{"id":57919,"date":"2024-06-25T11:48:26","date_gmt":"2024-06-25T11:48:26","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=57919"},"modified":"2024-07-03T16:47:34","modified_gmt":"2024-07-03T16:47:34","slug":"quaternary-ammonium-disinfectants-current-practices-and-future-perspective-in-infection-control-review-article","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no2\/quaternary-ammonium-disinfectants-current-practices-and-future-perspective-in-infection-control-review-article\/","title":{"rendered":"Quaternary Ammonium Disinfectants: Current Practices and Future Perspective in Infection Control: Review Article"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Microbial diseases have compromised human\nwell-being for a long time and will continue to do so, due to constant\ndevelopmental changes such as mutations.1<\/sup> These microbes become even\nmore deadly when they are obtained from clinics or medical institutions. The\ninfections caused by such microbes are termed Hospital Acquired infections\n(HAIs), which a patient or his associate gets during his tenure in a hospital\nor any other healthcare facility & that were absent at the time of\nadmission.2,3<\/sup>  HAIs become\nfatal because of excessive invasive devices, immunosuppressive drugs, and the frequent\nuse of inappropriate antimicrobial therapy.4 <\/sup> Several factors are reported to\ncontribute to HAIs like healthcare-associated factors, patient-related factors,\nand environment-related factors (Figure 1.0). Patients with acute illness\nparticularly in high-risk areas like Intensive care units, burn units,\ntransplant operation theatres, etc. are highly prone to get these infections due\nto contaminated hospital environments or the fomites which come in contact with\nthe patient directly or indirectly.4<\/sup>  <\/p>\n\n\n\n

To prevent HAIs, cleaning, disinfection, and\nsterilization are the most important control measures. Cleaning is a process\nthat involves washing (soap and water) and scrubbing to remove the filth,\nbioburden, and soil by physically removing organic matter, although it may not\nalways kill the germs. Disinfection on the other hand is a process of making an\nobject microbe free except spores with the use of chemicals known as\ndisinfectants. Sterilization destroys or eliminates all forms of microorganisms\nincluding bacterial spores. It employs both physical and chemical methods.5   <\/sup>The\nleading infection control and prevention guidelines also highlight the role of cleaning\n& disinfection in the control of nosocomial infections.6,7<\/sup><\/p>\n\n\n\n

However, research studies have reported that\ncleaning and disinfection are not sufficient to eliminate microbial loads.8-10<\/sup>\nContaminated surfaces and patients shed different microorganisms, and these\norganisms survive for longer duration on hospital surfaces.11,12 <\/sup> The concentration of these pathogens is\nadequate for transmission for an expanded duration. It is well-reported that environmental surfaces with microbial\ncontamination and related factors contribute significantly to the endemic and\npandemic exchange of potential microbes.13 <\/sup>Removal of microbial\nloads from the hospital environment is the major tool in controlling nosocomial\ninfections.14 <\/sup> However inefficient,\nirrational use of disinfectants and further challenges in the measurement of\nefficacy standards compromise the actual efficacy in practice and contribute to\nthe increase in the HAIs.   <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: <\/strong>Various factors associated with the cause of HAIs<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Epidemiology of HAIs<\/strong><\/p>\n\n\n\n

Infections from\ncontaminated environments have been well established. Various outbreaks have\nprovided proof that patients get infected by the healthcare-contaminated\nenvironment and surface inside.15<\/sup> As per World Health Organization\n(WHO) report, approximately 15% of total patients hospitalized worldwide suffer\nfrom HAIs. These infections are accountable for 4% – 56% of neonate deaths,\nwith an incident percentage of 76% in Africa and South-East Asia.2  <\/sup> In the US alone, HAIs involve yearly about 2\nmillion people and account for financial losses of approximately 4.5 billion\ndollars. In India and other developing nations, the issue of HAIs is\nsignificantly higher prompting well-being and money-related misfortunes.16   <\/sup>In 2014, CDC published a survey report on the prevalence of HAIs in the United\nStates involving 11282 patients from 183 healthcare facilities. It was reported\nthat approximately 4% of patients admitted to hospitals suffered from at least\none type of HAIs.  The major HAIs reported are Surgical site infections,\nGastrointestinal infections, Pneumonia, Urinary tract infections, and primary\nbloodstream infections including Catheter-associated bloodstream infections\nwith occurrence rates as 21.8%, 21.8%, 17.1%, 12.9%, and 9.9% respectively.17\n <\/sup>In India, a research study\nreported 33.6% of hospital-acquired urinary tract\ninfections in catheterized patients.18 <\/sup><\/p>\n\n\n\n

Disinfection & QACs <\/strong><\/p>\n\n\n\n

Disinfection is the cycle by which an article is liberated from the\npathogenic microbial entities except for spores by utilizing chemical compounds\nknown as disinfectants. Some disinfectants, known as chemical sterilant, also\ndestroy spores with long exposure times and are known as high-level\ndisinfectants.6-7<\/sup>  Cleaning\nwith cleaners and disinfectants plays a crucial role in the treatment of\nmicroorganisms, but the difficulties with estimating efficacy approaches have\nimpaired the real outcomes in practice.10,<\/sup> 13,<\/sup> 19<\/sup>  Every\ndisinfectant has its advantages and disadvantages and should be chosen based on\nits intended use or application. The normal characteristics of an ideal\ndisinfectant incorporate i) Broad spectrum efficacy; ii) user-friendly; iii)\nNon-corrosive and nature friendly.7,19,20<\/sup> Different chemical\ndisinfectants are currently used for disinfection like Alcohol; Oxidizing\nagents; Halogens; Aldehyde; Phenolic and QACs (Table 1.0). <\/p>\n\n\n\n

Table 1: List of chemical disinfectants with advantages and disadvantages<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

Chemical disinfectants groups<\/strong><\/p>\n<\/td>\n

\n

Advantages \/disadvantages<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Alcohols<\/strong><\/p>\n<\/td>\n

\n

Good skin disinfectants, should not be used on surfaces as they are flammable and reacts with different surface types. Like it tends to swell or harden the rubber <\/p>\n<\/td>\n<\/tr>\n

\n

Phenolics<\/strong><\/p>\n<\/td>\n

\n

Phenols are mild disinfectants for inanimate surfaces<\/p>\n<\/td>\n<\/tr>\n

\n

Halogens<\/strong><\/p>\n<\/td>\n

\n

Halogens include chlorine-generating compounds and iodine-based compounds. Chlorine generating compounds are the most economical but produce health hazardous fumes. Iodine and Idophores are weak disinfectants for inanimate surfaces and are commonly used as skin disinfectants<\/p>\n<\/td>\n<\/tr>\n

\n

Aldehydes<\/strong><\/p>\n<\/td>\n

\n

Aldehydes like formaldehyde, Glutaraldehyde, and Orthophthaldehyde (OPA) are considered to be high-level disinfectants but are toxic to users and the environment<\/p>\n<\/td>\n<\/tr>\n

\n

Oxidizing agents<\/strong><\/p>\n<\/td>\n

\n

Hydrogen peroxide, Superoxide water, and Peracetic acid are wide spectrum and fast antimicrobial agents but are corrosive (May rust metallic material like aluminum separation and metallic instruments, etc.)<\/p>\n<\/td>\n<\/tr>\n

\n

Quaternary ammonium compounds (QACs)<\/strong><\/p>\n<\/td>\n

\n

QACs based disinfectants are being used most in the healthcare sector, not only as good cleaners but also as good disinfectants. These disinfectants are user friendly<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Out of all these chemicals disinfectants\nQACs are being used extensively in the hospitals and healthcare industry due to\ntheir advantages which make them good disinfectants. The QACs are\nsubstituted ammonium compounds having a nitrogen atom in the center with a valency\nof five. Out of which four (R1 \u2013R4) are the substituted radicals i.e.\nHeterocyclic radicals or alkyl chain and the fifth (X–<\/sup>) is a halide,\nsulfate, or similar radical (Figure 2.0).7,19,20<\/sup><\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Basic structure of Quaternary ammonium compounds.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

QACs were first presented in 1916 when Walter A. Jacobs tried\nmodifying the hexamethylenetetramine molecule synthetically with the intent to\nget a new molecule having bactericidal properties.21<\/sup> <\/sup> It was demonstrated that the level of\nbactericidal activity was inferable from character, position, and the number of\ngatherings substituted in the benzene core.22<\/sup>  In 1935, it was reported by  G Domagk that the antimicrobial properties of\nQACs were not limited to the Hexamethylenetetramine molecule only.23   <\/sup>This threshold-breaking research paved\nthe way for the commercial application of QACs in antimicrobial use.  <\/sup>QACs are considered broad-spectrum antimicrobials\nbut are not sporicidal.24 <\/sup> <\/em>These compounds are effective against gram-positive\nand gram-negative bacteria, fungi, and viruses.25-27 <\/sup>Broad-spectrum\nantimicrobial properties and user-friendly properties make QACs an ideal choice\nfor disinfectants. However, there are controversies in the literature\nsupporting the claim that QACs can be used as sporicidal agents.28<\/sup> The\nuse of QACs is not limited to disinfection but is also being used in paints,\ncosmetics, agriculture, and other household products. For the extensive useful\nproperties, the QACs use has increased over the decades. The total production\nof QACs in the US in 1945 was about 3 million pounds, which increased to 7787\nmillion pounds in 1993 29<\/sup>.  <\/p>\n\n\n\n

Development of new-generation\nQACs <\/strong><\/p>\n\n\n\n

The introduction and commercial application of the QACs led to the\nlarge-scale use of these disinfectants in various fields.  It was found that the efficacy of the QACs\nwas better than the other disinfectants available at that time. In an efficacy\nstudy conducted on higher-order alkyl dimethyl benzyl ammonium chloride against\nS. aureus<\/em> and E. coli,<\/em> it was reported that QACs were more effective for gram\npositives than gram negatives and were also better in efficacy than other\ncommercially available disinfectants.30-32  <\/sup>Another study reported that QACs (Cetyl\nPyridium Chloride) was microbiocidal at higher dilutions under both acidic and\nalkaline conditions. The nontoxic behavior of the investigated QACs compound\nand its germicidal properties at various conditions made QACs exceptionally\nuseful & versatile disinfectants.33<\/sup> <\/p>\n\n\n\n

Resistance towards QACs<\/strong><\/p>\n\n\n\n

Exceptionally broad-spectrum antimicrobial properties and nontoxic\nbehavior of QACs resulted in wide-scale heavy use in the healthcare sector as\ndisinfectants. However, the overuse of QACs led to the emergence of anti-microbial\nresistance towards QACs. A study in 1952 by CE Chaplin demonstrated resistance\ntowards QACs. It was concluded that the acquired resistance was dependent on\nthe increased lipid contents of the cell wall of the microorganism.34<\/sup>\n Another study reported that P. aeruginosa<\/em> could not only survive but\neven multiply in Benzalkonium chloride solutions containing ammonium acetate\nbuffer.35<\/sup>  A similar study\nreported that at 200 \u03bcgml\u22121<\/sup> of benzalkonium chloride, 30% of the\nstrains were able to grow.36 <\/sup> To tackle the challenge of antimicrobial\nresistance towards QACs, manufacturers introduced newer and higher generation\nQACs in the next decades.37 <\/sup> These newer generation QACs were termed first,\nsecond, third, fourth, fifth, and so on.<\/p>\n\n\n\n

Antimicrobial activity of higher generation QACs disinfectants: <\/strong><\/p>\n\n\n\n

Literature suggests that newer-generation QACs were more effective than the previous ones. Several studies reported higher generation QACs to be less toxic than the previous ones, being active in hard water and showing higher efficacy. A study on two higher-level QACs disinfectants showed that both disinfectants were effective against all tested microorganisms except Bacillus subtilis<\/em> and the resistant strain of P. aeruginosa.<\/em>38   <\/sup>Another study tested the antimicrobial efficacy of disinfectants used in hospitals in India against MRSA, Enterobacter aerogenes, Klebsiella pneumoniae, Multidrug-resistant Acinetobacter baumannii, <\/em>and P. aeruginosa.<\/em>  Results demonstrated that the use of less toxic QACs in comparison to formaldehyde with mist spray agents was a good option for making the hospital environment free from microbes. For heavy contaminations, aldehyde and new QACs formulations were found to be the best disinfectants.39 <\/sup>Another study on third generation QACs showed that QACs disinfectants were as effective as formaldehyde and could be considered effective disinfectants and sterilization agents.40,41 <\/sup>Similar studies were conducted on the 5th<\/sup> generation QACs disinfectants and it was found that 5th<\/sup> generation QACs have higher efficacy than the 3rd<\/sup>  generation. Pirsaheb et al.<\/em> reported that 4th<\/sup> and 5th <\/sup>generation QACs disinfectants had higher efficacy as compared to other chemical disinfectants.42<\/sup>I\u00f1iguez-Moreno et al.<\/em> (2017) studied the antimicrobial activity of disinfectants commonly used in the food industry and reported that efficacy increases with the advancement of generation i.e. 5th<\/sup> generation QACs had higher efficacy than 3rd<\/sup> generation.43<\/sup> <\/p>\n\n\n\n

The sporicidal activity of QACs<\/strong><\/p>\n\n\n\n

As per the guidelines issued by CDC & National Center for disease\ncontrol, India (NCDC), QACs are non-sporicidal\nagents. A study conducted against C.\ndifficile<\/em> showed the poor sporicidal activity of QACs, validating the point\nmentioned in the guidelines.44<\/sup> \nIn another similar\nstudy, Deshaies et al. <\/em>(2018) tested 3rd<\/sup> and 4th<\/sup>-generation\nQACs disinfectants against C.<\/em> difficile <\/em>spores at recommended and\nhigher concentrations. None of the disinfectants showed sporicidal activity.45<\/sup>\n<\/p>\n\n\n\n

Quaternary ammonium compounds and COVID 19<\/strong><\/p>\n\n\n\n

Though QACs are in use for a long time, a significant rise in the\nconsumption of QACs was seen during the COVID-19 pandemic.46   <\/sup>The\nUnited States Environmental Protection Agency (USEPA) also highlighted the role\nof QACs disinfectants for COVID-19 prevention.47,48 <\/sup>A study reported\nthe virucidal efficacy of QACs against SARS-CoV-2 on treated surfaces in the\nyear 2021. It was found that the use of QACs led to a decrease in\ncommunicability and fomites transmission of SARS-CoV-2.29<\/sup> Another study\nby Marteinson et al.<\/em> (2022) reported that out of all disinfectants used in\nCanada during COVID-19, 80% of the disinfectants were QACs.The common QACs were Benzalkonium chloride (32%), alkyl dimethyl\nethyl benzyl ammonium chloride (17%), and didecyl dimethyl ammonium chloride\n(8%).49<\/sup> Despite large-scale usage of QACs disinfectants  few authors believe that the effectiveness of\nQACs against corona viruses must be evaluated using standard protocols.29<\/sup> <\/p>\n\n\n\n

Quaternary ammonium compounds, antimicrobial efficacy methods &\ngaps:<\/strong><\/p>\n\n\n\n

Existing literature has shown that the efficacy of most of the QACs disinfectant is performed using traditional methods like the Phenol coefficient method, Suspension method, swab method, or glass slide method. In another study, QACs were found effective when tested for germicidal efficacy against M. candidus, S. aureus, B. panis<\/em> vegetative spores, gram-negative E. coli <\/em>& Pseudomonas aeruginosa<\/em> using the glass slide method. On similar lines,  when the bactericidal efficiency of QACs was evaluated using the phenol coefficient method, these compounds were found to be bactericidal.50 <\/sup> In a similar study using the phenol coefficient method, the bactericidal efficiency of quaternary ammonium compounds was evaluated and these compounds were found to be bactericidal.51 <\/sup> Sadly,  the authenticity and reliability of these methods are in question due to lack of standardization of the efficacy methods.32,52-54<\/sup> Studies done by different researchers have shown contra-indicatory results concerning the efficacy of QACs. Pirsaheb et al.<\/em> (2016)  tested the efficacy of QACs using the traditional phenol coefficient method and the swab method. It was found that QACs have phenol coefficients <1  indicating the QACs disinfectants as weak disinfectants, while when tested in actual practice in laboratory conditions using swab methods, QACs disinfectants showed the best results.42 <\/sup> Contrary another study by Eyo et al.<\/em> (2018) demonstrated the non-effectiveness of tested QACs using the use-dilution test that was having highest phenol coefficient.55 <\/sup>Research studies have emphasized that selecting the right and effective product is very difficult due to the varieties of products, various claims by the manufacturers, and contraindicatory reports from literature.56 <\/sup>Though there is a lack of standardized methods, looking at the need of the hour, newer QACs are being synthesized.  Further, besides the discrepancies in testing methods, it has been reported that manufacturers use false claims on labels to promote and enhance sales Hence, better testing standards with strict guidelines for verifying the antimicrobial spectrum of these compounds are of utmost importance.57, 58 <\/sup>Literature also suggests that such data needs to be verified by independent investigations. Further, there is an urgent need to establish uniformity in the methods to evaluate the effectiveness of the QACs for their proper and effective utilization. In this context, newer standardized methods were developed by standard\/ harmonized organizations like the European Committee for Standardization (CEN) and the Association of official analytical collaboration (AOAC) International.59, 60<\/sup><\/p>\n\n\n\n

Newer standardized international methods<\/strong><\/p>\n\n\n\n

The antimicrobial efficacy of any disinfectant depends on different factors, which include the Initial microbial inoculum, Experimental conditions, Neutralizer, its toxicity, and the method used.61 <\/sup> Newer Standardized methods like EN (European norms) standards or AOAC international methods should be utilized for disinfectant efficacy as these methods are refined and harmonized.62,63 <\/sup>These methods include various validation steps like validation of microbial suspension, Validation of neutralizer, Validation of method, and other experimental conditions. Validation of Microbial suspension includes verification of the required number of microbes to be used in the disinfectant efficacy. Validation of the neutralizer includes the selection of the suitable neutralizer and verification of neutralizer toxicity. A good neutralizer should be non-toxic to the microbes and able to neutralize the carry-over effect of the disinfectants. Validation of method and experimental conditions involves the verification of the method and the experimental conditions in which the test is to be conducted. Efficacy results with these methods are more realistic than the traditional methods.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

The incidence of hospital-acquired infections (HAIs) are increasing. These infections become more fatal due to the use of invasive devices, immunosuppressive drugs, and the frequent use of inappropriate antimicrobial therapy. A practical measure to lower or control the HAIs is proper cleaning and disinfection. The use of Quaternary ammonium compounds (QACs) has gained a lot of attention in this context, especially during the COVID times. However, the lack of standardized methods to evaluate the efficacies of QACs is playing a major hurdle in the appropriate use of QACs. Misuse of inefficient QACs will increase the chances of microbes adapting and developing resistance against the same. Literature reports validate the gap in efficacy testing with traditional methods and emphasize the urgent need to establish uniformity in the methods to evaluate the effectiveness of the QACs for their proper and effective utilization. In this context, the use of European (EN) standards has gained a lot of attention and is proven to be more authentic and reliable. <\/p>\n\n\n\n

Acknowledgment<\/strong><\/p>\n\n\n\n

The authors acknowledge the Chitkara University, School of health sciences for supporting and motivating this study.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

We declare that we have no conflict of interest.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

We declare that there is no funding involved in this review study.<\/p>\n\n\n\n

References <\/strong><\/p>\n\n\n\n

  1. Institute of Medicine (US) Committee on Emerging Microbial Threats to Health, Lederberg J, Shope RE, Oaks SC Jr., eds. Emerging Infections: Microbial Threats to Health in the United States. Washington (DC): National Academies Press (US); 1992.<\/li>
  2. Khan HA, Baig FK, Mehboob R. Nosocomial infections: Epidemiology, prevention, control and surveillance. Asian Pacific Journal of Tropical Biomedicine. 2017;7(5):478-482. doi:10.1016\/j.apjtb.2017.01.019
     CrossRef <\/a><\/li>
  3. Rutala WA, Weber DJ. Disinfection and Sterilization in Health Care Facilities: What Clinicians Need to Know. Clinical Infectious Diseases. 2004;39(5):702-709. doi:10.1086\/423182
     CrossRef <\/a><\/li>
  4. Al-Tawfiq JA, Tambyah PA. Healthcare Associated Infections (HAI) Perspectives. Journal of Infection and Public Health. 2014;7(4):339-344. doi:10.1016\/j.jiph.2014.04.003
     CrossRef <\/a><\/li>
  5. Carling PC, Von Beheren S, Kim P, Woods C. Intensive care unit environmental cleaning: an evaluation in sixteen hospitals using a novel assessment tool. Journal of Hospital Infection. 2008;68(1):39-44. doi:10.1016\/j.jhin.2007.09.015
    CrossRef <\/a><\/li>
  6. Ministry of Health and Family Welfare, Government of India.National Guidelines for Infection Prevention and Control in Healthcare Facilities https:\/\/www.mohfw.gov.in\/pdf\/ National%20Guidelines %20for%20IPC%20in%20HCF%20-%20final%281%29.pdf<\/li>
  7. Rutala WA, Weber DJ. Guideline for disinfection and sterilization in healthcare facilities. [Internet].2019[cited 2019 Jan 5]. Available from : https:\/\/ www .cdc.gov\/infectioncontrol \/pdf\/guidelines\/disinfection-guidelines-H.pdf <\/li>
  8. Carling PC, Parry MF, Bruno-Murtha LA, Dick B. Improving environmental hygiene in 27 intensive care units to decrease multidrug-resistant bacterial transmission*. Critical Care Medicine. 2010;38 (4):1054-1059. doi:10.1097\/ccm.0b013e3181cdf705
     CrossRef <\/a><\/li>
  9. Dharan S, Mourouga P, Copin P, Bessmer G, Tschanz B, Pittet D. Routine disinfection of patients\u2019 environmental surfaces. Myth or reality? Journal of Hospital Infection. 1999;42(2):113-117. doi:10.1053\/jhin.1999.0567
     CrossRef <\/a><\/li>
  10. Russotto V, Cortegiani A, Raineri SM, Giarratano A. Bacterial contamination of inanimate surfaces and equipment in the intensive care unit. Journal of Intensive Care. 2015;3(1):54-61. doi:10.1186\/s40560-015-0120-5
     CrossRef <\/a><\/li>
  11. Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infectious Diseases. 2006;6(1). doi:10.1186\/1471-2334-6-130
     CrossRef <\/a><\/li>
  12. Dancer SJ. Controlling Hospital-Acquired Infection: Focus on the Role of the Environment and New Technologies for Decontamination. Clinical Microbiology Reviews. 2014;27(4):665-690. doi:10.1128\/cmr.00020-14
     CrossRef <\/a><\/li>
  13. Ayliffe GA, Collins BJ, Lowbury EJ. Cleaning and disinfection of hospital floors. BMJ. 1966;2(5511):442-445. doi:10.1136\/bmj.2.5511.442
    CrossRef <\/a><\/li>
  14. Weber DJ, Rutala WA. Environmental issues and nosocomial infections. Prevention and control of nosocomial infections. Baltimore: Williams and Wilkins. 1997:491-514.<\/li>
  15. Mythri H, Kashinath K. Nosocomial infections in patients admitted in intensive care unit of a Tertiary Health Center, India. Annals of Medical and Health Sciences Research. 2014;4(5):738. doi:10.4103\/2141-9248.141540
     CrossRef <\/a><\/li>
  16. Magill SS, Edwards JR, Bamberg W, et al. Multistate Point-Prevalence Survey of Health Care\u2013Associated Infections. New England Journal of Medicine. 2014;370(13):1198-1208. doi:10.1056\/nejmoa1306801
     CrossRef <\/a><\/li>
  17. Kamat U, Fereirra A, Amonkar D, Motghare D, Kulkarni M. Epidemiology of hospital acquired urinary tract infections in a medical college hospital in Goa. Indian Journal of Urology. 2009;25(1):76. doi:10.4103\/0970-1591.45542
    CrossRef <\/a><\/li>
  18. Otter JA, Yezli S, French GL. The Role Played by Contaminated Surfaces in the Transmission of Nosocomial Pathogens. Infection Control & Hospital Epidemiology. 2011;32(07):687-699. doi:10.1086\/660363
     CrossRef <\/a><\/li>
  19. Dvorak G, Disinfection 101, Center for food security and public health, Iowa State University, Ames, IA. [Internet].  2005 [cited 2018 Feb 8]. Available from: www.cfsph.iastate.edu<\/li>
  20. Jeffrey DJ. Chemicals used as disinfectants: active ingredients and enhancing additives. Revue Scientifique et Technique de l\u2019OIE. 1995;14(1):57-74. doi:10.20506\/rst.14.1.828
     CrossRef <\/a><\/li>
  21. Jacobs WA. The Bactericidal Properties Of The Quaternary Salts Of Hexamethylenetetramine. Journal of Experimental Medicine. 1916;23(5):563-568. doi:10.1084\/jem.23.5.563
     CrossRef <\/a><\/li>
  22. Jacobs WA, Heidelberger M, Amoss HL. The Bactericidal Properties Of The Quaternary Salts Of Hexamethylenetetramine. Journal of Experimental Medicine. 1916;23(5):569-576. doi:10.1084\/jem.23.5.569
     CrossRef <\/a><\/li>
  23. Domagk G. Eine neue Klasse von Desinfektionsmitteln. DMW – Deutsche Medizinische Wochenschrift. 1935;61(21):829-832. doi:10.1055\/s-0028-1129654
     CrossRef <\/a><\/li>
  24. Jiao Y, Niu LN, Ma S, Li J, Tay FR, Chen JH. Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance. Progress in Polymer Science. 2017 Aug 1;71:53-90.
     CrossRef <\/a><\/li>
  25. Haldar J, An D, Cienfuegos L\u00c1 de, Chen J, Klibanov AM. Polymeric coatings that inactivate both influenza virus and pathogenic bacteria. Proceedings of the National Academy of Sciences. 2006;103(47):17667-17671. doi:10.1073\/pnas.0608803103
     CrossRef <\/a><\/li>
  26. Ob\u0142\u0105k E, Piecuch A, Krasowska A, \u0141uczy\u0144ski J. Antifungal activity of gemini quaternary ammonium salts. Microbiological Research. 2013;168(10):630-638. doi:10.1016\/j.micres.2013.06.001
     CrossRef <\/a><\/li>
  27. Kenawy ER, Worley SD, Broughton R. The Chemistry and Applications of Antimicrobial Polymers:  A State-of-the-Art Review. Biomacromolecules. 2007;8(5):1359-1384. doi:10.1021\/bm061150q
     CrossRef <\/a><\/li>
  28. Nerandzic MM, Donskey CJ. A Quaternary Ammonium Disinfectant Containing Germinants ReducesClostridium difficileSpores on Surfaces by Inducing Susceptibility to Environmental Stressors. Open Forum Infectious Diseases. 2016;3(4):ofw196. doi:10.1093\/ofid\/ofw196
     CrossRef <\/a><\/li>
  29. Hora PI, Pati SG, McNamara PJ, Arnold WA. Increased Use of Quaternary Ammonium Compounds during the SARS-CoV-2 Pandemic and Beyond: Consideration of Environmental Implications. Environmental Science & Technology Letters. 2020;7(9):622-631. doi:10.1021\/acs.estlett.0c00437
     CrossRef <\/a><\/li>
  30. Dunn CG, Meyer AE. A Mixture of High Molecular Alkyl-dimethyl-benzyl-ammonium Chlorides as an Antiseptic. Experimental Biology and Medicine. 1936;35(3):427-429. doi:10.3181\/00379727-35-9005p
     CrossRef <\/a><\/li>
  31. DUNN CG. Antiseptic and Germicidal properties of a mixture of high molecular Alkyl\u2014Dimethyl\u2014Benzyl\u2014Ammonium Chlorides. American Journal of Epidemiology. 1937;26(1):46-53. doi:10.1093\/oxfordjournals.aje.a118339
     CrossRef <\/a><\/li>
  32. McCulloch EC, Hauge S, Migaki H. The Quaternary Ammonium Compounds in Sanitization. American Journal of Public Health and the Nations Health. 1948;38(4):493-503. doi:10.2105\/ajph.38.4.493
     CrossRef <\/a><\/li>
  33. Quisno R, Foter MJ. Cetyl Pyridinium Chloride. Journal of Bacteriology. 1946;52(1):111-117. doi:10.1128\/jb.52.1.111-117.1946
     CrossRef <\/a><\/li>
  34. Chaplin CE. Bacterial Resistance To Quaternary Ammonium Disinfectants. Journal of Bacteriology. 1952;63(4):453-458. doi:10.1128\/jb.63.4.453-458.1952
     CrossRef <\/a><\/li>
  35. Adair FW, Geftic SG, Gelzer J. Resistance of Pseudomonas to Quaternary Ammonium Compounds. I. Growth in Benzalkonium Chloride Solution. Applied Microbiology. 1969;18(3):299-302. doi:10.1128\/am.18.3.299-302.1969
     CrossRef <\/a><\/li>
  36. Sundheim G, Langsrud S, Heir E, Holck AL. Bacterial resistance to disinfectants containing quaternary ammonium compounds. International Biodeterioration & Biodegradation. 1998;41(3-4):235-239. doi:10.1016\/s0964-8305(98)00027-4
     CrossRef <\/a><\/li>
  37. Schaeufele PJ. Advances in quaternary ammonium biocides. Journal of the American Oil Chemists\u2019 Society. 1984;61(2):387-389. doi:10.1007\/bf02678799
     CrossRef <\/a><\/li>
  38. Hoseini SA, Shahcheraghi F, Ghaemmaghami A. Evaluation of the clinical efficacy of quaternary ammonium components (QAC) as surface disinfectant. Journal of Dentistry of Tehran University of Medical Sciences. 2006;3(4):190-4.<\/li>
  39. Sharma R, Singh M, Taneja N, Sharma M, Gupta PK, Rana JK. Comparative efficacy evaluation of disinfectants routinely used in hospital practice: India. Indian Journal of Critical Care Medicine. 2012;16(3):123-129. doi:10.4103\/0972-5229.102067
     CrossRef <\/a><\/li>
  40. Mishra P, Ramalakshmi K, Verma S, Shrivastava V. Comparative efficacy of 3rd generation quaternary ammonium compounds and formaldehyde for fumigation of operation theatres. Journal of Clinical & Experimental Research. 2013;1(3):47. doi:10.5455\/jcer.201332
     CrossRef <\/a><\/li>
  41. Rajkumar B, Kannan I. Evaluation of third generation quaternary ammonium compounds for the sterilisation of operation theatre. International Journal of Medical Research and Review. 2015;3(3):273-277. doi:10.17511\/ijmrr.2015.i3.051
     CrossRef <\/a><\/li>
  42. Pirsaheb M, Hossini H, Abiri R, Sharafi K, Poorhaghighat S. Investigating The Effect Of Free Aldehyde\/Phenol Antibacterial To Control The Common Hospital-Acquired Infections Including Pseudomonas Aeruginosa, Staphylococcus Aureus, Escherichia Coli, Acinetobacter, Enterococcus. Iioab Journal. 2016 Jan 1;7:572-7.<\/li>
  43. I\u00f1iguez-Moreno M, Avila-Novoa MG, I\u00f1iguez-Moreno E, Guerrero-Medina PJ, Guti\u00e9rrez-Lomel\u00ed M. Antimicrobial activity of disinfectants commonly used in the food industry in Mexico. Journal of Global Antimicrobial Resistance. 2017;10:143-147. doi:10.1016\/j.jgar.2017.05.013
    CrossRef<\/a><\/li>
  44. Fraise A. Currently available sporicides for use in healthcare, and their limitations. Journal of Hospital Infection. 2011;77(3):210-212. doi:10.1016\/j.jhin.2010.06.029
    CrossRef<\/a><\/li>
  45. Deshaies F, Ahmed D, Massicotte R, Pichette G, Belhumeur P, Mafu AA. Comparison of efficacy profiles for minimum lethal concentrations (MLCs) of some commonly used commercial hospital microbicidal detergent-disinfectant products for disinfectants and sporicidal activity. International Journal of Infection Control. 2012;8(2). doi:10.3396\/ijic.v8i2.013.12
     CrossRef <\/a><\/li>
  46. Vereshchagin AN, Frolov NA, Egorova KS, Seitkalieva MM, Ananikov VP. Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials. International Journal of Molecular Sciences. 2021;22(13):6793. doi:10.3390\/ijms22136793
     CrossRef <\/a><\/li>
  47. Zheng G, Filippelli GM, Salamova A. Increased Indoor Exposure to Commonly Used Disinfectants during the COVID-19 Pandemic. Environmental Science & Technology Letters. 2020;7(10):760-765. doi:10.1021\/acs.estlett.0c00587
     CrossRef <\/a><\/li>
  48. Sharma A, Singh N, Thomas A, Shrivastava PK, Sharma A. Quaternary Ammonium Compounds: Usage in Households during COVID-19 Pandemic, Boon, or Bane?.Asian Pac. J. Health Sci., (2022); DOI: 10.21276\/apjhs.2022.9.4S.26
     CrossRef <\/a><\/li>
  49. Marteinson SC, Lawrence MJ, Taranu ZE, et al. Increased use of sanitizers and disinfectants during the COVID-19 pandemic: identification of antimicrobial chemicals and considerations for aquatic environmental contamination. Environmental Reviews. Published online July 30, 2022. doi:10.1139\/er-2022-0035
    CrossRef <\/a><\/li>
  50. Johns CK. A Method for Assessing the Sanitizing Efficiency of Quaternary Ammonium and Hypochlorite Products. American Journal of Public Health and the Nations Health. 1947;37(10):1322-1327. doi:10.2105\/ajph.37.10.1322
    CrossRef <\/a><\/li>
  51. TUNCAN EU. Effect of Cold Temperature on Germicidal Efficacy of Quaternary Ammonium Compound, lodophor, and Chlorine on Listeria. Journal of Food Protection. 1993;56(12):1029-1033. doi:10.4315\/0362-028x-56.12.1029
     CrossRef <\/a><\/li>
  52. Tyski S, Bocian E, Laudy AE. Application of normative documents for determination of biocidal activity of disinfectants and antiseptics dedicated to the medical area: a narrative review. Journal of Hospital Infection. 2022;125:75-91. doi:10.1016\/j.jhin.2022.03.016
     CrossRef <\/a><\/li>
  53. Beuchat LR, Farber JM, Garrett EH, et al. Standardization of a Method To Determine the Efficacy of Sanitizers in Inactivating Human Pathogenic Microorganisms on Raw Fruits and Vegetables. Journal of Food Protection. 2001;64(7):1079-1084. doi:10.4315\/0362-028x-64.7.1079
     CrossRef <\/a><\/li>
  54. Van Klingeren B, Koller W, Bloomfield SF, et al. Assessment of the efficacy of disinfectants on surfaces. International Biodeterioration & Biodegradation. 1998;41(3-4):289-296. doi:10.1016\/s0964-8305(98)00020-1.
     CrossRef <\/a><\/li>
  55. Eyo AA, Ibeneme EO, Ogba OM, Asuquo AE. Antibacterial Efficacy of the In-Use Dilutions of Common Disinfectants against Pseudomonas aeruginosa Isolates in a Tertiary Care Hospital in Calabar, Nigeria. IOSR Journal of Pharmacy and Biological Sciences. 2018;13(3): 88-91. <\/li>
  56. Molinari JA, Gleason MJ, Cottone JA, Barrett ED. Cleaning and disinfectant properties of dental surface disinfectants. The Journal of the American Dental Association. 1988;117(1):179-182. doi:10.14219\/jada.archive.1988.0251
    CrossRef <\/a><\/li>
  57. Gerba CP. Quaternary Ammonium Biocides: Efficacy in Application. Applied and Environmental Microbiology. 2015;81(2):464-469. doi:10.1128\/AEM.02633-14
     CrossRef <\/a><\/li>
  58. Acosta-G\u00edo AE. Safer use of disinfectants for instrument reprocessing – a call to action. International Journal of Infection Control. 2008;4(1). doi:10.3396\/ijic.v4i1.008.08
     CrossRef <\/a><\/li>
  59. Tomasino SF. Development and assessment of disinfectant efficacy test methods for regulatory purposes. American Journal of Infection Control. 2013;41(5):S72-S76. doi:10.1016\/j.ajic.2012.11.007
     CrossRef <\/a><\/li>
  60. Gr\u00f6schel DHM. Disinfectant testing in the USA. Journal of Hospital Infection. 1991;18:274-279. doi:10.1016\/0195-6701(91)90033-5
     CrossRef <\/a><\/li>
  61. Langsrud S, Sundheim G. Factors influencing a suspension test method for antimicrobial activity of disinfectants. Journal of Applied Microbiology. 1998;85(6):1006-1012. doi:10.1111\/j.1365-2672.1998.tb05265.x
     CrossRef <\/a><\/li>
  62. Reybrouck G. The testing of disinfectants. International Biodeterioration & Biodegradation. 1998;41(3-4):269-272. doi:10.1016\/s0964-8305(98)00024-9
     CrossRef <\/a><\/li>
  63. Reybrouck G. International standardization of disinfectant testing: is it possible? Journal of Hospital Infection. 1991;18:280-288. doi:10.1016\/0195-6701(91)90034-6
    CrossRef <\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction Microbial diseases have compromised human well-being for a long […]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[115],"tags":[],"class_list":["post-57919","post","type-post","status-publish","format-standard","hentry","category-vol17no2"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/57919","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=57919"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/57919\/revisions"}],"predecessor-version":[{"id":59561,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/57919\/revisions\/59561"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=57919"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=57919"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=57919"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}