Intervention Review

You have free access to this content

Antibiotics for sore throat

  1. Anneliese Spinks1,*,
  2. Paul P Glasziou2,
  3. Chris B Del Mar2

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 5 NOV 2013

Assessed as up-to-date: 11 JUL 2013

DOI: 10.1002/14651858.CD000023.pub4


How to Cite

Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD000023. DOI: 10.1002/14651858.CD000023.pub4.

Author Information

  1. 1

    Griffith University, School of Medicine, Meadowbrook, Queensland, Australia

  2. 2

    Bond University, Centre for Research in Evidence-Based Practice (CREBP), Gold Coast, Queensland, Australia

*Anneliese Spinks, School of Medicine, Griffith University, University Drive, Meadowbrook, Queensland, 4031, Australia. anneliese.spinks@csiro.au. a.spinks@griffith.edu.au.

Publication History

  1. Publication Status: Edited (no change to conclusions), comment added to review
  2. Published Online: 5 NOV 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Bennike 1951

MethodsOpen study, quasi-randomised


Participants669 patients 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. Participants were excluded if they had a complication of tonsillitis on admission or if they had previous antibiotic treatment for the present sore throat


InterventionsAge-adjusted intramuscular penicillin twice daily for 6 days or no treatment as a control condition


OutcomesIncidence of rheumatic fever, otitis media, quinsy, sinusitis and symptoms of sore throat and headache


NotesNo antipyretics were administered to the control group. The use of antipyretics to participants in the treatment group was unstated


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskParticipants allocated to alternate conditions on alternate days

Allocation concealment (selection bias)High riskNo concealment of allocation present

Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding of participants or assessments

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskNo antipyretics were administered to the control group. The use of antipyretics to participants in the treatment group was unstated

Brink 1951

MethodsOpen study


Participants395 young adult males recruited into United States Air Force


InterventionsIntramuscular penicillin over 4 days, chlortetracycline for 3 days or no treatment as control group


OutcomesIncidence of rheumatic fever, otitis media and symptoms of sore throat, fever and headache


NotesNo antipyretics were administered


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised by Air Force serial number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
High risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Brumfitt 1957

MethodsOpen study


Participants121 young adult men, aged 18 to 21 years, recruited into United States Air Force. Participants were excluded from study if their temperature was below 99.3 degrees F, if they had sore throat for more than 72 hours prior to presentation, or if they had some other generalised illness


InterventionsIntramuscular penicillin twice-daily for 4 days or no treatment as a control condition


OutcomesIncidence of rheumatic fever and symptoms of sore throat and fever


NotesAspirin gargles were given 6-hourly. Whether participants were permitted to swallow the aspirin was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised by hospital bed number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
High risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Catanzaro 1954

MethodsSingle-blind, participants were unaware of treatment type, placebo-controlled trial. The outcome of treatment was not determined blind


Participants640 young adult males recruited into United States Air Force. Missing data were not explained
Data from participants who produced a GABHS-negative throat swab were excluded. Participants were excluded if they presented with a suppurative complication at the time of admission


InterventionsIntramuscular penicillin administered for 5 days, sulphonamide administered for 5 days or no treatment as a control condition


OutcomesIncidence of rheumatic fever


NotesAntipyretic use was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised by Air Force serial number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Chamovitz 1954

MethodsSingle-blind placebo study


Participants366 young adult males recruited into United States Air Force. Participants 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


InterventionsIntramuscular penicillin


OutcomesIncidence of rheumatic fever, otitis media and sinusitis


NotesAntipyretic use was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised by Air Force serial number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
Unclear riskParticipants did not know treatment type they were receiving. The outcome of treatment was not determined blind

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Chapple 1956

MethodsDouble-blind, placebo-controlled trial


Participants308 participants older than 2 years. Data from 283 participants included in analyses


InterventionsAge-adjusted oral penicillin, sulphadimidine or barium sulphate (placebo) administered for 5 days


OutcomesIncidence of rheumatic fever, otitis media and symptom of sore throat


NotesAll 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


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants randomised by random bottle dispensing

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Dagnelie 1996

MethodsRandomised, double-blind, placebo-controlled trial of penicillin V on the course and bacteriological response in patients with sore throat in general practice


Participants239 patients aged 4 to 60, presenting with sore throat to 37 General Practices in the Netherlands, who were clinically suspected of GABHS


InterventionsTreatment with either penicillin V or placebo


OutcomesResolution of sore throat, fever and return to daily activities (assessed by doctor and by diary for 7 days)


Notes* Need raw data to make this study comparable to the meta-analysis, however data are available for sore throat on day 3 and quinsy


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random sequence

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition of participants

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

De Meyere 1992

MethodsDouble-blind, placebo-controlled trial


Participants173 participants aged 5 to 50 years, from the Gent region of Belgium
Data were obtained from 173 participants on days 1 and 3
Data were obtained from 131 participants on days 2, 4, 5, 6 and 7
Participants 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, were in any high-risk situation as determined by the physician


InterventionsOral penicillin or oral placebo 3 times a day


OutcomesSymptom of sore throat
All data obtained, except from days 1 and 3, were self reported from a diary


NotesAntipyretics were used as required by participants. Use of antipyretics and other symptom-relieving methods was documented in a diary


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation method not documented

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Denny 1950

MethodsSingle-blind study. The outcome was determined blind on follow-up by physicians who did not know what treatment type each participant had received


Participants1602 young adult males recruited into United States Air Force


InterventionsIntramuscular penicillin for 4 days or no treatment as a control group


OutcomesIncidence of rheumatic fever only


NotesAntipyretic use was not stated


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised by Air Force serial number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
Unclear riskSingle blind study - assessment was conducted by physicians who were unaware of treatment condition

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not stated

Denny 1953

MethodsSingle-blind, randomised, placebo-controlled trial. Outcome determined blind by physicians who did not know treatment type


Participants103 young adult males recruited in the United States Air Force. Participants 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


InterventionsIntramuscular penicillin daily for 5 days, oral aureomycin or oral terramycin administered every 6 hours for 3 days or oral lactose placebo for 3 days as a control condition


OutcomesIncidence of acute rheumatic fever, otitis media, quinsy, sinusitis and symptoms of sore throat and headache


NotesNo antipyretics were administered


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants were randomly allocated to treatment groups by drawing a card from a deck

Blinding (performance bias and detection bias)
All outcomes
Unclear riskSingle-blind study - assessment was conducted by physicians who were unaware of treatment condition

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

El-Daher 1991

MethodsDouble-blinded, randomised controlled trial


Participants229 children with positive culture for GABHS


InterventionsEarly treatment with oral penicillin for 10 days versus oral placebo for 2 days followed by oral penicillin for 8 days


OutcomesSymptoms of sore throat and headache on day 3


NotesExamination of participants was done on day 3 before administering penicillin to placebo group


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition of participants

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Howe 1997

Methods22 GPs in one region of the UK recruited


Participants154 patients aged 16 to 60 years presenting to their GP with sore throat and for whom the GP would normally prescribe an antibiotic


InterventionsTherapy with either penicillin V (250 mg 4 times a day), cefixime (200 mg daily) or placebo


OutcomesResolution of a composite "symptom score" with time; eradication of GABHS. A diary was kept of symptom resolution over 7 days


Notes*Symptom results were bundled into a composite "symptom score". The raw data on sore throat, cough and fever resolution has been requested from the authors


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlock randomisation scheme (performed in blocks of 6)

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Krober 1985

MethodsDouble-blind placebo trial


Participants44 children presenting to a paediatric clinic. 26 of these participants yielded GABHS-positive throat swabs
Participants 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
Participants who produced GABHS-negative throat swabs were excluded from the study


InterventionsOral penicillin or similar looking and tasting oral placebo for the control condition, 3 times a day for 3 days


OutcomesSymptom of fever


NotesAntipyretic use was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants were randomised by table of random numbers

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Landsman 1951

MethodsDouble-blind, randomised, placebo-controlled trial


Participants95 participants who presented to general practice complaining of sore throat


InterventionsOral sulphonamide or similar looking and tasting oral placebo, for the control condition


OutcomesIncidence of sinusitis or quinsy or symptoms of sore throat or fever


NotesAntipyretic use was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised by random numbering of bottles

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Leelarasamee 2000

MethodsDouble-blind, randomised, placebo-controlled trial


Participants1217 patients aged over 5 years presenting to 4 community-based medical centres with complaints of fever or sore throat of less than 10 days duration


InterventionsParticipants were randomised to receive either amoxycillin or placebo for 7 days


OutcomesDuration of sore throat and fever. Incidence of complications and adverse reactions


NotesAntipyretics were given if deemed necessary by physicians


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random sequence

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSome loss to follow-up occurred

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Little 1997

MethodsUnblinded randomised trial


Participants716 patients aged 4 years and over, presenting to their GP with a sore throat, with an abnormal physical finding localised to the throat (e.g. inflamed tonsils or pharynx, etc.)


InterventionsParticipants were randomised to 3 groups. Participants in the first group were given an antibiotic for 10 days; those in the second group were given no prescription; and in the third group were given an offer of antibiotic prescription if the symptoms were not starting to settle after 3 days


OutcomesMain outcomes - duration of symptoms, satisfaction and compliance with and perceived efficacy of antibiotics, time off school or work. Participants given a daily diary in which to record symptoms and temperature. Participants who did not return diaries were followed up over the phone


NotesParticipants randomised, but neither participants nor doctors blinded to the therapy


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding of participants or assessors was performed

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition of participants

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

MacDonald 1951

MethodsOutcome determined blind


Participants82 young adult males recruited into the United States Air Force
41 in treatment group; 41 in control group


InterventionsOral sulphatriad or identical oral lactose placebo, administered to the control condition, taken every 4 hours


OutcomesSymptom of sore throat


NotesAntipyretics were administered to 1 participant in the treatment group and 2 participants in the control group


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised by Air Force serial number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
Low riskOutcomes were determined blind

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Middleton 1988

MethodsMulticentre, double-blind, randomised, placebo-controlled


Participants178 participants aged 4 to 29 years with streptococcal pharyngitis. Participants had symptom duration of less than 4 days. Results reported for 57 participants with severe illness only


Interventions8 individual doses of penicillin or placebo


OutcomesSymptoms of sore throat and fever


NotesPhone report after 48 hours used to measure outcome at day 3


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design used

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo attrition of participants

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Nelson 1984

MethodsAn oral placebo was used to single-blind participants, however outcome was not determined blind


Participants51 children aged 5 to 11 years. Sixteen participants were excluded because they did not produce GABHS-positive throat swabs, leaving 35 participants. Children with history of penicillin hypersensitivity were also excluded


InterventionsIntramuscular penicillin or oral syrup placebo as a control group


OutcomesSymptoms of sore throat and fever


NotesNo antipyretics were administered


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised to conditions by hospital number allocation

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
Unclear riskAn oral placebo was used to single-blind participants. However outcome was not determined blind

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Petersen 1997

MethodsRandomised placebo-controlled trial of participants' culture-negative for GABHS


Participants186 adults (aged 18 to 50) presenting to an ambulatory setting, whose chief complaint was sore throat and whose GABHS culture was subsequently found to be negative


InterventionsTreatment with either erythromycin (333 mg, 3 times daily) or placebo


OutcomesMain outcomes - time to improvement in sore throat, cough, activity level and sense of well-being. Participants completed a daily questionnaire on the progress of outcome measures. Follow-up visits were arranged 2 to 3 weeks after enrolment to repeat cultures, collect diaries and assess compliance


NotesIt is not clear how many participants kept diaries for the sore throat data in each group. Authors excluded GABHS-positive patients (15 out of 212 initially randomised)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low risk

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskIt is not clear how many participants kept diaries for the sore throat data in each group. Authors excluded GABHS-positive participants (15 out of 212 initially randomised)

Pichichero 1987

MethodsSingle-blind, randomised, placebo-controlled trial


Participants114 GABHS-positive children aged 4 to 18 years. Children were excluded from the study if: a throat swab was negative for GABHS; were allergic to penicillin; had received penicillin in past 7 days; had another acute illness within 7 days, had a GABHS-positive swab in past month, or had another concurrent infection that required antibiotics


InterventionsOral penicillin for 48 hours or an identical-looking and tasting oral placebo used for the control condition


OutcomesIncidence of otitis media, quinsy or sinusitis


NotesAntipyretics administered 4-hourly


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random sequence

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskSingle-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo participant attrition

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Siegel 1961

MethodsRandomised controlled trial


Participants1213 children aged 3 to 16 years. Suppurative complications occurring in participants in the control condition were treated with sulphonamides. Participants were excluded if they had a complication on admission


InterventionsIntramuscular penicillin or no treatment for the controls


OutcomesIncidence of rheumatic fever


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised by bed chart number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
High risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Taylor 1977

MethodsDouble-blind, randomised, placebo-controlled trial


Participants122 children aged 2 to 10 years. Children with positive Streptococcus throat swabs were excluded
9 children were excluded during trial because of pre-existing suppurative complications


InterventionsOral amoxycillin, oral cotrimoxazole or an oral placebo was administered by parents 3 times a day for 5 days


OutcomesIncidence of otitis media and sinusitis and symptoms of sore throat and fever


NotesAntipyretic use was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method of randomisation to groups was not documented

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Wannamaker 1951

MethodsSingle-blind study. The intervention outcomes were determined by physicians who were unaware of participant treatment allocation


Participants1974 young adult males recruited into the United States Air Force


InterventionsIntramuscular penicillin over 1 to 3 days or no treatment for the control condition


OutcomesIncidence of rheumatic fever


NotesAntipyretic use was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomised to groups by Air Force serial number

Allocation concealment (selection bias)High risk

Blinding (performance bias and detection bias)
All outcomes
Low riskSingle-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Whitfield 1981

MethodsDouble-blind, randomised, placebo-controlled trial


ParticipantsParticipants were people who presented to the General Practitioner with sore throat, aged more than 10 years. 745 participants were commenced on the study. Only 528 returned questionnaires. Participants were excluded if the General Practitioner thought the participant would demonstrate poor compliance; if they had previous reaction to penicillin; or a previous episode of rheumatic fever or acute nephritis


InterventionsOral penicillin 4 times a day for 5 days or identical-looking and tasting oral lactose placebo 4 times a day for 5 days


OutcomesSymptom of fever


NotesAntipyretic use was not documented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised by pre-determined random order

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear riskAntipyretic use was not documented

Zwart 2000

MethodsDouble-blind, randomised, placebo-controlled trial


Participants561 participants aged 15 to 60 years presenting with sore throat of less than 7 days duration


InterventionsPenicillin V for 7 days, penicillin V for 3 days followed by 4 days of placebo or placebo or 7 days


OutcomesResolution of symptoms and recurrence of sore throat


NotesAuthor was contacted for data that could be used in the meta-analysis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random sequence

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study design

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

Zwart 2003

MethodsDouble-blind, randomised, placebo-controlled trial


Participants156 children aged 4 to 15 years presenting with sore throat of less than 7 days duration with at least 2 of 4 Centor criteria


InterventionsPenicillin V for 7 days, penicillin V for 3 days followed by 4 days of placebo or placebo or 7 days


OutcomesDuration of symptoms of sore throat, occurrence of streptococcal sequelae


NotesAuthor was contacted for data that could be used in the meta-analysis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random sequence

Allocation concealment (selection bias)Low risk

Blinding (performance bias and detection bias)
All outcomes
Low risk

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Low riskAll relevant outcomes reported

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Barwitz 1999Participants were randomised to 2 GPs for subsequent treatment with different management protocols

Bass 1986Study used a Likert scale to measure severity and duration of symptoms. No raw scores are available for entry into meta-analysis

Bishop 1952Non-randomised allocation to treatment groups. (Quote) "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

Catanzaro 1958Study compared sulphonamides with other antibiotics. No control condition was used

Cruickshank 1960Study is another report of the data previously published by Brumfitt 1957

Dowell 2001Cough was the main complaint for patients, not sore throat

Gerber 1985Study compared 2 different regimens of penicillin. No placebo control group was used

Gerber 1989Assessed 2 regimes of penicillin. No control group used

Ginsburg 1980Study compared penicillin V with cefadroxil. No placebo control group was used

Guthrie 1988Study did not use control condition

Haverkorn 1971Participants not treated with antibiotics given antipyretics. Participants receiving antibiotics received no antipyretics. No control condition

Herz 1988No participant-centred outcomes, except return visits for URIs
Poor randomisation - out of a series of 202, the first and last 50 were assigned to antibiotics, with the middle 102 assigned to control

Howie 1970Illness was "cold or flu-like illness", not acute pharyngitis (exclusively). Soreness of throat not an outcome measure

Jensen 1991Participants were not randomly allocated to treatment groups and were not blinded to treatment

Kapur 2011No intervention was provided to participants. Study tracked natural course of illness only

Kolobukhina 2011Study investigated the combination of Ingavirin (antiviral medication) with an antibacterial agent in adults with viral respiratory infections. No comparison of antibiotics alone against placebo

Marlow 1989Participant 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 this meta-analysis

Massell 1951Study 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 given

McDonald 1985No data suitable for this meta-analysis were described although symptoms were recorded. The author was approached for these data, but no reply was received

Merenstein 1974No data on suppurative or non-suppurative complications
No data on day 3 for soreness of throat, fever or headache

Morris 1956Study observed effect of sulfadiazine on prevention of rheumatic fever only. No control condition was used

Nasonova 1999Study a controlled clinical trial without randomisation of participants

Pandraud 2002Investigation of effect of fusafungine on chronic conditions of follicular pharyngitis. Not relevant for this review

Randolph 1985No data on suppurative or non-suppurative complications
No data on day 3 or 7 for soreness of throat, fever or headache

Schalen 1985Primary complaint hoarseness, not sore throat. No patient-centred outcomes apart from hoarseness

Schalen 1993Patients presented for laryngitis and hoarseness, not pharyngitis

Schwartz 1981Study compared 7 versus 10 days of treatment with penicillin. No control group was used

Shevrygin 2000Study was a clinical trial without a control condition

Shvartzman 1993Study compared efficacy of amoxycillin against penicillin, no control condition was used

Stillerman 1986Study compared penicillin with cephalosporins, no control group was used

Stromberg 1988No placebo control group was used. Study compared different antibiotic regimens

Supajatura 2012Antibiotics were not offered as an intervention. Study investigated the efficacy of Mangosteen spray against placebo only

Todd 1984Primary complaint not sore throat - purulent nasopharyngitis instead

Valkenburg 1971Study did not involve any control measures. Data only given for participants not treated with antibiotics

 
Comparison 1. Antibiotics versus placebo for the treatment of sore throats: symptom of sore throat

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptom of sore throat on day 3153621Risk Ratio (M-H, Random, 95% CI)0.68 [0.59, 0.79]

 2 Symptom of sore throat on day 3: blind versus unblinded studies153621Risk Ratio (M-H, Random, 95% CI)0.68 [0.59, 0.79]

    2.1 Symptom of sore throat on day 3: blinded studies
122662Risk Ratio (M-H, Random, 95% CI)0.65 [0.54, 0.78]

    2.2 Symptom of sore throat on day 3: unblinded studies
3959Risk Ratio (M-H, Random, 95% CI)0.79 [0.60, 1.05]

 3 Symptom of sore throat on day 3: antipyretics versus no antipyretics51137Risk Ratio (M-H, Random, 95% CI)0.58 [0.48, 0.70]

    3.1 Symptom of sore throat on day 3: antipyretics administered
3455Risk Ratio (M-H, Random, 95% CI)0.52 [0.33, 0.81]

    3.2 Symptom of sore throat on day 3: no antipyretics administered
2682Risk Ratio (M-H, Random, 95% CI)0.62 [0.55, 0.70]

 4 Symptom of sore throat on day 3: GABHS-positive throat swab, negative swab, untested/inseparable153600Risk Ratio (M-H, Random, 95% CI)0.68 [0.59, 0.78]

    4.1 Symptom of sore throat on day 3: GABHS-positive throat swab
111839Risk Ratio (M-H, Random, 95% CI)0.58 [0.48, 0.71]

    4.2 Symptom of sore throat on day 3: GABHS-negative throat swab
6736Risk Ratio (M-H, Random, 95% CI)0.78 [0.63, 0.97]

    4.3 Symptom of sore throat on day 3: untested for GABHS culture or combined inseparable data
31025Risk Ratio (M-H, Random, 95% CI)0.89 [0.80, 1.00]

 5 Symptom of sore throat at one week (6 to 8 days)132974Risk Ratio (M-H, Random, 95% CI)0.49 [0.32, 0.76]

 6 Symptom of sore throat at one week (6 to 8 days): blind versus unblinded studies132944Risk Ratio (M-H, Random, 95% CI)0.57 [0.38, 0.86]

    6.1 Symptom of sore throat at 1 week (6 to 8 days): blinded studies
91616Risk Ratio (M-H, Random, 95% CI)0.62 [0.38, 1.03]

    6.2 Symptom of sore throat at 1 week (6 to 8 days): unblinded studies
41328Risk Ratio (M-H, Random, 95% CI)0.30 [0.08, 1.15]

 7 Symptom of sore throat at one week (6 to 8 days): GABHS-positive throat swab, GABHS-negative swab122524Risk Ratio (M-H, Random, 95% CI)0.48 [0.29, 0.80]

    7.1 Symptom of sore throat at 1 week (6 to 8 days): GABHS-positive throat swab
71117Risk Ratio (M-H, Random, 95% CI)0.29 [0.12, 0.70]

    7.2 Symptom of sore throat at 1 week (6 to 8 days): GABHS-negative throat swab
5541Risk Ratio (M-H, Random, 95% CI)0.73 [0.50, 1.07]

    7.3 Symptom of sore throat at 1 week (6 to 8 days): GABHS untested
3866Risk Ratio (M-H, Random, 95% CI)0.35 [0.03, 4.47]

 
Comparison 2. Antibiotics versus control for the treatment of sore throat: symptom of fever

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptom of fever on day 371334Risk Ratio (M-H, Random, 95% CI)0.71 [0.45, 1.10]

 2 Symptom of fever on day 3: blinded versus unblinded studies71334Risk Ratio (M-H, Random, 95% CI)0.71 [0.45, 1.10]

    2.1 Symptom of fever on day 3: blinded studies.
4703Risk Ratio (M-H, Random, 95% CI)0.82 [0.54, 1.23]

    2.2 Symptom of fever on day 3: unblinded studies.
3631Risk Ratio (M-H, Random, 95% CI)0.65 [0.31, 1.37]

 3 Symptom of fever on day 3: children compared with adults4657Risk Ratio (M-H, Random, 95% CI)0.51 [0.18, 1.46]

    3.1 Symptom of fever on day 3: children
261Risk Ratio (M-H, Random, 95% CI)1.27 [0.76, 2.13]

    3.2 Symptom of fever on day 3: adults
2596Risk Ratio (M-H, Random, 95% CI)0.29 [0.06, 1.51]

 4 Symptom of fever at 1 week (6 to 8 days)3777Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Antibiotics versus control for the treatment of sore throat: symptom of headache

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptom of headache on day 33911Risk Ratio (M-H, Random, 95% CI)0.44 [0.27, 0.71]

 2 Symptom of headache on day 3: blinded versus unblinded studies3911Risk Ratio (M-H, Random, 95% CI)0.44 [0.27, 0.71]

    2.1 Symptom headache on day 3: blinded studies
2436Risk Ratio (M-H, Random, 95% CI)0.33 [0.09, 1.20]

    2.2 Symptom of headache on day 3: unblinded studies
1475Risk Ratio (M-H, Random, 95% CI)0.55 [0.41, 0.72]

 
Comparison 4. Antibiotics versus placebo for the treatment of sore throat: incidence of complications

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Incidence of acute rheumatic fever within 2 months. Rheumatic fever defined by clinical diagnosis1610101Risk Ratio (M-H, Random, 95% CI)0.27 [0.12, 0.60]

 2 Incidence of acute rheumatic fever within 2 months. Penicillin versus placebo148175Risk Ratio (M-H, Random, 95% CI)0.27 [0.14, 0.50]

 3 Incidence of acute rheumatic fever within 2 months: early (pre-1975) versus late studies (post-1975)1610101Risk Ratio (M-H, Random, 95% CI)0.27 [0.12, 0.60]

    3.1 Incidence of acute rheumatic fever within 2 months: early (pre-1975) studies
107617Risk Ratio (M-H, Random, 95% CI)0.27 [0.12, 0.60]

    3.2 Incidence of acute rheumatic fever within 2 months: late (post-1975) studies
62484Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 4 Incidence of otitis media within 14 days. Otitis media defined by clinical diagnosis113760Risk Ratio (M-H, Random, 95% CI)0.30 [0.15, 0.58]

 5 Incidence of otitis media within 14 days: early (pre-1975) versus late studies (post-1975)113760Risk Ratio (M-H, Random, 95% CI)0.30 [0.15, 0.58]

    5.1 Incidence of otitis media within 14 days: early (pre-1975) studies
51837Risk Ratio (M-H, Random, 95% CI)0.30 [0.15, 0.62]

    5.2 Incidence of otitis media within 14 days: late (post-1975) studies
61923Risk Ratio (M-H, Random, 95% CI)0.28 [0.03, 2.74]

 6 Incidence of sinusitis within 14 days. Sinusitis defined by clinical diagnosis82387Risk Ratio (M-H, Random, 95% CI)0.48 [0.08, 2.76]

 7 Incidence of quinsy within 2 months. Quinsy defined by clinical diagnosis82433Risk Ratio (M-H, Random, 95% CI)0.15 [0.05, 0.47]

 8 Incidence of acute glomerulonephritis within 1 month. Acute glomerulonephritis defined by clinical diagnosis105147Risk Ratio (M-H, Random, 95% CI)0.22 [0.02, 2.08]

 
Summary of findings for the main comparison.

Antibiotics compared with placebo for sore throat

Patient or population: patients presenting with sore throat

Settings: community

Intervention: antibiotics

Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

AntibioticsPlacebo

Sore throat: day 30.660.720.68 to 0.763621 (15)High

Sore throat: day 70.180.650.55 to 0.762974 (13)High

Rheumatic fever0.0170.290.18 to 0.4410,101 (16)HighBased largely on risk in pre-1960 trials

Glomerulonephritis0.0010.220.07 to 1.325147 (10)LowSparse data: 2 cases only

Quinsy0.0230.140.05 to 0.392433 (8)High

Otitis media0.020.280.15 to 0.523760 (11)High

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.