ASP Scan (Weekly) for Aug 04, 2017

Molecular diagnostics for TB
Australian drug stewardship report
Diagnostic stewardship
Animal antibiotics in Denmark
Key role for vaccines
Stewardship in US hospitals
Resistant E coli
Death and MDR-TB

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

Molecular testing for drug-resistant tuberculosis shows promise

A study yesterday in Clinical Infectious Diseases suggests that molecular-based diagnostic tests for the detection of drug-resistant tuberculosis (TB) may predict treatment response better than traditional drug susceptibility testing (DST) methods.

In a retrospective study involving isolates from 171 multidrug-resistant TB and extensively drug-resistant TB patients in Lima, Peru, a team of researchers from Massachusetts sequenced the gyrA and gyrB genes; mutations in these genes are the main cause of fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis. They were looking to determine the significance of "intermediate" gyr mutations in treatment response and compare this with treatment response for "high-level" gyr mutations. They also wanted to see how gyr mutation detection compares with culture-based DST in predicting treatment outcome.

In a univariate analysis that controlled for other host and treatment factors, and compared with patients with isolates that didn't have gyr mutations, high-level gyr mutations were found to significantly predict poor treatment outcomes with a hazard ratio of 2.6. In comparison, the hazard ratio for intermediate gyr mutations was 1.3, which did not reach statistical significance. The researchers also found that resistance defined by the detection of either high-level or intermediate gyr mutations was also superior to resistance determined by culture-based ciprofloxacin DST in predicting poor treatment outcomes.

The authors write, "Our comparison with culture-based DST is the first to suggest that gyr mutation detection is as good, if not better, in identifying patients unlikely to respond to FQ treatment."
Aug 3 Clin Infect Dis study


Australian Commission publishes report on human antimicrobial use

The Australian Commission on Safety and Quality in Health Care (ACSQH) this week published its second annual report on antimicrobial use in human health, noting challenges like the increased prevalence of some antibiotic-resistant organisms and problems with improper prescribing, as well as areas for next steps, like implementing actions to control carbapenemase-producing Enterobacteriaceae (CRE).

The authors note that, since 2014, fluoroquinolone resistance in Escherichia coli from blood cultures has increase 2.5% and in Shigella sonnei it's up10.9%. They also note that the proportion of vancomycin-resistant Enterococcus faecium (VRE) isolates in the country increased have rapidly since 2005, and is now higher than that in any European nation. In addition, community-onset methicillin-resistant Staphylococcus aureus (MRSA) is now more common than healthcare-associated MRSA.

Regarding antibiotic prescribing, the report notes that, on any given day in an Australian hospital in 2015, 40.5% of patients were administered an antimicrobial. Of these, 23.3% of antimicrobial prescriptions were noncompliant with guidelines, and 21.9% were considered inappropriate. The authors also say that antibiotics used for surgical prophylaxis are often not required and are given for too long.

Action steps include reducing unnecessary prescribing in the community; taking steps to control CRE, which were outlined in an ACSQH report in May; monitoring resistant gonorrhea, minimizing the spread of VRE, and improving appropriate prescribing for surgical prophylaxis.
Aug 2 ACSQH news release
Aug 2 ACSQH full report


Doctors call for diagnostic stewardship to improve antibiotic use

Originally published by CIDRAP News Aug 1

A commentary yesterday in JAMA argues for diagnostic stewardship as an additional strategy to reduce inappropriate use of antibiotics.

While culture and non-culture–based diagnostic tests are necessary for helping establish the presence or absence of infection, the authors write, the process of ordering and interpreting those tests is complex. In addition, clinicians often order common tests for patients who aren't exhibiting symptoms specific for the disease process. For example, they order Clostridium difficile tests for patients who don't have diarrhea and urine cultures for patients without symptoms of urinary tract infection.

The authors argue that the problem with these tests, especially the increasingly sensitive molecular tests, is that they frequently produce false-positive results or fail to distinguish colonization from infection. The end result is overtreatment and inappropriate antibiotic use.

As a result, some hospitals have launched efforts to improve diagnostic stewardship by modifying the process of ordering, performing, and reporting diagnostic tests. Examples of diagnostic stewardship interventions include educational campaigns to teach clinicians appropriate indications and sampling for tests, removal of specific tests from electronic health records, and laboratory policies that include refusing to process specimens that are collected and handled inappropriately.

The authors go on to write that while the most beneficial form of diagnostic stewardship has not yet been defined, and thoughtful application of diagnostic stewardship principles should be applied to mitigate any potential unintended consequences and maintain clinician autonomy, implementing diagnostic stewardship can improve clinical care by reducing inappropriate testing, false-positive test results, and over-diagnosis. And they say that stewardship will be even more important with the expanding array of molecular diagnostic tests.
Jul 31 JAMA viewpoint


Commentary details success of antibiotic stewardship in Danish animals

Originally published by CIDRAP News Aug 1

Two Danish experts detailed the initiatives behind Denmark's successful antimicrobial stewardship efforts in food animals, highlighting a farmer overuse identification program, an antibiotic tax, and lab verification for antibiotic prescriptions as playing key roles.

Their analysis appeared yesterday in a National Academy of Medicine (NAM) commentary.

The two scientists noted that the use of antimicrobials in food-producing animals increased in Denmark from 2003 to 2009, partly as a result of more pigs in production. As a result of increased antimicrobial use, the Danish Veterinary and Food Administration established the "Yellow Card" intervention in 2011, designed to target pig farmers using high amounts of antimicrobials. It set national threshold limits for the use of antimicrobials in weaners, grower pigs, and adult pigs and could result in an injunction for farmers using too many drugs.

In addition, Danish officials adopted two measures in 2013: (1) a tax on antimicrobials that favored narrow-spectrum antimicrobials and vaccines compared with broad-spectrum compounds and (2) mandated annual lab verification of intestinal and respiratory infections for prescriptions written for group treatments.

"Together, these interventions, particularly those implemented [after] 2010, appear to have ended the otherwise increasing trend in antimicrobial usage observed since 1999," the authors wrote. "The antimicrobial resistance levels in Denmark continue to be lower than in most EU countries, which is most likely because of the detailed research and monitoring of antimicrobial use and resistance in food animals and in humans."
Jul 31 NAM commentary


US expert underscores vaccines as key element to fight drug resistance

Originally published by CIDRAP News Aug 1

Bruce Gellin, MD, MPH, former director of the US National Vaccine Program Office in the Department of Health and Human Services, in a commentary today underscored the important role that vaccines can play in combating antimicrobial resistance.

Writing for Stat, Gellin, now president of global immunization for the Sabin Vaccine Institute, outlined key steps to addressing the problem, such as developing new antibiotics and stewardship measures. He added, "Preventing infections in the first place will also reduce the need for antibiotics. That's where vaccines come in as an important part of the solution."

Gellin also noted, "In the context of the global trend in antibiotic resistance, we have been undervaluing all that vaccines offer to both individuals and communities."

He noted that vaccines help prevent the rise of antimicrobial resistance by preventing bacterial diseases such as pneumococcal infections, bacterial meningitis, and pneumonia, but their use against viral diseases can also reduce antibiotic use by preventing influenza and other viral infections that are often mistreated with antibiotics.
Aug 1 Stat commentary


Study: US comprehensive hospital ASP programs grew by 18% in 1 year

Originally published by CIDRAP News Jul 31

A new study from researchers at the US Centers for Disease Control and Prevention (CDC) assessed the success of the CDC's core elements of hospital antimicrobial stewardship programs (ASPs). Using data reported in the 2015 National Healthcare Safety Network's Annual Hospital Survey, the researchers found that uptake of the core elements increased from 40.9% in 2014 to 48.1% in 2015, a 17.6% bump. The results were published Jul 29 in Clinical Infectious Diseases.

The core elements are antimicrobial stewardship program leadership, accountability, drug expertise, action, tracking, reporting, and education. All hospitals included in the survey self-reported on activity for each element.

A total of 4,569 hospitals participated in the survey, with an average bed size of 164. Of the respondents, 48.1% reported uptake from all seven of the core elements, with nearly half of all larger hospitals reporting increases in antimicrobial stewardship programs. Teaching hospitals were 1.5 times more likely to implement all of the core elements, as were large facilities.

"Hospitals in the U.S. are making progress towards a national goal of universal presence of ASPs, but faster progress is needed. Efforts to support smaller hospitals will be especially important," the authors said.
Jul 29 Clin Infect Dis study


Study reports high drug resistance in Shiga toxin-producing E coli

Originally published by CIDRAP News Jul 31

High frequencies of antibiotic resistance were observed in strains of Shiga toxin–producing E coli (STEC) recovered from patients in Michigan during 2010 to 2014, researchers report in Emerging Infectious Diseases.

Of the 358 STEC isolates recovered from the Michigan Department of Health and Human Services Reference Laboratory, 31 (8.8%) were resistant to antibiotics. Eight of the isolates were O157, the strain that causes most foodborne illnesses in the United States, and 23 were non-O157. Resistance to ampicillin (7.4%) was most common, followed by trimethoprim/sulfamethoxazole (4.0%), and ciprofloxacin (0.3%). One strain was resistant to all drugs.

Notably, researchers found that resistance was twice as common for non-O157 (11.1%) than for O157 (5.5%) strains, and was independently associated with hospitalization (odds ratio, 2.4), indicating that resistance could cause more severe disease outcomes.

The authors also noted higher O157 resistance frequencies in Michigan compared with the rest of the nation, a finding they said indicates that selection pressures vary by location and source. And while no differences in resistance frequencies were observed for counties with high versus low antibiotic prescription rates, the authors suggest that selection pressure from antibiotic use on farms—not investigated in this study—may be affecting emerging STEC resistance in Michigan.

STEC contributes to 265,000 cases of foodborne illness annually in the United States. 
Jul 28 Emerg Infect Dis research letter


US data show sharp decline in deaths among MDR-TB patients

Originally published by CIDRAP News Jul 31

Death rates from MDR-TB have fallen by almost two-thirds in recent years, according to a study from CDC experts published in Clinical Infectious Diseases.

The investigators analyzed data from 1993 through 2013 from the CDC's National Tuberculosis Surveillance System and assessed factors associated with all-cause mortality. The database contained information on 3,434 MDR-TB cases, 96% of which involved adults.

The researchers found that the all-cause mortality rate decreased from 31% during 1993 through 2002 to 11% in 2003 through 2013. In addition, coverage of directly observed therapy, a key to successful, complete treatment, increased from 74% to 95% in the two study periods. The researchers also found that the effect of HIV on mortality greatly decreased from the earlier period to the latter.

Despite the apparent success of directly observed therapy, the authors point out that foreign-born MDR-TB patients living with HIV still have twice the risk of death compared with US-born patients with MDR-TB and HIV.
Jul 29 Clin Infect Dis study

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