Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 40 Records) |
Query Trace: Whichard J [original query] |
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Genomic analysis of azithromycin-resistant Salmonella from food animals at slaughter and processing, and retail meats, 2011-2021, United States
Ge B , Mukherjee S , Li C , Harrison LB , Hsu CH , Tran TT , Whichard JM , Dessai U , Singh R , Gilbert JM , Strain EA , McDermott PF , Zhao S . Microbiol Spectr 2023 e0348523 Macrolides of different ring sizes are critically important antimicrobials for human medicine and veterinary medicine, though the widely used 15-membered ring azithromycin in humans is not approved for use in veterinary medicine. We document here the emergence of azithromycin-resistant Salmonella among the NARMS culture collections between 2011 and 2021 in food animals and retail meats, some with co-resistance to ceftriaxone or decreased susceptibility to ciprofloxacin. We also provide insights into the underlying genetic mechanisms and genomic contexts, including the first report of a novel combination of azithromycin resistance determinants and the characterization of multidrug-resistant plasmids. Further, we highlight the emergence of a multidrug-resistant Salmonella Newport clone in food animals (mainly cattle) with both azithromycin resistance and decreased susceptibility to ciprofloxacin. These findings contribute to a better understating of azithromycin resistance mechanisms in Salmonella and warrant further investigations on the drivers behind the emergence of resistant clones. |
Multistate reptile- and amphibian-associated salmonellosis outbreaks in humans, United States, 20092018
Waltenburg MA , Perez A , Salah Z , Karp BE , Whichard J , Tolar B , Gollarza L , Koski L , Blackstock A , Basler C , Nichols M . Zoonoses Public Health 2022 69 (8) 925-937 Non-typhoidal Salmonella cause an estimated 1.4 million human illnesses, 26,000 hospitalizations and 400 deaths annually in the United States. Approximately 11% of these infections are attributed to animal contact. Reptiles and amphibians are known sources of salmonellosis; young children (aged <5 years) are disproportionately affected by reptile- and amphibian-associated salmonellosis (RAAS) outbreaks. We describe multistate RAAS outbreaks to characterize illnesses and inform prevention efforts. RAAS outbreaks were defined as ≥2 culture-confirmed human Salmonella infections with similar pulsed-field gel electrophoresis patterns and epidemiologic, laboratory or traceback evidence linking them to a common reptile/amphibian exposure. Data sources included the Animal Contact Outbreak Surveillance System; CDC Outbreak Response and Prevention Branch's outbreak management database; PulseNet, the national molecular subtyping network for foodborne disease surveillance in the United States; and the National Antimicrobial Resistance Monitoring System. Twenty-six RAAS outbreaks were reported during 2009–2018, resulting in 1465 illnesses and 306 hospitalizations. The outbreaks were associated with turtles (19), lizards (5), snakes (1) and frogs (1). Sixteen (61.5%) outbreaks were linked to small turtles (<4 inches), resulting in 914 illnesses. Forty-nine percent of outbreak-associated patients were aged <5 years. Of 362 patients/caregivers interviewed, 111 (30.7%) were aware that reptiles/amphibians can carry Salmonella. Among 267 patient isolates with antimicrobial susceptibility information, 20 (7.5%) were non-susceptible to ≥1 antibiotic used to treat human salmonellosis. RAAS outbreaks result in considerable morbidity, particularly among young children. Illnesses linked to small turtles are preventable through education, targeted outreach to caregivers and paediatricians, and when appropriate, enforcement. Historically, individual states and jurisdictions have enforced existing or promulgated new authorities to address outbreaks. Preventing future RAAS outbreaks requires addressing challenges related to the illegal sale/distribution of small turtles; and for legal reptile sales, providing information on RAAS risk to consumers at point of sale to support informed pet ownership decisions. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Zoonoses and Public Health published by Wiley-VCH GmbH. |
The Use of Whole-Genome Sequencing by the Federal Interagency Collaboration for Genomics for Food and Feed Safety in the United States.
Stevens EL , Carleton HA , Beal J , Tillman GE , Lindsey RL , Lauer AC , Pightling A , Jarvis KG , Ottesen A , Ramachandran P , Hintz L , Katz LS , Folster JP , Whichard JM , Trees E , Timme RE , McDermott P , Wolpert B , Bazaco M , Zhao S , Lindley S , Bruce BB , Griffin PM , Brown E , Allard M , Tallent S , Irvin K , Hoffmann M , Wise M , Tauxe R , Gerner-Smidt P , Simmons M , Kissler B , Defibaugh-Chavez S , Klimke W , Agarwala R , Lindsay J , Cook K , Austerman SR , Goldman D , McGarry S , Hale KR , Dessai U , Musser SM , Braden C . J Food Prot 2022 85 (5) 755-772 This multi-agency report developed under the Interagency Collaboration for Genomics for Food and Feed Safety (Gen-FS) provides an overview of the use of and transition to Whole-Genome Sequencing (WGS) technology to detect and characterize pathogens transmitted commonly by food and identify their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among federal agencies, including the National Institutes of Health (NIH); the Department of Health and Human Services' Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA); and the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS), Agricultural Research Service (ARS), and Animal and Plant Health Inspection Service (APHIS). We describe single nucleotide polymorphism (SNP), core-genome (cg) and whole-genome multi-locus sequence typing (wgMLST) data analysis methods as used in CDC's PulseNet and FDA's GenomeTrakr networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Gen-FS agency partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles), source attribution efforts, and increasing transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information (NCBI). Finally, we highlight the impact of current trends in the use of culture-independent diagnostics tests (CIDT) for human diagnostic testing on analytical approaches related to food safety. Lastly, we highlight what is next for WGS in food safety. |
One Health and antimicrobial resistance, a United States perspective
Bright-Ponte SJ , Walters BK , Tate H , Durso LM , Whichard JM , Bjork KE , Shivley CB , Beaudoin AL , Cook KL , Thacker EL , Singh R , Gilbert JM . Rev Sci Tech 2019 38 (1) 173-184 Antimicrobial drugs are a precious resource, responsible for saving millions of lives since their discovery. Unfortunately, some antimicrobials are rapidly losing their effectiveness due to the development and spread of antimicrobial resistance (AMR), a multi-faceted and complex problem affecting humans, animals, plants and the environment. While AMR is a global problem, in this paper, the authors briefly highlight some ongoing efforts in the United States of America aimed at integrating a One Health approach into policies and programmes that address this important health threat. |
National Antimicrobial Resistance Monitoring System: Two Decades of Advancing Public Health Through Integrated Surveillance of Antimicrobial Resistance.
Karp BE , Tate H , Plumblee JR , Dessai U , Whichard JM , Thacker EL , Robertson Hale K , Wilson W , Friedman CR , Griffin PM , McDermott PF . Foodborne Pathog Dis 2017 14 (10) 545-557 Drug-resistant bacterial infections pose a serious and growing public health threat globally. In this review, we describe the role of the National Antimicrobial Resistance Monitoring System (NARMS) in providing data that help address the resistance problem and show how such a program can have broad positive impacts on public health. NARMS was formed two decades ago to help assess the consequences to human health arising from the use of antimicrobial drugs in food animal production in the United States. A collaboration among the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the United States Department of Agriculture, and state and local health departments, NARMS uses an integrated "One Health" approach to monitor antimicrobial resistance in enteric bacteria from humans, retail meat, and food animals. NARMS has adapted to changing needs and threats by expanding surveillance catchment areas, examining new isolate sources, adding bacteria, adjusting sampling schemes, and modifying antimicrobial agents tested. NARMS data are not only essential for ensuring that antimicrobial drugs approved for food animals are used in ways that are safe for human health but they also help address broader food safety priorities. NARMS surveillance, applied research studies, and outbreak isolate testing provide data on the emergence of drug-resistant enteric bacteria; genetic mechanisms underlying resistance; movement of bacterial populations among humans, food, and food animals; and sources and outcomes of resistant and susceptible infections. These data can be used to guide and evaluate the impact of science-based policies, regulatory actions, antimicrobial stewardship initiatives, and other public health efforts aimed at preserving drug effectiveness, improving patient outcomes, and preventing infections. Many improvements have been made to NARMS over time and the program will continue to adapt to address emerging resistance threats, changes in clinical diagnostic practices, and new technologies, such as whole genome sequencing. |
Ceftriaxone-resistant nontyphoidal salmonella from humans, retail meats, and food animals in the United States, 1996-2013
Iwamoto M , Reynolds J , Karp BE , Tate H , Fedorka-Cray PJ , Plumblee JR , Hoekstra RM , Whichard JM , Mahon BE . Foodborne Pathog Dis 2016 14 (2) 74-83 BACKGROUND: Ceftriaxone resistance in Salmonella is a serious public health threat. Ceftriaxone is commonly used to treat severe Salmonella infections, especially in children. Identifying the sources and drivers of ceftriaxone resistance among nontyphoidal Salmonella is crucial. MATERIALS AND METHODS: The National Antimicrobial Resistance Monitoring System (NARMS) tracks antimicrobial resistance in foodborne and other enteric bacteria from humans, retail meats, and food animals. We examined NARMS data reported during 1996-2013 to characterize ceftriaxone-resistant Salmonella infections in humans. We used Spearman rank correlation to examine the relationships between the annual percentage of ceftriaxone resistance among Salmonella isolates from humans with isolates from retail meats and food animals. RESULTS: A total of 978 (2.9%) of 34,100 nontyphoidal Salmonella isolates from humans were resistant to ceftriaxone. Many (40%) ceftriaxone-resistant isolates were from children younger than 18 years. Most ceftriaxone-resistant isolates were one of three serotypes: Newport (40%), Typhimurium (26%), or Heidelberg (12%). All were resistant to other antimicrobials, and resistance varied by serotype. We found statistically significant correlations in ceftriaxone resistance between human and ground beef Newport isolates (r = 0.83), between human and cattle Typhimurium isolates (r = 0.57), between human and chicken Heidelberg isolates (r = 0.65), and between human and turkey Heidelberg isolates (r = 0.67). CONCLUSIONS: Ceftriaxone resistance among Salmonella Newport, Typhimurium, and Heidelberg isolates from humans strongly correlates with ceftriaxone resistance in isolates from ground beef, cattle, and poultry, respectively. These findings support other lines of evidence that food animals are important reservoirs of ceftriaxone-resistant Salmonella that cause human illness in the United States. |
Characterization of Resistance Genes and Plasmids from Outbreaks and Illness Clusters Caused by Salmonella Resistant to Ceftriaxone in the United States, 2011-2012.
Folster JP , Grass JE , Bicknese A , Taylor J , Friedman CR , Whichard JM . Microb Drug Resist 2016 23 (2) 188-193 Salmonella is an important cause of foodborne illness; however, quickly identifying the source of these infections can be difficult, and source identification is a crucial step in preventing additional illnesses. Although most infections are self-limited, invasive salmonellosis may require antimicrobial treatment. Ceftriaxone, an extended-spectrum cephalosporin, is commonly used for treatment of salmonellosis. Previous studies have identified a correlation between the food animal/retail meat source of ceftriaxone-resistant Salmonella and the type of resistance gene and plasmid it carries. In this study, we examined seven outbreaks of ceftriaxone-resistant Salmonella infections, caused by serotypes Typhimurium, Newport, Heidelberg, and Infantis. All isolates were positive for a plasmid-encoded blaCMY gene. Plasmid incompatibility typing identified five IncI1 and two IncA/C plasmids. Both outbreaks containing blaCMY-IncA/C plasmids were linked to consumption of cattle products. Three of five outbreaks with blaCMY-IncI1 (ST12) plasmids were linked to a poultry source. The remaining IncI1 outbreaks were associated with ground beef (ST20) and tomatoes (ST12). In addition, we examined isolates from five unsolved clusters of ceftriaxone-resistant Salmonella infections and used our plasmid-encoded gene findings to predict the source. Overall, we identified a likely association between the source of ceftriaxone-resistant Salmonella outbreaks and the type of resistance gene/plasmid it carries. |
Whole Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter.
Zhao S , Tyson GH , Chen Y , Li C , Mukherjee S , Young S , Lam C , Folster JP , Whichard JM , McDermott PF . Appl Environ Microbiol 2015 82 (2) 459-66 OBJECTIVES: The objectives of this study were to identify antimicrobial resistance genotypes for Campylobacter and to evaluate the correlation between resistance phenotypes and genotypes using in vitro antimicrobial susceptibility testing and whole-genome sequencing (WGS). METHODS: One hundred-fourteen Campylobacter sp. (82 C. coli and 32 C. jejuni) isolated from 2000-2013 from ill humans, retails meats and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth micro-dilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through BLASTx analysis. RESULTS: Eighteen resistance genes, including tetO, blaOXA-61, catA, lnuC, aph(2' ')-Ib, aph(2' ')-Ic, aph(2')-If, aph(2' ')-Ig, aph(2' ')-Ih, aac(6')-Ie/aph(2' ')-Ia, aac(6')-Ie/aph(2' ')-If, aac(6')-Im, aadE, sat4, ant(6'), aad9, aph(3')-Ic, aph(3')-IIIa, and mutations in two house-keeping genes (gyrA and 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin and ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. CONCLUSIONS: There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs. |
Identification and characterization of multidrug-resistant Salmonella enterica serotype Albert isolates in the United States.
Folster JP , Campbell D , Grass J , Brown AC , Bicknese A , Tolar B , Joseph LA , Plumblee JR , Walker C , Fedorka-Cray PJ , Whichard JM . Antimicrob Agents Chemother 2015 59 (5) 2774-9 Salmonella enterica is one of the most common causes of bacterial foodborne illness in the United States. Although most Salmonella infections are self-limiting, antimicrobial treatment is critical for invasive salmonellosis. Primary antimicrobial treatment options include fluoroquinolones or extended-spectrum cephalosporins and antimicrobial resistance to these drugs may complicate treatment. At present, Salmonella enterica is composed of more than 2,600 unique serotypes, which vary greatly in geographic prevalence, ecological niche, and ability to cause human disease and it is important to understand and mitigate the source of human infection, particularly when antimicrobial resistance is found. In this study, we identified and characterized 19 Salmonella enterica serotype Albert isolates from food animals, retail meat, and humans collected in the United States during 2005-2013. All 5 isolates from non-human sources were obtained from turkeys or ground turkey and epidemiologic data suggest poultry consumption or live poultry exposure as the probable source of infection. Salmonella ser. Albert also appears to be geographically localized to the Midwestern states of the U.S. All 19 isolates displayed multidrug resistance (MDR), including decreased susceptibility to fluoroquinolones and resistance to extended-spectrum cephalosporins. Turkeys are a likely source of multidrug resistant Salmonella Albert, and circulation of resistance plasmids, as opposed to expansion of a single resistant strain, is playing a role. More work is needed to understand why these resistance plasmids spread and how their presence and the serotype they reside in contribute to human disease. |
Outbreaks of Salmonella infections attributed to beef - United States, 1973-2011
Laufer AS , Grass J , Holt K , Whichard JM , Griffin PM , Gould LH . Epidemiol Infect 2014 143 (9) 1-11 Non-typhoidal Salmonella is estimated to be the most common bacterial cause of foodborne illness in the United States, causing an estimated one million domestically acquired foodborne illnesses annually. Recent, large outbreaks have highlighted the importance of ground beef as an important source of multidrug-resistant Salmonella. We analysed the epidemiology of salmonellosis outbreaks that were attributed to beef in the United States reported to the Centers for Disease Control and Prevention (CDC) from 1973 to 2011. During 1973-2011, of the 1965 outbreaks of Salmonella where a food vehicle was implicated, 96 were attributed to beef, accounting for 3684 illnesses. We observed a shift in the type of beef implicated in salmonellosis outbreaks, from roast to ground beef. Delicatessen-style roast beef cooked in commercial processing establishments was the predominant type during the 1970s and early 1980s; regulations on cooking and processing essentially eliminated this problem by 1987. Ground beef emerged as an important vehicle in the 2000s; it was implicated in 17 (45%) of the 38 beef-attributed outbreaks reported during 2002-2011. Although this emergence was likely due in part to increased participation in CDC's PulseNet, which was established in 1996, and proactive decisions by the United States Department of Agriculture's Food Safety and Inspection Service, stronger measures are needed to decrease contamination of ground beef with Salmonella. |
Comparative genomic analysis and virulence differences in closely related salmonella enterica serotype heidelberg isolates from humans, retail meats, and animals.
Hoffmann M , Zhao S , Pettengill J , Luo Y , Monday SR , Abbott J , Ayers SL , Cinar HN , Muruvanda T , Li C , Allard MW , Whichard J , Meng J , Brown EW , McDermott PF . Genome Biol Evol 2014 6 (5) 1046-68 Salmonella enterica subsp. enterica serovar Heidelberg (S. Heidelberg) is one of the top serovars causing human salmonellosis. Recently, an antibiotic-resistant strain of this serovar was implicated in a large 2011 multistate outbreak resulting from consumption of contaminated ground turkey that involved 136 confirmed cases, with one death. In this study, we assessed the evolutionary diversity of 44 S. Heidelberg isolates using whole-genome sequencing (WGS) generated by the 454 GS FLX (Roche) platform. The isolates, including 30 with nearly indistinguishable (one band difference) Xbal pulsed-field gel electrophoresis patterns (JF6X01.0032, JF6X01.0058), were collected from various sources between 1982 and 2011 and included nine isolates associated with the 2011 outbreak. Additionally, we determined the complete sequence for the chromosome and three plasmids from a clinical isolate associated with the 2011 outbreak using the Pacific Biosciences (PacBio) system. Using single-nucleotide polymorphism (SNP) analyses, we were able to distinguish highly clonal isolates, including strains isolated at different times in the same year. The isolates from the recent 2011 outbreak clustered together with a mean SNP variation of only 17 SNPs. The S. Heidelberg isolates carried a variety of phages, such as prophage P22, P4, lambda-like prophage Gifsy-2, and the P2-like phage which carries the sopE1 gene, virulence genes including 62 pathogenicity, and 13 fimbrial markers and resistance plasmids of the incompatibility (Inc)I1, IncA/C, and IncHI2 groups. Twenty-one strains contained an IncX plasmid carrying a type IV secretion system. On the basis of the recent and historical isolates used in this study, our results demonstrated that, in addition to providing detailed genetic information for the isolates, WGS can identify SNP targets that can be utilized for differentiating highly clonal S. Heidelberg isolates. |
Quinolone-resistant Salmonella enterica serotype Enteritidis infections associated with international travel
O'Donnell AT , Vieira AR , Huang JY , Whichard J , Cole D , Karp BE . Clin Infect Dis 2014 59 (9) e139-41 We found a strong association between nalidixic acid (NA)-resistant Salmonella serotype Enteritidis (SE) infections in the United States and recent international travel. |
Changing plasmid types responsible for extended-spectrum cephalosporin resistance in Escherichia coli O157:H7 in the USA, 1996-2009
Folster JP , Pecic G , Stroika S , Rickert R , Whichard JM . J Glob Antimicrob Resist 2014 2 (2) 87-91 Escherichia coli O157 is a major cause of food-borne illness. Plasmids are genetic elements that mobilise antimicrobial resistance determinants, including blaCMY beta-lactamases that confer resistance to extended-spectrum cephalosporins (ESCs). ESCs are important for treating a variety of infections. IncA/C plasmids are found among diverse sources, including cattle, the principal source of E. coli O157 infections in humans. IncI1 plasmids are common among E. coli and Salmonella from poultry and other avian sources. To broaden our understanding of the reservoirs of blaCMY, the types of plasmids carrying blaCMY among E. coli O157 were determined. From 1996 to 2009, 3742 E. coli O157 isolates were tested. Eleven isolates (0.29%) were ceftriaxone-resistant and had a blaCMY-2-containing plasmid. All four isolates submitted before 2001 as well as a single 2001 isolate had bla CMY encoded on IncA/C plasmids, whilst all five isolates submitted after 2001 and a single 2001 isolate had blaCMY carried on IncI1 plasmids. The IncI1 plasmids were ST2, ST20 and ST23. We conclude that cephalosporin resistance among E. coli O157:H7 is due to plasmid-encoded blaCMY genes and that plasmid types appear to have shifted from IncA/C to IncI1. This shift suggests either a change in plasmid type among animal reservoirs or that the organism has expanded into avian reservoirs. More analysis of human, retail meat and food animal isolates is necessary to broaden our understanding of the antimicrobial resistance determinants of ESC resistance among E. coli O157. |
Fluoroquinolone susceptibility testing of Salmonella enterica: detection of acquired resistance and selection of zone diameter breakpoints for levofloxacin and ofloxacin
Sjolund-Karlsson M , Howie RL , Crump JA , Whichard JM . J Clin Microbiol 2014 52 (3) 877-84 Fluoroquinolones (e.g., ciprofloxacin) have become a mainstay for treating severe Salmonella infections in adults. Fluoroquinolone resistance in Salmonella is mostly due to mutations in the topoisomerase genes, but plasmid-mediated quinolone resistance (PMQR) mechanisms have also been described. In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised the ciprofloxacin interpretive criteria (breakpoints) for disk diffusion and MIC test methods for Salmonella. In 2013, the CLSI published MIC breakpoints for Salmonella to levofloxacin and ofloxacin, but breakpoints for assigning disk diffusion results to susceptible (S), intermediate (I), and resistant (R) categories are still needed. In this study, the MICs and inhibition zone diameters for nalidixic acid, ciprofloxacin, levofloxacin, and ofloxacin were determined for 100 clinical isolates of nontyphi Salmonella with or without resistance mechanisms. We confirmed that the new levofloxacin MIC breakpoints resulted in the highest category agreement (94%) when plotted against the ciprofloxacin MICs and that the new ofloxacin MIC breakpoints resulted in 92% category agreement between ofloxacin and ciprofloxacin. By applying the new MIC breakpoints in the MIC zone scattergrams for levofloxacin and ofloxacin, the following disk diffusion breakpoints generated the least number of errors: ≥28 mm (S), 19 to 27 mm (I), and ≤18 mm (R) for levofloxacin and ≥25 mm (S), 16 to 24 mm (I), and ≤15 mm (R) for ofloxacin. Neither the levofloxacin nor the ofloxacin disk yielded good separation of isolates with and without resistance mechanisms. Further studies will be needed to develop a disk diffusion assay that efficiently detects all isolates with acquired resistance to fluoroquinolones. |
Characterization of blaCMY plasmids and their possible role in source attribution of Salmonella enterica serotype typhimurium infections
Folster JP , Tolar B , Pecic G , Sheehan D , Rickert R , Hise K , Zhao S , Fedorka-Cray PJ , McDermott P , Whichard JM . Foodborne Pathog Dis 2014 11 (4) 301-6 Salmonella is an important cause of foodborne illness; however, identifying the source of these infections can be difficult. This is especially true for Salmonella serotype Typhimurium, which is found in diverse agricultural niches. Extended-spectrum cephalosporins (ESC) are one of the primary treatment choices for complicated Salmonella infections. In Salmonella, ESC resistance in the United States is mainly mediated by blaCMY genes carried on various plasmids. In this study, we examined whether the characterization of blaCMY plasmids, along with additional information, can help us identify potential sources of infection by Salmonella, and used serotype Typhimurium as a model. In the United States, monitoring of retail meat, food animals, and ill persons for antimicrobial-resistant Salmonella is conducted by the National Antimicrobial Resistance Monitoring System. In 2008, 70 isolates (70/581; 12.0%) (34 isolates from retail meat, 23 food animal, and 13 human) were resistant to ceftriaxone and amoxicillin/clavulanic acid. All were polymerase chain reaction (PCR)-positive for blaCMY and 59/70 (84.3%) of these genes were plasmid encoded. PCR-based replicon typing identified 42/59 (71.2%) IncI1-blaCMY plasmids and 17/59 (28.8%) IncA/C-blaCMY plasmids. Isolates from chickens or chicken products with blaCMY plasmids primarily had IncI1-blaCMY plasmids (37/40; 92.5%), while all isolates from cattle had IncA/C-blaCMY plasmids. Isolates from humans had either IncA/C- blaCMY (n=8/12; [66.7%]) or IncI1- blaCMY (n=4/12 [33.3%]) plasmids. All of the IncI1-blaCMY plasmids were ST12 or were closely related to ST12. Antimicrobial susceptibility patterns (AST) and pulsed-field gel electrophoresis (PFGE) patterns of the isolates were also compared and differences were identified between isolate sources. When the source of a Typhimurium outbreak or sporadic illness is unknown, characterizing the outbreak isolate's blaCMY plasmids, AST, and PFGE patterns may help identify it. |
Increase in resistance to ceftriaxone and nonsusceptibility to ciprofloxacin and decrease in multidrug resistance among Salmonella strains, United States, 1996-2009
Medalla F , Hoekstra RM , Whichard JM , Barzilay EJ , Chiller TM , Joyce K , Rickert R , Krueger A , Stuart A , Griffin PM . Foodborne Pathog Dis 2013 10 (4) 302-9 BACKGROUND: Salmonella is a major bacterial pathogen transmitted commonly through food. Increasing resistance to antimicrobial agents (e.g., ceftriaxone, ciprofloxacin) used to treat serious Salmonella infections threatens the utility of these agents. Infection with antimicrobial-resistant Salmonella has been associated with increased risk of severe infection, hospitalization, and death. We describe changes in antimicrobial resistance among nontyphoidal Salmonella in the United States from 1996 through 2009. METHODS: The Centers for Disease Control and Prevention's National Antimicrobial Resistance Monitoring System conducts surveillance of resistance among Salmonella isolated from humans. From 1996 through 2009, public health laboratories submitted isolates for antimicrobial susceptibility testing. We used interpretive criteria from the Clinical and Laboratory Standards Institute and defined isolates with ciprofloxacin resistance or intermediate susceptibility as nonsusceptible to ciprofloxacin. Using logistic regression, we modeled annual data to assess changes in antimicrobial resistance. RESULTS: From 1996 through 2009, the percentage of nontyphoidal Salmonella isolates resistant to ceftriaxone increased from 0.2% to 3.4% (odds ratio [OR]=20, 95% confidence interval [CI] 6.3-64), and the percentage with nonsusceptibility to ciprofloxacin increased from 0.4% to 2.4% (OR=8.3, 95% CI 3.3-21). The percentage of isolates that were multidrug resistant (resistant to ≥3 antimicrobial classes) decreased from 17% to 9.6% (OR=0.6, 95% CI 0.5-0.7), which was driven mainly by a decline among serotype Typhimurium. However, multidrug resistance increased from 5.9% in 1996 to a peak of 31% in 2001 among serotype Newport and increased from 12% in 1996 to 26% in 2009 (OR=2.6, 95% CI 1.1-6.2) among serotype Heidelberg. CONCLUSIONS: We describe an increase in resistance to ceftriaxone and nonsusceptibility to ciprofloxacin and an overall decline in multidrug resistance. Trends varied by serotype. Because of evidence that antimicrobial resistance among Salmonella is predominantly a consequence of antimicrobial use in food animals, efforts are needed to reduce unnecessary use, especially of critically important agents. |
Occurrence of ß-lactamase genes among non-Typhi Salmonella enterica isolated from humans, food animals, and retail meats in the United States and Canada.
Sjolund-Karlsson M , Howie RL , Blickenstaff K , Boerlin P , Ball T , Chalmers G , Duval B , Haro J , Rickert R , Zhao S , Fedorka-Cray PJ , Whichard JM . Microb Drug Resist 2013 19 (3) 191-7 Non-Typhi Salmonella cause over 1.7 million cases of gastroenteritis in North America each year, and food-animal products are commonly implicated in human infections. For invasive infections, antimicrobial therapy is indicated. In North America, the antimicrobial susceptibility of Salmonella is monitored by the U.S. National Antimicrobial Resistance Monitoring System (NARMS) and The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). In this study, we determined the susceptibility to cephalosporins by broth microdilution among 5,041 non-Typhi Salmonella enterica isolated from food animals, retail meats, and humans. In the United States, 109 (4.6%) of isolates collected from humans, 77 (15.7%) from retail meat, and 140 (10.6%) from food animals displayed decreased susceptibility to cephalosporins (DSC). Among the Canadian retail meat and food animal isolates, 52 (13.0%) and 42 (9.4%) displayed DSC. All isolates displaying DSC were screened for beta-lactamase genes (bla(TEM), bla(SHV), bla(CMY), bla(CTX-M), and bla(OXA-1)) by polymerase chain reaction. At least one beta-lactamase gene was detected in 74/109 (67.9%) isolates collected from humans, and the bla(CMY) genes were most prevalent (69/109; 63.3%). Similarly, the bla(CMY) genes predominated among the beta-lactamase-producing isolates collected from retail meats and food animals. Three isolates from humans harbored a bla(CTX-M-15) gene. No animal or retail meat isolates harbored a bla(CTX-M) or bla(OXA-1) gene. A bla(TEM) gene was found in 5 human, 9 retail meat, and 17 animal isolates. Although serotype distributions varied among human, retail meat, and animal sources, overlap in bla(CMY)-positive serotypes across sample sources supports meat and food-animal sources as reservoirs for human infection. |
Outbreak of infections caused by Shigella sonnei with reduced susceptibility to azithromycin, United States
Sjolund Karlsson M , Bowen A , Reporter R , Folster JP , Grass JE , Howie RL , Taylor J , Whichard JM . Antimicrob Agents Chemother 2012 57 (3) 1559-60 Shigellosis is the third most common enteric bacterial infection in the United States (9).... |
Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and humans in the United States 2009
Folster JP , Pecic G , Singh A , Duval B , Rickert R , Ayers S , Abbott J , McGlinchey B , Bauer-Turpin J , Haro J , Hise K , Zhao S , Fedorka-Cray PJ , Whichard J , McDermott PF . Foodborne Pathog Dis 2012 9 (7) 638-45 Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) beta-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion. |
Characterization of multi-drug resistant Salmonella enterica serovar Heidelberg from a ground turkey-associated outbreak in the United States, 2011
Folster JP , Pecic G , Rickert R , Taylor J , Zhao S , Fedorka-Cray PL , Whichard J , McDermott P . Antimicrob Agents Chemother 2012 56 (6) 3465-6 Salmonella serotype Heidelberg is the fifth most common serotype that causes human disease in the United States and appears to be more invasive than other nontyphoidal serotypes (3, 6).... |
Drug-resistance mechanisms in Vibrio cholerae O1 outbreak strain, Haiti, 2010.
Sjolund-Karlsson M , Reimer A , Folster JP , Walker M , Dahourou GA , Batra DG , Martin I , Joyce K , Parsons MB , Boncy J , Whichard JM , Gilmour MW . Emerg Infect Dis 2011 17 (11) 2151-2154 To increase understanding of drug-resistant Vibrio cholerae, we studied selected molecular mechanisms of antimicrobial drug resistance in the 2010 Haiti V. cholerae outbreak strain. Most resistance resulted from acquired genes located on an integrating conjugative element showing high homology to an integrating conjugative element identified in a V. cholerae isolate from India. |
Characterization of isolates from a multi-drug resistant outbreak of Shiga toxin-producing Escherichia coli O145 infections in the United States
Folster JP , Pecic G , Taylor E , Whichard J . Antimicrob Agents Chemother 2011 55 (12) 5955-6 Shiga toxin-producing Escherichia coli (STEC) is an important cause of foodborne illness and several outbreaks of non-O157 serotype infections have been reported recently (10, 17).... |
International spread of an epidemic population of Salmonella enterica serotype Kentucky ST198 resistant to ciprofloxacin
Le Hello S , Hendriksen RS , Doublet B , Fisher I , Nielsen EM , Whichard JM , Bouchrif B , Fashae K , Granier SA , Jourdan-Da Silva N , Cloeckaert A , Threlfall EJ , Angulo FJ , Aarestrup FM , Wain J , Weill FX . J Infect Dis 2011 204 (5) 675-84 National Salmonella surveillance systems from France, England and Wales, Denmark, and the United States identified the recent emergence of multidrug-resistant isolates of Salmonella enterica serotype Kentucky displaying high-level resistance to ciprofloxacin. A total of 489 human cases were identified during the period from 2002 (3 cases) to 2008 (174 cases). These isolates belonged to a single clone defined by the multilocus sequence type ST198, the XbaI-pulsed-field gel electrophoresis cluster X1, and the presence of the Salmonella genomic island 1 variant SGI1-K. This clone was probably selected in 3 steps in Egypt during the 1990s and the early 2000s and has now spread to several countries in Africa and, more recently, in the Middle East. Poultry has been identified as a potential major vehicle for infection by this clone. Continued surveillance and appropriate control measures should be implemented by national and international authorities to limit the spread of this strain. (See the editorial commentary by Hedberg, on pages 665-6.) |
Characterization of bla(CMY)-encoding plasmids among Salmonella isolated in the United States in 2007
Folster JP , Pecic G , McCullough A , Rickert R , Whichard JM . Foodborne Pathog Dis 2011 8 (12) 1289-94 Salmonella enterica is one of the most common bacterial causes of foodborne illness, and nontyphoidal Salmonella is estimated to cause approximately 1.2 million illnesses in the United States each year. Plasmids are mobile genetic elements that play a critical role in the dissemination of antimicrobial resistance determinants. AmpC-type CMY beta-lactamases (bla(CMY)) confer resistance to extended-spectrum cephalosporins and beta-lactam/beta-lactamase inhibitor combinations and are commonly plasmid-encoded. A variety of plasmids have been shown to encode CMY beta-lactamases and certain plasmids may be associated with particular Salmonella serotypes or environmental sources. In this study, we characterized bla(CMY) beta-lactamase-encoding plasmids among Salmonella isolates. Isolates of Salmonella from specimens collected from humans in 2007 were submitted to the Centers for Disease Control and Prevention National Antimicrobial Resistance Monitoring System laboratory for susceptibility testing. Three percent (65/2161) of Salmonella isolates displayed resistance to ceftriaxone (minimum inhibitory concentration [MIC] ≥4 mg/L) and amoxicillin/clavulanic acid (MIC ≥32 mg/L), a combination associated with the presence of a bla(CMY) mechanism of resistance. Sixty-four (98.5%) isolates were polymerase chain reaction-positive for bla(CMY) genes. Transformation and conjugation studies showed that 95% (61/64) of the bla(CMY) genes were plasmid-encoded. Most of the bla(CMY)-positive isolates were serotype Typhimurium, Newport, Heidelberg, and Agona. Forty-three plasmids were replicon type IncA/C, 15 IncI1, 2 contained multiple replicon loci, and 1 was untypeable. IncI1 plasmids conferred only the bla(CMY)-associated resistance phenotype, whereas IncA/C plasmids conferred additional multi-drug resistance (MDR) phenotypes to drugs such as chloramphenicol, sulfisoxazole, and tetracycline. Most of the IncI1 plasmids (12/15) were sequence type 12 by plasmid multi-locus sequence typing. CMY beta-lactamase-encoding plasmids among human isolates of Salmonella in the United States tended to be large MDR IncA/C plasmids or single resistance determinant IncI1 plasmids. In general, IncI1 plasmids were identified among serotypes commonly associated with poultry, whereas IncA/C plasmids were more likely to be identified among cattle/beef-associated serotypes. |
Antimicrobial susceptibility to azithromycin among Salmonella enterica isolated in the United States
Sjolund-Karlsson M , Joyce K , Blickenstaff K , Ball T , Haro J , Medalla FM , Fedorka-Cray P , Zhao S , Crump JA , Whichard JM . Antimicrob Agents Chemother 2011 55 (9) 3985-9 Due to emerging resistance to traditional antimicrobial agents such as ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from humans, food animals and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy two Salmonella enterica serotype Typhi isolated from humans were also tested. For each isolate, minimum inhibitory concentrations (MICs) to azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-Typhi Salmonella isolates, azithromycin MICs among human isolates ranged from 1-32 mcg/mL whereas the MICs among the animal and retail meat isolates ranged from 2-16 mcg/mL and 4-16 mcg/mL, respectively. Among Salmonella ser. Typhi isolates the azithromycin MICs ranged from 4-16 mcg/mL. The highest MIC observed in the present study was 32 mug/mL and was detected in three isolates from humans belonging to serotypes Kentucky, Montevideo and Paratyphi A. Based on our findings, we propose an epidemiological cut-off value (ECOFF) of wild type ≤ 16 mcg/mL for azithromycin and Salmonella. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin and Salmonella enterica. |
Ciprofloxacin-resistant Salmonella enterica serotype Typhi, United States, 1999-2008
Medalla F , Sjolund-Karlsson M , Shin SH , Harvey E , Joyce K , Theobald L , Nygren BL , Pecic G , Gay K , Austin J , Stuart A , Blanton E , Mintz ED , Whichard JM , Barzilay EJ . Emerg Infect Dis 2011 17 (6) 1095-1098 We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999-2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset. |
Decreased susceptibility to ciprofloxacin among Shigella isolated in the United States 2006-2009
Folster JP , Pecic G , Bowen A , Rickert R , Carattoli A , Whichard JM . Antimicrob Agents Chemother 2011 55 (4) 1758-60 We characterized 20 Shigella isolates with decreased susceptibility to fluoroquinolones. Most patients (80%) from whom a travel history was obtained reported travel to South or Southeast Asia. Mutations within the quinolone resistance determining regions of gyrA and parC and plasmid-mediated resistance determinants (qnrB, qnrS, aac(6')-Ib-cr) were identified. The rise in antimicrobial resistance among Shigella may necessitate the increased use of extended-spectrum cephalosporins or macrolides in some patients. |
CTX-M-producing non-Typhi Salmonella spp. isolated from humans, United States
Sjolund-Karlsson M , Howie R , Krueger A , Rickert R , Pecic G , Lupoli K , Folster JP , Whichard JM . Emerg Infect Dis 2011 17 (1) 97-9 CTX-M-type Beta-lactamases are increasing among US Enterobacteriaceae isolates. Of 2,165 non-Typhi Salmonella isolates submitted in 2007 to the National Antimicrobial Resistance Monitoring System, 100 (4.6%) displayed elevated MICs (≥2 mg/L) of ceftriaxone or ceftiofur. Three isolates (serotypes Typhimurium, Concord, and I 4,5,12:i:-) contained blaCTX-M-5, blaCTX-M-15, and blaCTX-M-55/57, respectively. |
Antimicrobial resistance among invasive nontyphoidal Salmonella enterica in the United States, National Antimicrobial Resistance Monitoring System, 1996-2007
Crump JA , Medalla FM , Joyce KW , Krueger AL , Hoekstra RM , Whichard JM , Barzilay EJ . Antimicrob Agents Chemother 2011 55 (3) 1148-54 Nontyphoidal salmonellae (NTS) are important causes of community-acquired bloodstream infection. We describe patterns of antimicrobial resistance among invasive NTS in the United States. We compared bloodstream NTS isolates with those from stool submitted to the National Antimicrobial Resistance Monitoring System (NARMS) from 1996-2007. We described antimicrobial resistance among invasive strains by serogroup and serotype. Of the 19,302 NTS, 17,804 (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream isolates. The median age (range) of patients with and without bacteremia was 36 (0, 97) years and 20 (0, 105) years, respectively (p<0.001). Males (OR 1.21, 95% CI 1.06, 1.38) and those aged ≥65 years were at greater risk for invasive disease. Enteritidis, Typhimurium, and Heidelberg were the most common serotypes isolated from blood; Dublin, Sandiego, and Schwarzengrund were associated with the greatest risk for bloodstream isolation. Of invasive isolates 208 (19.8%) were resistant to ampicillin, 117 (11.1%) to chloramphenicol, and 26 (2.5%) to trimethoprim-sulfamethoxazole; 28 (2.7%) isolates were resistant to nalidixic acid and 26 (2.5%) to ceftriaxone. Antimicrobial resistance to traditional agents is common. However, the occurrence of nalidixic acid and ceftriaxone resistance among invasive NTS is cause for clinical and public health vigilance. |
Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States
Sjolund-Karlsson M , Rickert R , Matar C , Pecic G , Howie RL , Joyce K , Medalla F , Barzilay EJ , Whichard JM . Foodborne Pathog Dis 2010 7 (12) 1503-9 OBJECTIVE: We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a beta-lactamase. METHODS: In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of beta-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli. RESULTS: Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more beta-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC beta-lactamase gene bla(CMY.) Other beta-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines. CONCLUSIONS: Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase beta-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae. |
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