Rapid susceptibility test promising for optimal antibiotics in bacteremia
South Korean scientists have demonstrated strong potential of a rapid antimicrobial susceptibility test called QMAC-dRAST for selecting optimal targeted antibiotics for patients who have bacteremia, according to a study today in the Journal of Antimicrobial Chemotherapy.
The test is made by QuantaMatrix Inc, a South Korean company, and the study was conducted by researchers from the National University College of Medicine in Seoul and QuantaMatrix. They compared QMAC-dRAST, which can produce results within 6 hours, with MALDI-TOF MS, a type of mass spectrometry that can yield results in less than an hour and has been successfully used for selecting empirical antibiotics for bloodstream infections.
The investigators assessed 359 patients who had positive blood cultures, and infectious disease (ID) physicians decided on antibiotic regimens with consensus at each time point of receiving results of Gram staining, MALDI-TOF MS, and antimicrobial susceptibility testing (AST) using QMAC-dRAST.
The ID physicians with MALDI-TOF MS results chose optimal targeted antibiotics in 255 cases (71.0%), with appropriate antibiotic selection in 303 (84.4%). The proportion of optimal targeted antibiotic selection and appropriate antibiotic selection was significantly lower for resistant strains than for susceptible strains (62.5% vs 79.2% and 68.2% vs 100%, respectively).
QMAC-dRAST results led to optimal antibiotic treatment in 95 (91.3%) of the 104 cases receiving non-optimal targeted antibiotics. Optimal targeted treatments based on QMAC-dRAST results were possible in 322 (98.2%) of the 328 cases with monobacterial infection and in 345 (96.1%) of the 359 cases with monobacterial and polymicrobial infection.
The authors conclude, "MALDI-TOF MS has a high chance of failure in guiding ID physicians to optimal antibiotics, especially against resistant organisms. With increasingly common resistant organisms, rapid AST is needed to identify optimal targeted antibiotics early in bacteraemia."
Apr 30 J Antimicrob Chemother abstract
CARB-X announces new funding rounds
CARB-X today announced four new rounds of funding for companies seeking to develop novel antibiotics and other products to address drug-resistant infections.
Each of the four funding rounds has a specific scope and different application period: Round 1 will be restricted to non-traditional approaches, round 2 to vaccines and biotherapeutics, round 3 to diagnostics, and round 4 to direct-acting small molecule antibiotics. CARB-X is planning a webinar on May 16 to discuss the funding rounds and the application process.
Since its inception in June 2016, CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) has awarded more than $110 million in funding to 42 projects that seek to address high-priority drug-resistant bacteria. In addition to financial support, CARB-X also provides scientific and business advice to help move the projects through the early development phases.
"Our goal is to select the best, most innovative projects that have the potential to prevent, diagnose and treat drug-resistant infections that are killing hundreds of thousands of people each year worldwide," CARB-X executive director Kevin Outterson, JD, said in a press release. "We plan to grow the portfolio through these funding rounds and expand the number of different approaches to increase the chances of delivering urgently-needed medicines and diagnostics to patients."
Apr 30 CARB-X press release
CRE bloodstream infections linked to worse outcomes in poorer countries
The results of a multinational study yesterday in The Lancet Infectious Diseases show that carbapenem resistance is associated with longer hospital stays and increased mortality in patients with bloodstream infections in low- and middle-income countries (LMICs).
The study, conducted at 16 tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam from August 2014 through June 2015, included 297 patients with carbapenem-resistant Enterebacteriaceae (CRE) and carbapenem-susceptible Enterobaceteriaceae (CSE) infections.
The researchers wanted to compare outcomes in the two groups because while CRE bloodstream infections have been associated with poorer outcomes, most studies have been conducted in high-income countries. Multistate-modeling was used to estimate excess length of hospital stay associated with carbapenem resistance, and proportional subdistribution hazards models were applied to estimate the effect of carbapenem resistance on in-hospital death and probability of discharge alive.
Crude mortality was 20% for patients with CSE bloodstream infection (35 of 174) and 35% for those with CRE bloodstream infection (43 of 123 patients). Carbapenem resistance was associated with increased length of hospital stay (3.7 days, 95% confidence interval [CI], 0.3 to 6.9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio [HR], 1.75; 95% CI, 1.04 to 2.94), and decreased probability of discharge alive (HR, 0.61; 95% CI, 0.45 to 0.83).
Multilocus sequence typing of patient isolates identified various clades of Escherichia coli and Klebsiella pneumoniae (the two most common species of Enterobacteriaceae detected), with marginal overlap between strains in the CRE and CSE clades. Polymerase chain reaction screening of 208 isolates revealed that blaNDM and blaOXA-48-like were the most commonly identified carbapenemase-encoding genes.
"This study contributes to an improved understanding of the scale of the emerging threat of carbapenem-resistance in LMICs," the authors of the study write. "In the future, affordable surveillance mechanism, interventions to prevent infection, and management strategies should be developed to reduce the burden of bloodstream infections caused by CRE in LMICs."
An accompanying commentary says the findings indicate global action against CRE is needed. "At a minimum, every country should have a national action plan tasked with measuring the prevalence of CRE and other resistant phenotypes, promoting the prudent use of antibiotics in health care and in animal husbandry, immunising their population, and investing in water sanitation," write Federico Perez, MD, and Robert Bonomo, MD, of the Louis Stokes Cleveland Veteran Affairs Medical Center and Case Western Reserve University.
Apr 29 Lancet Infect Dis abstract
Apr 29 Lancet Infect Dis comment
Hospital intervention reduces treatment for asymptomatic bacteremia
Raising the threshold for identifying uropathogens from inpatient urine cultures averted treatment for asymptomatic bacteriuria and candiduria (ASB/C) in nearly a third of patients at an acute care hospital, Canadian researchers reported yesterday in JAMA Internal Medicine.
In a research letter, clinicians from Sunnybrook Health Sciences Centre in Toronto describe a controlled interrupted time series study conducted after the hospital raised the threshold for identifying and reporting growth in urine cultures from 104 colony-forming units per milliliter (CFU/mL) to 105 CFU/mL. With this change, all urine cultures with low colony counts (defined as 104 to 105 CFU/mL) were issued with a report stating that these organisms usually represent ASB/C, which does not require antibiotic therapy.
In the study, the clinicians compared the rate of monthly treatment for ASB/C in the period before and after the threshold was raised; secondary outcomes included days of antibiotic therapy and a composite clinical outcome of hospital readmission, death, or transfer to clinical care within 14 days.
Over 2 years, there were 609 patients (30%) with a low colony count and 1,432 (70%) with a high colony count, of which 608 and 690 were included in the analysis, respectively. The results showed that the intervention was associated with a reduction in antibiotic prescribing for ASB/C in the low-colony-count group compared with the high-colony-count group (incidence rate ratio, 0.14; 95% CI, 0.03 to 0.64, P = .01). There were no significant clinical changes between the two groups.
The authors say raising the threshold to 105 CFU/mL was associated with sustained reduction of antibiotic prescribing for ASB/C on the order of 70 fewer treatment courses per year, which would avert an estimated 14 adverse drug events annually.
Apr 29 JAMA Internal Med abstract