Nebulized antibiotics for ventilator-associated pneumonia: misleading analysis and interpretation of the data

I read with interest the recent systematic review of nebulized antibiotics for ventilator-associated
pneumonia 1]. I congratulate and applaud Zampieri and colleagues’ important work, but several
important issues should be noted.

First, there is one important methodological issue with the review. The data from
randomized controlled trials and observational studies were inappropriately pooled
together, which goes against the precept of pooling studies with similar design. In
fact, the pooling of data from randomized controlled trials and observational studies
is only recommended for the assessment of harm/adverse effects. Thus, results from
randomized controlled trials and results from observational studies should be separately
pooled.

Second, two of the included observational studies were case–control studies 2], 3], and therefore using the relative risk as the summary statistic is improper. Instead,
the odds ratio should be used as the summary statistic to pool data from observational
studies.

Third, the authors used the standardized mean difference as the summary statistic
for the continuous variables. As we know, the standardized mean difference is unitless
because it is a relative, rather than an absolute, measure of effect. Instead, the
authors should have used the mean difference.

Last, Kalin and colleagues’ study should be excluded from the review. This study does
not state why patients received inhaled colistin and how many patients received a
high, normal or low dose in the inhaled plus intravenous colistin group and the intravenous
colistin group 4]. Inadequate allocation may thus exist, resulting in a significant potential for selection
bias. Inclusion of this study leads to significant heterogeneity, as shown in the
forest plot for clinical cure.