Antibiotic and Antimicrobial Resistance: Everything we do (and don't) know
Antibiotic resistance is a major concern for healthcare professionals, particularly in regards to the types of cleaning products used in medical settings. Antibiotic resistance refers to the ability of pathogens to develop a resistance to things that would attempt to kill them--similar to a shield of defense. This means it can be extremely difficult to disinfect areas that have been contaminated with antibiotic resistant bacteria. In light of the COVID-19 pandemic, this has become an even greater concern to the medical and scientific community for two reasons: First, the increased use of antimicrobial and biocidal disinfectants could have unintended consequences by increasing bacterial resistance. Secondly, the inappropriate overprescribing of antibiotics may cause further antibiotic resistance.
What is the difference?
Antibiotic and antimicrobial resistance are similar but different. Antimicrobial resistance is the response of microbes, fungi, or viruses to solutions meant to kill them. These microbes naturally develop resistance as part of their defense mechanism after repeated exposure to a specific antimicrobial agent. It is important to note that no disinfectant is immune to antimicrobial resistance, although some disinfectants are easier to develop resistance to than others.
Antibiotic resistance occurs after an antibiotic has been used to treat a bacterial infection. Like antimicrobial resistance, this process also occurs slowly and over repeated exposure, but is often caused by human action. The most common causes are the over-prescribing of antibiotics to humans and the pervasive and preventative treatment of animals with antibiotics.
Antimicrobial resistance has been shown to contribute to antibiotic resistance in some cases, as both mechanisms interact with similar genes. However, the level of correlation between antimicrobial and antibiotic resistance is currently unknown.
Resistance and Hypochlorous Acid
While disinfectants can contribute to antimicrobial resistance, they do not cause antibiotic resistance. Some researchers conclude that antimicrobial resistance is inevitable when microbes are exposed to specific disinfectants over an extended period of time. Pathogens, just like all other living organisms, are made to adapt and survive. In particular, the research shows that repeatedly exposing pathogens to low levels of disinfectants (doses that fall below the lethal bactericidal concentration) have been more likely to trigger antimicrobial resistance. It is important to distinguish between the minimum quantity of a disinfectant needed to inhibit a pathogen, and the minimum quantity needed to achieve pathogen death (eg; 3 Log 10 reduction). In these cases, the research suggests using a disinfectant that can achieve pathogen death quickly and effectively is the best option to avoid the development of microbial resistance.
The research on the correlation between hypochlorous and antimicrobial resistance is still young. It is well-known that oxidizers (such as HOCl) generally cause irreversible damage to bacterial cells. Some studies have shown that HOCl can induce biofilm production in gram negative (non-enveloped) bacteria. Bacteria produce biofilm as an extra layer of protection. This biofilm layer can contain bacterial cells that are 100-1000 times more resistant to antibiotics than the host bacteria. However, there is also substantial scientific evidence showing HOCl's efficacy as a biofilm eliminator.
Only a few bacterial mechanisms that are specific to combatting HOCl have been identified. Researchers have found 3 transcriptional regulators (proteins involved in DNA gene expression) and 4 chaperone holdases (protein protectors) present in bacteria that are specific to combatting HOCl. Salmonella and E. coli have been found to develop a resistance to sodium hypochlorite (bleach). This resistance has been infrequent, and hypochlorite is also known to reduce antibiotic resistant genes by about 1 Log. Some research suggests that higher concentrations of chlorine in wastewater (2-32 mg/L) could decrease the quantity of antibiotic resistant genes accordingly.
In conclusion, there is still much we don't understand about how bacteria defends itself against a disinfectant attack. As tempting as it may be to generalize, or claim that bacteria can never develop a resistance to HOCl, that may not be true. What we do know is that HOCl is the most effective form of chlorine against pathogens, and as a strong oxidizer, is one of the most difficult disinfectants for bacteria to develop a defense response to. And if ineffective disinfection only contributes to bacterial resistance, then using a highly effective disinfectant like HOCl that can quickly inactivate bacteria without harmful health or environmental consequences is one of the best options.
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