Search

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina). Thirty-eight patients were identified with multiple NGS results from 82 samples: 11% were from single unifocal, 51% were from synchronous, and 38% were from metachronous tumors. Changes in EGFR, KRAS, PI3KCA, and TP53 variants were found in 22 patients' samples (58%). No changes were seen with longitudinal testing of multiple samples from single unifocal tumors, while changes were observed in 60% of synchronous and 71% of metachronous tumors. Of these, 26% of patients had AGA differences between samples. Acknowledging the limited sample size, a significant difference in overall survival was observed between synchronous separate primaries and metastasis. Repeat NGS testing of synchronous and metachronous NSCLC tumors may identify differing variants in >50% of patients. These changes may reflect separate primary lung carcinomas, tumor heterogeneity among intrapulmonary metastases, and clonal evolution. NGS testing of multiple tumors may enhance the identification of therapeutic targets for treatment decisions. [ABSTRACT FROM AUTHOR]

Background Antimicrobial resistance in nontyphoidal Salmonella (NTS) can limit treatment options. We assessed the contribution of international travel to antimicrobial-resistant NTS infections. Methods We describe NTS infections that were reported to the Foodborne Diseases Active Surveillance Network during 2018–2019 and screened for genetic resistance determinants, including those conferring decreased susceptibility to first-line agents (ciprofloxacin, ceftriaxone, or azithromycin). We used multivariable logistic regression to assess the association between resistance and international travel during the 7 days before illness began. We estimated the contribution of international travel to resistance using population-attributable fractions, and we examined reported antimicrobial use. Results Among 9301 NTS infections, 1159 (12%) occurred after recent international travel. Predicted resistance to first-line antimicrobials was more likely following travel; the adjusted odds ratio varied by travel region and was highest after travel to Asia (adjusted odds ratio, 7.2 [95% confidence interval, 5.5–9.5]). Overall, 19% (95% confidence interval, 17%–22%) of predicted resistance to first-line antimicrobials was attributable to international travel. More travelers than nontravelers receiving ciprofloxacin or other fluoroquinolones had isolates with predicted resistance to fluoroquinolones (29% vs 9%, respectively; P <.01). Conclusions International travel is a substantial risk factor for antimicrobial-resistant NTS infections. Understanding risks of resistant infection could help target prevention efforts. [ABSTRACT FROM AUTHOR]

The benefits of breastfeeding for mother and baby are strongly supported by research. However, lactating parents who return to school or work soon after delivery face many barriers to continued breastfeeding. This article presents a student-led initiative to support lactation at a large public university that emerged from advocacy efforts of student mothers of color. The socioecological model was used as a framework to understand and address the multifaceted influences on breastfeeding practices. Project activities included providing breastfeeding education to lactating parents and their partners, measuring availability and accessibility of lactation spaces, improving lactation spaces, connecting university stakeholders, and strengthening university lactation policies. The project achieved the following outcomes: formation of a stakeholder group with members across campus departments, improvement in accessibility and appropriateness of lactation spaces, provision of breastfeeding services through workshops and one-on-one appointments with lactation educators, and creation and dissemination of an online toolkit outlining parents' lactation rights and support available on campus. Comprehensive lactation support at universities is essential to enhance educational and professional equity for women and to promote postpartum and infant health. Throughout the project implementation, the team learned many lessons that can help guide similar university initiatives. [ABSTRACT FROM AUTHOR]

In 2018, we detected a novel Ehrlichia strain infecting Amblyomma neumanni ticks in Argentina. The novel strain is phylogenetically related to the ruminant pathogen E. ruminantium and represents a potential risk for veterinary and public health because A. neumanni ticks parasitize domestic and wild ruminants and bite humans. [ABSTRACT FROM AUTHOR]

A multidrug-resistant Salmonella enterica serotype Anatum strain reported in Taiwan was isolated in the United States from patients and from seafood imported from Asia. Isolates harbored 11 resistance determinants, including quinolone and inducible cephalosporin resistance genes. Most patients had traveled to Asia. These findings underscore the need for global One Health resistance surveillance. [ABSTRACT FROM AUTHOR]

There are few epidemiologic studies on the role of dogs in zoonotic parasitic transmission in the Circumpolar North. The objectives of this study were to: (a) estimate the faecal prevalence of Giardia spp. and Cryptosporidium spp. in dogs; (b) investigate potential associations between the type of dog population and the faecal presence of Giardia spp. and Cryptosporidium spp.; and (c) describe the molecular characteristics of Giardia spp. and Cryptosporidium spp. in dogs in Iqaluit, Nunavut. We conducted two cross‐sectional studies in July and September 2016. In July, the team collected daily faecal samples for 3 days from each of 20 sled dogs. In September, the team collected three faecal samples from each of 59 sled dogs, 111 samples from shelter dogs and 104 from community dogs. We analysed faecal samples for the presence of Giardia spp. and Cryptosporidium spp. using rapid immunoassay and flotation techniques. Polymerase chain reaction (PCR) and sequencing of target genes were performed on positive faecal samples. Overall, the faecal prevalence of at least one of the target parasites, when one faecal sample was chosen at random for all dogs, was 8.16% (CI: 5.52–11.92), and for Giardia spp. and Cryptosporidium spp., prevalence was 4.42% (CI: 2.58–7.49) and 6.12% (CI: 3.88–9.53), respectively. The odds of faecal Giardia spp. in sled dogs were significantly higher than those in shelter and community dogs (OR 10.19 [CI: 1.16–89.35]). Sequence analysis revealed that 6 faecal samples were Giardia intestinalis, zoonotic assemblage B (n = 2) and species‐specific assemblages D (n = 3) and E (n = 1), and five faecal samples were Cryptosporidium canis. Giardia intestinalis is zoonotic; however, Cryptosporidium canis is rare in humans and, when present, usually occurs in immunosuppressed individuals. Dogs may be a potential source of zoonotic Giardia intestinalis assemblage B infections in residents in Iqaluit, Nunavut, Canada; however, the direction of transmission is unclear. [ABSTRACT FROM AUTHOR]

Salmonella Infantis, a common contaminant of poultry products, is known to harbor mobile genetic elements that confer multi-drug resistance (MDR) and have been detected in many continents. Here, we report four MDR S. Infantis strains recovered from poultry house environments in Santa Cruz Island of the Galapagos showing extended-spectrum β-lactamase (ESBL) resistance and reduced fluoroquinolone susceptibility. Whole-genome sequencing (WGS) revealed the presence of the ESBL-conferring blaCTX-M-65 gene in an IncFIB-like plasmid in three S. Infantis isolates. Multi-locus sequence typing (MLST) and single nucleotide variant/polymorphism (SNP) SNVPhyl analysis showed that the S. Infantis isolates belong to sequence type ST32, likely share a common ancestor, and are closely related (1–3 SNP difference) to blaCTX-M-65-containing clinical and veterinary S. Infantis isolates from the United States and Latin America. Furthermore, phylogenetic analysis of SNPs following core-genome alignment (i.e., ParSNP) inferred close relatedness between the S. Infantis isolates from Galapagos and the United States. Prophage typing confirmed the close relationship among the Galapagos S. Infantis and was useful in distinguishing them from the United States isolates. This is the first report of MDR blaCTX-M-65-containing S. Infantis in the Galapagos Islands and highlights the need for increased monitoring and surveillance programs to determine prevalence, sources, and reservoirs of MDR pathogens. [ABSTRACT FROM AUTHOR]

Background Azithromycin is a recommended oral agent for treating nontyphoidal Salmonella (NTS), when antibiotics are indicated. Azithromycin nonsusceptibility among NTS is <1% in the United States. CDC, FSIS, and state health departments investigated an outbreak of azithromycin-nonsusceptible Salmonella serotype Newport infections to determine sources. Methods We classified isolates as the outbreak strain if they were within 11 alleles by core genome multilocus sequence typing. We defined a case as infection with the outbreak strain during June 2018–February 2019. After stratifying by gender and ethnicity, we compared food exposures ≤7 days before illness onset with those reported by healthy persons in the Foodborne Diseases Active Surveillance Network population survey (2006–2007). We used broth microdilution to determine antimicrobial susceptibility. Results We identified 218 case patients from 31 states; 49 of 176 (28%) were hospitalized and 2 died. Overall, 65% (121/187) were Hispanic, and 41% (70/169) visited Mexico in the 7 days before illness onset. Among travelers to Mexico, 71% (23/32) reported eating Mexican-style soft cheese; 16/23 (70%) recalled obtaining the cheese in Mexico. Among nontravelers, the proportion who ate Mexican-style soft cheese (30%, 18/60) was similar to that reported by healthy persons, whereas the proportion who consumed beef (91%, 60/66) was higher than reported by healthy persons (P = 0.04). The outbreak strain was detected in a sample of soft cheese obtained in Mexico, and in a cecal sample from a steer and a beef sample that was collected at FSIS-regulated establishments in the United States. Isolates were resistant to ampicillin and trimethoprim–sulfamethoxazole, nonsusceptible to azithromycin, and showed decreased susceptibility to ciprofloxacin. Conclusion This is the first documented outbreak of azithromycin-nonsusceptible Salmonella infections in the United States. Two food vehicles—soft cheese obtained in Mexico, and beef obtained in the United States—were epidemiologically and genetically associated with this outbreak. Further investigation is warranted to determine the routes of entry, prevalence, and spread of azithromycin-nonsusceptible Salmonella in US and Mexican cattle. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology ( P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.