Coverage From ID Week 2020

Finding pathologic antibodies to platelet factor 4 (PF4) in patients presenting with thrombosis with thrombocytopenia after receiving the ChAd0x1 nCoV-19 vaccine (AstraZeneca) for SARS-CoV-2 led investigators to recommend treatments that include a non-heparin anticoagulant, and to provide an 

 that also emphasizes avoiding platelet transfusion.

Marie Scully, MD, Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK, and colleagues investigated the thrombotic events in 22 patients that occurred 6 to 24 days after receiving the vaccination. These were primarily cerebral venous thrombosis, but also included arterial thrombosis as well as more common types of venous thromboembolism, including pulmonary.

"We identified a novel underlying mechanism associated with the presentation. On the basis of the clinical features and subsequent laboratory findings, we propose an altered therapeutic approach," Scully and colleagues announced.

, Douglas Cines, MD, Department of Pathology and Laboratory Medicine and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and James Bussel, MD, Department of Pediatrics, Weill Cornell Medicine, New York, New York, concurred that the findings suggested the course of treatment.

"Although the condition in several patients apparently improved when they were given low-molecular-weight heparin, it seems prudent to choose from among the non-heparin antithrombotic agents that are used to treat heparin-induced thrombocytopenia while the risk of bleeding is being mitigated," they indicated.

"We expect that the high mortality rate associated with VITT (vaccine-induced immune thrombotic thrombocytopenia) will decrease with earlier recognition and improved intervention," Cines and Bussel added.

Scully and colleagues explain that their decision to test for antibodies to PF4 was based on the presentation of progressive thrombosis and thrombocytopenia that is similar to patients with the rare heparin induced thrombocytopenia (HIT), which is also confirmed by the presence of anti-PF4 antibodies.The test for anti-PF4 antibodies was performed by means of enzyme-linked immunosorbent assays (ELISAs), and confirmed, in some cases, by means of a functional HIT assay.

To rule out the possible link of thrombosis to the SARS-CoV-2 virus, rather than to the vaccine, all patients were tested for, and found to have a negative SARS-CoV-2 PCR test at presentation.The 10 patients with samples available for testing were also found negative for SARS-CoV-2 antibodies.In each of the 10, levels of antibodies to the spike protein and the receptor binding domain (RBD) of the virus were within range expected from a dose of the vaccine.The investigators noted, however, that all patients had D-dimer levels that were much higher than would be expected in patients with acute venous thromboembolism.

Scully and colleagues warn against platelet transfusions in patients with this presentation, as these might provide a substrate for further antibody-mediated platelet activation and coagulopathy.Instead, their treatment algorithm includes consideration of glucocorticoids, and administration of intravenous immunoglobulin (IVIg) and non-heparin anticoagulant.

"Although evidence does not yet suggest that the use of heparin will exacerbate this condition, pending further data, we would recommend considering anticoagulation with the use of a non-heparin anticoagulant, such as argatroban, danaparoid, fondaparinux, or direct oral anticoagulants," Scully and colleagues advised.

Articles

Pathologic antibodies to platelet factor 4 in patients who developed clots after the AstraZeneca vaccine indicates treatment include non-heparin anticoagulant.

Pathogenesis of Clots Following COVID-19 Vaccine Suggests Choice of Treatments

Missed Diagnoses Common for C. Diff Infections,

 infections (C diff) is paramount and if not diagnosed in a timely manner it can result in delays in initiation of therapy and hospital re-admissions.

A team, led by Ioannis M. Zacharioudakis, MD, Division of Infectious Diseases and Immunology, Department of Medicine, NYU School of Medicine, examined the rate of missed community-onset C diff infection diagnosis and associated outcomes.

Microbiology laboratories often blind the C diff BioFire FilmArray GI Panel due to fear of an over-diagnosis.

The study included 144 adult patients with FilmArray GI Panel positives for C diff on hospital admission, but lacked dedicated C diff testing. Of this group, 18 individuals did not have concurrent dedicated C diff testing, while 8 patients were categorized as possible, 5 were deemed probably, and 4 were identified as definite missed CDI diagnosis.

The researchers found associated delays in initiation of appropriate therapy, intensive care unit admissions, hospital re-admission, colorectal surgery, and death or discharge to hospice.

In addition, 5 of 17 individuals lacked true risk factors for a C diff infection.

 FilmArray GI Panel results needs to be re-considered in patients presenting with community-onset colitis,” the authors wrote.

Recently, researchers found sepsis was a common 

 complication throughout a 12-month follow-up period and was most commonly observed in the cohort of patients with 3 or more C diff infection recurrences.

Investigators from around New England conducted a retrospective analysis of more than 46,000 adult patients with C diff infection in order to evaluate the clinical complications of C diff in patients with index and recurrent cases.

The investigators used the IQVIA PharMetrics Plus database to looks for patients aged 18-64 years with an index C diff episode that required inpatient stay or an outpatient visit, followed by a treatment for the infection. Treatments included vancomycin, fidaxomicin, metronidazole, rifaximin, or bezlotoxumab, or fecal microbiota transplant (FMT – though it was rare).

A total of 3129 patients (6.7%) experienced 1 recurrence, while 1% had 2 recurrences, and 0.3% had 3 or more recurrences. The study authors also noted that autoimmune diseases, such as ulcerative colitis, Crohn’s disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis, were present in 18%, 23%, 24%, and nearly 40% of patients, respectively, in patients with 0, 1, 2, or 3 or more C diff infection recurrences.

Antibiotics were prescribed for three-quarters of all patients in all groups in the 6 months preceding the index 

, the investigators found. Gastric acid-suppressing agents were prescribed in 28%, 33%, 39%, and 38%, respectively, in patients with 0, 1, 2, or 3 or more C diff infection recurrences, the study authors also noted.

During the 12-month follow-up period, the investigators observed sepsis in 16%, 27%, 33%, and 43%, respectively, in patients with 0, 1, 2, or 3 or more C diff infection recurrences. No patient had more than 2 sepsis episodes during the 12-month follow-up period. Additionally, subtotal colectomy or diverting loop ileostomy was performed in 4%, 7%, 9%, and 10% of patients, respectively, in patients with 0, 1, 2, or 3 or more C diff infection recurrences.

Rate and Consequences of Missed Clostridioides (Clostridium) difficile Infection Diagnosis from Non-reporting of Clostridioides difficile Results of the Multiplex GI PCR Panel: Experience from Two-Hospitals

Diagnostic Microbiology and Infectious Disease

With labs blinding a specific panel, a  C diff diagnosis can be masked and missed.

Can C Diff Being Overlooked?

 offer high efficacy and strong protection against the disease, It is still possible that individuals are able to contract the virus.

Perhaps no other population is more susceptible than healthcare workers who are on the frontlines and have face-to-face contact with sick patients regularly.

Investigators from the Medical University of South Carolina recently set out to surveil COVID-19 rates among care team members from their facility following vaccination.

For the study, care team members who were diagnosed with COVID-19 subsequent of receiving a vaccination with the Pfizer-BioNTech shot self-identified during online electronic contact tracing surveys.

The investigators recorded data including demographics, symptoms and dates of symptoms. The care team members who tested positive were linked to viral burden data from nasopharyngeal swabs tested on Abbott PCR platforms.

Findings from the study showed that of the 111 care team members who tested positive after vaccination, 99 tested positive following 1 dose and 12 tested positive following 2 doses at a median of 10 and 5 days, respectively.

Of the care team members who reported symptoms, 104 did so after a median of 7 days from the time of vaccination to symptom onset, with 8 of them reporting symptoms before vaccination, 9 on the day of vaccination, and 3, 6, and 11 of them at 1, 2, and 3 days after vaccination, respectively. The most frequent jobs testing positive were nurses and physicians.

Additional findings from contact tracing showed that sources of transmission were household clusters, local transmission, occupational acquisition and travel-related transmission.

The majority of the cases following a vaccination occurred in care team members with infection incubating prior to the shot.

 spoke to Scott Curry, MD, assistant professor in the college of medicine at the medical university of south Carolina, who presented the research at 

The Society for Healthcare Epidemiology of America Conference 2021

Results from the study data reinforce the need to adhere to public health measures by people who have been vaccinated.

Surveilling for COVID-19 Among Healthcare Workers Following Vaccination

The US Food and Drug Administration (FDA) has revoked the emergency use authorization (EUA) for investigational monoclonal antibody therapy bamlanivimab as a lone therapy for the treatment of mild-to-moderate 

 in adults and indicated pediatric patients.

The decision is based on continued assessment of emerging data—specifically geared toward SARS-CoV-2 variants that show resistance to lone bamlanivimab and reduced likelihood of treatment efficacy—that indicates a change in known and potential benefits of the monoclonal antibody versus the known and potential risks of its emergency use.

The Eli Lilly and Co. investigational therapy was originally granted its EUA on November 9, 2020, for the treatment of COVID-19 in adults and pediatric patients aged ≥12 years old weighing at least 40 kg, with positive SARS-CoV-2, and who are at high risk for progressing to severe COVID-19.

The decision proceeded a request from Eli Lilly to revoke the EUA, as they modified contracts with the federal government to assure adequate supply of etesevimab in combination with bamlanivimab—another available monoclonal antibody regimen from the company. 

"Lilly moved quickly to make bamlanivimab alone available as a potentially lifesaving medicine at a time when Americans were hardest hit by COVID-19," Daniel Skovronsky, MD, PhD, Lilly's chief scientific officer and president of Lilly Research Laboratories, said in a 

. "With the growing prevalence of variants in the US that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together."

As the FDA stressed in this EUA revocation, monoclonal antibody therapy is still authorized and even approved in some iterations for the very same treatment of COVID-19, including combination casirivimab and imdevimab (REGEN-COV) and combinated bamlanivimab and etesevimab. No emerging data would indicate that the benefit of these combination therapy regimens is compromised significantly by the prevalence of SARS-CoV-2 variants.

Since last month, approximately 1 in 5 sequenced SARS-CoV-2 viruses in the US were reported as variants likely resistant to lone bamlanivimab—a significant jump from the approximate 1 in 20 reported in mid-January this year.

Because no testing technologies are available for healthcare providers to test for SARS-CoV-2 variants prior to monoclonal antibody treatment, the FDA reasoned authorized regimens should entail those known to work broadly against all nationwide-circulating variants.

“While the risk-benefit assessment for using bamlanivimab alone is no longer favorable due to the increased frequency of resistant variants, other monoclonal antibody therapies authorized for emergency use remain appropriate treatment choices when used in accordance with the authorized labeling and can help keep high risk patients with COVID-19 out of the hospital,” Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. 

“We urge the American public to seek out these therapies when needed while we continue to use the best data available to provide patients with safe and effective treatments during this pandemic.”

The decision follows emerging data showing prevalent virus variants are unaffected by the monoclonal antibody.

FDA Revokes COVID-19 Emergency Authorization for Lone Bamlanivimab

Eli Lilly has requested the Food and Drug Administration rescind its Emergency Use Authorization for its COVID-19 therapy, Bamlanivimab. The company has made the request as part of its plan to use Bamlanivimab and etesevimab as a combination therapy for treatment of the virus.

This follows the modification of contracts with the United States government to ensure adequate supply of etesevimab to be used together with bamlanivimab. In addition, the company said with the emerging variants, the standalone therapy might not be as efficacious.

"Lilly moved quickly to make bamlanivimab alone available as a potentially lifesaving medicine at a time when Americans were hardest hit by COVID-19," said Daniel Skovronsky, MD, PhD, Lilly's chief scientific officer and president of Lilly Research Laboratories.  "With the growing prevalence of variants in the US that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together."

Over 400,000 American patients have been treated with bamlanivimab, which according to Lilly, potentially prevented more than 20,000 hospitalizations and at least 10,000 deaths during the worst of the pandemic in the US.

Lilly is not requesting the EUA withdrawal its therapy alone in any other jurisdiction. However, it did say the use of bamlanivimab with etesevimab, where authorized and available, is preferred.

Lilly, in collaboration with Amgen—the manufacturer of etesevimab—expects to manufacture sufficient supply of the therapies to meet global demand.

The company wants to transition to combination therapy of bamlanivimab and etesevimab together for COVID-19 treatment.

Lilly Asks FDA to Revoke its EUA for Bamlanivimab Alone

The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) met today to discuss the blood clots’ issue and offered guidance on heparin usage in these cases.  

CDC’s ACIP Decides Not to Vote on Recommendations for Johnson & Johnson COVID-19 Vaccine

New data indicates failed parasite clearance among Rwandan children is linked to a mutation also observed in southeast Asia.

Resistant Malaria Parasite Mutations Observed in Rwanda

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An interventional cardiologist discusses the observed cases of cerebral venous thrombosis in women administered the Johnson & Johnson COVID-19 vaccine.

Understanding Links Between COVID-19, Vaccines, and Thrombosis

More than half of urine cultures were found to be contaminated and 1 in 5 of the patients were prescribed an antibiotic.

Improving Urine Collection Poses Opportunity for Diagnostic Stewardship in Primary Care

The two measures were shown to prevent viral outbreaks if at least 60% of a population followed them.

Network Model Shows Combined Mask Wearing and Social Distancing Suppresses COVID-19 Spread

Social identity plays an important role in how antimicrobial stewards see their roles and influences how they communicated with prescribers.

Communication in Hospital-Based Antimicrobial Stewardship

The US Food and Drug Administration released an investigation report on the fall 2020 outbreak of Shiga toxin-producing Escherichia coli (STEC) O157:H7 linked to leafy greens grown in California and updated the Leafy Greens Action Plan.

Cattle Are Likely Source of Recent Outbreaks of E. Coli Associated With Leafy Greens

Is There a Better β-Lactam for Viridans Group Streptococci?

Carlos del Rio, MD, discusses the United States' pandemic situation in assessing the blood clot events observed in 6 Johnson & Johnson vaccine recipients.

What Does the Johnson & Johnson COVID-19 Vaccine Pause Mean?

Jason Gallagher, PharmD, adds context behind the FDA and CDC's decision to pause and review blood clotting events in 6 women given the company's COVID-19 vaccine.

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Pathogenesis of Clots Following COVID-19 Vaccine Suggests Choice of Treatments

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