Infectious Diseases

Introduction to Antibiotic Resistance

Antibiotic resistance is a cause of rising concern and a threat to public health. Antibiotics have been a monumental medical intervention. The fact that bacteria exist which are resistant to antibiotics is a threat to the population in general. These resistant bacteria have come into existence due to the evolutionary mechanism called Natural Selection. It is the process by which the already existing bacteria mutate, allowing them to reproduce and survive. The major reason for the occurrence of antibiotic resistance occurs is the misuse and overuse of antibiotics. Continuous use of antibiotics has resulted in the mutation of disease-causing bacteria, making them resistant to the effects of the antibiotics. Due to bacteria being resistant, it is difficult to cure illnesses by merely administering antibiotics to patients. This makes the treatment process longer as well as expensive

Literature Review of Antibiotic Resistance

There exist many classes of antibiotic resisting bacteria, one such type being NDM-1 (New Delhi Metallo Beta-Lactamase). As the name suggests, NDM-1 is said to have originated in New Delhi, India and especially found in the hospitals in India and Pakistan. It belongs to a group of enzymes called Metallo Beta Lactamases (MBLs). MBLs are a class B carbapenemase as they require zinc at their active sit and they cause the inactivation of antibiotics which are lactam based. Its original evolution was a random escape of a gene onto a plasmid DNA that could travel between bacterial species, capable of spreading infection. Coupled with heavy antibiotic use, it eventually mutated into its present form, that of an antibiotic resistor. The first case of NDM infection was detected in 2008. NDM is said to be the fusion of two previously existing antibiotic-resistant genes evolved to a new mutant (Khan, Maryam & Zarrilli, 2017). Bacteria with the NDM-1 gene are part of a group known as ‘superbugs’ which are difficult to treat. The bla-NDM gene that codes the NDM enzyme is easily mobilized, making it easily transmissible. Hence, the growing concern in the field of public health.

coli bacteria which produces NDM-1 can develop antibiotic resistance among microorganisms and transform them into pathogens (Khan, Maryam & Zarrilli, 2017). The NDM-1 producing E. coli infects the urinary tracts, lungs, blood and other wounds which causes diseases like pulmonary infection, diarrhoea and urinary tract infection. It is alarming how 17 different variants of NDM-1 have come into existence in the last few years. The NDM produced by bacterial isolates hydrolyzes beta-lactam antibiotics causing chaos in hospitals and communities (Miriagou et al., 2010). The gene encoding NDM-1 is carried by plasmids, moves to other microorganisms, thereby increasing the probability of drug-resistant strains of pathogenic microorganisms (Rolain et al., 2010).

The spreading of NDM-1 is seen as a health crisis by the World Health Organization. The NDM-1 has the potential to change the characteristics of a bacteria making it resistant to antibiotics. Some of the dangers of NDM-1 include easily transferable and capable of widespread transmission, lack of standardised tests for its detection, high prevalence of asymptomatic carriers and most importantly, lack pf antibiotic for its effective treatment. One of the most powerful antibiotics, Carbapenems, is normally used as a last resort by doctors against diseases. NDM-1 produces an enzyme known as carbapenemase which renders the antibiotics of the carbapenem group ineffective. Antibiotics like colistin and tigecycline (Shakil, Akram & Khan 2008) are effective against such microorganisms but there are cases where they cannot be implemented (for example, with Proteus Mirabilis) due to the resistance of those microorganisms (Williamson et al., 2012). Research has highlighted that colistin-resistant E. coli has been found to harbour NDM-1 (Yu et al., 2016; Delgado-Blas et al., 2016). Colistin is also known to have a toxic effect on people, subjecting it to further scrutiny.

A bacterium with a plasmid containing NDM-1 can be highly resistant. If an already resistive bacteria reacts with NDM-1, it may lead to the rapid spreading of infections, which may be dangerous as it is not treatable. Though routine antibiotic sensitivity testing is available for detecting resistance to beta-lactam antibiotics, specific testing for NDM-1 is not available.

Since the spread of NDM-1 is a global problem, due to accessibility to travelling causing it to easily, it is important to come up with strategies to deal with this crisis. Some of the strategies to combat the spreading of antibiotic resistors are – To formulate a National Action Plan, tracking progress and monitoring infections in patients so that as much information can be accumulated and researched upon, the better, introducing policies and programs to exercise control measures and prevent spreading of infection, regulating the use of antibiotics to prevent misuse and overuse, spreading awareness concerning the dangers of this issue and promoting healthy and hygienic ways of living.

An active surveillance system is required to monitor the spread of NDM-1 (Charan et al., 2012). This includes steps such as, regular monitoring of prescriptions to prevent inappropriate and irrational use of antibiotics. Another practice that requires serious attention and must be discouraged is the unethical promotional policies of big pharmaceutical companies. Doctors and clinicians should research the drugs and look seriously into the matter of antibiotic resistors while prescribing drugs, instead of blindly prescribing drugs based on the information provided to them by pharmaceutical companies. According to studies, transmission can be prevented by rapid identification in the patients, with relevant factors, educating hospital staff, immediate isolation in a private room, one on one nursing care and aggressive cleaning and disinfection was found to be effective (Savard et al., 2011).

Intervention Strategy: Claim

NDM-1 is a danger to the community and a threat to society. Since there is no cure for this at present, the need of the hour is to conduct more research in this area and come up with an effective NDM inhibitor as soon as possible. A specific test to detect the presence of NDM-1 is another thing that should be given priority to. A third possibility would be to come up with a powerful antibiotic that would tackle the effect of NDM-1. However, this solution is flawed, since we cannot be sure if another more powerful mutation would occur that would be resistant to the new antibiotic. Having said this, if I had a large amount of money, I would ideally like to invest it in promising research in this field such as the one along the lines of Isoliquiritin which is said to significantly inhibit NDM-1 (Wang et al., 2020). Maybe its compounds could be further developed into effective NDM-1 blockers. that should be given. As important it is to come up with an inhibitor or a test, it is more important to have a region-wise or country-wise surveillance in place to track and prevent the transmission of the bacteria. So, I would spend money on implementing a nation-wide surveillance action plan. An undertaking of such magnitude would require a lot of funds and I would be happy to invest in such an initiative.

A nation-wise surveillance action plan, in my opinion, would be a successful method to control the spread of antibiotic resistors like NDM-1. There have been instances in the past when these methods were implemented and have produced successful results. The Israel Ministry of Health, in 2007 had conducted a nationwide intervention in 2007. This initiative had succeeded in containing the spread of the dangerous pathogen and is viewed as a model for the healthcare field (Schwaber & Carmeli, 2014). Another nationwide initiative was carried out in Hong Kong when they were experiencing the spread of the superbug NDM-1. Their territory-wise surveillance program was highly successful in the identification of patients and adopting appropriate infection control strategies (Tsang et al., 2012).

There are various stages that would entail in a nation-wise surveillance action plan. For starters, guidelines would be issued by various healthcare facilities in the target country. The patients who are carriers of the NDM-1 would be physically separated from the non-carriers. They would then be isolated with a dedicated team to care for them. In the meantime, healthcare professionals would also be monitoring the active cases and collecting data concerning areas like the isolation status, measures adopted by different facilities and their comparison, environment cleaning protocols and lab results. Each hospital would have to provide daily updates on the cases and carriers. A significant association was observed between following the official protocols and a drop in the cases (Mitchell, Schwaber & Yehuda, 2014).

Active surveillance using microbiological strategies for screening and isolation purposes are to be followed. Screening at regular intervals (through swab and stool samples) need to be conducted. Site visits are to be conducted and details such as hand hygiene, implementation of standard precautions are to be focused upon. Since the pathogen is more common in hospitals and healthcare facilities, the protocols need to be carried out until there is no carrier remaining. Hence stringent isolation policies are to be mandated. Additionally, inappropriate prescription of antibiotics should be avoided, not just in healthcare facilities but also to the general population.

The idea behind a national surveillance plan is to produce data and implement the findings for control and prevention of the infection. With continuous effort, the total eradication of the pathogen is highly possible. Additionally, if the above examples of successes are to be taken into consideration, there will also be a reduction in the incidence rate of the infection.

Conclusion on Antibiotic Resistance

NDM-1 originated from India and is now a global threat to public health. The major reason behind the fear is that the NDM-1 is considered to be a superbug. This means it is resistant to most antibiotics, even Carbapenems. Carbapenems are a powerful group of antibiotics which are effective against most bacteria, including E. coli. But, it is rendered ineffective if the E. coli bacteria has the NDM-1 enzyme existing in it. Hence, due to the presence of antibiotic resistors like NDM-1, and its varied evolved and mutated forms (each more powerful and dangerous than its predecessor), treatment for various diseases becomes either ineffective, too expensive or the procedure is prolonged.

The NDM-1 inspection is widespread due to travelling to different parts of the world becoming common. The infection is found in almost all countries and is a major blow to the health sector. Only two antibiotics are have shown some degree of effect against the NDM, however, neither of them ideal for general use. These are colistin and tigecycline. Colistin is toxic to the general population and tigecycline has a limited effect against infections, making it ineffective against most infections. This infection is mostly prevalent in India and the roots of the cases found outside can be traced back to the Indian subcontinent as well, specifically hospitalization in India. On a visit to the subcontinent, an individual may become infected or become an asymptomatic carrier, carrying the bacteria in their gut (as that is commonly where they are found) and spreading it unknowingly. The risk of infection is higher in individuals who have been hospitalised in India or its neighbouring countries, Pakistan and Bangladesh.

To effectively combat infections involving NDM-1, it is important for healthcare professionals as well as caregivers to practise good hygiene, especially hand hygiene. The carriers must be isolated from the noncarriers to prevent further transmission. This issue is a serious medical concern. It has been identified by the WHO as a major threat to public health. Sadly, the resistance can be expressed through a variety of different bacteria and the symptoms may vary depending on the site of infection. Common sites include the urinary tract, blood, lungs and open wounds. The need of the hour is to research further into prospects involving the development of new antibiotics, NDM blockers and specific tests that will help speed up the identification process. In the absence of specific tests and medications, other intervening strategies need to be looked upon. For instance, employing a nationwide surveillance plan. Strict protocols and guidelines must be formulated and followed by the healthcare sector to trace, control and prevent widespread infection.

References for Antibiotic Resistance

Charan, J., Mulla, S., Ryavanki, S., & Kantharia, N. (2012). New Delhi Metallo–beta lactamase–1 containing Enterobacteriaceae: origin, diagnosis, treatment and public health concern. Pan African Medical Journal, 11(1).

Delgado-Blas, J. F., Ovejero, C. M., Abadia-Patino, L., & Gonzalez-Zorn, B. (2016). Coexistence of mcr-1 and blaNDM-1 in Escherichia coli from Venezuela. Antimicrobial Agents and Chemotherapy, 60(10), 6356–6358.

 Khan, A. U., Maryam, L., & Zarrilli, R. (2017). Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health. BMC Microbiology, 17(1), 101.

Miriagou, V., Cornaglia, G., Edelstein, M., Galani, I., Giske, C. G., Gniadkowski, M., Malamou-Lada, E., Martinez-Martinez, L., Navarro, F., Nordmann, P., Peixe, L., Pournaras, S., Rossolini, G. M., Tsakris, A., Vatopoulos, A., & Cantón, R. (2010). Acquired carbapenemases in Gram-negative bacterial pathogens: detection and surveillance issues. Clinical Microbiology and Infection, 16(2), 112–122.

Rolain, J. M., Parola, P., & Cornaglia, G. (2010). New Delhi metallo-beta-lactamase (NDM-1): towards a new pandemia? Clinical Microbiology and Infection, 16(12), 1699–1701.

Savard, P., Gopinath, R., Zhu, W., Kitchel, B., Rasheed, J. K., Tekle, T., Roberts, A., Ross, T., Razeq, J., Landrum, B. M., Wilson, L. E., Limbago, B., Perl, T. M., & Carroll, K. C. (2011). First NDM-Positive Salmonella sp. Strain Identified in the United States. Antimicrobial Agents and Chemotherapy, 55(12), 5957–5958.

Schwaber, M. J., & Carmeli, Y. (2013). An Ongoing National Intervention to Contain the Spread of Carbapenem-Resistant Enterobacteriaceae. Clinical Infectious Diseases, 58(5), 697–703.

Shakil, S., Akram, M., & Khan, A. U. (2008). Tigecycline: A Critical Update. Journal of Chemotherapy, 20(4), 411–419.

Tsang, K. Y., Luk, S., Lo, J. Y., Tsang, T. Y., Lai, S. T., & Ng, T. K. (2012). Hong Kong experiences the ‘ultimate superbug’: NDM-1 Enterobacteriaceae. Hong Kong Med J, 18(5), 439–441.

Wang, Y., Sun, X., Kong, F., Xia, L., Deng, X., Wang, D., & Wang, J. (2020). Specific NDM-1 Inhibitor of Isoliquiritin Enhances the Activity of Meropenem against NDM-1-positive Enterobacteriaceae in vitro. International Journal of Environmental Research and Public Health, 17(6), 2162.

Williamson, D. A., Sidjabat, H. E., Freeman, J. T., Roberts, S. A., Silvey, A., Woodhouse, R., Mowat, E., Dyet, K., Paterson, D. L., Blackmore, T., Burns, A., & Heffernan, H. (2012). Identification and molecular characterisation of New Delhi metallo-β-lactamase-1 (NDM-1)- and NDM-6-producing Enterobacteriaceae from New Zealand hospitals. International Journal of Antimicrobial Agents, 39(6), 529–533.

Yu, J., Tan, K., Rong, Z., Wang, Y., Chen, Z., Zhu, X., Wu, L., Tan, L., Xiong, W., Sun, Z., & Chen, L. (2016). Nosocomial outbreak of KPC-2- and NDM-1-producing Klebsiella pneumoniae in a neonatal ward: a retrospective study. BMC Infectious Diseases, 16(1), 563.

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