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Emergence of antibiotic resistance during selective digestive decontamination?
Letters to the Editor
158
Sir, Emergence
of antibiotic
resistance during decontamination?
selective
digestive
We have read with great interest Dr Webb’s editorial entitled ‘Antibiotic resistance associated with selective decontamination of the digestive tract [SDD]’ in the Journal, ’ for he is the microbiologist who was heavily reveals one intriguing involved in the Belfast SDD tria1.*13 The editorial observation not obvious from the original reports.‘T3 Dr Webb repeats three times that ‘strains sensitive to the SDD mixture can still colonize oropharyngeal mucosae and sometimes give rise to infection’ suggesting that the topical SDD drugs failed to eradicate oropharyngeal carriage. This may be because the gel used by the Belfast group for oropharyngeal decontamination did not ensure sufficiently protracted contact between the SDD drugs and the mucosal flora. Certainly, failure of SDD at this site has proved extremely uncommon following 4 days treatment with the original sticky carboxy-methylcellulose paste.4 Alternatively, there may have been a failure in the application technique: a similar gel preparation has been employed in Glasgow for two years without problem. It therefore seems possible that this report of failure of SDD against sensitive pseudomonas strains may be an artifact related to Belfast practice. The matter deserves further investigation as it has important implications. SDD is primarily designed to control endogenous infections caused by including aerobic potentially pathogenic microorganisms @‘PM) Gram-negative bacilli (enterobacteria, Pseudomonas aeruginosa) and yeasts. The regimen also has useful activity against most strains of Staphylococcus aureus. By design, SDD antimicrobials are likely to be inactive against indigenous flora such as viridans streptococci, enterococci and coagulase negative staphylococci (CNS). It follows that selection and possible overgrowth of these organisms has always been an accepted concomitant of SDD regimens. Demonstration of abnormal patterns of indigenous flora following the use of SDD is therefore not surprising and should not cause concern unless associated with increased infection caused by these low virulence organisms. There is a striking absence of such infection problems in the literature reviewed by Webb and others. Together with Ulm and Munster,5*6 Belfast is the only group that has studied CNS overgrowth in greater depth. The Belfast group writes ‘The gastro-respiratory sites of patients with SDD acquired a Gram-positive flora that was predominantly staphylococcal’. However, there were less Gram-positive secondary septicaemias and respiratory tract infections in the SDD vs control groups.’ Similarly, the Ulm and Munster trials have shown that respiratory tract infections with staphylococci and enterococci were less frequent in the SDD treated patients than in the control group (Table I). In the first French trial,
Letters Table
I.
Frequency
of Gram-positive
to the Editor
cocci as a cause of respiratory studies. Ulm
..______ -_______ ________.~~ No. of patients Stapylococcus epidermidis Staphylococcus aureus Enterococci
SDD 82 0 2 2
Trial’ .
159 tract injections
Munster
in two SDD
study6
control
SDD
control
83 9 9”
99 1 3 1
107 ii 4
overgrowth by Gram-positive cocci was significantly more frequent in the SDD group when compared with the concurrent control group.7 Moreover, enterococci and staphylococci were recovered in significantly higher numbers from rectal swabs of the SDD-treated patients OS controls. However, there were fewer Gram-positive infections in the SDD groups. Cerra from Minneapolis summarizes his experience as follows:s ‘There was a trend towards an increase in the incidence of stool cultures positive for enterococci during SDD-treatment, but this trend was not associated with the occurrence of clinical infections’. The Cape Town trial shows a rise of oropharyngeal enterococcal carriage up to 41% in both SDD and control groups without any evidence of clinical infection.” A recent published analysis from Bristol on the impact of SDD on enterococcal carriage and subsequent superinfection rate is in line with the earlier reports.” Webb does describe other reports of infection due to CNS” and enterococci’2 complicating the use of SDD but these were single patients only and similar episodes undoubtedly occur in traditional ICUs without SDD.13 Clearly, the Gram-positive revival predicted to emerge with SDD has still not occurred even after 10 years.ls SDD also inevitably exerts selective pressure for intrinsically resistant PPM such as methicillin-resistant Staphylococcus aUreUS (MRSA), if prevalent in the ICU.9,‘5 This is an altogether more serious matter as overgrowth with MRSA is highly undesirable in an ICU population even in the absence of infection. The protagonists of SDD have always accepted this situation and proposed microbiological surveillance of throat and rectal swabs obtained on admission to the ICU and throughout the period of SDD to allow early detection of the MRSA carriage.” Well established control measures including the addition of oral vancomycin to the paste/gel (2%) and suspension (4 x 250 mg) l7 and even the withdrawal of SDD,” can then be introduced. It is important not to confuse potential problems associated with SDD with the existence of an actual problem in traditional practice. Over the last ten years, there has been a remarkable paucity of reports concerning either overgrowth or infection with the ICU pathogens defined above.4 Webb refers to a ‘rise in gentamicin and polymyxin resistance to 50% during a
160
Letters
to the Editor
4-month period of SDD in a study from Paris.” However, this conclusion is based on the isolation of a resistant Serratia sp from four out of 38 faecal samples obtained from 23 patients.*’ Even supposing that these four specimens originated from four different long-stay ICU patients, the conclusion is difficult to understand. Moreover, superinfections with Serratia were not mentioned by the French investigators.*l Webb’s editorial is remarkable for the absence of a realistic standard of comparison for the effects of SDD. Data in this area should not be described against an implied ideal of maintained normal flora or an absence of all potential resistance problems, but rather against ICU experience when employing traditional antibiotic regimens. From this view point, the alternative to SDD is associated with well documented and often serious infections caused by resistant organisms, sometimes involving ICU closure.** In contrast 10 years of SDD practice has yielded reports largely confined to the elaboration of flora changes that may eventually prove to be harmful. It is the negative characteristics of SDD data that are remarkable not the positive findings elaborated by Webb. This said, concern about the selective pressures inevitably associated with SDD is clearly justified and we strongly support Webb’s pleas for close microbiological monitoring of all SDD regimens.
H. K. F. van Saene K. E. Unertl* S. R. Alcock** C. P. Stoutenbeekt
Dept. Medical Microbiology, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK. *Institut fiir Anaesthesiologie, Innenstadtkliniken Mtinchen, Ludwig-MaximiliansUniversitat, Miinchen, Germany. **Bacteriology Department, Western Infirmary, Glasgow, Scotland. ‘fDept. Intensive Care OLVG-Amsterdam, The Netherlands.
C. A. Hart
References 1. Webb CH. Antibiotic resistance associated with selective decontamination of the digestive tract. J Hasp Infect 1992; 22: 1-5. 2. Blair P, Rowlands BJ, Lowry K, Webb CH, Armstrong P, Smilie J. Selective 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. van Saene HK, Stoutenbeek CP, Stoller JK. Selective decontamination of the digestive tract in the intensive care unit: Current status and future prospects. Crit Care Med 1992; 20: 691-703.
Letters
to the Editor
161
5. Konrad F, Schwalbe B, Heeg K, Wagner H, Wiedeck H, Kilian J, Ahnefeld FL+‘. Kolonisations-, Pneumoniefrequenz und Resistenzentwicklung bei langzeitbeatmeten selektiver Dekontamination Intensivpatienten unter des Verdauungstraktes. Anaesthesist 1989; 38: 99-l 09. 6. Hartenauer U, Thulig B, Diemer W, Lawin P, Fegeler W, Kehrel R, Ritzerfeld W. Effect of selective flora suppression on colonisation, infection and mortality in critically ill patients: A one-year, prospective consecutive study. Crit Cnre Med 1991; 19: 463473. 7. Brun-Buisson C, Legrand P, Rauss A, Richard C, Montravers F, Besbes bcI, Meakins JL, Soussy CJ, Lemaire F. Intestinal decontamination for control of nosocomial multiresistant Gram-negative bacilli. Am Intevn Med 1989; 110: 873-881. 8. Cerra FB, Maddaus M.4, Dunn DL, Wells CL, Konstantinides NN, Lehmann SL, Mann HJ. Selective gut decontamination reduces noscomial infections and length of sta! but not mortality or organ failure in surgical intensive care unit patients. Arch Surg 1992; 127: 163-169. 9. Hammond JMJ, Potgieter PD, Saunders GL, Forder AA. Doubleblind studs of selective decontamination of the digestive tract in intensive care. Lam-et 1992; 340: j-9. 10. Humphrey H, Winter R, Pick A. The effect of selective decontamination of the digestive tract on gastrointestinal enterococcal colonisation in ITU patients. Interk~e Care Medicine 1992; 18: 459-463. 11. McCelland P, Coakley J, Williams PG, Bone J%LI, nlostafa SM. Staphylococcal peritonitis following selective decontamination of digestive tract. Lancet 1988; ii: 800. 12. Abu-Zidan FMA, McAteer E, Elhag KM. Selective contamination of the digestive tract in Kuwait. Crit Care Med 1989; 177 1364. 13. Hussain Z, Kuhn XI, Lannigan R, Austin TW’. iXlicrobiologica1 investigation of an outbreak of bacteraemia due to Streptococcus faecalis in an ICU. I?’ Hasp.” Infect 1988; 12:
263-271.
14. Gruneberg R. Infectious distractions. video nlarion ;\Ierrell Dow I,td. 1992. 15. Gastinne H. Wolff hLI. Delatour F. Faurisson F. Chevret S. A controlled trial in intensive care units of selective decontamination of the digestive tract Lvith nonabsorbable antibiotics. Neu: EngJ Med 1992; 326: 59+-599. 16. 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 Hasp Inject 1991; 18: 261-277. 17. van Saene HKF, Unertl KE, Stoutenbeek CP, Hart CA. Emergence of resistance during selective decontamination? J Ho@ Infect 1992; 21: 175-178. 18. Kaufhold A, Behrendt W, Krauss Th, van Saene H. Selective decontamination of the digestive tract and methicillin-resistant Strrphylorocczrs aureus. Lancet 1992; 339: 1411-1412. 19. Misset B, Mahe P, Kitzis ;\,ID, Conscience G, Goldstein FL%‘, Bleriot Jf’, Carlet J. Effect of selective decontamination on the faecal flora of patients in an intensive care unit [Abstr.]. Surg Res Comm 1990; 8: [Suppl.]: 15. 20. Misset B, Kitzis MD, Conscience G, Goldstein F\v, Fourrier A, Bleriot JP, Carlet J. Failure to achieve faecal sterilization during selective decontamination of the digestive tract [SDD] in ICU patients. 30th ICAAC, Atlanta, Georgia, USA, Amerirnn Societ) for Microbiology 1990; Abstr. 218. 21. I\‘Iisset B, Conscience G, Kitzis X’ID, nlahe P, Goldstein F\V, Bleriot JP, Carlet J. Selective decontamination of the digestive tract [SDD] with colistin, gentamicin and amphotericin B increases resistance to these antibiotics. Proceedings of the 1st International Conference on the Preewztion of Injection, I\;ice, France, CIPI, 1990: Abstr. PE1051. 22. Daschner F, Langmaack H, \%‘iedemann B. Antibiotic resistance in intensive care unit areas. ff Control 1983; 4: 382-387.
158
Sir, Emergence
of antibiotic
resistance during decontamination?
selective
digestive
We have read with great interest Dr Webb’s editorial entitled ‘Antibiotic resistance associated with selective decontamination of the digestive tract [SDD]’ in the Journal, ’ for he is the microbiologist who was heavily reveals one intriguing involved in the Belfast SDD tria1.*13 The editorial observation not obvious from the original reports.‘T3 Dr Webb repeats three times that ‘strains sensitive to the SDD mixture can still colonize oropharyngeal mucosae and sometimes give rise to infection’ suggesting that the topical SDD drugs failed to eradicate oropharyngeal carriage. This may be because the gel used by the Belfast group for oropharyngeal decontamination did not ensure sufficiently protracted contact between the SDD drugs and the mucosal flora. Certainly, failure of SDD at this site has proved extremely uncommon following 4 days treatment with the original sticky carboxy-methylcellulose paste.4 Alternatively, there may have been a failure in the application technique: a similar gel preparation has been employed in Glasgow for two years without problem. It therefore seems possible that this report of failure of SDD against sensitive pseudomonas strains may be an artifact related to Belfast practice. The matter deserves further investigation as it has important implications. SDD is primarily designed to control endogenous infections caused by including aerobic potentially pathogenic microorganisms @‘PM) Gram-negative bacilli (enterobacteria, Pseudomonas aeruginosa) and yeasts. The regimen also has useful activity against most strains of Staphylococcus aureus. By design, SDD antimicrobials are likely to be inactive against indigenous flora such as viridans streptococci, enterococci and coagulase negative staphylococci (CNS). It follows that selection and possible overgrowth of these organisms has always been an accepted concomitant of SDD regimens. Demonstration of abnormal patterns of indigenous flora following the use of SDD is therefore not surprising and should not cause concern unless associated with increased infection caused by these low virulence organisms. There is a striking absence of such infection problems in the literature reviewed by Webb and others. Together with Ulm and Munster,5*6 Belfast is the only group that has studied CNS overgrowth in greater depth. The Belfast group writes ‘The gastro-respiratory sites of patients with SDD acquired a Gram-positive flora that was predominantly staphylococcal’. However, there were less Gram-positive secondary septicaemias and respiratory tract infections in the SDD vs control groups.’ Similarly, the Ulm and Munster trials have shown that respiratory tract infections with staphylococci and enterococci were less frequent in the SDD treated patients than in the control group (Table I). In the first French trial,
Letters Table
I.
Frequency
of Gram-positive
to the Editor
cocci as a cause of respiratory studies. Ulm
..______ -_______ ________.~~ No. of patients Stapylococcus epidermidis Staphylococcus aureus Enterococci
SDD 82 0 2 2
Trial’ .
159 tract injections
Munster
in two SDD
study6
control
SDD
control
83 9 9”
99 1 3 1
107 ii 4
overgrowth by Gram-positive cocci was significantly more frequent in the SDD group when compared with the concurrent control group.7 Moreover, enterococci and staphylococci were recovered in significantly higher numbers from rectal swabs of the SDD-treated patients OS controls. However, there were fewer Gram-positive infections in the SDD groups. Cerra from Minneapolis summarizes his experience as follows:s ‘There was a trend towards an increase in the incidence of stool cultures positive for enterococci during SDD-treatment, but this trend was not associated with the occurrence of clinical infections’. The Cape Town trial shows a rise of oropharyngeal enterococcal carriage up to 41% in both SDD and control groups without any evidence of clinical infection.” A recent published analysis from Bristol on the impact of SDD on enterococcal carriage and subsequent superinfection rate is in line with the earlier reports.” Webb does describe other reports of infection due to CNS” and enterococci’2 complicating the use of SDD but these were single patients only and similar episodes undoubtedly occur in traditional ICUs without SDD.13 Clearly, the Gram-positive revival predicted to emerge with SDD has still not occurred even after 10 years.ls SDD also inevitably exerts selective pressure for intrinsically resistant PPM such as methicillin-resistant Staphylococcus aUreUS (MRSA), if prevalent in the ICU.9,‘5 This is an altogether more serious matter as overgrowth with MRSA is highly undesirable in an ICU population even in the absence of infection. The protagonists of SDD have always accepted this situation and proposed microbiological surveillance of throat and rectal swabs obtained on admission to the ICU and throughout the period of SDD to allow early detection of the MRSA carriage.” Well established control measures including the addition of oral vancomycin to the paste/gel (2%) and suspension (4 x 250 mg) l7 and even the withdrawal of SDD,” can then be introduced. It is important not to confuse potential problems associated with SDD with the existence of an actual problem in traditional practice. Over the last ten years, there has been a remarkable paucity of reports concerning either overgrowth or infection with the ICU pathogens defined above.4 Webb refers to a ‘rise in gentamicin and polymyxin resistance to 50% during a
160
Letters
to the Editor
4-month period of SDD in a study from Paris.” However, this conclusion is based on the isolation of a resistant Serratia sp from four out of 38 faecal samples obtained from 23 patients.*’ Even supposing that these four specimens originated from four different long-stay ICU patients, the conclusion is difficult to understand. Moreover, superinfections with Serratia were not mentioned by the French investigators.*l Webb’s editorial is remarkable for the absence of a realistic standard of comparison for the effects of SDD. Data in this area should not be described against an implied ideal of maintained normal flora or an absence of all potential resistance problems, but rather against ICU experience when employing traditional antibiotic regimens. From this view point, the alternative to SDD is associated with well documented and often serious infections caused by resistant organisms, sometimes involving ICU closure.** In contrast 10 years of SDD practice has yielded reports largely confined to the elaboration of flora changes that may eventually prove to be harmful. It is the negative characteristics of SDD data that are remarkable not the positive findings elaborated by Webb. This said, concern about the selective pressures inevitably associated with SDD is clearly justified and we strongly support Webb’s pleas for close microbiological monitoring of all SDD regimens.
H. K. F. van Saene K. E. Unertl* S. R. Alcock** C. P. Stoutenbeekt
Dept. Medical Microbiology, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK. *Institut fiir Anaesthesiologie, Innenstadtkliniken Mtinchen, Ludwig-MaximiliansUniversitat, Miinchen, Germany. **Bacteriology Department, Western Infirmary, Glasgow, Scotland. ‘fDept. Intensive Care OLVG-Amsterdam, The Netherlands.
C. A. Hart
References 1. Webb CH. Antibiotic resistance associated with selective decontamination of the digestive tract. J Hasp Infect 1992; 22: 1-5. 2. Blair P, Rowlands BJ, Lowry K, Webb CH, Armstrong P, Smilie J. Selective 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. van Saene HK, Stoutenbeek CP, Stoller JK. Selective decontamination of the digestive tract in the intensive care unit: Current status and future prospects. Crit Care Med 1992; 20: 691-703.
Letters
to the Editor
161
5. Konrad F, Schwalbe B, Heeg K, Wagner H, Wiedeck H, Kilian J, Ahnefeld FL+‘. Kolonisations-, Pneumoniefrequenz und Resistenzentwicklung bei langzeitbeatmeten selektiver Dekontamination Intensivpatienten unter des Verdauungstraktes. Anaesthesist 1989; 38: 99-l 09. 6. Hartenauer U, Thulig B, Diemer W, Lawin P, Fegeler W, Kehrel R, Ritzerfeld W. Effect of selective flora suppression on colonisation, infection and mortality in critically ill patients: A one-year, prospective consecutive study. Crit Cnre Med 1991; 19: 463473. 7. Brun-Buisson C, Legrand P, Rauss A, Richard C, Montravers F, Besbes bcI, Meakins JL, Soussy CJ, Lemaire F. Intestinal decontamination for control of nosocomial multiresistant Gram-negative bacilli. Am Intevn Med 1989; 110: 873-881. 8. Cerra FB, Maddaus M.4, Dunn DL, Wells CL, Konstantinides NN, Lehmann SL, Mann HJ. Selective gut decontamination reduces noscomial infections and length of sta! but not mortality or organ failure in surgical intensive care unit patients. Arch Surg 1992; 127: 163-169. 9. Hammond JMJ, Potgieter PD, Saunders GL, Forder AA. Doubleblind studs of selective decontamination of the digestive tract in intensive care. Lam-et 1992; 340: j-9. 10. Humphrey H, Winter R, Pick A. The effect of selective decontamination of the digestive tract on gastrointestinal enterococcal colonisation in ITU patients. Interk~e Care Medicine 1992; 18: 459-463. 11. McCelland P, Coakley J, Williams PG, Bone J%LI, nlostafa SM. Staphylococcal peritonitis following selective decontamination of digestive tract. Lancet 1988; ii: 800. 12. Abu-Zidan FMA, McAteer E, Elhag KM. Selective contamination of the digestive tract in Kuwait. Crit Care Med 1989; 177 1364. 13. Hussain Z, Kuhn XI, Lannigan R, Austin TW’. iXlicrobiologica1 investigation of an outbreak of bacteraemia due to Streptococcus faecalis in an ICU. I?’ Hasp.” Infect 1988; 12:
263-271.
14. Gruneberg R. Infectious distractions. video nlarion ;\Ierrell Dow I,td. 1992. 15. Gastinne H. Wolff hLI. Delatour F. Faurisson F. Chevret S. A controlled trial in intensive care units of selective decontamination of the digestive tract Lvith nonabsorbable antibiotics. Neu: EngJ Med 1992; 326: 59+-599. 16. 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 Hasp Inject 1991; 18: 261-277. 17. van Saene HKF, Unertl KE, Stoutenbeek CP, Hart CA. Emergence of resistance during selective decontamination? J Ho@ Infect 1992; 21: 175-178. 18. Kaufhold A, Behrendt W, Krauss Th, van Saene H. Selective decontamination of the digestive tract and methicillin-resistant Strrphylorocczrs aureus. Lancet 1992; 339: 1411-1412. 19. Misset B, Mahe P, Kitzis ;\,ID, Conscience G, Goldstein FL%‘, Bleriot Jf’, Carlet J. Effect of selective decontamination on the faecal flora of patients in an intensive care unit [Abstr.]. Surg Res Comm 1990; 8: [Suppl.]: 15. 20. Misset B, Kitzis MD, Conscience G, Goldstein F\v, Fourrier A, Bleriot JP, Carlet J. Failure to achieve faecal sterilization during selective decontamination of the digestive tract [SDD] in ICU patients. 30th ICAAC, Atlanta, Georgia, USA, Amerirnn Societ) for Microbiology 1990; Abstr. 218. 21. I\‘Iisset B, Conscience G, Kitzis X’ID, nlahe P, Goldstein F\V, Bleriot JP, Carlet J. Selective decontamination of the digestive tract [SDD] with colistin, gentamicin and amphotericin B increases resistance to these antibiotics. Proceedings of the 1st International Conference on the Preewztion of Injection, I\;ice, France, CIPI, 1990: Abstr. PE1051. 22. Daschner F, Langmaack H, \%‘iedemann B. Antibiotic resistance in intensive care unit areas. ff Control 1983; 4: 382-387.