Epidemiology of Pseudomonas aeruginosa in an intensive care unit using selective decontamination of the digestive tract

Antimicrob Agents Chemother

2018

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 -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.

Section: Discussionmentioning

confidence: 99%

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

Antimicrob Agents Chemother

2018

“…For example, admission to a room previously occupied by a patient doubles the risk for acquiring pathogenic organisms from the previous patient’s flora [ 79 – 81 ]. Patients receiving TAP can serve as reservoirs for Pseudomonas and other Gram-negative bacteria within the ICU [ 82 – 87 ].…”

Section: Introductionmentioning

confidence: 99%

Establishing the safety of selective digestive decontamination within the ICU population: a bridge too far?

2023

Trials

Background Infection prevention interventions within the intensive care unit (ICU) setting, whether studied within quality improvement projects or cluster randomized trials (CRT), are seen as low risk and grounded in an ethical imperative. Selective digestive decontamination (SDD) appears highly effective at preventing ICU infections within randomized concurrent control trials (RCCTs) prompting mega-CRTs with mortality as the primary endpoint. Findings Surprisingly, the summary results of RCCTs versus CRTs differ strikingly, being respectively, a 15-percentage-point versus a zero-percentage-point ICU mortality difference between control versus SDD intervention groups. Multiple other discrepancies are equally puzzling and contrary to both prior expectations and the experience within population-based studies of infection prevention interventions using vaccines. Could spillover effects from SDD conflate the RCCT control group event rate differences and represent population harm? Evidence that SDD is fundamentally safe to concurrent non-recipients in ICU populations is absent. A postulated CRT to realize this, the SDD Herd Effects Estimation Trial (SHEET), would require > 100 ICUs to achieve sufficient statistical power to find a two-percentage-point mortality spillover effect. Moreover, as a potentially harmful population-based intervention, SHEET would pose novel and insurmountable ethical issues including who is the research subject; whether informed consent is required and from whom; whether there is equipoise; the benefit versus the risk; considerations of vulnerable groups; and who should be the gatekeeper? Conclusion The basis for the mortality difference between control and intervention groups of SDD studies remains unclear. Several paradoxical results are consistent with a spillover effect that would conflate the inference of benefit originating from RCCTs. Moreover, this spillover effect would constitute to herd peril.

“…The limited data in the context of controlled SDD studies have revealed some subtle examples of cross-contamination and cross-infection (2,6,7,60,63). For example, some have reported the elimination of an endemic resistant Klebsiella isolate (7), while others have noted significant increases in frequency of resistant Acinetobacter isolates (63).…”

mentioning

confidence: 99%

“…In this same study, a significant reduction in rates of infections and overall pharyngeal colonization with Pseudomonas aeruginosa was noted in SDD recipients, and yet despite this, persistent rectal colonization was noted in some. Antibiogram and pyocine typing of the P. aeruginosa isolates indicated that this colonization in SDD patients represented a significant reservoir of persistent strains within the unit that caused a disproportionate number of infections in control patients (2).…”

mentioning

confidence: 99%

Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection?

Antimicrob Agents Chemother

1995

110

Selective decontamination of the digestive tract (SDD) has been evaluated as a method to prevent colonization and infection in ventilated patients in 40 trials. On the basis of an assumption that cross-infection would be reduced as a consequence of SDD and that this would distort the results of SDD studies that used concurrent controls, 14 studies used historic controls. To test this assumption, three observations from the two types of studies were compared. (i) The differences between observed and expected event rates for each study were used to perform a meta-analysis. This revealed that the summary odds ratios for bacteremia and respiratory infection were marked by significant heterogeneity (P > 0.95) and inconsistencies between those derived from studies with concurrent versus studies with historic controls. (ii) Where the data were available, the rates of acquisition of colonization in control groups were higher in studies with concurrent controls than in studies with historic controls. (iii) At least four studies with concurrent controls have shown a pattern of pathogenic isolates consistent with cross-infection between groups. These results are contrary to the initial assumption and suggest the possibility that SDD represents a major cross-infection hazard.Colonization and infection with gram-negative bacteria occur commonly in patients requiring prolonged intubation in intensive care units (ICUs) (12,20,62). Moreover, pneumonia is the most common fatal nosocomial infection, with mortality rates of 20 to 50% (12). In most instances, colonization of the gastrointestinal and respiratory tracts with pathogenic gramnegative bacteria precedes the development of infection in these patients. As an approach to prevent this progression from colonization through infection, the use of topical nonabsorbable antibiotics to selectively decontaminate the digestive tract (SDD) has been evaluated in 14 studies with historic controls (7,18,21,23,31,33,36,37,50,(52)(53)(54)63) and 26 studies with concurrent controls (1, 3, 4, 7, 9, 10, 15, 19, 22, 25, 27, 29, 32, 38, 42, 44-46, 49, 54-56, 58, 63, 65).A meta-analysis based on 22 randomized studies (4,142 patients) reported convincing evidence of a favorable effect of SDD on the incidence of respiratory infection (RI) with a reduction of approximately 63% (51). There may also be a difference in mortality as great as 20%, but this was shown to be statistically significant only when three studies (25,46,54) which had failed specific inclusion criteria for this meta-analysis were subsequently included. A criticism of this meta-analysis is that it failed to address the striking variability in RI rates in the control groups. In general, these rates were high (Ͼ40%) in studies in which a beneficial effect had been shown in contrast to studies that had not shown a beneficial effect (5).The interpretation of these studies is controversial (30,34,57,59,61). Issues of patient mix, study size, and design have been considered. In these studies, observer blinding is inherently difficult ...