Stewardship / Resistance Scan for Nov 27, 2019

Rapid susceptibility test
Vegetarians harboring superbugs
Fidaxomicin against C diff in kids

Scientists develop genotype-phenotype rapid susceptibility test

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

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

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

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