Chlorine Dioxide - A Versatile Chemical Disinfectant

Why Chlorine and Chlorine Dioxide Are Not the Same.

While chlorine dioxide has chlorine in its name and has a similar smell to chlorine, it differs from elemental chlorine in its chemical structure and behaviour. Discovered in 1814 by Sir Humphrey Davey, chlorine dioxide is a molecule consisting of two oxygen atoms and one chlorine atom, whereas chlorine exists as a diatomic molecule, meaning it consists of two chlorine atoms bonded together (Ganiev et al., 2016) (see Figure 1). 

Oxidising agents accept electrons from another substance, causing the other substance to lose electrons and become oxidised. Both chlorine dioxide and chlorine are oxidising agents. However, they have different oxidation capacities and strengths. Oxidation capacity refers to the number of electrons one molecule can obtain from another molecule. Chlorine dioxide can steal five electrons, whereas chlorine can take only two, making chlorine dioxide more effective than chlorine at lower concentrations (Ran et al., 2019). 

The oxidation potential describes how strongly an oxidiser reacts with an oxidisable substance. Chlorine dioxide has a lower potential than chlorine. It is not as reactive as chlorine and has been shown to produce little to no by-products compared to chlorine (Ran et al., 2019) due to the different reaction mechanisms. The first step in the reaction of chlorine dioxide with many organic compounds is a single-electron oxidation. This is different from electrophilic addition, which is what is observed with chlorine. This mechanism prevents the formation of harmful chlorinated organic compounds such as Haloacetic acid (HAAs) and Trihalomethanes (THMS), which are proven carcinogens (Hrudey et al., 2009). 

Chlorine dioxide is a more selective oxidiser than chlorine; this contributes to the effective microbicidal efficacy of chlorine dioxide at concentrations far lower than typically required for chlorine, which also results in a lower environmental impact (Wu et al., 2010) (Hrudey et al., 2009).

How Chlorine Dioxide works to Destroy Microorganisms

Literature indicates there is no single encapsulating mode of action, and chlorine dioxide has different biocidal effects depending on the type of organism. Chlorine dioxide causes the chemical disruption of cell walls and the inhibition of protein synthesis for bacteria, fungi and yeasts (Benarde et al., Wei et al., Wen et al.). The proteins are denatured for viruses, amino acids are modified, and genetic material is impaired (Miura and Shibata, Noszticzius et al., Alvarez and O’Brien). For bacterial spores, research suggests that chlorine dioxide causes severe bacterial cell inner membrane damage (Young and Setlow). For biofilms (the aggregation of microbial species, such as bacteria and fungi), chlorine dioxide can penetrate the slime layers and oxidise the polysaccharide matrix that holds the biofilm together (Kim et al., 2022).

Antimicrobial Resistance (AMR) happens when microorganisms develop the ability to overcome the drugs designed to kill them. The more resistant the microorganisms become to these drugs, the harder they are to kill. A similar interaction may occur when an insufficient disinfectant is used. This has led to a significant impact on the healthcare environment. Chlorine dioxide’s mode of action is not affected by these resistance pathways, as it is unaffected by defensive molecular features, such as cell walls. It steals electrons from within the microorganism, making it unstable and inevitably destroying it. This mode of action means that microorganisms cannot build resistance (Andrés et al., 2022; Noszticzius et al., 2013).

Chlorine Dioxide Point-of-Use Generation  

Chlorine dioxide has been used as a globally approved chemistry for the disinfection of many medical devices and surfaces by generating the active biocidal concentration at the point of use. The generation is typically done through a chemical reaction between sodium chlorite and an acid to create the active concentration. A disinfectant manufacturer has pioneered the inherent ease of use product designs that combine the precursor solutions of sodium chlorite and citric acid with the pull of a trigger, the bursting of a sachet, or the press of a pump at the point of use. 

The Use of Chlorine Dioxide as a Disinfectant in Healthcare 

Chlorine dioxide has been utilised as a chemical disinfectant to offer point-of-care disinfection (performed near or at the site of a patient) in various human medicine sectors, such as Ophthalmology, Otorhinolaryngology (ENT), Ultrasound, Endoscopy, Radiology, Urology, Emergency Services, Gynaecology and Obstetrics to name a few. These products are intended to disinfect non-invasive and invasive semi-critical medical equipment and devices, including endoscopes that cannot be sterilised and general surface disinfection, including floors, walls, countertops, and equipment. Chlorine dioxide is currently used in the following formats on the market:

• Decontamination wipes. A three-wipe system for the decontamination of non-lumened invasive and noninvasive medical devices such as nasendoscopes, laryngoscopes, transoesophageal echocardiographic probes, transvaginal and transrectal ultrasound probes. It comprises a cleaning wipe for the removal of soil and organic matter before high-level disinfection, a pre-impregnated wipe with the base solution, and when combined with an activator foam, generates chlorine dioxide for the high-level disinfection of medical devices in 30 seconds, and a sterile water rinsing wipe to remove chemical residues from the medical device after disinfection. 
• Disinfectant foams. The foam products comprise a dual-sided bottle; one chamber contains base solution, and the other has activator solution, which, when dosed or sprayed combine to generate the active chlorine dioxide for: 
  • The high-level disinfection of ophthalmic medical devices in two minutes, such as diagnostic contact lenses, reusable tonometers, pachymeters, and ophthalmic ultrasound probes (A-scan and B-scan probes). 
  • The intermediate-level disinfectant of non-invasive ultrasound probes, cables, plugs, probe holders, monitors, and control panels at the intermediate level in 30 seconds.
  • The sporicidal disinfection of hard, non-porous surfaces of medical equipment in two minutes such as IV poles, tourniquets, surfaces of transfusion pumps, dialysis machines, patient monitoring equipment, mattresses, bed rails, dressing trolleys, commodes, instrument tables, bench tops, general building, and fitting surfaces.

• Immersion disinfectant. The chlorine dioxide immersion disinfectant comprises a dual-sided laminated sachet, each side containing base and activator solution. Folding the sachet in half and applying pressure to one side separates the seal, leading to the two compartments mixing to generate chlorine dioxide ready to be added to five litres of water. This disinfectant was specifically designed for a 5-minute high-level disinfection cycle in a semi-automated washer disinfector for the disinfection of invasive and non-invasive, heat sensitive, non-lumened and single-lumened endoscopes, laparoscopes, or other suitable medical devices which are invasive either by body orifice or surgical procedure.  

The Importance of Water Quality in EWDs. 

Water impurities can adversely affect a medical device, (re-)processing procedures, and the patient. Tap water is often of insufficient quality for specific reprocessing activities and, therefore, generally needs water treatment to remove impurities or inactivate microorganisms that may be present.

 The Association for the Advancement of Medical Instrumentation (AAMI) published AAMI ST108:2023 - Water for the processing of medical devices, standard in 2023. This standard establishes the minimum requirements for water quality necessary to process medical devices intended for patient use effectively.

AAMI ST108:2023 outlines three types of water used in healthcare facilities:

1. Utility Water: water as it comes from the tap, predominantly used for medical device processing except for the final rinse, where critical Water is recommended.
2. Critical Water: extensively treated water that removes microorganisms and inorganic and organic materials, usually by a multistep treatment process. It is mainly used as the final rinse after high-level disinfection, for the final rinse for critical devices before sterilisation, and feedwater for process steam production. 
3. Steam: vaporised water produced by a centralised boiler or a generator/heat exchanger near the steriliser.

Utility water is suitable for all stages of the manual pre-clean until the stage of disinfectant dilution and final rinse. Here, the emphasis is on the Endoscope Washer Disinfector (EWD) manufacturer to decide on the type of water required, stipulated in the device's instructions for use (AAMI, 2023). Therefore, with the introduction of this guidance, it is speculated that there will be a shift in the use of critical water in EWDs.

 Other guidance on water quality used in EWDs, such as the Australian Standards AS 5369: 2023 – Reprocessing of reusable medical devices and other devices in health and nonhealth related facilities, the United Kingdom Health Technical Memorandum (HTM) 01-06 – Management and decontamination of flexible endoscopes, EN ISO 15883 - Washerdisinfectors - Part 4: Requirements and tests for washer-disinfectors employing chemical disinfection for thermolabile endoscopes also recognises that rinsing with microbial-free water is as significant in the reprocessing cycle as adequate high-level disinfection.

Biofilms and bacteria in the pipelines can supply contaminated water to EWDs. The EWDs themselves are challenging to disinfect due to their complex design. This leads to moist surfaces within them, leading to further bacterial proliferation, favouring biofilm formation. Contaminated water can compromise medical devices, which, if inadequately dried and stored, can provide favourable conditions for biofilm formation on the device and any ridges, indentations and lumen(s) present (de Bruijn A. & van Drongelen A., 2010, Roberts, 2013)). This poses a risk to the patient and staff handling the device. To prevent contamination of the water flowing through the EWDs and subsequent re-contamination of devices, it is paramount to for the water supplied to EWDs to be microbial-free (de Bruijn A & van Drongelen A., 2010).

Reverse Osmosis (RO) plays an integral part in producing quality water. It can remove microbial and ionic contaminants, lowering the outgoing water's conductivity levels by passing them through a semi-permeable membrane and a final 0.2μm filter. However, the significant concern of RO systems is biofouling (the growth and deposition of biofilms) of pipelines to the EWDs, the membranes, and the filters that purify the water passing through, which can lead to the presence of biofilm in the treated water (Flemming 2002). Endotoxins in rinse water are another significant concern. While RO systems are usually effective in removing endotoxins, if biofouling occurs, this can inhibit RO’s ability to remove endotoxins, resulting in contaminated rinse water.

The Use of Chlorine Dioxide in a Water Purification System

Chlorine dioxide is utilised in a Class I Medical Device water purification system (Medical Device Regulation (EU) 2017/745) that offers optional RO, chemical dosing in low concentrations, and filtration. The water purification system is listed in the Australian Register of Therapeutic Goods as a Class I medical device. It meets the requirements set by the AAMI ST108 and AS 5369 2023 for the acceptable levels of endotoxins in the rinse water, and also complies with EN ISO 15883 and HTM 01-06 guidance. 

The chlorine dioxide is dosed before the final 0.2μm filter, preventing bacterial proliferation and biofilm formation while simultaneously treating the 0.2μm filter used during an EWD’s decontamination cycle. This saves the user time and money as a separate manual disinfection process is not required to decontaminate the filter. 

Conclusion  

Since its discovery, chlorine dioxide has been integral to many industrial and healthcare applications owing to its versatility. Over the past 30 years a UK manufacturer has utilised a proprietary method for generating chlorine dioxide at the point of care. Chlorine dioxide products have been successfully utilised as a part of standard infection prevention and control procedures in healthcare. They destroy a broad spectrum of microorganisms in a short, uniform contact time. This allows quick turnaround of patient rooms.  

A water purification system that utilises chlorine dioxide for chemical dosing at low concentrations can also eliminate bacteria, preventing biofilm formation, and significantly lowering endotoxin levels, ensuring microbial-free water.  

References

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