Stewardship / Resistance Scan for Mar 16, 2021

News brief

FDA approves Melinta's Kimyrsa for skin infections

Melinta Therapeutics of Morristown, New Jersey, announced yesterday that the US Food and Drug Administration (FDA) has approved Kimyrsa (oritavancin) for treatment of adult patients with acute bacterial skin and skin-structure infections (ABSSSIs) caused by susceptible gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA).

Kimyrsa delivers a complete course of the lipoglycopeptide antibiotic oritavancin in a single, 1-hour 1,200 milligram (mg) intravenous infusion. The drug is an updated version of Orbactiv, which was approved by the FDA in 2014 for treatment of ABSSSIs and is infused over 3 hours.

The safety and efficacy of Kimyrsa was previously established in randomized clinical trials that showed that a single 1,200 mg infusion of Orbactiv was as effective 7 to 10 days of twice daily vancomycin in treating 1,987 ABSSSI patients, including 405 with documented MRSA infection. FDA approval was based on a pharmacokinetics study that showed the safety profile was favorable to Orbactiv.

Melinta says it plans to launch the drug this summer.

"We have responded to the requests of the medical community to provide an oritavancin product with a shorter infusion time," Melinta President and CEO Christine Ann Miller said in a company press release. "We believe that with the approval of Kimyrsa and product availability this summer, physicians and patients will now have a compelling new one-dose alternative to the current standard of multi-dose regimens for ABSSSI."

Nearly 14 million US patients develop ABSSSIs each year, with more than 3 million emergency department visits. The infections cost US hospitals roughly $4 billion annually.
Mar 15 Melinta press release

Central line-associated bloodstream infections rise during pandemic

A new study from researchers with the US Centers for Disease Control and Prevention shows a significant increase in central line–associated bloodstream infections (CLABSIs) in US acute care hospitals during the early months of the COVID-19 pandemic.

Published yesterday in Infection Control & Hospital Epidemiology, the study analyzed 13,136 inpatient units from 2,986 acute care hospitals and found that the standardized infection ratio (SIR) for CLABSI's in April, May, and June of 2020 climbed by 28% compared with the same months in 2019, from 0.68 to 0.87. Critical care units saw the greatest percentage increase (39%) in SIR, from 0.75 in 2019 to 1.04 in 2020, and ward locations experienced the second highest increase (13%). Critical care locations had the highest number of CLABSIs in the second quarter of 2020, with 1,911.

Among ward types, significant increases in the SIR occurred in pediatric medical-surgical wards (118%), neurosurgical critical care (108%), medical critical care (60%), and medical-surgical critical care (59%). The highest regional SIR in the second quarter of 2020 (1.07) was in the Upper Northeast and represented a 45% increase compared with 2019. Hospitals of all bed sizes saw increases in SIR.

The study authors say the changes in infection control practices that were made at acute care hospitals to accommodate increasing numbers of patients during the pandemic may have contributed to the increase in CLABSIs. From 2015 through 2019, there was a 31% decline in the national SIR for CLABSIs.

"The findings of this paper highlight a substantial increase in CLABSIs in hospitals throughout the United States coinciding with the COVID-19 pandemic," they wrote. "The results of this analysis can be used to understand the increase in HAI burden being placed on the nation’s healthcare system and to prioritize ongoing efforts to prevent infections and to drive patient safety."
Mar 15 Infect Control Hosp Epidemiol abstract

US school districts adopt antibiotic use standard for turkey products

An organization representing the 15 largest school districts in the United States announced last week that it is issuing a standard for responsible antibiotic use in turkey products sold to schools.

Under the new policy, the Urban School Food Alliance (USFA) will require that all turkey products purchased by its schools must be produced under a US Department of Agriculture process verified program that includes compliance with the Certified Responsible Antibiotic Use Standard (CRAU), which was developed in 2014 to minimize antibiotic use in poultry and give schools the option to buy poultry raised with responsible antibiotic use. The turkey industry is the most intensive user of medically important antibiotics, according to research from the Natural Resources Defense Council.

Poultry producers in conformance with CRAU are prohibited from administering antibiotics pre-hatch and from using medically important antibiotics for disease prevention, growth promotion, feed efficiency, or weight gain. They can only use medically important antibiotics to treat poultry diagnosed with a bacterial disease or control disease in poultry exposed to infectious bacteria.

Turkey is the second most served protein in USFA schools, which serve nearly 4 million students daily. The group issued a similar standard for chicken in 2014.

"Issuing this standard for responsible antibiotic use in turkey is the next step in the Urban School Food Alliance’s commitment to provide the healthiest food to students in all its member districts," Katie Wilson, PhD, USFA Executive Director, said in a press release. "By leveraging the collective purchasing power of Alliance districts, this standard sends an important message to the turkey industry and helps to improve the quality of food sold to the school marketplace."
Mar 11 USFA press release

News Scan for Mar 16, 2021

News brief

Study: US COVID infections may have been twice the number reported

Roughly 15.9 million asymptomatic US COVID-19 cases may have gone undetected as of Sep 30, 2020, which would double the cases reported to the Centers for Disease Control and Prevention (CDC) during that time, according to a research letter detailing a 6.6% nationwide SARS-CoV-2 seroprevalence rate.

The letter, written by Clinical Reference Laboratory scientists in Kansas and published today in JAMA Network Open, describes a national convenience sample of 61,910 generally healthy adult life insurance applicants evaluated for the presence of SARS-CoV-2 antibodies in September.

Of the 61,910 participants, 4,094 (6.6%) had coronavirus antibodies, or were seropositive, indicating previous COVID-19 infection. Slightly more women than men were seropositive (6.9% vs 6.4%). Seroprevalence rates varied widely by state and ranged from 2.8% in participants older than 70 years to 9.8% in those younger than 30.

Using this sample, the researchers estimated that 15.9 million (bootstrap 95% confidence interval, 15.5 million to 16.5 million) asymptomatic or undiagnosed COVID-19 infections may have occurred.

The authors noted that antibody testing may provide a more accurate estimate of coronavirus prevalence than acute COVID-19 testing because people with asymptomatic or mild illness may not get tested for infection. They added that the study findings also highlight the need for ongoing population-wide disease surveillance.

"Our estimate implied more than twice the number of infections than cases reported to Centers for Disease Control and Prevention, suggesting a more widespread pandemic," the researchers wrote. "The findings of this cross-sectional study suggest that, based on a sample from an otherwise healthy population, the overall number of SARS-CoV-2 infections in the US may be substantially higher than estimates based on public health case reporting."
Mar 16 JAMA Netw Open research letter

Low immune response noted in transplant recipients after COVID vaccine

Out of 436 solid organ transplant recipients, 82.6% did not have detectable antibody responses after the first dose of an mRNA COVID-19 vaccine, according to a JAMA research letter published yesterday.

Immunocompromised people have not been included in the trials for the Pfizer/BioNTech or Moderna mRNA COVID vaccines, so the researchers recruited US transplant recipients and gave them a first dose of either vaccine from Dec 16, 2020, to Feb 5, 2021. The median age of participants was 55.9, and 89% were white. Kidney (50.2%), liver (17.9%), and heart (15.1%) were the most common organ transplants, and the median time since the transplant was 6.2 years.

After a median of 20 days post-vaccination, serologic tests showed that 17.4% of participants had detectable antibody levels, but some patient factors affected this. For instance, 73.4% of participants were on an anti-metabolite maintenance immunosuppression regimen, which was associated with an adjusted incidence rate ratio (IRR) of 0.22 (95% confidence interval [CI], 0.15 to 0.34). Older participants were also less likely to display an immune response (aIRR, 0.83; 95% CI, 0.73 to 0.93 per 10 years).

The study did note that the 48% of the cohort who received the Moderna vaccine were more likely to develop an antibody response than the 52% who received the Pfizer/BioNTech vaccine (aIRR, 2.15; 95% CI, 1.29 to 3.57). The researchers did not suggest a possible mechanisms for this finding.

"These findings of poor antispike antibody responses in organ transplant recipients after the first dose of mRNA vaccines suggest that such patients may remain at higher early risk for COVID-19 despite vaccination," they conclude.
Mar 15 JAMA research letter

Pandemic tied to lower-than-optimal care of newborns

Two thirds of respondents to a survey on neonatal care during the pandemic said they would not facilitate Kangaroo Mother Care (KMC), which is skin-to-skin contact that can help preterm babies, according to a study published yesterday in BMJ Global Health.

The results also highlight uncertainties around guidelines for suspected or confirmed COVID-19–infected mothers, staff and resource shortages, and an overall 20% to 35% reduction of neonatal care.

The survey was conducted from Jul 13 to Oct 13, 2020, and included 1,120 healthcare workers, public health professionals, and policymakers from 62 countries, with an emphasis on low- and middle-income countries (LMICs).

Before the pandemic, KMC was routinely practiced by 85% of respondents, but it has since dropped to 55% in part due to earlier discharge (30.8%), reduced duration of skin-to-skin contact (26.5%), and complete disruption of KMC services (7%). Almost two-thirds (61.0%) said they would separate neonates and mothers with unknown, suspected, or confirmed COVID except when breastfeeding, and 24.1% said they would separate and prohibit breastmilk regardless of the mother's COVID status.

The survey also revealed that 44.6% of respondents thought that guidance around COVID-infected mothers was "somewhat clear but major issues remain" or worse.

"Our data show huge promise for many lives saved with universal KMC, so it's vital that we use this opportunity to strengthen care now and build back better after the pandemic," said lead author Suman P. N. Rao, MD, in a London School of Hygiene & Tropical Medicine (LSHTM) press release. She and senior author Joy Lawn, BMedci, MB, PhD, MPH, also contributed to a Feb 15 EClinicalMedicine paper that found continuing KMC despite COVID-19 risk could save more than 125,000 neonate lives, at the risk of up to 1,950 neonatal COVID deaths. They thus concluded that the benefit of providing KMC is 65 to 630 times higher than the risk of dying from COVID-19.

Survey respondents listed family reluctance to come on site and COVID-19 testing delays or unavailability as disrupting neonatal care. Respondents also report that staffing and resources reallocated to meet COVID-19 needs have affected care.
Mar 15 BMJ Glob Health study
Mar 15 LSHTM press release