The number of antimicrobial-resistant Salmonella serotypes hasn’t increased drastically in recent years, but drug-resistant Salmonella continues to pose a public health threat in the United States, particularly as resistance spreads across classes of drugs, necessitates the use of more expensive drugs, makes treatment less effective, and, in worse-case scenarios, leaves infections untreatable. A recent Centers for Disease Control and Prevention study identified increasing resistance to a class of drugs called Cephalosporins, which are commonly used to treat severe Salmonella infections in adults and are the main drug of choice when treating children, for whom the fluoroquinolone class of drugs is not recommended. Currently, about five percent of Salmonella strains are resistant to Cephalosporins, mostly in cases of Salmonella Heidelberg and Salmonella Newport. Cephalosporin resistance is the biggest current issue in drug-resistant Salmonella, said Robert Tauxe, deputy director of the Division of Foodborne, Waterborne, and Environmental Diseases at the National Center for Emerging and Zoonotic Infectious Diseases at the CDC. Bhushan Jayarao, director of the Animal Diagnostic Lab at Pennsylvania State University, echoed that sentiment, adding that Salmonella Typhimurium and Salmonella Heidelberg are at risk of acquiring CTX-M resistance to cephalosporins. CTX-M is one form of the beta-lactamase enzymes that breaks down cephalosporins (which are used to treat severe Salmonella infections in humans) and thereby confers resistance to the bacteria that produces this enzyme. READY-TO-EAT MEAT The CDC study found that the main mechanism of resistance to cephalosporins is the production of beta-lactamases, which are enzymes that manage to inactivate the antimicrobial agent. Of concern to the researchers is the fact that the genes related to antimicrobial resistance are often mobile, moving between bacteria and Salmonella serotypes, humans and animals. “The same genes were seen in several different kinds of Salmonella and in Salmonella collected from meat, animal and human samples, which shows that this gene is now pretty widespread,” said Maria Karlsson, research microbiologist with the National Antimicrobial Resistance Surveillance team at CDC. “The Salmonella are sharing this gene.” Assessing the genetic structure of resistance to provide evidence that the exact same genes are flowing from animal to food to humans and between types of Salmonella is an advanced method of public-health surveillance and is something the CDC hopes to do more of in the future, Tauxe said. It is typically difficult to trace the transmission of Salmonella strains within and between animal and human populations because of the rapidly changing nature of resistance patterns in bacteria. However, researchers from Penn State recently developed a way to identify and track Salmonella Typhimurium as it evolves and spreads. The research centers on virulence genes and regions of the bacteria’s DNA called CRISPRs, short for clustered regularly interspaced short palindromic repeats. CRISPRs are present in a large number of foodborne pathogens and can be used to identify antibiotic-resistance patterns within Salmonella Typhimurium. The researchers chose to study resistance and spread within Salmonella Typhimurium because it is the most frequently isolated serotype in humans, food, animals and the environment. Information garnered from the study of Salmonella Typhimurium isolates is now being applied to other serotypes, including Kentucky, Heidelberg, Enteritidis and Infantis. Additionally, Penn State researchers are engaged in studying antimicrobial resistance in pathogens other than Salmonella that are significant to animal and human health. The research includes looking at mechanisms associated with antimicrobial resistance and undertaking genome sequence analysis in order to determine which genetic determinants, aside from antibiotic0resistant genes, influence the emergence of antibiotic resistance. “I am very certain that, in the next couple of years, we will be able to identify key global genetic determinants in bacteria that make them more susceptible or drug-resistant,” Jayarao said. “The science of genomics and proper interpretation of the genome data will truly be able to find and answer for us.” Drug resistance within serotype Salmonella Kentucky has largely increased overseas in recent years, posing a significant problem in Africa and the Middle East and sounding an alarm among researchers, food-safety professionals and public health specialists in the U.S. “If it comes to this country and gets into our poultry farms, we will run out of antibiotics to treat it,” said Susan Vaughn Grooters, food-safety research and policy associate at the Center for Science in the Public Interest. Improper agricultural use of antibiotics is often pegged as a main contributor to the problem of drug-resistant Salmonella, but other studies have failed to find evidence that these practices contribute to increased antibiotic resistance. Other theories for the development of resistance exist, such as improper use of antibiotics among humans, or even, as Jayarao noted, the spread of antibiotic-resistant clonal types not influenced by antibiotic use in animals or humans. “The most recent evidence is to suggest the spread of CTX-M resistance that was first observed in Indonesia, then in India, Pakistan and the Middle East, which then spread to Europe and very recently has emerged in Canada and the U.S.,” Jayarao said. Consumer awareness of resistance and a demand for transparency surrounding it is important, as is increased regulation regarding antibiotic use. “This is a public-health crisis and a key area for interest for CSPI and food-safety advocates and should be on the radar screen of consumers far above issues that have been getting more attention but are actually much less urgent,” Grooters said. “We have to act before it’s too late. It’s not if a multi-drug-resistant outbreak that’s too deadly to treat will occur, but when.”