Clinical Outcomes of Patients With Nontyphoidal Salmonella Infections by Isolate Resistance-Foodborne Diseases Active Surveillance Network, 10 US Sites, 2004-2018.

BACKGROUND: Nontyphoidal Salmonella causes an estimated 1.35 million US infections annually. Antimicrobial-resistant strains are a serious public health threat. We examined the association between resistance and the clinical outcomes of hospitalization, length-of-stay ≥3 days, and death. METHODS: We linked epidemiologic data from the Foodborne Diseases Active Surveillance Network with antimicrobial resistance data from the National Antimicrobial Resistance Monitoring System (NARMS) for nontyphoidal Salmonella infections from 2004 to 2018. We defined any resistance as resistance to ≥1 antimicrobial and clinical resistance as resistance to ampicillin, azithromycin, ceftriaxone, ciprofloxacin, or trimethoprim-sulfamethoxazole (for the subset of isolates tested for all 5 agents). We compared outcomes before and after adjusting for age, state, race/ethnicity, international travel, outbreak association, and isolate serotype and source. RESULTS: Twenty percent of isolates (1105/5549) had any resistance, and 16% (469/2969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs 28%, P = .01) or have length-of-stay ≥3 days (20% vs 16%, P = .01). Deaths were rare but more common among those with any than no resistance (1.0% vs 0.4%, P = .01). Outcomes for patients whose isolates had clinical resistance did not differ significantly from those with no resistance. After adjustment, any resistance (adjusted odds ratio 1.23, 95% confidence interval 1.04-1.46) remained significantly associated with hospitalization. CONCLUSIONS: We observed a significant association between nontyphoidal Salmonella infections caused by resistant pathogens and likelihood of hospitalization. Clinical resistance was not associated with poorer outcomes, suggesting that factors other than treatment failure (eg, strain virulence, strain source, host factors) may be important.

Cruise Ship Travel in the Era of Coronavirus Disease 2019 (COVID-19): A Summary of Outbreaks and a Model of Public Health Interventions.

BACKGROUND: Cruise travel contributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission when there were relatively few cases in the United States. By 14 March 2020, the Centers for Disease Control and Prevention (CDC) issued a No Sail Order suspending US cruise operations; the last US passenger ship docked on 16 April. METHODS: We analyzed SARS-CoV-2 outbreaks on cruises in US waters or carrying US citizens and used regression models to compare voyage characteristics. We used compartmental models to simulate the potential impact of 4 interventions (screening for coronavirus disease 2019 (COVID-19) symptoms; viral testing on 2 days and isolation of positive persons; reduction of passengers by 40%, crew by 20%, and reducing port visits to 1) for 7-day and 14-day voyages. RESULTS: During 19 January to 16 April 2020, 89 voyages on 70 ships had known SARS-CoV-2 outbreaks; 16 ships had recurrent outbreaks. There were 1669 reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and 29 confirmed deaths. Longer voyages were associated with more cases (adjusted incidence rate ratio, 1.10, 95% confidence interval [CI]: 1.03-1.17, P < .003). Mathematical models showed that 7-day voyages had about 70% fewer cases than 14-day voyages. On 7-day voyages, the most effective interventions were reducing the number of individuals onboard (43.3% reduction in total infections) and testing passengers and crew (42% reduction in total infections). All four interventions reduced transmission by 80.1%, but no single intervention or combination eliminated transmission. Results were similar for 14-day voyages. CONCLUSIONS: SARS-CoV-2 outbreaks on cruises were common during January-April 2020. Despite all interventions modeled, cruise travel still poses a significant SARS-CoV-2 transmission risk.

Genomic Diversity, Antimicrobial Resistance, and Virulence Gene Profiles of Salmonella Serovar Kentucky Isolated from Humans, Food, and Animal Ceca Content Sources in the United States.

Salmonella serovar Kentucky is frequently isolated from chickens and dairy cattle, but recovery from humans is comparatively low based on the U.S. National Antimicrobial Resistance Monitoring System (NARMS) reports. We aimed to better describe the genetic diversity, antimicrobial resistance, and virulence determinants of Salmonella Kentucky isolates from humans, food animal ceca, retail meat and poultry products, imported foods and food products, and other samples. We analyzed the genomes of 774 Salmonella Kentucky isolates and found that 63% (54/86) of human isolates were sequence type (ST)198, 33% (29/86) were ST152, and 3.5% (3/86) were ST314. Ninety-one percent (570/629) of cecal isolates and retail meat and poultry isolates were ST152 or ST152-like (one allele difference), and 9.2% (58/629) were ST198. Isolates from imported food were mostly ST198 (60%, 22/37) and ST314 (29.7%, 11/37). ST198 isolates clustered into two main lineages. Clade ST198.2 comprised almost entirely isolates from humans and imported foods, all containing triple mutations in the quinolone resistance-determining region (QRDR) that confer resistance to fluoroquinolones. Clade ST198.1 contained isolates from humans, ceca, retail meat and poultry products, and imported foods that largely lacked QRDR mutations. ST152 isolates from cattle had a lineage (Clade 2) distinct from ST152 isolates from chicken (Clade 4), and half of ST152 human isolates clustered within two other clades (Clades 1 and 3), largely distinct from Clades 2 and 4. Although clinical illness associated with Salmonella Kentucky is low, ST198 appears to account for most human infections in the Unites States but is uncommon among ceca of domestic food animals and retail meat and poultry products. These findings, combined with human exposure data, suggest that fluoroquinolone-resistant ST198 infections may be linked to the consumption of food products that are imported or consumed while traveling. We also found unique differences in the composition of virulence genes and antimicrobial resistance genes among the clades, which may provide clues to the host specificity and pathogenicity of Salmonella Kentucky lineages.

Salmonella enterica Serotype Newport Infections in the United States, 2004-2013: Increased Incidence Investigated Through Four Surveillance Systems.

Newport is the third most common Salmonella enterica serotype identified among the estimated 1.2 million human salmonellosis infections occurring annually in the United States. Risk factors for infection and food items implicated in outbreaks vary by antimicrobial resistance pattern. We conducted a descriptive analysis of data from four enteric disease surveillance systems capturing information on incidence, demographics, seasonality, geographic distribution, outbreaks, and antimicrobial resistance of Newport infections over a 10-year period from 2004 through 2013. Incidence increased through 2010, then declined to rates similar to those in the early years of the study. Incidence was highest in the South and among children <5 years old. Among isolates submitted for antimicrobial susceptibility testing, 88% were susceptible to all antimicrobials tested (pansusceptible) and 8% were resistant to at least seven agents, including ceftriaxone. Rates of pansusceptible isolates were also highest in the South and among young children, particularly in 2010. Pansusceptible strains of Newport have been associated with produce items and environmental sources, such as creek water and sediment. However, the role of environmental transmission of Newport in human illness is unclear. Efforts to reduce produce contamination through targeted legislation, as well as collaborative efforts to identify sources of contamination in agricultural regions, are underway.

Ceftriaxone-Resistant Nontyphoidal Salmonella from Humans, Retail Meats, and Food Animals in the United States, 1996-2013.

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.

Antimicrobial Resistance Among Nontyphoidal Salmonella Isolated From Blood in the United States, 2003-2013.

BACKGROUND: Salmonella causes an estimated 100 000 antimicrobial-resistant infections annually in the United States. Salmonella antimicrobial resistance may result in bacteremia and poor outcomes. We describe antimicrobial resistance among nontyphoidal Salmonella blood isolates, using data from the National Antimicrobial Resistance Monitoring System. METHODS: Human nontyphoidal Salmonella isolates from 2003 to 2013 were classified as fully susceptible, resistant to ≥1 antimicrobial agent, or resistant to a first-line agent. Logistic regression was used to compare resistance patterns, serotypes, and patient characteristics for Salmonella isolated from blood versus stool and to determine resistance trends over time. RESULTS: Approximately 20% of blood isolates had antimicrobial resistance to a first-line treatment agent. Bacteremia was associated with male sex, age ≥65 years, and specific serotypes. Blood isolates were more likely to be resistant to ≥1 agent for serotypes Enteritidis, Javiana, Panama, and Typhimurium. Blood isolates were most commonly resistant to tetracycline (19%), and more likely resistant to a first-line agent (odds ratio, 1.81; 95% confidence interval, 1.56-2.11) than stool isolates. Ceftriaxone resistance increased in blood isolates from 2003 to 2013 (odd ratio, 1.12; 95% confidence interval, 1.02-1.22). CONCLUSIONS: Resistance to first-line treatment agents in patients with Salmonella bacteremia is a concern for public health and for informing clinical decisions. Judicious antimicrobial use is crucial to limit resistance.

Prophage induction is enhanced and required for renal disease and lethality in an EHEC mouse model.

Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2. Using the germ-free mouse, we show the essential role 933W induction plays in the virulence of EDL933 infection. An EDL933 derivative with a single mutation in its 933W prophage, resulting specifically in that phage being uninducible, colonizes the intestines, but fails to cause any of the pathological changes seen with the parent strain. Hence, induction of the 933W prophage is the primary event leading to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET, with a biosensor that specifically measures induction of the 933W prophage. Using this biosensor to measure 933W induction in germ-free mice, we found an increase three logs greater than was expected from in vitro results. Since the induced population produces and releases Stx2, this result indicates that an activity in the intestine increases Stx2 production.

Epidemiology and Antimicrobial Resistance of Campylobacter Infections in the United States, 2005-2018.

Background: Campylobacter is the most common cause of bacterial diarrhea in the United States; resistance to macrolides and fluoroquinolones limits treatment options. We examined the epidemiology of US Campylobacter infections and changes in resistance over time. Methods: The Foodborne Diseases Active Surveillance Network receives information on laboratory-confirmed Campylobacter cases from 10 US sites, and the National Antimicrobial Resistance Monitoring System receives a subset of isolates from these cases for antimicrobial susceptibility testing. We estimated trends in incidence of Campylobacter infection, adjusting for sex, age, and surveillance changes attributable to culture-independent diagnostic tests. We compared percentages of isolates resistant to erythromycin or ciprofloxacin during 2005-2016 with 2017-2018 and used multivariable logistic regression to examine the association of international travel with resistance. Results: Adjusted Campylobacter incidence remained stable or decreased for all groups analyzed since 2012. Among 2449 linked records in 2017-2018, the median patient age was 40.2 years (interquartile range, 21.6-57.8 years), 54.8% of patients were male, 17.2% were hospitalized, and 0.2% died. The percentage of resistant infections increased from 24.5% in 2005-2016 to 29.7% in 2017-2018 for ciprofloxacin (P < .001) and from 2.6% to 3.3% for erythromycin (P = .04). Persons with recent international travel had higher odds than nontravelers of having isolates resistant to ciprofloxacin (adjusted odds ratio [aOR] varied from 1.7 to 10.6 by race/ethnicity) and erythromycin (aOR = 1.7; 95% confidence interval, 1.3-2.1). Conclusions: Campylobacter incidence has remained stable or decreased, whereas resistance to antimicrobials recommended for treatment has increased. Recent international travel increased the risk of resistance.

Activation of a prophage-encoded tyrosine kinase by a heterologous infecting phage results in a self-inflicted abortive infection.

Bacteria in their struggle for survival have evolved or acquired defences against attacking phage. However, phage often contribute to this defence through mechanisms in which a prophage protects the bacterial population from attack by another, often unrelated, phage. The 933W prophage, which carries Shiga toxin genes that enhance pathogenicity of enterohaemorrhagic Escherichia coli strain O157:H7, also carries the stk gene encoding a eukaryotic-like tyrosine kinase that excludes (aborts) infection by phage HK97. This exclusion requires the kinase activity of Stk. Little, if any, protein tyrosine phosphorylation can be detected in a 933W lysogen prior to infection with HK97, while extensive Stk-mediated tyrosine phosphorylation is evident following infection. This includes autophosphorylation that stabilizes Stk protein from degradation. Although increased levels of Stk are found following HK97 infection, these higher levels are not necessary or sufficient for exclusion or protein phosphorylation. An HK97 open reading frame, orf41, is necessary for exclusion and Stk kinase activity. We hypothesize that interaction with gp41 stimulates Stk kinase activity. Exclusion of HK97 appears to be specific since other phages tested, λ, φ80, H-19B, λ-P22dis and T4rII, were not excluded. Infection of the 933W lysogen with a non-excluded phage fails to induce Stk-determined phosphorylation.

Don't get bugged: practical strategies for managing bedbug infestation in psychiatric rehabilitation programs.

Bedbug infestation has become a major problem in the United States. Infestations can be frightening and expensive and appear to be more prevalent in urban settings and low-income housing such as homeless shelters, public housing, and single-room occupancy apartments. This exposes consumers and staff of psychiatric rehabilitation agencies to higher risk of infestation. This brief report outlines practical suggestions for managing bedbug infestation in such agencies. Drawing on resources readily available on the Internet and the experience of Thresholds, a large provider of psychiatric rehabilitation services based in Chicago, this report describes strategies for responding to infestation. Providers need to assume that bedbug infestation is a significant risk and prepare accordingly. Assertive, persistent, and calm response is recommended.

Extensively Drug-Resistant Typhoid Fever in the United States.

Cases of extensively drug-resistant (XDR) typhoid fever have been reported in the United States among patients who did not travel internationally. Clinicians should consider if and where the patient traveled when selecting empiric treatment for typhoid fever. XDR typhoid fever should be treated with a carbapenem, azithromycin, or both.

Design and analysis of a health care clinic for homeless people using simulations.

PURPOSE: Improving quality of care is important in health care management. For health care clinics, reducing patient waiting time and improving throughput with efficient utilization of the workforce are important issues to achieve better quality of care. This paper seeks to introduce a simulation study on design and analysis of a health clinic for homeless patients in Lexington, Kentucky, USA. DESIGN/METHODOLOGY/APPROACH: Using the simulation model, the patient flow of the clinic and analyze quality of care for different staffing levels is simulated. In addition, the dependence of distributions on service times is investigated. Moreover, the impact of service time variability on quality of care (e.g. patient waiting time) is analyzed. FINDINGS: The necessary staffing level and utilizations to reduce patient waiting times and improve throughput to achieve better quality of care are obtained. In addition, it is shown that the system performance is primarily dependent on the mean and coefficients of variation, rather than a complete distribution, of service times. In addition, a piece-wise linear approximation formula is proposed so that patient waiting time in the clinic can be estimated for any variability with only two simulations. RESEARCH LIMITATIONS/IMPLICATIONS: The simulation method may need long model development time and long simulation executing time for complex systems. PRACTICAL IMPLICATIONS: The quality of care delivery in a health care clinic can be evaluated using simulations. The results presented in the paper provide an easier approach for medical practitioners to evaluate different scenarios, examine needed resources, and carry out what-if analysis to predictthe impact of any changes in the system, to determine an optimal system configuration. ORIGINALITY/VALUE: The paper shows that such models provide a quantitative tool for clinic operations and management to achieve better care quality. Moreover, it can be easily adapted to model other health care facilities, such as hospitals, emergency rooms, operating rooms, supply chain in health care industry.

A Review of the Microbial Production of Bioactive Natural Products and Biologics.

A variety of organisms, such as bacteria, fungi, and plants, produce secondary metabolites, also known as natural products. Natural products have been a prolific source and an inspiration for numerous medical agents with widely divergent chemical structures and biological activities, including antimicrobial, immunosuppressive, anticancer, and anti-inflammatory activities, many of which have been developed as treatments and have potential therapeutic applications for human diseases. Aside from natural products, the recent development of recombinant DNA technology has sparked the development of a wide array of biopharmaceutical products, such as recombinant proteins, offering significant advances in treating a broad spectrum of medical illnesses and conditions. Herein, we will introduce the structures and diverse biological activities of natural products and recombinant proteins that have been exploited as valuable molecules in medicine, agriculture and insect control. In addition, we will explore past and ongoing efforts along with achievements in the development of robust and promising microorganisms as cell factories to produce biologically active molecules. Furthermore, we will review multi-disciplinary and comprehensive engineering approaches directed at improving yields of microbial production of natural products and proteins and generating novel molecules. Throughout this article, we will suggest ways in which microbial-derived biologically active molecular entities and their analogs could continue to inspire the development of new therapeutic agents in academia and industry.