We’ve had a whirlwind of amazing talks, poster sessions, and networking sessions so far at ASM Microbe 2016. In our previous two Dispatches from ASM Microbe, we’ve covered microbiomes, for which research ranges from extremely basic (Which microbes are present? How do we quantify them?) to clinical applications (What microbiome characteristics are associated with health? How do we engineer a particular microbiome function?). Similarly, today's focus on antimicrobial resistance has both extremely basic and widely applicable research arms represented at ASM Microbe.
Resistance Genes Travel Locally and Internationally
Despite having many functions that benefit human health, our microbiomes can also contribute to detrimental disease-related outcomes. A Saturday, June 18th session highlighted the role of the human microbiome in harboring antibiotic resistance genes, which can result in drug-resistant infections if the genetic elements are transferred to pathogens. This "resistome" exists in part due to the high density of microbes and in part due to the prevalence of antimicrobial agents used in our arsenal against infection. The gut (covered by Willem van Schaik), pediatric gut (covered by Aimee Moore), and oral cavity (covered by Adam Roberts) can all act as major reservoirs that harbor drug-resistant microbial members, sometimes without detection or deleterious health effects. Real danger lies in these resistance genes being transferred between species to generate multidrug-resistant strains. But where do the genes conferring resistance arise, and how are they spread within our communities?
As previously discussed on mBiosphere, the agricultural sector is a major player in antibiotic exploitation, with resulting resistance development. This morning brings a session on antimicrobial resistance transmission in agricultural and food environments, beginning with Lance Price, who presented the use of genomic epidemiology to study the misuse of antibiotics in livestock. Price's research has focused on how antibiotic resistance genes originating in livestock can move into the human community through colonization of industrial slaughterhouse workers and through contaminated meat. E. coli is a common contaminant in livestock, and also the most common cause of urinary tract infections (UTIs). Price's work has tied some lineages (though not others) of UTI-causing E. coli to foodborne sources (which he refers to as foodborne UTIs, or FUTIs).
Jean-Yves Madec also tracks the movement of drug-resistant genes between humans, agriculture, and the environment, as well as the role of fruits and vegetables in the spread of these dangerous strains. He highlighted the role of globalization in spreading resistant strains and resistance genes, such as the transfer of mcr-1 from France to Tunesia in contaminated chickens. Antoine Andremont's work has shown that the spread of acquired resistance is tied to selection, and that the further away from selection (e.g., in remote areas), the fewer resistant isolates are present in local flora and fauna.
Globalization makes movement of these dangerous microbes faster and easier than ever before. Given the prevalence of extended-spectrum β-lactamases already in the food chain, it can seem futile to fight their spread, and Frank Aarestrup addressed the question of whether we have already lost this battle. Aarestrup claimed hope is not entirely lost, citing the previous decrease in antibiotic use in some agriculture sectors, such as the voluntary ban of cephalosporins in pig production, that has proven effective in reducing E. coli with extended-spectrum cephalosporinase in pigs.
The Case for Antimicrobial Stewardship
Rather than throwing in the towel, antimicrobial stewardship—the careful use of antimicrobial drugs with a goal of minimizing unnecessary use—is an option covered in several sessions during the conference. At a Saturday morning session, a panel discussed the current controversies surrounding antibiotic stewardship. Marc Leone and Jeroen Schouten debated antibiotic de-escalation (ADE) ($), a strategy to switch to narrower-spectrum antibiotics, as a means to decrease spread of multidrug-resistant bacteria. An ADE strategy may not offer direct savings from decreased drug administration but reduces the number of resistant bacterial isolates in the ICU. However, Schouten stressed the lack of high-quality data to support ADE, and instead urged a focus on early discontinuation strategy. Bojana Beovic spoke on the benefits of switching from intravenous to oral drug administration, which can shorten hospital stays. Clinicians often continue intravenous administration because they or their patients perceive this route to be more effective.This practice emphasizes the need to educate doctors and patients alike in order to optimize antibiotic stewardship programs.
The good news is that these nascent stewardship programs have had success in decreasing the spread of antibiotic resistance! A Saturday afternoon session on antibiotic stewardship success stories highlighted examples of clinical, patient, and agricultural settings where stewardship programs have had significant impact. Despite this evidence, the overall impact of stewardship programs remains controversial. Sunday morning, Matthew Samore and Bruce Lee discussed the use of mathematical modeling to predict the outcome of stewardship programs. Samore and Lee have predicted the impacts that a large-scale national intervention for antibiotic stewardship could have: their models estimate that the institution of such programs could avert nearly 620,000 hospital-acquired infections. Further, their research supports a greater effort across a group of interconnected health care facilities over independent efforts, demonstrating that treating stewardship programs like a public good, as proposed by ASM CEO Stefano Bertuzzi, is indeed the most effective way to control this problem.
Two sessions covered new therapies that may complement stewardship programs to protect efficacy of the antibiotics already in our arsenal. A Sunday morning session covered new antimicrobial agents in the pipeline. Presentations by Michael Pucci, Mel Spigelman, and Peter Warn discussed therapeutic developments for antibacterial, antituberculosis, and antifungal agents. Eric Desarbre described work on BAL30376, a molecule that combines a siderophore, monobactam, and two types of β-lactamase inhibitor molecules. This two-in-one strategy hopes to sensitize β-lactamase-resistant strains while simultaneously exposing the cells to the siderophore-borne antibiotic monobactam, a similar strategy covered in a previous mBiosphere blog post.
Antibiotic alternatives are also gaining in popularity as antibiotic efficacy wanes. Some of these alternative treatment strategies will be discussed in an afternoon session today. Robert Hancock will present his research on cationic peptides produced by the innate immune system as a potential strategy. Some of these small peptides have novel anti-biofilm properties that may confer them broad use in the clinic.
Antonio Degiandomenico presented bi-specific antibodies as a means to control bacterial infection, illustrating the anti-pseudomonal activity of the recently developed BiS2αPa and BiS3αPa constructs. Bi-specific antibodies, composed of two different antigen-recognition variable regions, have been used as cancer and antiviral strategies, and are now gaining popularity as potential antibacterial agents.
These Sunday sessions should have left ASM Microbe attendees hopeful that resistance issues can be addressed, given the right resources. A failure to enable this research would be catastrophic: recent reports by the Pew Charitable Trust and Wellcome Trust have highlighted the dangers of ignoring the increasing prevalence of antibiotic-resistant infections. In early June, ASM joined a long list of concerned organizations to send a letter to the U.S. Senate in support of the Promise for Antibiotics and Therapeutics for Health (PATH) Act. The PATH Act decreases regulatory hurdles related to clinical trial design, and may speed treatment for those with serious infections who currently have limited options.
Tomorrow’s Dispatches from ASM Microbe will cover the last full day of the conference, with a spotlight on issues surrounding emerging infectious diseases.