Antibiotics for treatment of sore throat in children and adults

Anneliese Spinks; Paul P Glasziou; Chris B Del Mar

doi:10.1002/14651858.CD000023.pub5

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Figure 1

Study flow diagram for the 2021 review update.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

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.

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Figure 5

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).

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Figure 6

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.

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Figure 7

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.

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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

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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)

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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

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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

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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

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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)

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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)

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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

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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

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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

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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

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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

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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)

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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

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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

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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

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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

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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)

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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

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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)

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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

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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

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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

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Summary of findings 1. Antibiotics compared with control for sore throat

Outcomes	Anticipated absolute effects (95% CI)		Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with control	Risk with antibiotics	Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sore throat: day 3	660	462 (396 to 528)	RR 0.70 (0.60 to 0.80)	3730 (16 studies)	⊕⊕⊕⊝ Moderate^a
Sore throat: 1 week	190	95 (65 to 143)	RR 0.50 (0.34 to 0.75)	3083 (14 studies)	⊕⊕⊕⊝ Moderate^a
Fever: day 3	197	148 (104 to 211)	RR 0.75 (0.53 to 1.07)	1443 (8 studies)	⊕⊕⊕⊕ High
Headache: day 3	421	206 (143 to 295)	RR 0.49 (0.34 to 0.70)	1020 (4 studies)	⊕⊕⊕⊕ High
Rheumatic fever (within 2 months, clinical diagnosis)	190	61 (34 to 110)	Peto OR 0.32 (0.18 to 0.58)	12,132 (17 studies)	⊕⊕⊕⊝ Moderate^a	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 (10 studies)	⊕⊝⊝⊝ Low^b	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 (7 studies)	⊕⊕⊕⊕ High
Otitis media (within 14 days, clinical diagnosis)	20	5 (3 to 11)	Peto OR 0.21 (0.11 to 0.40)	3646 (10 studies)	⊕⊕⊕⊕ High
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). CI: confidence interval; OR: odds ratio; RR: risk ratio
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded one level for high level of heterogeneity. ^bDowngraded two levels for serious imprecision relating to very small number of reported cases.

Summary of findings 1. Antibiotics compared with control for sore throat

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Comparison 1. Antibiotics versus control for the treatment of sore throat: symptoms of sore throat

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]

Comparison 1. Antibiotics versus control for the treatment of sore throat: symptoms of sore throat

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

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]

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

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

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]

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

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

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]

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

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