Short‐course versus prolonged‐course antibiotic therapy for hospital‐acquired pneumonia in critically ill adults

Richard Pugh; Chris Grant; Richard PD Cooke; Ged Dempsey

doi:10.1002/14651858.CD007577.pub2

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Figure 1

'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 2

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

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Analysis 1.1

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 1 28‐day mortality.

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Analysis 1.2

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 2 Recurrence of pneumonia.

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Analysis 1.3

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 3 28‐day antibiotic‐free days.

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Analysis 1.4

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 4 ITU mortality.

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Analysis 1.5

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 5 Non‐resolution of pneumonia.

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Analysis 1.6

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 6 In‐hospital mortality.

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Analysis 1.7

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 7 Recurrence due to multi‐resistant organism.

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Analysis 1.8

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 8 Duration of ITU stay.

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Analysis 1.9

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 9 Duration of hospital stay.

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Analysis 1.10

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 10 Duration of mechanical ventilation.

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Analysis 1.11

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 11 28‐day mechanical ventilation‐free days.

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Analysis 1.12

Comparison 1 Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP, Outcome 12 Mortality associated with VAP.

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Analysis 2.1

Comparison 2 Discontinuation of antibiotics according to Clinical Pulmonary Infection Score, Outcome 1 30‐day mortality.

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Analysis 2.2

Comparison 2 Discontinuation of antibiotics according to Clinical Pulmonary Infection Score, Outcome 2 Episodes of superinfection or antimicrobial resistance.

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Analysis 2.3

Comparison 2 Discontinuation of antibiotics according to Clinical Pulmonary Infection Score, Outcome 3 Duration of antibiotic therapy.

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Analysis 2.4

Comparison 2 Discontinuation of antibiotics according to Clinical Pulmonary Infection Score, Outcome 4 Duration of ITU stay.

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Analysis 3.1

Comparison 3 Discontinuation of antibiotics according clinical guideline, Outcome 1 Recurrence of pneumonia.

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Analysis 3.2

Comparison 3 Discontinuation of antibiotics according clinical guideline, Outcome 2 Duration of antibiotic therapy.

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Analysis 3.3

Comparison 3 Discontinuation of antibiotics according clinical guideline, Outcome 3 In‐hospital mortality.

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Analysis 3.4

Comparison 3 Discontinuation of antibiotics according clinical guideline, Outcome 4 Duration of ITU stay.

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Analysis 3.5

Comparison 3 Discontinuation of antibiotics according clinical guideline, Outcome 5 Duration of hospital stay.

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Analysis 3.6

Comparison 3 Discontinuation of antibiotics according clinical guideline, Outcome 6 Duration of mechanical ventilation.

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Analysis 4.1

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 1 28‐day mortality.

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Analysis 4.2

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 2 Recurrence of pneumonia.

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Analysis 4.3

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 3 28‐day antibiotic‐free days.

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Analysis 4.4

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 4 Duration of antibiotic therapy.

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Analysis 4.5

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 5 In‐hospital mortality.

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Analysis 4.6

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 6 ITU mortality.

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Analysis 4.7

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 7 Non‐resolution of pneumonia.

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Analysis 4.8

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 8 Recurrence due to resistant organism.

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Analysis 4.9

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 9 ITU duration of stay.

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Analysis 4.10

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 10 Duration of hospital stay.

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Analysis 4.11

Comparison 4 Discontinuation of antibiotic therapy according to serum procalcitonin level, Outcome 11 Duration of mechanical ventilation.

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Summary of findings for the main comparison. Should short (fixed duration)‐course antibiotic therapy versus prolonged‐course antibiotic therapy be used for critically ill patients with hospital‐acquired pneumonia?

Should short (fixed duration)‐course antibiotic therapy versus prolonged‐course antibiotic therapy be used for critically ill patients with hospital‐acquired pneumonia?
Patient or population: critically ill patients with hospital‐acquired pneumonia Settings: ICU Intervention: short (fixed duration)‐course antibiotic therapy Comparison: prolonged course antibiotic therapy
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Prolonged‐course antibiotic therapy	Short (fixed duration)‐course antibiotic therapy
28‐day mortality	Study population		OR 1.08 (0.66 to 1.76)	431 (2 studies)
	186 per 1000	198 per 1000 (131 to 287)
	Medium‐risk population
	270 per 1000	285 per 1000 (196 to 394)
28‐day mortality ‐ NF‐GNB	Study population		OR 0.71 (0.32 to 1.56)	127 (1 study)	See comment
	302 per 1000	235 per 1000 (122 to 403)
	Medium‐risk population
	302 per 1000	235 per 1000 (122 to 403)
28‐day mortality ‐ MRSA	Study population		OR 1.28 (0.32 to 5.09)	42 (1 study)	See comment
	238 per 1000	286 per 1000 (91 to 614)
	Medium‐risk population
	238 per 1000	286 per 1000 (91 to 614)
Recurrence of pneumonia	Study population		OR 1.37 (0.87 to 2.17)	508 (3 studies)
	245 per 1000	308 per 1000 (220 to 413)
	Medium‐risk population
	227 per 1000	287 per 1000 (203 to 389)
Recurrence of pneumonia ‐ NF‐GNB	Study population		OR 2.18 (1.14 to 4.16)	176 (2 studies)
	247 per 1000	417 per 1000 (272 to 577)
	Medium‐risk population
	241 per 1000	409 per 1000 (266 to 569)
Recurrence of pneumonia ‐ MRSA	Study population		OR 1.56 (0.12 to 19.61)	49 (2 studies)
	370 per 1000	478 per 1000 (66 to 920)
	Medium‐risk population
	298 per 1000	398 per 1000 (48 to 893)
28‐day antibiotic‐free days		The mean 28‐day antibiotic‐free days in the intervention groups was 4.02 higher (2.26 to 5.78 higher)		431 (2 studies)
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; MRSA: methicillin‐resistant Staphylococcus aureus; NF‐GNB: non‐fermenting Gram‐negative bacilli; OR: odds 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.

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Summary of findings 2. Discontinuation of antibiotics according to Clinical Pulmonary Infection Score for critically ill adults with hospital‐acquired pneumonia

Discontinuation of antibiotics according to Clinical Pulmonary Infection Score for critically ill adults with hospital‐acquired pneumonia
Patient or population: critically ill adults with hospital‐acquired pneumonia Settings: ICU Intervention: discontinuation of antibiotics according to Clinical Pulmonary Infection Score
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Discontinuation of antibiotics according to Clinical Pulmonary Infection Score
30‐day mortality	Study population		OR 0.33 (0.1 to 1.03)	81 (1 study)	See comment
	310 per 1000	129 per 1000 (43 to 316)
	Medium‐risk population
	310 per 1000	129 per 1000 (43 to 316)
Episodes of superinfection or antimicrobial resistance	Study population		OR 0.29 (0.09 to 0.92)	81 (1 study)	See comment
	333 per 1000	126 per 1000 (43 to 315)
	Medium‐risk population
	333 per 1000	126 per 1000 (43 to 315)
Duration of antibiotic therapy	See comment	See comment	Not estimable	81 (1 study)	See comment
Duration of ITU stay	See comment	See comment	Not estimable	81 (1 study)	See comment
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; ITU: intensive therapy unit; OR: odds 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.

Summary of findings 2. Discontinuation of antibiotics according to Clinical Pulmonary Infection Score for critically ill adults with hospital‐acquired pneumonia

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Summary of findings 3. Discontinuation of antibiotics according to clinical guideline for hospital‐acquired pneumonia in critically ill adults

Discontinuation of antibiotics according to clinical guideline for hospital‐acquired pneumonia in critically ill adults
Patient or population: patients with hospital‐acquired pneumonia in critically ill adults Settings: ICU Intervention: discontinuation of antibiotics according to clinical guideline
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Discontinuation of antibiotics according to clinical guideline
Recurrence of pneumonia	Study population		OR 0.88 (0.48 to 1.59)	290 (1)	See comment
	193 per 1000	174 per 1000 (103 to 275)
	Medium‐risk population
	193 per 1000	174 per 1000 (103 to 275)
Duration of antibiotic therapy		The mean duration of antibiotic therapy in the intervention groups was 2 lower (3.21 to 0.79 lower)		290 (1)	See comment
In‐hospital mortality	Study population		OR 0.8 (0.49 to 1.29)	290 (1)	See comment
	371 per 1000	321 per 1000 (224 to 432)
	Medium‐risk population
	371 per 1000	321 per 1000 (224 to 432)
Duration of ICU stay		The mean duration of ICU stay in the intervention groups was 0.2 lower (1.75 lower to 1.35 higher)		290 (1)	See comment
Duration of hospital stay		The mean duration of hospital stay in the intervention groups was 0.3 higher (3.63 lower to 4.23 higher)		290 (1)	See comment
Duration of mechanical ventilation		The mean duration of mechanical ventilation in the intervention groups was 0.3 lower (1.79 lower to 1.19 higher)		290 (1)	See comment
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
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.

Summary of findings 3. Discontinuation of antibiotics according to clinical guideline for hospital‐acquired pneumonia in critically ill adults

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Summary of findings 4. Discontinuation of antibiotic therapy according to serum procalcitonin level for hospital‐acquired pneumonia in critically ill adults

Discontinuation of antibiotic therapy according to serum procalcitonin level for hospital‐acquired pneumonia in critically ill adults
Patient or population: hospital‐acquired pneumonia in critically ill adults Settings: ICU Intervention: discontinuation of antibiotic therapy according to serum procalcitonin level
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Discontinuation of antibiotic therapy according to serum procalcitonin level
28‐day mortality	Study population		OR 0.66 (0.39 to 1.14)	308 (3 studies)
	265 per 1000	192 per 1000 (123 to 291)
	Medium‐risk population
	258 per 1000	187 per 1000 (119 to 284)
Recurrence of pneumonia	Study population		OR 2.06 (0.74 to 5.7)	66 (1 study)	See comment
	286 per 1000	452 per 1000 (229 to 695)
	Medium‐risk population
	286 per 1000	452 per 1000 (229 to 695)
28‐day antibiotic‐free days		The mean 28‐day antibiotic‐free days in the intervention groups was 2.8 higher (1.39 to 4.21 higher)		167 (2 studies)
Duration of antibiotic therapy days		The mean duration of antibiotic therapy in the intervention groups was 3.2 lower (4.45 to 1.95 lower)		308 (3 studies)
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
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.

Summary of findings 4. Discontinuation of antibiotic therapy according to serum procalcitonin level for hospital‐acquired pneumonia in critically ill adults

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Comparison 1. Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 28‐day mortality Show forest plot	2	431	Odds Ratio (M‐H, Random, 95% CI)	1.08 [0.66, 1.76]

1.1 NF‐GNB	1	127	Odds Ratio (M‐H, Random, 95% CI)	0.71 [0.32, 1.56]
1.2 MRSA	1	42	Odds Ratio (M‐H, Random, 95% CI)	1.28 [0.32, 5.09]
1.3 Non NF‐GNB/MRSA	1	232	Odds Ratio (M‐H, Random, 95% CI)	1.65 [0.73, 3.73]
1.4 Unspecified organism	1	30	Odds Ratio (M‐H, Random, 95% CI)	0.93 [0.21, 4.11]
2 Recurrence of pneumonia Show forest plot	3	508	Odds Ratio (M‐H, Random, 95% CI)	1.37 [0.87, 2.17]

2.1 NF‐GNB	2	176	Odds Ratio (M‐H, Random, 95% CI)	2.18 [1.14, 4.16]
2.2 MRSA	2	49	Odds Ratio (M‐H, Random, 95% CI)	1.56 [0.12, 19.61]
2.3 Non NF‐GNB/MRSA	2	253	Odds Ratio (M‐H, Random, 95% CI)	0.98 [0.55, 1.78]
2.4 Unspecified organism	1	30	Odds Ratio (M‐H, Random, 95% CI)	1.17 [0.14, 9.59]
3 28‐day antibiotic‐free days Show forest plot	2	431	Mean Difference (IV, Random, 95% CI)	4.02 [2.26, 5.78]

3.1 NF‐GNB	1	127	Mean Difference (IV, Random, 95% CI)	4.5 [2.25, 6.75]
3.2 MRSA	1	42	Mean Difference (IV, Random, 95% CI)	8.0 [4.14, 11.86]
3.3 Non NF‐GNB/ MRSA	1	232	Mean Difference (IV, Random, 95% CI)	3.70 [2.09, 5.31]
3.4 Unspecified organism	1	30	Mean Difference (IV, Random, 95% CI)	2.3 [1.03, 3.57]
4 ITU mortality Show forest plot	2	107	Odds Ratio (M‐H, Random, 95% CI)	0.85 [0.37, 1.91]

5 Non‐resolution of pneumonia Show forest plot	1	77	Odds Ratio (M‐H, Fixed, 95% CI)	1.80 [0.65, 5.02]

5.1 NF‐GNB	1	49	Odds Ratio (M‐H, Fixed, 95% CI)	1.89 [0.49, 7.40]
5.2 MRSA	1	7	Odds Ratio (M‐H, Fixed, 95% CI)	11.0 [0.28, 433.80]
5.3 Non NF‐GNB/MRSA	1	21	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.16, 6.25]
6 In‐hospital mortality Show forest plot	1	401	Odds Ratio (M‐H, Fixed, 95% CI)	1.09 [0.71, 1.67]

6.1 NF‐GNB	1	127	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.36, 1.53]
6.2 MRSA	1	42	Odds Ratio (M‐H, Fixed, 95% CI)	1.47 [0.43, 4.95]
6.3 Non NF‐GNB/MRSA	1	232	Odds Ratio (M‐H, Fixed, 95% CI)	1.32 [0.72, 2.42]
7 Recurrence due to multi‐resistant organism Show forest plot	1	110	Odds Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.95]

8 Duration of ITU stay Show forest plot	2	431	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐2.30, 2.27]

8.1 NF‐GNB	1	127	Mean Difference (IV, Random, 95% CI)	0.90 [‐5.40, 7.20]
8.2 MRSA	1	42	Mean Difference (IV, Random, 95% CI)	2.90 [‐8.39, 14.19]
8.3 Non NF‐GNB/MRSA	1	232	Mean Difference (IV, Random, 95% CI)	2.70 [‐1.88, 7.28]
8.4 Unspecified organism	1	30	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐4.61, 1.41]
9 Duration of hospital stay Show forest plot	1	30	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐4.11, 2.11]

10 Duration of mechanical ventilation Show forest plot	2	107	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.57, 0.55]

11 28‐day mechanical ventilation‐free days Show forest plot	2	431	Mean Difference (IV, Random, 95% CI)	0.47 [‐0.97, 1.92]

11.1 NF‐GNB	1	127	Mean Difference (IV, Random, 95% CI)	1.50 [‐1.77, 4.77]
11.2 MRSA	1	42	Mean Difference (IV, Random, 95% CI)	‐1.30 [‐6.37, 3.77]
11.3 Non NF‐GNB/MRSA	1	232	Mean Difference (IV, Random, 95% CI)	‐1.20 [‐3.54, 1.14]
11.4 Unspecified organism	1	30	Mean Difference (IV, Random, 95% CI)	1.30 [‐0.03, 2.63]
12 Mortality associated with VAP Show forest plot	1	77	Mean Difference (IV, Fixed, 95% CI)	1.0 [‐8.85, 10.85]

Comparison 1. Short (fixed)‐course antibiotic therapy versus prolonged‐course antibiotic therapy for HAP

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Comparison 2. Discontinuation of antibiotics according to Clinical Pulmonary Infection Score

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 30‐day mortality Show forest plot	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.10, 1.03]

2 Episodes of superinfection or antimicrobial resistance Show forest plot	1	81	Odds Ratio (M‐H, Fixed, 95% CI)	0.29 [0.09, 0.92]

3 Duration of antibiotic therapy Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

4 Duration of ITU stay Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Discontinuation of antibiotics according to Clinical Pulmonary Infection Score

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Comparison 3. Discontinuation of antibiotics according clinical guideline

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Recurrence of pneumonia Show forest plot	1	290	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.48, 1.59]

2 Duration of antibiotic therapy Show forest plot	1	290	Mean Difference (IV, Fixed, 95% CI)	‐2.0 [‐3.21, ‐0.79]

3 In‐hospital mortality Show forest plot	1	290	Odds Ratio (M‐H, Fixed, 95% CI)	0.80 [0.49, 1.29]

4 Duration of ITU stay Show forest plot	1	290	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐1.75, 1.35]

5 Duration of hospital stay Show forest plot	1	290	Mean Difference (IV, Fixed, 95% CI)	0.30 [‐3.63, 4.23]

6 Duration of mechanical ventilation Show forest plot	1	290	Mean Difference (IV, Fixed, 95% CI)	‐0.30 [‐1.79, 1.19]

Comparison 3. Discontinuation of antibiotics according clinical guideline

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Comparison 4. Discontinuation of antibiotic therapy according to serum procalcitonin level

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 28‐day mortality Show forest plot	3	308	Odds Ratio (M‐H, Random, 95% CI)	0.66 [0.39, 1.14]

2 Recurrence of pneumonia Show forest plot	1	66	Odds Ratio (M‐H, Fixed, 95% CI)	2.06 [0.74, 5.70]

3 28‐day antibiotic‐free days Show forest plot	3	308	Mean Difference (IV, Random, 95% CI)	2.80 [1.39, 4.21]

4 Duration of antibiotic therapy Show forest plot	3	308	Mean Difference (IV, Random, 95% CI)	‐3.20 [‐4.45, ‐1.95]

5 In‐hospital mortality Show forest plot	1	101	Odds Ratio (M‐H, Fixed, 95% CI)	0.63 [0.25, 1.58]

6 ITU mortality Show forest plot	1	66	Odds Ratio (M‐H, Fixed, 95% CI)	0.76 [0.26, 2.22]

7 Non‐resolution of pneumonia Show forest plot	1	66	Odds Ratio (M‐H, Fixed, 95% CI)	1.17 [0.38, 3.62]

8 Recurrence due to resistant organism Show forest plot	1	66	Odds Ratio (M‐H, Fixed, 95% CI)	1.75 [0.49, 6.21]

9 ITU duration of stay Show forest plot	2	167	Mean Difference (IV, Random, 95% CI)	‐2.68 [‐6.01, 0.66]

10 Duration of hospital stay Show forest plot	1	101	Mean Difference (IV, Fixed, 95% CI)	‐2.40 [‐6.40, 1.60]

11 Duration of mechanical ventilation Show forest plot	2	167	Mean Difference (IV, Random, 95% CI)	‐0.35 [‐3.24, 2.54]

Comparison 4. Discontinuation of antibiotic therapy according to serum procalcitonin level

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