918. Typhoid Fever in the US Pediatric Population, 1999–2015, and the Potential Benefits of New Vaccines

Abstract Background In the United States, typhoid fever is rare. About 300 typhoid cases are reported to CDC annually through the National Typhoid and Paratyphoid Fever Surveillance (NTPFS) system. Most are acquired during international travel and while visiting friends and relatives. CDC recommends pretravel vaccination of at-risk children with one of two currently available vaccines: oral (age ≥6 years) or injectable (age ≥2 years). In anticipation of licensure of new protein-conjugate typhoid vaccines that could be administered to children ≥6 months old, we characterized clinical, epidemiologic, and antimicrobial resistance data of pediatric typhoid fever cases reported to CDC. Methods We reviewed laboratory-confirmed Salmonella enterica serotype Typhi infections reported to NTPFS and antimicrobial resistance data on Typhi isolates in the National Antimicrobial Resistance Monitoring System (NARMS) from 1999 to 2015. Results Of 2,051 pediatric (≤18 years) cases of typhoid fever, 80% had traveled internationally within 30 days of illness onset (most frequently to South Asia [82%]), 81% were hospitalized (median duration 6 days; range 0–77 days), and none died. Eight hundred twenty-seven (40%) were <6 years old; 219 (26%) were 6 months–2 years old. While 76% of pediatric cases were vaccine eligible (travelers ≥2 years old), only 6% were known to be vaccinated. Of 2,020 isolates tested for antimicrobial susceptibility, 1,211 (60%) had decreased susceptibility or resistance to ciprofloxacin, of which 277 (23%) were also resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole (multidrug-resistant [MDR]). None were resistant to ceftriaxone or azithromycin. MDR isolates were more likely in children than adults (16% vs. 9%, P < 0.05) and in travel-associated than domestically acquired cases (16% vs. 6%, P < 0.05). Conclusion Among pediatric cases of typhoid fever, 94% of currently vaccine-eligible travelers were unvaccinated. Emphasis on current vaccine indications and an effective pretravel typhoid vaccine for children between 6 months and 2 years old available during routine immunization visits could begin to reduce the burden of disease, and help prevent drug-resistant infections, in this vulnerable age group. Disclosures All authors: No reported disclosures.

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Typhoid Fever in the US Pediatric Population, 1999–2015: Opportunities for Improvement

Clinical Infectious Diseases ◽

10.1093/cid/ciaa914 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jarred McAteer ◽

Gordana Derado ◽

Michael Hughes ◽

Amelia Bhatnagar ◽

Felicita Medalla ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Typhoid Fever ◽

Antimicrobial Susceptibility ◽

Pediatric Population ◽

The United States ◽

International Travel ◽

Typhoid Vaccine ◽

Illness Onset ◽

New Public Health

Abstract Background Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. Methods We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC’s National Antimicrobial Resistance Monitoring System from 1999 through 2015. Results 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0–50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). Conclusions Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.

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Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.4.1037-1042.2001 ◽

2001 ◽

Vol 45 (4) ◽

pp. 1037-1042 ◽

Cited By ~ 94

Author(s):

Daniel F. Sahm ◽

James A. Karlowsky ◽

Laurie J. Kelly ◽

Ian A. Critchley ◽

Mark E. Jones ◽

...

Keyword(s):

United States ◽

Streptococcus Pneumoniae ◽

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

The United States ◽

Multidrug Resistant ◽

Fluoroquinolone Resistance ◽

Resistance Patterns ◽

Changing Patterns ◽

Resistance To Penicillin

ABSTRACT Although changing patterns in antimicrobial resistance inStreptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniaeantimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997–1998 and 1998–1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997–1998 were encountered in 1998–1999. This longitudinal surveillance study of resistance inS. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

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Geographical Pattern of Infectious Diseases and Infection Prevention for Travellers

Tutorial Topics in Infection for the Combined Infection Training Programme ◽

10.1093/oso/9780198801740.003.0071 ◽

2019 ◽

Author(s):

Desmond Hsu ◽

Zahir Osman Eltahir Babiker

Keyword(s):

Infectious Diseases ◽

Migratory Birds ◽

Sunshine Duration ◽

The United States ◽

International Travel ◽

Travel Health ◽

Health Advice ◽

Visiting Friends And Relatives ◽

Main Determinants ◽

Key Aspects

Infectious diseases are transmitted either directly from person to person via direct contact or droplet exposure, or indirectly through a vector organism (mosquito or tick) or a non-biological physical vehicle (soil or water). Vector-borne infectious diseases are highly influenced by climate factors such as temperature, precipitation, altitude, sunshine duration, and wind. Therefore, climate change is a major threat for the emergence and re-emergence of infectious diseases, e.g. re-emergence of dengue fever in some parts of southern Europe. The natural reservoirs of infectious diseases are either humans (anthroponoses) or animals (zoonoses). Population movement due to travel or civil unrest risks introducing non-immune populations to regions that are endemic for certain infectious diseases. By contrast, global trade contributes to the movement of animals or arthropods across the world and this poses a major risk for introducing infectious diseases to previously non-endemic settings, e.g. rats on board commercial ships and the global spread of hantaviruses; international trade in used car tyres and the risk of introducing flavivirus-infected mosquitoes into non-endemic settings; and the contribution of migratory birds to the introduction and the spread of West Nile virus in the United States. The unprecedented growth of international travel facilitates the swift movement of pathogens by travellers from one region to another. The main determinants of travel-related infections are destination country, activities undertaken during travel, and pre-existing morbidities. Therefore, the pre-travel consultation aims to assess potential health hazards associated with the trip, give advice on appropriate preventative measures, and educate the traveller about their own health. Attitudes towards seeking pre-travel health advice vary by the type of traveller. For example, those visiting friends and relatives (VFRs) in their country of origin are less likely to seek pre-travel health advice compared to tourists and therefore stand a higher chance of presenting with preventable infections such as malaria. The key aspects of a pre-travel consultation include: ● comprehensive risk assessment based on the demographic and clinical background of the traveller as well as the region of travel and itinerary.

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Antimicrobial Resistance Genes in Multidrug-Resistant Salmonella enterica Isolated from Animals, Retail Meats, and Humans in the United States and Canada

Microbial Drug Resistance ◽

10.1089/mdr.2012.0177 ◽

2013 ◽

Vol 19 (3) ◽

pp. 175-184 ◽

Cited By ~ 33

Author(s):

LaShanda M. Glenn ◽

Rebecca L. Lindsey ◽

Jason P. Folster ◽

Gary Pecic ◽

Patrick Boerlin ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Resistance Genes ◽

Salmonella Enterica ◽

The United States ◽

Multidrug Resistant ◽

Antimicrobial Resistance Genes ◽

Retail Meats

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Mapping Twenty Years of Antimicrobial Resistance Research Trends

10.1101/2021.03.01.433375 ◽

2021 ◽

Author(s):

Christian F Luz ◽

Magnus van Niekerk ◽

Julia Keizer ◽

Nienke Beerlage-de Jong ◽

Annemarie Braakman-Jansen ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Research Output ◽

The United States ◽

Multidrug Resistant ◽

Future Research ◽

Topic Modelling ◽

African Region ◽

Comprehensive Overview ◽

Mdr Tb ◽

Global Threat

Background: Antimicrobial resistance (AMR) is a global threat to health and healthcare. In response to the growing AMR burden, research funding also increased. However, a comprehensive overview of the research output, including conceptual, temporal, and geographical trends, is missing. Therefore, this study uses topic modelling, a machine learning approach, to reveal the scientific evolution of AMR research and its trends, and provides an interactive user interface for further analyses. Methods: Structural topic modelling (STM) was applied on a text corpus resulting from a PubMed query comprising AMR articles (1999-2018). A topic network was established and topic trends were analysed by frequency, proportion, and importance over time and space. Findings: In total, 88 topics were identified in 158616 articles from 166 countries. AMR publications increased by 450% between 1999 and 2018, emphasizing the vibrancy of the field. Prominent topics in 2018 were Strategies for emerging resistances and diseases, Nanoparticles, and Stewardship. Emerging topics included Water and environment, and Sequencing. Geographical trends showed prominence of Multidrug-resistant tuberculosis (MDR-TB) in the WHO African Region, corresponding with the MDR-TB burden. China and India were growing contributors in recent years, following the United States of America as overall lead contributor. Interpretation: This study provides a comprehensive overview of the AMR research output thereby revealing the AMR research response to the increased AMR burden. Both the results and the publicly available interactive database serve as a base to inform and optimise future research.

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Antimicrobial Resistance and Genomic Characterization of Salmonella Dublin Isolates in Cattle from the United States.

10.1101/2021.03.23.436584 ◽

2021 ◽

Author(s):

Mariela Srednik ◽

Kristina Lantz ◽

Jessica A Hicks ◽

Brenda R Morningstar-Shaw ◽

Tonya A Mackie ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Systemic Disease ◽

The United States ◽

Multidrug Resistant ◽

Severe Illness ◽

Valuable Insight ◽

Antimicrobial Drugs ◽

Salmonella Dublin ◽

Genomic Characterization

Salmonella enterica subspecies enterica serovar Dublin is a host-adapted serotype in cattle, associated with enteritis and systemic disease. While rare in humans, it can cause severe illness, including bacteremia, with hospitalization and death. In the United States, S. Dublin has become one of the most multidrug-resistant serotypes . The objective of this study was to characterize S. Dublin isolates from sick cattle by analyzing phenotypic and genotypic antimicrobial resistance (AMR) profiles, the presence of plasmids, and phylogenetic relationships. S. Dublin isolates (n=140) were selected from submissions to the NVSL for Salmonella serotyping (2014 – 2017) from 21 states. Isolates were tested for susceptibility against 14 class-representative antimicrobial drugs. Resistance profiles were determined using the ABRicate with Resfinder and NCBI databases, AMRFinder and PointFinder. Plasmids were detected using ABRicate with PlasmidFinder. Phylogeny was determined using vSNP. We found 98% of the isolates were resistant to more than 4 antimicrobials . Only 1 isolate was pan-susceptible and had no predicted AMR genes. All S. Dublin isolates were susceptible to azithromycin and meropenem. They showed 96% resistance to sulfonamides, 97% to tetracyclines, 95% to aminoglycosides and 85% to beta-lactams . The most common AMR genes were: sulf2 and tetA (98.6%), aph(3'')-Ib and aph(6)-Id (96.4%), floR (94.3%), and blaCMY-2 (85.7%). All quinolone resistant isolates presented mutations in gyr A. Ten plasmid types were identified among all isolates with IncA/C2, IncX1, and IncFII(S) being the most frequent. The S. Dublin isolates show low genomic genetic diversity. This study provided antimicrobial susceptibility and genomic insight into S . Dublin clinical isolates from cattle in the U.S. Further sequence analysis integrating food and human origin S . Dublin isolates may provide valuable insight on increased virulence observed in humans.

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165. Emergence of Extensively Drug-Resistant Salmonella enterica Serotype Typhi Infections—United States, 2008–2020

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.165 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S99-S100

Author(s):

Felicita Medalla ◽

Louise Francois Watkins ◽

Michael Hughes ◽

Meseret Birhane ◽

Layne Dorough ◽

...

Keyword(s):

United States ◽

Typhoid Fever ◽

The United States ◽

Empiric Therapy ◽

Salmonella Typhi ◽

International Travel ◽

Drug Resistant ◽

Extensively Drug Resistant ◽

Large Outbreak ◽

Control And Prevention

Abstract Background Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions. Methods Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin. Results During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states. Conclusion Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq. Disclosures All Authors: No reported disclosures

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Trends in Susceptibility of Escherichia coli from Intra-Abdominal Infections to Ertapenem and Comparators in the United States According to Data from the SMART Program, 2009 to 2013

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05186-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3606-3610 ◽

Cited By ~ 49

Author(s):

Sibylle H. Lob ◽

Krystyna M. Kazmierczak ◽

Robert E. Badal ◽

Meredith A. Hackel ◽

Samuel K. Bouchillon ◽

...

Keyword(s):

United States ◽

Escherichia Coli ◽

Antimicrobial Resistance ◽

Statistical Significance ◽

The United States ◽

Multidrug Resistant ◽

Content Type ◽

E Coli ◽

Smart Data ◽

Abdominal Infections

ABSTRACTAntimicrobial resistance inEnterobacteriaceae, including resistance to carbapenems, is increasing worldwide. However, using U.S. Study for Monitoring Antimicrobial Resistance Trends (SMART) data for 2009 to 2013, no statistically significant decreasing susceptibility trends were found overall forEscherichia coliisolates from patients with intra-abdominal infections. In the subset of isolates from community-associated infections, susceptibility to levofloxacin decreased significantly and the increasing rate of multidrug-resistantE. coliapproached statistical significance. In 2013, ertapenem, imipenem, and amikacin showed the highest susceptibility rates (≥99%) and fluoroquinolones the lowest (<70%). The 10 non-ertapenem-susceptible isolates (0.3% of allE. coliisolates) encoded one or more carbapenemases, extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, or non-ESBL β-lactamases.

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Emergence of multidrug-resistant Salmonella enterica serotype Typhi with decreased ciprofloxacin susceptibility in Bangladesh

Epidemiology and Infection ◽

10.1017/s0950268805004759 ◽

2005 ◽

Vol 134 (2) ◽

pp. 433-438 ◽

Cited By ~ 20

Author(s):

M. RAHMAN ◽

A. K. SIDDIQUE ◽

S. SHOMA ◽

H. RASHID ◽

M. A. SALAM ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Blood Culture ◽

Typhoid Fever ◽

Diffusion Zone ◽

Salmonella Enterica ◽

Treatment Guidelines ◽

Screen Test ◽

Break Point ◽

Multidrug Resistant ◽

Optimum Treatment

During 1989–2002, we studied the antimicrobial resistance of 3928 blood culture isolates of Salmonella enterica serotype Typhi (S. Typhi) in Dhaka, Bangladesh. Overall 32% (1270) of the strains were multidrug-resistant (MDR, resistant to chloramphenicol, ampicillin and trimethoprim–sulphamethoxazole); first detected in 1990 (rate of 8%), increased in 1994 (44%), declined in 1996 (22%, P<0·01 compared to 1994) and re-emerged in 2001 (36%) and 2002 (42%, P<0·01 compared to 1996). An increased MIC of ciprofloxacin (0·25 μg/ml) indicating decreased susceptibility to ciprofloxacin was detected in 24 (18·2%) out of 132 randomly selected strains during 1990–2002; more frequently in MDR than susceptible strains (46·3% vs. 5·5%, P<0·001), and the proportion of them rose to 47% in 2002 from 8% in 2000 (P<0·01). Ciprofloxacin (5 μg) disk diffusion zone diameters of [les ]24 mm as break-point had 98% sensitivity and 100% specificity when compared with a ciprofloxacin MIC of 0·25 μg/ml as break-point for decreased susceptibility; being a useful and easy screen test. All strains were susceptible to ceftriaxone. The emergence of MDR S. Typhi with decreased ciprofloxacin susceptibility will further complicate the therapy of typhoid fever because of the lack of optimum treatment guidelines.

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