Stewardship / Resistance Scan for Sep 04, 2020

News brief

Urinary culture intervention linked to lower antibiotic prescribing

An intervention to reduce antibiotic treatment for asymptomatic bacteriuria (ASB) at a Toronto hospital was safe and associated with reduced exposure to unnecessary antibiotics, Canadian researchers reported this week in Infection Control and Hospital Epidemiology.

In a prospective observational study conducted at Mount Sinai Hospital in Toronto, which implemented an intervention in 2013 to stop processing midstream urine cultures (MSUs) from patients unless the laboratory was called, researchers interviewed 1,678 patients with an MSU order on days 0 and 4 to ask about urinary symptoms and any adverse events. From 2017 to 2019, day 30 follow-up was added.

The primary outcome was serious adverse events due to not processing MSUs. Secondary outcomes included nonserious adverse events, rates of cultures submitted and processed, proportion of patients prescribed urinary tract infection (UTI)-directed antibiotics, and laboratory workload.

Among 912 and 459 patients followed to days 4 and 30, respectively, no serious adverse events attributable to not processing MSU cultures were identified. However, 6 patients (0.7%) had prolonged urinary symptoms potentially associated with not processing MSU cultures.

The researchers estimated that 4 patients missed having empiric antibiotics stopped in response to negative MSU cultures, and 99 antibiotic courses for asymptomatic bacteriuria (ASB) and 8 antibiotic-associated adverse events were avoided. The rate of submitted MSU samples and proportion of patients receiving empiric UTI-directed antibiotics did not change. The proportion of MSU cultures processed declined from 59% to 49% (P < .0001), and total laboratory workload was reduced by 185 hours.

"In conclusion, not processing MSU cultures from medical and surgical inpatients is safe, and it reduces inappropriate ASB therapy and laboratory workload," the authors of the study wrote. "We believe that the benefits of reduced antibiotic use outweigh the harm of persistent symptoms in a very few patients."
Sep 2 Infect Control Hosp Epidemiol abstract

 

Antibiotic prescribing frequent in ill Kenyan children, study finds

US and Kenyan researchers reported yesterday in Clinical Infectious Diseases that antibiotic treatment was high in a cohort of Kenyan children with undifferentiated fever, despite a low prevalence of bacterial illness.

The researchers examined clinical presentation and management of Kenyan children with fever at five hospitals or clinics from 2014 through 2017. The aim of the study was to characterize which variables are associated with higher odds of antibiotic therapy in both malaria-negative and malaria-positive children and to evaluate the concordance of diagnosis of bacterial illness with antibiotic treatment. All five sites were in malaria-endemic regions of Kenya, and all children in the study were tested for malaria by blood smear microscopy.

Of the 5,737 children enrolled in the study, 68% (3,902) were prescribed antibiotic therapy, while 14% (812) received a primary diagnosis of bacterial illness. In 777 children (14%), bacterial illness was given as the differential diagnosis. Nearly two thirds of those given antibiotics (64%) had neither a primary nor differential diagnosis of bacterial illness.

On multivariate analysis, a negative malaria test was associated with a sevenfold increase in the odds of receiving an antibiotic (odds ratio, 7.1; 95% confidence interval [CI], 5.6 to 9.1). Other factors associated with increased odds of antibiotic therapy included age 1 to 4 years; reporting of head, ears, eyes, nose, and throat symptoms; and having a flush toilet in the home.

"Based on these results and given the degree of diagnostic uncertainty, providers seem highly reluctant to discharge febrile children without empiric antibiotic treatment," the authors of the study wrote.

They suggested that providers in these settings, lacking point-of-care tests beyond those for malaria, may benefit from improved clinical education and implementation of enhanced guidelines for clinical decision-making.
Sep 3 Clin Infect Dis abstract

News Scan for Sep 04, 2020

News brief

Early trials of Russian COVID-19 vaccine show safety, immune response

Today The Lancet published the results of two nonrandomized trials (called Sputnik V) of a Russian COVID-19 vaccine candidate, which showed no serious adverse events and demonstrated that the vaccine elicited an antibody response in study participants within 21 days of administration. The phase 1/2 trials were conducted in 76 healthy adults.

The two phase 1/2 trials included a frozen formulation of the vaccine, and another involving a lyophilized (freeze-dried) formulation of the vaccine. Both vaccines are based on two adenovirus vectors, modified with the SARS-CoV2 spike protein. In both formulations, participants received two doses of the vaccine, at day 0 and day 21. Follow-up was 42 days.

No serious adverse events were noted in the 42 days. Mild events included pain at the injection site (44 of 76 participants; 58%), hyperthermia (50%), headache (42%), and muscle and joint pain (24%)

All 40 participants in the phase 2 trial showed neutralizing antibody responses by day 21, with 85% having neutralizing antibody responses by day 14. The study was funded by Russia's Ministry of Health.

In an accompanying commentary, Naor Bar-Zeev, PhD and Tom Inglesby, MD, both of Johns Hopkins University, wrote that although the studies were small, the results are promising.

Most notably, the development of two vaccine formulations is an advantage in a global pandemic. "A lyophilised formulation could mean stability within the existing global vaccine refrigerated cold chain that is needed to maintain vaccine efficacy from factory to recipient, a hurdle other vaccines are yet to address," Bar-Zeev and Inglesby wrote.

There were key limitations, however. Older adults were excluded from the trials, and only 2 participants were not white. A planned phase 3 trial of 40,000 people should help gather information about how the vaccine performs in the wider population.
Sep 4 Lancet study
Sep 4 Lancet commentary

 

Experts unveil ethics-based strategy for distributing COVID-19 vaccines

A team of 19 global health experts, led by Ezekiel Emanuel, MD, PhD, chair of Medical Ethics and Health Policy in the Perelman School of Medicine at the University of Pennsylvania, propose a new framework for distributing a future COVID-19 vaccine: focus on preventing premature deaths. The framework appeared yesterday in Science.

While some groups, including the National Academy of Sciences, have called for distributing a vaccine first to healthcare workers and the elderly, and the World Health Organization (WHO) has said vaccine dose distribution should be in proportion to a nation's population, Emanuel and colleagues said both strategies are ethically flawed.

Instead, phase 1 of the Fair Priority Model focuses on distributing the vaccine to people determined by a country to be at risk from premature death from COVID-19, a calculation derived from "standard expected years of life lost." Phase 2 would focus on vaccinating groups based on the extent to which people would be spared from poverty, and phase 3 would focus on countries with high transmission rates.

Focusing on years of life lost is an equitable model, the experts say, because, "it regards all deaths as important but earlier deaths as particularly important. Thus, it integrates the aims of limiting harm and of prioritizing the least advantaged, particularly because early deaths are more frequent in low-income countries and are a proxy for being disadvantaged overall."

"It will be up to political leaders, the WHO, and manufacturers to implement this model," Emanuel said in a University of Pennsylvania news release. "Decision-makers are looking for a framework to ensure that everyone throughout the world can be vaccinated, so that we can stop the spread of this virus."
Sep 3 Science article

Sep 3 University of Pennsylvania news release

 

Study suggests Rocky Mountain wood ticks not a CWD vector

A new study in mSphere suggests that Rocky Mountain wood ticks may not play a role in the transmission of chronic wasting disease (CWD).

The study, conducted by researchers at Creighton University, investigated the possibility that Dermancentor andersoni, a tick species that overlaps with CWD throughout the northwest United States and southwest Canada and is a vector of several bacterial and viral pathogens, may also be a vector for the spread of CWD. The mechanism of CWD spread is not definitively known, but it likely occurs by animal exposure to environmental sources of prions such as soil, blood, urine, feces, decaying carcasses, or maternal transmission.

CWD is a fatal neurologic disease affecting members of the deer family in 26 states, three Canadian provinces, and Finland, Norway, South Korea, and Sweden. No human cases have occurred.

To test the theory that D andersoni may be a vector for CWD, the researchers inoculated 10 hamsters with uninfected brain homogenate, and 10 with hyper-infected (HY-infected) brain homogenate, then applied D andersoni nymphs to the hamsters in two stages. In the early group, nymphs were applied to 5 uninfected and 5 HY-infected hamsters at day 83 post-infection and removed at day 88. In the late group, nymphs were applied to the 10 remaining hamsters at day 126 post-infection and removed at day 131. All of the hamsters in the late group developed hyperexcitability and ataxia at 143 days post-infection, while none of the mock-infected hamsters developed clinical signs.

The researchers then collected midgut contents from the engorged D andersoni nymphs that fed on the two groups of hamsters and inoculated groups of five hamsters with the tick midgut content or whole blood from either uninfected or HY-infected hamsters from the early and late groups. The tick blood meal came from nymphs that fed on the same hamsters that blood was collected from.

The results of the animal bioassay showed that none of the hamsters inoculated with tick midgut contents or blood from uninfected hamsters developed signs of clinical disease by day 500 or 550, while two of the five hamsters infected with blood from HY-infected late-group hamsters developed hyperexcitability and ataxia consistent with HY-infection. All other hamsters with either tick midgut contents or blood from the early or late HY-infected hamsters remained asymptomatic.

"Overall, under the conditions tested, tick midgut contents do not contain sufficient prion infectivity to cause clinical disease when inoculated into hamsters," the authors of the study wrote.
Sep 2 mSphere study

 

Three countries add more cases to polio totals

Three countries—Afghanistan, Chad, and the Democratic Republic of the Congo (DRC)—reported new polio cases in the past week, according to the latest update from the Global Polio Eradication Initiative (GPEI).

Afghanistan reported three wild poliovirus type 1 (WPV1) cases, one each from Hilmand, Kandahar, and Khost provinces, raising its total for the year to 40. The country also reported 13 more circulating vaccine-derived poliovirus type 2 (cVDPV2) cases across six different provinces, raising that number for 2020 to 54.

In Africa, Chad reported three more cVDPV2 cases, all from Logone Oriental province, putting its total for the year at 60 from two different outbreaks, one of them linked to the Jigawa outbreak in Nigeria. Also, the DRC reported one cVDPV2 case in Equateur province, the same area battling an Ebola outbreak, bringing its number for 2020 to 26.
Sep 3 GPEI update

 

More high-path H5 avian flu detected in Russian poultry, waterfowl

Russia reported eight more highly pathogenic H5 avian flu outbreaks in poultry, plus a detection in a wild swan, part of recent activity in the country's southwest, according to notifications from the World Organization for Animal Health (OIE).

Start dates for the latest poultry outbreaks range from Aug 25 to Sep 1. Four occurred in earlier-affected Omsk oblast, and four were reported in neighboring Tyumen oblast. All involved backyard poultry, and taken together, the virus killed 243 of 966 susceptible birds. Culling operations are in progress. So far, veterinary officials haven't reported the full subtype.

In early August, Russia reported two poultry outbreaks involving H5N8 in Chelyabinsk oblast.
In another development, the Russia detected highly pathogenic H5 in four mute swans, apparently found dead on August 28 in Tyumen oblast.
Sep 3 OIE report on H5 in Russian poultry
Sep 3 OIE report on H5 in Russian waterfowl

ASP Scan (Weekly) for Sep 04, 2020

News brief

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

Urinary culture intervention linked to lower antibiotic prescribing

An intervention to reduce antibiotic treatment for asymptomatic bacteriuria (ASB) at a Toronto hospital was safe and associated with reduced exposure to unnecessary antibiotics, Canadian researchers reported this week in Infection Control and Hospital Epidemiology.

In a prospective observational study conducted at Mount Sinai Hospital in Toronto, which implemented an intervention in 2013 to stop processing midstream urine cultures (MSUs) from patients unless the laboratory was called, researchers interviewed 1,678 patients with an MSU order on days 0 and 4 to ask about urinary symptoms and any adverse events. From 2017 to 2019, day 30 follow-up was added.

The primary outcome was serious adverse events due to not processing MSUs. Secondary outcomes included nonserious adverse events, rates of cultures submitted and processed, proportion of patients prescribed urinary tract infection (UTI)-directed antibiotics, and laboratory workload.

Among 912 and 459 patients followed to days 4 and 30, respectively, no serious adverse events attributable to not processing MSU cultures were identified. However, 6 patients (0.7%) had prolonged urinary symptoms potentially associated with not processing MSU cultures.

The researchers estimated that 4 patients missed having empiric antibiotics stopped in response to negative MSU cultures, and 99 antibiotic courses for asymptomatic bacteriuria (ASB) and 8 antibiotic-associated adverse events were avoided. The rate of submitted MSU samples and proportion of patients receiving empiric UTI-directed antibiotics did not change. The proportion of MSU cultures processed declined from 59% to 49% (P < .0001), and total laboratory workload was reduced by 185 hours.

"In conclusion, not processing MSU cultures from medical and surgical inpatients is safe, and it reduces inappropriate ASB therapy and laboratory workload," the authors of the study wrote. "We believe that the benefits of reduced antibiotic use outweigh the harm of persistent symptoms in a very few patients."
Sep 2 Infect Control Hosp Epidemiol abstract

 

Antibiotic prescribing frequent in ill Kenyan children, study finds

US and Kenyan researchers reported yesterday in Clinical Infectious Diseases that antibiotic treatment was high in a cohort of Kenyan children with undifferentiated fever, despite a low prevalence of bacterial illness.

The researchers examined clinical presentation and management of Kenyan children with fever at five hospitals or clinics from 2014 through 2017. The aim of the study was to characterize which variables are associated with higher odds of antibiotic therapy in both malaria-negative and malaria-positive children and to evaluate the concordance of diagnosis of bacterial illness with antibiotic treatment. All five sites were in malaria-endemic regions of Kenya, and all children in the study were tested for malaria by blood smear microscopy.

Of the 5,737 children enrolled in the study, 68% (3,902) were prescribed antibiotic therapy, while 14% (812) received a primary diagnosis of bacterial illness. In 777 children (14%), bacterial illness was given as the differential diagnosis. Nearly two thirds of those given antibiotics (64%) had neither a primary nor differential diagnosis of bacterial illness.

On multivariate analysis, a negative malaria test was associated with a sevenfold increase in the odds of receiving an antibiotic (odds ratio, 7.1; 95% confidence interval [CI], 5.6 to 9.1). Other factors associated with increased odds of antibiotic therapy included age 1 to 4 years; reporting of head, ears, eyes, nose, and throat symptoms; and having a flush toilet in the home.

"Based on these results and given the degree of diagnostic uncertainty, providers seem highly reluctant to discharge febrile children without empiric antibiotic treatment," the authors of the study wrote.

They suggested that providers in these settings, lacking point-of-care tests beyond those for malaria, may benefit from improved clinical education and implementation of enhanced guidelines for clinical decision-making.
Sep 3 Clin Infect Dis abstract

 

Stewardship intervention tied to significantly less carbapenem use

Originally published by CIDRAP News Sep 1

A policy involving mandatory infectious disease (ID) consultation and post-prescription review with feedback (PPRF) was tied to in sustained reduction in the use of carbapenem antibiotics at two hospitals in Washington state, researchers reported yesterday in Clinical Infectious Diseases.

In a retrospective study conducted at the University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC), researchers evaluated the impact of the policy on antibiotic consumption and clinical outcomes over a 6-year period, comparing the pre-intervention period with the post-intervention period. The policy, which was prompted by a critical shortage of meropenem in November 2015, required mandatory ID consultation and PPRF for all meropenem and imipenem use beyond 72 hours.

The primary outcome of the study was meropenem and imipenem days of therapy (DOT) per 1,000 patient-days. Secondary outcomes included meropenem and imipenem initiation and 30-day mortality and hospital length of stay (LOS).

There were 4,066 and 2,552 patients in the pre- and post-intervention periods, respectively. During the pre-intervention period, meropenem and imipenem DOT/1,000 patient-days remained stable, then dropped sharply after introduction of the intervention, falling by 72.1% (95% CI, 66.9% to 76.6%; P < 0.001) at UWMC and by 43.6% (95% CI, 20.7% to 59.9%; P = 0.001) at HMC, with a sustained effect over 4 years. In addition, although the intervention did not address use until 72 hours after initiation, there was a significant decline in meropenem and imipenem initiation in the post-intervention period, with a 64.9% reduction (95% CI, 58.7% to 70.2%; P < 0.001) at UWMC and a 44.7% reduction (95% CI, 28.1% to 57.4%; P < 0.001) at HMC.

No significant differences were found between the pre- and post-intervention periods in 30-day mortality or hospital LOS.

"Our study shows that PPRF combined with a potential mandatory ID consultation can serve as an impactful yet relatively low-resource intervention that can significantly reduce carbapenem consumption without compromising clinical outcomes," the authors of the study wrote.
Aug 31 Clin Infect Dis abstract

 

Paper highlights promise of bacteriophage therapy

Originally published by CIDRAP News Aug 31

A new paper in Open Forum Infectious Diseases lays out some of the lessons learned from cases of antibiotic-resistant infections treated with bacteriophage therapy.

For the paper, researchers with the Center for Innovative Phage Applications and Therapeutics (IPATH) at the University of California, San Diego, reviewed nearly 2 years of consult requests for bacteriophage therapy and examined outcomes from the first 10 cases at the center treated with intravenous (IV) bacteriophage therapy. IPATH was launched in 2018 to expand clinical use of the bacteria-killing viruses against multidrug-resistant infections.

Of the 785 requests from patients and physicians, 82% were for treatment of bacterial infections, primarily those caused by Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus. Bacteriophage therapy was administered to 17 of 119 patients in whom it was recommended, and the median time from request to administration was 170 days.

Review of the first 10 cases, seven of which had successful outcomes, showed that administration of IV and nebulized bacteriophage therapy appears safe, may be safely administered by outpatients, and can be used to suppress infections. The review also found that bacterial resistance to bacteriophage therapy can develop but can be overcome with new phages, that combining phages and antibiotics can lead to successful outcomes despite the presence of in vitro antibiotic resistance, and that treatment failure can occur despite in vitro phage susceptibility.

"In conclusion, our experience with BT [bacteriophage therapy] for a variety of indications highlights the promise of BT for multiple clinical indications," the authors of the paper wrote. "Significant work is needed to identify predictors of success and for design of clinical trials that will lead to more widespread use."
Aug 27 Open Forum Infect Dis abstract

 

European drug makers call for new reimbursement models for antibiotics

Originally published by CIDRAP News Aug 31

The BEAM (Biotech companies in Europe combating Antimicrobial Resistance) Alliance late last week urged the European Union (EU) and individual member states to adopt new reimbursement models for antibiotics.

In a paper on its website, the alliance, which includes 70 small- and medium-sized European companies involved in antibiotic development, called on the European Commission to create a new pull incentive framework that would help make new antibiotics more commercially viable and to provide guidance to member states on the size of the incentives that would be required.

The group also encouraged member states to champion and adopt a new EU legislative framework that would encourage the development of new antibiotics and to create new reimbursement models similar to those adopted in the United Kingdom and Sweden. 

"Because new antibiotics are (appropriately) held in reserve, developers of new medicines have struggled financially or have gone bankrupt," the alliance said. "The BEAM Alliance and the co-signatories of this paper urge the EU and its member states to urgently act and fix the broken economics around investment into the development and commercialization of antimicrobials."

In another paper posted on its website last week, the alliance applauded the launch of the AMR Action Fund, a nearly $1 billion effort by pharmaceutical companies to support late-stage antibiotic development announced earlier this summer. But the group noted that the fund "must be matched by a commercial ecosystem that is supportive of innovation in the field, so that the antibacterial drugs developed as a result of this funding can be truly viable from a market as well as scientific and clinical perspective."
Aug 28 BEAM Alliance paper on new reimbursement models
Aug 27 BEAM Alliance reflection paper on the AMR Action Fund

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