Inhospitable to bacteria

Healthcare Associated Infections (HCAI) continues to be a problem globally. In the UK, since 2009 monitored organisms such as Clostridium difficile and MRSA have displayed marked reductions in associated patient infections. These reductions are attributed to improved clinical and public awareness of infection control as well as improved implementation of these control measures.
   
Hand washing, spatial and temporal control of infected personal (and articles) have all largely contributed. Penalties for non-compliance with HAI targets can be severe. Although the figures are moving in the right direction reductions of HAIs should persist.
   
When existing control measures have been optimised alternate mechanisms for the control of pathogenic bacteria in hospital environments should be explored, to ensure numbers for hospital acquired infections continue to fall and future patient health is continued to be safeguarded. One such option is the integration of antimicrobial additives into polymers or other materials to imbue them with properties which make surfaces inhospitable to bacteria and other microorganisms.

Environmental microorganism control
Control of bacteria in the hospital usually takes place via the use of antimicrobial agents of varying efficacy depending on the hygienic requirements of the environment. Highly efficacious cleaning agents utilising, for example strong oxidising agents, may offer both bactericidal and sporicidal solutions but can, in the long term, provoke material damage.

Common disinfectant active substances based on quaternary ammonium compounds can provide immediate antibacterial action, but residual effects are limited due to evaporation or removal from disinfected surfaces and the risk of subsequent recontamination. There is then, the continuous requirement for knowledge of appropriate cleaning and disinfection products within the hospital environment to ensure use of chemical products is optimal for both controls of problem organisms, and to protect surfaces from material damage. Bacterial populations are displaying increased resistance to disinfectants based on quaternary ammonium salts (QUATs) and that resistance to QUATS may evoke further resistance to antimicrobials such as antibiotics. Despite these concerns, disinfectants remain the primary non-antibiotic medicated control mechanism for areas of hygiene concern.

Integrated protection
Inorganic agents such as silver are evidenced to provide long lasting effective antimicrobial effectiveness. By deploying such technology as a manufacturing additive, materials which can usually support microbial growth can be imbued with antimicrobial properties and provide protection from microbial growth. Although the antibacterial effects of silver have been known since ancient time’s deployment of these materials antimicrobial properties as additives is relatively new. This technology is increasingly understood, and its potential beginning to be realised, in sectors including food production/packaging, medical environments and the home.

Safe use of antimicrobial products
Biocidal products including antimicrobials are regulated globally, to protect humans and the environment from substances which may pose a risk. In the EU, control of biocidal product use and sale is achieved via the Biocidal product Regulation, and in the US via FIFRA (Federal Insecticide, Fungicide, and Rodenticide Act) under the justification of the Environmental Protection Agency (EPA).
   
Biocides when incorporated into plastics can be considered ‘treated articles’- that is articles which have been treated with a biocidal substance but are not actually biocidal products. This classification waives many of the regulatory requirements present for biocidal products and active substances. Within the EU, treated articles and are indirectly regulated through the requirement for treated article labelling information which specifies information should be provided relating to the nature of the active substance utilised.
   
This labelling requirement was put in place to protect people and the environment from the effects of hazardous substances which when incorporated into articles may evade chemical compliance monitoring systems.

Testing/proof of efficacy
One of the requirements for making a biocidal or indeed antimicrobial claim within the EU is substantiation. We should then be able to backup any claim we make for a treated article or product. Antimicrobial polymers are usually assessed via the international standard ISO22196 Measurement of antibacterial activity on plastics and other non-porous surfaces. Testing to this standard allows generation of reproducible and comparable results when assessing the antibacterial properties of products incorporating an antimicrobial substance.

Pathogenic (disease causing) microorganisms
Bacteria can be broadly divided into two groups, Gram positive and Gram negative, and this division is based on the structure of the bacteria’s cell wall (external membrane). This grouping also gives excellent indication of the innate properties of these organisms. 
   
Both Gram positive and Gram negative bacteria contain species which cause major issues in healthcare. MRSA, which is a multi-drug resistant variant of the Gram positive Staphylococcus aureus, is perhaps the most infamous. This organism is responsible for a range of complications such as skin infections and more seriously blood infections. Klebsiella pneumonia is another significant problem in the health care environment, causing a range of problems including pneumonia as well as a variety of other disease such as surgical wound infection. The Gram negative Klebsiella pneumonia is also further complicated by widespread multi drug resistance, with CRE (Carbapenem-resistant Enterobacteriaceae) resistant to many antibiotics of the penicillin family.
   
In the UK, the problem of multi drug resistant E.coli increases, with Extended Spectrum Beta Lactamase (ESBL) bacteria providing another example of multi drug resistance problems in a healthcare setting. ESBL E. coli are perhaps best known for disease related to the urinary tract and can be a problem related to catheters.
   
Antimicrobials such as silver work in a different manner to traditional actives present in disinfectants as well as antibiotics. Silver, in an ionic state, exerts multiple deleterious effects on the microbial cell including damage to the cell wall/envelope, protein denaturation, potential DNA damage and general free radical mediated toxicity. With no specific site of attack (which is, for example, the means by which antibiotics exert their antibacterial action) evolution of resistance is considerably difficult, with no significant clinically significant resistance reported.

A need for antimicrobial polymers?
Articles within the hospital environment are known to harbour pathogenic bacteria or other microbes for extended periods of time. The H1N1 virus genome has been reported to survive on surfaces for as long as 24 hours (3). A recent study examined various articles within an operating room and measured percentages of these articles which harboured bacteria. 23.3 per cent yielded growth, whilst 57 per cent of these organisms were identified as clinical pathogens.
   
Long term persistence of bacteria is also a problem. Bacteria such as Enterococcus spp. (including VRE another multi drug resistant pathogen Staphylococcus aureus (including MRSA) are evidenced to survive for many months on hard surface. Gram negative species such as Actinobacteria, E.coli, Pseudomonas spp. and Klebsiella spp. are also reported to survive for extended periods.
   
In another study, during a two year assessment, a total of 290 environmental samples were analysed, in three different wards. The percentage of equipment in each ward that displayed contamination level varied between 22 per cent and 38 per cent, and more than 50 per cent of the equipment sampled was highly contaminated. P. aeruginosa was repeatedly isolated from sinks (10 times), from the taps’ biofilm (16 times), and from the showers and bedside tables (twice).
   
Effective cleaning and disinfection as well as patient and staff awareness of infection control measures remains the primary method of action for control of environmental contamination. Working alongside these measures, integrated antimicrobial protection can provide a second line of defence against the effects of contamination of articles and surfaces both within the hospital environment and in any hygiene sensitive location generally.

Having material which performs well in laboratory based antimicrobial results for antimicrobial incorporating materials is the first stage in validating any associated claims for an antimicrobial product. Although these test requirements have stringent conditions and procedures by which the tested material and organisms are subjected, the question of how treated materials may perform in the ‘real world’ is a common one.
   
BioCote have published a series of case studies which address the concern of how antimicrobial surfaces behave in environments including, but not exclusive to, healthcare. A peer reviewed study, published in the Journal of Infection Prevention demonstrated a 95.8 per cent reduction in bacteria between two wards, where ‘ward A’ contained BioCote treated products and ‘Ward B’ contained non treated products. BioCote have also performed a similar study in a care home, demonstrating a 94.8 per cent reduction in total microorganism counts when comparing a unit with and without BioCote treated products.

BioCote have also demonstrated antiviral performance of treated surfaces, proving the ability of BioCote technology incorporated into a variety of substrates such as polycarbonate and ABS to deactivate the Influenza H1N1 virus by up to 99.99 per cent. A further study demonstrates visually, via epiflourecent microscopy and molecular dyes, the ability of BioCote’s antimicrobial technology to inhibit biofilm formation of treated plastic.
   
These case studies, plus others, can be download at www.biocote.com/library

Antibiotic resistance – AM polymers a part of the answer?
The concern over antibiotic resistant bacteria continues to grow. Current statistics shown in the UK antibiotic prescription actually increased by six per cent between 2010 and 2013, and consequent the target is to bring prescription levels back down to their 2010 levels. As reported numbers of AMR bacteria continue to grow and the discovery void for new drugs, in the short term, is persisting the pharmaceutical industry must (perhaps with government or other bodies assistance) act. 
   
The discovery of the new drug teixobactin has raised hopes, however in world where methods to control multi drug resistance pathogenic bacteria are more limited, the exploration of integrated antimicrobial protection in surfaces in a health care environment should be explored.

Further information
www.biocote.com