Guideline

 

Selective decontamination of the digestive tract 

 

 

 

 

SDD committee ICV

 

Dr. A. Beishuizen, internist-intensivist (chairman)

Drs. R.B.G.E. Breukers, internist-intensivist

Dr. Y.L. Debets-Ossenkop, microbiologist

Dr. E.L. Swart, hospital pharmacist

M. van der Hout, senior ICU nurse

Introduction

 

Selective digestive decontamination (SDD) has been introduced in 1984 by Stoutenbeek as a method to prevent infections in patients on prolonged mechanical ventilation [1]. These infections, especially lower respiratory infections, are a major cause of morbidity and mortality in ICU patients. Most ICU-acquired infections are caused by aerobic Potentially Pathogenic Micro-organisms (PPM), usually after the development of colonisation. Colonisation with PPM occurs rapidly in the majority of patients. The reservoirs of these bacteria are the digestive tract, other colonized patients and contaminated environments. From these reservoirs different routes may lead to colonization. The concept of colonisation resistance, as proposed by van der Waaij, is based upon a beneficial effect of the anaerobic flora in resisting colonisation by PPM (appendix I) along the digestive tract [2].

SDD aims to eliminate selectively PPM and yeasts from the oropharyngeal cavity and gastrointestinal tract without disturbing the anaerobic flora. The cornerstone of SDD is the treatment and prevention of carriership of PPM by the topical administration (throat, stomach) of non-absorbable antimicrobial agents (colistin [polymyxin E], tobramycin, amphotericin B; all three together: PTA).

 

 

The terminology for infections that has been used is the following:

 

Primary endogenous:            Infections caused by pathogens present on admission (> 50%)

Secondary endogenous:        Infections caused by pathogens not present on admission, but developing after acquired colonization in ICU (30%)

Exogenous:                             Infections caused by pathogens not present on admission and developing without preceding colonization (20%)

 

The proposed benefits of SDD include the prevention of primary and secondary endogenous infections and the limitation of antibiotic resistance by eliminating the intestinal reservoir of Gram-negative bacteria. High hygienic standards (hand desinfection, isolation, sterilisation of equipment, protective clothing, cleaning of the patients environment) should be present to prevent exogenous and secondary endogenous infections.

 

Therefore, SDD is a four-component strategy and all four components should be applied in order to prevent and control these 3 types of infection.

 

Component 1 (primary endogenous):           parenteral antibiotics (cefotaxime)

Component 2 (secondary endogenous):      topical PTA (vide inferior)

Component 3 (exogenous):                          optimal hygienic standards

Component 4:                                                surveillance cultures (oropharynx, rectum)

 

SDD has been a controversial and much criticized intervention in the ICU. However, the BMJ-meta-analysis (33 randomized trials) showed that SDD reduces the number of respiratory infections with 65% [3]. In addition, analyzing combined data from the 16 SDD studies using the whole 4-component protocol (3361 patients), a 20% reduction in mortality was found. No superinfections or the occurrence of resistant micro-organisms were observed. Two other meta-analyses also reported decreased mortality among patients who were treated with SDD [4,5]. In spite of these impressive results the Stichting Werkgroep Antibioticabeleid (SWAB) advised against routine use of SDD in mechanically ventilated patients by questioning the validity of the meta-analyses, the small number of patients and the possible selection of intrinsic resistant micro-organism [6].

For the first time in a single centre trial, which was well designed and executed, de Jonghe et al. [7] confirmed the findings from the already mentioned powerful meta-analyses. They found odds ratios for ICU mortality and hospital mortality of 0.59 and 0.71. In addition, SDD-treated patients had a shorter duration of ventilation and total antibiotic costs were less for these patients. Surprisingly, a decreased colonization with resistant aerobic Gram-negative bacteria was found over a 27-month period.

Recently, the Dutch Society of Intensive Care (NVIC) developed a guideline ‘prevention of bacterial pneumonia and mortality during mechanical ventilation’ in which it was stated the classical four-component SDD leads to significant reductions in the number of pneumonias and mortality and that it does not lead to selection of induction of resistant [9]. In addition, it was shown that SDD is cost effective.

 

 

Main goal:      to eliminate pathological colonization from the (whole) patient with topical therapy (only systemic antibiotics for established infection) and give systemic prophylaxis/early therapy to prevent early endogenous infection and till topical antibiotics have done there work and the patient is “clean”.

 

Indication:      expected duration of mechanical ventilation of at least 48 h.

                        expected length of ICU stay of at least 72 h.

 

 

 

 

SDD-regimen

 

Standard regimen

 

1.      cefotaxime 4 dd 1 gr. intravenously during the first 3 days.

2.      oropharyngeal application 4dd 0.5 g (» erwt) of SDD paste

3.      application via nasogastric tube 4 dd 10 ml of SDD suspension

4.      when a duodenal or jejunely tube is present: 4 dd 5 ml through the NG tube and 5 ml through the duodenal/jejunal tube

 

Additive regimen

 

1. If surveillance culture of the throat contains yeast, oropharyngeal application of the SDD paste 8 dd instead of 4 dd, until two surveillance cultures are negative.
2. In case of proven cephalosporin allergy, cotrimoxazol 2 dd 960mg mg iv during 3 days will be given instead of cefotaxime.
3. SDD paste application around a tracheostomy 4 dd.
4. When a colostoma or an ileostoma is in situ a SDD-suppository (containing 200 mg amphotericin-B, tobramycin 40 mg and polymyxin E 100 mg)  2 dd  in the distal part of the gut.

 

 

 

 

 

 

Practical aspects

 

Cultures

 

·         Take "start" cultures (carrier state) of throat, feces (or rectum if no feces are produced), wounds (unless directly postoperative) and sputum (and blood cultures if patient might be bacteriemic). The rectum should also be cultured in patients with an ileo- or colostoma, as well as the feces from the stoma.

 

·         Surveillance: twice weekly (monday/thursday) cultures of throat, anus/perineum and when negative once weekly. Negative cultures are defined as the absence of Gr- rods, S. aureus and yeasts. The culture results will be presented in a semi-quantitative manner: +, ++, +++, and not as cfu. Results will focus on growth of Gr-rods, S. Aureus and yeasts.

 

·         The second culture after admission should at least have a time interval of 3 days (otherwise cultures will still be positive).

 

·         Sputum culture on admission (carrier state) and when indicated: purulent sputum or pneumonia.

 

 

General

.

·         Clean the mouth with sterile saline 4 times/day and apply SDD-paste in the mouth, especially the gums. Approximately 0.25-0.5 g of the paste is applied between the lower lip and gum.  A contact time of at least 20 minutes is required for effective decontamination. After each dose of SDD paste, apply sterile Vaseline to the lips for protection. Brush teeth twice daily.

 

·         Rectum/feces will contain Gr- rods, S. aureus and/or yeast until the SDD has reached the rectum, so vigorous efforts are needed to promote bowel movement, such as laxatives (first choice Movicolon), enemas, or even neostigmine (also see ‘obstipatie protocol’ in the ICV guideline booklet). Thus, every patient on SDD should receive Movicolon, magnesiumoxide and the lowest dose of opioids).

 

·         If throat contains Gr- rods, S. aureus or yeast in the first routine culture after the start of SDD: check the application of the SDD, and increase frequency to 8 dd until cultures are negative, than back to normal (4 dd).

 

·         If rectum/feces contains Gr- rods, S. aureus or yeast in the first routine culture after the first bowel movement/production of feces: increase bowel movements (see above), and increase SDD-solution to 8 dd until the cultures become negative.

 

·         This SDD regimen should result in a "clean" ICU in a short period, without cross-infections because hardly any bacteria can "stick" in the throat: the local concentration of the antibiotics will nearly always be above MBC. One caution: Proteus/Serratia are insensitive for colistin, but will be covered by the tobramycin.

 

·         Don’t give sucralfate concomitant with the SDD: it inactivates the colistin.

 

·         Endpoint of SDD regimen: when the patient is extubated.

 

·         Cefotaxim provides component of SDD casu quo aims to prevent and control primary endogenous infections.

 

·         Ceftriaxon will continue to be the cephalosporin of choice in the treatment of infections.

 

 

Infections 

 

·         Patients with a clinical suspicion of infection on admission to the ICU will be treated with antibiotics according to standard clinical practice (Antibiotica beleid 2003). Patients being treated with imipenem/cilastin, meropenem, ciprofloxacin, ceftriaxon or ceftazidim on admission will continue this medication and will not additionally receive cefotaxime as part of SDD.

 

·         Colonization-impairing antibiotics as amoxicillin, penicillin derivates or benzylpenicillin, piperacilline/tazobactam and amoxicillin-clavulanic acid will be discouraged and as a part of SDD or for the treatment of respiratory infections and should be replaced by cefotaxime.

 

·         When the bacteria are insensitive for cefotaxime, than switch to another antibiotic (cotrimoxazol), but preferably use no (extended) penicillin (negative effects on the colonization resistance).

 

·         Cefotaxime 4dd1gram during 3 days but switch to ceftriaxon (maximal 7 days) when there is suspicion for pneumonia and sputum cultures are clearly positive (+++)

 

·         Bronchopneumonia (see table 2,3): Ceftriaxon with the addition of tobramycin in case of ‘hospital’ PPM or E. coli.

 

·         When start-cultures of sputum definitively show Pseudomonas: switch cefotaxime to ceftazidim/tobramycin.

 

·         Atypical pneumonia: switch to levofloxacin (1-2dd500 mg iv or po), erythromycin(4dd 500mg-1gr) or clarithromycin (2dd500mg, only available for oral administration).

 

·         Sinusitis: drainage, start ceftriaxon/gentamicin during 5 days. Further adjustment according to cultures. ‘Community’ PPM: ceftriaxon. ‘Hospital’ PPM: continue combination therapy. Also notice the ‘sinusitis op de ICV’ guideline.

 

·         UTI: Only when systemic symptoms are present. The CAD should be replaced after 24 hrs of therapy. Cave: exogenous source (negative cultures throat/rectum). Vaginal carriage can be the source of PPM causing bladder infections in woman.

 

·         Catheter sepsis: remove line, it is rarely need to give systemic antibiotics, unless a fresh heart valve prosthesis is present ( short course of vancomycin). If the temperature does not drop within 24 h new cultures should be taken, and treatment should be initiated.

 

·         Intra-abdominal infection: ceftriaxon/gentamicin/metronidazol (metronidazol only for 3 days). Preemptive treatment with fluconazole should be strongly considered.  Cave: blind loops, corpus alienum. Also SDD suppositories in vagina or SDD suspension (as enema) in case of bacterial overgrowth in the rectum.

 

·         Enterococcal infection: The source of infection/sepsis should be identified and eliminated as soon as possible. Vancomycin (intravenously for at least 5 days) is indicated.

References

 

1.      Stoutenbeek et al. Int Care Med 1984;10:185-192.

2.      van der Waaij, D, et al. Journal of Hygiene 1971:69:405–11.

3.      D’Amico R, et al. BMJ 1998;316:1275-85.

4.      SDD trialists’ group. BMJ 1993;307:525-32.

5.      Nathans AB, et al. Arch Surg 1999;134:170-176.

6.      Bonten MJM, et al. NTvG 2001;145:353-357.

7.      De Jonghe E, et al. Lancet 2003;362:1011-1016.

8.      Chastre J, Fagon  Y. Ventilator-associated Pneumonia. AJRCCM 2002;165: 867 - 903.

9.      NVIC Richtlijn. Het voorkomen van bacteriele longontsteking en sterfte tijdens beademing. J.H.Rommes, P.E. Spronk, P.H.J. van der Voort, H.K.F. van Saene, D.F. Zandstra. (www.nvic.nl).

Appendix  I.

 

Classification of microorganisms based upon their intrinsic pathogenic capacity. The intrinsic pathogenicity-index (IPI) is the ratio between the number of ICU patients with an infection caused by the microorganism x  the number of ICU patients who are carrier of that microorganism. 'Home' PPM are carried in the throat and gut of  healthy persons. Patients with underlying illnesses carry both 'home' as well as 'hospital' PPM.

MRSA = meticillin-resistent Staphylococcus Aureus. PPM = potentially pathogenic micro-organism.

 

Intrinsic pathogenic capacity		Source	Microorganism	Flora
Low pathogenicity IPI = 0.01	Body-own flora	Throat     Gut     Vagina     Skin	Peptostreptococci, Veillonella spp, Streptococcus viridans   Bacteroides spp, Clostridium spp, enterococci, E. coli   Peptostreptococci, Bacteroides spp, lactobacilli   Propionibacterium acnes, Coagulase negative stafylococci	Normal
Intemediate pathogenicity IPI = 0.3 – 0.6	‘home’ PPM           ‘hospital’ PPM	Throat       Gut   Throat and gut	S. pneumoniae, H. influenzae, Moraxella catarrhalis, S. Aureus, Candida spp   E. coli,  S. Aureus, Candida spp   Klebsiella, Proteus, Morganella, Enterobacter, Citrobacter, Serratia, Pseudomonas, Acinetobacter spp, MRSA.	Normal           Abnormal
High pathogenicity IPI = 0.9 –1.0	‘Epidemic’ micro-organisms	Throat   Gut	Neisseria meningitidis   Salmonella spp	Abnormal

 

 

Appendix II.

 

Clinical  radiological and microbiological criteria for diagnosing ventilator-associated pneumonia (VAP) using non-invasive methods.  VAP is defined according to the criteria of the American College of Chest Physicians-American Thoracic Society consensus conferences and modified CDC criteria (8).

 

1.      New, persisting or progressive infiltrates on chest radiographs

2.      Purulent tracheal secretions

3.      Temperature >38.5^o C or < 35.5^o C

4.      Leucocytes > 10 x 10⁹/L or < 3.0 x 10⁹/L

5.      Positive culture with PPM from a tracheal aspirate > +++  or > 10⁴ cfu/ml

 

 

Appendix III.

Three types of VAP: incidence, causative microorganisms, and time of onset.

 

Type of pneumonia	incidence	causative PPM	Time of onset
Primary endogenous	50%	'home' and 'hospital'	< 7 days from admission
Secondary endogenous	30%	'hospital'	> 7 dagen from admission
Exogenous	20%	'hospital'	Any time point