WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.
In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.
Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.
Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.
Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.
Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.
“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.
“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.
In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.
In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.
Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).