Evolution of Antimicrobial Resistance in the Era of COVID-19

Antimicrobial resistance is a slow-growing phenomenon that could even be a reason for a future pandemic. Due to inappropriate diagnosis and consumption of antibiotics, the bacteria have become resistant to the antibiotics used. In the era of COVID-19, this blind consumption of antibiotics has rapidly increased due to the period of quarantine and fear of the disease. Ligue to the fear of the pandemic, especially in ru, rural areas, many patients avoid going to the hospital and consuming antibiotics without any prescription. Various retrospective studies have shown a relationship between bacterial co-infection and AMR, which is increased in the era of COVID-19. Also, the secondary bacterial infections associated with the pandemic of COVID-19 have added to the risk of antimicrobial resistance. The viral effect on the respiratory system is favorable for bacterial infection, as in the case of COVID-19 affecting the respiratory tract followed by cobacterial infection in some cases. COVID-19 has affected AMR in many aspects. Proper antibiotic resistance tests should be performed before prescribing any antibiotics to the patient to reduce the chances of AMR, especially in such an obnoxious situation of COVID-19. This crucially calls for a brand new and effective plan of action to attenuate the influence of the pandemic on antimicrobial resistance. Statistics of various countries in matters of antimicrobial resistance have shown an increase in AMR due to the concentration of health workers, researchers, and population on the Review Article Gupta and Patil; JPRI, 33(60A): 633-642, 2021; Article no.JPRI.79541 634 pandemic associated with COVID-19. This calls for the necessity to aware the population worldwide about antimicrobial resistance and how it could be a hidden menace in the future and could probably prove to be a matter of concern as it would worsen the condition of the patients in a particular disease and would decrease the various possible aspects of the treatment especially in case of treatment based on antibiotics.


INTRODUCTION
Antimicrobial resistance(AMR) is seen to be emerging as a threat to effective prevention and treatment in the 21 st century [1]. AMR can be explained in regards to antibiotic resistance developed over decades in the bacteria causing infections resulting in the ineffectiveness of any new antibiotic in the market on the resistant bacteria [1]. Accurate secondary bacterial infection characterization is critical in the clinical management of the most severe COVID-19 cases, might save lives, and enhance patient outcomes a commitment to antimicrobial stewardship across the pandemic's progress [2]. In patients of covid 19, bacterial co-infections associated with COVID-19 have been reported, which will ultimately add up to the possibility of increased antimicrobial resistance [3].
The obnoxious situation that we are hit with, the COVID-19 is reported to be contributing to the risk of antimicrobial resistance through medical management (i.e., by reported cases of bacterial co-infections), although the reported cases of secondary bacterial infections associated with COVID-19 are less as compared to the reports of usage of the antibiotics when treating COVID -19 patient [4]. Bacterial and fungal infections of various types have been reported in patients of COVID-19, along with resistance to antimicrobials leading to worse outcomes and even death [5].

RETROSPECTIVE STUDIES, FACTS, AND FINDINGS OF BACTERIAL CO-INFECTION AND AMR IN DIFFERENT COUNTRIES
According to a retrospective study done at Wuhan Union Hospital, it was found that bacterial co-infections were associated with the severity in the case of patients hospitalized. It is also evident that the gram-negative bacteria, most commonly A. bau,mannii, and K. pneumonia, were the cause of oco-infection-infections and were also highly resistant to antimicrobials [6]. A retrospective cohort analysis conducted at a A study survey among the European citizens reported that the percentage of the participants in the survey involved in the usage of antibiotics in the treatment of flu-like symptoms and known that antibiotics do not act against viral infections was found to be 20%. On the other hand, 14% of the participants admitted that they took antibiotics to treat acute rhinitis or cold [11]. A study survey in the UK amidst the adults reported that the percentage of participants of the survey that didn't know that antibiotics do not act against cold and cough was 38% [12]. According to a survey, Sweden's comprehension of anti and the possibility of AMR is good and homogenous. Only one-fifth of the participants were assured with the myth that antibiotics treat the common cold more effectively [12].

NTS-non-typhoidal salmonella
In the usage of antimicrobial agents such as ampicillin, chloramphenicol, sulphonamides, and tetracycline, the cases of multi-drug resistance are frequent in Non-typhoidal Salmonella [17,18].

Various Aspects in which COVID-19 Impacts AMR
Secondary bacterial infections have long been thought to be a significant cause of illness and death in viral infections, and they have also been documented in COVID-19 patients, but only a tiny percentage [20]. Antibiotics are misused during the pandemic to self-limit the upper respiratory tract infection in non-hospitalized settings [21,22]. AMR is expected to cause 1,30,000 more fatalities by the end of 2020 owing to the present state of the COVID-19 epidemic [20].
Due to the lack of beds in hospitals and the weakened immune systems of the COVIDinfected patients, they are more prone to secondary bacterial infections or co-infections [23,24,25]. Multidrug resistance is reported as using inappropriate antibiotics in COVID-19 patients [23,26].
Even though antibiotic prescribing practices differ by region, enlarged work pressure and psychological stress on medical practitioners make adhering to community hospital antimicrobial stewardship policies more complex. Despite the reality that empiric antibiotics hurt later clinical output, the research suggests that secondary bacterial infections influence only a tiny chunk of COVID-19 victims [27]. Finally, the increased hospital utilization of antibiotics in the case of COVID-19 victims throughout the preliminary phases of the COVID-19 pandemic may impact the total antimicrobial resistance, influencing the load of diseases for later generations. Moreover, the pandemic of COVID-19 has created a severe and extensive global economic crisis, with the potential to fuel a substantial increase in global poverty levels. Lower-and middle-income countries (LMICs) are projected to agonize disproportionately, with many people who are already poor being driven further into poverty [27].
Despite the difficulty in distinguishing pneumonia caused by bacterial infection from pneumonia caused by COVID-19 infection and the lack of antiviral therapy with proven efficacy in treating COVID-19 patients, particularly the critically ill patients, antibiotics must be utilized as a part of an empirical strategy. To avoid considerably more difficult repercussions, it is critical to take antibiotics responsibly even during the pandemic. However, due to antibiotic usage and the increasing percentage of antimicrobial resistance, this concept raises worries about the effects [28].

Antibiotic Selection Difficulties for COVID-19 Victims in LMI
Suppose the danger of necessitating invasive mechanical ventilation justifies the usage of antibiotics to cure hospital acquhospital-acquired infections. In that case, the scarcity of ventilators in LMICs reduces this probability and should thus considerably decrease unwanted antimicrobial usage. Even though temporary peripheral venous catheters are associated with frequent numb with an f case of infections of bloodstream infection tions in LMICs, risk the s involved in case of the rising figures of COVID-19-infected patients who are hospitalized, which will result in a greater dependence on antibiotics to combat hospital-acquired infections associated with the catheter. Antimicrobial use, along with infectioncontrol strategies, could assist in reducing this risk. Research findings indicate that, in the case of similar pathogenic bacterias, disparities occur among HIC and LMIC in terms of communities at risk, associated symptoms, the prevalence of spread of pathogenic bacteria, and drug sensitivity. The potential danger of COVID-19 may provide chances for LMICs to enforce antimicrobial stewardship programs by WHO guidelines, such as antimicrobial stewardship team education and training, advances in medical guidelines, resistance monitoring, and antibiotic use monitoring [29].

Strategies to Attenuate Consequence of COVID-19 on AMR
The health care system needs to balance the imbalance in antibiotics and microbial investigations [30]. Assessment of the articles, reports, and studies about the enlarged possibility of AMR due to the pandemic of COVID-19 plays an essential role in the development of attenuation strategies [31]. AMR should be made as an essential basic in clinical practices [32].
Diagnostics should be more appropriate in this challenging time of the pandemic of COVID-19 in terms of identifying the proper organism involved as the cause of the secondary bacterial infection (30). A support system must be built to support the researchers and their confidence, encouraging them to carry on with the AMR research and monitoring [33]. The formation and appearance of networks of collaborators coming up in the covid 19 era should be encouraged to help us with their motive to handle issues regarding the covid 19 pandemic [33].
International campaigns like the biennial World Antibiotic Awareness Week raise awareness of AMR and the importance of antibiotic stewardship More regularly washing hands (e.g., through Hand Hygiene Day) appears to pay off when hygiene practices are prioritized. Usage of antibiotics should be with caution and care, in case of empirical therapy in advance for occurrence with a strong possibility of microbial co-infection and the statistics of resistance taken into consideration. In reaction to microbiological discoveries, empirical prescriptions should be rapidly re-evaluated and changed. [27].

Antimicrobial Stewardship Program and COVID-19
Antimicrobial stewardship denotes collaborative, integrated programs and initiatives to promote appropriate antimicrobial treatment regimens, including dose, length of treatment, and other factors [28]. Antimicrobial stewardship programs can observe and improve compliance with the help of treatment guidelines during pandemics of respiratory viruses accompanied by bacterial coinfections and diseases such as pneumonia and ARDS. Severe COVID-19 instances have been treated with broad-spectrum antibiotics. Despite the complexity of distinguishing COVID-19 from bacteria associated pneumonia, the uncertainty about bacterial superinfections, the lack of precise antiviral treatment for the prevailing pandemic, and the high death rates, antibiotics should be considered to be part of the empirical therapy for the most severe suspected or confirmed COVID-19 cases (e.g., patients necessitating mechanical ventilation). Antibiotics should, however, be administered with caution and caution during such a pandemic [28].

Monitoring AMR in the Era of Covid-19: A Challenge
Due to lack of time and increase of burden and responsibilities on health care professionals and population, the whole attention is being shifted towards working on Covid-19. This has affected the participation and involvement in AMR research and has also led to the discontinuation in maintaining the accounts of and monitoring AMR. Recently developed and implemented systems of monitoring for Covid-19 can be utilized to fortify environmental monitoring of antimicrobial resistance [33].

Statistics and Facts
 In Wuhan, antibiotics were preferred for treatment in 95% of patients, and antivirals were given to 21% [34].  As per the fourth GLASS report, the 2019 data collection regarding AMR by WHO estimates 3 106 602 laboratories confirmed cases of infections in 70 countries [35].

COMBINED EFFECTS OF BACTERIAL AND VIRAL PATHOGENS
It is evident that viral infection like COVID-19 affecting the respiratory tract also promotes bacterial growth by altering the function of the innate immune system [29]. It is also evident that due to the impact of immune response throughout a viral infection like covid, there is a modification in the anatomy of the respiratory tract, which has been known to sabotage the immune system's defenses against the pathogenic virus or bacteria [29].In the case of infected SARS-CoV-2 subjects, the pulmonary alveoli filled with puss and fluid favors and provide the suitable medium for the growth of P. aeruginosa and S. aureus-like bacteria [29].

Bacterial Coinfection and Subsequent Infections Predictors (Clinical, Biomarkers)
There is a need for more research into the predictive ability of various clinical or laboratory investigations during the patient's hospitalization for coinfections. Complete data collection must be harmonized across randomized trials, studies, and varied patient profiles, along with adequate microbiological investigations [20]. Clinicians have employed biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) to aid in diagnosing infections associated with bacteria. In severe cases, it may be high. COVID-19 patients have a limited lifespan due to the virus. Use in determining how long and how often antibiotics should be given [36].

Access of Antimicrobials
COVID-19 has impacted antibiotic availability by altering supply chains and worldwide antimicrobial manufacture, resulting in modifications in consumption levels.
The vulnerability of the network of antibiotics was emphasized not so long ago when a single Chinese manufacturer was shut down, resulting in a worldwide scarcity of piperacillintazobactam. Fears of scarcity have prompted the European Medicines Agency to take "urgent and synchronized measures to stop and reduce medicine deficits inside the EU."As a result of COVID-19, nations that produce and trade antibiotics are increasingly facing domestic demand, leading to a drop in shipments, as observed in India. This may result in a request for expanded antibiotic production beyond the production hubs of India and China. COVID-19 is supposed to be leading to modifications in antibiotic use, which would have a parallel impact on supply chain shortfalls; eleven producers have claimed azithromycin scarcity to the United States Food And drug, possibly due to its use for COVID-19 medication [33].

Antimicrobial use in COVID-19 Patients
Antimicrobials are administered to up to 70% of COVID-19 patients in either an inpatient facility or outpatient care setting, which will support AMR [33]. Antimicrobials are being used because they are thought to influence SARS-CoV-2 negatively. This could lead to resistance in pathogenic microbes that co-infect or cocolonize (37). Cheap, quick diagnostics in community settings may detect infections like SARS-CoV-2 earlier, mainly in the face of imprecise symptomatology, and hence reduce antibiotic use. This will be especially relevant in low-and middle-income countries where antibiotics are available without a prescription and testing is emphasized, whereas vaccinations may take more time to become more widely utilized [33][34][35][36][37][38][39][40][41][42][43][44][45].

CONCLUSION
This review demonstrates the effect of the covid 19 pandemic on antimicrobial resistance and vice-versa. AMR, which has been a hidden menace, is discussed covid 19 to create awareness regarding future risks with AMR. The importance of correct diagnosis about the secondary bacterial infections is mentioned, as it was found to be out of focus in the covid 19 era due to the burden on health care professionals. We are realizing the fact that covid 19 has piqued our curiosity leading to unbalanced monitoring of the AMR, which will now be encouraged. An account of bacterial and fungal co-infection in covid 19 patients along with retrospective studies from different countries are discussed in this review to draw knowledge about the link between AMR and COVID-19.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.

DISCLAIMER
The products used for this research are commonly and predominantly used in our research area and country. There is no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.