Stewardship / Resistance Scan for Oct 01, 2020

News brief

Dutch group recommends restrictive antibiotic use in COVID patients

Based on available evidence and antibiotic stewardship principles, a committee of Dutch clinicians and researchers is recommending restrictive use of antibiotics in COVID-19 patients, according to guidelines published yesterday in Clinical Microbiology and Infection.

With the intention of developing evidence-based recommendations for the use of antibiotics in patients with a respiratory infection and suspected or confirmed COVID-19, the Dutch Working Party on Antibiotic Policy conducted a review and analysis of literature on COVID-19 and bacterial co-infections and secondary infections.

They set out to answer four key questions about the risk of bacterial pneumonia in patients with suspected or confirmed COVID-19, the causative bacterial species, the optimal approach to diagnosing or refuting bacterial pneumonia, and the optimal antibiotic choice.

The committee found that bacterial co-infection upon admission occurred in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred in up to 15% of patients. But not enough evidence was available to answer the other questions.

The committee agreed that clinicians should always assess the risk of a bacterial infection in patients with suspected COVID-19 and that antibiotic therapy should be considered if the clinician has a high suspicion of bacterial co-infection in a patient with radiologic findings and/or inflammatory markers compatible with bacterial co-infection.

But they also said maximum efforts should be undertaken to obtain sputum and blood culture samples and conduct pneumococcal urinary antigen testing and suggested that antibiotics be stopped if results show no signs of bacterial pathogens after 48 hours.

The committee recommended an antibiotic treatment duration of 5 days in patients with COVID-19 and suspected bacterial respiratory infection, contingent upon improvement in signs, symptoms, and inflammatory markers.

The committee says larger, prospective studies on the epidemiology of bacterial co-infections and secondary infections in COVID-19 patients are needed to confirm their conclusions.
Sep 30 Clin Microbiol Infect study

Study: California ASP mandate associated with C diff reduction, MRSA rise

A study today in Infection Control & Hospital Epidemiology shows that California's antimicrobial stewardship program (ASP) mandate was associated with a decrease in Clostridium difficile infection (CDI) rates and an increase in methicillin-resistant Staphylococcus aureus (MRSA) rates in acute care hospitals.

To evaluate the impact of a 2014 law that required acute care hospitals in California to adopt and implement an ASP, researchers analyzed hospital-level data covering 2013 through 2017 from the Centers for Medicare and Medicaid (CMS) Hospital Compare, Provider of Service, and Medicare Cost Reports files. They then compared the MRSA and CDI standardized infection ratio (SIR) for California acute care hospitals with those in other states.

In 2013, the average SIR in California hospitals was 0.79 for MRSA, compared with 0.94 for hospitals in other states, and the average CDI SIR was 1.01, versus 0.77 for other states. In 2015, 2016, and 2017, California hospitals had 23%, 30%, and 20% increases in MRSA SIRs compared with other states, while the CDI SIR decreased by 20%, but only in 2017.

Although the decrease in CDI SIR was expected because the ASP mandate restricted antibiotic use in California hospitals, the authors of the study say the increase in MRSA SIR may be the result of more proactive identification of antibiotic-resistant pathogens. They also note that the impact of ASPs is likely stronger for gram-negative microorganisms because most of the restricted antibiotics are for gram-negative infections (MRSA is gram-positive).

The authors add that more data on postintervention years are needed to assess the long-term impact of the California mandate and that ASP mandates in other states should be studied.
Oct 1 Infect Control Hosp Epidemiol abstract

Analysis: AMR Action Fund won't fix broken antibiotic market

A pharmaceutical industry effort to fund development of new antibiotics through investment in small companies could buy time for reforms to address the underlying market problems facing antibiotic development but will not fix those problems on its own, according to a new analysis in Open Forum Infectious Diseases.

The AMR Action Fund, launched in June by 20 of the world's largest pharmaceutical companies, aims to invest $1 billion in small antibiotic companies with promising products, with the goal of bringing two to four new antibiotics to market by 2030.

Although many of these large drug makers have abandoned antibiotic development because of the lack of financial return on antibiotics, the hope is that their money and technical assistance can help the smaller companies, which struggle financially, bring innovative new products to market and boost the antibiotic development pipeline.

But the analysis of the AMR Action Fund by clinicians with the University of Pittsburgh Department of Medicine and the VA Pittsburgh Healthcare System suggests that while the fund will provide a financial lifeline to struggling companies, it does not address the biggest problem—the low reimbursement for new antibiotics and the need to de-link reimbursement from numbers of prescriptions.

The analysis also highlights how the fund fails to address three particular issues that have contributed to the financial failure of new antibiotics for carbapenem-resistant bacteria: slow clinical uptake by clinicians; the relatively small number of carbapenem-resistant infections that occur in the United States; and an excess of new agents that aren't superior to current antibiotics.

"The Fund's major weaknesses are that it does not directly address the 3 issues identified in our case study, nor will it fix the broken marketplace," the authors wrote. "Its most important charge will be to buy time to convince governments to enact reimbursement reforms ('pull' incentives) or implement new antibiotic development models."
Sep 30 Open Forum Infect Dis abstract

News Scan for Oct 01, 2020

News brief

Loss of taste or smell accurately predicts COVID-19, study finds

A study shows four out of five people with recent loss of smell and/or taste tested positive for COVID-19 antibodies, and 39.8% of those did not have a cough or fever.

COVID-19 is known to cause a loss of taste and/or smell, but the SARS-CoV-2 antibody status of people experiencing these symptoms was previously unknown. A PLOS Medicine study today sought to explore the significance of loss of taste/smell as a predictor of COVID status.

Researchers enrolled 590 people during the peak of the COVID-19 outbreak in London who self-reported a loss of taste/smell via telemedicine consultation in the previous month. Of the participants with loss of smell and/or taste, 76.6% were seropositive (carried antibodies for SARS-CoV-2), with participants experiencing smell loss alone nearly three times as likely to be seropositive than participants experiencing taste loss alone (odds ratio 2.86; 95% confidence interval, 1.27 to 6.36; P < 0.001), suggesting that loss of smell is a highly specific symptom of COVID-19.

The authors conclude, "In a community-based population, the vast majority of participants with new onset loss of smell were seropositive for SARS-CoV-2 antibodies. Acute loss of sense of smell needs to be considered globally as a criterion for self-isolation, testing, and contact tracing in order to contain the spread of COVID-19."

Significantly, 39.8% of the COVID-19–positive participants had neither cough nor fever. An over-reliance on cough and fever as the main symptoms of COVID-19 may be misguided, and the researchers advocate for urgent recognition of loss of smell as a key symptom of COVID-19. The authors wrote, "Counterintuitively, people with minor symptoms, such as isolated smell loss, who remain systemically well pose the highest public health threat."

"Our findings suggest that people who notice a loss in their ability to smell every day house-hold odors such as garlic, coffee, and perfumes should self-isolate and seek PCR [polymerase chain reaction] testing," senior author Rachel Batterham, PhD, MSc, of the University College London, said in a PLOS press release. "Loss of sense of smell needs to be recognized globally by policy makers as a key symptom of COVID-19."
Oct 1 PLOS Med study
Oct 1 PLOS press release

Higher risk of COVID-19 death found in psychiatric patients

In the first known study of COVID-19 psychiatric patients and mortality, a JAMA Network Open study yesterday showed that patients with diagnosed psychiatric disorders have significantly higher risk of death.

The cohort study of 1,685 patients at Yale New Haven Health System, a five-hospital system in the Northeast, studied patient mortality data from Feb 15 through May 27 using a Kaplan-Meier statistical analysis to compare survival rates. The study identified 473 patients (28%) previously diagnosed as having psychiatric disorders.

The overall mortality rate for all patients was 18.9%, with 318 hospital deaths. COVID-19–positive patients with psychiatric diagnoses had a significantly higher risk of hospital death, with a 4-week mortality rate of 44.8%, versus 31.5% for non-psychiatric patients.

Patients with psychiatric diagnoses tended to be older, female, white, non-Hispanic, with other medical comorbidities. After adjusting for demographic characteristics, comorbidities, and hospital location, psychiatric patients had a 1.5 times higher risk of death (hazard ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.003).

"The finding is similar to previous findings: individuals with concurrent psychiatric and medical diagnoses had poorer outcomes and higher mortality," the study authors wrote.

The authors noted that psychiatric disorders are associated with shortened life expectancy in general—by as much as 10 years—but it is unclear why psychiatric illness predisposes patients to COVID-19–related mortality. There may be an association of psychiatric disorders with inflammatory processes, immune function, or an increased risk from psychotropic medications, the authors suggest.
Sep 30 JAMA Netw Open study

Three more fatal Ebola cases reported in DRC outbreak; 128 cases, 53 fatal

Three retrospective probable Ebola deaths from July have been added to the total in the Democratic Republic of the Congo (DRC) Equateur province, the United Nations Office for the Coordination of Human Affairs (UN OCHA) said in a statement today.

The development lifts the outbreak total to 128 cases and 53 deaths. The three additional probable cases are all in Bolomba health zone, including one in Boyenge health area, which had not previously reported any confirmed or probable cases. UN OCHA also said response teams and medical supplies arrived in Lusengo health zone, the newest affected area in the outbreak.

The outbreak in Equateur province was first detected in June in the same area where an Ebola outbreak in 2018 sickened 54 people, 33 of them fatally.
Oct 1 UN OCHA report

HPV vaccine shown to help prevent cervical cancer

While human papillomavirus (HPV) vaccinations have been linked to lower cervical cancer rates for years, researchers from the Karolinska Institutet in Solna, Sweden, say their study is the first population study looking at not only pre-cancer indicators but also actual, invasive cervical cancer.

The results, published today in the New England Journal of Medicine, suggest a rate of 47 cases of cervical cancer per 100,000 vaccinated women versus 94 cases per 100,000 in unvaccinated women, with an overall risk reduction of 63%—88% in those vaccinated earlier in life.

From 2006 through 2017, the researchers followed almost 1.7 million Swedish girls and women between the ages of 10 and 30, of whom more than 500,000 were vaccinated against HPV. After adjusting for all covariates such as age, residential area, follow-up time, and parental factors, including income and disease history, the study found the incidence rate ratio was 0.12 in women who had been vaccinated before age 17 and 0.47 in those who had been vaccinated between age 17 and 30.

Overall incident rate ratio was 0.37, which translated to a 63% lower risk of cervical cancer—but among those who were vaccinated before age 17, the incidence rate ratio noted above translates to an 88% lower risk of cervical cancer.

"Girls vaccinated at a young age seem to be more protected, probably because they are less likely to have been exposed to HPV infection and given that HPV vaccination has no therapeutic effect against a pre-existing infection," senior author Pär Sparén, PhD, said in a Karolinska press release.
Oct 1 N Engl J Med study
Sep 30 Karolinska Institutet news release

WHO sounds alarm about monkeypox outbreak in DRC

The World Health Organization (WHO) today detailed a monkeypox outbreak in the DRC, with 4,594 suspected cases reported so far this year, 171 of them fatal, with illnesses spread across 17 of the country's 26 provinces.

Monkeypox is endemic in the DRC, but the number reported so far this year has already outpaced the country's totals for this time of year for 2019 and 2018. Tests confirmed monkeypox in 39 of 80 samples sent to the lab at Institut National de Recherche Biomédicale (INRB).

Hardest-hit provinces include Sankuru, Mai-Ndombe, and Equateur, with the latter province also battling and Ebola outbreak and all of the country grappling with the COVID-19 pandemic. The WHO said one of the areas it's most concerned about is Inongo health district in Mai-Ndombe province, where a fourth of the territory is affected.

More than half (58%) of the suspected cases involve people over age 5, but the case-fatality rate for children younger than 5 is 4.2%, compared with 3.4% in the older age-group.

The WHO warned that many of the provinces are juggling other disease outbreaks with stretched financial resources, along with armed conflict and violence. And it notes that proximity to forests puts many residents, including hunters, in contact with animal reservoirs. It said it is gathering more information about cases and lab capacity and that the support of partners such as the US Centers for Disease Control and Prevention (CDC) is critical.
Oct 1 WHO statement

Vietnam detects more H5N1 and H5N6 avian flu in poultry

Vietnam today reported more highly pathogenic avian flu outbreaks in poultry, one from H5N1 and three from H5N6, according to the latest notifications from the World Organization for Animal Health (OIE).

The H5N1 outbreak struck village birds in Ca Mau province in the far south of the country. It began on Sep 3 and killed 63 of 243 birds. The source of the virus isn't known, and culling and vaccination were among the response steps. Vietnam reported its last H5N1 outbreak on Sep 11 in village birds in Tra Vinh province, also in the south.

Meanwhile, three more H5N6 outbreaks were detected in village birds in two different provinces, two in Nghe An in the north and one in Kon Tum in the central part of the country. The outbreaks began from Aug 26 to Sep 24, and, taken together, the virus killed 377 of 1,422 birds. The survivors were culled, and vaccination was ordered for birds in the area. Vietnam is among the Asian countries that have reported sporadic H5N6 outbreaks, with the last one reported on Sep 11.
Oct 1 OIE report on H5N1 in Vietnam
Oct 1 OIE report on H5N6 in Vietnam