More hospitalization, complications for kids with COVID-19 than with flu

Hospitalization and respiratory complications were more frequent in children and adolescents with COVID-19 during the early months of the pandemic than in those diagnosed as having influenza in past flu seasons, an international team of researchers reported today in Pediatrics.

The multinational cohort study reviewed 19 databases in the United States, Germany, France, Spain, and South Korea for data on patients under the age of 18 with a clinical diagnosis of COVID-19 or a positive test result from SARS-CoV-2 from January through June 2020. The researchers described baseline demographics, comorbidities, symptoms, and outcomes, and included a cohort of children and adolescents diagnosed with influenza during the 2017-18 flu season for comparison.

A total of 242,158 children and adolescents with COVID-19, and 9,769 hospitalized for COVID-19, were included in the study. Most of the hospitalizations were seen in children ages 0 to 4. Comorbidities including asthma, heart disease, obesity, cancer, chromosomal disorder, and congenital malformations were more common in hospitalized COVID-19 patients than in those diagnosed as having COVID-19. The most commonly observed symptoms were fever and cough. Hospitalization was observed in 0.3% to 1.3% of the cohort, with undetectable 30-day fatality. Hypoxemia and pneumonia were the most common complications.

Comparison of outcomes in those with COVID-19 versus more than 2 million children diagnosed as having flu in 2017-18 showed that hospitalization was between 5-fold and 13-fold higher for COVID-19. Pneumonia and hypoxemia were more common for children and adolescents with COVID-19, as was multisystem inflammatory syndrome in children (MIS-C), which was rare among both cohorts. Children with COVID-19 also presented with higher rates of breathing difficulty, loss of smell, and gastrointestinal symptoms than children with seasonal influenza.

"Overall, all outcomes were more frequent in children and adolescents with COVID-19 diagnosis than those with a diagnosis of seasonal influenza in 2017–2018, suggesting more severe disease prognosis in children with COVID-19 than influenza," the study authors write. "Future research is needed to characterize and determine the long-term outcomes of children and adolescents affected with COVID-19."
Aug 20 Pediatrics study

Survey shows health not at baseline 1 month after COVID hospitalization

Almost 85% of COVID-19 patients hospitalized said they were not back to their pre-COVID health 1 month after discharge, and even short hospital stays were tied to prolonged symptoms, according to survey results published in the Journal of Hospital Medicine yesterday.

The researchers interviewed US adults hospitalized for COVID-19 a median of 47 days after their hospitalization, which took place from Aug 24, 2020, to Jan 26, 2021. Respondents were a median of 60 years old and stayed a median of 5 days. More than half (54.9%) reported new or worsened cardiopulmonary symptoms, 16% had new or increased oxygen use, and 52.8% had problems with daily living. Overall, 84.2% said their health was not what it was pre-COVID, and 16.8% said that on a scale of 0 to 100, with 100 being pre-COVID health, they were at 50 or less.

A longer hospital stay was associated with increased odds of cardiopulmonary issues, such as coughing, and it was also linked to disability (adjusted odds ratio [aOR], 1.82 per additional week and 2.06, respectively). Women were twice as likely to have new cardiopulmonary symptoms (aOR, 2.24), while Black and Hispanic people were less likely to report new symptoms (aOR, 0.31 and 0.38, respectively).

About 77% of patients with a new disability were discharged without home services, which the researchers say could have had an impact on their health.

"This isn't patients saying, 'I can't run quite as far as I used to.' This is them saying 'I can't walk, I can't cook, I can't shower.' The effects are devastating," said co-lead author C. Terri Hough, MD, in a University of Michigan (U of M) press release. "Unfortunately, we saw this even among patients with quite short hospital stays."

The survey also looked at financial stressors post-hospitalization and found that 23% had used up their savings, 20% had to change their job or become unemployed, and 40% needed a loved one to take time off from work to look after them.
Aug 18 J Hosp Med study
Aug 18 U of M press release

Study highlights racial/ethnic disparities in excess deaths from COVID-19

A study today in Morbidity and Mortality Weekly Reports (MMWR) highlights high excess mortality from COVID-19 among racial and ethnic minorities in the United States.

Using data from the National Vital Statistics System, US researchers assessed US excess mortality incidence rates (IRs) by race/ethnicity and age-group from Dec 19, 2019, through Jan 2, 2021. Among all racial/ethnic groups, excess mortality IRs were higher in those ages 65 and older (426.4 to 1,033.5 excess deaths per 100,000 person-years) than in those ages 25 to 64 (30.2 to 221.1) and those 25 years of age and younger (2.9 to 14.1).

Among those under the age of 65, Blacks and American Indian or Alaska Native (AI/AN) had the highest excess mortality IRs, while Black and Hispanic persons had the highest excess IRs among those 65 and older. Among Black and Hispanic persons ages 65 and over, more than 1,000 excess deaths occurred per 100,000 person-years compared with the number of deaths expected to occur.

The findings also illustrate the changing impact of the pandemic over time for different subgroups. Among those aged 65 years and older, excess mortality IRs peaked from April to June 2020 for Black adults, while remaining consistently elevated among Hispanic adults, and increasing from April-June 2020 to October-December 2020 for AI/AN, non-Hispanic Native Hawaiian or other Pacific Islander (NH/PI), and White adults.

"These findings underscore the disproportionate prevalence of excess mortality during the COVID-19 pandemic in 2020 among racial/ethnic minority groups of all ages in the United States, which have been driven, in part, by factors such as occupational risk, socioeconomic factors, housing conditions, reduced access to health care, and discrimination," the authors write.

"Identifying factors that contribute to racial/ethnic disparities in mortality, either directly or indirectly attributable to COVID-19, can help guide tailored public health prevention strategies and equitable allocation of resources, including COVID-19 vaccination (see related CIDRAP News story), to achieve greater health equity."
Aug 20 MMWR study

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Study finds antibiotics, other medications in urban streams

Screening of a network of urban streams in Baltimore revealed high concentrations of pharmaceuticals, including antibiotics, researchers reported this week in Environmental Science & Technology.

The analysis of 371 water samples collected weekly over the course of a year (November 2017 to November 2018) detected 37 unique compounds belonging to 11 pharmaceutical classes. The antibiotic trimethoprim was the most frequently detected compound (137 detections in 371 samples), while acetaminophen was the compound with the highest concentrations. Antidepressants were also frequently detected.

Among the sites tested, higher concentrations and more compounds were found in streams with higher population densities.

Using their weekly estimates to calculate the annual loads of pharmaceuticals at the outflow point (Baltimore's Inner Harbor), the researchers estimated that the equivalent of 30,000 tablets of acetaminophen, 1,700 doses of antibiotics, and 30,000 doses of antidepressants flow into the harbor each year.

The authors note that because the sewage produced by residents of this urban stream network is transplanted to a wastewater treatment plant outside the watershed, the source of the compounds is likely leaking sewer pipes rather than wastewater effluent.

"These results demonstrate the importance of developing, maintaining, and improving sewage infrastructure to protect water resources from pharmaceutical contamination," they wrote.
Aug 18 Environ Sci Technol abstract

COVID-19 restrictions in Australia linked to lower community antibiotic use

Originally published by CIDRAP News Aug 19

COVID-19 restrictions in Australia were associated with a substantial decline in community dispensing of antibiotics for respiratory infections, researchers reported this week in the British Journal of Clinical Pharmacology.

Using national claims data on antibiotic dispensing from November 2015 through October 2020, a team led by researchers at the University of New South Wales (UNSW) Sydney conducted an interrupted time series analysis to investigate monthly trends in antibiotic dispensing and face-to-face and telehealth consultations with general practitioners (GPs). COVID-19 restrictions began in Australia in January 2020 with restrictions on travel from high-risk countries, ramped up in March 2020 with school closure and limits on gatherings, then were relaxed in May 2020.

The researchers observed a 17% increase in the monthly rate of antibiotic dispensing in March 2020, but from April onward there was a sustained 36% decline in the monthly rate of antibiotic dispensing, adjusted for seasonality.

The mean monthly rate of antibiotic dispensing for April through October 2020 fell to 56.8 per 1,000 population, from 91.1 per 1,000 population for the corresponding period in 2019. Dispensing of antibiotics primarily used for respiratory infections (roxithromycin, amoxicillin, and clarithromycin) fell by 51% to 69%, while antibiotics used for non-respiratory infections (flucloxacillin, metronidazole, and trimethoprim) were unchanged.

Antibiotics dispensed by GPs decreased from 63.5 per 1,000 population from April through October 2019 to 37.0 per 1,000 population during the corresponding period in 2020. GP consultation rates remained stable overall, but telehealth consultations accounted for 31% of consultations from April 2020 onward.

The study authors say the findings could inform post-pandemic antimicrobial stewardship practices.

"The 'natural experiment' arising from the public health responses to the COVID-19 pandemic is a unique occasion to inform antimicrobial prescribing guidelines, highlighting the potential reduction in antibiotic prescribing by GPs and specialists for respiratory viral infections," the study authors wrote. 
Aug 17 Br J Clin Pharmacol study

Study: Stopping, de-escalating antibiotics didn't worsen patient outcomes

Originally published by CIDRAP News Aug 19

A review of stewardship interventions at a Japanese hospital suggests that the use of carbapenems and anti–methicillin-resistant Staphylococcus aureus (MRSA) antibiotics can be safely reduced without worsening patient outcomes, researchers reported this week in the American Journal of Infection Control.

The antimicrobial stewardship program (ASP) at the hospital reviewed all cases for which carbapenems and anti-MRSA antibiotics were used, focusing on dose, duration of use, therapeutic impact, and adverse effect, then made recommendations to prescribing physicians when the course of therapy was completed. Recommendations included discontinuation, de-escalation, and changes in antibiotic use. Analysis of these interventions focused on clinical and microbiologic outcomes in patients treated from December 2018 through November 2019.

While previous studies have looked at the effects of similar interventions on antibiotic use, the study authors say this is the first to investigate the effect of such interventions on clinical and microbiologic outcomes.

The analysis found that favorable clinical responses were obtained in 165 of 184 cases (89.7%) in which the interventions were accepted, compared with 14 of 19 cases (73.7%) in which the intervention was not accepted. In addition, all-cause 30-day mortality was lower in the accepted group than in the not-accepted group (1.1% vs 10.5%). But there were no significant differences on the infection-related 30-day mortality between the accepted and not-accepted patients (0.5% and 0%, respectively). Microbiologic outcomes were similar between the two groups.

Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than in the not-accepted group: 8 days versus 14 days, respectively, for carbapenems and 10 days versus 15.5 days, respectively, for anti-MRSA antibiotics.

"In our ASP, the interventions did not worsen the clinical and microbiological outcomes," they wrote.
Aug 17 Am J Infect Control abstract

New Asian clinical trial network aims to tackle resistant infections

Originally published by CIDRAP News Aug 18

The National University of Singapore (NUS) has received a $1.8 million grant from the Wellcome Trust to establish a clinical trial network focused on antibiotic-resistant infections.

The Asian Clinical Research Network will carry out clinical trials to help develop the most effective ways to treat drug-resistant infections and help improve access to clinically relevant and vulnerable populations. It's the first such network established in Asia, a region with high rates of antibiotic resistance.

The United Nations estimates that antibiotic-resistant infections could cause 10 million deaths a year by 2050, and experts predict that half of those deaths could come from Asia.

"A clinical research network based in Asia will significantly increase the quality and efficiency of clinical trials in the region, resulting in an improved understanding of drug-resistant infections, improved treatment of those infections and an increase in the supply of new drugs to fight antimicrobial resistance," Hsu Li Yang, an infectious disease expert and Vice Dean of the NUS Saw Swee Hock School of Public Health, said in a university press release. "The joint funding will also spur research collaboration and capacity building both in Singapore and the region to jointly develop solutions to the issue of antimicrobial resistance."

NUS will host the center and work with other partners in Singapore to run the clinical trials.

"We are thrilled to launch this important clinical research network with NUS and partners," said Tim Jinks, PhD, head of the Drug Resistant Infections Priority Program at the Wellcome Trust. "This multi-institutional and international collaboration will strengthen and build research capabilities in Asia and support world-class science." 
Aug 17 NUS press release

Indian report notes gaps in guidance on antibiotic use in food animals

Originally published by CIDRAP News Aug 17

A new report by an Indian public interest research and advocacy organization highlights gaps in global recommendations on antibiotic use in food-producing animals and calls for more uniform guidance from the Tripartite United Nations (UN) organizations.

The report from the Centre for Science and Environment notes that while the WHO, the UN Food and Agriculture Organization (FAO), and the World Organization for Animal Health (OIE) all have their own guidance on the use of antibiotics in food-producing animals, there is significant overlap in the antibiotics considered critical for human medicine and veterinary medicine. For example, 47 of the antimicrobials listed by the OIE as being important for veterinary medicine are also on the WHO's list of critically important antibiotics for human medicine.

The report also points out a lack of coherence among the organizations on how antibiotics should be used in food-producing animals. Although there is uniform agreement that critically important antibiotics for human medicine should not be used for growth promotion in livestock, there is less agreement on whether they should be used for disease prevention and control in herds and flocks, or whether critically important antibiotics should be used to treat sick animals.

"Clearly, there is need for more clarity, coherence and, most importantly, a uniform message from the Tripartite organizations," the authors write. "In the absence of this, chances of consensus among national-level animal- and human-health stakeholders are low and the possibility for misinterpretation remains high. This can result in limited action, leading to misuse and overuse of critically important antimicrobials in the food-producing animal sector."

The authors say the organizations should develop uniform guidance that contains a clear message about which critically important antibiotics can be used across the food-animal sector, how they should be used, and which should be prohibited immediately or phased out. They also call for the Tripartite organizations to develop a better understanding of how countries are using critically important antibiotics in food-producing animals, and the levels of resistance to those antibiotics.

The report also contains recommendations for the Indian government to develop a roadmap and policy framework for conserving the use of these antibiotics in the food-animal sector. 
Aug 16 Centre for Science and Environment report

Antibiotic stewardship in hospitalized seniors tied to better outcomes

Originally published by CIDRAP News Aug 16

An analysis of hospitalized geriatric patients found that rigorous de-escalation and curtailing of antibiotics was associated with reductions in hospital readmission and mortality, US researchers reported last week in JAC-Antimicrobial Resistance.

In the study, researchers compared a cohort of patients ages 65 and older at a 256-bed teaching hospital who received ASP interventions from January through June 2017 with a control group of patients in the same age-group at the same hospital who had received antibiotics before the intervention (January through June 2015).

The ASP included de-escalation of empiric or definitive antibiotic therapy, change in duration of therapy, and discontinuation of therapy. The stewardship team met daily to discuss and convey recommendations. Patients included in the study had diagnoses of pneumonia (PNA), urinary tract infection, acute bacterial skin and skin-structure infection (ABSSSI), and complicated intra-abdominal infection.

Overall, there was more than 95% adherence to stewardship recommendations, the majority of which were de-escalations (64%) and discontinuations (24%) and resulted in a significant decrease of broad-spectrum antibiotic use.

Analysis of outcomes showed that the 30-day hospital readmission rate fell from 24.9% in the control group to 9% in the ASP group, with the biggest declines observed among patients diagnosed with PNA and ABSSSI. The rate of 30-day readmission for Clostridioides difficile infection fell from 2.4% to 0.30%.  Mortality fell from 9.6% in the control group to 5.4% post-intervention.

In addition, antibiotic expenditures fell from $23.30 per adjusted patient day to $4.30 following implementation of the ASP.

"Studying the association between ASP efforts and patient outcomes is of great importance as it increases our understanding of how ASPs contribute to the patient’s overall quality of care," the authors wrote. "We show that a stringent ASP can be safely implemented in an elderly hospitalized patient population without discernible adverse outcomes."
Aug 12 JAC-Antimicrob Resist study

Survey finds stewardship lagging in French nursing homes

Originally published by CIDRAP News Aug 16

A survey of French nursing homes shows there is large room for improvement in antibiotic stewardship, researchers reported yesterday in JAC-Antimicrobial Resistance.

Of the 417 nursing homes in the Grand Est region of northeastern France invited to participate in the survey, only 75 (18%) responded. The survey included 35 questions covering four topics: Nursing home characteristics, current antibiotic stewardship practices, attitudes toward antibiotic stewardship, and opinions on strategies to promote stewardship.

Core elements of antibiotic stewardship programs were overall present in fewer than half of the participating nursing homes, but only 3% did not have any stewardship activities in place. No specific nursing home characteristic was associated with the level of implementation of stewardship activities.

The three most implemented stewardship activities were antibiotic consumption monitoring (65%), antibiotic plan documentation (56%), and antibiotic prescription guide distribution (54%). Only 13% performed audit and feedback on antibiotic prescribing, and only 23% and 29% offered training on infection management and antibiotic prescribing for medical staff and nursing staff, respectively.

Participants positively perceived antibiotic stewardship and suggestions to improve stewardship in nursing homes, with the greatest interest in training for physicians, distribution of antibiotic prescribing guides, and audit and feedback.

"This survey shows that ABS [antibiotic stewardship] programmes are insufficiently implemented in French NHs [nursing homes], even though the medical and nurse coordinators who participated in this survey seemed aware this is a public health priority," the study authors wrote.

While France does not require nursing homes to have stewardship programs, there are regional initiatives promoting stewardship. The authors suggest that core elements for nursing home stewardship be defined at a national level and that regional health authorities could then take a lead role in implementing those elements. 
Aug 15 JAC-Antimicrob Resist study

Program linked to better antibiotic choice in penicillin-allergic patients

Originally published by CIDRAP News Aug 16

A low-cost intervention aimed at improving perioperative antimicrobial prophylaxis for patients with penicillin allergy was associated with higher use of cephalosporins and lower antibiotic costs, researchers reported today in Infection Control & Hospital Epidemiology.

The intervention at Emory University School of Medicine was based on the results of a survey of anesthesia providers at the hospital (who are responsible for perioperative antibiotic selection). It included a decision support algorithm that recommends cephalosporins (cefazolin or cefuroxime) for all patients without a history of severe delayed hypersensitivity reactions to penicillin, along with a screening questionnaire to help identify those patients. The survey results were also used to design two educational presentations to introduce the algorithm.

Analysis of patients who received perioperative antibiotics from January 2017 through August 2019 at the hospital showed that the percentage of penicillin-allergic patients receiving a cephalosporin increased from roughly 34% to more than 80% following implementation of the algorithm and the associated educational presentations. No severe adverse events were reported. There was also a reduction in second-line agents associated with the intervention that was accompanied by a 58% reduction in the antibiotic cost for each penicillin-allergic patient.

"These findings emphasize the ongoing need for strategies to risk-stratify patients with penicillin allergy labels so that they can receive appropriate targeted antimicrobial coverage," the study authors write. "Our study results also suggest that transitioning penicillin-allergic patients to first-line therapy has significant benefits with respect to decreased use of higher-cost, less-effective second-line antibiotic agents."
Aug 16 Infect Control Hosp Epidemiol abstract