Stewardship / Resistance Scan for Oct 21, 2019

News brief

Electronic advisory plus education tied to lower antibiotic prescribing

A study today in Infection Control & Hospital Epidemiology has determined that an electronic best practice advisory combined with prescriber education was associated with reduced antibiotic prescribing for adults with acute bronchitis.

Wisconsin researchers conducted the quasi-experimental study involving ambulatory adults who had a primary diagnosis of acute bronchitis from 2016 through 2018. The patients sought care at Aurora Health Care facilities in eastern Wisconsin and northeastern Illinois. Aurora implemented an antimicrobial stewardship program involving a passive, prescriber-directed, electronic best-practice advisory coupled with prescriber education in 15 emergency clinics and more than 30 urgent care clinics in December 2016 and at more than 150 ambulatory clinics in September 2017.

The study included 81,975 patients in the pre-intervention period and 89,571 in the post-intervention period. The researchers discovered that antibiotic prescribing rates decreased from 60.8% (49,877 of 81,975 patients) pre-intervention to 51.4% (46,018 of 89,571) post-intervention, or a 9.4-percentage-point drop. The greatest decrease was seen in emergency departments (47.6% to 29.1%; 18.5 percentage points), followed by ambulatory care (58.6% to 45.1%; 13.5) and urgent care clinics (66.9% to 58.0%; 8.9).

The authors write, "This analysis combined with previous studies highlights the necessity of multimodal antimicrobial stewardship interventions in the ambulatory setting." They add, however, "Despite a promising reduction in antibiotic prescribing in this study, prescribing rates remain far above the expected appropriate rates."
Oct 21 Infect Control Hosp Epidemiol abstract


European study shows alarming rise in H pylori resistance

Resistance rates for antibiotics commonly used to treat Helicobacter pylori infection are rising at an alarming rate, according to a study presented today at a gastroenterology meeting in Barcelona.

The study analyzed 1,232 patients with H pylori infections across 18 countries in Europe and found that resistance to clarithromycin rose from 9.9% in 1998 to 21.6% in 2018, while resistance to levofloxacin rose from 14.1% to 16.3% and resistance to metronidazole increased from 33.1% to 39.1%. The countries with the highest rates of primary clarithromycin resistance were Italy (36.9%), Croatia (34.6%), and Greece (30%).

"H. pylori infection is already a complex condition to treat, requiring a combination of medications," lead researcher Francis Megraud, MD, a professor of bacteriology at the University of Bordeaux, said in a press release from United European Gastroenterology (UEG) Week 2019. "With resistance rates to commonly used antibiotics such as clarithromycin increasing at an alarming rate of nearly 1% per year, treatment options for H. pylori will become progressively limited and ineffective if novel treatment strategies remain undeveloped."

H pylori infection causes inflammation of the stomach lining and can lead to peptic ulcers. The bacteria is also associated with lymphoma and gastric cancer.  Megraud said that if resistance to current H pylori therapies continues at the current pace, incidence rates of gastric cancer and peptic ulcers could remain high.

The World Health Organization has identified clarithromycin-resistant H pylori as a high priority pathogen for antibiotic research and development.
Oct 21 UEG Week 2019 press release


Study suggest market exclusivity vouchers could be costly

Using transferrable market exclusivity vouchers to incentivize new antibiotic development could end up costing taxpayers billions, according to a paper yesterday in Clinical Infectious Diseases.

Under the Re-Valuing Antimicrobial Products (REVAMP) Act, a bill introduced in Congress in June 2018, manufacturers that gain Food and Drug Administration (FDA) approval for critically needed, novel antibiotics would receive a 12-month transferrable market exclusivity extension voucher that could be applied to an existing brand-name drug or sold to another manufacturer. The idea was that allowing pharmaceutical companies to extend market exclusivity on high-revenue drugs and forestall competition from generics could provide a financial incentive to develop new antibiotics. Although the legislation did not advance to a full vote, the idea is among the financial "pull" incentives that have been proposed to promote antibiotic development.

To understand the potential economic implications of the REVAMP Act, researchers from Harvard Medical School and Brigham and Women's Hospital identified 10 antibiotics approved by the FDA from 2007 through 2016 that would have qualified for the voucher and matched each antibiotic, according to the rules proposed under the legislation, to the 10 fast-track drugs with the highest revenue facing generic entry within the 4 years following the antibiotic's approval (the bill stipulated that drugs receiving the voucher had to have been given fast-track status by the FDA). They then calculated the per-drug and total societal costs of the vouchers over a decade.

The 10 drugs had a median annual revenue prior to generic entry of $249 million. Accounting for a 75% spending reduction after generic entry, the analysis calculated that the median spending associated with an exclusivity voucher was $187 million, and that total spending associated with a 12-month exclusivity extension for all 10 drugs was $4.5 billion. 

The researchers argue that while exclusivity extensions are a popular policy option for lawmakers because they don't require a spending-line item when passed by Congress, their analysis shows that the incentive can be costly from a societal perspective.

"As focus continues to grow on ways to encourage generation of new antibiotics as a complement to other strategies to reduce antimicrobial resistance—such as improved antibiotic stewardship—our results raise important concerns about the overall cost of transferable exclusivity vouchers," they write.
Oct 20 Clin Infect Dis abstract


Study highlights sensitivity of rapid carbapenemase detection test

Swiss researchers report in Clinical Microbiology and Infection that a new rapid carbapenamase detection test is reliable for the screening and detection of carbapenemase-producing organisms (CPOs) and produces quicker results, but that the relatively low specificity of the test may require the use of additional confirmatory methods.

To evaluate the performance of Becton-Dickinson's Phoenix CPO Detect Test, which detects class A, B, and D carbapenemases in gram-negative bacteria and received FDA clearance earlier this year, researchers from the Institute of Microbiology at Lausanne University Hospital performed retrospective and prospective analysis on a collection of 185 molecularly-characterized bacterial isolates and 295 conventional isolates, respectively. The 185 molecularly characterized isolates included 92 CPO and 93 non-CPO strains, and the 295 isolates included 135 with suspected carbapenemase production and 156 without.    

In the retrospective study, the CPO test exhibited 92.4% accuracy (95% confidence interval [CI], 87.6 to 95.8), 97.8% sensitivity (95% CI, 92.4 to 99.7), and 87.1% specificity (95%, 78.6 to 83.2) for carbapenemase detection, and provided a classification to class A, B, and D for 81.3% of detected carbapenemases with 94.6% accuracy (95% CI, 86.7 to 98.5).

In the prospective study, the CPO test show 77.8% accuracy (95% CI, 68.8 to 84.5), 100% sensitivity (95% CI, 91.2 to 100), and 67.7% specificity (95% CI, 57.3 to 77.1) on 135 CPO-suspicious isolates and 98.8% accuracy and specificity (95% CI, 95.6 to 99.9) on 160 non-CPO suspicious isolates.

The analysis also found that, compared to routine testing methods, the implementation of the CPO test allowed a mean reduction of 21.3 hours in turnaround time (TAT), 16.8 minutes in hands-on time, and an overall cost reduction of 45%. The researchers suggest the significantly decreased TAT observed with the Phoenix CPO Detect test may have a positive impact on therapeutic and infection control decisions, including antibiotic de-escalation and escalation, as well as costly patient isolation measures.

"Overall, the implementation of the Phoenix CPO Detect test may have a positive impact on laboratory workflows but also on therapeutic and infection control decisions," the authors of the study write.

The authors report grants from Becton-Dickinson during the conduct of the study.
Oct 18 Clin Microbiol Infect study


Study: Antibiotic prescribing rises before some chronic disease diagnoses

A study to examine antibiotic use patterns before and after patients are diagnosed with underlying health conditions found that levels increased before some chronic conditions, like asthma and heart failure, but not others. A team from University College London published its findings today in Clinical Infectious Diseases.

For the study, the investigators looked at a UK primary care database, focusing on adults without earlier comorbidities who were registered from 2008 through 2015. They estimated rates of antibiotic prescribing in the 12 months before and after diagnosis of several health conditions and for controls who didn't have underlying health issues. Conditions included new-onset stroke, coronary heart disease, heart failure, peripheral arterial disease, asthma, chronic kidney diseases, diabetes, or chronic obstructive pulmonary disease (COPD).

Of 1,071,94 patients included in the study, 106,540 (9.9%) were diagnosed with one of the health conditions. For asthma, heart failure, and COPD, antibiotic prescribing rates increased 1.9- to 2.3-fold in the 4 to 9 months that preceded diagnosis. Prescribing then declined to stable levels within 2 months of diagnosis.

However, for diabetes, the trend was less marked. And for those with vascular conditions, prescribing rates increased immediately before diagnosis, remaining 30% to 39% higher than baseline. Among the control group, prescribing rates increased by 17% to 28% in the months before and after doctors' visits.

The authors said antibiotic prescribing appears to increase rapidly before patients are diagnosed as having conditions that have respiratory symptoms, such as COPD, heart failure, and asthma, then drop off afterward. Patterns suggest that respiratory symptoms might be diagnosed as infection and that earlier diagnosis of certain underlying health issues could be a way to reduce unnecessary antibiotic prescribing.
Oct 21 Clin Infect Dis abstract

News Scan for Oct 21, 2019

News brief

Study offers clear evidence of enterovirus in acute flaccid myelitis cases

A new study in Nature Medicine offers the first clear evidence of enterovirus (EV) in the cerebrospinal fluids of patients with acute flaccid myelitis (AFM) – a mysterious, polio-like illness that can cause paralysis in otherwise healthy children.

Since 2012, the United States has tracked more than 500 AFM cases, which have increased biennially. AFM cases in 2014, 2016, and 2018 occurred during and near outbreaks of enteroviruses (EV-D68 and EV-A71 infections), and researchers and clinicians have described associations between enterovirus infections and the subsequent development of AFM.

But less than half of AFM case-patients have evidence of EV infections in nonsterile biologic specimens, including nasal swabs and stool specimens. This study evaluated EV in the CSF samples of 42 American children with the illness, mostly in 2018. Researchers found evidence of EV in 29 of 42 AFM cases, and only 4 out of 58 controls.

"Pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM," the authors said.

The authors conclude by suggesting that, like polio, a vaccine may be the best way to control AFM. Thus, continued efforts to understand the etiology of the illnesses must be made.
Oct 21 Nat Med study


MERS infects 1 more in Saudi Arabia

Saudi Arabia's Ministry of Health (MOH) recently announced another human MERS-CoV case, the second this month from Khamis Mushait in the southwestern part of the country.

The patient is a 73-year-old man whose exposure to MERS-CoV (Middle East respiratory syndrome coronavirus) is listed as primary, meaning he likely didn't contract the virus from another patient. His exposure to camels is unknown.

The country has now reported eight cases so far in October, up from four reported for the whole month of September.

In its latest monthly summary regarding the virus, the World Health Organization (WHO) said that, through September, 2,468 cases have been reported globally, along with 851 related deaths. The vast majority have been reported from Saudi Arabia.
Oct 19 MOH update

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