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Antibiotic resistance associated with selective decontamination of the digestive tract
Journal
of Hospital
Infection
(1992)
22, 1-5
EDITORIAL
Antibiotic resistance decontamination
associated with of the digestive
selective tract
C. H. Webb Department
of Bacteriology, Royal Victoria Hospital, Grosvenor Belfast BT12 6BA, Northern Ireland, UK Accepted for publication
Road,
30 June 1992
Summary:
Selective decontamination of the digestive tract (SDD) appears to reduce infection, particularly pneumonia, in intensive care, and some patients benefit markedly. Gram-positive overgrowth and antibiotic resistance in both Gram-positive and Gram-negative organisms has been recorded. However, the clinical and epidemiological significance of these observations is still debated. Future studies will need to be of sufficient size and duration to provide good quality data on which the safety and efficacy of SDD can be properly judged.
Keywords:
Selective
decontamination;
intensive
care;
antibiotic
resistance.
It is now almost a decade since Stoutenbeek’ and colleagues reported the use of selective decontamination of the digestive tract (SDD) to reduce infection in trauma patients in intensive care units (ICUs). It is now widely used in ICUs but its efficacy and microbiological safety remain controversial. Some patient categories appear to benefit more than others2 from SDD and selective use in mixed ICUs is a probable future trend. It is self evident that SDD could exercise selective pressure in individual patients and the ICU as a whole which might give rise to antibiotic resistance and overgrowth. Many regimens have been described but the ‘standard’ SDD comprising topical amphotericin, tobramycin and polymyxin combined with a short course of i.v. cefotaxime has been most widely assessed. All SDD regimens have gaps in their spectrum, particularly in relation to Gram-positive organisms. Aerobic Gram-negative bacilli (AGNB) and pseudomonads may display intrinsic or acquired resistance and, over time, the ICU microbial milieu might show a drift towards SDD resistant strains. The volume and quality of available information on resistance is limited. In many reports of SDD trials there are only passing comments and often Correspondence 01954701/92/090001+05
to: Dr
C. H. Wetb 0 1992 The Hospd
SOS.0010
1
Infection
Society
2
Editorial
there are no supporting data provided. This may be partly due to the relatively small scale and short duration of most SDD studies. Repeat isolates of the same multiresistant strain can skew data particularly when a long-stay ICU patient is colonized by a resistant organism. A distinction also needs to be made between colonization and infection with these strains, and the criteria used to define a clinical infection can greatly influence the results obtained. This is particularly relevant in cases of nosocomial pneumonia where no wholly satisfactory cultural criteria for infection exist. Also topical antibiotic mixtures give rise to very high concentrations on the decontaminated mucosal surfaces and so in-vitro resistance may be overcome in vim. Conversely some strains sensitive to the SDD mixture can still colonize oropharyngeal mucosae and sometimes give rise to infection3 Overgrowth on decontaminated mucosae with coagulase-negative staphylococci, enterococci and Staphylococcus aureus has been widely reported.*p@ and several groups have recorded worrying oxacillin-, Blair et al. noted early colonization of tobramycin- or multi-resistance.“6,8 SDD and control patients by coagulase-negative staphylococci resistant to gentamicin, tobramycin, netilmicin and amikacin.* Typing of sample strains by pyrolysis mass spectroscopy suggests that cross colonization between SDD cases and controls readily occurred in this concurrent study (J. Magee, pers. comm.). Further studies using polyacrylamide gel electrophoresis of whole-cell protein have confirmed this impression.’ In this ICU, in which standard SDD has been used in an unselective manner for over 30 months 83% of coagulase-negative staphylococci from surveillance cultures were resistant to tobramycin (1991 figures: unpublished data). Documented reports of Gram-positive sepsis are still relatively few but S. aureus peritonitis,” enterococcal septicaemia” and oxacillin-resistant S. uureus pneumonia’ have been recorded. Tetteroo and colleagues, who used SDD successfully in oesophageal resection, experienced an excess of late mixed and Gram-negative infections in SDD patients who had completed a lo-day course of decontamination.‘* Many workers seem to have failed to assess adequately the impact of Gram-positive colonization/infection in their SDD trials13 and so there is probably some under-reporting of this problem. Pugin et ~1.‘~ have recently reported a study in which topical vancomycin was included in the SDD regimen and i.v. cefotaxime was omitted: S. uureus pneumonia was greatly reduced but not eliminated. There can be little doubt that most if not all SDD regimens promote Gram-positive overgrowth and that there is a strong selective pressure towards resistance. This may initially be restricted to the drugs in the SDD regimen but broad-spectrum resistance is clearly encouraged. Methicillin-resistant S. uureus and enterococci with high-level aminoglycoside or glycopeptide resistance must be a cause for serious concern. While Gram-positive sepsis in SDD patients is still apparently
Resistance
with
SDD
3
uncommon one has to consider that perhaps it is only a matter of time before it appears. There are two separate issues concerned with the question of resistant AGNB and pseudomonads in SDD. One is the effect of the topical antibiotic cocktail in selecting or inducing resistant strains. The second is the likelihood of encountering cefotaxime resistance, or broad-spectrum p-lactamase resistance as a result of heavy iv cefotaxime prescribing. Concern over both of these issues has been expressed.13~‘5@ The interrelationship between colonization by AGNB of decontaminated mucosae, SDD drug resistance and infection in SDD patients is not straightforward. Armstrong et aL3 have shown that sensitive pseudomonas strains can colonize the oropharynx and sometimes infect patients receiving standard SDD. These workers also showed that certain pyocine types become endemic in the ICU irrespective of whether they were sensitive or resistant to the SDD regimen. It is possible that the effect of SDD is to narrow the diversity of AGNB species in the ICU rather than cause a process of simple selection of resistant strains. Polymyxin-resistance rates of up to 15 % have been reported, comprising largely of the intrinsically resistant species, Proteus, Morganella, Xanthomonas and some strains of Serratia. There is greater diversity in reported prevalence of aminoglyocoside resistance to AGNB. Tobramycin-resistance rates of less than 5% have been recorded in several studies.5,‘7m19During the l&month concurrent SDD trial of Blair et cd.* tobramycin resistance varied widely and was generally higher in SDD patients. Misset et al. have reported a rise in gentamicin and polymyxin resistance to 50% during a 4-month period.*’ Aminoglycoside-resistant Pseudomonas spp. have shown a tendency to increase in some studies2*5 and the standard SDD regimen may encourage strains which successfully colonize the oropharynx to become endemic in the ICU.3 Resistance rates to cefotaxime of 10-l 5% are common1*4~‘8 and may be subject to wide fluctuations. * In this respect snapshot prevalence data are of limited value because it is inevitable that from time to time resistant AGNB will be detected. There is, as yet, little reliable evidence to suggest that these strains are becoming endemic in ICUs using standard SDD. In long-term follow-up of two ICUs using SDD unselectively, cefotaxime resistance has remained stable at around 10% (S. Alcock, pers. comm.) and 15% (Regional ICU, Royal Victoria Hospital, Belfast, UK; 1991 figures, unpublished data). The general level of prescribing of broad-spectrum cephalosporins in ICUs is very high and may greatly exceed that which is involved in the use of SDD. However, a reduction in empirical prescribing is not an automatic benefit of SDD unless a strict protocol is enforced. There are insufficient data available to judge whether SDD influences the occurrence of extended spectrum /&lactamases in AGNB. Indeed, topical SDD has been used to eliminate Klebsiella spp. harbouring such enzymes.6T21
4
Editorial
Low concentrations of antibiotic in the gut may promote the selection of resistant strains and van Saene has argued that the pharmacodynamics of cefotaxime and stability of tobramycin in faeces make the standard SDD regimen the optimal choice.** However, the great diversity of patient categories and SDD regimens which have been used make it difficult to draw firm conclusions. A further complication arises when additional prophylactic or therapeutic antibiotics are added to the SDD regimen, and where this occurs SDD could be judged as having failed.” It would appear that Gram-positive bacterial overgrowth and resistance is a widespread and potentially serious problem. Resistance and superinfection with AGNB remains an issue which requires monitoring over a longer period. Pseudomonas superinfection may be a particular hazard in the longer term. Greater care in patient matching and larger, longer studies will be needed in future. Close microbiological monitoring specifically directed towards the detection of problem strains will be essential and this may need to be continued in the wards after ICU discharge. The clinical performance of SDD must also be audited on a long-term basis so that any benefit can be weighed against the microbiological hazards. The author manuscript
would like to acknowledge and Dr J. G. Barr, who
the help of MS Julie reviewed the text.
Lyness,
who
word-processed
the
References 1. Stoutenbeek CP, van Saene HKF, Miranda DR, Zandstra DF. The effect of selective decontamination of the digestive tract on colonisation and infection in multiple trauma patients. Intensive Cure Med 1984; 10: 185-192. BJ, Lowry K, Webb H, Armstrong P, Smilie J. Selective 2. Blair P, Rowlands decontamination of the digestive tract: a stratified, randomised, prospective study in a mixed intensive care unit. Surgery 1991; 110: 303-310. 3. Armstrong PJ, Barr JG, Webb CH, Blair PH, Rowlands BJ. Epidemiology of Pseudomonas aeruginosa in an intensive care unit using selective decontamination of the digestive tract. J Hasp Infect 1992; 20: 199-208. 4. Konrad F, Schwalbe B, Heeg K et al. Kolonisations-Pneumoniefrequenz und Resistenzent-Wilklung bei langzeitbeatmeten Intensivepatienten unter selektiver Dekontamination des Verdauungstraktes. Anaesthesist 1989; 38: 99-109. 5. Nau R, Ruchel R, Mergerian H, Wegener U, Winklemann T, Prange HW. Emergence of antibiotic-resistant bacteria during selective decontamination of the digestive tract. J Antimicrob Chemother 1990; 25: 881-883. C, Legrand P, Rauss A et al. Intestinal decontamination for control of 6. Brun-Buisson nosocomial multiresistant Gram-negative bacilli. Ann Intern Med 1989; 110: 873-881. 7. Sydow M, Burchardi H, Crozier TA, Ruchel R, Busse C, Seyde WC. Einfluss der selektiven Dekontamination auf nosokomiale Infecktionen, Erregerspektrum and Antibiokaresistenz bei langzeitbeatmeten Intensivpatienten. Anaesth Intensivther Natfallmed 1990; 25: 416423. 8. Aitchison JM, van den Ende J, van Rensburg HCG, Opperman KR. Prospective study of the selective parenteral and enteral antibiotic regimen (SPEAR) in critically ill surgical patients (Abstr.). 17th International Congress on Chemotherapy, Berlin 1991; Abstract No. 460. 9. Pope CM, Erwin P, Barr JG, Bamford KB. Epidemiology of coagulase-negative staphylococci in an intensive care unit selectively employing SDD (Abstr.). 7th
Resistance
with
SDD
5
International
10. 11. 12.
13. 14. 15. 16. 17. 18.
Symposium on staphylococci and staphylococcal infections, Stockholm 1992; Abstract No. 145. McClelland P, Coakley J, Williams PG, Bone JM, Mostafa SM. Staphylococcal peritonitis following selective decontamination of digestive tract. Lancet 1988; ii: 800. Abu-Zidan FMA, McAteer E, Elhag M. Selective decontamination of the digestive tract in Kuwait. Crit Care Med 1989; 17: 1364. Tetteroo GWM, Wagenvoort JHT, Ince C, Bruining HA. Effects of selective decontamination on Gram-negative colonisation, infections and development of bacterial resistance in oesophageal resection. Intensive Care Med 1990; 16: S22+228. Daschner F. Emergence of resistance during selective decontamination of the digestive tract. Eur J Clin Microbial Infect Dis 1992; 11: l-3. Pugin J, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. JAMA 1991; 265: 27042710. Heizmann WR. SDD and the novel extended broad spectrum 8-lactamases. J Antimicrob Chemother 1990; 26: 295-296. Hemmer R. Effect of SDD upon antibiotic resistance (Abstr). First European Consensus Conference of Intensive Care Medicine, Paris 1991. Daschner F. Geiger K. Selektive Darmdekontamination-ia oder nein? Klin Wochenschr 1991; 69 (Suppl.-XXVII): 1-5. Ledingham I McA, Alcock SR, Eastaway AT, McDonald JC, McKay IC, Ramsay G. Triule regimen of selective decontamination of the digestive tract, svstemic cefotaxime. and microbiological surveillance for prevention of acquired infection in intensive care. Lancet 1988; 1: 785-790.
19.
20. 21. 22.
Stoutenbeek antibiotics
CP, van Saene HKF, Zandstra DF. The effect of oral non-absorbable on the emergence of resistant bacteria in patients in an intensive care unit. J Antimicrob Chemother 1987; 19: 513-520. Misset B, Mahe P, Kitzis G et al. Effect of selective decontamination on the faecal flora of patients in an intensive care unit (Abstr.) Surg Res Comm 1990; 8 (Suppl.): 1.5. Taylor ME, Oppenheim BA. Selective decontamination of the gastrointestinal tract as an infection control measure. J Hasp Infect 1991; 17: 271-278. van Saene HKF, Stoutenbeek CP, Hart CA. Selective decontamination of the digestive tract (SDD) in intensive care patients: a critical evaluation of the clinical, bacteriological and epidemiological benefits. J Hosp Infect 1991; 18: 261-277.
of Hospital
Infection
(1992)
22, 1-5
EDITORIAL
Antibiotic resistance decontamination
associated with of the digestive
selective tract
C. H. Webb Department
of Bacteriology, Royal Victoria Hospital, Grosvenor Belfast BT12 6BA, Northern Ireland, UK Accepted for publication
Road,
30 June 1992
Summary:
Selective decontamination of the digestive tract (SDD) appears to reduce infection, particularly pneumonia, in intensive care, and some patients benefit markedly. Gram-positive overgrowth and antibiotic resistance in both Gram-positive and Gram-negative organisms has been recorded. However, the clinical and epidemiological significance of these observations is still debated. Future studies will need to be of sufficient size and duration to provide good quality data on which the safety and efficacy of SDD can be properly judged.
Keywords:
Selective
decontamination;
intensive
care;
antibiotic
resistance.
It is now almost a decade since Stoutenbeek’ and colleagues reported the use of selective decontamination of the digestive tract (SDD) to reduce infection in trauma patients in intensive care units (ICUs). It is now widely used in ICUs but its efficacy and microbiological safety remain controversial. Some patient categories appear to benefit more than others2 from SDD and selective use in mixed ICUs is a probable future trend. It is self evident that SDD could exercise selective pressure in individual patients and the ICU as a whole which might give rise to antibiotic resistance and overgrowth. Many regimens have been described but the ‘standard’ SDD comprising topical amphotericin, tobramycin and polymyxin combined with a short course of i.v. cefotaxime has been most widely assessed. All SDD regimens have gaps in their spectrum, particularly in relation to Gram-positive organisms. Aerobic Gram-negative bacilli (AGNB) and pseudomonads may display intrinsic or acquired resistance and, over time, the ICU microbial milieu might show a drift towards SDD resistant strains. The volume and quality of available information on resistance is limited. In many reports of SDD trials there are only passing comments and often Correspondence 01954701/92/090001+05
to: Dr
C. H. Wetb 0 1992 The Hospd
SOS.0010
1
Infection
Society
2
Editorial
there are no supporting data provided. This may be partly due to the relatively small scale and short duration of most SDD studies. Repeat isolates of the same multiresistant strain can skew data particularly when a long-stay ICU patient is colonized by a resistant organism. A distinction also needs to be made between colonization and infection with these strains, and the criteria used to define a clinical infection can greatly influence the results obtained. This is particularly relevant in cases of nosocomial pneumonia where no wholly satisfactory cultural criteria for infection exist. Also topical antibiotic mixtures give rise to very high concentrations on the decontaminated mucosal surfaces and so in-vitro resistance may be overcome in vim. Conversely some strains sensitive to the SDD mixture can still colonize oropharyngeal mucosae and sometimes give rise to infection3 Overgrowth on decontaminated mucosae with coagulase-negative staphylococci, enterococci and Staphylococcus aureus has been widely reported.*p@ and several groups have recorded worrying oxacillin-, Blair et al. noted early colonization of tobramycin- or multi-resistance.“6,8 SDD and control patients by coagulase-negative staphylococci resistant to gentamicin, tobramycin, netilmicin and amikacin.* Typing of sample strains by pyrolysis mass spectroscopy suggests that cross colonization between SDD cases and controls readily occurred in this concurrent study (J. Magee, pers. comm.). Further studies using polyacrylamide gel electrophoresis of whole-cell protein have confirmed this impression.’ In this ICU, in which standard SDD has been used in an unselective manner for over 30 months 83% of coagulase-negative staphylococci from surveillance cultures were resistant to tobramycin (1991 figures: unpublished data). Documented reports of Gram-positive sepsis are still relatively few but S. aureus peritonitis,” enterococcal septicaemia” and oxacillin-resistant S. uureus pneumonia’ have been recorded. Tetteroo and colleagues, who used SDD successfully in oesophageal resection, experienced an excess of late mixed and Gram-negative infections in SDD patients who had completed a lo-day course of decontamination.‘* Many workers seem to have failed to assess adequately the impact of Gram-positive colonization/infection in their SDD trials13 and so there is probably some under-reporting of this problem. Pugin et ~1.‘~ have recently reported a study in which topical vancomycin was included in the SDD regimen and i.v. cefotaxime was omitted: S. uureus pneumonia was greatly reduced but not eliminated. There can be little doubt that most if not all SDD regimens promote Gram-positive overgrowth and that there is a strong selective pressure towards resistance. This may initially be restricted to the drugs in the SDD regimen but broad-spectrum resistance is clearly encouraged. Methicillin-resistant S. uureus and enterococci with high-level aminoglycoside or glycopeptide resistance must be a cause for serious concern. While Gram-positive sepsis in SDD patients is still apparently
Resistance
with
SDD
3
uncommon one has to consider that perhaps it is only a matter of time before it appears. There are two separate issues concerned with the question of resistant AGNB and pseudomonads in SDD. One is the effect of the topical antibiotic cocktail in selecting or inducing resistant strains. The second is the likelihood of encountering cefotaxime resistance, or broad-spectrum p-lactamase resistance as a result of heavy iv cefotaxime prescribing. Concern over both of these issues has been expressed.13~‘5@ The interrelationship between colonization by AGNB of decontaminated mucosae, SDD drug resistance and infection in SDD patients is not straightforward. Armstrong et aL3 have shown that sensitive pseudomonas strains can colonize the oropharynx and sometimes infect patients receiving standard SDD. These workers also showed that certain pyocine types become endemic in the ICU irrespective of whether they were sensitive or resistant to the SDD regimen. It is possible that the effect of SDD is to narrow the diversity of AGNB species in the ICU rather than cause a process of simple selection of resistant strains. Polymyxin-resistance rates of up to 15 % have been reported, comprising largely of the intrinsically resistant species, Proteus, Morganella, Xanthomonas and some strains of Serratia. There is greater diversity in reported prevalence of aminoglyocoside resistance to AGNB. Tobramycin-resistance rates of less than 5% have been recorded in several studies.5,‘7m19During the l&month concurrent SDD trial of Blair et cd.* tobramycin resistance varied widely and was generally higher in SDD patients. Misset et al. have reported a rise in gentamicin and polymyxin resistance to 50% during a 4-month period.*’ Aminoglycoside-resistant Pseudomonas spp. have shown a tendency to increase in some studies2*5 and the standard SDD regimen may encourage strains which successfully colonize the oropharynx to become endemic in the ICU.3 Resistance rates to cefotaxime of 10-l 5% are common1*4~‘8 and may be subject to wide fluctuations. * In this respect snapshot prevalence data are of limited value because it is inevitable that from time to time resistant AGNB will be detected. There is, as yet, little reliable evidence to suggest that these strains are becoming endemic in ICUs using standard SDD. In long-term follow-up of two ICUs using SDD unselectively, cefotaxime resistance has remained stable at around 10% (S. Alcock, pers. comm.) and 15% (Regional ICU, Royal Victoria Hospital, Belfast, UK; 1991 figures, unpublished data). The general level of prescribing of broad-spectrum cephalosporins in ICUs is very high and may greatly exceed that which is involved in the use of SDD. However, a reduction in empirical prescribing is not an automatic benefit of SDD unless a strict protocol is enforced. There are insufficient data available to judge whether SDD influences the occurrence of extended spectrum /&lactamases in AGNB. Indeed, topical SDD has been used to eliminate Klebsiella spp. harbouring such enzymes.6T21
4
Editorial
Low concentrations of antibiotic in the gut may promote the selection of resistant strains and van Saene has argued that the pharmacodynamics of cefotaxime and stability of tobramycin in faeces make the standard SDD regimen the optimal choice.** However, the great diversity of patient categories and SDD regimens which have been used make it difficult to draw firm conclusions. A further complication arises when additional prophylactic or therapeutic antibiotics are added to the SDD regimen, and where this occurs SDD could be judged as having failed.” It would appear that Gram-positive bacterial overgrowth and resistance is a widespread and potentially serious problem. Resistance and superinfection with AGNB remains an issue which requires monitoring over a longer period. Pseudomonas superinfection may be a particular hazard in the longer term. Greater care in patient matching and larger, longer studies will be needed in future. Close microbiological monitoring specifically directed towards the detection of problem strains will be essential and this may need to be continued in the wards after ICU discharge. The clinical performance of SDD must also be audited on a long-term basis so that any benefit can be weighed against the microbiological hazards. The author manuscript
would like to acknowledge and Dr J. G. Barr, who
the help of MS Julie reviewed the text.
Lyness,
who
word-processed
the
References 1. Stoutenbeek CP, van Saene HKF, Miranda DR, Zandstra DF. The effect of selective decontamination of the digestive tract on colonisation and infection in multiple trauma patients. Intensive Cure Med 1984; 10: 185-192. BJ, Lowry K, Webb H, Armstrong P, Smilie J. Selective 2. Blair P, Rowlands decontamination of the digestive tract: a stratified, randomised, prospective study in a mixed intensive care unit. Surgery 1991; 110: 303-310. 3. Armstrong PJ, Barr JG, Webb CH, Blair PH, Rowlands BJ. Epidemiology of Pseudomonas aeruginosa in an intensive care unit using selective decontamination of the digestive tract. J Hasp Infect 1992; 20: 199-208. 4. Konrad F, Schwalbe B, Heeg K et al. Kolonisations-Pneumoniefrequenz und Resistenzent-Wilklung bei langzeitbeatmeten Intensivepatienten unter selektiver Dekontamination des Verdauungstraktes. Anaesthesist 1989; 38: 99-109. 5. Nau R, Ruchel R, Mergerian H, Wegener U, Winklemann T, Prange HW. Emergence of antibiotic-resistant bacteria during selective decontamination of the digestive tract. J Antimicrob Chemother 1990; 25: 881-883. C, Legrand P, Rauss A et al. Intestinal decontamination for control of 6. Brun-Buisson nosocomial multiresistant Gram-negative bacilli. Ann Intern Med 1989; 110: 873-881. 7. Sydow M, Burchardi H, Crozier TA, Ruchel R, Busse C, Seyde WC. Einfluss der selektiven Dekontamination auf nosokomiale Infecktionen, Erregerspektrum and Antibiokaresistenz bei langzeitbeatmeten Intensivpatienten. Anaesth Intensivther Natfallmed 1990; 25: 416423. 8. Aitchison JM, van den Ende J, van Rensburg HCG, Opperman KR. Prospective study of the selective parenteral and enteral antibiotic regimen (SPEAR) in critically ill surgical patients (Abstr.). 17th International Congress on Chemotherapy, Berlin 1991; Abstract No. 460. 9. Pope CM, Erwin P, Barr JG, Bamford KB. Epidemiology of coagulase-negative staphylococci in an intensive care unit selectively employing SDD (Abstr.). 7th
Resistance
with
SDD
5
International
10. 11. 12.
13. 14. 15. 16. 17. 18.
Symposium on staphylococci and staphylococcal infections, Stockholm 1992; Abstract No. 145. McClelland P, Coakley J, Williams PG, Bone JM, Mostafa SM. Staphylococcal peritonitis following selective decontamination of digestive tract. Lancet 1988; ii: 800. Abu-Zidan FMA, McAteer E, Elhag M. Selective decontamination of the digestive tract in Kuwait. Crit Care Med 1989; 17: 1364. Tetteroo GWM, Wagenvoort JHT, Ince C, Bruining HA. Effects of selective decontamination on Gram-negative colonisation, infections and development of bacterial resistance in oesophageal resection. Intensive Care Med 1990; 16: S22+228. Daschner F. Emergence of resistance during selective decontamination of the digestive tract. Eur J Clin Microbial Infect Dis 1992; 11: l-3. Pugin J, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. JAMA 1991; 265: 27042710. Heizmann WR. SDD and the novel extended broad spectrum 8-lactamases. J Antimicrob Chemother 1990; 26: 295-296. Hemmer R. Effect of SDD upon antibiotic resistance (Abstr). First European Consensus Conference of Intensive Care Medicine, Paris 1991. Daschner F. Geiger K. Selektive Darmdekontamination-ia oder nein? Klin Wochenschr 1991; 69 (Suppl.-XXVII): 1-5. Ledingham I McA, Alcock SR, Eastaway AT, McDonald JC, McKay IC, Ramsay G. Triule regimen of selective decontamination of the digestive tract, svstemic cefotaxime. and microbiological surveillance for prevention of acquired infection in intensive care. Lancet 1988; 1: 785-790.
19.
20. 21. 22.
Stoutenbeek antibiotics
CP, van Saene HKF, Zandstra DF. The effect of oral non-absorbable on the emergence of resistant bacteria in patients in an intensive care unit. J Antimicrob Chemother 1987; 19: 513-520. Misset B, Mahe P, Kitzis G et al. Effect of selective decontamination on the faecal flora of patients in an intensive care unit (Abstr.) Surg Res Comm 1990; 8 (Suppl.): 1.5. Taylor ME, Oppenheim BA. Selective decontamination of the gastrointestinal tract as an infection control measure. J Hasp Infect 1991; 17: 271-278. van Saene HKF, Stoutenbeek CP, Hart CA. Selective decontamination of the digestive tract (SDD) in intensive care patients: a critical evaluation of the clinical, bacteriological and epidemiological benefits. J Hosp Infect 1991; 18: 261-277.