May 27, 2015 — A recent study suggests that some disinfectants commonly used in hospitals may be ineffective against certain types of the HPV virus.

Briefly, the reprocessing of contaminated reusable medical instrumentation is crucial to prevent the transmission of diseases, including those caused by antibiotic-resistant bacteria and viruses. “Reprocessing” refer to the cleaning and either disinfection or sterilization of a reusable device.

Whereas non-critical instruments such as stethoscopes generally pose a low risk of infection requiring low- or intermediate-level disinfection to ensure patient safety, critical instruments such as orthopedic implants typically pose a high risk of infection requiring sterilization.[1,2]

Gastrointestinal (GI) endoscopes and intracavitary ultrasound probes (e.g., rectal, vaginal) are classified as semi-critical because they contact mucous membranes or non-intact skin during routine clinical use, but ordinarily not sterile tissues.  These instruments demand high-level disinfection (or sterilization) to prevent disease transmission.[1-3]

While required by the FDA to be sporicidal, albeit usually during impractically long exposure times of several hours, high-level disinfectants rapidly destroy virtually every known pathogenic microorganism including high numbers of resistant mycobacteria, sometimes in as few as 5 or 10 minutes.[4]



Quality and Safety Services for Hospitals, Manufacturers, Patients:  Click here to read about Dr. Muscarella’s quality and safety services designed to identify the causes of, and to prevent, healthcare-associated infections, including “superbug” outbreaks linked to contaminated endoscopes and other reusable medical equipment.



Human papillomavirus (HPV)

Human papillomavirus (HPV) is a community-acquired pathogen of which more than 100 types have been identified. In fact, HPV infection is the most common sexually transmitted infection worldwide.[5]

This small, non-enveloped virus is responsible for almost all cervical cancers, and several high-risk types of HPV, including types 16 and 18, have been causally linked to ano-genital and oropharyngeal cancers.[5,6]

The risk of HPV transmission in the clinical setting is controversial. Certain reusable devices, including intracavitary ultrasound probes, may become contaminated with this virus during their routine use.[7-10]

Raising the specter of patient-to-patient transmission, recently published data — which are a focus of this article — suggest that, for some high-level disinfectants, HPV identified on the surfaces of these instruments may be significantly more difficult to inactivate than previously published.[7-10]

The Meyers et al. (2014) study

Recently published data by Meyers et al. (2014) suggest that some types of HPV may be resistant to a number of disinfectants commonly used in the healthcare setting, increasing the risk of disease transmission.[7-9]

These investigators performed a series of suspension tests comparing the relative effectiveness of 11 disinfectants for the inactivation of native, infectious HPV virions (type 16).[7]  Three of these tested disinfectants were:

  • 2% glutaraldehyde (Cidex; Advanced Sterilization Products);
  • 3.4% glutaraldehyde (Cidex Plus; Advanced Sterilization Products); and
  • 0.55% ortho-phthalaldehyde solution (Cidex OPA; Advanced Sterilization Products).

Each of these is cleared by the FDA for high-level disinfection and is commonly used in the U.S. for reprocessing intracavitary ultrasound probes and GI endoscopes.

Briefly, Meyers et al. (2014) suspended HPV in the disinfectant prepared according to its respective manufacturer’s instructions. The resulting solution, one for each of the 11 disinfectants, was mixed and then incubated for 45 minutes at room temperature. (In general, this contact time is longer than required by each disinfectant’s labeling to be effective.) After incubation, a neutralizer was added, the solution centrifuged, and the HPV then assayed for infectivity.[7]

Table 1, Panel A summarizes this study’s findings.

Meyers et al. (2014) report that neither the tested 2% glutaraldehyde solution nor the 0.55% ortho-phthalaldehyde solution reduced the infectivity of the HPV when each was used according to its respective FDA-cleared labeling.[7]

Similarly, Meyers et al. (2014) found, too, that both the ortho-phthalaldehyde and 3.4% glutaraldehyde solutions failed to reduce HPV’s infectivity during a contact time of as long as 24 hours (at room temperature), which is an extended contact time that, at least according to this latter high-level disinfectant’s label, is ordinarily sporicidal.[11]

HPV as a “marker” for high-level disinfection?

As a consequence of their findings, Meyers et al. (2014) emphasize evaluating high-level disinfectants as much for their demonstrated tuberculocidal (and sporicidal) activities as for their documented inactivation of HPV.[7-10]

The relative resistance of HPV to different disinfectants commonly used in the medical and dental settings had not been previously studied primarily because, as Meyers et al. (2014) discuss:

  • establishment of an adequate culture system for the in vitro replication of this virus’s infectious virions had not been feasible (as is required to produce and study a sufficiently high number of infectious virus particles); and
  • a suitable assay for evaluating HPV’s infectivity after exposure to a disinfectant had not been adequately developed.[7,8]

Instead, a disinfectant’s inactivation of HPV generally has been presumed, with the general understanding that such non-enveloped viruses are more susceptible to disinfection than mycobacteria.[12]

One potentially important consequence of their findings, Meyers et al. (2014) suggest that the traditional paradigm for comparing the relative effectiveness of different microorganisms and viruses may require reevaluation.[7-10,12]

In vitro replication of HPV

Overcoming both of these testing limitations, Meyers et al. (2014) developed validated and reproducible methods for both the in vitro replication of infectious HPV and for assaying HPV’s infectivity, both before and after its exposure to a disinfectant.

In addition to the tested 2% glutaraldehyde and 0.55 % ortho-phthalaldehyde solutions — neither of which reportedly reduced the infectivity of HPV (type 16), despite both being commonly used, FDA-cleared high-level disinfectants[7] — these investigators similarly compared the effectiveness of 9 other disinfectants for their respective inactivation of HPV, including:

  • 70% isopropyl alcohol;
  • a 0.525% hypochlorite solution (Activate; Deardorff Fitzsimmons); and
  • a 1.2% peracetic acid-based disinfectant (Steriplex SD Plus; sBioMed).[7]

Of these 11 tested disinfectants, Meyers et al. (2014) report that only these latter two disinfectants (the 0.525% hypochlorite solution and the 1.2% peracetic acid-based disinfectant) inactivated native, infectious HPV virions by more than 4 logs (e.g., 99.99%) during a contact time of 45 minutes at room temperature[*].[7]  Neither solution is cleared by the FDA for high-level disinfection, however.



Quality and Safety Services for Hospitals, Manufacturers, Patients:  Click here to read about Dr. Muscarella’s quality and safety services designed to identify the causes of, and to prevent, healthcare-associated infections, including “superbug” outbreaks linked to contaminated endoscopes and other reusable medical equipment.



The Ryndock et al. (2015) study

Similarly, Ryndock et al. (2015) investigated the effectiveness of a number of different disinfectants for the inactivation of HPV (types 16 and 18), including 0.55% ortho-phthalaldehyde (Cidex OPA).

These investigators also tested the effectiveness of both a 0.87% hypochlorite solution (Pure Bright Germicidal Ultra Bleach; KIK International) and the Trophon EPR (Nanosonics, Ltd), which is an automated device cleared by the FDA for high-level disinfection of ultrasound probes[**].[8]

Their findings were presented, in 2015, as a poster at the annual conference of The Society for Healthcare Epidemiology of America (SHEA) in Orlando (FL).[8]

Table 1, Panel B summarizes Ryndock et al.’s (2015) findings.

Like Meyers et al. (2014), Ryndock et al. (2015) report that 0.55% ortho-phthalaldehyde did not significantly reduce the infectivity of HPV.[7.8]

In contrast, however, these latter investigators found that the Trophon EPR significantly reduced the infectivity of HPV, reporting that this device’s nebulized mist of 35% hydrogen peroxide is the first FDA-cleared high-level disinfectant shown to completely inactivate HPV (types 16 and 18) during challenging standardized testing conditions.[8]

Further, Ryndock et al. (2015) suggest that, in lieu of an FDA-cleared glutaraldehyde or ortho-phthalaldehyde solution, the Trophon EPR be considered for the effective high-level disinfection of intracavitary ultrasound probes.[10,13]

The relative resistance of HPV

These two reports by Meyers et al. (2014) and Ryndock et al. (2015), each evaluating the resistance of HPV to a number of different disinfectants including some commonly used high-level disinfectants, warrant review and commentary.

Whereas a high-level disinfectant is expected to be sporicidal and destroy all pathogenic microorganisms including mycobacteria and viruses, both Meyers et al. (2014) and Ryndock et al. (2015) suggest exceptions and that HPV appears to be significantly more resistant to certain disinfecting chemistries than previously recognized.

In those clinical settings where the risk of transmission of HPV via contaminated semi-critical instruments may be a concern, these two reports conclude, therefore, that the selection of a sufficiently effective high-level disinfectant may require additional consideration.

More specifically, Meyers et al. (2014) report that HPV (type 16) is highly resistant to, and its infectivity is not significantly reduced by: (i) 2% glutaraldehyde; (ii) 3.4% glutaraldehyde; or (iii) 0.55% ortho-phthalaldehyde (when each was used according to its respective labeling).

Meyers et al. (2014) also report that HPV may remain infectious even after a 24-hour exposure to both 0.55% ortho-phthalaldehyde and 3.4% glutaraldehyde (and presumably, 2% glutaraldehyde, too), each of which is labeled in the U.S. to achieve high-level disinfection.[11,14,15]

Because of the potentially significant implications of these results to public health and healthcare-associated infections, independent confirmation of the ineffectiveness of these commonly used high-level disinfectants for the inactivation of HPV (types 16 and 18) is recommended.

FDA oversight of high-level disinfectants

Meyers et al. (2014) express concerns about the FDA’s current regulation, classification and standardized testing of high-level disinfectants.

In particular, these investigators, along with Ryndock et al. (2015), recommend that infection control practices be reevaluated to address the potential for HPV transmission during the reuse of certain medical instruments.

Meyers et al. (2014) also emphasize that, for those clinical settings where the risk of transmission of HPV via contaminated semi-critical instruments may be a concern, the selected high-level disinfectant – especially for such instruments as intracavitary ultrasound probes, which may become contaminated with HPV during routine clinical use[16-18] – have been adequately tested and demonstrated to completely inactivate HPV.[7-10] These instructions and guidance seem reasonable.

Instrument cleaning

Instrument cleaning is the first and most important reprocessing step. Some studies report, however, that despite cleaning using wipes labeled to achieve low-level disinfection, for example, instruments may remain contaminated with HPV and other microorganisms.[16-18]

Moreover, Alfa (2015) has suggested that not only the head of intracavitary ultrasound probes (which enters the patient), but also its handle (which may contact the patient indirectly) is a potential vector for HPV transmission.[19] guidance recommending the use of a high-level disinfectant demonstrated to inactivate all types of potentially pathogenic microorganisms, including HPV, therefore seems appropriate.[19]

Is absence of proof the proof of absence?

It is acknowledged that reports of HPV transmissions resulting directly from contaminated intracavitary ultrasound probes are scant.

The absence of proof is not the proof of absence, however, and the potential for reusable instruments to transmit HPV, due to the use of a disinfectant that is ineffective against HPV, is well-taken and justifies further study and investigation.

Indeed, the studies by Meyers et al. (2014) and Ryndock et al. (2015) reporting that one or more high-level disinfectants (when used according to their respective labeling) may not effectively inactivate HPV seems significant.

Lumened devices

The importance and application of these reports by Meyers et al. (2014) and Ryndock et al. (2015) to the selection, use and effective disinfection of other types of semi-critical instruments, too, that may also become contaminated with HPV, including GI endoscopes and other lumened instruments, are unclear, but also warrants further study and investigation.

The Trophon EPR High-Level Disinfection System

Ryndock et al.’s (2015) findings and claims — like those of others who also demonstrated the effectiveness of the Trophon EPR for high-level disinfection, in general, and for its complete inactivation of HPV (types 16 and 18), in particular — are newsworthy, although their corroboration and peer review are recommended.[7,13]

[According to its manufacturer, additional testing of this automated device’s 35% hydrogen peroxide mist to confirm its materials’ compatibility is unnecessary, as this high-level disinfectant has been “approved” for use with many brands of probes (unpublished data).]

Whether this device’s novel technology may be labeled in the future for the high-level disinfection of other types of reusable medical instruments is also unclear, but possible.

Conclusions

Some disinfectants commonly used in hospitals may be ineffective against certain types of the HPV virus, according to a recent study. Therefore, selection of a disinfectant demonstrated to inactivate HPV may be necessary when this virus’s potential transmission in the clinical setting by a contaminated device, such as an intracavitary ultrasound probes, is a realized concern.

Use of a high-level disinfectant shown to inactivate all types of potentially pathogenic microorganisms — including HPV — is an important consideration. Additional studies that independently confirm the ineffectiveness of some commonly used high-level disinfectants for the inactivation of HPV is recommended.


Disclosure, related reading

This review, or digital white paper, by Dr. Muscarella discussing HPV’s demonstrated resistance to certain high-level disinfectants was sponsored, in part, by a grant from Nanosonics, Ltd (Sydney, Australia), the manufacturer of the Trophon EPR High-Level Disinfection System, which this review discusses.

Click here to read Dr. Muscarella’s related article, “The Trophon EPR Ultrasound Transducer High-Level Disinfection System: A Commentary.


Footnotes

[*] A standardized virucidal test recognized by the FDA and EPA and used to evaluate and test the effectiveness of disinfectants (in support of their respective labeling claims) generally requires demonstration of both a 4 log reduction in the virus’s infectivity and complete inactivation of the virus.

[**] The FDA cleared the Trophon EPR in February, 2011, for the high-level disinfection of ultrasound transducers (see: FDA clearance No.: 103059).

References:  Click here.


Article by: Lawrence F Muscarella, PhD (posted 5/27/2015, Rev A; updated 7/29/2015, Rev A).

Lawrence F Muscarella PhD is the owner of LFM Healthcare Solutions, LLC, a Pennsylvania-based quality improvement and consulting company that provides safety services for hospitals, manufacturer and the public.  Email him (Larry@LFM-HCS.com) with your inquiries, including requests to write review articles and white papers such as is presented herein.

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