­­The Hidden Pandemic: COVID-19’s Impact on Antimicrobial Resistance

By Theresa Hoang, Biodefense MS Student

Introduction

The COVID-19 global pandemic has threatened public health security by adversely altering the health of patients and overwhelming hospital systems throughout the world. Not only is COVID-19 a global health threat, but antimicrobial resistance (AMR) is a public health crisis too. AMR happens when microbes become resistant to antimicrobials that are designed to kill them.[1] AMR contributes to healthcare-associated infections (HAI)­ in patients, which spreads within healthcare facilities and throughout the community and environment.[2] The CDC reports that “each year in the U.S., at least 2.8 million people are infected with antibiotic-resistant bacteria or fungi, and more than 35,000 people die as a result.”1 AMR is a serious public health concern, especially during the pandemic, because experts have noted that COVID-19 may have reversed the progress on reducing AMR by creating a “perfect storm” for antibiotic-resistant infections in healthcare settings.[3] How has the COVID-19 pandemic impacted AMR in clinical patients, and why is it important? This issue is important because it affects patients, who are undergoing antibiotic treatments, and healthcare systems that are trying to prevent the spread of AMR. The current literature has discussed extensively the direct and indirect effects of the COVID-19 pandemic on AMR. A group of authors focuses on the increase of secondary drug-resistant infections and how they are affecting COVID-19 patients. Another group discusses the deterioration of healthcare systems allowing AMR transmission to escalate. Other authors analyze the disruption of antibiotic stewardship and its adverse effects during the pandemic. To fight against this growing pandemic, patients should work together with their healthcare providers to learn about the troubling effects of AMR and how to prevent it from spreading by practicing enhanced antimicrobial stewardship.

Secondary Drug-Resistant Infections from AMR

The surge in AMR during the pandemic has resulted in a rise of secondary drug-resistant infections. The three drug-resistant microorganisms that will be discussed are methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacterales (CREs), and Candida auris.

Scanning Electron Micrograph of MRSA (from CDC)

Methicillin-resistant Staphylococcus aureus

MRSA is commonly spread in healthcare facilities and communities, and it can cause staphylococcus infections that are usually difficult to treat because of its resistance to some antibiotics.[4] Segala et. al explain that, during the pandemic, MRSA co-infections have increased significantly in COVID-19 patients who were admitted to intensive care units (ICUs).[5] “Up to 86.4% of all COVID-19 patients admitted to the ICU received a wide spectrum antibiotic therapy,” which helps treat against a vast majority of co-infections, including MRSA.5 However, exposing patients to these unnecessary antibiotics in a combination therapy can induce AMR. In another case study completed in Italy on mechanically ventilated patients, researchers compared the proportion of ventilator associated pneumonia (VAP) due to MRSA, between COVID-19 patients and non-COVID-19 patients.5 They found VAP rates were significantly higher in COVID-19 patients due to receiving a broad spectrum antibiotic therapy. Their findings also suggest there is higher rate of MRSA colonization and environmental contamination in COVID-19 ICUs.5 MRSA has not only evolved to become more resistant to antibiotics, but it continues to spread and colonize in healthcare facilities and other communities, in addition to infecting COVID-19 patients at increasing rates.

Infographic of the Risk of CRE Infections (from CDC)

Carbapenem-Resistant Enterobacterales (CREs)

Carbapenem-resistant Enterobacterales (CREs), formerly known as CR Enterobacteriaceae and nicknamed “Nightmare bacteria,” are a large group of different types of Gram-negative bacteria, such as Escherichia coli (E. coli) and Klebsiella pneumoniae, that commonly causes multiple infections in humans and in healthcare settings. CREs also develop resistance to a group of antibiotics called carbapenems.[6] CRE infections are spread from person-to-person by infecting or colonizing people (without causing infections or symptoms), specifically contact with wounds or stool, and through medical devices that have not been properly cleaned.[7]

CREs are a threat to public health because they are difficult to treat and are resistant to almost all available antibiotics.6 Their resistance comes from producing carbapenemases, which are enzymes that spread to other germs and cause resistance in carbapenems, rendering them ineffective.4 The CDC states that high levels of antibiotic resistance in CREs necessitate more toxic and less effective treatments, harming patient outcomes.7

Studies have shown that CRE infections are increasing among COVID-19 patients. According to a recent review on CRE infections during the pandemic, “secondary infections caused by CR-Klebsiella pneumoniae (Cr-Kp) show high prevalence of co-infection in COVID-19 patients.”5 Researchers have noticed that CR-Kp colonization and infections were associated with a high mortality rate in COVID-19 patients and increased use of antimicrobial agents.5 This represents a significant challenge for both infection control and clinical practice because as new antibiotics continue to be overused, CRE infections continue to rise and manifest in healthcare facilities and throughout communities.

Candida auris on CHROMagar Candida after Salt Sab Dulcitol Broth enrichment (from CDC)

Candida auris

Candida auris is an emerging multidrug-resistant (MDR) yeast that brings severe infections and spreads easily between hospitalized patients and nursing home residents through skin-to-skin contact.4 It can also cause invasive infections by entering the bloodstream, and even cause wound and ear infections.[8] Moreover, C. auris can trigger outbreaks in healthcare settings by contaminating hospital surfaces and medical equipment, especially if they are used for COVID-19 critical care. This indicates that patients are at high risk of C. auris colonization and infections.[9]

C. auris is an extreme public health threat to communities, and it has become a more serious concern during the pandemic. Since some patients with severe COVID-19 have required intubation and other invasive devices, they are put at a higher risk of C. auris infections; the pandemic may have contributed to an increase in these cases.[10] In another report from the CDC, 39 cases of C. auris have appeared in Florida during the pandemic that were attributed to “unconventional personal protective equipment (PPE) practices and environmental contamination.”[11] Risk factors like these have caused critically ill COVID-19 patients with C. auris infections to stay longer at ICUs and require antifungal drugs for long periods of time.5 This proves that improper and extended use of PPE has played a role in self-contamination and transmission of C. auris among COVID-19 patients.5 To prevent C. auris from spreading, especially among COVID patients, it must be detected immediately and IPC practices must be implemented.

Overall, the three different pathogens share a common goal, which is to induce AMR and increase secondary infections among patients. These drug-resistant microorganisms are a few out of the many other agents that have impacted patients during the COVID-19 pandemic.

AMR Implications for Healthcare Systems

Additionally, during the COVID-19 pandemic, the exacerbation of healthcare systems has increased transmission of AMR. Studies have shown that the rise of AMR in healthcare facilities was caused by a variety of factors, such as prolonged stays in the ICU,[12] overcrowding,[13] “contaminated PPE, increased workload among hospital staff, and prolonged glove usage.”[14] Furthermore, “shortages of PPE, staff shortages, fatigue, and deployment of inexperienced staff members with only basic training” are other factors that may contribute to the increased risk of AMR.[15] These determinants not only led to a surge in AMR, but also increases in morbidity, mortality, and healthcare costs for patients.14

To reduce AMR from escalating any further, Rawson et. al propose that social distancing, increased hand hygiene practice, and pre-emptive discharge of patients and cancellation of routine procedures are potential interventions that healthcare systems can implement during the pandemic.13 In addition, Knight et. al mention “enhanced infection prevention and PPE usage and control measures, in response to the COVID-19 pandemic, will help prevent infections and limit the spread of AMR.”15 Therefore, better health infrastructure and enhanced IPC measures set in place mean minimization of AMR amongst patients.

Disruption of Antimicrobial Stewardship

Disruption of antibiotic stewardship is another problem that needs to be addressed with the rise of AMR driven by COVID-19. Antimicrobial stewardship (AMS) is “promoting the appropriate use of antimicrobials, improving patient outcomes, reducing AMR, and decreasing spread of infections caused by multidrug-resistant organisms (MDROs).”[16] However, AMS has not been emphasized enough during the pandemic. For instance, researchers are concerned that increased antibiotic use during the pandemic could enhance the long-term threat of AMR.[17] Popescu states that “misuse and overprescribing of antibiotics, poor stewardship, and generalized lack of surveillance,” are some reasons why AMR continues to be a public health problem.[18]

Moreover, misinformation on antibiotic use (whether it is low public awareness or increased consumption of them) is another factor that may enhance the rise and spread of AMR.[19] For example, Arshad et. al explain that 44% of respondents to a population survey in Australia assumed that antibiotics could treat or prevent COVID-19, and university students in Jordan who believed in conspiracy theories around COVID-19 also thought antibiotics can cure it.[20] Additionally, clinical uncertainty about the disease process and pathology of an infection can increase antibiotic use. “When clinicians do not have all the necessary information to truly understand what is happening to the patient, they tend to prescribe more antibiotics.”17 Altogether, these factors can increase the spread of AMR and disrupt AMS.

In contrast, Toro-Alzate et. al argue that “telemedicine consultations could be useful to educate patients on improving antibiotic use.”19 But at the same time, they mention how telemedicine can also increase over-prescription of antibiotics due to physicians’ decision making.19 Because they are not with patients in-person, healthcare providers tend to misdiagnose more often and not order as much lab tests with these remote services.

#BeAntibioticsAware: Do I really need antibiotics? (from CDC)

Another AMS strategy is using social media to manage online media campaigns that combat misinformation of antibiotic use. Some organizations, such as WHO and Nigeria Centre for Disease Control, correct antimicrobial misinformation and discuss ineffectiveness of antibiotics as a treatment for COVID-19 by using their digital platforms.20 Taking everything into consideration and how the pandemic impacted the public health community, AMS must be further improved and emphasized among patients and healthcare providers to reduce AMR.

Are Hospital Stays of COVID-19 Patients (with AMR) Longer than Those of Non-COVID Patients?

The literature does not yet analyze the question of whether the length of hospital stays for COVID-19 patients with AMR are longer compared to hospital stays of non-COVID-19 patients. One study has claimed that AMR has led to adverse consequences for patients, including “more prolonged hospital admissions.”[21] Srinivasan mentions and compares the patient discharge data and AMR rates between patients with influenza-like illness and COVID-19.11 Yet, the data between patients with flu and COVID-19 were collected at different time frames.

Source: CAPT Arjun Srinivasan, MD, USPHS (CDC PowerPoint)

In the current literature, there is no evidence and comparison recorded between hospital stays of COVID-19 and non-COVID patients during the pandemic, over the same time period. Considering that the surge in AMR has been driven by the pandemic, and that it has caused ill patients to stay at hospitals based on their conditions, it is hypothesized that COVID-19 patients with AMR have stayed at the hospitals much longer than non-COVID patients during the pandemic. To examine this gap, further research needs to be conducted by attempting to gather data through a survey and compare hospital stay rates between COVID-19 and non-COVID patients from different hospitals in the Northern Virginia area. This would also explore the critical steps needed to treat patients with AMR and to mitigate its transmission before discharging patients.

Conclusion

Antibiotics save lives but any time antibiotics are used, they can induce side effects and lead to AMR.4 Along with the rise in AMR, COVID-19 has compounded this issue, creating more challenges for patients and hospital systems to overcome. The surge of secondary infections among patients, the exacerbation of hospital infrastructures, and the disruption of antimicrobial stewardship are the results of COVID-19’s impact on AMR.

Bibliography

Arshad, Mehreen, Syed Faisal Mahmood, Mishal Khan, and Rumina Hasan. 2020. “COVID-19, Misinformation, and Antimicrobial Resistance.” BMJ371 (November): m4501. https://doi.org/10.1136/bmj.m4501.

CDC. 2021. “Candida auris.” Centers for Disease Control and Prevention. July 19, 2021. https://www.cdc.gov/fungal/candida-auris/index.html.

CDC. 2021. “CRE: Healthcare-Associated Infections (HAI).” Centers for Disease Control and Prevention. April 7, 2021. https://www.cdc.gov/hai/organisms/cre/index.html.

​​CDC. 2021. “Patients | CRE | HAI”. Centers for Disease Control and Prevention. February 18, 2021. https://www.cdc.gov/hai/organisms/cre/cre-patients.html.

CDC. 2020. “What Exactly Is Antibiotic Resistance?” Centers for Disease Control and Prevention. March 13, 2020. https://www.cdc.gov/drugresistance/about.html.

CDC. 2020. “Where Antibiotic Resistance Spreads.” Centers for Disease Control and Prevention. March 10, 2020. https://www.cdc.gov/drugresistance/about/where-resistance-spreads.html.

Centers for Disease Control and Prevention (U.S.). 2019. “Antibiotic Resistance Threats in the United States, 2019.” Centers for Disease Control and Prevention (U.S.). https://doi.org/10.15620/cdc:82532.

Jul 27, Chris Dall | News Reporter | CIDRAP News | and 2021. n.d. “CDC Reports Two Outbreaks of Pan-Resistant Candida Auris.” CIDRAP. Accessed October 6, 2021. https://www.cidrap.umn.edu/news-perspective/2021/07/cdc-reports-two-outbreaks-pan-resistant-candida-auris.

Chowdhary, Anuradha, and Amit Sharma. 2020. “The Lurking Scourge of Multidrug Resistant Candida Auris in Times of COVID-19 Pandemic.” Journal of Global Antimicrobial Resistance 22 (September): 175–76. https://doi.org/10.1016/j.jgar.2020.06.003.

“COVID-19 & Antibiotic Resistance | CDC.” 2021. June 8, 2021. https://www.cdc.gov/drugresistance/covid19.html.

Hsu, Jeremy. “How Covid-19 is Accelerating the Threat of Antimicrobial Resistance.” BMJ: British Medical Journal (Online) 369, (May 18, 2020). http://dx.doi.org.mutex.gmu.edu/10.1136/bmj.m1983.

Knight, Gwenan M., Rebecca E. Glover, McQuaid C. Finn, Ioana D. Olaru, Gallandat Karin, Quentin J. Leclerc, Naomi M. Fuller, et al. 2021. “Antimicrobial Resistance and COVID-19: Intersections and Implications.” ELife 10. http://dx.doi.org/10.7554/eLife.64139.

Majumder, Md Anwarul Azim, Sayeeda Rahman, Damian Cohall, Ambadasu Bharatha, Keerti Singh, Mainul Haque, and Marquita Gittens-St Hilaire. 2020. “Antimicrobial Stewardship: Fighting Antimicrobial Resistance and Protecting Global Public Health.” Infection and Drug Resistance 13: 4713–38. http://dx.doi.org/10.2147/IDR.S290835.

Manning, Mary Lou, Edward J. Septimus, Elizabeth S. Dodds Ashley, Sara E. Cosgrove, Mohamad G. Fakih, Steve J. Schweon, Frank E. Myers, and Julia A. Moody. 2018. “Antimicrobial Stewardship and Infection Prevention—Leveraging the Synergy: A Position Paper Update.” American Journal of Infection Control 46 (4): 364–68. https://doi.org/10.1016/j.ajic.2018.01.001.

Popescu, Saskia. 2019. “The Existential Threat of Antimicrobial Resistance.” Bulletin of the Atomic Scientists 75 (6): 286–89. https://doi.org/10.1080/00963402.2019.1680053.

Rawson, Timothy M, Luke S P Moore, Enrique Castro-Sanchez, Esmita Charani, Frances Davies, Giovanni Satta, Matthew J Ellington, and Alison H Holmes. 2020. “COVID-19 and the Potential Long-Term Impact on Antimicrobial Resistance.” Journal of Antimicrobial Chemotherapy 75 (7): 1681–84. https://doi.org/10.1093/jac/dkaa194.

Segala, Francesco Vladimiro, Davide Fiore Bavaro, Francesco Di Gennaro, Federica Salvati, Claudia Marotta, Annalisa Saracino, Rita Murri, and Massimo Fantoni. 2021. “Impact of SARS-CoV-2 Epidemic on Antimicrobial Resistance: A Literature Review.” Viruses 13 (11): 2110. https://doi.org/10.3390/v13112110.

​​Srinivasan, Arjun. “The Intersection of Antibiotic Resistance (AR), Antibiotic Use (AU), and COVID-19.” Centers for Disease Control and Prevention. February 10, 2021. https://www.hhs.gov/sites/default/files/antibiotic-resistance-antibiotic-use-covid-19-paccarb.pdf.

Sun Jin, Louisa and Fisher, Dale. 2021. “MDRO Transmission in Acute Hospitals during the COVID-19 Pandemic.” Wolters Kluwer Health, Inc. (34) 4: 365–371.

Toro-Alzate, Luisa, Karlijn Hofstraat, and Daniel H de Vries. 2021. “The Pandemic beyond the Pandemic: A Scoping Review on the Social Relationships between COVID-19 and Antimicrobial Resistance.” International Journal of Environmental Research and Public Health 18 (16): 1–20. https://doi.org/10.3390/ijerph18168766.        

Vidyarthi, Ashima Jain, Arghya Das, and Rama Chaudhry. 2021. “Antimicrobial Resistance and COVID-19 Syndemic: Impact on Public Health.” Drug Discoveries & Therapeutics 15 (3): 124–29. https://doi.org/10.5582/ddt.2021.01052.


[1] CDC. 2020. “What Exactly Is Antibiotic Resistance?” Centers for Disease Control and Prevention. March 13, 2020. https://www.cdc.gov/drugresistance/about.html.

[2] CDC. 2020. “Where Antibiotic Resistance Spreads.” Centers for Disease Control and Prevention. March 10, 2020. https://www.cdc.gov/drugresistance/about/where-resistance-spreads.html.

[3] “COVID-19 & Antibiotic Resistance | CDC.” 2021. June 8, 2021. https://www.cdc.gov/drugresistance/covid19.html.

[4] Centers for Disease Control and Prevention (U.S.). 2019. “Antibiotic Resistance Threats in the United States, 2019.” Centers for Disease Control and Prevention (U.S.). https://doi.org/10.15620/cdc:82532.

[5] Segala, Francesco Vladimiro, Davide Fiore Bavaro, Francesco Di Gennaro, Federica Salvati, Claudia Marotta, Annalisa Saracino, Rita Murri, and Massimo Fantoni. 2021. “Impact of SARS-CoV-2 Epidemic on Antimicrobial Resistance: A Literature Review.” Viruses 13 (11): 2110. https://doi.org/10.3390/v13112110.

[6] CDC. 2021. “CRE: Healthcare-Associated Infections (HAI).” Centers for Disease Control and Prevention. April 7, 2021. https://www.cdc.gov/hai/organisms/cre/index.html.

[7] CDC. 2021. “Patients | CRE | HAI”. Centers for Disease Control and Prevention. February 18, 2021. https://www.cdc.gov/hai/organisms/cre/cre-patients.html

[8] CDC. 2021. “Candida auris.” Centers for Disease Control and Prevention. July 19, 2021. https://www.cdc.gov/fungal/candida-auris/index.html.

[9] Chowdhary, Anuradha, and Amit Sharma. 2020. “The Lurking Scourge of Multidrug Resistant Candida Auris in Times of COVID-19 Pandemic.” Journal of Global Antimicrobial Resistance 22 (September): 175–76. https://doi.org/10.1016/j.jgar.2020.06.003.

[10] Jul 27, Chris Dall | News Reporter | CIDRAP News | and 2021. n.d. “CDC Reports Two Outbreaks of Pan-Resistant Candida Auris.” CIDRAP. Accessed October 6, 2021. https://www.cidrap.umn.edu/news-perspective/2021/07/cdc-reports-two-outbreaks-pan-resistant-candida-auris.

[11] Srinivasan, Arjun. “The Intersection of Antibiotic Resistance (AR), Antibiotic Use (AU), and COVID-19.” Centers for Disease Control and Prevention. February 10, 2021. https://www.hhs.gov/sites/default/files/antibiotic-resistance-antibiotic-use-covid-19-paccarb.pdf.

[12] Vidyarthi, Ashima Jain, Arghya Das, and Rama Chaudhry. 2021. “Antimicrobial Resistance and COVID-19 Syndemic: Impact on Public Health.” Drug Discoveries & Therapeutics 15 (3): 124–29. https://doi.org/10.5582/ddt.2021.01052.

[13] Rawson, Timothy M, Luke S P Moore, Enrique Castro-Sanchez, Esmita Charani, Frances Davies, Giovanni Satta, Matthew J Ellington, and Alison H Holmes. 2020. “COVID-19 and the Potential Long-Term Impact on Antimicrobial Resistance.” Journal of Antimicrobial Chemotherapy 75 (7): 1681–84. https://doi.org/10.1093/jac/dkaa194.

[14] Sun Jin, Louisa and Fisher, Dale. 2021. “MDRO Transmission in Acute Hospitals during the COVID-19 Pandemic.” Wolters Kluwer Health, Inc. (34) 4: 365–371.

[15] Knight, Gwenan M., Rebecca E. Glover, McQuaid C. Finn, Ioana D. Olaru, Gallandat Karin, Quentin J. Leclerc, Naomi M. Fuller, et al. 2021. “Antimicrobial Resistance and COVID-19: Intersections and Implications.” ELife 10. http://dx.doi.org/10.7554/eLife.64139.

[16] Manning, Mary Lou, Edward J. Septimus, Elizabeth S. Dodds Ashley, Sara E. Cosgrove, Mohamad G. Fakih, Steve J. Schweon, Frank E. Myers, and Julia A. Moody. 2018. “Antimicrobial Stewardship and Infection Prevention—Leveraging the Synergy: A Position Paper Update.” American Journal of Infection Control 46 (4): 364–68. https://doi.org/10.1016/j.ajic.2018.01.001.

[17] Hsu, Jeremy. “How Covid-19 is Accelerating the Threat of Antimicrobial Resistance.” BMJ: British Medical Journal (Online) 369, (May 18, 2020). http://dx.doi.org.mutex.gmu.edu/10.1136/bmj.m1983.

[18] Popescu, Saskia. 2019. “The Existential Threat of Antimicrobial Resistance.” Bulletin of the Atomic Scientists 75 (6): 286–89. https://doi.org/10.1080/00963402.2019.1680053.

[19] Toro-Alzate, Luisa, Karlijn Hofstraat, and Daniel H de Vries. 2021. “The Pandemic beyond the Pandemic: A Scoping Review on the Social Relationships between COVID-19 and Antimicrobial Resistance.” International Journal of Environmental Research and Public Health 18 (16): 1–20. https://doi.org/10.3390/ijerph18168766.          

[20] Arshad, Mehreen, Syed Faisal Mahmood, Mishal Khan, and Rumina Hasan. 2020. “COVID-19, Misinformation, and Antimicrobial Resistance.” BMJ 371 (November): m4501. https://doi.org/10.1136/bmj.m4501.

[21] Majumder, Md Anwarul Azim, Sayeeda Rahman, Damian Cohall, Ambadasu Bharatha, Keerti Singh, Mainul Haque, and Marquita Gittens-St Hilaire. 2020. “Antimicrobial Stewardship: Fighting Antimicrobial Resistance and Protecting Global Public Health.” Infection and Drug Resistance 13: 4713–38. http://dx.doi.org/10.2147/IDR.S290835.

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