinical diagnosis | ||||
Study flow diagram for the 2021 review update.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Funnel plot of comparison: 1 Antibiotics versus control for the treatment of sore throats: symptom of sore throat, outcome: 1.1 Symptom of sore throat on day 3.
Funnel plot of comparison: 1 Antibiotics versus control for the treatment of sore throat: symptom of sore throat, outcome: 1.6 Symptom of sore throat at 1 week (6 to 8 days).
Funnel plot of comparison: 4 Antibiotics versus control for the treatment of sore throat: incidence of complications, outcome: 4.1 Incidence of acute rheumatic fever within 2 months. Rheumatic fever defined by clinical diagnosis.
Funnel plot of comparison: 4 Antibiotics versus control for the treatment of sore throat: incidence of complications, outcome: 4.4 Incidence of otitis media within 14 days. Otitis media defined by clinical diagnosis.
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 1: Symptom of sore throat on day 3
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 2: Symptom of sore throat on day 3: early (pre‐1975) versus late studies (post‐1975)
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 3: Symptom of sore throat on day 3: blind versus unblinded studies
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 4: Symptom of sore throat on day 3: antipyretics versus no antipyretics
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 5: Symptom of sore throat on day 3: GABHS‐positive throat swab, negative swab, untested/inseparable
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 6: Symptom of sore throat at 1 week (6 to 8 days)
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 7: Symptom of sore throat at 1 week (6 to 8 days): early (pre‐1975) versus late (post‐1975)
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 8: Symptom of sore throat at 1 week (6 to 8 days): blind versus unblinded studies
Comparison 1: Antibiotics versus control for the treatment of sore throat: symptoms of sore throat, Outcome 9: Symptom of sore throat at 1 week (6 to 8 days): GABHS‐positive throat swab, GABHS‐negative swab
Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 1: Symptom of fever on day 3
Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 2: Symptom of fever on day 3: blinded versus unblinded studies
Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 3: Symptom of fever on day 3: children compared with adults
Comparison 2: Antibiotics versus control for the treatment of sore throat: symptoms of fever, Outcome 4: Symptom of fever at 1 week (6 to 8 days)
Comparison 3: Antibiotics versus control for the treatment of sore throat: symptoms of headache, Outcome 1: Symptom of headache on day 3
Comparison 3: Antibiotics versus control for the treatment of sore throat: symptoms of headache, Outcome 2: Symptom of headache on day 3: blinded versus unblinded studies
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 1: Incidence of acute rheumatic fever within 2 months. Rheumatic fever defined by clinical diagnosis
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 2: Incidence of acute rheumatic fever within 2 months. Penicillin versus placebo
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 3: Incidence of acute rheumatic fever within 2 months: early (pre‐1975) versus late studies (post‐1975)
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 4: Incidence of otitis media within 14 days. Otitis media defined by clinical diagnosis
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 5: Incidence of otitis media within 14 days: early (pre‐1975) versus late studies (post‐1975)
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 6: Incidence of sinusitis within 14 days. Sinusitis defined by clinical diagnosis
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 7: Incidence of quinsy within 2 months. Quinsy defined by clinical diagnosis
Comparison 4: Antibiotics versus control for the treatment of sore throat: incidence of complications, Outcome 8: Incidence of acute glomerulonephritis within 1 month. Acute glomerulonephritis defined by clinical diagnosis
| Antibiotics compared with control for sore throat | ||||||
| Patient or population: adults and children presenting with sore throat Settings: community Intervention: antibiotics Comparison: control (placebo or no treatment) | ||||||
| Outcomes | Anticipated absolute effects (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with control | Risk with antibiotics
| |||||
| Sore throat: day 3 | 660 | 462 (396 to 528) | RR 0.70 (0.60 to 0.80) | 3730 | ⊕⊕⊕⊝ |
|
| Sore throat: 1 week | 190 | 95 (65 to 143) | RR 0.50 (0.34 to 0.75) | 3083 | ⊕⊕⊕⊝ |
|
| Fever: day 3 | 197 | 148 (104 to 211) | RR 0.75 (0.53 to 1.07) | 1443 | ⊕⊕⊕⊕ |
|
| Headache: day 3 | 421 | 206 (143 to 295) | RR 0.49 (0.34 to 0.70) | 1020 | ⊕⊕⊕⊕ |
|
| Rheumatic fever (within 2 months, clinical diagnosis) | 190 | 61 (34 to 110) | Peto OR 0.32 (0.18 to 0.58) | 12,132 | ⊕⊕⊕⊝ | Based largely on risk in pre‐1960 trials |
| Glomerulonephritis (within 1 month, clinical diagnosis) | 1 | 0 (0 to 2) | Peto OR 0.07 (0.00 to 1.32) | 5147 | ⊕⊝⊝⊝ | Sparse data: 2 cases only in the placebo group |
| Quinsy (within 2 months, clinical diagnosis) | 23 | 3 (1 to 11) | Peto OR 0.16 (0.07 to 0.35) | 2367 | ⊕⊕⊕⊕ |
|
| Otitis media (within 14 days, clinical diagnosis) | 20 | 5 (3 to 11) | Peto OR 0.21 (0.11 to 0.40) | 3646 | ⊕⊕⊕⊕ |
|
| The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for high level of heterogeneity. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Symptom of sore throat on day 3 Show forest plot | 16 | 3730 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.60, 0.80] |
| 1.2 Symptom of sore throat on day 3: early (pre‐1975) versus late studies (post‐1975) Show forest plot | 16 | 3730 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.60, 0.80] |
| 1.2.1 Symptom of sore throat on day 3: early (pre‐1975) studies | 6 | 1141 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.56, 0.69] |
| 1.2.2 Symptom of sore throat on day 3: late (post‐1975) studies | 10 | 2589 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.60, 0.88] |
| 1.3 Symptom of sore throat on day 3: blind versus unblinded studies Show forest plot | 16 | 3730 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.60, 0.80] |
| 1.3.1 Symptom of sore throat on day 3: blinded studies | 12 | 2662 | Risk Ratio (M‐H, Random, 95% CI) | 0.65 [0.54, 0.78] |
| 1.3.2 Symptom of sore throat on day 3: unblinded studies | 4 | 1068 | Risk Ratio (M‐H, Random, 95% CI) | 0.81 [0.65, 1.01] |
| 1.4 Symptom of sore throat on day 3: antipyretics versus no antipyretics Show forest plot | 5 | 1137 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.48, 0.70] |
| 1.4.1 Symptom of sore throat on day 3: antipyretics administered | 3 | 455 | Risk Ratio (M‐H, Random, 95% CI) | 0.52 [0.33, 0.81] |
| 1.4.2 Symptom of sore throat on day 3: no antipyretics administered | 2 | 682 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.55, 0.70] |
| 1.5 Symptom of sore throat on day 3: GABHS‐positive throat swab, negative swab, untested/inseparable Show forest plot | 15 | 3600 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.59, 0.78] |
| 1.5.1 Symptom of sore throat on day 3: GABHS‐positive throat swab | 11 | 1839 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.48, 0.71] |
| 1.5.2 Symptom of sore throat on day 3: GABHS‐negative throat swab | 6 | 736 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.63, 0.97] |
| 1.5.3 Symptom of sore throat on day 3: untested for GABHS culture or combined, inseparable data | 3 | 1025 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.80, 1.00] |
| 1.6 Symptom of sore throat at 1 week (6 to 8 days) Show forest plot | 14 | 3083 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.34, 0.75] |
| 1.7 Symptom of sore throat at 1 week (6 to 8 days): early (pre‐1975) versus late (post‐1975) Show forest plot | 14 | 3083 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.34, 0.75] |
| 1.7.1 Symptom of sore throat at 1 week (6 to 8 days): early (pre‐1975) studies | 6 | 1140 | Risk Ratio (M‐H, Random, 95% CI) | 0.14 [0.08, 0.27] |
| 1.7.2 Symptom of sore throat at 1 week (6 to 8 days): late (post‐1975) studies | 8 | 1943 | Risk Ratio (M‐H, Random, 95% CI) | 0.73 [0.55, 0.97] |
| 1.8 Symptom of sore throat at 1 week (6 to 8 days): blind versus unblinded studies Show forest plot | 14 | 3053 | Risk Ratio (M‐H, Random, 95% CI) | 0.57 [0.39, 0.82] |
| 1.8.1 Symptom of sore throat at 1 week (6 to 8 days): blinded studies | 9 | 1616 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.38, 1.03] |
| 1.8.2 Symptom of sore throat at 1 week (6 to 8 days): unblinded studies | 5 | 1437 | Risk Ratio (M‐H, Random, 95% CI) | 0.43 [0.20, 0.91] |
| 1.9 Symptom of sore throat at 1 week (6 to 8 days): GABHS‐positive throat swab, GABHS‐negative swab Show forest plot | 12 | 2524 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.29, 0.80] |
| 1.9.1 Symptom of sore throat at 1 week (6 to 8 days): GABHS‐positive throat swab | 7 | 1117 | Risk Ratio (M‐H, Random, 95% CI) | 0.29 [0.12, 0.70] |
| 1.9.2 Symptom of sore throat at 1 week (6 to 8 days): GABHS‐negative throat swab | 5 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 0.73 [0.50, 1.07] |
| 1.9.3 Symptom of sore throat at 1 week (6 to 8 days): GABHS untested | 3 | 866 | Risk Ratio (M‐H, Random, 95% CI) | 0.35 [0.03, 4.47] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Symptom of fever on day 3 Show forest plot | 8 | 1443 | Risk Ratio (M‐H, Random, 95% CI) | 0.75 [0.53, 1.07] |
| 2.2 Symptom of fever on day 3: blinded versus unblinded studies Show forest plot | 8 | 1443 | Risk Ratio (M‐H, Random, 95% CI) | 0.75 [0.53, 1.07] |
| 2.2.1 Symptom of fever on day 3: blinded studies | 4 | 703 | Risk Ratio (M‐H, Random, 95% CI) | 0.82 [0.54, 1.23] |
| 2.2.2 Symptom of fever on day 3: unblinded studies | 4 | 740 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.43, 1.21] |
| 2.3 Symptom of fever on day 3: children compared with adults Show forest plot | 5 | 766 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.31, 1.26] |
| 2.3.1 Symptom of fever on day 3: children | 2 | 61 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.76, 2.13] |
| 2.3.2 Symptom of fever on day 3: adults | 3 | 705 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.21, 1.10] |
| 2.4 Symptom of fever at 1 week (6 to 8 days) Show forest plot | 4 | 886 | Risk Ratio (M‐H, Random, 95% CI) | 0.91 [0.55, 1.52] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Symptom of headache on day 3 Show forest plot | 4 | 1020 | Risk Ratio (M‐H, Random, 95% CI) | 0.49 [0.34, 0.70] |
| 3.2 Symptom of headache on day 3: blinded versus unblinded studies Show forest plot | 4 | 1020 | Risk Ratio (M‐H, Random, 95% CI) | 0.49 [0.34, 0.70] |
| 3.2.1 Symptom of headache on day 3: blinded studies | 2 | 436 | Risk Ratio (M‐H, Random, 95% CI) | 0.33 [0.09, 1.20] |
| 3.2.2 Symptom of headache on day 3: unblinded studies | 2 | 584 | Risk Ratio (M‐H, Random, 95% CI) | 0.57 [0.45, 0.72] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Incidence of acute rheumatic fever within 2 months. Rheumatic fever defined by clinical diagnosis Show forest plot | 17 | 12132 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.36 [0.26, 0.50] |
| 4.2 Incidence of acute rheumatic fever within 2 months. Penicillin versus placebo Show forest plot | 14 | 8407 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.26 [0.18, 0.40] |
| 4.3 Incidence of acute rheumatic fever within 2 months: early (pre‐1975) versus late studies (post‐1975) Show forest plot | 15 | 9984 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.30 [0.20, 0.45] |
| 4.3.1 Incidence of acute rheumatic fever within 2 months: early (pre‐1975) studies | 10 | 7617 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.30 [0.20, 0.45] |
| 4.3.2 Incidence of acute rheumatic fever within 2 months: late (post‐1975) studies | 5 | 2367 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Not estimable |
| 4.4 Incidence of otitis media within 14 days. Otitis media defined by clinical diagnosis Show forest plot | 10 | 3646 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.21 [0.11, 0.40] |
| 4.5 Incidence of otitis media within 14 days: early (pre‐1975) versus late studies (post‐1975) Show forest plot | 10 | 3646 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.21 [0.11, 0.40] |
| 4.5.1 Incidence of otitis media within 14 days: early (pre‐1975) studies | 5 | 1837 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.25 [0.12, 0.52] |
| 4.5.2 Incidence of otitis media within 14 days: late (post‐1975) studies | 5 | 1809 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.05 [0.01, 0.31] |
| 4.6 Incidence of sinusitis within 14 days. Sinusitis defined by clinical diagnosis Show forest plot | 7 | 2270 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.46 [0.10, 2.05] |
| 4.7 Incidence of quinsy within 2 months. Quinsy defined by clinical diagnosis Show forest plot | 7 | 2367 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.16 [0.07, 0.35] |
| 4.8 Incidence of acute glomerulonephritis within 1 month. Acute glomerulonephritis defined by clinical diagnosis Show forest plot | 10 | 5147 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.07 [0.00, 1.32] |
