Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator‐associated pneumonia

Danilo Cortozi Berton; Andre C Kalil; Paulo José Zimermann Teixeira

doi:10.1002/14651858.CD006482.pub3

Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator‐associated pneumonia

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Referencias

References to studies included in this review

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estudios excluidos
otras referencias

The Canadian Clinical Care Trials Group. A randomised trial of diagnostic techniques for ventilator‐associated pneumonia. New England Journal of Medicine 2006;355(25):2619‐30.

Fagon JY, Chastre J, Wolff M, Gervais C, Parer‐Aubas S, Stéphan F, et al. Invasive and noninvasive strategies for management of suspected ventilator‐associated pneumonia. A randomised trial. Annals of Internal Medicine 2000;132:621‐30.

Ruiz M, Torres A, Ewig S, Marcos MA, Alcon A, Lledo R, et al. Noninvasive versus invasive microbial investigation in ventilator‐associated pneumonia: evaluation of outcome. American Journal of Respiratory and Critical Care Medicine 2000;162:119‐25.

Sanchez‐Nieto JM, Torres A, Garcia‐Cordoba F, El‐Ebiary M, Carrillo A, Ruiz J, et al. Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator‐associated pneumonia: a pilot study. American Journal of Respiratory and Critical Care Medicine 1998;157:371‐6.

Solé Violán J, Fernandez JA, Benitez AB, Cardenosa Cendrero JA, Rodriguez de Castro F. Impact of quantitative invasive diagnostic techniques in the management and outcome of mechanically ventilated patients with suspected pneumonia. Critical Care Medicine 2000;28:2737‐41.

References to studies excluded from this review

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estudios incluidos
otras referencias

Cai S, Zhang J, Qian G. Impact of quantitative and qualitative pathogen culture on the outcome of ventilator‐associated pneumonia. Chinese Journal of Tuberculosis and Respiratory Diseases 2001;24:494‐7.

Additional references

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estudios excluidos

Alvarez‐Lerma F. Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU‐Acquired Pneumonia Study Group. Intensive Care Medicine 1996;22:387‐94.

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital‐acquired, ventilator‐associated, and healthcare‐associated pneumonia. American Journal of Respiratory and Critical Care Medicine 2005;171:388‐416.

Chastre J, Fagon JY. Ventilator‐associated pneumonia. American Journal of Respiratory and Critical Care Medicine 2002;165:867‐903.

Dupont H, Mentec H, Sollet JP, Bleichner G. Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator‐associated pneumonia. Intensive Care Medicine 2001;27:355‐62.

Grossman RF, Fein A. Evidence‐based assessment of diagnostic tests for ventilator‐associated pneumonia: executive summary. Chest 2000;117(4 (Suppl 2)):177‐81.

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Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org. The Cochrane Collaboration, 2011.

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Ibrahim EH, Ward S, Sherman G, Schaiff R, Fraser VJ, Kollef MH. Experience with a clinical guideline for the treatment of ventilator‐associated pneumonia. Critical Care Medicine 2002;29:1109‐15.

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Ioanas M, Ferrer, R, Angrill J, Ferrer M, Torres A. Microbial investigation in ventilator‐associated pneumonia. European Respiratory Journal 2001;17(4):791‐801.

Iregui M, Ward S, Sherman G, Fraser VJ, Kollef M. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator‐associated pneumonia. Chest 2002;122:262‐8.

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org. 2009: Wiley, 2011.

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Luna CM, Vujacich P, Niederman MS, Vay C, Gherardy C, Matera J, et al. Impact of BAL data on the therapy and outcome of ventilator‐associated pneumonia. Chest 1997;111:676‐85.

Porzecanski I, Bowton DL. Diagnosis and treatment of ventilator‐associated pneumonia. Chest 2006;130:597‐604.

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.

Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator‐associated pneumonia: a systematic review. Critical Care Medicine 2005;33:2184‐93.

Shorr AF, Sherner JH, Jackson WL, Kollef MH. Invasive approaches to the diagnosis of ventilator‐associated pneumonia: a meta‐analysis. Critical Care Medicine 2005;33:46‐53.

Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta‐analysis. BMJ 2001;323:101‐5.

Teixeira PJZ, Seligman R, Hertz FT, Cruz DB, Fachel JMG. Inadequate treatment of ventilator‐associated pneumonia: risk factors and impact on outcomes. Journal of Hospital Infection 2007;65:361‐7.

Torres A, Ewig S. Diagnosing ventilator‐associated pneumonia. New England Journal of Medicine 2004;350:433‐5.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

CCCTG 2006

Methods	Duration: 28 days Parallel design Blinded assessment of outcomes: not met Withdrawals described and were they acceptable: met
Participants	Sample size = 739 APACHE II (severity) ‐ Invasive quantitative = 20.1 ± 6.4 ‐ Non‐invasive qualitative = 19.8 ± 6.2 Duration on mechanical ventilation before study (days): not informed Previous use of antibiotics ‐ Invasive quantitative = 227/365 (62.2%) ‐ Non‐invasive qualitative = 241/374 (64.4%) VAP suspected: new or persistent radiographic infiltrate plus any 2 of the following: fever > 38.3 ºC; leukocytosis or neutropenia, purulent endotracheal secretions, increasing oxygen requirement, potentially pathogenic bacteria from endotracheal secretion
Interventions	Invasive quantitative versus non‐invasive qualitative
Outcomes	Mortality ‐ Invasive quantitative = 69/365 (18.9%) ‐ Non‐invasive qualitative = 69/374 (18.4%) Antibiotic change ‐ Invasive quantitative = 271/365 (74.2%) ‐ Non‐invasive qualitative = 279/474 (74.6%) Intensive care unit (ICU) stay (days) ‐ Invasive quantitative = 12.3 (95% CI 10.9 to 13.8) ‐ Non‐invasive qualitative = 12.2 (95% CI 10.9 to 14.2) ‐ Duration of mechanical ventilation (days) ‐ Invasive quantitative: 8.9 (95% CI 7.4 to 10.7) ‐ Non‐invasive: qualitative: 8.8 (95% CI 7.0 to 10.7) Appropriateness of initial antibiotic choice ‐ Invasive quantitative = 341/365 (93.4%) ‐ Non‐invasive qualitative = 353/374 (94.3%)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central telephone system, with a variable, undisclosed block size
Allocation concealment (selection bias)	Low risk	As above
Blinding (performance bias and detection bias) All outcomes	High risk	Physicians were aware of the patient's treatment assignments
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 patient withdrew consent 2 days after randomisation
Selective reporting (reporting bias)	Low risk	Primary and secondary outcomes have been reported in the pre‐specified way and adequately reported
Other bias	Low risk

Fagon 2000

Methods	Duration: 28 days Parallel design Blinded assessment of outcomes: not met Withdrawals described and were they acceptable: met
Participants	Sample size = 413 SAPS (severity) ‐ Invasive quantitative = 44 ± 15 ‐ Non‐invasive qualitative = 42 ± 14 Duration on mechanical ventilation before study (days) ‐ Invasive quantitative = 10.4 ± 10.2 ‐ Non‐invasive qualitative = 10.7 ± 10.0 Previous use of antibiotic ‐ Invasive quantitative = 105/204 (51.5%) ‐ Non‐invasive qualitative = 103/109 (49.3%) VAP suspected: new or progressive radiographic infiltrate plus 1 of the following: fever > 38.3 ºC, leukocytosis or purulent tracheal secretion
Interventions	Invasive quantitative versus non‐invasive qualitative
Outcomes	Mortality ‐ Invasive quantitative = 63/204 (30.9%) ‐ Non‐invasive qualitative = 81/209 (38.8%) Antibiotic change not informed Intensive care unit (ICU) stay (days) ‐ Invasive quantitative = 26.7 ± 23.9 ‐ Non‐invasive qualitative = 25.1 ± 28.5 Duration of mechanical ventilation (days) not informed Appropriateness of initial antibiotic choice ‐ Invasive quantitative = 203/204 (99%) ‐ Non‐invasive qualitative = 185/209 (88.5%)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random number tables were used to assign patients in blocks of 8, with stratification according to treatment centre
Allocation concealment (selection bias)	Low risk	As above
Blinding (performance bias and detection bias) All outcomes	High risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	High risk	All patients were followed up
Selective reporting (reporting bias)	Low risk	Primary and secondary outcomes have been reported in the pre‐specified way and adequately reported
Other bias	Low risk	Not detected

Ruiz 2000

Methods	Duration: 30 days Parallel design Blinded assessment of outcomes: not met Withdrawals described and were they acceptable: met
Participants	Sample size = 76 APACHE II (severity) ‐ Invasive quantitative = 20 ± 6 ‐ Non‐invasive quantitative = 19 ± 6 Duration on mechanical ventilation before study (days) ‐ Invasive quantitative = 6 ± 4 ‐ Non‐invasive quantitative = 6.2 ± 5 Previous use of antibiotic ‐ Invasive quantitative = 26/33 (70%) ‐ Non‐invasive quantitative = 33/39 (87%) VAP suspected: new or progressive radiographic infiltrate plus 2 of the following: fever > 38.3 ºC or hypothermia < 35 ºC, leukocytosis or leucopenia, purulent tracheal secretion
Interventions	Invasive quantitative versus non‐invasive quantitative
Outcomes	Mortality ‐ Invasive quantitative = 14/37 (38%) ‐ Non‐invasive quantitative = 18/39 (46%) Antibiotic change ‐ Invasive quantitative: 10/37 (28%) ‐ Non‐invasive quantitative: 7/39 (18%) Intensive care unit (ICU) stay (days) ‐ Invasive quantitative = 21 ± 15 ‐ Non‐invasive quantitative = 21 ± 18 Duration of mechanical ventilation (days) ‐ Invasive quantitative = 19 ± 15 ‐ Non‐invasive quantitative = 20 ± 24 Appropriateness of initial antibiotic choice ‐ Invasive quantitative = 27/37 (73%) ‐ Non‐invasive quantitative = 31/39 (79.4%)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation table into 1 of the 2 groups
Allocation concealment (selection bias)	Low risk	As above
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	All patients were followed up
Selective reporting (reporting bias)	Unclear risk	No data to evaluate
Other bias	Low risk	Not detected

Sanchez‐Nieto 1998

Methods	Duration: not informed Parallel design Blinded assessment of outcomes: not met Withdrawals described and were they acceptable: met
Participants	Sample size = 51 APACHE II (severity) ‐ Invasive quantitative = 15 ± 5 ‐ Non‐invasive quantitative = 18 ± 5 Duration on mechanical ventilation before study (days) ‐ Invasive quantitative = 11 ± 8 ‐ Non‐invasive quantitative = 11 ± 15 Previous use of antibiotic ‐ Invasive quantitative = 20/24 (83%) ‐ Non‐invasive qualitative = 19/27 (70%) VAP suspected: new or progressive radiographic infiltrate plus 2 of the following: fever > 38.3 ºC or hypothermia, < 35 ºC; leukocytosis or leucopenia, purulent respiratory secretions
Interventions	Invasive quantitative versus non‐invasive quantitative
Outcomes	Mortality ‐ Invasive quantitative = 11/24 (46%) ‐ Non‐invasive qualitative = 7/27 (26%) Antibiotic change ‐ Invasive quantitative = 10/24 (42%) ‐ Non‐invasive qualitative = 4/27 (15%) Intensive care unit (ICU) stay (days) ‐ Invasive quantitative = 28 ± 17 ‐ Non‐invasive qualitative = 26 ± 18 Duration of mechanical ventilation (days) ‐ Invasive quantitative: 23 ± 12 ‐ Non‐invasive quantitative: 20 ± 17 Appropriateness of initial antibiotic choice ‐ Invasive quantitative = 14/24 (58.3%) ‐ Non‐invasive qualitative = 23/27 (85.1%)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation table into 1 of the 2 groups
Allocation concealment (selection bias)	Low risk	As above
Blinding (performance bias and detection bias) All outcomes	High risk	Open study
Incomplete outcome data (attrition bias) All outcomes	High risk	All patients were followed up
Selective reporting (reporting bias)	Unclear risk	No data to evaluate
Other bias	Low risk	Not detected

Solé Violán 2000

Methods	Duration: not informed Parallel design Blinded assessment of outcomes: not met Withdrawals described and were they acceptable: met
Participants	Sample size = 88 APACHE II (severity) ‐ Invasive quantitative = 15.8 ± 0.9 ‐ Non‐invasive qualitative = 15.0 ± 0.9 Duration on mechanical ventilation before study (days) ‐ Invasive quantitative = 7.8 ± 1.1 ‐ Non‐invasive qualitative = 7.3 ± 0.9 Previous use of antibiotic ‐ Invasive quantitative = 16/45 (35.5%) ‐ Non‐invasive qualitative = 19/43 (44.1%) VAP suspected: new radiographic infiltrate plus 2 of the following: fever > 38.5 ºC, leukocytosis or leukopenia, purulent tracheal secretions
Interventions	Invasive quantitative versus non‐invasive qualitative
Outcomes	Mortality ‐ Invasive quantitative = 10/45 (22.2%) ‐ Non‐invasive qualitative = 9/43 (20.9%) Antibiotic change ‐ Invasive quantitative = 15/45 (33.3%) ‐ Non‐invasive qualitative = 5/43 (11.6%) Intensive care unit (ICU) stay (days) ‐ Invasive quantitative = 23.6 ± 3.1 ‐ Non‐invasive qualitative = 22.4 ± 3.1 Duration of mechanical ventilation (days) ‐ Invasive quantitative: 19.9 ± 2.8 ‐ Non‐invasive qualitative: 19.2 ± 3.0 Appropriateness of initial antibiotic choice ‐ Invasive quantitative = 42/43 (93.3%) PS: 2/45 inadequacy (isolated organism treated with only 1 effective antibiotic) ‐ Non‐invasive qualitative = 42/43 (97.6%) PS: 1/43 inadequacy
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation table into 1 of the 2 groups
Allocation concealment (selection bias)	Low risk	As above
Blinding (performance bias and detection bias) All outcomes	Unclear risk	It is not stated on the paper
Incomplete outcome data (attrition bias) All outcomes	Low risk	3 patients were excluded because of transfer to another institution
Selective reporting (reporting bias)	Unclear risk	No data to evaluate
Other bias	Low risk	Not detected

APACHE: acute physiology and chronic health evaluation
ICU: intensive care unit
SAPS: simplified acute physiologic score
VAP: ventilator‐associated pneumonia

Characteristics of excluded studies [ordered by study ID]

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estudios incluidos

Study	Reason for exclusion
Cai 2001	The study is not clearly randomised and is a cross‐over study

Data and analyses

Open in table viewer

Comparison 1. Quantitative versus qualitative culture

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	3	1240	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.75, 1.11]
Open in figure viewer Analysis 1.1 Comparison 1 Quantitative versus qualitative culture, Outcome 1 Mortality.
2 Antibiotic change Show forest plot	2	827	Risk Ratio (M‐H, Random, 95% CI)	1.53 [0.54, 4.39]
Open in figure viewer Analysis 1.2 Comparison 1 Quantitative versus qualitative culture, Outcome 2 Antibiotic change.
3 Duration on mechanical ventilation (days) Show forest plot	2	827	Mean Difference (IV, Fixed, 95% CI)	0.58 [‐0.51, 1.68]
Open in figure viewer Analysis 1.3 Comparison 1 Quantitative versus qualitative culture, Outcome 3 Duration on mechanical ventilation (days).
4 ICU stay (days) Show forest plot	3	1240	Mean Difference (IV, Fixed, 95% CI)	0.95 [‐0.14, 2.04]
Open in figure viewer Analysis 1.4 Comparison 1 Quantitative versus qualitative culture, Outcome 4 ICU stay (days).

Open in table viewer

Comparison 2. Invasive versus non‐invasive method

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	5	1367	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.78, 1.11]
Open in figure viewer Analysis 2.1 Comparison 2 Invasive versus non‐invasive method, Outcome 1 Mortality.
2 Antibiotic change Show forest plot	4	954	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.87, 3.21]
Open in figure viewer Analysis 2.2 Comparison 2 Invasive versus non‐invasive method, Outcome 2 Antibiotic change.
3 Duration on mechanical ventilation (days) Show forest plot	4	954	Mean Difference (IV, Fixed, 95% CI)	0.61 [‐0.47, 1.68]
Open in figure viewer Analysis 2.3 Comparison 2 Invasive versus non‐invasive method, Outcome 3 Duration on mechanical ventilation (days).
4 ICU stay (days) Show forest plot	5	1367	Mean Difference (IV, Fixed, 95% CI)	0.94 [‐0.13, 2.01]
Open in figure viewer Analysis 2.4 Comparison 2 Invasive versus non‐invasive method, Outcome 4 ICU stay (days).

Open in table viewer

Comparison 3. Invasive quantitative versus non‐invasive quantitative

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	2	127	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.54, 2.41]
Open in figure viewer Analysis 3.1 Comparison 3 Invasive quantitative versus non‐invasive quantitative, Outcome 1 Mortality.

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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Figure 3

Forest plot of comparison: 1 Quantitative versus qualitative culture, outcome: 1.1 Mortality.

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Figure 4

Forest plot of comparison: 1 Quantitative versus qualitative culture, outcome: 1.2 Antibiotic change.

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Figure 5

Forest plot of comparison: 1 Quantitative versus qualitative culture, outcome: 1.3 Duration on mechanical ventilation (days).

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Figure 6

Forest plot of comparison: 1 Quantitative versus qualitative culture, outcome: 1.4 ICU stay (days).

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Analysis 1.1

Comparison 1 Quantitative versus qualitative culture, Outcome 1 Mortality.

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Analysis 1.2

Comparison 1 Quantitative versus qualitative culture, Outcome 2 Antibiotic change.

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Analysis 1.3

Comparison 1 Quantitative versus qualitative culture, Outcome 3 Duration on mechanical ventilation (days).

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Analysis 1.4

Comparison 1 Quantitative versus qualitative culture, Outcome 4 ICU stay (days).

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Analysis 2.1

Comparison 2 Invasive versus non‐invasive method, Outcome 1 Mortality.

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Analysis 2.2

Comparison 2 Invasive versus non‐invasive method, Outcome 2 Antibiotic change.

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Analysis 2.3

Comparison 2 Invasive versus non‐invasive method, Outcome 3 Duration on mechanical ventilation (days).

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Analysis 2.4

Comparison 2 Invasive versus non‐invasive method, Outcome 4 ICU stay (days).

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Analysis 3.1

Comparison 3 Invasive quantitative versus non‐invasive quantitative, Outcome 1 Mortality.

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Comparison 1. Quantitative versus qualitative culture

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	3	1240	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.75, 1.11]

2 Antibiotic change Show forest plot	2	827	Risk Ratio (M‐H, Random, 95% CI)	1.53 [0.54, 4.39]

3 Duration on mechanical ventilation (days) Show forest plot	2	827	Mean Difference (IV, Fixed, 95% CI)	0.58 [‐0.51, 1.68]

4 ICU stay (days) Show forest plot	3	1240	Mean Difference (IV, Fixed, 95% CI)	0.95 [‐0.14, 2.04]

Comparison 1. Quantitative versus qualitative culture

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Comparison 2. Invasive versus non‐invasive method

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	5	1367	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.78, 1.11]

2 Antibiotic change Show forest plot	4	954	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.87, 3.21]

3 Duration on mechanical ventilation (days) Show forest plot	4	954	Mean Difference (IV, Fixed, 95% CI)	0.61 [‐0.47, 1.68]

4 ICU stay (days) Show forest plot	5	1367	Mean Difference (IV, Fixed, 95% CI)	0.94 [‐0.13, 2.01]

Comparison 2. Invasive versus non‐invasive method

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Comparison 3. Invasive quantitative versus non‐invasive quantitative

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	2	127	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.54, 2.41]

Comparison 3. Invasive quantitative versus non‐invasive quantitative

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Referencias

References to studies included in this review

CCCTG 2006 {published data only}

Fagon 2000 {published data only}

Ruiz 2000 {published data only}

Sanchez‐Nieto 1998 {published data only}

Solé Violán 2000 {published data only}

References to studies excluded from this review

Cai 2001 {published data only}

Additional references

Alvarez‐Lerma 1996

ATS/IDSA 2005

Chastre 2002

Dupont 2001

Grossman 2000

Higgins 2011

Ibrahim 2002

Ioanas 2001

Iregui 2002

Lefebvre 2011

Luna 1997

Porzecanski 2006

RevMan 2011 [Computer program]

Safdar 2005

Shorr 2005

Sterne 2001

Teixeira 2007

Torres 2004

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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