When President Trump signed the Consolidated Appropriations Act 2019 into law last month, the bill provided the U.S. Food and Drug Administration (FDA) with “$500,000 to test Antibiotic Resistance in Imported Seafood.” By specifically funding a testing program, Congress emphasized the importance of detecting and monitoring antimicrobial pathogens on imported seafood, including shrimp. 

Congress’s creation of a new testing program coincides with the publication of two academic studies highlighting the rapid rate at which antibiotic resistance genes spread in aquaculture.

The first study found that the use of antibiotics in aquaculture feed may actually increase the presence and spread of antibiotic-resistant genes in the digestive tracks of farm-raised fish.

The second study described a novel way to combat a new antimicrobial-resistant gene discovered on bacteria taken from Indian shrimp that is otherwise “very resistant” to a popular “front line, last resort” antibiotic. The lead author of the study called the presence of the antimicrobial-resistant gene “alarming” because “here it is sitting on shrimp that people are eating.” The study reported that the antimicrobial-resistant gene at issue was just one of a handful of similar genes that have emerged from India.

For the United States, the continued significant growth in shrimp imports from India increases the risk posed by antibiotic resistant pathogens on seafood. India supplied roughly two out of every five pounds of imported shrimp consumed in this country last year. India also supplied half of the shrimp entry lines rejected by the FDA due to veterinary drug residues and due to the presence of salmonella.

In just the first two months of 2019, the FDA refused twenty-six (26) entry lines of Indian shrimp for reasons related to banned antibiotics and another seven (7) entry lines of Indian shrimp for reasons related to salmonella.

Antibiotics Administered Through Feed in Aquaculture May Help Develop Antibiotic- Resistant Genes in the Digestive Tracks of Fish

In a study published in the journal Microbiome, nine researchers from educational institutions in Germany, Denmark, and Brazil conducted an experiment to investigate the presence and spread of antibiotic resistant genes (ARGs) and mobile genetic elements (MGEs). They looked at the gut microbiome of Piaractus mesopotamicus (pacu) that had been treated with florfenicol, “a broad-spectrum fluorine derivative of chloramphenicol frequently used in aquaculture . . .” As the study explains, in the past, the presence and mobility of ARGs and MGEs had been tested by scientists in fish feces, fishmeal, and sediments of aquaculture sites. 

Dr. Michael Schloter, the head of the Research Unit for Comparative Microbiome Analyses (COMI) at HelmholtzZentrum münchen (Germany), and his multinational team analyzed the consequences of oral administration of the antibiotic florfenicol through the pacu’s feed for 34 days. 

The team took samples straight from the digestive tracts of these fish to test for relevant genetic changes in their gut bacteria. These samples indicated that, under stress, there was “an increased potential for the mobilization of ARGs during the antibiotic exposure.” 

The results of the experiment found that administration of the antibiotic caused a spike in the genes responsible for resistance to that antibiotic. 

It is generally believed that pieces of DNA called plasmids are the main reason why genes become resistant to antibiotics. Based on the results of this experiment, the research team concluded that resistance is also spread between bacteria without the involvement of plasmid. 

The researchers noted, “our study highlights the risk of using in-feed antibiotic during aquaculture production due to the potential increase of ARG mobilization and dispersion.” In a press release regarding the study, Dr. Schloter observed: 

“[O]ur data certainly lead us to question whether and to what extent we should continue to use antibiotics in the world’s increasing number of aquacultures.”

Novel Strategy Developed to Combat New Antimicrobial-Resistant Genes Coming Out of India

In another study, a team of Canadian researchers from the Public Health Agency of Canada, the University of Manitoba, and Simon Fraser University addressed potential responses to the emergence of a new antimicrobial-resistance gene, VCC-1. 

As explained in the study, VCC-1, a β-lactamase gene, was discovered in 2015, in Vibrio cholerae bacteria found on shrimp imported from India into Canada that was being sold in a Canadian grocery store. “β-lactamase genes code for enzymes that can break down β-lactams, which are a critically important class of antimicrobials.” The study notes that VCC-1 is just one of a handful of β-lactamase genes that have emerged from India.

The researchers explained that VCC-1 was found in a non-toxogenic strain of Vibrio cholerae on the shrimp from India and was additionally found in non-toxogenic Vibrio cholerae off of the German coastline. “The danger is that it’s a short jump from non-toxogenic V. cholerae to its toxogenic siblings.” 

VCC-1 is “very resistant” to carbapenem, a “front line, last resort” antibiotic according to the study. The lead author of the study, Brian Mark, PhD, Professor, Department of Microbiology, University of Manitoba, observed that VCC-1’s resistance to carbapenem was “alarming” because “here it is sitting on shrimp that people are eating.”

Professor Mark’s research team found that the introduction of avibactam blocked the antibiotic-resistant enzyme in VCC-1. As Professor Mark explains, “[I]f you add avibactam to the carbapenem, it becomes really potent, because you blocked the VCC-1, which was enabling resistance.” 

The study also reported that the FDA had recently approved a combination drug containing avibactam and another antibiotic, ceftazidime.

This study was a follow-up to an article published by officials at the National Microbiology Laboratory of the Public Health Agency of Canada and the Centre for Food-Borne,

Environmental, and Zoonotic Infectious Diseases three years ago. That earlier article reported “the discovery of a novel Ambler class A carbapenemase that was identified in a nontoxigenic strain of Vibrio cholera (N14-02106) isolated from shrimp that was sold for human consumption in Canada.” 

The prior article observed that “[t]he presence of VCC-1 in a V. cholerae isolate found in frozen shrimp could result in distribution through the food chain across wide geographical areas and population groups.” Further, the article explained that:

“The isolate was from a farmed shrimp from India, where limited control of antimicrobial use encourages the emergence of multidrug-resistant organisms both in the environment and in health care settings.”

Overall, the Canadian officials emphasized the importance of the operation of surveillance systems to detect and monitor the spread of antimicrobial resistant pathogens: “One of the core goals of the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) is to monitor major meat commodities for antimicrobial resistance. The authors concluded their article by starkly warning that:

“[T]his work highlights the need for inclusion of food and, possibly, environmental sources in antimicrobial resistance surveillance, as we will likely see an increase in the diversity of carbapenemases. Understanding and tracking of the potential spread from the environment into the clinic will be important for future infection control measures.”

Read More About the Scientific Studies and Congress’s Mandate to FDA

Read the study “Oral Administration of Antibiotics Increased the Potential Mobility of Bacterial Resistance Genes in the Gut of the Fish Piaractus Mesopotamicus,” Microbiome (Feb. 2019) 7:24 here: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-019-0632-7

Read the HelmhotzZentrum münchen’s German Research Center for Environmental Health’s press release “Antibiotic Resistances Spread Faster than So Far Thought” (Feb. 18, 2019) here: https://www.helmholtz-muenchen.de/en/aktuelles/latest-news/press-information-news/article/45924/index.html

Find the study “Molecular Basis for the Potent Inhibition of the Emerging Carbapenemase VCC-1 by Avibactam,” Antimicrobial Agents and Chemotherapy (Feb. 2019) here: https://aac.asm.org/content/early/2019/01/24/AAC.02112-18

Read the American Society for Microbiology’s press release “Investigators Figure Out How to Block New Antibiotic Resistance Gene” (Feb. 19, 2019) here: https://www.asm.org/Press-Releases/Investigators-Figure-Out-How-to-Block-New-Antibiot

Read the study “Characterization of VCC-1, a Novel Ambler Class A Carbapenemase from Vibrio Cholerae Isolated from Imported Retail Shrimp Sold in Canada,” Antimicrobial Agents and Chemotherapy (Feb. 2016) here: https://aac.asm.org/content/60/3/1819

Review the Conference Report accompanying the Consolidated Appropriations Act 2019 here:  https://www.congress.gov/116/crpt/hrpt9/CRPT-116hrpt9.pdf