ASP Scan (Weekly) for Nov 29, 2019

Rapid susceptibility test
Vegetarians harboring superbugs
Fidaxomicin against C diff in kids
Educational outpatient stewardship
Antibiotic overuse in Saudi Arabia, Pakistan
Funds for resistant gonorrhea

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

Scientists develop genotype-phenotype rapid susceptibility test

Originally published by CIDRAP News Nov 27

Scientists from Harvard University and the Massachusetts Institute of Technology report that a diagnostic test they developed allows simultaneous detection of genotype and phenotype, enabling rapid and accurate antibiotic susceptibility determination in under 4 hours, according to their findings detailed in a letter in Nature Medicine.

The authors note that growth-based tests are constrained by the speed at which bacteria reproduce, and genotypic assays are limited by the ever-growing diversity and complexity of antibiotic resistance mechanisms in bacteria. So they developed an antibiotic susceptibility test (AST) that detects both genotype and phenotype of microbes to enhance speed and accuracy.

Their test, GoPhAST-R (combined genotypic and phenotypic AST through RNA detection—pronounced "go faster") can detect a pathogen's genotype and phenotype in a single rapid assay that simultaneously generates data on resistance prediction and molecular epidemiology. The test detects specific messenger RNA expression signatures in bacteria after they are briefly exposed to antibiotics. The scientists validated the test using three common antibiotic classes— luoroquinolones, aminoglycosides and carbapenems—in five pathogens that have a propensity for multidrug resistance.

They determined an accuracy of 94% to 99% within 4 hours using blood samples and note that their approach yields phenotype information 24 to 36 hours faster than other tests.

The authors conclude, "GoPhAST-R has the potential for even faster phenotypic AST on timescales that can inform early antibiotic decisions and thus transform infectious disease practice."
Nov 25 Nat Med letter


Study finds lower rates of drug-resistant bacteria in omnivores

Originally published by CIDRAP News Nov 27

Just in time for the US Thanksgiving tradition of carnivorous feasting, Dutch researchers report that vegetarians and pescatarians (vegetarians who eat fish) have higher rates of carriage of antibiotic-resistant Enterobacteriaceae than non-vegetarians do, indicating that eating meat is not an important risk factor in harboring certain types of superbugs.

The findings appeared this week in the Journal of Antimicrobial Chemotherapy.

Given that extended-spectrum beta-lactamase (ESBL)– and plasmid-mediated AmpC (pAmpC)–producing Enterobacteriaceae are common on Dutch meat products, the investigators sought to determine whether vegetarians are at a lower risk of carrying ESBL/pAmpC-producing Escherichia coli or Klebsiella pneumoniae (ESBL-E/K) compared with people who eat meat. Their analysis included 785 vegetarians, 392 pescatarians, and 365 non-vegetarians.

Fecal sampling determined that 8.0% of vegetarians (95% confidence interval [CI] and 6.3%-10.1%), 6.9% of pescatarians (95% CI, 4.8%-9.8%) carried ESBL-E/K microbes—compared with only 3.8% of non-vegetarians (95% CI, 2.3%-6.3%).
Nov 25 J Antimicrob Chemother abstract


Phase 3 trial shows good results for fidaxomicin against C difficile in kids

Originally published by CIDRAP News Nov 27

The narrow-spectrum antibiotic fidaxomicin has shown good efficacy against Clostridioides difficile infection (CDI) in adults. Now, in a phase 3 trial published today in Clinical Infectious Diseases, the drug outperformed vancomycin against CDI in children and adolescents.

The trial, dubbed the SUNSHINE study, enrolled 142 children ages 0 to 17 years who had CDI diagnosed according to clinical criteria and diagnostic testing in one of 39 sites in the United States, Canada, or Europe. Thirty of the patients were younger than 2 years old. Patients were randomized 2:1 to 10 days of treatment with either twice-daily oral fidaxomicin or four-times-daily oral vancomycin.

The researchers reported a clinical response rate (no evidence of CDI) of 77.6% (76/98) in the fidaxomicin group and 70.5% (31/44) in the vancomycin group. Global cure (clinical response plus no CDI recurrence) was noted in 68.4% of fidaxomicin patients and 50.0% of vancomycin patients. Adverse events were noted in 73.5% of fidaxomicin patients, compared with 75.0% in the other group.

The data reflect similar findings of a previous phase 3 trial in adults.

An accompanying commentary by Larry Kociolek, MD, of Northwestern University, noted, "The SUNSHINE trial is a major step forward in addressing the need for evidence-based CDI treatment options in children. However, to continue to move the needle for C. difficile research in children, a deeper understanding of the pathogenesis, clinical microbiology, and immunology of CDI in children is needed."
Nov 27 Clin Infect Dis study
Nov 27 Clin Infect Dis commentary


Educational stewardship program tied to better antibiotic prescribing

Originally published by CIDRAP News Nov 25

A comprehensive educational antimicrobial stewardship program (ASP) implemented in 214 Spanish primary care clinics was tied to improved use of antibiotics and a sustained reduction of infections caused by extended-spectrum beta-lactamase (ESBL)-producing E coli, according to a new study in The Lancet Infectious Diseases.

In total, 1,387 physicians participated in the ASP from 2014 to 2017 in outpatient primary care clinics serving more than 1.9 million patients across a wide area of Spain. The ASP combined educational presentations on correct prescribing; practice-based diagnostic and treatment guidelines; case-based, in-person discussions with clinicians about their prescribing practices; and audit and feedback reports. Researchers analyzed data from January 2012 (before implementation) through December 2017.

The investigators noted a 36.5% rate of inappropriate antibiotic prescribing in 2014, compared with a 26.9% rate in 2017. Ciprofloxacin use dropped 15.9% and cephalosporin use 22.6% after ASP implementation, and both reductions were sustained. The use of antibiotics recommended in guidelines, meanwhile, increased: Amoxicillin use climbed 22.2%, while fosfomycin use rose 6.1%.

The incidence of ESBL-producing E coli in urine samples declined 65.6%, down 0.028 cases per 1,000 inhabitants. Before the ASP was begun, the rate of that resistant pathogen had been increasing.

The study was funded by the Instituto de Salud Carlos III and the Spanish government.

In a related commentary in the same journal, two Johns Hopkins experts who were not involved in the study wrote, "Understanding whether the intervention can persist in the long-term and which of its components must be hardwired into the clinic workflow to achieve sustainability are important next steps. Elements of the investigators' work, such as education via a massive open online course and tools developed for audit, feedback, and peer review, can and should be disseminated and implemented in other ambulatory practices, such that optimal antibiotic prescribing in the outpatient setting becomes the norm, not the exception."
Nov 22 Lancet Infect Dis study
Nov 22 Lancet Infect Dis commentary


Studies note high rates of improper antibiotic use in Saudi Arabia, Pakistan

Originally published by CIDRAP News Nov 25

A two-hospital study in Saudi Arabia highlights inappropriate antibiotic use in patients both with and without sepsis, while a second study in the same journal—Antimicrobial Resistance & Infection Control—notes antibiotic overprescribing in hospitals in Lahore, Pakistan.

The case-control study in Riyadh, Saudi Arabia, involved 157 patients with sepsis and 158 without. All patients with sepsis received antibiotics, while 87.3% of controls received the drugs. The researchers compared antibiotic use before and after management by critical care response teams (CCRTs).

Overall appropriateness was 59.6% in sepsis patients and 50.7% in controls. In addition, only 48.5% of antimicrobials prescribed by CCRTs were de-escalated by a primary team within 4 days across both study groups. Individual appropriateness was highest with piperacillin/tazobactam (87.1%) and colistin (78.3%) and lowest with meropenem (16.7%) and imipenem (25.0%).

The authors concluded, "Empiric use and inadequate de-escalation of broad-spectrum antimicrobials were major causes for inappropriate antimicrobial use in CCRT patients."
Nov 21 Antimicrob Resist Infect Control Saudi Arabia study

In the second study, Pakistani scientists analyzed data on 1,185 patients who, over a 2-month period in 2017, were prescribed antibiotics in one of four acute-care hospitals in the capital city, two public and two private. Among those patients, 70.3% received at least one antibiotic that was deemed inappropriate based on guidelines. Of the 27.2% of patients who had respiratory tract infections, 62.8% received inappropriate antibiotic therapy.

Macrolides were tied to the highest rate of inappropriate prescribing—74.6%—followed by penicillins (71.0%), carbapenems (70.9%), cephalosporins (67.2%), and fluoroquinolones (64.2%). The inappropriate rate for aminoglycosides, in contrast, was 35.8%.
Nov 21 Antimicrob Resist Infect Control Pakistan study


CARB-X announces funding for drug targeting resistant gonorrhea

Originally published by CIDRAP News Nov 25

CARB-X today announced funding of up to $4.1 million for VenatoRx Pharmaceuticals, Inc to develop a new class of oral antibiotics to treat multi-drug-resistant (MDR) Neisseria gonorrhoeae

"Neisseria gonorrhoeae are highly adept at avoiding the action of antibiotics that are meant to kill them. Some strains resist even last-resort antibiotics and these superbugs continue to build resistance at an alarming rate," said Kevin Outterson, JD, executive director of CARB-X, in a press release. VenatoRx could receive an additional $8.9 million if it meets certain project milestones.

Each year, 78 million people worldwide are infected with the gonorrhea, and half of all infections are resistant to at least one antibiotic, CARB-X said. VenatoRx's product is a novel non-beta-lactam penicillin-binding protein inhibitor that has acts against select gram-negative bacteria, including N gonorrhoeae. 

The award is CARB-X's second for VenatoRX, and the 51st the organization has made since its inception in 2016. The awards together exceed $154 million.

CARB-X stands for the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, and the organization has pledged to invest up to $500 million between 2016-2021 to support the development of new antibiotics, rapid diagnostics, vaccines and other life-saving products.
Nov 25 CARB-X press release

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