Incidences of Pseudomonas aeruginosa-Associated Ventilator-Associated Pneumonia within Studies of Respiratory Tract Applications of Polymyxin: Testing the Stoutenbeek Concurrency Postulates

ABSTRACT

Regimens containing topical polymyxin appear highly effective at preventing ventilator-associated pneumonia (VAP) overall and, more so, VAP caused by Gram-negative bacteria. However, Stoutenbeek's postulates that VAP incidences within studies of topical antibiotics depend on the context of whether the component (control and intervention) groups of each study were concurrent versus nonconcurrent remain untested. The literature was searched for concurrent control (CC) versus nonconcurrent control (NCC) designed studies of respiratory tract applications of topical polymyxin to mechanically ventilated (MV) patients that reported incidences of Pseudomonas-associated ventilator-associated pneumonia (PsVAP). Studies of various interventions other than topical polymyxin (nonpolymyxin studies) served to provide additional points of reference. The PsVAP incidences within the component groups of all studies were benchmarked against groups from observational studies. This was undertaken by meta-regression using generalized estimating equation methods. Dot plots, caterpillar plots, and funnel plots enable visual benchmarking. The PsVAP benchmark (and 95% confidence interval [CI]) derived from 102 observational groups is 4.6% (4.0 to 5.3%). In contrast, the mean PsVAP within NCC polymyxin intervention groups (1.6%; CI, 1.0 to 4.5%) is lower than that of all other component group categories. The mean PsVAP within CC polymyxin control groups (9.9%; CI, 7.6 to 12.8%) is higher than that of all other component group categories. The PsVAP incidences of control and intervention groups of studies of respiratory tract applications of polymyxin are dependent on whether the groups were within a concurrent versus nonconcurrent study. Stoutenbeek's concurrency postulates are validated.