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Xingmin Sun, PhD, assistant professor, Molecular Medicine, University of South Florida, shares current progress on developing a vaccine for Clostridium difficile infection.
Interview transcript (slightly modified for readability)
The major virulent factors [for Clostridium difficile (C difficile)] are the 2 large toxins (TcdA & TcdB), therefore, those are the major targets for our vaccine. We generated a chimeric fusion protein, "designated mTcd138 containing the glucosyltransferase and cysteine proteinase domains of TcdB and the receptor binding domain (RBD) of TcdA," according to the study abstract. To ensure that [the fusion protein] was toxic, "2 point mutations were introduced in the glucosyltransferase domain of TcdB, which essentially eliminates mTcd138 toxicity."
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The results of a new study have revealed that carbapenem resistance conferred by plasmids can be transferred among unrelated bacteria in the health care setting, underscoring the need for more granular laboratory testing methods in public health institutions to investigate outbreaks of antibiotic-resistant pathogens. The study was presented at the 2018 ASM Microbe meeting in Atlanta, Georgia, on June 10, 2018.
According to the US Centers for Disease Control and Prevention (CDC), carbapenem-resistant Enterobacteriaceae (CRE) are responsible for more than 9000 health care-associated infections and 600 deaths each year in the United States, making them an urgent public health threat.
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A pooled analysis of the findings from the Investigating Gram-Negative Infections Treated with Eravacycline (IGNITE 1; NCT01844856) and IGNITE 4 (NCT01978938) phase 3, randomized, double-blind trials have confirmed the non-inferiority of eravacycline compared to the carbapenem class of antibiotics in the treatment of complicated intra-abdominal infections (cIAIs).
“In the IGNITE 1 and IGNITE 4 studies, eravacycline demonstrated excellent clinical cure rates for commonly observed Gram-negative pathogens. Favorable microbiological and clinical responses were observed for eravacycline against Enterobacteriaceae and Acinetobacter baumannii (A baumannii) Gram-negative pathogens that were third- and fourth-generation cephalosporin-resistant, [extended spectrum β-lactamase]-producing, or multi-drug resistant,” said 2018 ASM Microbe meeting poster presenter Kristen Ditch, PharmD, a Medical Science Liaison with Tetraphase Pharmaceuticals, the developer of eravacycline.
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The Centers for Disease Control and Prevention (CDC) has announced another a multistate outbreak of Salmonella, this time, linked to pre-cut melon.
As of June 8, 2018, 60 cases of Salmonella Adelaide have been reported spanning 5 states; a little more than half (31) of these individuals have required hospitalization for their infections. To date, no deaths have been reported.
The infected individuals range from 1 to 97 years in age, with a median age of 67, according to the CDC. Available data indicate that 65% of those who have fallen ill are female. The reported dates of illness range from April 30 to May 28; however, according to the CDC, Salmonella can take up to 2 to 4 weeks to diagnose and report. As such, any illnesses that have occurred after May 28 may not have been reported yet.
For the most recent case counts associated with the outbreak, be sure to check out the
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In the Keynote address of the ASM Microbe 2018 meeting, Anne Schuchat, MD, Principal Deputy Director, US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, provided some history and insights on CDC’s role in safeguarding public health when the microbial world collides with the human world.
The themes that ran through her talk delivered on June 9 were the virtues of remaining humble when it comes to dealing with bacteria and in learning from adversity and failure. She is familiar with both during her time at CDC.
Humility is necessary when facing the microbial world. With advances in knowledge and technology, one can fall into the trap of feeling in control. But microorganisms have been around eons longer than us and have learned to adapt or die. “Microbes literally live their lives in log phase. They are always adapting and always adjusting,” said Dr. Schuchat.
In dealing with the moving target of microorganisms, accepting that failures will occur is a must. What comes next is crucial. Failure in an infection control effort, such as occurred during the first outbreak of Legionnaire’s disease in 1976 during an American Legion convention in Philadelphia, Pennsylvania, can be devastating. Or, as happened as the CDC faced withering public criticism over their response to the outbreak, the failure can galvanize institutional efforts to hunker down and solve the problem.
Even with resolve, knowledge, and prevention strategies in place, problems can arise. The result, exemplified by influenza, can be a loss of control over a situation where microbial control was presumed. Influenza control efforts have been ongoing for a century. And yet, CDC surveillance data showed that the 2017-2018 influenza season was the highest in terms of influenza-related hospital admission since data collection began. That was a humbling and disturbing year for CDC.
The H3N2 influenza virus has changed its structure over the past 50 years with increased glycosylation of surface antigens. This has made it tougher to mount effective vaccines. Influenza viruses are adept at testing the water, with antigenic changes that favor spread of infection being retained and changes that are not quickly discarded. A recent series of outbreaks of influenza in Asia caused by the H7N9 virus is a sobering example. The initial few waves of the infection gave way to fewer cases and the sense that some control had been restored. Then a fifth wave of infection dwarfed the others in terms of case numbers.
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