Taking Aim at Antibiotic-Resistant Bacteria During COVID

Even in the midst of the coronavirus disease 2019 (COVID-19) pandemic, we should not forget that about 500 people in the United States die each day from antibiotic-resistant organisms. That was one of the points stressed by Admiral Brett Giroir, the nation’s Assistant Secretary of Health at the US Department of Health and Human Services (HHS) during the 2020 Fall Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. The public portion of the meeting was held online September 9 and 10.

One difference between COVID-19 and multidrug-resistant organisms (MDROs) is that the MDRO is a silent epidemic, comparatively. However, headway is being made.Amanda Cash, DrPH, MPH, a senior health policy analyst at HHS pointed out that from 2012 to 2017, overall deaths from MDROs dropped 18%, and in hospitals they dropped 30%.

It was evident to me that all of this may have changed with the advent of the COVID-19 pandemic.

Arjun Srinvasan, MD, the associate director for healthcare-associated infection prevention programs for the US Centers for Disease Control and Prevention (CDC), pointed out that there are bacterial coinfections that occur with COVID-19 along with antibiotic usage patterns. Preliminary CDC analysis indicates that, COVID-19 leads to a much longer hospital length-of-stay than influenza-like illnesses, 8.44 days compared with 5.88 days, respectively, a finding which was echoed by a number of presenters. Patients with COVID-19 experience a similar number of positive bacterial cultures as they do influenza-like illnesses, 12% in each group. However, during the pandemic, preliminary data reviled that, patients with COVID-19 were more likely to contract healthcare-acquired infections (HAIs), possibly due to longer hospital stays. The most common MDRO infecting patients with COVID-19 was methicillin-resistant Staphylococcus aureus (MRSA), followed closely by extended spectrum beta-lactamases (ESBL)-producing organisms. MRSA caused just under half of the COVID-19 hospital-acquired antibiotic resistant infections.

Kevin Kavanagh, MD

CDC preliminary data also found that during the pandemic, total hospitalizations in the United States decreased by approximately 25%. However, inpatient antibiotic usage did not markedly change. The most common types of antibiotics prescribed were ceftriaxone for presumptive community acquired pneumonia, which increased by 22% in April and then fell during the summer, and azithromycin, possibly used in conjunction with hydroxychloroquine, the rate of which increased by 55% in April and then also fell. It was evident to me that in both cases the usage pattern represents changes in both diagnostic ability and treatment recommendations.

Outpatient visits fell by 60%, with antibiotic prescriptions falling by 40%. Azithromycin has been the most commonly prescribed outpatient antibiotic and, with the exception of the COVID-19 hotspots New York or New Jersey, its use also decreased.

From this presentation and others, I concluded that the fall in outpatient visits may have been due to not only a reluctance to seek care, but also to fewer respiratory infections as a result of implementing public health preventive measures.

Emily Heil, PharmD, a board member of the Society of Infectious Diseases Pharmacists, reported similar findings with only 3.5% of patients with COVID-19 having a bacterial coinfection on admission and overall, 14.3% of patients developing a coinfection. However nearly three quarters of all patients were prescribed an antibiotic, usually broad spectrum. Seventy-four percent of the time a fluoroquinolone or cephalosporin was prescribed, which are often the targets of stewardship programs.

Kalvin Yu, MD, the medical director at Becton Dickinson & Co., also reported that COVID-19 hospitalized patients have a higher death rate, higher intensive care unit (ICU) utilization, and longer length-of-stay than COVID-19–negative patients. Mortality for those in the ICU was 38.2% for COVID positive vs. 13% for COVID-19–negative patients and even more pronounced mortality differences were observed for non-ICU admissions, with mortality rates of 10.9% and 1.8%, respectively. Twenty-four percent of COVID-19–positive patients were admitted to the ICU compared with 17% of COVID-19–negative patients. Length-of-stay was 8.7 days and 5.1 days, respectively.

Antibiotics were used in 68% of COVID-19–positive patients, compared to 46% of COVID-19–negative patients. Antibiotics used in COVID-19–positive patients were already those with antibiotic resistance problems including, Ceftriaxone, macrolides, and vancomycin. Finally, Yu presented data regarding COVID positive patients havinga high rate of S aureus, including MRSA infections. Pseudomonas and Candida occur more frequently in COVID-19–positive than COVID-19–negative patients.

Multiple presenters, including Hana Balkhy, MD, the executive director for infection prevention and control atthe World Health Organization, and Andrew Singer, PhD, UK Centre for Ecology & Hydrology, also stressed that less than 10% of COVID-19–hospitalized patients had or developed a bacterial coinfection, but approximately 70% were on antibiotics.

However, of the patients who die, the incidence of coinfections may be higher. Cornelius Clancy, MD, the chief of the infectious diseases section at VA Pittsburgh Health Care System, reviewed nearly 500 published autopsy reports and concluded that between 35% to 40% of patients who die with COVID-19 have histopathological findings consistent with a pulmonary coinfection.

Heil stressed that the above observations underscore the need for antibiotic stewardship programs. But stewardship activities decreased as pharmacists were shifted to COVID-19–related activities such as writing new therapeutic guidelines and updates, overseeing clinical trials, emergency use authorizations, and the administration of novel medications. To compound matters, in many institutions, staff were also laid off for budgetary considerations. “This loss of personnel may have long-term consequences,” Heil warned.

The impact of telehealth on antibiotic stewardship was discussed by Gail Golab, the chief veterinary officer, scientific affairs and public policy at the American Veterinary Medical Association. Several peer-reviewed reports have found that antibiotics for respiratory and ear infections are prescribed at a higher rate in human telemedicine than in-person visits. This appears to be a consequence of not being able to perform a physical exam or laboratory evaluation, making antibiotic prescription clinical guidelines more difficult to follow. However, it has also been shown that telehealth can help implement antibiotic stewardship programs which have led to lower antimicrobial use.

All of this points to the need for an effective COVID-19 vaccine and innovative strategies to expand testing.

Sean O’Leary, MD, a professor specializing in pediatric infectious diseases at the University of Colorado, stressed that vaccines that sit in refrigerators do not save lives, vaccinations given to suspectable patients do. And all is dependent upon public vaccination acceptance. Childhood vaccines are well accepted with 94.7% of children receiving the measles, mumps, and rubella vaccinations. However, influenza vaccination has only a 45% compliance rate. O’Leary reviewed research from Yale², which examined acceptance of a SARS-CoV-2 vaccine: More respondents reported they would receive a COVID-19 vaccine compared with a flu vaccine.The one exception was the Black population who had the lowest acceptance, even though their communities are severely impacted by COVID-19.

O’Leary reviewed an August 25 to 27, 2020 STAT/Harrris poll³ found that the majority of the respondents (78%) from both political parties feel the COVID-19 vaccine is driven more by politics than science. Both the CDC and US Food and Drug Administration setting possible goals before the election fueled this paranoia along with the initiative’s name of Warp Speed. O’Leary stressed that messaging regarding the safety of vaccines needs to be done carefully so as not to create a “backfire effect,” where the message, although accurate, further entrenches the antivaccination beliefs of the recipient.

It is exceedingly difficult to remove misinformation from the minds of those who are not willing to be vaccinated. You may actually reinforce the myth by making it more familiar, by providing too many arguments, or threatening the holder’s world view.

O’Leary described 3 components of a message designed to debunk a myth: Focus on core facts, explicitly say the myth is false, and offer an explanation as to why the misinformation has occurred.

The most important way to encourage vaccination is to have the vaccine recommended by the provider.

An important advance in monitoring the spread of COVID-19 is the pool testing of multiple samples using a single test. This technique conserves resources and efficiently identifies carriers.

This concept was elevated to a new level by Sean Norman, MSc, PhD, the director of the molecular microbial ecology lab at the University of South Carolina, who described the utility of pool testing sewage. This innovative approach allows an unbiased testing of SARS-CoV-2 levels in the community, which includes both symptomatic and asymptomatic carriers. Results from such testing can guide community decisions on how to reopen activities in our society. In addition, a more targeted application is the monitoring of individual office buildings or university dorms. A positive test can then be used to identify carriers with targeted case tracking.

COVID-19 is a severe illness and stressor on our healthcare system that is rapidly changing the practice of medicine. Patients afflicted with COVID-19 have an increased susceptibility to antibiotic-resistant infections both from prolonged hospitalizations and the use of immunocompromising agents such as dexamethasone. MRSA was found to be the most common antibiotic-resistant organism in these patients. A finding arguably produced by a culmination of ineffective past strategies to control MDROs let alone prepare for a pandemic.

The United States has endured both supply shortages and disruptions in the antibiotic supply chain, affecting availability of antibiotics for tuberculosis and sexually transmitted infections, a result of ineffective preparation and a slow and anemic response at the beginning of the pandemic.

As aptly stated by Srinvasan: “The pandemic laid bare the fact that our healthcare-associated infections and antibiotic use and resistance programs at both the state and facility level are both significantly underfunded and understaffed, in too many instances where one meets in this area a challenge set up for failure.”

The most important consensus which was echoed throughout the conference was that social distancing and wearing a mask cannot only help with COVID-19, but may also profoundly decrease the flu season.

It’s all up to us.

References:

1. Rawson TM, Moore LSP, Zhu N, et al. Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing [published online ahead of print, 2020 May 2]. Clin Infect Dis. 2020;ciaa530. doi:10.1093/cid/ciaa530
2. Malik AA, McFadden SM, Elharake J, Omer SB. Determinants of COVID-19 vaccine acceptance in the US [published online ahead of print, 2020 Aug 12]. EClinicalMedicine. 2020;100495. doi:10.1016/j.eclinm.2020.100495
3. Silverman E.Poll: Most Americans believe the Covid-19 vaccine approval process is driven by politics, not science.STAT.Aug. 31, 2020.Accessed Sept. 14, 2020. https://www.statnews.com/pharmalot/2020/08/31/most-americans-believe-the-covid-19-vaccine-approval-process-is-driven-by-politics-not-science/​