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AMR -- The insidious and silent pandemic ‘in making’

As we trudge under the COVID-19 for over a year alluring with the threat of the third wave of the pandemic, healthcare experts alert that it’s not just the virus, but an allied traitor — Anti Microbial Resistance (AMR) — is another threat lurking behind the current outbreak. As the COVID-19 virus leads to bacterial infections—and bacteria are becoming increasingly resistant to treatment with antibiotics, it is helping to fuel another silent pandemic -- antimicrobial resistance. Many healthcare experts are alerting that COVID-19 is accelerating the perils of AMR.

With the extensive usage of steroids on the COVID-19-positive patients snowballing into a bigger threat, healthcare authorities inform that a collective strategy can help tackle AMR, or it might be another devastation in making. According to healthcare experts, before the pandemic, the status of AMR was approximately 48.3 percent. A recently published study has shown an overall incidence of secondary infection of 3.6 percent (91.4 percent bacterial and 5.4 percent fungal), with 47.1 percent being multi-drug resistant organisms.

The COVID-19 virus has sunken its claws in such a way that the patients are led to inappropriate use of a broad spectrum of antibiotics. While the focus has been heavily on tackling the virus, there is little awareness of AMR, but healthcare professionals highlight that AMR needs to be addressed with the same urgency as COVID-19. AMR is the fifth leading cause of death as per global data -- after cancer, diarrhoea, and road traffic accidents. According to experts, if we look at deaths attributable to AMR every year -- Asia amounts to maximum, followed by Africa. India has been the hotbed of AMR. The New Delhi Metallobetalactamase (NDM bug) started in New Delhi in 2006 and soon spread across the globe. India leads in the total antibiotic consumption in the world. The country has been referred to as ‘The AMR capital of the world'. (Int J Community Med Public Health. 2017)

Explaining that AMR is high in India, Dr. Sumit Ray, Medical Superintendent and Critical Care Specialist, Holy Family Hospital, said, "The resistance among Gram-negative bacilli, particularly, Klebseilla, Acinetobacter, E. Coli and Pseudomonas have always been extremely high -- to the tune of nearly 2/3rd of these bacteria being resistant to fourth-generation antibiotics. Post-pandemic, it is difficult to say if AMR has worsened, but, the possibility cannot be ruled out."

Informing that high levels of resistance are seen to key antimicrobials in bugs isolated from Covid patients compared to the Indian Council of Medical Research (ICMR) data in previous years, Kamini Walia, Senior Scientist, ICMR, informed that Acinetobacter Baumanii - Aminoglycoside showed 20.4 percent in ICMR 2019 data, and in Covid-19, it was 16 percent. In Klebsiella pneumoniae antibiotics class on ICMR 2019, data was 50 percent and COVID data indicated to be 33.5 percent.

"In COVID times, a lot of over-prescribing of antimicrobials happened in asymptomatic/mild patients as well as the hospitalized patients to prevent possible secondary bacterial infections. Data from our study shows that most patients are initiated on broad-spectrum empirical antimicrobials at the time of admission, and if the patient is doing better, there is a tendency to continue the antimicrobials even if the culture report is negative. This empirical overuse of broad-spectrum antimicrobials provides fertile ground for future outbreaks with highly drug-resistant pathogens. It is always recommended that the antimicrobials be de-escalated when the culture result is received. Excessive use of broad-spectrum antimicrobials in hospitals may result into pathogens becoming increasingly drug-resistant and posing great challenges to physicians to treat nosocomial infections due to Gram-negative pathogens in the ICU settings," Walia said.

Pointing that more than 70 percent of COVID-19 patients are being administered broad-spectrum antibiotics, Dr Gunjan Chanchalani, Physician and Intensivist, informed that out of it, less than 10 percent actually reveal the need for the same, adding that even before COVID-19, almost four out of five upper respiratory infections were prescribed antibiotics, despite the fact that they have a viral etiology and are self-limiting.

Citing the reason for use of excess antibiotic usage during COVID-19 pandemic, Dr. Ray said, "The reason why Covid could possibly be a bigger threat is two-fold. One is the high use of steroids and immunosuppressive which can lead to secondary bacterial infections. The patient’s ability to fight these infections is reduced due to the steroids and immunosuppressive, and there is the use of more antibiotics for a longer duration to counter that, leading to further selection pressure among the bacteria for the survival of the most resistant. The second reason is the sheer volume of cases that require hospitalization and ICU care leading to more use of antibiotics, sometimes irrationally."

Apart from the use of steroids and immunomodulatory agents, Dr. Chanchalani emphasized on other reasons like -- putting infection control practice compliance to a toss, fear of missing a secondary infection and lack of specific treatment for COVID-19 and the associated higher mortality of the same, and lack of awareness among the medical field due to mixopathy in India. She added that the research has also shown that most antibiotics prescribed during COVID -19 are from the 'watch' and 'reserve' category of the WHO aware Classification (2019).”

Doctors and experts inform that medicines can’t be subscribed under pressure. Unfortunately, in this pandemic, the family insists to dispense antibiotics – irrational use of ivermectin, hydroxychloroquine, itolizumab, lopinavir, ritonavir and favipiravir won’t help – education or right medicine, right dose at right time, tracking of prescription practices, reporting, auditing and feedback and accountability of prescribing doctors, pharmacy and Anti Microbial Stewardship Practices (AMSP) is the need of the hour.

Combating AMR with AMSP

AMR makes infections harder to treat as it increases the risk of disease and severe illness, leading to death. For over a year, the irrational antibiotic prescription practices could be creating drug-resistant bugs. Clinicians inform that restricting inappropriate or unnecessary use of antibiotics, mechanisms for effective AMSP structure and process should be instituted where it is lacking.

Elucidating about the key AMSP practices, Walia said, “We should prioritize the creation of AMSP teams that should include a clinical pharmacist and a physician trained in infectious diseases, a clinical microbiologist, an informatics specialist, a hospital epidemiologist, and an infection-control specialist. Antibiograms should be generated periodically, and emphasis should be laid on drafting guidelines for antibiotic use in hospitals based on hospital antibiograms. Guidelines for antimicrobial treatment and prophylaxis need to be available in all healthcare systems. Periodical training and certification of hospital staff on AMSP should be done.
"Hospitals can decide to practice prescription audit and feedback or formulary restriction as acceptable to clinicians.”

She further added that capacity for stewardship programs such as monitoring, reporting, and audit, information systems to monitor and track progress and develop innovative strategies should be created. Therapy based on standard guidelines and patients' clinical status should be ensured to control the use of restricted antimicrobials for empirical treatment.

“Other important interventions include directed therapy based on early microscopy tests, immunological and rapid molecular tests, antibiotic “time outs”, de-escalation of therapy, daily adjustment of doses and dosing intervals, change of broad-spectrum antibiotics after culture results are available, and shortening treatment duration in prophylactic use,” added Walia.

Informing that AMSP is important as AMR is always a bigger threat to those with comorbidities, particularly diabetes and other immune-compromised states, as the ability to clear infections is reduced, and these patients have a protracted hospital course leading to more use of antibiotics, further heading towards a vicious cycle.

“Patients undergoing medical procedures mentioned are in any situation more vulnerable to severe or prolonged infections. Having associated Covid-19 makes the situation life-threatening, but, by itself, Covid in these situations probably doesn’t add to AMR,” Dr. Ray informed.

Seconding it, Dr Chanchalani said, “The risk of secondary infections is higher in patients with co-morbid conditions due to impaired ability of the host to fight bacterial pathogens and increased hospital stay due to the co-morbid condition.

Mentioning about immune-compromised patients or those who have undergone medical procedures, Walia said, “Patients who had undergone transplants, or those with chronic diseases, on chemotherapy, or having extended hospital stays, previous courses of antibiotics, steroids, and total parenteral nutrition are at higher risk for bacterial and fungal infections. As per ICMR data from previous years and in Covid-19 patients, secondary bacterial infections/nosocomial infections are most of the time caused by multidrug-resistant Gram-negative


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