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Selective decontamination of the gastrointestinal tract as an infection control measure
Journal
of Hospital
Infection
(1991)
17, 271-278
Selective decontamination tract as an infection M. E. Taylor Department
of Microbiology, Accepted
of the gastrointestinal control measure
and B. A. Oppenheim Withington
for publication
Hospital,
Manchester
18 February
1991
MZO 8LR
Summary:
An outbreak caused by a Klebsiella aerogenes resistant to ceftazidime, cefuroxime, cefotaxime, ampicillin and piperacillin and sensitive to aminoglycosides, imipenem and temocillin occurred in a teaching hospital’s busy multi-disciplinary Intensive Care Unit over a 3-month period. Four patients had bacteraemia and a further four were colonized. Traditional infection control measures failed to eradicate the outbreak. The introduction of a selective gastrointestinal decontamination regimen consisting of tobramycin, amphotericin and colistin as a gel to the oropharynx, nose and rectum and a suspension via a nasogastric tube resulted in rapid disappearance of the outbreak strain with no new isolates being detected clinically or in surveillance specimens over an 8-week period. Keywords:
Cross
infection;
critical
care;
antibiotics;
drug
resistance.
Introduction In the 1970s Klebsiella spp. showing plasmid-mediated resistance to multiple antibiotics caused many hospital epidemics especially in the Intensive Care Unit (ICU).’ Intestinal colonization was shown to be an important reservoir of the organism* and hands a major route of transmission.3 Based on these epidemiological findings control measures such as identifying colonized patients by culture of faeces, improved handwashing techniques, isolation of colonized and infected patients, and restriction of antibiotic usage4 were advocated. Topical antibiotics such as polymixin, used to prevent pharyngeal colonization with Pseudomonas spp. were tried, but resulted in an increase in pneumonias due to polymixin-resistant bacilli. ’ Selective gastrointestinal decontamination (SDD) was introduced in Groningen, Holland in 1981 in an attempt to reduce the incidence of endemic infections in trauma patients in ICU,‘j and subsequently has been used for this purpose in other centres.7-9 SDD has been used successfully to control an outbreak caused by a Klebsiella aerogenes producing a plasmid-mediated extended spectrum B-lactamase.” Correspondence chester M20
to: Dr
B. A.
Oppenheim,
Department
of Microbiology,
With&ton
Hospital,
Man-
8LR.
0195s6701/91/040271+08
‘C, 1991 The Hospital
$03 00/O
271
Infection
Socxty
272
M. E. Taylor
and B. A. Oppenheim
Therefore, when traditional infection control measures failed to eradicate a similar outbreak in our hospital, SDD was tried. Subjects
and
methods
Hospital setting The ICU is multi-disciplinary, with six beds on the main ward and two isolation cubicles. However, during the period described, the nursing complement was deemed sufficient to staff adequately only four beds to nationally agreed levels. During the 3-month outbreak period there were 36 admissions: the duration of stay ranged from 8 hours to more than 60 days. Epidemiological survey Thirty-eight environmental samples were taken from around the ICU, the dirty utility room attached to it and the kitchen area used by the ICU staff. Sites sampled included bed surfaces, window ledges, flower vases, technical machinery, fans and air vents. Hands of medical, nursing, and physiotherapy staff were sampled by impression plates on two occasions such that 14 pairs of hands were sampled altogether. Throat swabs and rectal swabs or faecal samples were taken to screen patients on admission to the unit and twice weekly during their stay. Sampling was continued for 2 months after the last isolate of the epidemic strain. To assesswhether the SDD regimen influenced the overall infection rate on the unit, routine clinical specimens from two groups of patients were compared. Group 1 was 15 patients admitted during the outbreak but before the SDD regimen was instituted. These patients were on the unit for a total of 189 patient-days. Group 2 was 18 patients admitted during the period that the SDD regimen was being carried out, and were on the unit for a total of 180 days. Both groups consisted of all patients admitted to the unit for more than 48 hours over consecutive 2-month study periods. The patients in both groups were of similar ages and had similar underlying diseases. Details of antibiotic usage on the unit over the same two periods of 2-months duration were studied. Microbiology Environmental swabs and staff hands were plated onto a layered blood agar (Oxoid blood agar base no. 2). Screening throat and rectal swabs (faeces) were plated onto blood agar as above; MacConkey agar without salt (Oxoid); GC agar (Difco) with added supplements and vancomycin, trimethoprim and polymixin as selective agents to detect yeasts. Rectal swabs (faeces) only were plated onto a blood agar plate with added neomycin to detect faecal streptococci. Screening swabs subsequent to initial admission were placed into Brain Heart Infusion Broth (Oxoid), incubated at 37°C overnight and plated onto MacConkey agar. Clinical specimens were processed as routine for the laboratory. All lactose-fermenting
Outbreak
control
Gram-negative rods were identified several antibiotics.
by SDD
further
273
and tested for sensitivity
to
Characterization
of isolates Isolates were identified by the API 20E system, sensitivity testing was by the Stokes method using Diagnostic Sensitivity Test Agar (Oxoid) with the following discs ampicillin (10 pg), piperacillin (75 pg), cefuroxime (30 pg), ceftazidime (30 pg), cefotaxime (30 pg), gentamicin (10 pg), netilmicin (30 pg), tobramycin (10 pg), amikacin (30 pg), aztreonam (30 pg), ciprofloxacin (5 pg), imipenem (10 pg), temocillin (30 pg) and colistin (10 pg). Sensitivities were confirmed by minimal inhibitory concentrations (MICs) to ceftazidime, cefotaxime, imipenem, ciprofloxacin and aztreonam, by a broth dilution technique using Nutrient Broth (Oxoid). A double disc synergy test with co-amoxiclav against ceftazidime, cefotaxime and aztreonam was performed. Selected isolates were referred for phage typing, serotyping and isoelectric focusing.
Control
measures
Control measures were instituted in three phases (Figure 1). Initial control measures included alerting all staff on the unit to the presence of the outbreak, reminding them of the importance of traditional infection control measures especially handwashing, and restriction of antibiotic usage with avoidance of cephalosporins, piperacillin and ciprofloxacin. When this failed new admissions were restricted, the unit cleaned thoroughly and the remaining colonized patient isolated in a side room. Following further new cases SDD was implemented. Patients admitted to the unit and likely to remain there longer than 48 hours were administered the following antimicrobials 4-hourly; colistin (2 Mu), amphotericin (500 mg) and tobramycin (80 mg) in a sorbitol solution base via a nasogastric tube and a gel containing 2% each of the above antimicrobials applied round the gum margins, oropharynx, nose and rectum. For one patient who had a vaginal
Table
I. Comparison (group
Specimen
Blood
of clinical specimens received from ICU 2) the selective intestinal decontamination Patient group
cultures
% of total specimens growing potential pathogens
Sputa
1 2 :.
40 13 86
Intravascular lines Urines
1 2 :
2: 45 46 89
before (group regimen
1)
and
during
% of positive specimens growing Gram-negative aerobes 21 0 79 32 49 20 40 62
274
M. E. Taylor
reservoir of colonization well.
and B. A. Oppenheim
and a colostomy the gel was applied to these sites as
Results Patient isolates Two slightly different strains of K. aerogenes were found. The most frequently isolated had an API 20E profile of 7215773. Three patients who had received ciprofloxacin had isolates with the profile number 5215773, and with ciprofloxacin MICs of 4 mg 1-‘. The outbreak strain was not phage typable, was of serotype K16 and possessed a /3-lactamase with a p1 of 7.6 on isoelectric focusing. It was resistant to ampicillin, piperacillin, cefuroxime, ceftazidime (MIC = 32mgl-‘), cefotaxime (MIC = 16mg 1-l) and aztreonam (MIC = 128 mg 1-l) and sensitive to the aminoglycosides, imipenem (MIC = O-125 mg l-l), temocillin and colistin. Ciprofloxacin sensitive strains had MICs of 0.5 mg 1-l. Synergy between clavulanate in co-amoxiclav and ceftazidime, cefotaxime and aztreonam was demonstrable when a double disc synergy test was performed.” Description of the outbreak The outbreak strain was isolated initially from the blood culture of a septicaemic patient in whom empirical treatment with ceftazidime failed clinically and bacteriologically. Treatment with imipenem resulted in a rapid clinical and bacteriological response. The second isolate was from sputum and subsequently blood culture of a patient in an adjacent bed to the index patient. The third, fourth, sixth and eighth patients developed colonization without clinical signs of infection but the fifth and seventh patients were both colonized in multiple sites and developed septicaemia due to the outbreak strain. No patients died as a result of infection with the outbreak strain (Figure 1). Epidemiological results Environmental screening and screening of staff hands revealed no outbreak isolates. Effects of control measures The environmental screening procedures were of no value in elucidating an initial focus for the epidemic strain or in showing secondary sources that could contribute to its continued transmission. The outbreak strain could not be eradicated by traditional infection control measures, which were probably doomed to fail in view of the low nurse to patient ratio at that time. Following the initiation of SDD the strain was eliminated rapidly. During SDD the following reductions in numbers of routine clinical specimens received by the laboratory from ICU were noted: blood cultures 19%, sputa
Outbreak
r
Hond WOS empt loci A”1 iblc r&3 kict
,hing zed. #tic ion
Environmental and staff hond screen
control
Ku closed for cleaning Isolationof colonized and infected potiente
by SDD
Selective lntestinol Decontominotion instituted
275
Sdt tctil ye Inte tstin lOI Deconr omi notion diru Ttia wed
Figure 1. Outbreak of a Klebsiella aerogenes resistant to extended spectrum cephalosporins on an ICU showing the time course of the outbreak, dates of admission and discharge of patients (large boxes), colonization (shaded areas), infective episodes (solid areas) and infection control measures.
3 1%) urines 20% and intravascular lines 23 % . There was also a reduction in the percentage of specimens growing potential pathogens and in the percentage of those growing Gram-negative aerobes (Table I). By studying clinical records it was noted that there was also a reduction in the numbers of clinical infections during the SDD period. There was a reduction of 38.7% on the antibiotic costs for antibiotics used to treat clinical infections during the SDD regimen compared with before it was started. However, when the cost of the antibiotics for the SDD regimen were added to this the overall costs were 40% higher during the SDD period than previously. Of the 18 patients admitted during the SDD regimen six had enterococci in their initial screening rectal or throat swabs. Of the remaining 12 patients 7 (58%) became colonized with enterococci on SDD of whom one developed clinical signs of infection due to enterococci. Only two (11 O/o>of the 18 patients became colonized with staphylococci and both of these were also colonized with enterococci. No Gram-negative aerobes resistant to the SDD drugs or ceftazidime emerged during the SDD regimen and no patients
became
colonized
with
yeasts. Discussion
It has been micro-organisms
shown previously that airborne transmission of in the ICU using modern airflow systems is negligible,12
276
M. E. Taylor
and B. A. Oppenheim
and that fomites contribute to infection to a negligible degree.13 Hospital staff hands appear as the main means of transfer of nosocomial bacteria3 and adequate handwashing has been emphasized as the single most important procedure for preventing nosocomial infection.14 However, handwashing discipline among hospital staff is poor” and studies have shown that the reduction in cross-infection by implementing strict hand antisepsis is negligible. i6 Other traditional measures such as isolating infected patients may have little effect too.” Therefore, we were not alone in finding that traditional infection control measures failed to eliminate our outbreak. The fact that several patients had severe diarrhoea at the initiation of the outbreak and that the unit was very busy and understaffed at the time probably contributed to the failure. Closing the ICU completely was considered and indeed has been carried out in previous outbreaks due to multi-resistant organisms4 We decided to try SDD to eliminate the outbreak as it had been used previously with success in a similar situation.” Several recent reviews describe the principles and aims of SDD and evaluate its uses.‘8-20 The major aim is to prevent acquisition of, and eliminate colonization by, Gram-negative aerobic bacilli using non-absorbable antibiotics, leaving the anaerobic flora intact to prevent recolonization with Gram-negative aerobic bacilli. We chose the antibiotic regimen of van Saene et ~1.~as the outbreak strain was sensitive to those antibiotics. We used an oropharyngeal paste as well as the gastrointestinal solution since previous studies have shown that oropharyngeal decontamination is important for preventing nosocomial pneumonia.*l We did not use the systemic component of the SDD regimen for two reasons. The idea of using systemic antibiotics for the first few days is to prevent early pulmonary infections by community acquired organisms whereas our only aim was to halt an outbreak due to a nosocomial K. aerogenes. Also our outbreak strain was resistant to cefotaxime and we were trying to avoid cephalosporin use in an attempt to prevent the selection of resistant organisms. As in the situation described by Brun-Buisson et al.,” our epidemic was eliminated rapidly by SDD and our findings support previous reports of colonization rates of the upper gastrointestinal tract by Gram-negative bacilli being reduced to O--S% by 7 days when SDD is instituted.18 In contrast to Brun-Buisson et al.,” however, we found a reduction in the overall incidence of nosocomial infections on the ICU with the institution of SDD. This may be because we applied a gel-based paste of the antimicrobials to the oropharynx whereas the previous study only applied an oropharyngeal povidone-iodine solution to tracheally intubated patients. These findings would support the importance of the role of oropharyngeal decontamination in infection prevention.*’ We did not find any emergence of Gram-negative bacilli resistant to the SDD regimen, which is consistent with previous findings. ‘,** We found fewer specimens being sent to the
Outbreak
control
by SDD
277
laboratory for microbiological examinationz3 and savings on parenteral antibiotics.7,9 However, we found the additional antibiotic costs using SDD were very high, as did previous workers.24 Our outbreak isolate was a K. aerogenes that produced an extended-spectrum p-lactamase. Klebsiella aerogenes producing plasmid-mediated extended spectrum p-lactamases are emerging”~25~27 and have been responsible for outbreaks on the continent, especially in France.*” Our isolate is being further characterized to determine the mechanism of resistance. SDD appears to be a useful tool for eradicating outbreaks due to Gram-negative aerobic bacilli. It may increase in importance with the emergence of organisms producing plasmid-mediated extended spectrum p-lactamases. Traditional infection control measures, especially handwashing, are much cheaper than SDD but require sufficient numbers of nursing staff on an ICU to make them a practical solution. We wish to thank Drs Edwards, Mortimer, implementing the selective gastrointestinal outbreak: the Division of Hospital Infection. Dr F. Mbosdeen for performing isoelectric
Nightingale regimen CPHL, focusing:
and Shelly for their co-operation and for permission to report Colindale for serotvping isolates;
in the and
References 1. Casewell MW, Phillips I. Aspects of the plasmid-mediated antibiotic resistance and epidemiology of Klebsiella species. Am J Med 1981; 70: 459-462. 2. Selden R, Lee S, Wang WLL, Bennett JV, Eickhoff TC. Nosocomial Klebsiella infections. Intestinal colonisation as a reservoir. Ann Intern Med 1971; 74: 6.57-664. 3. Casewell MW, Phillips I. Hands as a route of transmission for Klebsiella species. Br Med J 1977; 2: 13151317. 4. Weinstein RA, Kabins SA. Strategies for prevention and control of multiple drug-resistant nosocomial infection. Am J Med 1981; 70: 449454. TW, Du Moulin GC, Hedley-Whyte J, Bushnell LS, Gilbert JP, Feingold DS. 5. Feeley Aerosol polymixin and pneumonia in seriously ill patients. N Engl J Med 1975; 293: 471475. 6. van Saene HKF, Stoutenbeek CP, Miranda DR, Zandstra DF. A novel approach to infection control in the intensive care unit. Acta Anaesthesiol Belg 1983; 34: 1933208. 7. Ledingham IMc A, Alcock SR, Eastaway AT, McDonald JC, MacKay IC, Ramsay G. Triple regimen of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in intensive care. Lam-et 1988; 1: 785-790. K, Ruckdeschel G, Selbmann HK et al. Prevention of colonisation and 8. Unertl infections in long-term ventilated patients by local antimicrobial respiratory prophylaxis. Intensive Care Me& 1987; 13: 106-l 13. 9. Kerver ATH. Rommes TH. Mevissen-Verhaee E,4E et al. Prevention of colonisation and infection in critically ili patients: a prospect&e randomised study. Crit Care Med 1988;
16: 1087-1093. 10.
11.
Brun-Buisson C, Legrand nosocomial multiresistant care unit. Ann Intern Med Jarlier V, Nicolas MH, beta-lactamases conferring enterobacteriaceae: hospital 867-878.
P, Rauss A et al. Intestinal decontamination for control of Gram-negative bacilli. Study of an outbreak in an intensive 1989; 100: 873-881. Fournier G, Phillipon A. Extended broad-spectrum transferrable resistance to newer beta-lactams in prevalence and susceptibility patterns. Rev Znf Dis 1988; 10:
278 12. 13. 14.
1.5. 16. 17.
18. 19.
20. 21.
22.
23.
24.
25.
26. 27.
M. E. Taylor
and B. A. Oppenheim
Wood M. Protective isolation reviewed. Presented at the Sixteenth Annual Symposium. University of Southampton, England, Sept 17-20, 1985. Gaya H. Infection control in intensive care. Br J Anaesth 1976; 48: 9-l 2. Garner JS, Favero MS. CDC guidelines for the prevention and control of nosocomial infections. Guideline for handwashing and hospital environmental control, 198.5. Supersedes guideline for hospital environmental control published in 1981. Am J Infect Control 1986; 14: 11&129. Albert RK, Condie F. Handwashing patterns in medical intensive-care units. N Engl J Med 1981; 304: 1465-1466. Daschner FD, Frey P, Wolff G, Baumann PC, Suter P. Nosocomial infections in intensive care wards: A multicenter prospective study. Intensive Care Med 1982; 8: 5-9. Preston GA, Larson EL, Stamm WE. The effect of private isolation rooms on patient care practices, colonisation and infection in an intensive care unit. Am J Med 1981; 70: 641-645. Ramsey G. The role of selective decontamination of the digestive tract a review. Surg Infect 1990; 2: 26-31. Meijer K, van Saene HKF, Hill JC. Infection control in patients undergoing mechanical ventilation: traditional approach versus a new development-selective decontamination of the digestive tract. Heart Lung 1990; 19: 11-20. Stoutenbeek CP, van Saene HKF. Infection prevention in intensive care by selective decontamination of the digestive tract. J Crit Care 1990; 5: 137-l 56. Stoutenbeek CP, van Saene HKF, Miranda DR, Zandstra DF, Langrehr D. The effect of oropharyngeal decontamination using topical non-absorbable antibiotics on the incidence of nosocomial respiratory tract infections in multiple trauma patients. J Trauma 1987; 27: 357-364. Stoutenbeek CP, van Saene HKF, Zandstra DF. The effect of oral non-absorbable antibiotics on the emergence of resistant bacteria in patients in an intensive care unit. J Antimicrob Chemother 1987; 19: 513-520. Miranda DR, van Saene HKF, Stoutenbeek CP, Zandstra DF. Environment and costs in surgical intensive unit. The implication of selective decontamination of the digestive tract (SDD). Acta Anaesthesiol Belg 1983; 3: 223-232. Ulrich C, Harinck-de Weerd JE, Bakker NC, Jacz K, Doornbos L, de Ridder VA. Selective decontamination of the digestive tract with norfloxacin in the prevention of ICU-acquired infections: a prospective randomised study. Intensive Care Med 1989; 15: 424-43 1. Sirot J, Chanal C, Petit A, Sirot D, Labia R, Gerbaud G. Klebsiella pneumoniae and other enterobacteriaceae producing novel plasmid-mediated beta-lactamases markedly active against third generation cephalosporins: epidemiologic studies. Rev Infect Dis 1988; 10: 8.50-859. Philippon A, Labia R, Jacoby G. Extended-spectrum p-lactamases. Antimicrob Agents Chemother 1989; 33: 1131-1136. Philippon A, Ben Redjeb S, Fournier G, Ben Hassen A. Epidemiology of extended spectrum P-lactamases. Infection 1989; 17: 347-354.
of Hospital
Infection
(1991)
17, 271-278
Selective decontamination tract as an infection M. E. Taylor Department
of Microbiology, Accepted
of the gastrointestinal control measure
and B. A. Oppenheim Withington
for publication
Hospital,
Manchester
18 February
1991
MZO 8LR
Summary:
An outbreak caused by a Klebsiella aerogenes resistant to ceftazidime, cefuroxime, cefotaxime, ampicillin and piperacillin and sensitive to aminoglycosides, imipenem and temocillin occurred in a teaching hospital’s busy multi-disciplinary Intensive Care Unit over a 3-month period. Four patients had bacteraemia and a further four were colonized. Traditional infection control measures failed to eradicate the outbreak. The introduction of a selective gastrointestinal decontamination regimen consisting of tobramycin, amphotericin and colistin as a gel to the oropharynx, nose and rectum and a suspension via a nasogastric tube resulted in rapid disappearance of the outbreak strain with no new isolates being detected clinically or in surveillance specimens over an 8-week period. Keywords:
Cross
infection;
critical
care;
antibiotics;
drug
resistance.
Introduction In the 1970s Klebsiella spp. showing plasmid-mediated resistance to multiple antibiotics caused many hospital epidemics especially in the Intensive Care Unit (ICU).’ Intestinal colonization was shown to be an important reservoir of the organism* and hands a major route of transmission.3 Based on these epidemiological findings control measures such as identifying colonized patients by culture of faeces, improved handwashing techniques, isolation of colonized and infected patients, and restriction of antibiotic usage4 were advocated. Topical antibiotics such as polymixin, used to prevent pharyngeal colonization with Pseudomonas spp. were tried, but resulted in an increase in pneumonias due to polymixin-resistant bacilli. ’ Selective gastrointestinal decontamination (SDD) was introduced in Groningen, Holland in 1981 in an attempt to reduce the incidence of endemic infections in trauma patients in ICU,‘j and subsequently has been used for this purpose in other centres.7-9 SDD has been used successfully to control an outbreak caused by a Klebsiella aerogenes producing a plasmid-mediated extended spectrum B-lactamase.” Correspondence chester M20
to: Dr
B. A.
Oppenheim,
Department
of Microbiology,
With&ton
Hospital,
Man-
8LR.
0195s6701/91/040271+08
‘C, 1991 The Hospital
$03 00/O
271
Infection
Socxty
272
M. E. Taylor
and B. A. Oppenheim
Therefore, when traditional infection control measures failed to eradicate a similar outbreak in our hospital, SDD was tried. Subjects
and
methods
Hospital setting The ICU is multi-disciplinary, with six beds on the main ward and two isolation cubicles. However, during the period described, the nursing complement was deemed sufficient to staff adequately only four beds to nationally agreed levels. During the 3-month outbreak period there were 36 admissions: the duration of stay ranged from 8 hours to more than 60 days. Epidemiological survey Thirty-eight environmental samples were taken from around the ICU, the dirty utility room attached to it and the kitchen area used by the ICU staff. Sites sampled included bed surfaces, window ledges, flower vases, technical machinery, fans and air vents. Hands of medical, nursing, and physiotherapy staff were sampled by impression plates on two occasions such that 14 pairs of hands were sampled altogether. Throat swabs and rectal swabs or faecal samples were taken to screen patients on admission to the unit and twice weekly during their stay. Sampling was continued for 2 months after the last isolate of the epidemic strain. To assesswhether the SDD regimen influenced the overall infection rate on the unit, routine clinical specimens from two groups of patients were compared. Group 1 was 15 patients admitted during the outbreak but before the SDD regimen was instituted. These patients were on the unit for a total of 189 patient-days. Group 2 was 18 patients admitted during the period that the SDD regimen was being carried out, and were on the unit for a total of 180 days. Both groups consisted of all patients admitted to the unit for more than 48 hours over consecutive 2-month study periods. The patients in both groups were of similar ages and had similar underlying diseases. Details of antibiotic usage on the unit over the same two periods of 2-months duration were studied. Microbiology Environmental swabs and staff hands were plated onto a layered blood agar (Oxoid blood agar base no. 2). Screening throat and rectal swabs (faeces) were plated onto blood agar as above; MacConkey agar without salt (Oxoid); GC agar (Difco) with added supplements and vancomycin, trimethoprim and polymixin as selective agents to detect yeasts. Rectal swabs (faeces) only were plated onto a blood agar plate with added neomycin to detect faecal streptococci. Screening swabs subsequent to initial admission were placed into Brain Heart Infusion Broth (Oxoid), incubated at 37°C overnight and plated onto MacConkey agar. Clinical specimens were processed as routine for the laboratory. All lactose-fermenting
Outbreak
control
Gram-negative rods were identified several antibiotics.
by SDD
further
273
and tested for sensitivity
to
Characterization
of isolates Isolates were identified by the API 20E system, sensitivity testing was by the Stokes method using Diagnostic Sensitivity Test Agar (Oxoid) with the following discs ampicillin (10 pg), piperacillin (75 pg), cefuroxime (30 pg), ceftazidime (30 pg), cefotaxime (30 pg), gentamicin (10 pg), netilmicin (30 pg), tobramycin (10 pg), amikacin (30 pg), aztreonam (30 pg), ciprofloxacin (5 pg), imipenem (10 pg), temocillin (30 pg) and colistin (10 pg). Sensitivities were confirmed by minimal inhibitory concentrations (MICs) to ceftazidime, cefotaxime, imipenem, ciprofloxacin and aztreonam, by a broth dilution technique using Nutrient Broth (Oxoid). A double disc synergy test with co-amoxiclav against ceftazidime, cefotaxime and aztreonam was performed. Selected isolates were referred for phage typing, serotyping and isoelectric focusing.
Control
measures
Control measures were instituted in three phases (Figure 1). Initial control measures included alerting all staff on the unit to the presence of the outbreak, reminding them of the importance of traditional infection control measures especially handwashing, and restriction of antibiotic usage with avoidance of cephalosporins, piperacillin and ciprofloxacin. When this failed new admissions were restricted, the unit cleaned thoroughly and the remaining colonized patient isolated in a side room. Following further new cases SDD was implemented. Patients admitted to the unit and likely to remain there longer than 48 hours were administered the following antimicrobials 4-hourly; colistin (2 Mu), amphotericin (500 mg) and tobramycin (80 mg) in a sorbitol solution base via a nasogastric tube and a gel containing 2% each of the above antimicrobials applied round the gum margins, oropharynx, nose and rectum. For one patient who had a vaginal
Table
I. Comparison (group
Specimen
Blood
of clinical specimens received from ICU 2) the selective intestinal decontamination Patient group
cultures
% of total specimens growing potential pathogens
Sputa
1 2 :.
40 13 86
Intravascular lines Urines
1 2 :
2: 45 46 89
before (group regimen
1)
and
during
% of positive specimens growing Gram-negative aerobes 21 0 79 32 49 20 40 62
274
M. E. Taylor
reservoir of colonization well.
and B. A. Oppenheim
and a colostomy the gel was applied to these sites as
Results Patient isolates Two slightly different strains of K. aerogenes were found. The most frequently isolated had an API 20E profile of 7215773. Three patients who had received ciprofloxacin had isolates with the profile number 5215773, and with ciprofloxacin MICs of 4 mg 1-‘. The outbreak strain was not phage typable, was of serotype K16 and possessed a /3-lactamase with a p1 of 7.6 on isoelectric focusing. It was resistant to ampicillin, piperacillin, cefuroxime, ceftazidime (MIC = 32mgl-‘), cefotaxime (MIC = 16mg 1-l) and aztreonam (MIC = 128 mg 1-l) and sensitive to the aminoglycosides, imipenem (MIC = O-125 mg l-l), temocillin and colistin. Ciprofloxacin sensitive strains had MICs of 0.5 mg 1-l. Synergy between clavulanate in co-amoxiclav and ceftazidime, cefotaxime and aztreonam was demonstrable when a double disc synergy test was performed.” Description of the outbreak The outbreak strain was isolated initially from the blood culture of a septicaemic patient in whom empirical treatment with ceftazidime failed clinically and bacteriologically. Treatment with imipenem resulted in a rapid clinical and bacteriological response. The second isolate was from sputum and subsequently blood culture of a patient in an adjacent bed to the index patient. The third, fourth, sixth and eighth patients developed colonization without clinical signs of infection but the fifth and seventh patients were both colonized in multiple sites and developed septicaemia due to the outbreak strain. No patients died as a result of infection with the outbreak strain (Figure 1). Epidemiological results Environmental screening and screening of staff hands revealed no outbreak isolates. Effects of control measures The environmental screening procedures were of no value in elucidating an initial focus for the epidemic strain or in showing secondary sources that could contribute to its continued transmission. The outbreak strain could not be eradicated by traditional infection control measures, which were probably doomed to fail in view of the low nurse to patient ratio at that time. Following the initiation of SDD the strain was eliminated rapidly. During SDD the following reductions in numbers of routine clinical specimens received by the laboratory from ICU were noted: blood cultures 19%, sputa
Outbreak
r
Hond WOS empt loci A”1 iblc r&3 kict
,hing zed. #tic ion
Environmental and staff hond screen
control
Ku closed for cleaning Isolationof colonized and infected potiente
by SDD
Selective lntestinol Decontominotion instituted
275
Sdt tctil ye Inte tstin lOI Deconr omi notion diru Ttia wed
Figure 1. Outbreak of a Klebsiella aerogenes resistant to extended spectrum cephalosporins on an ICU showing the time course of the outbreak, dates of admission and discharge of patients (large boxes), colonization (shaded areas), infective episodes (solid areas) and infection control measures.
3 1%) urines 20% and intravascular lines 23 % . There was also a reduction in the percentage of specimens growing potential pathogens and in the percentage of those growing Gram-negative aerobes (Table I). By studying clinical records it was noted that there was also a reduction in the numbers of clinical infections during the SDD period. There was a reduction of 38.7% on the antibiotic costs for antibiotics used to treat clinical infections during the SDD regimen compared with before it was started. However, when the cost of the antibiotics for the SDD regimen were added to this the overall costs were 40% higher during the SDD period than previously. Of the 18 patients admitted during the SDD regimen six had enterococci in their initial screening rectal or throat swabs. Of the remaining 12 patients 7 (58%) became colonized with enterococci on SDD of whom one developed clinical signs of infection due to enterococci. Only two (11 O/o>of the 18 patients became colonized with staphylococci and both of these were also colonized with enterococci. No Gram-negative aerobes resistant to the SDD drugs or ceftazidime emerged during the SDD regimen and no patients
became
colonized
with
yeasts. Discussion
It has been micro-organisms
shown previously that airborne transmission of in the ICU using modern airflow systems is negligible,12
276
M. E. Taylor
and B. A. Oppenheim
and that fomites contribute to infection to a negligible degree.13 Hospital staff hands appear as the main means of transfer of nosocomial bacteria3 and adequate handwashing has been emphasized as the single most important procedure for preventing nosocomial infection.14 However, handwashing discipline among hospital staff is poor” and studies have shown that the reduction in cross-infection by implementing strict hand antisepsis is negligible. i6 Other traditional measures such as isolating infected patients may have little effect too.” Therefore, we were not alone in finding that traditional infection control measures failed to eliminate our outbreak. The fact that several patients had severe diarrhoea at the initiation of the outbreak and that the unit was very busy and understaffed at the time probably contributed to the failure. Closing the ICU completely was considered and indeed has been carried out in previous outbreaks due to multi-resistant organisms4 We decided to try SDD to eliminate the outbreak as it had been used previously with success in a similar situation.” Several recent reviews describe the principles and aims of SDD and evaluate its uses.‘8-20 The major aim is to prevent acquisition of, and eliminate colonization by, Gram-negative aerobic bacilli using non-absorbable antibiotics, leaving the anaerobic flora intact to prevent recolonization with Gram-negative aerobic bacilli. We chose the antibiotic regimen of van Saene et ~1.~as the outbreak strain was sensitive to those antibiotics. We used an oropharyngeal paste as well as the gastrointestinal solution since previous studies have shown that oropharyngeal decontamination is important for preventing nosocomial pneumonia.*l We did not use the systemic component of the SDD regimen for two reasons. The idea of using systemic antibiotics for the first few days is to prevent early pulmonary infections by community acquired organisms whereas our only aim was to halt an outbreak due to a nosocomial K. aerogenes. Also our outbreak strain was resistant to cefotaxime and we were trying to avoid cephalosporin use in an attempt to prevent the selection of resistant organisms. As in the situation described by Brun-Buisson et al.,” our epidemic was eliminated rapidly by SDD and our findings support previous reports of colonization rates of the upper gastrointestinal tract by Gram-negative bacilli being reduced to O--S% by 7 days when SDD is instituted.18 In contrast to Brun-Buisson et al.,” however, we found a reduction in the overall incidence of nosocomial infections on the ICU with the institution of SDD. This may be because we applied a gel-based paste of the antimicrobials to the oropharynx whereas the previous study only applied an oropharyngeal povidone-iodine solution to tracheally intubated patients. These findings would support the importance of the role of oropharyngeal decontamination in infection prevention.*’ We did not find any emergence of Gram-negative bacilli resistant to the SDD regimen, which is consistent with previous findings. ‘,** We found fewer specimens being sent to the
Outbreak
control
by SDD
277
laboratory for microbiological examinationz3 and savings on parenteral antibiotics.7,9 However, we found the additional antibiotic costs using SDD were very high, as did previous workers.24 Our outbreak isolate was a K. aerogenes that produced an extended-spectrum p-lactamase. Klebsiella aerogenes producing plasmid-mediated extended spectrum p-lactamases are emerging”~25~27 and have been responsible for outbreaks on the continent, especially in France.*” Our isolate is being further characterized to determine the mechanism of resistance. SDD appears to be a useful tool for eradicating outbreaks due to Gram-negative aerobic bacilli. It may increase in importance with the emergence of organisms producing plasmid-mediated extended spectrum p-lactamases. Traditional infection control measures, especially handwashing, are much cheaper than SDD but require sufficient numbers of nursing staff on an ICU to make them a practical solution. We wish to thank Drs Edwards, Mortimer, implementing the selective gastrointestinal outbreak: the Division of Hospital Infection. Dr F. Mbosdeen for performing isoelectric
Nightingale regimen CPHL, focusing:
and Shelly for their co-operation and for permission to report Colindale for serotvping isolates;
in the and
References 1. Casewell MW, Phillips I. Aspects of the plasmid-mediated antibiotic resistance and epidemiology of Klebsiella species. Am J Med 1981; 70: 459-462. 2. Selden R, Lee S, Wang WLL, Bennett JV, Eickhoff TC. Nosocomial Klebsiella infections. Intestinal colonisation as a reservoir. Ann Intern Med 1971; 74: 6.57-664. 3. Casewell MW, Phillips I. Hands as a route of transmission for Klebsiella species. Br Med J 1977; 2: 13151317. 4. Weinstein RA, Kabins SA. Strategies for prevention and control of multiple drug-resistant nosocomial infection. Am J Med 1981; 70: 449454. TW, Du Moulin GC, Hedley-Whyte J, Bushnell LS, Gilbert JP, Feingold DS. 5. Feeley Aerosol polymixin and pneumonia in seriously ill patients. N Engl J Med 1975; 293: 471475. 6. van Saene HKF, Stoutenbeek CP, Miranda DR, Zandstra DF. A novel approach to infection control in the intensive care unit. Acta Anaesthesiol Belg 1983; 34: 1933208. 7. Ledingham IMc A, Alcock SR, Eastaway AT, McDonald JC, MacKay IC, Ramsay G. Triple regimen of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in intensive care. Lam-et 1988; 1: 785-790. K, Ruckdeschel G, Selbmann HK et al. Prevention of colonisation and 8. Unertl infections in long-term ventilated patients by local antimicrobial respiratory prophylaxis. Intensive Care Me& 1987; 13: 106-l 13. 9. Kerver ATH. Rommes TH. Mevissen-Verhaee E,4E et al. Prevention of colonisation and infection in critically ili patients: a prospect&e randomised study. Crit Care Med 1988;
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