Activeforever CIDEX Plus Solution User Manual

Efficacy of High-Level Disinfection

®

with CIDEX

OPA Solution

OPA Solution

ospital-acquired infections (HAIs) pose a

eat to patient safety, affecting

H

the Unit

serious thr
more than 2 million patients every year in

ed States and many more worldwide.
result, they have received increasing attention from
healthcare professionals, as well as state and federal
regulatory agencies, hospital administrators, payors,
the media, and patients. A number of campaigns are
underway to reduce the incidence of HAIs, focusing on
prevention practices and changes in reimbursement.
The Joint Commission has added preventable infections
as one of its National Patient Safety Goals,2and the
Association for Professionals in Infection Control
and Epidemiology (APIC) has launched a campaign
emphasizing prevention of HAIs and other adverse

3

events.

In addition, the Centers for Medicare
and Medicaid Services will no longer provide
reimbursement for the added cost of care of patients

4

with several types of HAIs.

The implications of these
initiatives are far-reaching for hospitals and infection
prevention professionals.

With more than 10 million
gastrointestinal endoscopic

“CIDEX®OPA

and 500,000 flexible
bronchoscopic procedures

Solution...is proven
effective against a
broad range of
viruses, fungi,
and mycobacteria.”

performed every year in the

5,6

United States,

reusable
flexible endoscopes have
the potential to play a role
in HAIs. During clinical
use, endoscopes are
contaminated by multiple
microorganisms, and
failure to appropriately

clean, disinfect, or sterilize endoscopes has resulted
in nosocomial outbreaks and serious infections.

esult, pr

a r
delic
saf

ety and maint

oper cl

ate endoscopes are crucial to ensure patient

eaning and disinf

ain optimal function.

ection of expensive,

7,9

The clinic
established efficacy of detergents and disinfectants
clearly plays a key part in instrument processing,
and their selection is an important clinical and risk
management decision.

High-Level Disinfection

Endoscopes and other devices that contact muc
membranes but normally do not cross the blood
barrier are, by definition, semi-critical devices and
must undergo high-level disinfection. According to
APIC, this means elimination of many or all pathogenic
organisms, except bacterial spores.
disinfectants cleared for use with semi-critical
medical devices must demonstrate 100% kill of 10
to 106mycobacteria in the presence of 2% horse
serum in quantitative tests and pass the sporicidal

10

High-level

1

As a

7,8

ous

all

5

As

test of AOAC International, the Association of

ytical Communities.

Anal

11

Liquid chemical germicides that are high-level
disinfectants ideally should offer effectiveness, speed,
and ease of use and be compatible with a variety of

erials used in medical devices. These chemicals

mat
also should not be noxious or toxic to personnel.
The high-level disinfectant CIDEX®OPA Solution
(0.55% ortho-phthalaldehyde) (Advanced Sterilization
Products [ASP], Division of Ethicon, Inc.) meets these
criteria and, in nearly 10 years of clinical use and
efficacy testing, is proven effective against a broad
range of viruses, fungi, and mycobacteria.

CIDEX®OPA Solution

CIDEX®OPA Solution was introduced by ASP in
1999 to meet the need for effective, fast, easy-to-use
high-level disinfection and to address staff concerns
about the saf
Solution is bactericidal, sporicidal, virucidal, fungicidal,
and tuberculocidal. It achieves high-level disinfection
in 12 minutes at room temperature and also has been
cleared for marketing in the United States for use
in automatic endoscope reprocessors (high-level
disinfection in 5 minutes at 25ºC). Extensive
testing has shown that the high-level disinfectant is
non-corrosive and is compatible with a wide variety of
materials commonly found in endoscopes and other
medical devices. (See Table 1) It also is gentler on
flexible endoscopes than peracetic acid.

Table 1: Materials Shown To Be Compatible with
CIDEX®OPA Solution*

Metals

• Aluminum • Anodized aluminum

• Brass • Carbon steel

• Chrome-plated brass/steel • Copper

• Nickel-plated brass • Nickel-silver alloy

y

• Stainless-steel/titanium • Tungsten carbide/

Plastics & Elastomers

Acetal • Acrylonitrile-butadiene-styrene (ABS)

•

• Nylon • Polyamide

• Polycarbonate • Polyethylene

• Polypropylene • Polystyrene

• Polysulfone • Polyvinyl chloride (PVC)

• PTFE • Kraton G

• Natural rubber latex • Polychloraprene (Neoprene)

• Polyurethane • Silicone rubber

ethyl

y

ol

P

•

es

y

(pol

Adhesives

• Cyanoacrylate • EPO-TEK 301 epoxy

• EPO-TEK 353 epoxy

Dental Materials

• Addition silicone • Polyether

• Polysulphide

ta on fil

*Da

ety of glutaraldehyde. CIDEX OPA

12

vanadium steel

ene terephthalate • Polymethylmethacrylate

(acrylic)

er)

t

e at ASP.

•

7

2

CIDEX®OPA Solution has no offensive odor. In contrast

o glutaraldehyde, the Occupational Safety & Health

t
Administration has not set permissible exposure limits

or CIDEX OPA Solution and does not require special

f
venting or air monitoring in areas where the solution
is used or monitoring of staff who work with it. Local
regulations may vary, but generally the solution can be
discarded with running water into an ordinary drain.

®

CIDEX

OPA Solution is ready to use from the bottle
and requires no mixing or activation. Test strips are
used to verify that the germicide has maintained
the minimum effective concentration (MEC) of 0.3%
CIDEX OPA Solution. Tests have shown that even
reused, stressed solution diluted to the MEC remains
bactericidal, sporicidal, virucidal, fungicidal, and

13–17

tuberculocidal at room temperature.
Solution has a 14-day r

euse life and an open-bottle

CIDEX OPA

shelf life of 75 days. Unopened bottles have a shelf
life of two years when stored at 15–30°C. Although
provided at a near-neutral pH of 7.5, the solution is
stable for use over a wide range of pH (3-9).

Efficacy

The efficacy of CIDEX®OPA Solution as a high-level
disinfectant has been established through extensive
evaluation by ASP over the past 10 years. A summary
of key efficacy testing follows.

Methodology

Two types of quantitative tests have been used
predominantly to evaluate the efficacy of CIDEX
Solution. The first type utilized suspensions of
microorganisms diluted 1:10 into the solution at a
specified concentration and temperature. After a
specified period (usually minutes), a neutralizer was
added or the microorganisms were removed from the
suspension by vacuum filtration and then rinsed. The
number of viabl

ganisms r

e or

emaining aft
to the solution then was determined by quantitative
assay and compared quantitatively with organisms
that had no exposure to the solution. The reduction
in viable microorganisms is expressed as a log of the
number of organisms.

A second, more stringent test type evaluated the
efficacy of CIDEX®OPA Solution in inactivating
microorganisms, including methicillin-resistant

Staphylococcus aureus (MRSA), vancomycin-resistant
Enterococcus faecalis (VRE), and viruses that had dried

onto a flat solid surface. After exposure to CIDEX OPA
Solution, the microbes were recovered, rinsed, and
quantitatively assayed.

CIDEX®OPA Solution has been cleared for mark
in the United States as a high-level disinfectant for
reusable medical and dental equipment processed at

er e

®

OPA

xposur

eting

e

20°C (12 minutes) and at 25°C (5 minutes).* Because
the solution is used ar

ound the world and claims vary
by country, evaluations also have been done based on
other times and t

emperatures. Testing shows that
CIDEX OPA Solution is bactericidal when instruments
are processed at 20°C for five minutes.

Mycobacteria

Effective control of mycobacteria is crucial in preventing
the transmission of disease by contaminated medical
devices. Mycobacteria demonstrating resistance to
aldehyde-based disinfectants (i.e., glutaraldehyde and
formaldehyde) have caused nosocomial infections in
the United States and elsewhere, and glutaraldehyde­resistant mycobacteria have been isolated from flexible
endoscope reprocessing machines.
problem, the efficacy of reused CIDEX®OPA Solution
was tested against glutaraldehyde-resistant
Mycobacterium chelonae. The test was based on a
protocol determined by the Environmental Protection
Agency (EPA) to simulate clinically reused disinfectants.
Suspensions of

M. chelonae were exposed to reused

0.5% OPA at 20°C. The result: 5-log reduction after
5 minutes and complete kill (of 10
units/mL) after 15 minutes. By comparison, a solution
of reused 2.0% glutaraldehyde showed a 4-log
reduction in 20 minutes at 20°C.

Similar assays with Mycobacterium bovis (BCG) were
done with 0.2% OPA. Results showed a complete kill

.5 log10) of viable mycobacteria after 5 minutes at

(
20°C. In contrast, although this mycobacterium was
not resistant to glutaraldehyde, 2.0% glutaraldehyde
gave a 2-log reduction after 10 minutes at the same
temperature.

13

Subsequent studies have provided more information
about the effic

acy of CIDEX

®

OP

a 2001 comparison of the mycobactericidal activity of

tho

or

-phthalaldehyde (OP

dialdehydes by quantit

A), glut

e suspension testing found

ativ

Table 2: Bactericidal Efficacy Test with CIDEX®OPA
Solution, 5 Minutes at 20°C

Organism Tested Result

ylococcus aureus(ATCC 6538) No growth

Staph
Salmonella choleraesuis (ATCC 10708) No growth

seudomonas aeruginosa(AT

P

Methicillin-resistant

(MRSA) (ATCC 33592) No growth

Vancomycin-resistant

CC 51299)

T

(VRE) (A

Staph

ylococcus aureus
Enterococcus hirae (CIP 58.55) .5 log reduction
Pseudomonas aeruginosa (ATCC 103467) .5 log reduction

*When used or reused in a legally marketed AER that can be set to a
minimum of 25C.

3

CC 15442) No growth

Staphylococcus aureus

Enterococcus faecalis

(CIP 4.83) .5 l

18,19

To address this

6

colony-forming

13

A Solution. For example,

aldehyde, and other

ar

owth

No gr

og reduction

0

1

2

3

4

5

6

0.3% OPA vs.

C. difficile

vegetative cells

at 20°C

0.3% OPA vs.

C. difficile

spores

at 20°C

0.3% OPA vs.

C. difficile

spores
at 25°C

0.5% OPA vs.

C. difficile

spores
at 25°C

Log of Survivors

0 min. 2 min. 5 min.

10 min. 12 min. 15 min.

Tes t Conditions

that a 0.5% OP
both “clean” and “dirty” conditions.

A was rapidly mycobactericidal under

19

In particular,

the solution was active against glutaraldehyde-resistant

19

strains of mycobacteria.
quantit

ative suspension protocol found that OPA is

Another study using a

effective as a tuberculocidal disinfectant: at MEC levels,

A achieved a 6-log

OP

bovis

in nearly one-sixth the time required with

glutaraldehyde (5.5 minutes versus 32 minutes).

eduction of Mycobacterium

r

10

20

In a study of the mechanisms of the mycobacterial
action of ortho-phthalaldehyde, glutaraldehyde, and
chlorhexidine diacetate, Fraud and colleagues concluded
that, “The rapid micobactericidal effect of OPA probably
arises from its more efficient penetration across
biological membranes.”

21

Antibiotic-Resistant Bacteria

Drug-resistant bacterial infection is a widespread health
concern, and some controversy exists as to whether
resistance to antibiotics is somehow related to resistance
to disinfectants. Two common drug-resistant organisms,

®

MRSA (ATCC

#33592) and VRE (ATCC® #51299), have

been tested with CIDEX® OPA Solution.

As in the efficacy tests with mycobacteria, these assays
evaluated reused CIDEX®OPA Solution in conformance
with EPA specifications. Stainless steel carriers coated
with bacteria were submerged in reused solution diluted
to 0.3% at 20°C. After a 10-minute exposure, carriers
were placed into individual containers of culture
medium containing an agent that neutralizes
ortho-phthalaldehyde. Each strain was
used in triplicate tests involving 10 carriers

Figure 1. OPA Solution Versus Clostridium Difficile at Various
Study Conditions.

each. No organisms survived exposure to
the dilute solution, illustrating that the
antibiotic-resistant strains of

S. aureus

and E. faecalis demonstrate no increased
resistance to dilute CIDEX OPA Solution.

17

Clostridium Difficile

Clostridium difficile, a spore-forming,
gram-positive anaerobic bacillus, is the
leading cause of antibiotic-associated
diarrhea in hospitalized patients. The serious
health effects of
colitis, blood poisoning, and even death.
This, combined with an increasing prevalence
and incidence, make C. difficile a significant
healthcare issue.

A recent study, results of which were
presented at the APIC 2008 Annual
Conference, evaluated the biocidal activity
of an ortho-phthalaldehyde solution
(prepared from CIDEX
against C. difficile. Results showed that
OPA is efficacious against the vegetative

C. difficile include diarrhea,

22

®

OPA Solution)

orm and achieves a significant reduction of the spore

f
form of

C. difficile. (See Figure 1) In particular, there
were no surviving C. difficile vegetative cells observed
after a 2-minute exposure in 0.3% OPA at 20° C. With
the spor

e form of

C. dif

ficile,

a 2.4 l

og

r

10

eduction was

demonstrated with 0.3% OPA and at least 4.9 log

eduction with 0.5% OPA after a five-minute exposure.

r

Viruses

Hepatitis B and C viruses (HBV and HCV)—the most
prevalent blood-borne viruses
transmitted infectious agents that are a major cause
of acute hepatitis and chronic liver disease, including
cirrhosis and cancer. Disinfection of HBV is assayed
with an

in vitro test using duck hepatitis B virus as a
surrogate for HBV.

o test the efficacy of CIDEX® OP

T
the HBV surrogate, a suspension of duck hepatitis
B virus was dried on a Petri dish, then exposed to

0.3% or

tho

-phthalaldehyde f
The bottom of the dish was scraped, and the resulting
suspension was passed though a filtration column to
remove the CIDEX OPA Solution. In the immuno­fluorescence assay, the number of viable virus
particles was reduced by more than 4 logs after
exposure to 0.3% CIDEX OPA Solution.

Similar tests were done with bovine viral diarrhea virus,
a surrogate for HCV. For these tests, virus suspensions
also contained 5% horse serum as organic soil. This

4

24

—are parenterally

A Solution against

or 5 minutes at 20°C.

15

10

23

e was dried on Petri dishes and recovered as

0

1

2

3

4

5

6

7

8

9

0246810121416

Exposu

re Time (minutes)

SA vs OPA + 5% serum
PA vs OPA + 5% serum
SA vs OPA + 20% serum
PA vs OPA + 20% serum
SA vs OPA + 40% serum
PA

vs OPA + 40% serum

mixtur
described above. Exposure to 0.5% CIDEX

®

OPA Solution

for 5 minutes at 20°C caused a .4-log reduction in the

15

number of viable virus particles.

(See Table 3)

Table 3: Virucidal Test with CIDEX®OPA Solution,
5 Minutes at 20°C (Pass Test=

Virus Tested Result

Adenovirus Type 5 Pass test
Herpes Simplex Type 1 (HSV1) Pass test
HSV 2 Pass test
Influenza A (Hong Kong) Pass test
Coxsackievirus Type B3 Pass test
Polio Type 1 (Brunhilde strain) Pass test
Rhinovirus Type 37 Pass test
Vaccinia Pass test

ype 1 Pass test

HIV T
Cytomegalovirus Pass test
Human Coronavirus Pass test
Rotavirus (Strain WA) Pass test
Duck Hepatitis B Virus (surrogate for Hepatitis B) Pass test
Bovine viral diarrhea virus (surrogate for Hepatitis C) Pass test
Rotavirus (Strain WA) Pass test
Feline calicivrus as (surrogate for Norovirus) Pass test
Avian influenza A (H5N1) virus Pass test
Canine Parvovirus Pass test
Hepatitis A virus Pass test

.3-log Reduction)

Temperature

The effect of temperature on biocidal activity was further
assessed in quantitative tests of

Bacillus subtilis spores
(ATCC #19659). Suspensions of spores were diluted
into various concentrations of CIDEX®OPA Solution
and tested at 35°C, 40°C, 45°C, and 50°C. Results
showed that the solution is sporicidal and that, within
defined parameters, study temperature has a bigger
influence on the degree of sporicidal activity than the
concentration of the solution. For example, a
reduction in the number of viable spores occurred with
2-hour exposure to 0.05% disinfectant at 50°C, and a

oncentrated

eduction was observ

og r

3-l
solution of 0.3% OP

A at 35

ed in the mor

16

°C.

e c

Organic Soil

Cleaning of instruments before disinfection is the
first step in removing bioburden from instruments.
However, manual cleaning is known to have variable
results,
disinfection. To assess the impact of an organic load
on bactericidal activity of 0.3% CIDEX®OPA Solution,
suspensions of S. aureus and Pseudomonas aeruginosa
were exposed to 0.3% CIDEX OPA Solution at room
temperature (20°C) in the presence of 0%, 5%, 20%,
and 40% horse serum. For exposure times of up t
5 minutes, bactericidal activity decreased with increasing
concentration of horse serum. However, when exposure
to 0.3% CIDEX OPA Solution was 10 minutes or longer,
these concentrations of horse serum did not prevent
.7-log reduction of viable bacteria.

25

potentially reducing the effectiveness of

17

>6-log

o

e 2. Biocidal Activity of 0.3% CIDEX

Figur

Biocidal activity of 0.3% CIDEX®OPA Solution was evaluated in
the presence of variable amounts of horse serum. Suspensions of
Staphyloccoccus aureus (SA) or Pseudomonas aeruginosa (PA) were
diluted 1:10 into 0.3% OPA+horse serum. After exposure to disinfectant,
viable organisms were assayed quantitatively.

®

A Solution.

OP

17

Summary

For more than 10 years, CIDEX®OPA Solution has
been successfully utilized by healthcare facilities
worldwide to high-level disinfect reusable medical and
dental devices. As part of its commitment to infection
prevention, ASP has conducted extensive tests to
evaluate the efficacy of CIDEX OPA Solution. Results
show that CIDEX OPA Solution is bactericidal—including
for MRSA and VRE—mycobactericidal, sporicidal, and
virucidal—including for surrogates for HBV and HCV.

®

CIDEX
wide variety of devices, including delicate and costly
flexible gastroenterology endoscopes. This range of
applications is possible because of the solution’s broad
mat
materials compatibility is simple standardization of
pr
developed for disinfection of many items.

The f
Solution also contribute to rapid turnaround time,
allowing smaller inventories of instruments and
pot

ealized by eliminating the monitoring of air and

r
personnel exposure required with glutaraldehyde.

Combined, these factors demonstrate why CIDEX
Solution makes both clinical and economic sense for
facilities seeking an effective, more cost-efficient
option for instrument reprocessing. Furthermore,
the efficacy testing and quality assurance measures
applied by ASP should be an important consideration

or healthc

f

ontrol and prevention of HAIs.

c

5

OPA Solution is currently used to disinfect a

erials c

es

oc

ompatibility. An important benefit of broad

ocols—a single protocol can be

sing pr

ot

ast processing time and ease of use of CIDEX

ential c

t savings. Cos

os

sonnel as they work toward the

e per

ar

t savings also might be

n

®

®

OP

OPA

A

References

www.ActiveForever.com

1. Centers for Disease Control and Prevention. Public health focus: Surveillance, prevention and control of nosocomial infections. Morbidity and Mortality
Weekly Report. 1992;41(42):783–787.

2. Joint Commission 2009 National Patient Safety Goals—Hospital 2008.

3. APIC Vision 2012. Washington, D.C.: Association for Professionals in Infection Control and Epidemiology.

4. Mitka M. Public, priv

5. Mehta A, Prakash U, Garland R, et al. Prevention of flexible bronchoscopy-associated infection. Chest. 2005;128:1742–1755.

6. Nelson D, Jarvis W, Rut
2003;24:532–537.

7. Rutala W, Weber D. Disinfection of Endoscopes: Review of new chemical sterilants used for high-level disinfection. Infect Control Hosp Epidemiol.
1999;20:69–76.

8. Spach D, Silverstein F, Stamm W. Transmission of infection by gastrointestinal endoscopy and bronchoscopy. Ann Intern Med. 1993;118:117–128.

er M. ICRE-1108: Instrument processing overview: cleaning, disinfection, sterilization. http://www.iceinstitute.com/. Accessed Nov. 11, 2008.

9. Mill

10. Association for Professionals in Infection Control and Epidemiology (APIC). Disinfection and sterilization principles; 2002.

11. Committ

12. Abraham J, Abdelshehid C, Lee H, et al. Effects of Steris 1™ sterilization and Cidex®ortho-phthalaldehyde high-level disinfection on durability of
new-generation flexible ureteroscopes. J Endourol. 2007;21:985–992.

13. Roberts C, Chan-Myers H. Efficacy of dilute ortho-phthalaldehyde solutions with glutaraldehyde-resistant mycobacteria. American Society for

Microbiol

14. Roberts C, Chan-Myers H, Ascenzi J. Activity of dilute ortho-phthalaldehyde solutions against drug-resistant bacteria. American Society for
Microbiology; 2001; Olando.

15. Roberts C, Chan-My
2008;36:223–226.

16. Chan-Myers H, Roberts C. The role of temperature and concentration on the sporicidal activity of ortho-phthalaldehyde. Society for Healthcare
Epidemiologists of America; 2001; Baltimore.

17. Chan-Myers H, Roberts C. Effect of temperature and organic soil concentration on biocidal activity of ortho-phthalaldehyde solution. Association for
Professionals in Infection Control and Epidemiology (APIC); 2000.

18. van Klingeren B, Pullen W. Glutaraldehyde resistant mycobacteria from endoscope washers. Hosp Infect. 1993;25:147–149.

19. Fraud S, Maillard J, Russell A. Comparison of the mycobactericidal activity of ortho-phthalaldehyde, glutaraldehyde and other dialdehydes by a
quantitative suspension test. J Hosp Infect. 2001;48:214–221.

20. Gregory A, Schaalje G, Smart J, Robison R. The mycobactericidal efficacy of ortho-phthalaldehyde and the comparative resistance of Mycobacterium
bovis, Mycobacterium terrae, and Mycobacterium chelonae. Infect Control Hosp Epidemiol. 1999;20:324–330.

21. Fraud S, Hann A, Maillard J, Russell A. Effects of ortho-phthalaldehyde, glutaraldehyde and chlorhexidine diacetate on Mycobacterium chelonae and
Mycobacterium abscessus strains with modified permeability. JAC. 2003;51:575–584.

22. Agency for Healthcare Research and Quality. Potentially deadly infection doubles among hospital patients over last 5 years. Statistical Brief #50; 2008.

23. Chan-Myers H, Roberts C. Evaluation of the biocidal efficacy of ortho-phthalaldehyde solution with vegetative and spore forms of Clostridium difficile.
Association for Professionals in Infection Control and Epidemiology (APIC); June 15–19, 2008; Denver.

24. Sattar S, Tetro J, Springthorpe V, Guilivi A. Preventing the spread of hepatitis B and C viruses: where are germicides relevant? Am J Infect Control.
2001;29:187–197.

25. Alf
retrograde choliangiopancreatography duodenoscopes used in Canadian centers. Infect Control Hosp Epidemiol. 2002;23:198–206.

ee on Antimicrobial Efficacy Testing. Methods Committee Report. J AOAC Int. 2008;91:68B–72B.

ogy; 1998; Atlanta.

a M, Olson N, Degagne P, Jackson M. A survey of reprocessing methods, residual viable bioburden, and soil levels in patient-ready endoscopic

ate insurers refusing to pay hospitals for costs of avoidable errors. JAMA. 2008;299:2495–2496.

ala W, et al. Multi-society guideline for reprocessing flexible gastrointestinal endoscopes. Infect Control Hosp Epidemiol.

ers H, Favero M. Virucidal activity of ortho-phthalaldehyde solutions against hepatitis B and C viruses. Am J Infect Control.

This white paper was funded by Advanced Sterilization Products.

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