Stewardship / Resistance Scan for Apr 26, 2019

News brief

Study shows decline in outpatient antibiotic use in Denmark

Outpatient antibiotic use in central Denmark fell by nearly 20% from 2011 through 2015, Danish researchers report in a new study in BMC Infectious Diseases.

Using data from the Danish National Health Service Prescription Database, the researchers examined recent time trends in the utilization of narrow- and broad-spectrum antibiotics in central Denmark and the variation in antibiotic use by sex, age, and municipality of residence from 2006 through 2015. They found that, after a slight increase from 2006 through 2011, the overall rate of redeemed prescriptions for antibiotics fell from 290 per 1,000 person-years in 2011 to 236/1,000 person-years in 2015—a decline of 17%. The decreasing trend in antibiotic use over time was observed in all municipalities, mainly due a decrease in narrow-spectrum antibiotics. Among people aged 65 and over, the decline in use began in 2013 and was less pronounced.

The analysis also found that antibiotic use in 2015 remained higher among women (289/1,000 person-years) than men (182/1,000 person-years) and among the very old (520/1,000 person-years in people over 85) versus those in middle-age (204/1,000 person-years in people ages 45 to 65). In addition, there was a 1.6-fold geographical variation in antibiotic use in 2015 that was not explained by age and sex differences, and a continuous increasing trend in broad-spectrum antibiotic use was observed in women over 65 and men over 85, primarily related to increasing use of combinations of penicillins with beta-lactamase inhibitors.  Notably, 2015 marked the first time that prescribing of broad-spectrum antibiotics surpassed prescribing of narrow-spectrum antibiotics.

The authors of the study say the data show there is room for improvement in antibiotic prescribing, and that a greater focus on avoiding unnecessary broad-spectrum antibiotic use is needed.
Apr 24 BMC Infect Dis study

 

Spanish hospital study highlights inappropriate empiric antibiotic therapy

An observational study conducted in two Spanish hospitals has found that inappropriate empiric antibiotic therapy (IEAT) is frequent in patients with febrile neutropenia (FN) and bloodstream infections, especially those caused by multidrug-resistant gram-negative pathogens, Spanish researchers reported yesterday in Clinical Infectious Diseases.

The researchers wanted to investigate IEAT in patients with FN—a common complication of chemotherapy—because the epidemiology of bloodstream infections in these patients has been changing in recent decades, with an increase in gram-negative bacilli (GNB) and multidrug-resistant strains. At the same time, Infectious Diseases Society of America (IDSA) guidelines for empiric antibiotic therapy in FN have not been updated to reflect this change, making appropriate empiric therapy more of a challenge.

In the observational study, 1,615 episodes of bloodstream infection in 1,309 patients with high-risk FN were documented. Gram-negative microorganisms accounted for 56% of bloodstream infections and gram-positives 43%, with Escherichia coli (24%), coagulase-negative Staphylococci (21%), and Pseudomonas aeruginosa (18%) the most frequently isolated organisms. Multidrug-resistant gram-negative bacilli (MDR-GNB) accounted for 24% of all cases. Even though IDSA recommendations were followed 87% of the time, 24% of patients received IEAT, and patients with infections caused by MDR-GNB were more likely to receive IEAT than patients without MDR strains (39% vs. 7%).

Analysis of outcomes showed that patients who received IEAT had significantly higher mortality than those who received appropriate therapy (36% vs. 24%). When considering individual organisms, only patients with infection caused by P aeruginosa had significantly higher mortality when receiving IEAT (48% vs. 31%). Multivariate analysis identified IEAT (odds ratio [OR], 2.41; 95% confidence interval, 1.19 to 4.91), septic shock at onset (OR, 4.62; 95% CI, 2.49 to 8.56), and pneumonia (OR, 3.01; 95% CI, 1.55 to 5.83) as independent risk factors for mortality in patients with P aeruginosa bloodstream infections.

"These results should encourage a reassessment of the current FN guidelines and the use of new approaches to predict MDR infections," the authors of the study conclude.
Apr 25 Clin Infect Dis abstract

News Scan for Apr 26, 2019

News brief

UCLA and Cal State quarantine students, faculty exposed to measles

Yesterday the University of California, Los Angeles and California State University, Los Angeles campus announced a quarantine of 280 students and faculty exposed to students who have measles, according to news reports.

The news came the same day California officials said 38 people have been confirmed with measles in the state so far this year. Five of those cases are from LA County, including one student each from the two universities.

The latest possible exposure to the virus on UCLA's campus took place on Apr 9, officials said. A student with the disease attended classes on Apr 2, 4, and 9. The student at Cal State was reported to have visited the library while contagious.

"We are still awaiting medical records from 119 students and eight faculty members to determine whether they are immune to the measles," said UCLA Chancellor Gene Block in a statement. Bock said the quarantine will last up to 48 hours, until proof of immunity is established.

Measles has resurged in the United States, with almost 700 cases reported this year — the most in any year since the virus was eliminated in 2000. Most outbreaks in the US are currently tied to international travel.
Apr 25 UCLA statement
Apr 25 LA Times story

 

Five countries report new polio cases

Multiple countries reporting ongoing polio activity reported new cases this week, including wild poliovirus infections in Afghanistan and Pakistan and vaccine-derived polio cases and positive contacts in Nigeria, the Democratic Republic of Congo (DRC), and Somalia, according to the latest weekly update from the Global Polio Eradication Initiative (GPEI).

In Afghanistan, three wild poliovirus type 1 (WPV1) cases were reported, two from different districts in Hilmand province and one from Uruzgan province. The respective paralysis onset dates were Mar 6, Mar 23, and Mar 20. The new cases lift the country's total for the year to six WPV 1 cases.

Meanwhile, the GPEI noted early notification of two WPV1 cases, both from Khyber Pakhtunkhwa province, one a patient from Bannu district with an Apr 2 paralysis onset and the other from North Waziristan district with an Apr 4 paralysis onset. When the cases are confirmed, the number of cases from Pakistan this year will reach eight.

In Africa, Nigeria reported two vaccine-derived poliovirus type 2 (cVDPV2) cases, one a patient from Kwara state with a Mar 20 paralysis onset and the other a patient from Niger state with a Mar 18 paralysis onset. The developments lift Nigeria's total for 2019 to seven cases. DRC health officials reported one cVDPV2 case from Kasai state with a paralysis onset of Feb 8, its first of 2019. Also, the country reported two cVDPV2 community isolates, also from Kasai state. The GPEI said with the addition of the Kasai state cases the DRC is now affected by five separate cVDPV2 outbreaks.

Elsewhere in Africa, Somalia reported one cVDPV2 case and a related contact from Sool province. The patient had a Mar 15 paralysis onset, and the confirmation of the case marks the country's first cVDPV2 illness for 2019.
Apr 26 GPEI weekly update

 

New report covers vaccine platform potential for countermeasure development

Over the past several years, vaccine platform technologies have been developed that enable the rapid production of multiple products from a single system, which may help medical countermeasure development evolve away from a less efficient "one bug one drug" approach, according to a report released yesterday by Johns Hopkins Center for Health Security.

The report covers major scientific and policy issues related to vaccine platforms and how they are understood in government, academia, and industry, according to a Center for Health Security news release.

Amesh Adalja, MD, senior scholar at the center and leader of team that wrote the report, said, "platforms have the potential to accelerate the vaccine development timeline and the work in this report will hopefully catalyze the discussion of how the power of platform vaccine technologies can be harnessed as a pandemic tool." The report was funded by the Open Philanthropy Project.

The group said as pandemic preparedness matures, integrating new vaccine platform technologies into countermeasure development has the potential to impact resilience to both global catastrophic biologic risks and other epidemic threats. They tie in findings from existing evidence, informational interviews, and a workshop held with subject matter experts. And they make five main recommendations that center around platform and nonplatform vaccine technology proliferation; focusing platform-based assessments on accelerating manufacturing rather than speeding regulatory developments; supporting traditional vaccine development; prioritizing mRNA-based vaccines; and giving special consideration to platform technologies, given market conditions.
Apr 25 Center for Health Security news release
Apr 25 Center for Health Security vaccine platform report

 

High viral loads linked to fatal H5N1 cases

A new study in Clinical Infectious Diseases uses nasal and fecal samples to estimate viral loads in human patients with avian influenza H5N1, finding that higher viral loads are linked to fatal cases.

The study was based in Indonesia. Since 2005, Indonesia has recorded 200 human infections with clade 2.1 highly pathogenic avian influenza A/H5N1 virus, and the cases have a high case-fatality rate of 84%.

Researchers collected specimens from 180 H5N1 patients between 2007 and 2015, representing 90% of all Indonesian patients and 20% of reported H5N1-infected patients globally. They also tested for resistance to oseltamivir, an antiviral drug.

Feces and blood had the highest concentrations of H5N1 RNA, and higher viral loads correlated with fatal cases. Genes that conferred resistance to antivirals were also more prevalent in fatal cases.
Apr 26 Clin Infect Dis study

ASP Scan (Weekly) for Apr 26, 2019

News brief

Study shows decline in outpatient antibiotic use in Denmark

Outpatient antibiotic use in central Denmark fell by nearly 20% from 2011 through 2015, Danish researchers report in a new study in BMC Infectious Diseases.

Using data from the Danish National Health Service Prescription Database, the researchers examined recent time trends in the utilization of narrow- and broad-spectrum antibiotics in central Denmark and the variation in antibiotic use by sex, age, and municipality of residence from 2006 through 2015. They found that, after a slight increase from 2006 through 2011, the overall rate of redeemed prescriptions for antibiotics fell from 290 per 1,000 person-years in 2011 to 236/1,000 person-years in 2015—a decline of 17%. The decreasing trend in antibiotic use over time was observed in all municipalities, mainly due a decrease in narrow-spectrum antibiotics. Among people aged 65 and over, the decline in use began in 2013 and was less pronounced.

The analysis also found that antibiotic use in 2015 remained higher among women (289/1,000 person-years) than men (182/1,000 person-years) and among the very old (520/1,000 person-years in people over 85) versus those in middle-age (204/1,000 person-years in people ages 45 to 65). In addition, there was a 1.6-fold geographical variation in antibiotic use in 2015 that was not explained by age and sex differences, and a continuous increasing trend in broad-spectrum antibiotic use was observed in women over 65 and men over 85, primarily related to increasing use of combinations of penicillins with beta-lactamase inhibitors.  Notably, 2015 marked the first time that prescribing of broad-spectrum antibiotics surpassed prescribing of narrow-spectrum antibiotics.

The authors of the study say the data show there is room for improvement in antibiotic prescribing, and that a greater focus on avoiding unnecessary broad-spectrum antibiotic use is needed.
Apr 24 BMC Infect Dis study

 

Spanish hospital study highlights inappropriate empiric antibiotic therapy

An observational study conducted in two Spanish hospitals has found that inappropriate empiric antibiotic therapy (IEAT) is frequent in patients with febrile neutropenia (FN) and bloodstream infections, especially those caused by multidrug-resistant gram-negative pathogens, Spanish researchers reported yesterday in Clinical Infectious Diseases.

The researchers wanted to investigate IEAT in patients with FN—a common complication of chemotherapy—because the epidemiology of bloodstream infections in these patients has been changing in recent decades, with an increase in gram-negative bacilli (GNB) and multidrug-resistant strains. At the same time, Infectious Diseases Society of America (IDSA) guidelines for empiric antibiotic therapy in FN have not been updated to reflect this change, making appropriate empiric therapy more of a challenge.

In the observational study, 1,615 episodes of bloodstream infection in 1,309 patients with high-risk FN were documented. Gram-negative microorganisms accounted for 56% of bloodstream infections and gram-positives 43%, with Escherichia coli (24%), coagulase-negative Staphylococci (21%), and Pseudomonas aeruginosa (18%) the most frequently isolated organisms. Multidrug-resistant gram-negative bacilli (MDR-GNB) accounted for 24% of all cases. Even though IDSA recommendations were followed 87% of the time, 24% of patients received IEAT, and patients with infections caused by MDR-GNB were more likely to receive IEAT than patients without MDR strains (39% vs. 7%).

Analysis of outcomes showed that patients who received IEAT had significantly higher mortality than those who received appropriate therapy (36% vs. 24%). When considering individual organisms, only patients with infection caused by P aeruginosa had significantly higher mortality when receiving IEAT (48% vs. 31%). Multivariate analysis identified IEAT (odds ratio [OR], 2.41; 95% confidence interval, 1.19 to 4.91), septic shock at onset (OR, 4.62; 95% CI, 2.49 to 8.56), and pneumonia (OR, 3.01; 95% CI, 1.55 to 5.83) as independent risk factors for mortality in patients with P aeruginosabloodstream infections.

"These results should encourage a reassessment of the current FN guidelines and the use of new approaches to predict MDR infections," the authors of the study conclude.
Apr 25 Clin Infect Dis abstract

 

Study finds FMT significantly reduces hospital costs for recurrent C diff

Originally published by CIDRAP News Apr 24

Researchers in Denmark report that the use of fecal microbiota transplantation (FMT) reduced hospital costs in patients with recurrent Clostridioides difficile infection (rCDI) by 42%, according to a study in Therapeutic Advances in Gastroenterology.

The single-center study, conducted at a public hospital in Denmark, included all adult patients who were referred for FMT from January 2014 through December 2015 and costs related to donor screening, laboratory processing, and clinical FMT application. The researchers calculated both the costs of FMT and the patient-related hospital costs 1 year before FMT and 1 year after FMT. Cost drivers included hospital admission days, intensive care unit (ICU) admission days, antibiotics use, outpatient visits, telephone consultations, and costs related to the FMT procedure.

Analysis of 50 consecutive adult patients with rCDI who were referred for FMT showed that the weighted average cost of an outpatient FMT procedure (applied by colonoscopy or nasojejunal tube) was €3,095 ($3,463). Total annual costs per rCDI patient dropped from €56,415 pre-FMT to €32,816 post-FMT ($63,132 to $36,723), with cost reductions driven by reductions in both the number of hospital admissions and the length of stay for each admission. The median number of days of hospital admission, including ICU days, fell 45%, from 37 days to 20 days. Sensitivity analyses demonstrated cost reductions in all scenarios.

The researchers say the study is the first to provide direct costs of FMT and to calculate derived hospital cost savings from the procedure, which has shown success in resolving rCDI in 70% to 90% of patients in observational and randomized trials.

"The introduction of new treatments is usually very expensive, but here we have a form of treatment that on top of everything also saves society millions of Euro every month. If we can establish a system that safeguards both patients and donors, then it'll be of huge benefit for everyone," lead study author Christian Lodberg Hvas, PhD, a consultant in the department of hepatology and gastroenterology at Aarhus University Hospital, said in a university press release.
Apr 10 Therap Adv Gastroenterol study
Apr 23 Aarhus University press release

 

Delayed antibiotics therapy tied to worse outcomes for Enterobacteriaceae

Originally published by CIDRAP News Apr 24

A study yesterday in Open Forum Infectious Diseases indicates that, in patients with Enterobacteriaceae infections, delayed antibiotic therapy had a stronger impact on outcomes and costs than carbapenem resistance did, though the effects of the two characteristics are synergistic.

For the study, researchers with Allergan, medical research firm Evidera, and the Albany College of Pharmacy and Health Sciences identified all admissions with evidence of a serious Enterobacteriaceae infection from a large US hospital database from July 2011 through September 2014. They were looking to determine the independent and combined impact of carbapenem-resistant Enterobacteriaceae (CRE) and delayed appropriate antibiotic therapy—defined as receipt of an antibiotic with activity against all index pathogens more than 2 days after the index date—on clinical and economic outcomes among patients hospitalized with Enterobacteriaceae infections.

Although both factors have been associated with worse outcomes, and patients with CRE infections often receive inappropriate or delayed antibiotic therapy, few studies have attempted to simultaneously weigh the contribution of each factor. Outcomes included duration of antibiotic therapy, hospital length of stay (LOS), in-hospital costs, discharge destination, and composite mortality (in-hospital death or discharge to hospice).

Among the 50,069 patients who met all selection criteria, 514 patients (1.0%) had infections caused by CRE, and the rest had carbapenem-susceptible Enterobacteriaceae (CSE). Overall, 55.4% of CRE patients received delayed appropriate antibiotic therapy versus 32.5% of CSE patients.

Multivariate-adjusted analysis revealed that, irrespective of CRE status, delayed appropriate antibiotic therapy was associated with longer durations of antibiotic therapy and LOS, lower likelihood of discharge to home, and greater likelihood of the composite mortality outcome. The worst outcomes were observed in patients with CRE who received delayed appropriate therapy.

"Our findings have important implications for clinical practice, as they suggest that the worse outcomes typically associated with Enterobacteriaceae infection, regardless of carbapenem susceptibility status, can potentially be mitigated by timely appropriate antimicrobial therapy," the authors of the study write. They add that the findings highlight the need for rapid diagnostics for earlier detection of drug-resistant gram-negative pathogens and decision-support system tools to identify patients at high risk of infections caused by these pathogens.
Apr 23 Open Forum Infect Dis abstract

 

Antibiotic development collaboration involving 2 drug firms announced

Originally published by CIDRAP News Apr 24

San Diego-based Forge Therapeutics announced today that it has entered into a partnership with Swiss drug maker Basilea Pharmaceutica to discover, develop, and commercialize novel antibiotics.

According to a company press release, Basilea will pay Forge to access its Blacksmith chemistry platform, a drug-discovery platform that identifies small molecule inhibitors of metalloenzymes, which support a variety of biological functions in bacteria. Basilea will apply the Blacksmith platform to develop inhibitors against two well-characterized metalloenzyme targets.

"We are excited to partner with Basilea, a global leader in anti-infective research and development, to pursue novel metalloenzyme targets that have significant promise in this challenging therapeutic area," said Forge CEO Zachary A. Zimmerman, PhD. "Linking our novel chemistry with Basilea's deep drug development and commercial expertise will be a powerful combination in addressing the global threat of antibacterial resistance."

Under the collaboration, Forge is eligible to receive potential development and sales milestone payments of up $167 million per target and tiered royalties upon commercialization of each antibiotic.
Apr 24 Forge Therapeutics press release

 

Diagnostic stewardship intervention reduces inappropriate use of GI test

Originally published by CIDRAP News Apr 23

Implementing a "hard stop" in a hospital's electronic medical record system significantly reduced inappropriate use of a rapid diagnostic test for gastrointestinal pathogens and saved more than $160,000 over 15 months, researchers from the University of Nebraska Medical Center report today in Infection Control and Hospital Epidemiology.

In a quasi-experimental study conducted at an 830-bed tertiary care medical center, the researchers measured the impact of a diagnostic stewardship intervention on the use of the FilmArray Gastrointestinal Panel (GIPP), a rapid multiplex panel that can detect 22 common pathogens in patients who have diarrhea.

The hospital has used the GIPP since 2015 in lieu of traditional stool culture, but concerns about inappropriate use led to an antimicrobial stewardship program (ASP) intervention that included updated guidelines on appropriate use and an order validation alert in the electronic medical record. The alert appears when users attempt to order the GIPP more than once per admission or in patients hospitalized more than 72 hours, and an override requires clinicians to call the microbiology lab director.

A comparison of the preintervention period (January 2016 through March 2017) and the postintervention period (April 2017 though March 2018) showed that the rate of GIPP test ordering dropped from 7.48 per 1,000 patient-days to 5.24 per 1,000 patient-days. The Poisson model estimated a 30% reduction in GIPP ordering rates between the two periods (relative risk, 0.70; 95% confidence interval, 0.63 to 0.78, P < .001). Furthermore, the rate of inappropriate tests ordered declined from 21.5% to 4.9% (P < .001). When including encounters in which the GIPP was initiated but not completed, testing was reduced by 46%, for a potential savings of $168,000.

The authors of the study conclude, "Responsible test ordering of low-yield tests such as the GIPP leads to significant cost savings without affecting high-quality patient care. This study and our results highlight the value of diagnostic stewardship in ASP and collaboration with the microbiology laboratory."
Apr 23 Infect Control Hosp Epidemiol abstract

 

Study: High variability in prescribing by Canadian family physicians

Originally published by CIDRAP News Apr 22

A new study by Canadian researchers has found substantial inter-physician variability in antibiotic prescribing that was not explained at all by differences in patients. The findings appeared in the Journal of Antimicrobial Chemotherapy.

To describe predictors of overall antibiotic prescribing and inter-physician variability among family physicians in Ontario, researchers from Public Health Toronto looked at prescribing rates over 5 years and evaluated the association of patient-, physician-, and clinic-level characteristics with those rates. Using electronic medical records and linked databases containing demographic information on patients and physicians, they evaluated nearly 4 million physician-patient encounters, with 322,129 unique patients cared for by 313 physicians at 41 primary care clinics.

Overall, physicians prescribed a median of 54 antibiotics per 1,000 encounters. Patients' age and sex were highly correlated with antibiotic prescriptions, particularly in girls aged 3 to 5 years, who were associated with the highest antibiotic prescribing rates compared with males 65 years of age and older (odds ratio [OR], 4.01; 95% confidence interval [CI], 3.89 to 4.13). The only significant physician-level predictor was a median daily patient volume of more than 20 patients, compared with more than 10 (adjusted OR, 1.28; 95% CI, 1.06 to 1.55).

The analysis also found, however, that patient-level covariates had little impact on the variability of physician prescribing. The median ORs with and without patient characteristics were 1.68 and 1.69, respectively, which was interpreted as meaning that the odds of receiving an antibiotic prescription in the same patient randomly encountering two different physicians varied by 1.7-fold, simply by seeing different physicians. In addition, except among children ages 0 to 11, physician identifiers explained more of the antibiotic prescribing than all patient characteristics, including comorbidities and healthcare use.

The authors of the study say the findings provide supporting evidence that antibiotic prescribing rates don't need to be adjusted for patient characteristics when used for peer comparison of family physicians working in similar practice settings.
Apr 19 J Antimicrob Chemother study

 

Review highlights factors linked with prescribing in primary, dental care

Originally published by CIDRAP News Apr 22

In another study in the Journal of Antimicrobial Chemotherapy, a team of British researchers reviewed published literature and identified 30 factors associated with the decision to prescribe antibiotics to adults with acute conditions in primary care and primary dental care.

For the two-part review, the researchers identified 689 publications across primary care and 432 across dental care for review. Of these, nine and seven studies, respectively, were included in the final review. They covered 46 countries, of which 12 were low- and middle-income countries (LMICs).

A total of 30 modifiable and non-modifiable factors associated with prescribing were identified across both the umbrella review of primary care studies and the systematic review of primary dental studies. Among the 30 factors identified, the most frequent were "patient/condition characteristics," "patient influence," and "treatment skills." The two factors that were unique to dental studies were "procedure possible," and "treatment skills." None of the factors identified related only to LMICs.

The authors of the study say the identification of these factors should assist the theory-informed design of new interventions—and fine-tuning of existing interventions—aimed at helping clinicians in primary care and dental care optimize antibiotic prescribing.
Apr 19 J Antimicrob Chemother study

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