Quantitative versus qualitative cultures of respiratory secretions in patients with ventilator-associated pneumonia

Review question
We wanted to determine whether quantitative cultures of respiratory secretions are effective in reducing mortality in immunocompetent patients with ventilator-associated pneumonia compared with qualitative cultures. We also evaluated changes in antibiotic use, length of intensive care unit (ICU) stay and mechanical ventilation.

Background
Ventilator-associated pneumonia (VAP) is a condition which occurs in patients mechanically ventilated for more than 48 hours, which can significantly increase the mortality of ICU patients. The best method for diagnosing VAP and identifying the causative organism (bacteria) is uncertain. Both invasive and non-invasive techniques are used to obtain samples of respiratory secretions and these can be analysed quantitatively (with a threshold count of the bacterial growth to differentiate between infection and colonisation of the lower airways) or qualitatively (presence or absence of pathogenic germs in the culture). The rationale for using quantitative cultures of respiratory secretions sampled from patients with VAP is to differentiate the infectious organisms (those with a higher concentration) from colonising organisms (those with lower concentration), thereby optimising antibiotic therapy.

Study characteristics
After reviewing 5064 articles we found three randomised controlled trials (RCTs) (1240 participants) comparing invasive methods using quantitative cultures, versus the non-invasive method using qualitative cultures. Two additional RCTs (127 participants) compared invasive versus non-invasive methods, both using quantitative cultures. We combined all five RCTs (1367 participants) to compare invasive versus non-invasive interventions for diagnosing VAP.

Key results
The cumulative all-cause mortality was 25.4% (159/626) in the qualitative group and 23.1% (142/614) in the quantitative group over the duration of the trials. There were no statistically significant differences between the use of quantitative cultures versus qualitative (risk ratio (RR) 0.91; 95% confidence interval (CI) 0.75 to 1.11). When we analysed all five studies, a total of 1367 patients were included. The cumulative all-cause mortality was 26.6% (184/692) in the non-invasive group and 24.7% (167/675) in the invasive group over the duration of the trials. The invasive versus non-invasive intervention analysis showed no evidence of mortality reduction (RR 0.93; 95% CI 0.78 to 1.11). The pooled data from trials did not show a significant influence on antibiotic change, but there was significant heterogeneity amongst the studies and the publication bias analysis for the antibiotic change analysis suggests that significant publication bias is likely (Egger's regression (intercept: 1.909; standard error: 0.436; P value (two-sided): 0.048). The analysis did not show significant differences in days on mechanical ventilation and in the length of ICU stay between either the quantitative versus qualitative culture groups or the invasive versus non-invasive method groups.

Quality of the evidence
The body of evidence supports moderately robust conclusions regarding the objective of our review. We use the word moderately because the sample size was of moderate size, even though this was the largest sample size evaluated to date: five RCTs with a total of 1367 participants. The results were consistent with respect to the mortality outcome, days on ventilation and days in the ICU. However, the results were less consistent with respect to antibiotic change.

Conclusion
Evidence from trials included in this review indicates that there is no clinical advantage in the use of quantitative over qualitative cultures, nor in using invasive over non-invasive diagnostic approaches. The evidence is current to October 2014.

Authors' conclusions: 

There is no evidence that the use of quantitative cultures of respiratory secretions results in reduced mortality, reduced time in ICU and on mechanical ventilation, or higher rates of antibiotic change when compared to qualitative cultures in patients with VAP. We observed similar results when invasive strategies were compared with non-invasive strategies.

Read the full abstract...
Background: 

Ventilator-associated pneumonia (VAP) is a common infectious disease in intensive care units (ICUs). The best diagnostic approach to resolve this condition remains uncertain.

Objectives: 

To evaluate whether quantitative cultures of respiratory secretions and invasive strategies are effective in reducing mortality in immunocompetent patients with VAP, compared with qualitative cultures and non-invasive strategies. We also considered changes in antibiotic use, length of ICU stay and mechanical ventilation.

Search strategy: 

We searched CENTRAL (2014, Issue 9), MEDLINE (1966 to October week 2, 2014), EMBASE (1974 to October 2014) and LILACS (1982 to October 2014).

Selection criteria: 

Randomised controlled trials (RCTs) comparing respiratory samples processed quantitatively or qualitatively, obtained by invasive or non-invasive methods from immunocompetent patients with VAP and which analysed the impact of these methods on antibiotic use and mortality rates.

Data collection and analysis: 

Two review authors independently reviewed the trials identified in the search results and assessed studies for suitability, methodology and quality. We analysed data using Review Manager software. We pooled the included studies to yield the risk ratio (RR) for mortality and antibiotic change with 95% confidence intervals (CI).

Main results: 

Of the 5064 references identified from the electronic databases (605 from the updated search in October 2014), five RCTs (1367 patients) met the inclusion criteria. Three studies compared invasive methods using quantitative cultures versus non-invasive methods using qualitative cultures, and we used them to answer the main objective of this review. The other two studies compared invasive versus non-invasive methods, both using quantitative cultures. We combined all five studies to compare invasive versus non-invasive interventions for diagnosing VAP. The studies that compared quantitative and qualitative cultures (1240 patients) showed no statistically significant differences in mortality rates (RR 0.91; 95% CI 0.75 to 1.11). The analysis of all five RCTs showed there was no evidence of reduction in mortality in the invasive group versus the non-invasive group (RR 0.93; 95% CI 0.78 to 1.11). There were no significant differences between the interventions with respect to the number of days on mechanical ventilation, length of ICU stay or antibiotic change.

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