Disinfectant resistance: A serious threat to public health
Disinfectants are one of the most widely used forms of protection against infection by pathogens, in addition to biosecurity; however, their misuse can have undesirable consequences. Bacterial strains can develop resistance using the same mechanisms employed against antibiotics. Globally, the morbidity and mortality caused by nosocomial infections are continuously rising and are associated with resistance to disinfectants. The WHO has shown that in healthcare facilities where good infection prevention and control practices are followed, 70% of these can be prevented.
The abusive and inappropriate use of disinfectants constitutes a factor in the increase of resistance genes to antibiotics and disinfectants, respectively. Disinfectants diluted and released into the environment could increase bacterial tolerance through phenotypic adaptation, gene mutation, and horizontal gene transfer.
How does microorganism resistance to disinfectants occur?
Resistance to disinfectants can occur through several mechanisms. Some microorganisms can transfer resistance genes to disinfectants among themselves, allowing for the spread of this resistance across diverse microbial populations. The reasons that can lead to increased resistance are as follows:
Number and location of microorganisms
The higher their number, the longer the disinfection time required. Microbiologist Earle Spaulding demonstrated that it took 30 minutes to kill 10 spores of Bacillus atrophaeus (Bacillus subtilis) and 3 hours to kill 100,000 spores of B. atrophaeus. Therefore, the prior cleaning operation is very important, as it significantly reduces the number of microorganisms and shortens the exposure time required to destroy the entire microbial load, thus increasing the margin of safety. It is proven that aggregated cells are harder to destroy than monodispersed cells.
Medical instruments with multiple parts that must be disassembled, and endoscopes that have cracks, joints, and channels, are more difficult to disinfect than equipment with flat surfaces because the penetration of the disinfectant into all parts of the equipment is more difficult. There must be no air gaps, and the equipment must be completely submerged for the entire duration of exposure. Hard-to-reach areas are exposed to lower concentrations of disinfectant, allowing less sensitive strains to survive.
Innate resistance of microorganisms
Spores are resistant to disinfectants because their coat and cortex act as a barrier; mycobacteria have a waxy cell wall that prevents the entry of the disinfectant, and gram-negative bacteria possess an outer membrane that acts as a barrier to disinfectant absorption. With the exception of prions, bacterial spores possess the highest innate resistance to chemical disinfectants, followed by coccidia (e.g., Cryptosporidium), mycobacteria (e.g., M. tuberculosis), non-lipid or small viruses (e.g., Poliovirus and Coxsackievirus), fungi (e.g., Aspergillus and Candida), vegetative bacteria (e.g., Staphylococcus and Pseudomonas), and lipid or medium-sized viruses (e.g., herpes and HIV).
Concentration and potency of disinfectants
The more concentrated the disinfectant, the more effective it is and the shorter the time required for microbial destruction (exception: iodophors). The potency of the disinfectant is also important. Spaulding demonstrated that 70% isopropyl alcohol destroyed 104 M. tuberculosis in 5 minutes, while a simultaneous test with 3% phenol required 2-3 hours to achieve the same level of microbial destruction.
Physical and chemical factors (temperature, pH, relative humidity, and water hardness)
An increased temperature helps increase the activity of most disinfectants, but sometimes, an excessive increase degrades the disinfectant, reducing its potency.
An increased pH increases the activity of glutaraldehyde and quaternary ammonium compounds, but decreases that of phenols, hypochlorites, and iodine.
Relative humidity influences the activity of gaseous disinfectants, such as ethylene oxide, chlorine dioxide, and formaldehyde.
Water hardness decreases the effectiveness of certain disinfectants because divalent cations in hard water (magnesium, calcium) interact with the disinfectant and form insoluble precipitates.
Organic and inorganic matter
Organic matter (serum, blood, pus, etc.) influences the activity of disinfectants through a chemical reaction, resulting in a complex with low efficacy. Usually, chlorine- and iodine-based disinfectants are targeted. Another mechanism is that organic matter acts as a physical barrier.
Inorganic matter influences the activity of disinfectants through the formation of salt crystals, an aspect studied since 1950.
Once again, this demonstrates the importance of the cleaning process, which easily removes these two types of matter.
Duration of exposure
The minimum contact times specified by the manufacturer must be respected; otherwise, there is a risk of the disinfectant losing its effectiveness. In general, longer contact times are more effective than shorter ones.
Biofilms
These are microbial clusters tightly attached to surfaces that cannot be easily removed. They are found in the water supply lines of dental units, in medical devices such as pacemakers, hemodialysis systems, urinary catheters, venous catheters, contact lenses, etc. Bacteria in biofilms are up to 1,000 times more resistant to antimicrobials than the same bacteria in suspension. They can be resistant to disinfectants through multiple mechanisms, including genotypic variation of the bacteria, microbial production of neutralizing enzymes, and physiological gradients within the biofilm, such as pH. Chlorine, chloramine, and peracetic acid have proven their effectiveness in inactivating biofilm bacteria.
How do we measure the efficacy of disinfection?
By using a logarithmic scale to show the relative number of microorganisms eliminated by the disinfectant, starting from 1 million.
1-LOG: destroys 90% of microorganisms, leaving 100,000
2-LOG: destroys 99% of microorganisms, leaving 10,000
3-LOG: destroys 99.9% of microorganisms, leaving 1,000
4-LOG: destroys 99.99% of microorganisms, leaving 100
5-LOG: destroys 99.999% of microorganisms, leaving 10
6-LOG: destroys 99.9999% of microorganisms, leaving 1
To be sure of the disinfectant's efficiency, it is recommended that it offer at least a 4-LOG destruction of microorganisms. A 6-LOG reduction rate is the most effective, representing almost sterilization.
Between 2017 and 2019, an epidemiological study was conducted by the Department of Epidemiology, IP USMF Nicolae Testemițanu, analyzing the sensitivity/resistance to disinfectants of 40 strains of microorganisms from 17 species (S. aureus, S. epidermidis, S. haemolyticus, E. faecalis, E. faecium, S. liquefaciens, C. freundi, P. rettgeri, E. coli, E. aerogenes, K. oxytoca, P. aeruginosa, K. pneumoniae, P. mirabilis, B. cepacia, A. baumanii, P. fluorescens). The researched strains were isolated from patients with septic-purulent infections (SPI) who were hospitalized within the republican-level medical institution. 16 types of disinfectants from the following groups were used: oxidants, alcohols, aldehydes, quaternary ammonium compounds – QAC, QAC+aldehydes, QAC+amine, chlorine compounds.
High resistance to disinfectants was highlighted in gram-positive strains (35.77%), including E. faecalis (76.93%), E. faecium (46.15%), and S. aureus (38.63%). The sensitivity of the strains varied between 18.75% and 95.12%. High sensitivity values were observed for oxidants (83.10%), alcohols (85.40%), and aldehydes (93.75%), while resistance was observed for quaternary ammonium compounds (QAC) (58.50%), QAC+amines (40.0%), chlorine compounds (37.50%), and QAC+aldehydes (34.15%).
Periodic evaluation of the sensitivity/resistance of microorganisms to disinfectants frequently used in healthcare facilities is necessary to monitor efficacy and to continue making the best decisions for the prevention of nosocomial infections.
Bibliography:
- https://www.cdc.gov/infectioncontrol/guidelines/disinfection/efficacy.html
- https://www.cleanroomtechnology.com/news/article_page/Avoiding_disinfectant_resistance/206586
- https://theconversation.com/how-does-resistance-to-disinfectants-happen-were-on-the-road-to-answering-the-question-155752
- https://www.sciencedirect.com/science/article/abs/pii/S0013935121001912
- Diana Spătaru – Assessment of sensitivity/resistance of nosocomial strains to disinfectants, IP Nicolae Testemițanu State University of Medicine and Pharmacy
