ASP Scan (Weekly) for Mar 31, 2017

Antibiotic tax credit
Antibiotic overprescribing
Drug-tainted manure affects soil
Fighting MRSA biofilms
C diff in surgical patients
Diagnostic test competition
MDR-TB in African migrants
Stewardship in Aruba

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

Legislation calls for tax credits for new antibiotics, diagnostic tests

US lawmakers today introduced legislation that would provide a tax credit for new antibiotics and diagnostic tests.

The Reinvigorating Antibiotic and Diagnostic Innovation (READI) Act, H.R. 1840, would amend the Internal Revenue Code of 1986 to provide a tax credit for 50% of the clinical testing expenses for new antibiotics that treat a serious or life-threating infections and new rapid diagnostic tests. The bill, introduced by US Representatives Mike Thompson (D-CA) and Erik Paulsen (R-MN), is modeled on the orphan drug tax credit, meant to provide incentives to pharmaceutical companies to invest in treatments for rare disease.

The idea is to encourage drug makers to develop new antibiotics, which are expensive to develop and don't produce the type of financial returns that drugs for chronic conditions do. There are currently only 40 antibiotics in the development pipeline, and 70% of those are in already-existing classes.

"Most pharmaceutical companies have retreated from antibiotic research and development because antibiotics are difficult and costly to develop and fail to provide a profit," Henry Chambers, MD, chief of the division of infectious diseases at San Francisco General Hospital, said in a press release from the Infectious Diseases Society of America (IDSA). "The READI Act will provide a much-needed incentive for companies to develop the new antibiotics that patients so desperately need."

IDSA President William Powderly, MD, added that new rapid diagnostic tests are equally necessary. "Without rapid tests, we must often treat empirically—before we know exactly what type of infection a patient has—which can lead to antibiotic overuse," he said.

IDSA was one of 41 medical organizations, pharmaceutical companies, and diagnostics companies that signed a letter of support for the legislation.
Mar 31 IDSA press release


German GP antibiotic prescribing for respiratory illness found wanting

Originally published by CIDRAP News Mar 29

German general practitioners (GPs) follow national guidance on prescribing antibiotics for acute lower respiratory infections only about a quarter of the time, according to a study yesterday in PLoS One.

Researchers analyzed data from 2009 to 2013 from electronic health records of 12,880 patients. GPs prescribed antibiotics in 41% of consultations.

GPs' decision on whether or not to prescribe an antibiotic meshed with national guidelines 52% of the time, and agreement with the guidelines on antibiotic choice occurred 51% of the time. "Hence," the authors write, "a congruent prescribing decision and a prescription of recommendation was found in only 25% of antibiotic prescriptions."

Further, about 73% of antibiotics prescribed for cough and 78% for acute bronchitis were incongruent to the guidelines. In contrast, only about 28% of antibiotics prescribed for community acquired pneumonia did not match national recommendations.

"Our results show that there is a big gap between guideline recommendation and actual prescribing, in the decision to prescribe and the choice of antibiotic agent," the authors conclude. "This gap could be closed by periodic quality circles on antibiotic prescribing for GPs."
Mar 28 PLoS One study


Manure from cattle given antibiotics alters soil microbiome, study finds

Originally published by CIDRAP News Mar 29

Manure from cattle that were administered antibiotics can dramatically raise antibiotic-resistance levels and alter the bacterial and fungal makeup of the surrounding soil, according to a study today in the Proceedings of the Royal Society B.

A team led by Virginia Tech researchers analyzed soil samples from 11 US dairy farms. They measured the prevalence of four antibiotic-resistant genes in soil samples near manure piles and not near them. The difference for two of the resistance genes was not significant. But for ampC (related to beta-lactam resistance) and tetO and tetW (related to tetracycline resistance), the rates were 421% and 3,283% higher, respectively, in the manure-exposed soils.

The authors wrote, "This was potentially expected for ampC, given the treatment of cattle with cephapirin benzathine, but not for tetO, given that farm managers did not report any recent use of tetracyclines."

The investigators also discovered that bacterial community composition at manure-exposed sites was dominated by Acinetobacter bacteria, known for their resistance to cephalosporins. Fungal composition was also altered in manure-exposed soil. In addition, microbes with greater antibiotic-resistance showed higher stress levels.

"The development of antibiotic resistance can be an energy-sucker for a microorganism, and would explain why we've seen higher stress levels. We need to continue to investigate this possible link," said lead author Michael Strickland, PhD, in a Virginia Tech news release.
Mar 29 Proc R Soc B study
Mar 28 Virginia Tech news release


Study finds accurate food safety advice sorely lacking in cookbooks

Originally published by CIDRAP News Mar 29

Two common disinfectants effectively combat biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA), researchers reported yesterday in Antimicrobial Resistance and Infection Control.

The organization of bacteria into biofilms is a common mode of pathogen survival, since it increases their ability to withstand antibiotics, disinfectants, and hosts' immune response. Biofilm formation is being increasingly recognized as an infection control problem, and it can lead to increased drug resistance and treatment failure.

German researchers tested the ability of the disinfectants octenidine, chlorhexidine, polyhexanid, and chloroxylenol to combat MRSA biofilms in the lab.

They found that octenidine and chlorhexidine performed well, inhibiting MRSA in biofilms with reduction rates of 94 ± 1% and 91 ± 1%, respectively, while polyhexanid had a maximum efficacy of only 81 ± 7%. Chloroxylenol was not effective, with an efficacy of 15.8 ± 27%. The researchers also found that the topical decolonization agent mupirocin was not effective.
Mar 28 Antimicrob Resist Infect Control study


Antibiotic use, ICU admission seen as factors for C diff in surgical patients

Originally published by CIDRAP News Mar 28

A study yesterday in Antimicrobial Resistance and Infection Control describes the incidence rate and risk factors for Clostridium difficile infection (CDI) among surgical patients in Serbia.

In the case-control study, investigators with the Military Medical Academy, a 1,200-bed hospital in Belgrade, Serbia, prospectively identified all patients who had new healthcare-associated (HA), lab-confirmed postoperative CDI from January 2011 through December 2012. The incidence rate was defined as the number HA CDIs per 10,000 patient-days and per 1,000 patients. To determine risk factors, the investigators compared every surgical patient with HA CDI with two control patients without CDI.

Of the 29,033 surgical patients treated during the study period, 67 were diagnosed with CDI, for an incidence rate of 2.6 per 10,000 patient-days and 2.3 per 1,000 patients. The investigators identified three independent risk factors associated with CDI in surgical patients: previous administration of carbapenems, use of third-generation cephalosporins, and admission to the intensive care unit. In-hospital morality was nine times higher in the CDI patients compared with control patients.

"CDI is an important HA infection in population of surgical patients, and this study emphasizes the importance of the wise use of antibiotics and other infection control strategies to prevent HA CDI, decrease incidence and in-hospital mortality rate," the authors conclude.
Mar 27 Antimicrob Resist Infect Control study


NIH announces semifinalists in bacterial diagnostic competition

Originally published by CIDRAP News Mar 27

The National Institutes of Health (NIH) today said it has selected 10 semifinalists in the first phase of a federal prize competition that will award up to $20 million for innovative tests that can rapidly diagnose bacterial infections and identify antibiotic resistant bacteria.

The 74 concept submissions for the Antimicrobial Resistance Diagnostic Challenge were evaluated by an independent panel of scientific and clinical experts, based on several criteria. In particular, the judges considered whether the submissions demonstrated novel and innovative technology, whether implementation would improve clinical decision-making and reduce antibiotic resistance, and whether the concepts would produce actionable results relevant to their intended use. The likelihood of success as a commercial diagnostic system was also considered.

The contest is sponsored by the NIH and the Biomedical Advanced Research and Development Authority (BARDA) in support of the National Action Plan for Combating Antibiotic-Resistant Bacteria. The hope is that new rapid, point-of-care diagnostic tests will be able to distinguish between viral and bacterial infections and detect and characterize antibiotic-resistant bacteria within hours rather than days, thereby cutting down on the unnecessary and inappropriate antibiotic use that causes resistance.

"Diagnostics that are fast, accurate, and easy-to-use are critical to address antibiotic resistance that could imperil not only each person's health but also our nation's security from natural and intentional threats," BARDA Director Rick Bright, PhD, said in an NIH press release. "The exciting technology envisioned by our challenge's semifinalists may help us put better tools at the patient's side."

Semifinalists will each receive $50,000 to develop their concepts into prototypes. Submissions of prototypes and analytical data for the second phase of the competition are due Sep 4. NIH is expected to announce up to three winners on Jul 31, 2020. The winners will share up to $20 million, subject to the availability of funds.
Mar 27 NIH press release


ECDC says MDR-TB cases in African migrants have risen to 25

Originally published by CIDRAP News Mar 27

European health officials report that 25 cases of multidrug-resistant tuberculosis (MDR-TB) among migrants from the Horn of Africa appear to be part of a chain of recent transmission.

In a rapid risk assessment issued today, the European Centre for Disease Prevention and Control (ECDC) reports that whole-genome sequencing (WGS) analysis indicates that all 25 cases belong to a single cluster and differ by only one single nucleotide polymorphism, an indication of recent transmission from a common source of infection. According to the ECDC report, available data suggest the origin of the cluster strain stems from the Horn of Africa. All cases have a recent history of migration from Somalia (22), Eritrea (2), and Ethiopia (1).

The cluster was initially reported by the ECDC in December 2016, when it involved 16 cases, with the first infections identified between February and August 2016. As of Mar 14, isolates from the cluster have been reported from Germany (13), Switzerland (8), Austria (2), Finland (1), and Sweden (1). In addition, Germany has reported a culture-negative and a culture-positive case with epidemiologic links, and a likely case that's awaiting WGS. France is reporting two cases under investigation.

Although it's unclear whether transmission took place in the patients' countries of origin, along the migration route, or in the destination country, the ECDC says preliminary analysis of the cases in Switzerland suggests most patients reported symptoms at arrival or before. Migrants from war-torn or impoverished countries may be at increased risk of TB or MDR-TB because of inadequate healthcare in their country of origin and exposure to destitution and poor social conditions along the migration route.

The ECDC says the clearest risk of transmission is within the affected migrant population, and that the risk to the European Union/European Free Trade Association population is low. But the agency is urging rapid investigation of exposure risk factors, including the travel history and itineraries of patients and their contacts. 
Mar 27 ECDC rapid risk assessment


Checklist helps increase appropriate use of antibiotics in Aruba

Originally published by CIDRAP News Mar 27

Introduction of an antibiotic checklist increased appropriate use of antibiotics at a hospital in Aruba, according to a new study in the International Journal of Infectious Diseases.

For the study, investigators conducted a prospective cohort trial from August 2015 through January 2016 at Aruba's only hospital. The aim of the study was to compare the periods before and after the implementation of an antibiotic checklist consisting of seven quality indicators (QIs) that define appropriate antibiotic treatment of bacterial infections in the hospital. Among the checklist items are taking at least two blood cultures from a patient before starting antibiotic therapy, adjusting dosing based on renal function, documenting in the patient's file the indication for antibiotic treatment, and adjusting therapy when culture results are available.

Recent research by the team indicated that implementation of the checklist had resulted in more appropriate antibiotic use in the Netherlands. Aruba, a constituent country of the Netherlands that struggles with high antimicrobial resistance rates, seemed like a good test case to see if the checklist could provide similar results in a different setting.

Eligible patients at the 288-bed hospital included adults who had a suspected bacterial infection and were treated with intravenous antibiotics. For all patients, data were collected on adherence to the QIs. There were 150 patients in the baseline group and 173 in the intervention group. The primary end point was the QI sum score, calculated by the patient's sum of performed checklist items divided by the total number of QIs that applied to each patient.

Overall, the checklist was used in 63.3% of the patients, which was high compared with the 23.2% in the Dutch study. The percentage of patients with a QI sum score of 50% or greater was more than three times higher in the intervention group compared with the baseline group (odds ratio, 3.67). But performance did not improve on each individual QI; the largest increase was seen in the collection of blood cultures, adjustment to renal function, and documentation of the indication for antibiotic treatment.

"Further initiatives are necessary for further improvement, especially to improve antibiotic guideline adherence," the authors write. "Completion of the antibiotic checklist was high, suggesting that the implementation of the checklist is possible outside the Netherlands."
Mar 24 Int J Infect Dis abstract

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