Delayed antibiotics for symptoms and complications of respiratory infections

Geoffrey KP Spurling; Chris Del Mar; Liz Dooley; Ruth Foxlee

doi:10.1002/14651858.CD004417.pub2

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Figure 1

Pain on day 3

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Analysis 1.1

Comparison 1 Fever, Outcome 1 Fever on day 3.

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Analysis 1.2

Comparison 1 Fever, Outcome 2 Fever on day 7.

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Analysis 2.1

Comparison 2 Adverse events, Outcome 1 Vomiting.

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Analysis 2.2

Comparison 2 Adverse events, Outcome 2 Diarrhoea.

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Analysis 2.3

Comparison 2 Adverse events, Outcome 3 Rash.

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Analysis 2.4

Comparison 2 Adverse events, Outcome 4 Stomach ache.

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Analysis 2.5

Comparison 2 Adverse events, Outcome 5 Reconsultation rate.

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Analysis 3.1

Comparison 3 Pain, Outcome 1 Pain on day 3.

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Analysis 3.2

Comparison 3 Pain, Outcome 2 Pain on day 7.

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Analysis 4.1

Comparison 4 Malaise, Outcome 1 Malaise on day 3.

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Analysis 5.1

Comparison 5 Cough, Outcome 1 Cough on day 3.

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Analysis 5.2

Comparison 5 Cough, Outcome 2 Cough on day 7.

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Analysis 6.4

Comparison 6 Malaise severity, Outcome 4 Malaise severity day 3.

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Analysis 6.8

Comparison 6 Malaise severity, Outcome 8 Malaise severity day 7.

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Analysis 6.9

Comparison 6 Malaise severity, Outcome 9 Last day of crying.

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Analysis 7.4

Comparison 7 Pain severity, Outcome 4 Pain severity day 3.

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Analysis 7.7

Comparison 7 Pain severity, Outcome 7 Pain severity day 7.

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Analysis 8.1

Comparison 8 Paracetamol consumption, Outcome 1 Spoons/day.

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Analysis 9.1

Comparison 9 Fever Severity, Outcome 1 Fever severity on day 3.

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Analysis 9.2

Comparison 9 Fever Severity, Outcome 2 Fever severity on day 7.

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Analysis 9.3

Comparison 9 Fever Severity, Outcome 3 Fever severity on day 1.

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Table 1. Quality of Included Studies

Study	Randomisation	Allocation concealed	Co‐interventions	Compliance Measured	Blinding	Outcome measures	Intention to treat	Total /11
Pichichero 1987	Yes (1)	Unsure (0)	Unsure (0)	Yes (1)	Care Provider, Patient (2)	relevant (1)		7/11
					Unsure for outcome assessor (0)	withdrawals not reported (0)	yes (1)
						Timing of outcome assessment comparable (1)
Gerber 1990	Yes (1)	Yes (1)	avoided (1)	Yes (1)	No blinding (0/3)	relevant (1)	unsure (0)	7/11
						withdrawals reported (1)
						Timing of outcome assessment comparable (1)
El Daher 1991	Yes (1)	Unsure (0)	avoided (1)	Unsure (0)	Care Provider, Patient (2)	Relevant (1)
					Unsure for outcome assessor (0)	Withdrawals ‐ unsure (0)	No (0)	6/11
						Timing of outcome assessment comparable (1)
Little 1997	Yes (1)	Yes (1)	Unsure (0)	Yes (1)	No (0)	Relevant (1)	Yes (1)	7/11
						Withdrawals reported (1)
						Timing of outcome assessment comparable (1)
Dowell 2001	Yes (1)	Unsure (0)	Unsure (0)	Yes (1)	Outcome assessor (1)	Relevant (1)	Unsure	6/11
					Not the care provider nor the patient (0)	Withdrawals reported (1)
						Timing of outcome assessment comparable (1)
Little 2001	Yes (1)	Unsure (0)	Avoided (1)	Yes (1)	No (0)	Relevant (1)	Yes (1)	7/11
						Withdrawals reported (1)
						Timing of outcome assessment comparable (1)
Arroll 2002	Yes (1)	Yes (1)	Unsure (0)	Unsure (0)	Care Provider, Patient (2)	Relevant (1)	Yes (1)	7/11
					Outcome assessor ‐ unsure (0)	Withdrawal reported ‐ unsure (0)
						Timing of outcome assessment comparable (1)

Table 1. Quality of Included Studies

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Table 2. Summary of Outcomes

Study	Outcome	Favours	Result (with 95% CI)	Notes	Compliance	%Scripts Filled
Pichichero 1987 (pharyngitis)	Fever Severity on Day 3	Immediate Antibiotics	SMD 0.40 (0.05 to 0.75)		Immediate Group 100%
	Malaise Severity on Day 3	No Difference	WMD 0.20 (‐0.11 to 0.51)		Delayed Group 100%
	Reconsultation rate	No Difference	OR 0.83 (0.30 to 2.29)
	Pain Severity on Day 3	No Difference	WMD 0.30 (‐0.15 to 0.75)
Gerber 1990 (pharyngitis)	Recurrence rate	No Difference			Immediate Group 88%
					Delayed Group 93%
El Daher 1991 (pharyngitis)	Vomiting	Immediate Antibiotics	OR 25.00 (8.65 to 72.25)		Not Reported
	Pain on Day 3	Immediate Antibiotics	OR 14.51 (7.14 to 29.50)
	Malaise on Day 3	Immediate Antibiotics	OR 16.49 (5.68 to 47.83)
	Fever Severity on Day 3	Immediate Antibiotics	WMD 0.90 (0.50 to 1.30)
Little 1997 (sore throat)	Vomiting	No Difference	OR 0.99 (0.49 to 2.04)			Immediate Group 99%
	Diarrhoea	No Difference	OR 1.22 (0.66 to 2.26)			Delayed Group 31%
	Rash	No Difference	OR 0.93 (0.41 to 2.11)
	Stomach Ache	No Difference	OR 0.82 (0.53 to 1.27)
	Fever (>37.0 degrees)	Immediate Antibiotics
	Sore throat	No Difference
	Cough	No Difference
	Malaise	No Difference
	Analgesic Use	No Difference
	Time Off Work	No Difference
Dowell 2001 (cough)	Cough duration	No Difference				Immediate Group ‐ not reported but all received a script at the first consultation
						Delayed Group 45%
Little 2001 (otitis media)	Diarrhoea	Delayed Antibiotics	OR 0.45 (0.22 to 0.91)			Immediate Group 98.5%
	Rash	No Difference	OR 1.21 (0.41 to 2.58)			Delayed Group 24%
	Patients with Pain on Day 3	No Difference	OR 1.93 (0.96 to 3.88)
	Patients with Pain on Day 7	No Difference	OR 6.55 (0.33 to 128.35)
	Patients with Malaise on Day 3	Immediate Antibiotics	OR 2.62 (1.44 to 4.76)
	Malaise Severity Day 3	Immediate Antibiotics	WMD 0.43 (0.11 to 0.75)
	Malaise Severity on Day 7	No Difference	WMD 0.01 (‐0.11 to 0.13)
	Pain Severity on Day 3	Immediate Antibiotics	WMD 0.75 (0.26 to 1.24)
	Pain severity on Day 7	No Difference	WMD 0.12 (‐0.04 to 0.28)
	Paracetamol consumption	Immediate antibiotics	WMD 0.59 (0.25 to 0.93)
	Last Day of Crying	Immediate antibiotics	WMD 0.69 ( 0.31 to 1.07)
Arroll 2002 (common cold)	Patients with Fever on Day 3	No Difference	OR 0.75 (0.22 to 2.6)			Immediate group 89% (95% CI; 76%‐94%)
	Patients with Fever on Day 7	No Difference	OR 0.68 (0.15 to 3.17)			Delayed Group 48% (95% CI; 35%‐60%)
	Patients with Diarrhoea	No Difference	OR 0.79 (0.53 to 1.19)
	Patients with Pain on Day 3	No Difference	OR 1.47 (0.58 to 3.77)
	Patients with Pain on Day 7	No Difference	OR 0.31 (0.03 to 3.03)
	Patients with Cough on Day 3	No Difference	OR 0.90 (0.37 to 2.18)
	Patients with Cough on Day 7	No Difference	OR 0.72 (0.32 to 1.58)
	Fever Severity Day 3	No Difference	WMD ‐0.24 (‐0.48 to 0.00)
	Fever Severity on Day 7	Delayed Antibiotics	WMD ‐0.32 (‐0.57 to ‐0.07)	Mean temperature for both <37 deg C

Table 2. Summary of Outcomes

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Table 3. Results of data requests

Study	? Other studies	Raw data
Arroll 2002	Responded	Obtained
Dowell 2001	Responded	No response
El‐Daher 1991	No response	No response
Gerber 1990	No response	No response
Little 1997	Responded	Unavailable
Little 2001	Responded	Obtained
Pichichero 1987	Responded	No response

Table 3. Results of data requests

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Comparison 1. Fever

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Fever on day 3 Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected

2 Fever on day 7 Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 1. Fever

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Comparison 2. Adverse events

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Vomiting Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected

2 Diarrhoea Show forest plot	3		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Rash Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Stomach ache Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Reconsultation rate Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. Adverse events

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Comparison 3. Pain

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain on day 3 Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected

2 Pain on day 7 Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected

Comparison 3. Pain

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Comparison 4. Malaise

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Malaise on day 3 Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected

Comparison 4. Malaise

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Comparison 5. Cough

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cough on day 3 Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Cough on day 7 Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 5. Cough

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Comparison 6. Malaise severity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4 Malaise severity day 3 Show forest plot	2		Mean Difference (IV, Random, 95% CI)	Totals not selected

8 Malaise severity day 7 Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

9 Last day of crying Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 6. Malaise severity

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Comparison 7. Pain severity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4 Pain severity day 3 Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7 Pain severity day 7 Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 7. Pain severity

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Comparison 8. Paracetamol consumption

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Spoons/day Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 8. Paracetamol consumption

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Comparison 9. Fever Severity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Fever severity on day 3 Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Totals not selected

2 Fever severity on day 7 Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

3 Fever severity on day 1 Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 9. Fever Severity

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