Selective digestive decontamination, a seemingly effective regimen with individual benefit or a flawed concept with population harm?

Abstract

Selective digestive decontamination (SDD) regimens, variously constituted with topical antibiotic prophylaxis (TAP) and protocolized parenteral antibiotic prophylaxis (PPAP), appear highly effective for preventing ICU-acquired infections but only within randomized concurrent control trials (RCCT’s). Confusingly, SDD is also a concept which, if true, implies population benefit. The SDD concept can finally be reified in humans using the broad accumulated evidence base, including studies of TAP and PPAP that used non-concurrent controls (NCC), as a natural experiment. However, this test implicates overall population harm with higher event rates associated with SDD use within the ICU context.

Staphylococcus aureus hitchhiking from colonization to bacteremia via Candida within ICU infection prevention studies: a proof of concept modelling

“…The postulate, that interaction between Candida and Staphylococcal colonization facilitates bacteremia occurrence, is supported by extensive preclinical evidence but proof of concept in the clinical context is lacking [1][2][3][4][5][6][7][8]. Here, the "hitchhiking" postulate, and the postulated effect of concurrency, have been tested by confronting three candidate causal models with published data from broadly selected ICU infection prevention studies wherein groups of patients had received various study interventions and other exposures.…”

“…The three part boxes represent the binomial proportion data for Candida and Staphylococcus VAP (v_can_n, v_sr_n) and candidemia (b_can_n) or bacteremia (b_sr_n) counts with the number of patients as the denominator which is logit transformed using the logit link function in the generalized model untested assumption that the concurrency effect is negligible, versus being either less evident or not observed within studies using non-concurrent control groups, [10,12,13,37]. Rebound colonization on TAP withdrawal is also a difficult to quantify ecological effect [8,38,39].…”

“…On the other hand, the numerous studies of various interventions for preventing infection acquired by patients receiving mechanical ventilation (MV) within the intensive care unit (ICU) literature can be perceived “in toto” as a single natural experiment of the group level effects of a range of antibiotic, anti-fungal and anti-septic exposures given as prophylaxis. These exposures are known to influence colonization with pathogenic bacteria and Candida [ 8 ]. Of note, the antibiotic-based interventions, as selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD), combine two singleton exposures, being topical antibiotic prophylaxis (TAP) and antifungal prophylaxis.…”

Structural equation modelling the relationship between anti-fungal prophylaxis and Pseudomonas bacteremia in ICU patients

“…The interaction underlying these paradoxical observations, potentially explains how ICU-acquired gram-negative bacteremia might occur seemingly without preceding colonization [ 18 , 35 , 36 ]. They also could account for the bacteremia prevention effects observed in large studies of antibiotic-based interventions of SDD regimens containing topical polymyxin and tobramycin combined with amphotericin as the anti-fungal [ 20 , 21 ], whereas the largest SDD study, where the same TAP regimen was combined with nystatin [ 22 ], failed to demonstrate any prevention effects against any bacteremia, or candidemia, end-points.…”

“…Moreover, the SDD concept invokes population effects which need to be considered in any analysis. Several SDD studies in the ICU setting avoided these anticipated contextual effects by using either non-concurrent or no control group patients [ 18 – 22 ].…”