Antibiotics for exacerbations of chronic obstructive pulmonary disease

Daniela J Vollenweider; Harish Jarrett; Claudia A Steurer‐Stey; Judith Garcia‐Aymerich; Milo A Puhan

doi:10.1002/14651858.CD010257

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Respuestas clínicas Cochrane
Guías
Temas

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Topics

Temas

Figure 1

Study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

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

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Forest plot of comparison: 1 Antibiotics versus placebo, outcome: 1.1 Treatment failure up to 4 weeks (no resolution or deterioration after trial medication of any duration or death when explicitly stated due to exacerbation or additional course of antibiotics).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Forest plot of comparison: 1 Antibiotics versus placebo, outcome: 1.2 Treatment failure within 4 weeks ‐ current drugs only.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Forest plot of comparison: 1 Antibiotics versus placebo, outcome: 1.3 Adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Forest plot of comparison: 1 Antibiotics versus placebo, outcome: 1.4 All‐cause mortality.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 Antibiotics versus placebo, Outcome 1 Treatment failure up to 4 weeks (no resolution or deterioration after trial medication of any duration or death when explicitly stated due to exacerbation or additional course of antibiotics).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 Antibiotics versus placebo, Outcome 2 Treatment failure within 4 weeks ‐ current drugs only.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 Antibiotics versus placebo, Outcome 3 Adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 Antibiotics versus placebo, Outcome 4 All‐cause mortality.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 Antibiotics versus placebo, Outcome 5 Duration of hospital stay (days).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 Antibiotics versus placebo, Outcome 6 Improvement in dyspnoea measured at the end of the study period.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 Antibiotics versus placebo, Outcome 7 Health‐related quality of life or functional status measures.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.8

Comparison 1 Antibiotics versus placebo, Outcome 8 Re‐exacerbations within ≥ 2 to 6 weeks since beginning of index exacerbation (rates).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.9

Comparison 1 Antibiotics versus placebo, Outcome 9 Days off work.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. Antibiotics for exacerbations of chronic obstructive pulmonary disease

Antibiotics for exacerbations of chronic obstructive pulmonary disease
Patient or population: patients with exacerbations of chronic obstructive pulmonary disease Settings: outpatient and inpatient reported together in the same table (see subgroups) Intervention: antibiotics versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Antibiotics versus placebo
Treatment failure up to 4 weeks¹ Subgroup: outpatient	275 per 1000	206 per 1000 (165 to 259)	RR 0.75 (0.60 to 0.94)	931 (7 studies)	⊕⊕⊝⊝ low ^2,3	Antibiotics: ‐ amoxicillin‐clavulanic acid ‐ trimethoprim/sulphamethoxazole ‐ oxytetracycline ‐ amoxicillin ‐ amoxicillin and co‐trimoxazol
Treatment failure up to 4 weeks¹ Subgroup: inpatient	520 per 1000	401 per 1000 (338 to 473)	RR 0.77 (0.65 to 0.91)	612 (4 studies)	⊕⊕⊕⊕ high ⁴	Antibiotics: ‐ amoxicillin‐clavulanic acid and trimethoprim/sulphamethoxazole ‐ doxycycline ‐ tetracycline hydrochloride or chloramphenicol ‐ penicillin and streptomycin
Treatment failure up to 4 weeks¹ Subgoup: ICU	565 per 1000	107 per 1000 (45 to 254)	RR 0.19 (0.08 to 0.45)	93 (1 study)	⊕⊕⊕⊕ high	Antibiotics: ‐ ofloxacine
All‐cause mortality Subgroup: inpatients	35 per 1000	36 per 1000 (13 to 92)	OR 1.02 (0.37 to 2.79)	531 (4 studies)	⊕⊕⊝⊝ low ^5,6	Antibiotics: ‐ tetracycline hydrochloride or chloramphenicol ‐ penicillin and streptomycin ‐ chloramphenicol ‐ doxycycline
All‐cause mortality Subgroup: ICU	217 per 1000	55 per 1000 (16 to 167)	OR 0.21 (0.06 to 0.72)	93 (1 study)	⊕⊕⊕⊕ high ⁷	Antibiotics: ‐ ofloxacine
Adverse events ‐ diarrhoea	18 per 1000	45 per 1000 (19 to 99)	OR 2.62 (1.11 to 6.17)	698 (3 studies)	⊕⊕⊕⊕ high	Antibiotics: ‐ amoxicillin‐clavulanic acid ‐ amoxicillin ‐ ofloxacine
Adverse events ‐ overall (adverse events not separated)	74 per 1000	109 per 1000 (76 to 154)	OR 1.53 (1.03 to 2.27)	1243 (5 studies)	⊕⊕⊕⊝ moderate ⁸	Antibiotics: ‐ amoxicillin‐clavulanic acid ‐ doxycycline ‐ amoxicillin ‐ ofloxacine
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; ICU: intensive care unit; OR: odds ratio; 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.
¹ no resolution or deterioration after trial medication of any duration or death when explicitly stated due to exacerbation or additional course of antibiotics. ² (‐ 1 inconsistency). Discrepancy between the statistical significance of the meta‐analysis that includes all trials (RR 0.75; 95% CI 0.60 to 0.94) vs. the meta‐analysis that is restricted to currently used drugs (amoxicillin‐clavulanic acid, trimethoprim/sulphamethoxazole, doxycycline, penicillin; RR 0.80; 95% CI 0.63 to 1.01). ³ (‐1 limitations). For one trial (Blasi) not all results are available. ⁴ (no downgrading). The heterogeneity was caused by two small trials that contribute only 14% to the pooled estimate. Two larger trials have the most weight in the meta‐analysis and show almost identical point estimates, therefore we did not downgrade for inconsistency. ⁵ (‐1 inconsistency). Substantial heterogeneity across trials with the largest trial showing an increase in mortality and the three small trials suggesting a decrease in mortality. ⁶ (‐ 1 imprecision). Wide 95% CI that precludes any conclusion about the effects of antibiotics on mortality in inpatients. ⁷ (no downgrading). The CI is relatively wide; however, because the upper limit of the 95% CI (0.72) as the most conservative effect estimate shows an at least moderate effect of antibiotics on mortality we did not downgrade. ⁸ (‐ 1 imprecision). Lower limit of 95% CI is very close to 1.0 and it is uncertain if lower limit would be below 1.0 with additional trials.

Summary of findings for the main comparison. Antibiotics for exacerbations of chronic obstructive pulmonary disease

Ir a la tabla de la revisión

Table 1. Type and dose of antibiotic used

Study	Antibiotic	Dose	Duration	Currently available and used?	Co‐interventions	Control
ABC 2009	Amoxicillin‐clavulanic acid (oral)	1.5 g/day	7 days	Yes	Oral prednisolone 30 mg for 7 days	Placebo for 7 days and oral prednisolone 30 mg for 7 days
Allegra 1991	Amoxicillin‐clavulanic acid (oral)	2 g/day	5 days	Yes		Placebo
Alonso Martinez 1992	Trimethoprim‐sulphamethoxazole or amoxicillin/clavulanic acid	1.9 g/day	8 days	Yes
Anthonisen 1987	Trimethoprim/sulphamethoxazole (oral)	1.9 g/day	10 days	Yes		Placebo
	Amoxicillin (oral)	1 g/day
	Doxycycline(oral)	0.1 to 0.2/day
Berry 1960	Oxytetracycline (oral)	1 g/day	5 days	No		Placebo
Daniels 2010	Doxycycline (oral)		7 days	Yes	IV prednisolone taper	Placebo plus IV prednisolone taper
Elmes 1957	Oxytetracycline (oral)	1 g/day	5 to 7 days	No		Placebo
Fear 1962	Oxytetracycline (oral)	1 g/day	7 days	No		placebo
Jørgensen 1992	Amoxicillin (oral)	1.5 g/day	7 days	Yes		placebo
Llor 2012	Amoxicillin/clavulanate (oral)	1.5 g/day	8 days	Yes		Placebo
Manresa 1987	Cefaclor (oral)	1.5 g/day	8 days	Yes		placebo
Nouira 2001	Ofloxacin (oral)	400 mg/day	10 days	Yes		placebo
Petersen 1967	Chloramphenicol (oral)	2 g/day	10 days	No		placebo
Pines 1968	Penicillin (parenterally)	1 g/day	14 days	Yes		placebo
Pines 1972	Tetracycline hydrochloride (oral) or Chloramphenicol	2 g/day	12 days	No		placebo
Sachs 1995	Amoxicillin 1.5 g/day 1.9 g/day (oral)	1.5 g/day	7 days	yes		placebo
Sachs 1995	or co‐trimoxazole	1.9 g/day	7 days	yes		placebo
IV: intravenous.

Table 1. Type and dose of antibiotic used

Ir a la tabla de la revisión

Comparison 1. Antibiotics versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Treatment failure up to 4 weeks (no resolution or deterioration after trial medication of any duration or death when explicitly stated due to exacerbation or additional course of antibiotics) Show forest plot	12	1636	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.62, 0.81]

1.1 Outpatient	7	931	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.60, 0.94]
1.2 Inpatient	4	612	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.65, 0.91]
1.3 ICU	1	93	Risk Ratio (M‐H, Fixed, 95% CI)	0.19 [0.08, 0.45]
2 Treatment failure within 4 weeks ‐ current drugs only Show forest plot	8	1175	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.64, 0.91]

2.1 Outpatient	5	790	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.63, 1.01]
2.2 Inpatient	3	385	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.55, 0.92]
3 Adverse events Show forest plot	5		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

3.1 Diarrhoea	3	698	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.62 [1.11, 6.17]
3.2 Dyspepsia	2	605	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.69 [0.28, 1.73]
3.3 Pain in mouth	1	270	Peto Odds Ratio (Peto, Fixed, 95% CI)	7.73 [0.80, 74.98]
3.4 Exanthema, itching	3	698	Peto Odds Ratio (Peto, Fixed, 95% CI)	3.83 [0.77, 19.11]
3.5 Overall (adverse events not separated)	5	1243	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.53 [1.03, 2.27]
4 All‐cause mortality Show forest plot	5	624	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.54 [0.25, 1.16]

4.1 Inpatients	4	531	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.02 [0.37, 2.79]
4.2 ICU patients	1	93	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.21 [0.06, 0.72]
5 Duration of hospital stay (days) Show forest plot	3	202	Mean Difference (IV, Random, 95% CI)	‐3.04 [‐8.83, 2.76]

6 Improvement in dyspnoea measured at the end of the study period Show forest plot	2	300	Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐0.96, 0.15]

6.1 Outpatients	1	35	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.97, 0.97]
6.2 Inpatients	1	265	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐1.27, 0.07]
7 Health‐related quality of life or functional status measures Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

8 Re‐exacerbations within ≥ 2 to 6 weeks since beginning of index exacerbation (rates) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9 Days off work Show forest plot	1	88	Mean Difference (IV, Fixed, 95% CI)	‐5.18 [‐6.08, ‐4.28]

Comparison 1. Antibiotics versus placebo

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet