Journal
of Hospital
Infection
(1992)~ 20, 51-54
Question
and answer
It is an accepted practice to use 2% glutaraldehyde for 14 days to disinfect endoscopes. The employment of 20 endoscope procedures during this period reduces the concentration of 2% glutaraldehyde to nearly 1 O/O. At 1 O/O concentration human immunodeficiency virus (HIV) in neat serum was not inactivated up to 15 min.’ In practice, many more than 20 endoscopy procedures are performed within 14 days. Hence, what would be the criteria to determine the frequency for changing the solution? We do not accept that 2% activated alkaline glutaraldehyde can be used continuously to disinfect endoscopes for 14 days after activation. We do, however, endorse its efficacy for that period providing it is not repeatedly re-used.2 Several factors will influence efficacy: the concentration and post-activation age of the disinfectant; its dilution due to carry-over of detergent from cleansing; the number, size and complexity of the instruments processed and the amount of organic material or other inactivating materials present. Our own studies indicate that if a KeyMed Autodisinfector is used to process 20 flexible gastrointestinal endoscopes, either over a single half-day session, or several sessions during a week, the glutaraldehyde level drops from a starting concentration of 2.16-2.49% to 1.38-1.94% (see Table I). Similar results were also obtained using an Olympus EWlO machine. et al.’ demonstrated a more dramatic fall in concentration to 1% Hanson whilst processing GI endoscopes, although the processing method was not identified. During manual techniques the fall in concentration was much slower and in our studies there was no appreciable fall after processing 40 rigid cystoscopes over 2 days, presumably because the instruments were smaller and more thoroughly drained or dried before transfer to the disinfectant. The technique used for aldehyde determination in our studies was as follows (personal communication, Johnson and Johnson Medical Ltd): a 5 ml sample was added to a stirred 50 ml volume of water in a beaker and the pH adjusted to 3.0 with 0.1 M hydrochloric acid. To this was added 15 ml of aqueous hydroxylamine hydirochloride 10% w/v, at a pH previously adjusted to 3.0 with either 0.1 M hydrochloric acid or 0.1 M sodium hydroxide. After the pH had stabilized, the mixture was titrated with 0.1 M sodium hydroxide back to a pH of 3.0. Each ml of 0.1 M sodium hydroxide was equivalent to 0.005005 g glutaraldehyde. Glutaraldehyde degrades to polymers which retain some of the aldehyde groups of the original molecules.3 Since the assay method depends upon a 0195-6701/92/010051
+O4 $03.00/O
0 1992 The Hosptal
51
Infection
Society
52 Table
Question I. Glutaraldehyde
Method
Automated KeyMed Autodisinfector
concentrations
Type of instrument
Disinfectant
Flexible GI endoscope
Flexible GI endoscope Rigid cystoscopes
* 14-day post-activation product. ‘Cidex’ (Johnson and Johnson Medical Ltd).
answer
assayed during disinfection No. of instruments
automated No. of days’ use
and manual
endoscope
Concentration glutaraldehyde
of (%)
Pre-
Post-
‘Cidex’*
20 18
2.22 2.25
1.70 1.38
‘Asep’*
20 20
2.16 2.18
1.62 1.72
20 18
2.22 2.49
1.70 1.94
2.20
2.14
2.14
2.01
28’ (Coventry
Chemicals
‘Totacide Manual
and
‘Asep’ ‘Asep’
28’
14+ accessories 40
2
Ltd), ‘Asep’ (Galen Ltd.), ‘Totacide
reaction with aldehyde groups, it will not accurately reflect the extent of chemical degradation occurring in the disinfectant solution. However, the glutaraldehyde solutions were only used for periods up to 5 days (well within the 14 or 28-day recommended use-life), so dilution would be the dominant process leading to reduction of glutaraldehyde concentration. Comparison of the results obtained from the half-day sessions with those obtained over several days supports this. It is strongly recommended that this, or an alternative method, is used to assay aldehyde concentrations when evaluating new disinfection machines and when setting up manual or automated decontamination procedures for different types of endoscope. Simple dipstick indicators, which assess aldehyde concentration, are available (Sterilog Info-Chem Inc., New Jersey, USA) but these are difficult to interpret.4 Whether or not a lower concentration of glutaraldehyde will suffice depends upon several factors including the contact time, the presence of organic material and the target microorganisms. Table II reviews some of the recent studies of glutaraldehyde efficacy. Most of this work has been carried out using 2% activated alkaline glutaraldehyde but in some countries 1% and/or acid-based formulations are used, which are more stable but less effective.’ These are probably of greater value to the small-volume or occasional user, but are not widely used for endoscopes in the UK. It would appear that, with the exception of bacterial spores and mycobacteria, bacteria and viruses are highly susceptible to 2% glutaraldehyde and much lower concentrations will normally suffice. The professional societies and manufacturers, after carefully reviewing published data, currently recommend immersion in 2% glutaraldehyde for
Table Test organism
Contact time
HIV
1 min > 1.5 min 2 min
(cell-free)
(cell-associated) HBV HBV DHBV DHBV
5 10 2 2.5
Question
and
Review:
activity
II.
Concentration (“/I
min min min min
53
answer
Organic material present
of glutaraldehyde Type
of test
2 1 2
Serum Serum No
Surface Surface Surface
0.1 2 0.63 2
Plasma Plasma Plasma Serum
Suspension Suspension Suspension Surface
Reference
Hanson
et al.’
Kobayashi et al.‘” Bond et al.” Tsiquaye & Barnard’* Murray et al.‘”
Poliovirus SAB 1AN
1
2
Serum
Surface
Tyler
min
Mycobacterium tuberculosis
10 min 10 min
2 2
No Sputum
Surface Surface
Best et a1.‘5
2.0 1.5 1.0
No No No
Surface Surface Surface
Babb & Bradley (unpublished)
2-O? 1.5t l.OT
No No No
Surface Surface Surface
2
Yeast
Suspension
Babb et al.z
0.2 0.2*
Yeast Yeast
Suspension Suspension
Babb & Bradley (unpublished)
Bacillus subtilis var. niger
lh
2h 4h 3h 4h >24h 3h
Pseudomonas aeruginosa
1.5 min 4 min
* 7 days post-activation. t 14 days post-activation. HIV= Human immunodeficiency
virus,
HBV=
hepatitis
B virus,
DHBV=duck
et a1.14
hepatitis
B virus.
4 min between patients undergoing gastrointestinal endoscopy,’ and 20 min (or 1 h if the patient has a mycobacterial infection) for bronchoscopy.6 Although 3-10 h has been recommended for sterilization of invasive endoscopes, spores are rarely, if ever, a cause of infection and high-grade disinfection by immersion in glutaraldehyde for at least 10 min is recommended if mycobacteria are not considered a problem. Longer immersions are not usually possible during a busy session with few instruments. Although Hanson et al.’ demonstrated that HIV in neat serum was not inactivated using 1% glutaraldehyde up to 15 min, they were able to demonstrate the total elimin.ation of HIV from GI endoscopes used on patients with AIDS by thorough cleaning alone with 0.5% neutral detergent for 2 min in an Autodisinfector. 7,8 The effectiveness of cleaning alone has also been demonstrated in other studies.’ In conclusion, and having discussed the problem with the disinfectant manufacturers, we would recommend that glutaraldehyde can be re-used for endoscopes providing the concentration does not fall appreciably below
54
Question
and
answer
1.5% and that, in the case of alkaline-activated glutaraldehyde, the use-life does not exceed the manufacturers’ post-activation life of 14 or 28 days. It is strongly recommended that aldehyde concentrations are assayed when evaluating new aldehyde disinfectants, machines and when formulating a policy for a particular range of endoscopes so that glutaraldehyde exchange can be effected as and when appropriate. It would appear that, with the possible exception of atypical mycobacteria and bacterial spores, concentrations of 1.5% glutaraldehyde are highly effective for the well within the contact times disinfection of clean instruments recommended by the professional societies and the disinfectant manufactures. Ensuring items are thoroughly clean and well-drained before immersion in glutaraldehyde will extend the margin of safety and the use-life of the disinfectant.
J. R. Babb C. R. Bradley A. R. Barnes
Hospital
Infection
Research Laboratory, QC Dept., Pharmacy, Dudley Road Hospital, Birmingham B18 7&H
References of HIV on surfaces. 1. Hanson PJV, Gor D, Jeffries DJ, Collins JV. Chemical inactivation Br MedJ 1989; 298: 862-864. CR, Ayliffe GAJ. Sporicidal activity of glutaraldehydes and 2. Babb JR, Bradley hvnochlorites and other factors influencing their selection for the treatment of medical equipment. J Hosp Infect 1980; 1: 63-75. S. Rembaum A. Svnthesis and characterization of nolvfelutaraldehvdel. A 3. Marael pote%ial reagent for protein’immobilisation and cell preparation. i\j;lcromoZecuhs 1980; 13: 19-24. Russell AD. Assessment of ‘Cold Sterilog Glutaraldehyde Monitor’. r 4. Power EGM, Hosp Infect 1988; 11: 376-380. Cleaning and disinfection of equipment for Society of Gastroenterology. 5. British gastrointestinal flexible endoscopy: interim recommendations of a Working Party. Gut 1988; 29: 113&1151. Society. Bronchoscopy and infection control. Lancet 1989; 2: 270-271. 6. British Thoracic G et al. Contamination of endoscopes used in AIDS 7. Hanson PJV, Clarke JR, Nicholson patients. Lancet 1989; 1: 86-88. JV. Elimination of high titre HIV from 8. Hanson PJV, Gor D, Jeffries DJ, Collins fibreoptic endoscopes Br MedJ 1990; 31: 657-659. CEA, Ayliffe GAJ, Melikian V. Recent advances in the 9. Babb JR, Bradley CR, Deverill cleaning and disinfection of fibrescopes. J Hasp Infect 1981; 2: 329-340. H, Tsuzuki M, Koshimuzu K et al. Susceptibility of hepatitis B virus to 10. Kobayashi disinfectants or heat. J Clin Microbial 1984; 20: 214216. of hepatitis B virus by 11. Bond WW, Favero MS, Petersen NJ, Ebert JW. Inactivation intermediate to high level disinfectant chemicals. r Clin Microbial 1983; 18: 5355538. KN, Barnard J. Evaluation of the efficacy of disinfectants against Hepatitis B 12. Tsiquaye virus in the duck hepatitis model. Abstract Proceedings of 2nd International Infection Society. 1990. SM, Freiman JS, Vickery K, Lim D, Cossart YE, Whiteley RK. Duck hepatitis 13. Murray B virus: a model to assess efficacy of disinfectants against hepadnavirus infectivity. Epidemiol Infect 1991; 106: 435443. GAJ, Bradley CR. Virucidal activity of disinfectants: studies with the 14. Tyler R, Ayliffe poliovirus. J Hosp Infect 1990; 15: 339-345. VS Kennedy ME. Efficacies of selected disinfectants 15. Best M, Sattar SA, Spingthorpe against Mycobacterium tuberculosis. 2 Clini Microbial 1990; 28: 22342239.
of Hospital
Infection
(1992)~ 20, 51-54
Question
and answer
It is an accepted practice to use 2% glutaraldehyde for 14 days to disinfect endoscopes. The employment of 20 endoscope procedures during this period reduces the concentration of 2% glutaraldehyde to nearly 1 O/O. At 1 O/O concentration human immunodeficiency virus (HIV) in neat serum was not inactivated up to 15 min.’ In practice, many more than 20 endoscopy procedures are performed within 14 days. Hence, what would be the criteria to determine the frequency for changing the solution? We do not accept that 2% activated alkaline glutaraldehyde can be used continuously to disinfect endoscopes for 14 days after activation. We do, however, endorse its efficacy for that period providing it is not repeatedly re-used.2 Several factors will influence efficacy: the concentration and post-activation age of the disinfectant; its dilution due to carry-over of detergent from cleansing; the number, size and complexity of the instruments processed and the amount of organic material or other inactivating materials present. Our own studies indicate that if a KeyMed Autodisinfector is used to process 20 flexible gastrointestinal endoscopes, either over a single half-day session, or several sessions during a week, the glutaraldehyde level drops from a starting concentration of 2.16-2.49% to 1.38-1.94% (see Table I). Similar results were also obtained using an Olympus EWlO machine. et al.’ demonstrated a more dramatic fall in concentration to 1% Hanson whilst processing GI endoscopes, although the processing method was not identified. During manual techniques the fall in concentration was much slower and in our studies there was no appreciable fall after processing 40 rigid cystoscopes over 2 days, presumably because the instruments were smaller and more thoroughly drained or dried before transfer to the disinfectant. The technique used for aldehyde determination in our studies was as follows (personal communication, Johnson and Johnson Medical Ltd): a 5 ml sample was added to a stirred 50 ml volume of water in a beaker and the pH adjusted to 3.0 with 0.1 M hydrochloric acid. To this was added 15 ml of aqueous hydroxylamine hydirochloride 10% w/v, at a pH previously adjusted to 3.0 with either 0.1 M hydrochloric acid or 0.1 M sodium hydroxide. After the pH had stabilized, the mixture was titrated with 0.1 M sodium hydroxide back to a pH of 3.0. Each ml of 0.1 M sodium hydroxide was equivalent to 0.005005 g glutaraldehyde. Glutaraldehyde degrades to polymers which retain some of the aldehyde groups of the original molecules.3 Since the assay method depends upon a 0195-6701/92/010051
+O4 $03.00/O
0 1992 The Hosptal
51
Infection
Society
52 Table
Question I. Glutaraldehyde
Method
Automated KeyMed Autodisinfector
concentrations
Type of instrument
Disinfectant
Flexible GI endoscope
Flexible GI endoscope Rigid cystoscopes
* 14-day post-activation product. ‘Cidex’ (Johnson and Johnson Medical Ltd).
answer
assayed during disinfection No. of instruments
automated No. of days’ use
and manual
endoscope
Concentration glutaraldehyde
of (%)
Pre-
Post-
‘Cidex’*
20 18
2.22 2.25
1.70 1.38
‘Asep’*
20 20
2.16 2.18
1.62 1.72
20 18
2.22 2.49
1.70 1.94
2.20
2.14
2.14
2.01
28’ (Coventry
Chemicals
‘Totacide Manual
and
‘Asep’ ‘Asep’
28’
14+ accessories 40
2
Ltd), ‘Asep’ (Galen Ltd.), ‘Totacide
reaction with aldehyde groups, it will not accurately reflect the extent of chemical degradation occurring in the disinfectant solution. However, the glutaraldehyde solutions were only used for periods up to 5 days (well within the 14 or 28-day recommended use-life), so dilution would be the dominant process leading to reduction of glutaraldehyde concentration. Comparison of the results obtained from the half-day sessions with those obtained over several days supports this. It is strongly recommended that this, or an alternative method, is used to assay aldehyde concentrations when evaluating new disinfection machines and when setting up manual or automated decontamination procedures for different types of endoscope. Simple dipstick indicators, which assess aldehyde concentration, are available (Sterilog Info-Chem Inc., New Jersey, USA) but these are difficult to interpret.4 Whether or not a lower concentration of glutaraldehyde will suffice depends upon several factors including the contact time, the presence of organic material and the target microorganisms. Table II reviews some of the recent studies of glutaraldehyde efficacy. Most of this work has been carried out using 2% activated alkaline glutaraldehyde but in some countries 1% and/or acid-based formulations are used, which are more stable but less effective.’ These are probably of greater value to the small-volume or occasional user, but are not widely used for endoscopes in the UK. It would appear that, with the exception of bacterial spores and mycobacteria, bacteria and viruses are highly susceptible to 2% glutaraldehyde and much lower concentrations will normally suffice. The professional societies and manufacturers, after carefully reviewing published data, currently recommend immersion in 2% glutaraldehyde for
Table Test organism
Contact time
HIV
1 min > 1.5 min 2 min
(cell-free)
(cell-associated) HBV HBV DHBV DHBV
5 10 2 2.5
Question
and
Review:
activity
II.
Concentration (“/I
min min min min
53
answer
Organic material present
of glutaraldehyde Type
of test
2 1 2
Serum Serum No
Surface Surface Surface
0.1 2 0.63 2
Plasma Plasma Plasma Serum
Suspension Suspension Suspension Surface
Reference
Hanson
et al.’
Kobayashi et al.‘” Bond et al.” Tsiquaye & Barnard’* Murray et al.‘”
Poliovirus SAB 1AN
1
2
Serum
Surface
Tyler
min
Mycobacterium tuberculosis
10 min 10 min
2 2
No Sputum
Surface Surface
Best et a1.‘5
2.0 1.5 1.0
No No No
Surface Surface Surface
Babb & Bradley (unpublished)
2-O? 1.5t l.OT
No No No
Surface Surface Surface
2
Yeast
Suspension
Babb et al.z
0.2 0.2*
Yeast Yeast
Suspension Suspension
Babb & Bradley (unpublished)
Bacillus subtilis var. niger
lh
2h 4h 3h 4h >24h 3h
Pseudomonas aeruginosa
1.5 min 4 min
* 7 days post-activation. t 14 days post-activation. HIV= Human immunodeficiency
virus,
HBV=
hepatitis
B virus,
DHBV=duck
et a1.14
hepatitis
B virus.
4 min between patients undergoing gastrointestinal endoscopy,’ and 20 min (or 1 h if the patient has a mycobacterial infection) for bronchoscopy.6 Although 3-10 h has been recommended for sterilization of invasive endoscopes, spores are rarely, if ever, a cause of infection and high-grade disinfection by immersion in glutaraldehyde for at least 10 min is recommended if mycobacteria are not considered a problem. Longer immersions are not usually possible during a busy session with few instruments. Although Hanson et al.’ demonstrated that HIV in neat serum was not inactivated using 1% glutaraldehyde up to 15 min, they were able to demonstrate the total elimin.ation of HIV from GI endoscopes used on patients with AIDS by thorough cleaning alone with 0.5% neutral detergent for 2 min in an Autodisinfector. 7,8 The effectiveness of cleaning alone has also been demonstrated in other studies.’ In conclusion, and having discussed the problem with the disinfectant manufacturers, we would recommend that glutaraldehyde can be re-used for endoscopes providing the concentration does not fall appreciably below
54
Question
and
answer
1.5% and that, in the case of alkaline-activated glutaraldehyde, the use-life does not exceed the manufacturers’ post-activation life of 14 or 28 days. It is strongly recommended that aldehyde concentrations are assayed when evaluating new aldehyde disinfectants, machines and when formulating a policy for a particular range of endoscopes so that glutaraldehyde exchange can be effected as and when appropriate. It would appear that, with the possible exception of atypical mycobacteria and bacterial spores, concentrations of 1.5% glutaraldehyde are highly effective for the well within the contact times disinfection of clean instruments recommended by the professional societies and the disinfectant manufactures. Ensuring items are thoroughly clean and well-drained before immersion in glutaraldehyde will extend the margin of safety and the use-life of the disinfectant.
J. R. Babb C. R. Bradley A. R. Barnes
Hospital
Infection
Research Laboratory, QC Dept., Pharmacy, Dudley Road Hospital, Birmingham B18 7&H
References of HIV on surfaces. 1. Hanson PJV, Gor D, Jeffries DJ, Collins JV. Chemical inactivation Br MedJ 1989; 298: 862-864. CR, Ayliffe GAJ. Sporicidal activity of glutaraldehydes and 2. Babb JR, Bradley hvnochlorites and other factors influencing their selection for the treatment of medical equipment. J Hosp Infect 1980; 1: 63-75. S. Rembaum A. Svnthesis and characterization of nolvfelutaraldehvdel. A 3. Marael pote%ial reagent for protein’immobilisation and cell preparation. i\j;lcromoZecuhs 1980; 13: 19-24. Russell AD. Assessment of ‘Cold Sterilog Glutaraldehyde Monitor’. r 4. Power EGM, Hosp Infect 1988; 11: 376-380. Cleaning and disinfection of equipment for Society of Gastroenterology. 5. British gastrointestinal flexible endoscopy: interim recommendations of a Working Party. Gut 1988; 29: 113&1151. Society. Bronchoscopy and infection control. Lancet 1989; 2: 270-271. 6. British Thoracic G et al. Contamination of endoscopes used in AIDS 7. Hanson PJV, Clarke JR, Nicholson patients. Lancet 1989; 1: 86-88. JV. Elimination of high titre HIV from 8. Hanson PJV, Gor D, Jeffries DJ, Collins fibreoptic endoscopes Br MedJ 1990; 31: 657-659. CEA, Ayliffe GAJ, Melikian V. Recent advances in the 9. Babb JR, Bradley CR, Deverill cleaning and disinfection of fibrescopes. J Hasp Infect 1981; 2: 329-340. H, Tsuzuki M, Koshimuzu K et al. Susceptibility of hepatitis B virus to 10. Kobayashi disinfectants or heat. J Clin Microbial 1984; 20: 214216. of hepatitis B virus by 11. Bond WW, Favero MS, Petersen NJ, Ebert JW. Inactivation intermediate to high level disinfectant chemicals. r Clin Microbial 1983; 18: 5355538. KN, Barnard J. Evaluation of the efficacy of disinfectants against Hepatitis B 12. Tsiquaye virus in the duck hepatitis model. Abstract Proceedings of 2nd International Infection Society. 1990. SM, Freiman JS, Vickery K, Lim D, Cossart YE, Whiteley RK. Duck hepatitis 13. Murray B virus: a model to assess efficacy of disinfectants against hepadnavirus infectivity. Epidemiol Infect 1991; 106: 435443. GAJ, Bradley CR. Virucidal activity of disinfectants: studies with the 14. Tyler R, Ayliffe poliovirus. J Hosp Infect 1990; 15: 339-345. VS Kennedy ME. Efficacies of selected disinfectants 15. Best M, Sattar SA, Spingthorpe against Mycobacterium tuberculosis. 2 Clini Microbial 1990; 28: 22342239.
