Stewardship / Resistance Scan for Dec 03, 2018

News brief

Procalcitonin-guided therapy reduces antibiotic duration, study finds

The use of an algorithm that recommends stopping antibiotics for lower respiratory tract infections (LRTIs) based on procalcitonin (PCT) levels was associated with reduced antibiotic duration without increasing adverse outcomes, researchers at an academic tertiary care hospital report today in Open Forum Infectious Diseases.

The single-center clinical trial, conducted at Johns Hopkins Bayview Medical Center, evaluated PCT-guided antibiotic therapy for LRTI by comparing antibiotic duration in a control group of 200 patients admitted prior to the intervention with antibiotic duration in a post-intervention group of 174 patients. The intervention involved daily measurements of PCT values with a rapid sensitive assay and review by an infectious disease (ID) pharmacist and an ID physician; antibiotic discontinuation was recommended if serial PCT values fell 80%.

The primary and secondary end points were total antibiotic duration per LRTI episode and antibiotic days of therapy (DOT) per 1,000 patient-days present. Overall adverse outcomes at 30 days included death, transfer to an intensive care unit, Clostridioides difficile infection, and post-discharge antibiotic prescription for LRTI.

Providers complied with the PCT algorithm in 70% of encounters. Overall, the median antibiotic duration in the PCT group was lower than in the control group (5 days vs 6 days, P = 0.052), and total days of antibiotic therapy were significantly lower (1,883 vs 2,039 DOT/1,000 patient-days present).

When stratified by admitting diagnosis, median antibiotic durations were significantly shorter in the PCT group for pneumonia (6 vs 7 days, P = 0.045) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD, 4 days vs 3 days, P < 0.001). Total antibiotic use was significantly shorter in the PCT group for AECOPD (788 vs. 1,513 DOT), but not for pneumonia (2,259 vs 2,360 DOT). There were no significant differences between the two groups in rates of adverse outcomes at 30 days.

The authors of the study conclude, "Overall, our study demonstrates that PCT-guided cessation of antibiotic therapy, when undertaken as a stewardship intervention, is a safe and effective strategy to reduce antibiotic use in patients with LRTI."
Dec 3 Open Forum Infect Dis abstract

'Expected Practice' may decrease antibiotic use for common infections

In another study today in Open Forum Infectious Diseases, researchers at the Los Angeles County + University of Southern California Medical Center report that an intervention requiring clinicians to adhere to "Expected Practice" around short-course antibiotic therapy was tied to decreased antibiotic use for common infections.

As the authors of the study explain, Expected Practice is a mechanism that educates providers about evidence-based medicine practice while also establishing an institutional requirement for standard practice. "Expected Practices set an institution's expectation for how its providers practice medicine, and hence set stronger standards of care compared to clinical guidelines, which are typically viewed more as literature-based suggestions or expert consensus," they write.

The Expected Practice around short-course antibiotic therapy was developed by a workgroup of primary and specialty care experts at the hospital and based on multiple randomized clinical trials that have demonstrated that shorter courses of antibiotics are as effective as longer courses for many common bacterial infections. Under the intervention, providers were expected to adhere to shorter antibiotic courses for common infections unless deviations could be clinically justified. The authors say one of the benefits of Expected Practice is that it alleviates provider concerns that they could be individually exposed to blame if they prescribed short-course antibiotic therapy and the clinical outcome was bad.

In a quasi-experimental pre-/post- quality improvement study, the researchers compared average antibiotic DOT and total antibiotic exposure in the 12 months prior to implementation of the intervention and the 12 months post-intervention, focusing on patients diagnosed as having urinary tract infections (UTIs), skin and other soft-tissue infections (SSTIs), pneumonia, and ventilator-associated pneumonia (VAP). When adjusted for all covariates of interest, average antibiotic DOTs decreased 10%, 11%, 11%, and 27% for UTIs, SSTIs, pneumonia, and VAP, respectively, after the introduction of Expected Practice.

Decreases for antibiotic exposure were even larger, falling by 17%, 13%, 29%, and 35% for UTIs, SSTIs, pneumonia, and VAP, respectively. An assessment of in-house mortality found no changes post-intervention.

The authors conclude that Expected Practice is a promising new psychological tool to promote effective antibiotic stewardship.
Dec 3 Open Forum Infect Dis abstract

Study: UTI management bundle cuts inappropriate antibiotics, treatment

Implementation of a UTI management bundle at a Canadian hospital was associated with a 75% reduction in antibiotic treatment for asymptomatic bacteriuria (AB) and improved management of UTIs, researchers reported today in Infection Control and Hospital Epidemiology.

The UTI management bundle instituted at Moncton Hospital in New Brunswick consisted of four components: nursing education, prescriber education, laboratory intervention, and pharmacy prospective audit and feedback. The intervention concentrated on appropriate indications for urine culture, UTI diagnosis, and appropriate treatment according to institutional guidelines. To determine the potential effectiveness of the bundle, researchers at the hospital conducted a retrospective chart review of consecutive inpatients with positive urinary cultures before and after implementation. Primary outcome measures included overall adherence to institutional UTI management, appropriate antibiotic use and duration of therapy, and rates of inappropriate therapy for AB.

Chart review found that, within the pre-intervention study population of 276 patients, 165 (59.8%) were found to have AB, of whom 111 (67.3%) were treated with antimicrobials. Of the 268 patients reviewed post-intervention, 133 (49.6%) were found to have AB, and 22 of the 133 (16.5%) were treated with antimicrobials. Thus, a 75.5% reduction of inappropriate AB treatment was achieved. The absolute risk reduction in AB treated after implementation of the UTI bundle was 50.8% (95% confidence interval, 40.3% to 59.3%), with a number needed to treat of two. Total days of avoidable antibiotic therapy decreased from 781 to 138 from the pre- to post-intervention periods.

In addition, educational components of the bundle were linked to a substantial decrease in nonphysician-directed urine sample submission, and adherence to a UTI management algorithm improved substantially in the intervention period, with a notable decrease in fluoroquinolone prescription for empiric UTI treatment.

"Our study has shown that the laboratory-based intervention, in both noncatheterized and catheterized patients as part of a UTI management bundle, is effective in reducing the inappropriate treatment of AB and improving overall adherence to best practice," the authors of the study conclude.
Dec 3 Infect Control Hosp Epidemiol study

News Scan for Dec 03, 2018

News brief

Immune globulin shows promise for severe Zika thrombocytopenia

An analysis of Puerto Rican Zika patients who had thrombocytopenia, a rare complication, found that, in those with the severest cases, immune treatments may be more effective than platelet transfusion. A team from the US Centers for Disease Control and Prevention (CDC) and Puerto Rico reported its findings today in Open Forum Infectious Diseases.

The researchers scoured the medical records of 37,878 patients infected with Zika virus in 2016 and found that 47 (0.1%) had thrombocytopenia, including 12 people who had a severe form of the complication, which is marked by low blood platelets. Most patients were adults, and 53% were male. For patients with severe disease, platelet levels were at their lowest at a median 6 days after symptom onset, and for those with the milder form, platelet levels were lowest a median of 5 days post onset.

Of those with severe thrombocytopenia, all had bleeding, 4 (33%) were admitted to the intensive care unit, and 1 (8%) died. Of the 12 patients, 11 received intravenous immune globulin (IVIG) or corticosteroids, and 9 responded to clinical treatment.

Of five patients with severe thrombocytopenia who received intravenous immunoglobulin, median platelet increase was 112 X 10⁹/L (range, 65 to 202 X 10⁹/L), which was higher than four patients who received receive platelet transfusion, for whom the median platelet count increase was 8.5 X 10⁹ (range, -6 to 52 X 10⁹/L), which the researchers said resulted in minimal response.

The investigators said the cases from the Puerto Rico series nearly doubles the number of documented cases of severe thrombocytopenia in Zika patients that could be due to immune thrombocytopenia (ITP). They also noted the investigation is the first to determine the population incidence of Zika virus (ZIKV)-linked thrombocytopenia, which was 1.4 cases per 100,000 population.

"Regardless of the mechanism, the findings from this investigation demonstrate that timely diagnosis of ITP among patients with ZIKV associated severe thrombocytopenia is crucial to initiating life-saving interventions," they wrote.
Dec 3 Open Forum Infect Dis abstract

WHO reports successful end to polio outbreak in Syria

The World Health Organization (WHO) announced that a polio outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) detected in Syria 18 months ago has been successfully stopped.

The outbreak began in June of 2017 in the Deir ez-Zor governorate in eastern Syria. A total of 74 polio cases were linked to the outbreak, and the most recent patient suffered onset of paralysis on Sep 21, 2017. No international spread was noted, the WHO said.

"Surveillance is stronger today than it was 18 months ago, when the initial cases were detected," said Chris Maher, the manager for polio eradication for the WHO's Eastern Mediterranean Region. "Access for both surveillance and immunization is dramatically better, and immunity levels have been increased as a result of the comprehensive outbreak response conducted across Syria."

In 2013, the same region of Syria was affected by an outbreak of wild poliovirus type 1 (WPV1).

The WHO warned that Syria is at risk for re-infection because of a deteriorated health infrastructure, ongoing fighting, and internal population movements.
Dec 2 WHO news release

UK announces vaccine innovation center; Canada boosts CEPI coffers

In hopes of speeding the development of vaccines against emerging infectious disease threats, UK officials announced a dedicated Vaccines Manufacturing Innovation Center (VMIC), which will be led by the University of Oxford's Jenner Institute, and at the G20 meeting over the weekend in Buenos Aires, Canadian Minister Justin Trudeau announced $1 million ($765,750 in US dollars) more for the Coalition for Epidemic Preparedness Innovations (CEPI).

A news release today from the University of Oxford said the VMIC signals a major commercial opportunity and way to protect the nation against pandemic threats. It is designed to address a gap in late-stage vaccine manufacturing and will allow the development and production of vaccines for clinical trials and at moderate scale for epidemic threats to the UK population.

The center is slated to begin operations by 2022 and will be located on a new site at The Oxford Science Park. It is funded through £66 million ($84 million) from the UK Government's Industrial Strategy Challenge Funds Medicines Manufacturing Challenge. Additional funding of £10 million ($12.7 million) will come from commercial and other partners. Three academic centers will run the VMIC: the University of Oxford, Imperial College, and the London School of Hygiene and Tropical Medicine.

Meanwhile, CEPI's CEO Richard Hatchett, MD, said in a statement yesterday that the group is grateful that Canada has increased its contribution and that the current Ebola outbreak in the Democratic Republic of the Congo is a timely reminder of the devastation diseases can cause. "It's only through collective action that we can hope to protect the world from the threat of epidemics and we warmly welcome Canada's contribution to that effort," he said.

Canada was one of the groups that provided an initial investment after CEPI was formed in 2017 with a goal of streamlining and funding vaccine candidates targeting three diseases: Middle East respiratory syndrome coronavirus (MERS-CoV), Lassa virus, and Nipah virus. So far, CEPI has received $630 milllion from Australia, Belgium, Canada, the European Commission, Germany, Japan, Norway, the Bill & Melinda Gates Foundation, and Wellcome Trust.
Dec 3 Oxford press release
Dec 2 CEPI statement

Report: TB research funding climbed to new heights in 2017 but still lags

Research and development funding for tuberculosis (TB) rose to $772 million in 2017, the highest ever and the second year in a row that funding topped $700 million but still well short of what is needed, according to a new report released today by Treatment Action Group (TAG) and the United Nations–hosted Stop TB Partnership.

During the first-ever United Nations High-Level Meeting on TB, held during the UN General Assembly in September 2018, TAG reported a $1.3 billion gap annually, which represents the difference between what the Stop TB Partnership says the world needs to invest in TB R&D from 2016 to 2020 (a total of $9 billion, or about $2 billion per year) and current funding.

"In order to hit $9 billion in funding for the 2016-2020 period, the world will now have to invest almost as much ($7.5 billion) in the three years from 2018 to 2020, since investments in 2016 and 2017 only amounted to $1.5 billion combined," TAG said in a press release.

That money will likely come in the form of government commitments, as more than 60% of current TB funding comes from the public sector.
Dec 3 TAG press release