The science behind disinfectants

Disinfectants in Healthcare

The use of disinfectants in the healthcare industry is vital in order to reduce healthcare associated infections (HCAI) caused by a range of bacterial species such as; Clostridioides difficile (formerly Clostridium difficile), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), carbapenemase producing enterobacterales (CPE), and methicillin-resistant Staphylococcus aureus (MRSA). There are a few fundamental strategies that can be implemented in hospitals to reduce the presence of such pathogenic bacteria, viruses and more that are the root cause of HCAIs.

The first is frequent use of effective disinfectant products which are effective against a broad-range of microbes including bacterial endospores. Appropriate disinfectant use by cleaning staff, whilst following good cleaning and disinfection practices, will reduce the presence of microbes.

Secondly, the regular cleaning of surfaces will prevent the development of dry-biofilms on surfaces, which are exceptionally difficult to fully remove without an effective disinfectant. It should also be noted that there should be a special focus on ‘high-touch surfaces’, such as bed rails and frames, handles, IV poles, and keyboards, to minimise the spread of microbes.

The third is ensuring that the disinfectant used retains antimicrobial efficacy by using an auditing system such as labels, colour coding, or chemical indicator to indicate when the disinfectant was prepared. This will prevent cleaning staff from using disinfectant solutions that are old and therefore diminished in antimicrobial efficacy.

Oxidation potential

There are a wide range of active ingredients approved for use in disinfectant products created for the healthcare industry. Whilst their mechanisms and modes of action vary, chlorine- and peroxy-based disinfectants work primarily through oxidation. Oxidation is defined as the loss of electrons from a molecule. Electrons form the bonds within molecules and, once lost, the bonds are broken and the molecule will break up. Since cells are made up of molecules that can be oxidised (specifically proteins and other molecules consisting of amino acids), the cell will lyse, (break up, die, etc.) if it comes into contact with an oxidising agent. The ability of a molecule to oxidise is known as the oxidation potential. Each type of cell may need a specific amount of oxidation to lyse, but in short, the higher the oxidation potential, the faster the cell will be lysed.

Active ingredient Oxidation potential (V) Solution Vapourisers
Ozone 2.07 No Yes
Peracetic acid 1.81 Yes Yes
Hydrogen peroxide 1.78 Yes Yes
Chlorine dioxide 1.57 Yes No
Chlorine (NaDCC donor) 1.36 Yes No

Oxidation potential of some common active ingredients that work by an oxidative mechanism.

To ensure the maximum use of a chemical’s oxidation potential, the preparation must be correct. Ideally, a ready-made solution would be available, however, this is rarely achievable and never cost effective. The vast majority of ready-made solutions contain less than 5% active ingredient and the remainder is just water. It always makes economic sense to generate a usable disinfectant on site. Therefore, an easy-to-use dilution system that does not put the user at any harm is essential in your choice of disinfectant.

In conclusion, there are many active ingredients currently available, each with its own advantages and disadvantages. Many NHS Trusts use NaDCC, Chlorine dioxide, or other Chlorine agents, despite their many disadvantages. This is largely due to an unawareness of alternatives, or a level of comfortability with Chlorine, as it’s been in use for over 100 years and is associated with smelling clean. Swapping to a non-chlorine disinfectant will prevent on average 1 tonne of Chlorine from being released into the environment, and now there are viable alternatives in ISPAA products, it is both cost effective, personnel-effective, and environmentally effective to move away from Chlorine.

Chlorine Releasing Tablets

Sodium dichloroisocyanurate (NaDCC)

Chlorine in the form of NaDCC is a well-known and commonly used disinfectant in the healthcare sector. The chlorine smell is widely associated with cleanliness and it reassures users and patients that an area has been cleaned or disinfected. However, chlorine has many drawbacks in ecology, material compatibility, efficacy, health and safety, and cost.

Firstly, chlorine is known to be ecologically harmful, as well as harmful to the end user. As an elemental active ingredient, it cannot degrade beyond being chlorine; bioaccumulation is inevitable. It is also highly harmful to the end user, with common reports of headaches and nausea, and less common but still frequent reports of occupational asthma and development of COPD.

Chlorine typically comes as NaDCC tablets. The formulation of a tablet has many benefits over liquid formulations in that it can’t be spilled or mishandled, and over/underpreparing a solution is difficult as the tablets can be counted out for the correct strength. Although it is possible to get chlorine tablets that contain a detergent, they still perform worse in the presence of soiling and a cleaning step using a detergent is required before the disinfectant can be used somewhat reliably.

Pros Cons
Tablet formulation with and without detergent 2-step cleaning (clean then disinfect to maintain efficacy)
Short-term cost effective Up to 10,000ppm needed in soiled conditions
Good efficacy in clean conditions Very unsafe for the user and the environment
General structure of NaDCC Sodium dichoroisocyanurate

Sodium dichloroisocyanurate (NaDCC)

Chlorine Dioxide

Chlorine dioxide is another chlorine-based oxidising agent active ingredient that has gained some attention for its use as a surface disinfectant. Disinfectant products that use chlorine dioxide as an active ingredient requires the generation of chlorine dioxide before it can be used. These products either use tablets or liquids to achieve the goal of generating the active ingredient. Chlorine dioxide comes in many formats, from liquid sachets to tablets. The tablet format is beneficial again as it’s much safer to handle and eliminates the risk of spillages. Handling these concentrated starting chemicals as solutions can be hazardous if spilled on skin due to the toxic and corrosive nature of the chemicals.

Chlorine dioxide differs from NaDCC products because it is a gas dissolved in a liquid. This means that when used to clean a surface, the gas readily diffuses out of the solution at a rate of 0.145 sqcm/sec resulting in inhalation of above WEL concentrations. Chlorine dioxide has similar toxicity to chlorine; respiratory problems, occupational asthma, headaches, and nose bleeds are a common complaint by cleaning staff using chlorine-based disinfectants.

This gas diffusion coefficient also results in inhibited efficacy, as demonstrated in a complete literature review by NHS Scotland.

Chlorine dioxide, like chlorine, is inhibited by soiled conditions regardless of the presence of detergent. It has a broad range of efficacy like all oxidisers; however, it is not particularly potent owing to its relatively low oxidation potential.

Pros Cons
Reasonably commonly used in hospitals 2-step cleaning required
Good efficacy in clean conditions Deficient in soil
Very good for use in water treatment Awkward preparation if solution is used
General structure of chlorine dioxide with unpaired electron

Chlorine dioxide

Peracetic Acid (PAA, “pre-formed PAA”, “traditional PAA”)

PAA is used in a wide range of high-level industries, from agriculture and food manufacturing to water treatments. It is known to be extremely effective even at very low strengths (~5ppm). PAA is usually a very strong liquid that holds unstable PAA at a very hazardous and corrosive 50,000ppm ready for diluting down. Large industrial sites have the facilities to accommodate this, however, healthcare environments typically do not. PAA also smells very vinegary and is often disliked by end users. This may result in preparing a weaker strength to counteract this.

PAA is highly effective and is minimally inhibited by soiled conditions. Unlike chlorine and chlorine dioxide, PAA acts as a nucleophilic catalyst, meaning it targets the nucleus of atoms, in this case, of amino acids, and catalytically breaks them down into their primary components. As it’s a catalyst, it then reconstitutes itself to continue to be effective, despite soiled conditions that would otherwise inhibit activity. In other words, it’s not “used up” in soiled conditions. This adds to its biocidal efficacy and ensures continuing activity throughout its use.

A key disadvantage of PAA is that it’s very corrosive to many materials and will readily degrade plastics and rubbers, largely in part to the stabilisers needed to maintain a very high concentration of a very unstable chemical for a shelf life of 12-24 months. As PAA is unstable, it will degrade after use to its non-harmful by-products of oxygen, water and acetic acid (which degrades into oxygen, CO2, and water), leaving no potential for bioaccumulation.

Because of these features, PAA is highly effective against C. difficile spores in very short contact times, making PAA a very desirable disinfectant for healthcare.

Pros Cons
Widely efficacious Corrosive
Environmentally friendly Difficult to use
Effective sporicide Vinegar smell
Peracetic acid molecule

Peracetic acid

In Situ Peracetic Acid (ISPAA)

ISPAA is a form of PAA that’s been developed more recently with the intention of overcoming the many issues associated with PAA, whilst retaining its excellent and broad-spectrum efficacy. ISPAA is generated from precursors held in a tablet or granule formulation that will react when dissolved in solution to form peracetic acid in situ. This method of generation is a step up from 0ppm to the desired ppm, rather than a step-down dilution, eliminating the need for additional COSHH assessments and health and safety requirements.

There are no reported respiratory issues or WEL set in the UK for peracetic acid, and the ISPAA format prevents any possibility of splashing or aerosolisation in preparation.

As there is no stock solution of PAA being held, there is minimal requirement for stabilisers, significantly reducing the corrosion properties associated. ISPAA can be tailored to contain a corrosion inhibitor to further minimise these effects. It’s also feasible to tailor ISPAA to contain perfumes, detergents and pH neutralisers to ensure a user-friendly and surface-friendly formulation with excellent cleaning and disinfection properties.

On the whole, ISPAA overcomes all issues associated with PAA and can be considered a “new generation” type of PAA.

Quaternary Ammonium Compounds (QACs)

QACs are diffusers that rely on a mechanism of action by which they diffuse across a membrane and then lyse the membrane from the inside. This is typically less efficient than oxidation as is reflected in contact times.

QACs commonly come as a pre-impregnated wipe or a concentrated stock solution. Wipes are a convenient format, but are not environmentally sustainable. This is for 2 reasons;

  • The wipes themselves are plastic and cannot be biodegradable (if they were to be made biodegradable, would simply degrade after prolonged contact with a biocide).

  • QACs themselves are large, synthetic molecules that readily bioaccumulate, and have been shown to accumulate to measurable and notable levels in the human body. This, plus surface accumulation, is at sufficient levels to result in antimicrobial resistance.

Since QACs are mildly effective and synthetic, it’s possible to tailor the formulation to be very usable, allowing the addition of surfactants for good cleaning properties and perfumes to improve odour. In summary, the range of use of QACs is average, with standard surface and environmental cleaning and some disinfection purposes. They are, however, not particularly or broadly efficacious.

Pros Cons
Convenient - wipes Bioaccumulates
Easy to perfume Leads to antimicrobial resistance
Quaternary Ammonium Compound

General structure of QACs
R groups are alkyl and aryl substituents
X is a halogen such as chlorine or bromine