Oral decontamination (2% gentamicin, 2% colstin, and 2% vancomycin paste) has been shown to reduce pneumonia and mortality in ventilator dependent patients without an increased incidence of antibiotic resistance [Am J Respir Crit Care Med 164: 382, 2001; Crit Care Med 32: 126, 2004]. The CDC still does not recommend oral decontamination routinely [CDC Morbidity and Mortality Weekly Report, Vol. 53 (No. RR-3): March 26, 2004] although it may be indicated in some – Marino recommends it in patients 1) on the vent > 1 week 2) with severely impaired lung function 3) at increased risk for aspiration, and 4) with recurrent pneumonia in the ICU.
Selective digestive decontamination (SDD) involves oral cavity paste, GI tract solution, and IV antibiotics for ~ 4 days. Its goal is to eliminate harmful bacteria while allowing native flora to thrive. It is highly controversial [J Am Coll Surg 188: 225, 1999; JAMA286: 335, 2001] because while it has been shown to reduce rates of infection [Intensive Care Med 29: 677, 2003], it is labor-intensive and thought by some to increase the incidence of antibiotic resistance, especially in areas with endemic levels of MRSA and VRE. Selective oral decontamination (SOD) relies on oral cavity paste, GI tract solution, but no intravenous agents.
Data In Support of SDD
German RCT (546 patients)
There are three recent level I trials in support of SDD. The first, from Germany, was a randomized, prospective study of 546 patients in the SICU or trauma ICU. Patients were stratified according to APACHE-II scores. They were then randomized to receive either 2 # 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. Infection rate was significantly reduced in the SDD group (risk ratio 0.477; 95% CI 0.367–0.620; p < 0.001), especially pneumonias (6 versus 29, p < 0.007), other lower respiratory tract infections (39 versus 70, p < 0.007), bloodstream infections (14 versus 36, p < 0.007), and urinary tract infections (36 versus 60, p < 0.042). Also, significantly fewer patients acquired severe organ dysfunction (63 versus 96 patients, p < 0.0051; RR 0.636; 95% CI 0.463–0.874), especially renal dysfunction (17 versus 38; p < 0.018). Overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20–29 on admission (20 versus 38 fatalities, p < 0.0147; RR 0.508; 95% CI 0.295–0.875); there was also a favorable trend at 1 year (51 versus 60 fatalities; p < 0.0844; RR, 0.720; 95% CI, 0.496–1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis. [Am J Respir Crit Care Med 166: 1029, 2002]
Netherlands RCT (934 patients)
The second, from the Netherlands, was a prospective, randomized, controlled, unblinded clinical trial of 934 patients admitted to a surgical or medical ICU. 466 were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime. 468 were assigned standard treatment (standard oropharyngeal care consisted of rinsing the mouth with water four times daily and tooth brushing twice daily. Prophylaxis for stress ulcers was not given routinely. If necessary H2-receptor antagonists or PPI were given to reduce gastric acidity. Enteral feeding was started as early as possible, generally on the first or second day. Systemic antibiotics for proven or suspected infections were given as clinically indicated). In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0•02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with methicillin-resistant Staphylococcus aureus. Authors’ interpretation: in a setting with low prevalence of VRE and MRSA, SDD can decrease ICU and hospital mortality and colonization with resistant gram-negative aerobic bacteria [Lancet 362: 1011, 2003]
Netherlands RCT #2 (5939 patients, 13 ICUs)
The third, also from the Netherlands, compared SDD and SOD to control. Both SDD and SOD lowered the risk of death (OR 0.83 [0.72-0.97] and 0.86 [0.74-0.99], respectively) and gram negative infection (OR 0.43 [0.24-0.77] and 0.49 [0.27-0.87], respectively), without increasing the incidence of antimicrobial resistance. Importantly, antibiotic usage patterns were significantly different between groups (“…During treatment with SDD as compared with standard care, the use of antimicrobial agents with antianaerobic activity was reduced by 27.8% for broad-spectrum penicillins, 45.7% for carbapenems, and 11.6% for lincosamides. Furthermore, quinolone use (mainly ciprofloxacin) was reduced by 31.4%. In contrast, systemic use of cephalosporins increased by 86.6%“). Notably, the cost per-day of SOD and SDD were $1 and $12, respectively [de Smet AM et al. NEJM 360: 20, 2009]
Cochrane Database Meta-Analysis
A recent Cochrane meta-analysis of 36 RCTs, which included 6914 patients, demonstrated that SDD reduces both mortality and RTI in adult patients receiving intensive care treatment, and that SOD reduces RTI (but not mortality). Further, the authors state that “The risk of resistance occurring as a negative consequence of antibiotic use was appropriately explored only in one trial which did not show any such effect“ [Liberati A et al. Cochrane Database Syst Rev CD000022: 2009]. Importantly, this analysis does not include data from [de Smet AM et al. NEJM 360: 20, 2009. Although most studies show a trend towards improved survival in SDD-treated patients, the majority are too small to show a significant survival benefit. It appears that studies which only use topical antibiotics do not affect mortality (ex. many earlier studies), whereas those that do use concurrent IV abx show significant decreases in mortality [Curr Opin Crit Care 8: 139, 2002]
Concerns Regarding SDD
SDD and Antibiotic Resistance
Two RCTs evaluated the impact of SDD on antimicrobial resistance amongst AGNB as primary endpoint. An earlier French RCT [Ann Intern Med 110: 873, 1989] showed that the addition of enteral antimicrobials to parenteral antimicrobials controls carriage and infections due to extended spectrum beta-lactamase producing Klebsiella. The Dutch study previously mentioned [Lancet 363: 1011, 2003] demonstrated that carriage of AGNB resistant to imipenem, ceftazidime, ciprofloxacin, tobramycin and polymyxins occurred in 16% of SDD patients compared to 26% of control patients with a RR of 0.6 (95% CI 0.5–0.8). SDD prophylaxis appears not to be active against VRE and MRSA and may promote gut overgrowth of these intrinsically resistant Gram-positive bacteria. Two American RCTs studied VRE carriage and infection as the primary endpoints, and found no difference between test and control groups [Clin Infect Dis 22: 997, 1996; Transplantation 73: 1904, 2002]. There are seven RCTs conducted in ICUs where MRSA was endemic at the time of the trial, they report a trend towards a higher MRSA carriage and infection rates in patients receiving SDD [Silvestri et. al, Infection Control in the Intensive Care Unit, Springer, Milan pp. 297–312, 2005]. The addition of enteral vancomycin to the classical SDD is required to control MRSA in ICUs with endemic MRSA [Silvestri et. al]. VRE did not emerge in any of the studies using enteral vancomycin.
Notably, both a Cochrane Review [Liberati A et al. Cochrane Database Syst Rev CD000022: 2009] and a recent randomized, controlled trial including almost 6000 patients [de Smet AM et al. NEJM 360: 20, 2009] failed to find any evidence of an increase in antibiotic resistance following initiation of SDD
Efficacy in ICUs with High Antimicrobial Resistance
Some authors suggest that data from European ICUs, which generally have lower rates of resistant organisms than ICUs in the United States, cannot be extrapolated to other countries.