Correspondence Address:
Dr. Saibal Chakravorty
T-21, SECTOR-11, NOIDA UP-201301
India

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“Antimicrobials consist of medicines such as antibiotics, antivirals, antifungals, and antiparasitic which are used to prevent and treat infections in humans, animals, and plants.”[1] According to the World Health Organization (WHO), “Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi, and parasites change over time and no longer respond to medicines making infections harder to treat and increasing the risk of disease spread, severe illness and death. As a result of drug resistance, antibiotics and other antimicrobial medicines become ineffective and infections become increasingly difficult or impossible to treat.”[1]

The rapid global spread and increased prevalence of COVID-19 cases prompted the WHO to declare the disease as pandemic on March 11, 2020.[2] We are in the mid of novel coronavirus pandemic (2020–present), which is the most significant health crisis since the H1N1 swine flu pandemic (2009) and Dengue virus epidemic (2021).[3] Draconian measures have been taken worldwide to combat this public health event and try to slacken the spread of the virus.[4] Apart from the pandemic, AMR has become a constant threat to the global economy and health issues over the past several years.[3]

To combat the public health crisis, the various governments have published guidelines related to COVID-19 management for hospital inpatient setting.[3],[5] In particular, for the infection prevention and control, it is recommended that for any quarantined COVID-19–positive patient or a suspect with SARS-CoV-2 infection, precautions should be taken against direct contact with potential contaminated surfaces, aerosols, and droplets with extra vigilance on hygiene, sterilization, and antimicrobial stewardship practices in health-care setting.[5] Although these practices have helped reduce the spread of the virus, the burden of AMR has increased significantly.[6]

At the beginning of the outbreak and before the pandemic was declared, data regarding bacterial infections in COVID-19 patients were minimal. Few studies have revealed that COVID-19 patients contract secondary bacterial infection, quantifying to around 1%–10%.[3] This was in comparison to the previous H1N1 pandemic when 12%–19% of admitted patients with pneumonia contracted secondary bacterial co-infection.[7] Furthermore, many studies were conducted that showed that COVID-19 disease and bacterial infection appeared to be interrelated in severity of COVID-19 infection. A UK study with a sample size of 836 patients with SARS-CoV-2 infection has shown that 3.2% of these cases had bacterial co-infection, especially in those with early COVID-19 hospitalization, i.e., day 0–5 postadmission.[8]

Despite the relatively low reported secondary infection, there is comparatively increased antibiotic consumption to treat COVID-19 patients. However, the inappropriate use or overuse of antibiotics acted as a significant driver for the emergence of AMR.[9] The prime culprits for hospital-acquired infections worldwide are the so-called ESKAPE pathogens – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.[10] A meta-analysis study with 3338 cases across 24 studies including both inpatient isolation and critical care COVID-19 patients reported that 71.9% of COVID-19 patients received antibiotics (95% confidence interval [CI] 56.1%–87.7%) as treatment.[11]

C-reactive protein is a biomarker typically elevated in bacterial infections and not in viral infections but is raised in patients with COVID-19.[7] The blood investigations revealed increased C-reactive protein levels and procalcitonin in patients with positive SARS-CoV-2 virus, which ultimately led the physicians to empirically use antibiotics to treat COVID-19 patients.[7],[12] A study from Wuhan depicted analysis of 191 adult COVID-19 patients during hospital admission, which consisted of both nonsurvivors and survivors of the disease who were found to have sepsis as the most frequently observed complication.[13] Another meta-analysis study reported that there is a disparity in bacterial co-infection levels where the overall proportion of COVID-19 patients in the intensive care unit was 14% (95% CI 5%–26%, n = 204) compared to 4% of COVID-19 patients from inpatient hospitalization and outpatient attendance (95% CI 1%–9%, n = 1979).[14] Around 45% of the patients receive antibiotic treatment to prevent secondary infection.[3] The practice of empiric antibacterial prescription has the potential to escalate an already worrisome public health burden of AMR.

The second reason is that the use of antimicrobial soaps and disinfectants by the community and the hospital has excessively increased over this pandemic period. These products contain biocides that are antimicrobials and further lead to the emergence of AMR.[3] Interestingly, more than half of the antimicrobials produced across the continent are used in the practice of livestock production.[6] Animals are administered low-dose antibiotics over a prolonged time to promote growth which has encouraged AMR emergence. AMR organisms present in animals get transmitted to humans via meat products and contact with personnel working in production process.[6]

While a viral pandemic has an immediate impact, AMR has a prolonged impact which has the potential to escalate deaths due to various other diseases. More than half of COVID-19–deceased patients had fungal and bacterial co-infections, while some deaths were due to AMR. It was observed that a large number of death in past pandemics were associated with AMR.[15] [Figure 1] depicts the determinants of AMR in the past, present, and future pandemics at all levels of society which have interrelated and interdependent factors.[6] Studies have estimated 1.27 million deaths in 2019 which positions just behind mortality due to COVID-19 and tuberculosis, which almost amounts to death due to HIV (680,000) and malaria (627,000) worldwide.[15],[16]{Figure 1}

Beyond the scope of this review, there is also evidence of viral and fungal co-infections in COVID-19 patients. Further research is necessary to validate these findings beyond the COVID-19 pandemic for augmented control of AMR. Furthermore, the WHO recommends that “Antimicrobial therapy should be assessed daily for de-escalation.”[1] It is hoped that valuable lessons can be drawn from the COVID-19 pandemic.

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