Today we finally had some good news in our fight against coronavirus disease 2019 (COVID-19). Eli Lilly announced preliminary results to their SARS-CoV-2 neutralizing antibody product, LY-CoV555, which was reported to have 

. In an investor news release they stated that in a Phase 2 randomized double-blind controlled trial they observed a 72% decrease in hospitalizations or ER visits with LY-CoV555.

This is excellent news after the mediocre findings of the recent randomized trial of remdesivir which found outcome differences of “

Eli Lilly stated LY-CoV555 was “well tolerated” without the observation of any drug-related serious events. And that adverse events were similar to placebo. However, the exact incidence of milder drug reactions which could affect patient acceptance were not given in the news release.

Eli Lilly also observed that most hospitalizations occurred in patients who had an increased age or BMI. Underscoring the importance of the co-morbidities of age and obesity in COVID-19 disease.

A related product, convalescent serum, was found to have clinical efficacy when it was given within 3 days of diagnosis and in high concentration. And although given an FDA emergency authorization, its overall benefit has since been panned in the news media.

One may ask, why are the Eli Lilly results different from the positive, but somewhat disappointing, results of convalescent serum? The short answer is, they are not. LY-CoV555 targets the same clinical sweet spot where convalescent serum was found to be most effective.

In the Eli Lilly trial, LY-CoV555 was given to patients with mild to moderate symptoms and within 3 days of their diagnosis. In other words, similar to convalescent serum, initial results demonstrate that LY-CoV555 is effective if given in the early stages of the disease, soon after diagnosis. In addition, Eli Lilly’s product is designed to be composed of highly effective neutralizing antibodies.

Meeting these patient administration requirements on a mass scale is almost an impossible task with convalescent serum. There just is not enough to have it in everyone’s urgent treatment center. But the Eli Lilly product is composed of a high concentration of highly effective neutralizing antibodies, which hopefully can be manufactured in great enough quantities to become a bridge to a vaccine.

One cautionary note was a statement: “Viral RNA sequencing revealed putative LY-CoV555-resistance variants in placebo and all treatment arms. The rate of resistance variants was numerically higher in treated patients (8 percent) versus placebo (6 percent).”

Thus, as with any anti-viral agent, viral resistance might possibly develop. This is to be expected. Nature adapts and RNA viruses are known to have a proclivity to mutate. This is often observed in phage therapy where there is described a dance of mutations between the bacteria and 

. However, in this instance, the viral mutations are beneficial when you are wanting to kill an evolving bacteria, but are detrimental when targeting the virus itself.

LY-CoV555 targets an “epitope in the SARS-CoV-2 spike region”. This is the same region many vaccines are targeting. So far, SARS-CoV-2 has not appeared to mutate at a very fast rate regarding its spike protein region. However, the development of resistance to LY-CoV555 will still need to be carefully monitored, since the emergence of a new resistant viral strain could impact the efficacy of not only monoclonal antibodies but also of future vaccines.

There would be less of a concern if LY-CoV555 was targeted and effective in the few who were severely sick, but it appears its application is most beneficial when given early and possibly to the masses. But, it is probably not realistic that LY-CoV555 can be produced in high enough volume to be available to all. No SARS-CoV-2 product to date has been able to even approach this goal. As observed in the Eli Lilly study, those newly diagnosed patients who are obese or have advanced age are the most likely to become hospitalized, and I feel initially this innovative product should be targeted toward these high-risk patients.

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Eli Lilly stated LY-CoV555 was “well tolerated” without the observation of any drug-related serious events. And that adverse events were similar to placebo. However, the exact incidence of milder drug reactions which could affect patient acceptance were not given.

Eli Lilly Neutralizing Antibodies: Breakthrough for COVID-19 Treatment?

In his long and distinguished career, the Brent James, MD, an internationally known health care expert, worked on both the insurance and provider sides. James is currently pushing a system called direct to business, which allows large employers and large hospital systems in a region to contract directly, cutting out the health insurer middleman. James recently sat down with 

 and provided examples of how such a system might bolster infection control and prevention. “Time after time, I’ve seen it dramatically improve clinical outcomes and reduce costs,” says James.

Direct to business arrangements. What are they? How they come about?

Why did they set up in the first place? You know, the best way I know to introduce it: Some years ago, I was asked to chair a strategic planning committee at Intermountain. Eventually it produced our population health initiative. In the committee, I had senior executives from across the system, including the three senior leaders from our own health plan, Intermountain Select Health, the largest commercial insurer in the region. Well as we were working our way through, I asked a question. I said: “Exactly how does an insurance company add value?” We came up with a list of 10 major items, there are lots of smaller ones just to give you a flavor for it. They do something called transaction processing, insurance claims processing—surprisingly difficult, by the way, real expertise around that. Actuarial risk analysis. Part of that is reinsurance. When you reinsure a patient. It’s for really high-cost patients. They did a certain amount of benefit design. They did a certain amount of customer support. Oh, a big one. They did network formation, where they found a sufficient number of hospitals, clinics, physicians to supply all health needs for the uninsured population. The list goes on. We did the analysis. The thing that we found is, number one, almost all of them were available as commodities in the general market. You could purchase them, outsource them, the claims process and the actuarial risk analysis, for example. You could purchase them at very good prices competently done in the external market. The only element that they couldn't outsource was network formation. But we realized that the system was large enough that it could form its own network. They had a sufficient blend of physicians and facilities that they can handle that on their own. The second piece, we came back next and said, “All right, given that this is the value add, how much should it cost?” We express it as percentage of the premium dollar. The answer we got was between 4% and 8% of the premium dollar. Seemed low. But I checked in our community. We had a number of nonprofit insurers. Desert Mutual Benefit Administrators, the DMBA, that’s the LDS Church’s self-insurance plan. PEHP, that’s the public employees health plan. It’s a consortium of public employee groups from around the state [Utah]. Educators Mutual, that’s for schoolteachers. They were all running at about 4%. That’s roughly where Medicare runs too, just in passing. It turns out the 4% to 8% estimate was pretty reasonable. Oh, the trick. Major for-profit insurers will pull somewhere between about 15% and 20% of the premium dollar to put on to their bottom line in the stock market. And it was that difference, let’s say between 6% and 18%. Twelve percent of the premium dollar is a lot of money. And that was the economic argument that if a large integrated system could go direct to self-insured employers, ERISA plans, that they could then through negotiation, decide how to divide that pie of 12% of the premium dollar. Now, frankly, given that it’s the health system that puts it together, and the health system that has to do the care management within it, I’m prejudice. I think it ought to swing a little bit more to the care delivery system side. But that’s what made it so very attractive. Now let’s shift gears and go to the other side, the care management side. A lot of insurance companies claim that that’s how they added value. That’s how they justified the additional spend. Fact is, we’ve proven that care management works much better at the level of the care delivery system than at the level of insurance. And we had our data showing that makes sense. It happens better if it’s closer to the point of action, where a patient interacts with the system, and the insurance companies are kind of two giant steps away. We knew that, “Oh, if you start to manage care, that’s where you get into the whole population health thing.” We estimated that we could drop the cost of care by 30% to 50%. So, you’ve got, let’s say, 14% here, but then you’ve got over here, you’ve got waste elimination to better care management. The cool thing about the waste elimination, the way you get it is to improve your clinical outcomes. The money aligns to your mission, better clinical outcomes, lower costs. And you’ve got an even bigger pot of money to share.

How does it standardize care and prevent defensive medicine?

Well, a classic. It was an infection control case. The patient went in for open heart surgery. He developed an infection, a post-op infection from a staph epidermidis, a common bacterium that lives on everyone’s skin and it’s usually completely innocuous. This was a strange variant. The patient had a very fast, bad course and died. Shortly after he died, his estate sued the hospital and the physicians because we didn’t prophylax that staph epidermidis. Turns out it was right in the protocol. They had a list of organisms that we did prophylax. They had a list that they purposefully did not. It turns out that we had the evidence based best standard. It doesn’t say you have to do everything. He just says that you deliver good care, and by consensus in our infectious disease staff, and the consensus among our physicians and nurses, that was best care. And what we did is we pulled out the protocol and then showed it to the plaintiff’s attorney. Once again, another lawsuit dropped fairly quickly before you go through all the trouble of preparation. That’s where the real money goes, by the way, in discovery and preparation. We had a long list of those cases. Now imagine the opposite happens. Imagine you have the standard, and you need to verify. All right, well, two things. We had built into every protocol, it was just boilerplate our attorneys have helped us with, it said this protocol is designed for the general use of most patients, but may need to be adapted to specific use of a particular patient by the patient’s caregiver. All right, it was right there in the protocol. It was honest, it’s exactly how we used it. It also became number two. That’s when you need the note. When you need that six-word note is when you choose to vary. You just need a clinical explanation, but it became a marker: “Oh, this is where I need the note to protect me.” You see, I have to tell you honestly on long experience, it reduced our malpractice risk because it established a legitimate written standard of care. And it told us in the document so on that our malpractice risk went down.

What about defensive medicine? That’s a big problem.

There are two elements to that too. The first was this. What turned out what was happening…. We investigated this a bit. So, you measure variation in care. one guy’s doing it one way, another person is doing it a different way. Third person’s doing it differently still, and we go back and ask him why, why did you do that? And nearly always they come back and say defensive medicine. It was a really common response. What we discovered, though, is it probably wasn’t defensive medicine that was just plain old garden variation. I was doing it in my opinion with very little support. Right. So, it was a marker for variation, and it probably wasn’t a legitimate answer. To be honest. It’s just a handy hook to hang your hat on when somebody challenges about why you’re doing this in this crazy way. You see, well, that kind of went away, but you have to give that pressure relief valve. On average, you know, we did this for over 125 protocols. You vary about 5% to 15% typically. I used to say it this way to my colleagues just to make it real easy: “Look, guys, we’re tracking protocol brands. You will get as much scrutiny for complying with protocols as for complying too little. If you’re different from your colleagues, we want to take a look. The first time that really played out was in infectious disease interestingly enough. John Burke, the head of infectious disease, had a system. If you had an inpatient who developed an inpatient infection, it was like he got a console from ID in about three or four seconds. You just called up the program. You had to tell it the sites of infection you’re interested in, but then it did an epidemiologic evaluation of that patient. The first screen listed: Here are the most likely causative pathogens in our experience at this hospital. It gives you a differential of causative pathogens. There’s a 72% chance it’s this one. Oh, with this pattern of sensitivities, there’s a 59% chance it’s this one. There’s a 31% chance with this one. With each sensitivity in probability order. If you went one screen ahead, it said, here’s the best antibiotics to treat this set of infections. It actually gives you several choices. It was in priority order by efficacy number one, and then if it had several similar efficacies, it prioritized them in cost order. And if you saw one you like, give me a number two. It ordered the drug, it alerted the nurses. If you had level testing, it automatically did the level testing. Now initially, people were really kind of watchful around this thing. Did it deliver good care, as you would expect from any good group of clinicians. But it turned out to work and it worked pretty well. The real problem is, oh, two months later, they came to us and said, “You know, we don’t really need to see the differential. Just show us a list of antibiotics. It will shorten our time.” And then they came back and said, “Don’t show us the whole list of antibiotics. We pretty much always want the one on the top. Just show us the top one.” It reduced it to a single click, single return. And it took the time that when I was practicing surgery, it used to take me 10 to 15 minutes. It probably cut it by half. You see, that was really popular. But then we saw the downside. The downside was John Burke, using the same system, started to pick up cases where they should have buried, and didn't. It made it so dang easy to follow the protocol that, you know, people aren’t thinking as hard as they should. But it turns out the same system that detected it…. At the time at LDS hospital, you might get a console from ID even if you didn’t order one. Because John Burke was monitoring the whole hospital and he’d come by on cases that looked like they needed a little expert oversight and just show up. They learned how to interact with their colleagues in a positive way. What we saw—by the way, this was published in 

—was a rather dramatic drop in…. Well, it was infection related mortality was what they were tracking in that study. And side-by-side with it, a drop in costs. I love the way that one of our ID docs said it. He said it was more targeted therapies where you were getting the right therapy to the right patient at the right time.

You know, I’ve been looking for my whole career for things that make this happen faster and better. Time after time, I’ve seen it dramatically improve clinical outcomes and reduce costs. Sometimes it’s a real uphill fight. And frankly, on my side, it mostly has to do with administration worried about the revenues. When you move into these straight to business relationships, technically, it’s a form of shared savings, and it solves the financial side so that medically we can do what’s right. And I’m pretty sanguine about it. I like it a lot. I think it’s a good way to practice medicine that will make us better doctors, help us learn faster, and help us deliver dramatically better care to our patients. I hope it takes over the world. I think it will make us better doctors and a better practice in general.

Oh, yes. Oh, yes. The examples I just used were all infection, weren’t they?

This interview has been edited for clarity and length.

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Brent James, MD: “If you had an inpatient who developed an inpatient infection, it was like he got a console from ID in about three or four seconds. You just called up the program. You had to tell it the sites of infection you’re interested in, but then it did an epidemiologic evaluation of that patient.”

Q&A: How Direct to Business Coverage Can Help Infection Care

Bug of the Month helps educate readers about existing and emerging pathogens of clinical importance in healthcare facilities today. Each column explores the Bug of the Month's etiology, the infections it can cause, the modes of transmission, and ways to fight its spread. The pathogen profiles will span bacterial, viral, fungal and parasitic species. We encourage you to use Bug of the Month as a teaching tool to help educate healthcare personnel and start a dialogue about microbiology-related imperatives.

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Bug of the Month helps educate readers about existing and emerging pathogens of clinical importance in healthcare facilities today.

Bug of the Month: I Can Be Deadly for Cystic Fibrosis Patients

As respiratory virus season nears, this would normally be the time hospitals would work to start planning for flu vaccination distribution and metrics for visitor restrictions. This year though … things are different. Normally visitor restrictions are about limiting the number for each patient, and no children under the age of 12. Visitor restrictions though, in the era of coronavirus disease 2019 (COVID-19) is vastly different.

For many, we have just started to have conversations about relaxing visitor restrictions that were implemented for COVID-19. Most hospitals 

have implemented stringent visitor restrictions

 that don’t allow anyone to visit, even during end of life. While an understandable public health and infection prevention measure, it has generated some concern. Hospitals have scrambled to find ways to ensure that families and loved ones are able to stay up to date and help make stressful medical decisions in this remote setting.

From ensuring calls several times a day to providing tablets for video chatting, these are measures that had to be quickly enacted for not only medical care, but also patient and family satisfaction. As Jason Karlawish, MD, 

, “When this pandemic is over, we ought to compare the outcomes of care in hospitals that recognized the role of caregiver and had programs like HELP and those that did not. I’d bet we would find that when caregivers were present, resources and lives were saved. Even more valuable will be the dignity we preserved when faced with a pandemic that threatened humanity. With these insights, we’ll change ‘visitor rules’ to recognize the need for a caregiver for persons with cognitive impairment.”

Now though, as we move to open things a bit in areas with lower community transmission, the question is – how do we relax things safely? Masks for all, but what if a visitor refuses to wear a mask? Many are opting to limit visitors to one per patient in an incremental process. The challenge though, will be doing this slowly as to avoid straining visitor screening measures.

One thing we’ll have to consider is how will this impact the potential for healthcare-onset cases of COVID-19. With universal masking in hospital still, the potential for a visitor to remove their mask or introduce COVID-19 to a patient is much more likely, especially with a disease that is frequently asymptomatic. This piece will be particularly challenging as the asymptomatic aspects of COVID-19 make healthcare-associated cases highly dependent on testing – but how often? Aside from testing on admission, should patients be screened as they are allowed visitors?

Therein lies the challenge of infection prevention in a COVID-19 world – the nuances that make healthcare-associated cases hard to understand and much more complex than just an incubation period. Moreover, this also begs the question if a healthcare-onset definition for COVID-19 will be present in the 2021 Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) chapters that we rely on for surveillance. These critical pieces need to be addressed as we not only navigate the longevity of the COVID-19 pandemic, but also consider the role of visitors.

Most hospitals have implemented stringent visitor restrictions that don’t allow anyone to visit, even during end of life. While an understandable public health and infection prevention measure, it has generated some concern.

Visiting Hours: Time to Re-evaluate Restrictions Caused by COVID

A vascular access consultation order is placed, and the process begins. What is the patient’s admission diagnosis? Ordered medications? Expected length of stay? What is their vascular access history and what might they need in the future? Are there any physical, psychological, or perceptual barriers in regard to the placement of a vascular access device (VAD)? What is the patient, nursing staff, and physician preference in VAD? All these questions are addressed by the vascular access specialist working in today’s healthcare environment.

As healthcare has evolved, so too has the role of those working in the vascular access specialty. At my 117-bed community hospital, I have been a part of much of this evolution. When I started placing peripherally inserted central catheters (PICC) 7 years ago, I knew very little about vascular access as a specialty. PICC placement was a skill I had wanted to learn since I witnessed my first placement while still in nursing school and, once I became part of the “PICC Team,” I worked hard to improve my skill.

I did not look at vascular access in a holistic way, and I did little in the way of assessment prior to placing an ordered PICC. As my knowledge grew, I joined national professional organizations, attended local chapter meetings, and read professional journals, and it became clear that the PICC nurse was evolving into the vascular access nurse. I realized the next step would be forming a vascular access team.

The vascular access team at my facility was created 2 years ago with the goal of improving patient outcomes and increasing staff and patient satisfaction. Although we have never had a large number of central line-associated bloodstream infections (CLABSIs), one of our biggest goals was to prevent CLABSI by ensuring that only the most skilled inserters place PICC and midlines and that daily rounding by specialists is performed on all central lines. Although our infection preventionist is not an official member of the vascular access team, we do work closely with her to update and create new policies and interventions pertaining to vascular access. We also work together to stay current on best practices and to trial any products we feel might benefit our patients in reducing infection rates.

Our close working relationship with the infection preventionist stems from the fact that we trust each other to keep what is best for patients at the center of everything we do. We also have great respect for each other’s expertise and recognize that our specialties intersect in many areas.

Although both vascular access and infection prevention have their own focus, our commonality is in ensuring patients get the care they need while minimizing their chances of nosocomial infections. Infection preventionists have a wide scope, as infections can be caused by many factors while in the hospital, from medical devices to the hands of the healthcare workers caring for them. Vascular access specialists focus on the devices placed into the bloodstream of patients in order to deliver needed medications, allow access for dialysis, or accurately monitor blood pressure. It is because we know that these devices can be a conduit for life-threatening infectious agents that infection preventionists are vital to our specialty.

Since we are a smaller facility with a team of 2 vascular access nurses, we only officially round on central lines; however, we are called daily to assess VADs of all types, intervene when necessary, and replace VADs when required. Our objective is to get the patient through their hospital stay with the least invasive vascular access device that is appropriate for their condition while experiencing as few needle sticks as possible. Not only do fewer vascular access devices and needle sticks decrease cost and increase patient satisfaction, but each time the skin is broken there is an increased risk for infection. As we continue to grow our team, our goal is to provide care for all VADs as they each provide an entry into the same circulatory system and are therefore capable of serving as a source of serious (even deadly) infection. We were working toward this goal when COVID hit and both delayed our plans and helped justify our team.

My community hospital of 117 licensed beds received our first possible case of coronavirus disease 2019 (COVID-19) on a Sunday afternoon in March. The patient was in a negative pressure room in our intensive care unit (ICU), and a vascular access consult was ordered. Due to the patient’s condition and multiple ordered medications, a PICC line was selected as the most appropriate device. I had personally never placed a vascular access device while wearing airborne precautions personal protective equipment (PPE), but I did remember our infection control nurse teaching me how to don the powered air-purifying respirators (PAPR), gown, gloves, and shoe covers in the correct order. As the ICU staff assisted me into the PPE, I wondered about the feasibility of performing a sterile procedure while covered almost head to toe in PPE, but I knew the patient needed vascular access.

Because of my experience as a vascular access specialist and my collaboration with infection preventionists both at my facility and through professional organizations and journals, I was able to place a PICC that successfully delivered the needed medications. That patient ended up being discharged home at the completion of their stay while only undergoing 1 needle stick for vascular access during their stay at my facility.

Less than 24 hours after placing that PICC line I met with our infection control nurse to discuss how the COVID-19 team was going to interact with the vascular access team. We collaborated to create a plan for best protecting our team of 2 from exposure while also ensuring that our patients were protected from further infection caused by a vascular access device. In addition, the infection control nurse and I met with the directors of the lab, the medical floor, and the intensive care unit to discuss ways to minimize exposure of their staff to the patients with confirmed COVID-19 infection.

We also spoke with the emergency department and the hospitalists to plan for the vascular access needs of these patients. When it became clear we would have to change some of our normal practice to work within the national PPE shortage while still protecting staff, we worked together with our materials department to ensure we would have the needed supplies.

One concern we had was maintaining ideal positioning of vascular access devices once they were placed; to this end, we ordered a subcutaneous securement device we had been trialing. Although there were many areas of the country where PPE shortages did negatively impact healthcare systems, the incident command center at our facility was able to maintain an adequate supply for our staff. Through teamwork we were all able to navigate the unknown waters of COVID-19 while providing the highest level of care for all of our patients and protecting our staff.

The healthcare team is composed of different specialists from widely varied backgrounds. Although we each have our own focus, we all work together to care for our patients in an effective and efficient manner. Collaboration between specialties is vital to maximizing patient outcomes while minimizing complications. Although complications with vascular access devices are sometimes dismissed as a necessary evil associated with hospitalization, through the collaboration of vascular access specialists and infection preventionists we can decrease complications, decrease costs, and increase positive outcomes for our patients.

Maya Gossman, RN, is a vascular access nurse at Stillwater Medical Center in Stillwater, Oklahoma.

Although both vascular access and infection prevention have their own focus, our commonality is in ensuring patients get the care they need while minimizing their chances of nosocomial infections.

How This Vascular Access Nurse Relies on an Infection Preventionist

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) duringthe 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 

(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.

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 

 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 

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 

 from Yale, 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 

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.

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.

Taking Aim at Antibiotic-Resistant Bacteria During COVID

Infection preventionists are needed to help schools reopen properly, says Kevin Kavanagh, MD, a member of 

’s Editorial Advisory Board. Kavanagh worries that the push to reopen schools may be setting society up for a new wave of coronavirus disease 2019 (COVID-19). And even before COVID-19 hit, Kavanagh points out, schools were not safe havens for children. They’re more like germ factories. “Our schools in many areas are just plain dying, their infrastructure is crumbling,” says Kavanagh. “Their windows don’t open. The air really is not safe…. They are not healthy buildings.”

Doctor Kavanagh, you’re writing an article for the October issue of 

 about some of the problems involved in trying to reopen schools in the midst of the COVID-19 pandemic. What did you find out?

Well, one thing is, is that we really do need to pay attention to the science, and we need to guard our children. That’s probably two of the most important factors. There are too many that think well, we can just open up schools and we don’t need to do much different rather than putting our children in school because they’re very low risk. Well, there’s two factors which I think you need to realize. One is that the children do become infected with the virus almost as frequently as adults and they can spread the virus. They’re just asymptomatic carriers. One study found that approximately 80% of children who are infected with the SARS-CoV-2 virus are asymptomatic. But that does not mean that they cannot spread it to their parents and guardians who are looking after them. And also close to 24% of teachers are at high risk for developing COVID-19. The second factor is that even though children are not at very high risk of dying from COVID-19, they still may develop long-term effects from this virus. And this includes those that are asymptomatic carriers. In children less than age 19, only about 2% are hospitalized. But even those children, in children who are asymptomatic, may be at risk for long-term damage and effects on their heart. It’s not likely to happen, but it certainly can. As you know, we have recent reports out of Penn State that up to 15% of college football players who tested positive for COVID-19—and this includes both symptomatic and asymptomatic patients—has a mild carditis. And this may present many years down the line with a cardiomyopathy. Now you’ll hear people say, “Well, we don’t know what that means. They’re asymptomatic, so they probably won’t develop anything.” Well, the problem with that narrative is, is we just don’t know. And dilated cardiomyopathy, which is the most common type, almost 50% of those are idiopathic, or you do not know what caused them. And it’s felt to be caused by an asymptomatic, viral myocarditis. And so, this is cause for concern. And as you know, children can also rarely develop that Kawasaki-like disease, which can occur in approximately 1% or less of those that develop COVID-19. And that is a severe illness and can be very, very life-threatening.

 for our October print issue, you also write about how school buildings in general aren’t really safe for our children.

Well, that’s correct. Our schools in many areas are just plain dying, their infrastructure is crumbling. Their windows don’t open. The air really is not safe. Even before COVID-19, it was well known that if your child goes to school, you may well get more colds and also could come down with the flu. They are not healthy buildings. We do need to take this time and upgrade the infrastructure of our schools. This includes bigger classrooms, more hand-washing stations, but also better circulation of air, filtration of air, and cleaning of the air. Look what the airline industry has done for airplanes. They place a number of people inside a small metal tube, but rarely are you hearing about them getting infections. Why? They have excellent circulation of air, excellent cleaning of air, they require everyone to wear masks. And whenever possible they are employing social distancing. The same needs to be done for schools, wearing of masks and social distancing—not and/or—but both. And social distancing needs to be a minimum of six feet. One of the things we’ve learned about this virus is that under certain circumstances, it can aerosolize and this includes loud speech, actively screaming, talking loudly. And in that case, cloth masks and the six-foot rule may not be enough. And this is the reason why you also need a variety of interventions, including upgrading the school’s air systems.

I think that the US Centers for Disease Control and Prevention has guidelines for office buildings that are refurbishing in terms of their airflow to make sure they’re safe before they open, is that not the case?

I believe that is correct. And the same should apply for schools. It really is crucial. We need to pay attention to the infrastructure, we need to learn to live with the virus. Now some will say, well, this epidemic will go away. Well, you know, it really doesn’t matter. Our children are our most precious asset, they should be in a healthy environment. And if it cuts down on the spread of the flu, the spread of colds, of other pathogens, that investment will be well worth it. This is something we really need to do. And we need to open up schools at a time when it is safe to do so. What I mean by that is a community spread of the virus needs to be low and currently we are getting into almost an untenable position where neither alternative is good. Where students stay home, and they will possibly suffer psychological damage and loss of socialization skills. Or if they go to school, it’s too risky. And all of this is a result of society not following public health advice and driving down the community infection rate and our test positivity rate to less than one. And I’m saying less than one. You will hear less than five. But that is a bare minimum, the number five. New York City is having trouble opening up schools, and their test positivity rate is less than one.

Who would oversee the refurbishing of schools?

I would think it would be under the state departments of education. If you go into local governments, it’s going to be really a whack-a-mole approach with different standards everywhere and the virus doesn’t care. It’s not different everywhere. It is the same entity. And strategies that work in one place will work in another and strategies that don’t work in one place won’t work in another. And certainly, it’s going to require grants, either state or federal funding in order to get this infrastructure up to speed. And this will also stimulate the economy. Similar to going to war with an outside adversary, believe me, this virus is the same thing. We need to really invest in infrastructure, not only in schools, but office buildings and restaurants. All of this will require money. I think state grants would be great. And I also think that that’s a way to stimulate our economy, let alone increase the safety of our children.

Do infection preventionists fit in this scenario at all with schools and school safety?

Well, definitely. I think you’ll find that infection preventionists in this type of climate are just not healthcare employed personnel. They need to be everywhere. They need to be in business. They need to be in schools. And, of course, they need to be in our healthcare system. But it is crucial to be in schools, to advise schools on the type of restrooms to have, on the type of social distancing, on how to set up a cafeteria, on how to filter air, on the type of PPE needed. And we do need to get the same quality of PPE for our teachers that is available for healthcare personnel. So yes, we need to look at this as not a healthcare problem, but as a societal problem, and infection preventionists are absolutely key in getting us back on track, both with the economy and getting us to be safe, as safe as we can be when we leave our homes.

Kevin Kavanagh, MD: “I think you’ll find that infection preventionists in this type of climate are just not healthcare employed personnel. They need to be everywhere. They need to be in business. They need to be in schools. And, of course, they need to be in our healthcare system. But it is crucial to be in schools…”

Q&A: Infection Preventionists Should Head Back to School

To meet unprecedented expansion needs, the Children’s Hospital of Philadelphia (CHOP) revamped its infection prevention team by adding more staff and making sure that the staff had a diversified background. This resulted in a 23% decrease in healthcare-associated infections (HAIs) between 2014 and 2018, according to a study in the 

. This reduction in HAIs occurred even as patient days, central line days, ventilator days, and device utilization increased each year. Investigators with CHOP noted that HAIs account for about 72,000 deaths each year in the United States, roughly 1 in 31 inpatients.

CHOP investigators also note that the role of the infection preventionist (IP) has grown in recent years, thanks in part to state and federal mandates concerning the reporting of healthcare-acquired infections (HAIs). This focus on HAI surveillance diverts the IP’s attention away from other infection control duties.

“In addition, IPs have a more prominent role as frontline responders to public health emergencies related to both emerging and re-emerging infectious diseases, such as pandemic H1N1 influenza, Ebola virus disease, outbreaks of vaccine-preventable diseases (eg, measles) and rising antimicrobial resistance,” the study states. “Furthermore, device-related outbreaks, such as those associated with contaminated heater-cooler units and duodenoscopes, require prompt investigation and resource-intensive responses. The latter have underscored the need for enhanced infection prevention and control (IPC) oversight and increased regulatory scrutiny of high-level disinfection and sterilization programs.”

CHOP created a 3-tier career ladder for its infection preventionists and drew equally from nursing, public health, and laboratory scientist backgrounds. Using a framework developed by the Association for Professionals in Infection Prevention and Epidemiology (APIC) that recognizes novice, proficient and expert IPs, the CHOP career ladder consists of Infection Preventionist I, Infection Preventionist II, and Senior Infection Preventionist. The IP staff grew from 4 to 9, and added the additional support roles of hand hygiene program manager, infection prevention associate and a clinical practice analyst. These changes expanded the education and consultative range of the department, as measured by a 33% increase in environmental rounding and a 7-fold increase in performance of isolation audits.

“The core strategies we chose to implement were to increase staffing due to organization growth, create career ladders to recruit and retain talented IPs and to add cost-efficient supporting team roles,” the study states. “These strategies will allow our team to keep pace with the rapid expansion of our organization and growing complexity of the field, while continuing to promote safer patient outcomes.”

Investigators with CHOP developed an algorithm for 5 key HAIs: central line associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator associated pneumonia (VAP), and healthcare-associated viral infections. There was a statistically significant reduction in rates of harm across the 5 key HAIs, the study says.

The study states that CHOP’s infection control department takes the novel approach of providing supporting roles in infection prevention, which can serve as “entry level positions for future IPs while providing cost-effective support for the needs of the program. Diversifying roles and creating support staff benefits the team by increasing the productivity of the department and providing a deeper bench so that IPs can focus on broader activities requiring specific subject matter expertise. In addition, this staffing structure engages employees in career development in alignment with the APIC competencies to support retention and increased employee satisfaction….”

Diversifying roles and creating support staff benefits the team by increasing the productivity of the department and providing a deeper bench so that IPs can focus on broader activities requiring specific subject matter expertise.

Expanding Size, Variety of Infection Prevention Team Pays Off

As the fight against coronavirus disease 2019 (COVID-19) continues, the consumer market for gadgets to keep you from touching doorknobs and elevator buttons, and gizmos to disinfect your phone, your packages, your groceries, glasses, shoes, and the air you breathe—just to name a few—is mind-boggling. Similarly, lots of new and old technologies are being marketed to the healthcare sector, promising cleaning and disinfection on all kinds of surfaces contaminated with SARS-CoV-2.

For instance, ultraviolet germicidal irradiation(UVGI) is a type of ultraviolet (UV) light that is composed of 3 types of light—UVA, UVB, and UVC.UVC is the most effective of all germicidal light. It was first used in the 

 as a method to disinfect air. It was during this time that the spread of airborne infections by droplet nuclei was discovered, and also the bactericidal effects of sunlight (UV) to prevent that spread. Despite early successes in applying UVGI, its use fell out of favor.

However, in the 1980s, an increase in infections from tuberculosis (TB) led to renewed interest in UVGI. It was found to be safe and very effective in disinfecting the air, preventing transmission of a variety of airborne infections in addition to TB.

When it comes to disinfecting the air, there are 3 primary methods of applying UVC systems against infectious agents in the air: upper-air, coil irradiation, and airstream disinfection. Upper-air systems are typically installed in room spaces, such as above patient beds, in waiting rooms, corridors and break areas, etc., where they kill airborne microorganisms that inherently circulate into the path of the UVC light.

Coil irradiation and airstream disinfection systems are installed within air handling units or duct runs within HVAC systems, downstream of cooling coils, to keep coils clean and to provide supplemental kill ratios in airstreams and on filter surfaces. Reduction of potential pathogens in the air can help prevent resettling onto surfaces, helping to contribute to a reduction in microorganism transmissions.

In healthcare, we hear a lot about UVC being used to disinfect surfaces more so than air or water. It relies on a short wavelength of light to break down microorganisms by naturally damaging their DNA and RNA, rendering them unable to replicate. Since viruses are not considered microorganisms, UVC does not actually “kill” viruses. Instead, it inactivates the virus and prevents any illnesses it might spread.

UVC has been shown to be effective in reducing pathogenic microorganisms present on frequently touched surfaces and is already being used in some hospital settings for disinfecting rooms, surfaces, and equipment. Interestingly, the US 

Centers for Disease Control and Prevention

 (CDC) lists UVC as one of the most promising methods of disinfecting air-filtering face masks, such as the N95, for reuse when there is a shortage of personal protective 

 (PPE).UVC devices are an effective means of reducing concentrations of airborne and surface microorganisms that can lead to healthcare-associated infections (HAIs).

Until very recently, UVC wavelength devices for disinfection of surfaces had not yet been proven effective against COVID-19. There were only data to support effectiveness against other coronaviruses with fairly similar RNA structures to the virus that causes COVID-19. However, on May 21, 2020, Xenex recently tested its LightStrike™ robot specifically on SARS-CoV-2 in a biomedical lab in Texas, and found that, in 2 minutes, it was able to achieve a reduction of the virus greater than 99.99% within about a 3-foot radius.

So, the effectiveness of UVC for reduction of microorganisms including bacteria, viruses, and fungi has been proven time and again. But using UVC radiation to disinfect is not simple and requires lots of protocols to use safely. The radiation must be contained, often in a device of some kind, be it a light box, robot, or tower. When UVC light is used to disinfect a room, people must be cleared from the room before the device is turned on because it can be harmful to eyes and skin. Sometimes the robots need to be repositioned to eliminate “shadowing,” which blocks the UV light from touching the surface intended for disinfection. Installing UVC lights to irradiate a room or determining the placement of mobile devices is also a complicated process and must be appropriately validated to work effectively. Some systems are very costly. Lastly, and most importantly, all surfaces need to be free of any soil or bioburden in order for the UV light to touch the surface and for disinfection to occur, therefore, it does not replace cleaning. It can be a powerful tool used as an adjunct to a thorough cleaning process.

The effectiveness of UVC for reduction of microorganisms including bacteria, viruses, and fungi has been proven time and again. But using UVC radiation to disinfect is not simple and requires lots of protocols to use safely.

UVC Light: Powerful Disinfectant, But Not Easy to Use

There have been no human trials and, as yet, no commercial partners, but there’s certainly been a lot of interest in what amounts to personal protective equipment (PPE) that you can spray on and will, inventors assert, straitjacket SARS-CoV-2, protecting the subject from COVID-19.

As Aashish Manglik, one of the inventors of what he and his team of researchers at the University of California, San Francisco, put it in a school 

, their invention, AeroNabs, “may help reshape the course of the pandemic worldwide.” The inventors are in talks with companies who would help manufacture and distribute AeroNabs. The product would be used once a day and administered by a shelf-stable inhaler or nasal spray. The preprint 

 on which these claims are made can be found on the bioRxiv website.

Peter Walter, PhD, professor of biochemistry and biophysics at UCSF and one of the inventors, said in the press release that “far more effective than wearable forms of personal protective equipment, we think of AeroNabs as a molecular form of PPE that could serve as an important stopgap until vaccines provide a more permanent solution to COVID-19.”

The inventors say that they used protein engineering on nanobodies, which are antibody-like immune proteins that naturally occur in llamas, camels and other animals.

“Though they function much like the antibodies found in the human immune system, nanobodies offer a number of unique advantages for effective therapeutics against SARS-CoV-2,” Manglik said in the press release.

Nanobodies are much smaller than human antibodies, for instance, and that makes them easier to manipulate and modify. Their simple structure makes them more stable, as well. They’re relatively inexpensive and easy to produce: “scientists insert the genes that contain the molecular blueprints to build nanobodies into E. coli or yeast, and transform these microbes into high-output nanobody factories,” according to the press release. “The same method has been used safely for decades to mass-produce insulin.”

The infamous spikes on the SARS-CoV-2 virus are proteins that enable it to invade and infect ACE2 receptorcells in the lungs. When those spikes become active, their receptor-binding domains (RBDs) become exposed and will then attach itself to the ACE2.

The inventors devised a triple nanobody that can smother the RBDs on SARS-CoV-2. This triple nanobody is 200,000 times more potent than a single nanobody alone.

“The most potent of these nanobodies, however, not only acts as a sheath over RBDs, but also like a molecular mousetrap, clamping down on spike in its closed, inactive state, which adds an additional layer of protection against the spike–ACE2 interactions that lead to infection,” according to the press release.

Walter said for those who won’t respond to a COVID-19 vaccine when it comes along, or who might not have access to the vaccine, AeroNabs would act as a permanent line of defense against the coronavirus.

Peter Walter, PhD: “We think of AeroNabs as a molecular form of PPE that could serve as an important stopgap until vaccines provide a more permanent solution to COVID-19.”