Stewardship / Resistance Scan for Sep 14, 2020

News brief

Rapid diagnostics, stewardship linked to quicker time to optimal antibiotics

The introduction of a rapid diagnostic test (RDT) in conjunction with antimicrobial stewardship (AMS) activities and infectious disease (ID) consultation at an academic tertiary medical center was associated with shortened time to optimal antibiotic therapy in patients with bloodstream infections, University of Maryland researchers reported in Open Forum Infectious Diseases.

In the retrospective quasi-experimental study, researchers with the University of Maryland's School of Medicine and School of Pharmacy compared time to optimal antibiotic therapy and clinical outcomes in patients with gram-negative bloodstream infection (GN BSI) during three different periods: pre-RDT/AMS, post-RDT/pre-AMS, and post-RDT/AMS.

Rapid testing was conducted with Verigene Blood-Culture Gram-Negative, a microarray RDT that detect eight key organisms and six genetic resistance determinants within 2.5 hours. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infections.

Altogether, 832 patients were included in the study; 237 pre-RDT/AMS, 308 post-RDT/pre-AMS, and 237 post-RDT/AMS. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%, P < 0.0001), and the time to optimal therapy decreased with the introduction of RDT (47 hours vs 24.9 hours vs 26.5 hours, P = 0.09).

Using multivariable modeling, the researchers determined that ID consult was an effect modifier, and therefore the results were stratified by presence of ID consult. Within the ID consult stratum, controlling for source infection and for intensive care unit stay, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% confidence interval [CI], 1.04 to 1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01 to 1.64) improved time to optimal therapy compared with the pre-RDT/AMS period. The effect was not observed in the stratum without ID consult.

"In conclusion, introduction of RDT in GN BSI resulted in significant decrease in time to optimal antibiotic therapy, by a median of approximately 22 hours from blood culture draw," the study authors wrote. "Additionally, the overall proportion of patients placed on optimal antibiotic therapy increased."
Sep 12 Open Forum Infect Dis abstract

UK study supports oral antibiotics for patients with bone, joint infections

A study by UK researchers published today in Clinical Infectious Diseases indicates that findings of the Oral Versus Intravenous Antibiotics (OVIVA) trial can be implemented into clinical practice.

The OVIVA trial, conducted in the United Kingdom, found that oral antibiotic therapy was non-inferior to intravenous therapy when used during the first 6 weeks in patients with bone and joint infections (BJIs). The results of the trial were initially presented in 2017 and published in 2019, but to date there have been no reports describing their reproducibility in real-world settings.

To determine whether the OVIVA findings can be replicated, researchers with the Royal National Orthopaedic Hospital, which implemented changes in practice in 2017 based on the results, looked at all patients diagnosed as having BSI at the hospital in the 12 months pre- and post-implementation. Outcomes included treatment failure, adverse drug reactions (ADRs), ADR-related hospital readmission, hospital length of stay (LOS), and treatment costs. Patient follow-up was conducted by an outpatient parenteral antibiotic therapy (OPAT) service.

In their analysis of 328 patients (145 pre- and 183 post-implementation), the researchers found that 66.1% of patients were switched to a suitable oral antibiotic regimen post-implementation. The rate of treatment failure was more common post-implementation (18.6%) compared with pre-implementation (13.6%), but Kaplan-Meier analysis of infection-free survival at 12 months did not demonstrated any statistical difference between the two groups (P = .154). Subgroup analysis showed that in the post-implementation period, treatment failure was more common in patients who required IV antibiotics due to lack of suitable options (IV, 26.7% vs oral, 14.3%).

ADRs requiring close monitoring or change of treatment were more common post-implementation (37.1% vs 21% pre-implementation), but ADR-related hospital readmissions were similar in both groups (2.2% vs 2.1%). The post-implementation group showed a reduction in 4 days in the median LOS and a median cost reduction of £ 2,764.28 (US $3,558) per patient.

The authors of the study conclude, "These findings provide a useful guide for hospitals implementing the results of the OVIVA trial. Larger multicenter studies are required to better understand the differences in antibiotic regimens in varying patient groups and against specific pathogens."
Sep 14 Clin Infect Dis study

Antibiotic overuse noted after discharge in pneumonia, UTI patients

A study of patients diagnosed as having pneumonia and urinary tract infections (UTIs) at 46 hospitals in Michigan found that about half had antibiotic overuse after discharge, researchers reported late last week in Clinical Infectious Diseases.

The retrospective cohort study, led by researchers with Michigan Medicine, looked at patients treated for pneumonia or UTI at hospitals in the Michigan Hospital Medicine Safety Consortium from July 2017 through 2019 to quantify the proportion of patients discharged with antibiotic overuse, which was defined as unnecessary antibiotic use, excess antibiotic duration, or suboptimal fluoroquinolone use. The researchers used linear regression analysis to assess hospital-level association between antibiotic overuse after discharge in patients treated for pneumonia versus patients treated for UTI.

Of the 21,825 patients treated for infection (12,445 pneumonia, 9,380 UTI), 49.1% had antibiotic overuse after discharge, including 56.9% of patients treated for pneumonia and 38.7% of patients treated for UTI. The median duration of antibiotic overuse after discharge was 4 days. In patients treated for pneumonia, 63.1% of overuse days after discharge were due to excess antibiotic duration, while in patients treated for UTI, 43.9% of overuse days were due to unnecessary antibiotic treatment of asymptomatic bacteriuria.

The percentage of patients discharged with antibiotic overuse varied fivefold among hospitals, from 15.9% to 80.6%, and was strongly correlated between conditions. For every 10% increase in patients treated at a hospital for UTI who had overuse after discharge there was an 8.5% increase in patients treated for pneumonia who had overuse after discharge.

The authors of the study said the findings suggest prescribing culture, physician behavior, and organizational processes all play a role in overprescribing after discharge.

"Given the ubiquity of overuse after discharge, it is imperative that stewardship programs enact interventions to improve prescribing—which often means stopping antibiotics—at care transitions," they wrote, adding that easier methods of tracking antibiotics at discharge could enable more complete national measures of antibiotic use.
Sep 11 Clin Infect Dis abstract

News Scan for Sep 14, 2020

News brief

Experts: Using death certificates alone undercounts COVID-19 fatalities

A group of experts from Stanford and Harvard universities, as well as the Dana-Farber Cancer Institute, propose a new model for measuring direct, indirect, and excess deaths from COVID-19 in the United States, and they say relying solely on death certificates likely undercounts the true death toll COVID-19 has taken in the United States. Their proposal is published in the Annals of Internal Medicine.

The authors write that, before a standardized case definition was published in early April and testing rates were very low, practitioners likely did not attribute all deaths in patients infected with SARS-CoV-2 to COVID-19. Also, COVID-19 deaths are coded manually, resulting in reporting delays and frequent updates to the official count, with substantial variation across states.

The authors suggest that state and federal public health officials adopt the Centers for Disease Control and Prevention's (CDC's) "but for" principle, commonly used when assessing the death toll of natural disasters: "But for the [pandemic], would the person have died when he/she did?"

To estimate the direct and indirect death rate, the authors then suggest counting all deaths from pneumonia, influenza-like illness, and COVID-19, then subtracting the expected seasonal number of cases of pneumonia and influenza computed from trends in the previous 5 years per the CDC.

"Correct attribution of direct and indirect deaths and estimation of excess mortality are complementary goals that are critical to our understanding of the pandemic and its effect on human life," the authors write.
Sep 11 Ann Intern Med study

Good personal relationships may protect against COVID-19 lockdown stress

People with high-quality marriages reported greater mental health and well-being than singles or those with a low-quality relationship during COVID-19 lockdowns in Austria, a study published late last week in PLOS One found.

Researchers at Danube University Krems conducted an online survey of a representative 1,005-person sample 4 weeks after lockdowns were instituted in Austria on Mar 16. The 543 respondents with solid marriages scored better on all mental health scales for depression, anxiety, stress, well-being, sleep quality, and quality of life than the 272 singles and the 190 with shaky marriages. Singles scored better than those with weak relationships.

Depressive and anxiety scores varied by strength of respondent relationship, from 13% to 35% for depression and 12% to 32% for anxiety. The mean score on the Quality of Marriage Index was 36.95 among the 733 respondents in a relationship. Scores above 34 are considered to indicate strong relationships. The mean score in those with poor relationships was 24.15, while it was 41.43 in those with good marriages.

Those with weak relationships were 3.5 more likely than those with strong relationships to generate scores indicating depression on the Patient Health Questionnaire-9. They were also 3.4 times more likely to have high scores on the Generalized Anxiety Disorder-7 scale and 2.0 times more likely to demonstrate impaired sleep quality on the Insomnia Severity Index.

The authors noted that their findings back those from previous studies that showed that solid marriages are protective against depression and anxiety and that no relationship is better for mental health than a weak one.

"Relationship per se was not associated with better mental health, but the quality of the relationship was essential," the authors wrote. "It underlines the fact that not only but especially in times like this, the choice of partner should be carefully considered."
Sep 11 PLOS One study

Norway reports chronic wasting disease in wild reindeer in new area

Norwegian health officials have confirmed a wild reindeer hunted in central southern Norway earlier this month has tested positive for chronic wasting disease (CWD), a deadly prion disease found in cervids like deer and elk.

This is the first time a reindeer in that part of Norway has been found to be CWD-positive and indicates disease spread. Material from a lymph node tested positive, while brain tissue was found negative.

The wild reindeer has classical CWD, which is contagious to other cervids, as opposed to atypical CWD, which can be seen in older animals. The animal was hunted in Hardangervidda, a southern mountain plateau region home to between 8,000 and 10,000 wild reindeer.

"Since 2016, more than 100,000 cervids have been tested for CWD in Norway. From Hardangervidda, 3520 wild reindeer have been tested and found to be CWD negative. Of these, 518 have been tested already in 2020 without positive findings," the Norwegian Veterinary Institute said in a press release.
Sep 11 Norwegian Veterinary Institute press release

With 3 new infections, DRC Ebola outbreak rises to 121 cases, 48 deaths

Three more Ebola cases were reported in the Democratic Republic of the Congo (DRC) Equateur province outbreak, including one in a newly affected health area, the United Nations Office for the Coordination of Humanitarian Affairs (UN OCHA) said recently in its latest situation update.

The newly affected area is Bontole, bringing the number of health areas that have reported cases to 39, though just 10 currently have active cases. he 3 new cases, reported on Sep 10, bring the outbreak total to 121. No new deaths were reported, keeping the fatality count at 48.

OCHA said free health care is an essential tool for battling the outbreak, and though doctor's visits are free, patients are still expected to pay for treatment, forcing some to self-medicate or seek care from traditional healers, raising the risk of virus spread. It also said population movements are worrying in Equateur province, and stepped efforts are underway to better track the movement of contacts and understand the reasons for population displacements in the area.
Sep 12 UN OCHA update

H5N8 avian flu strikes more poultry in Russia

Russia today reported eight highly pathogenic H5N8 avian flu outbreaks in poultry in two neighboring western Siberia oblasts that had recently reported a spate of high-path H5 outbreaks, according to a notification from the World Organization for Animal Health (OIE).

All of the outbreaks occurred in backyard birds, four in Tyumen oblast and four in Omsk oblast. The events began between Sep 1 and Sep 7, killing 483 of 1,560 susceptible birds. Culling is under way.

So far, the source of the virus isn't known. H5 was recently detected in waterfowl found dead in Tyumen oblast. In In early August, Russia reported two H5N8 outbreaks in village and backyard birds in Chelyabinsk oblast, west of the two latest locations.

In a recent risk assessment on the avian flu situation in Russia, the UK Department for Environment, Food, and Rural Affairs (DEFRA) noted that large outbreaks in Europe in 2016 involving H5N8 were heralded by summer outbreaks in Russia, and it urged poultry owners to remain vigilant.
Sep 14 OIE report on H5N8 in Russia
Sep 4 DEFRA report