OBJECTIVES: . The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance for typhoid fever cases caused by Salmonella enterica serovar Typhi (Typhi). Here we describe the characteristics of the first two cases of mph(A)-positive azithromycin-resistant Typhi identified through US surveillance. METHODS: . Isolates were submitted to public health laboratories, sequenced, and screened for antimicrobial resistance determinants and plasmids, as part of CDC PulseNet's routine genomic surveillance. Antimicrobial susceptibility testing and long-read sequencing were also performed. Basic case information (age, sex, travel, outcome) was collected through routine questionnaires; additional epidemiological data was requested through follow-up patient interviews. RESULTS: . The patients are related and both reported travel to India (overlapping travel dates) before illness onset. Both Typhi genomes belong to the GenoTyphi lineage 4.3.1.1 and carry the azithromycin-resistance gene mph(A) on a PTU-FE (IncFIA/FIB/FII) plasmid. These strains differ genetically from mph(A)-positive Typhi genomes recently reported from Pakistan, suggesting independent emergence of azithromycin resistance in India. CONCLUSIONS: . Cases of typhoid fever caused by Typhi strains resistant to all available oral treatment options are cause for concern and support the need for vaccination of travelers to Typhi endemic regions. US genomic surveillance serves as an important global sentinel for detection of strains with known and emerging antimicrobial resistance profiles, including strains from areas where routine surveillance is not conducted.

BACKGROUND: Nontyphoidal Salmonella causes an estimated 1.35 million U.S. 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 2004-2018. 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 five 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 (1,105/5,549) had any resistance and 16% (469/2,969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs. 28%, P=0.01) or have length-of-stay ≥3 days (20% vs. 16%, P=0.01). Deaths were rare, but more common among those with any than no resistance (1.0% vs. 0.4%, P=0.01). 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 (e.g., strain virulence, strain source, host factors) may be important.

BACKGROUND: COVID-19 vaccines are highly efficacious, but SARS-CoV-2 infections post-vaccination occur. We characterized COVID-19 cases among fully vaccinated persons with an outcome of death. METHODS: We analyzed COVID-19 cases voluntarily reported to CDC by US health departments during January 1, 2021-April 30, 2021. We included cases among U.S. residents with a positive SARS-CoV-2 test 14 days after completion of an authorized primary vaccine series and who had a known outcome (alive or death) as of May 31, 2021. When available, specimens were sequenced for viral lineage and death certificates were reviewed for cause(s) of death. RESULTS: Of 8,084 reported COVID-19 cases among fully vaccinated persons during the surveillance period, 245 (3.0%) died. Compared with patients who remained alive, those who died were older (median age 82 years vs. 57 years, P <0.01), more likely to reside in a long-term care facility (51% vs. 18%, P <0.01), and more likely to have at least one underlying health condition associated with risk for severe disease (64% vs. 24%, P <0.01). Among 245 deaths, 191 (78%) were classified as COVID-19-related. Of 106 deaths with available death certificates, COVID-19 was listed on 81 (77%). There were no differences in the type of vaccine administered or the most common viral lineage (B.1.1.7). CONCLUSIONS: COVID-19 deaths are rare in fully vaccinated persons, occurring most commonly in those with risk factors for severe disease, including older age and underlying health conditions. All eligible persons should be fully vaccinated against COVID-19 and follow other prevention measures to mitigate exposure risk.

OBJECTIVES: Most patients with Campylobacter infections do not require antibiotics; however, they are indicated in severe cases. Clinical breakpoints for many antibiotics have not yet been established by the Clinical and Laboratory Standards Institute, making antibiotic selection for resistant infections challenging. During an outbreak of pet store puppy-associated extensively drug resistant (XDR) Campylobacter jejuni infections resistant to seven classes of antibiotics, several patients required antibiotics. The aims of this study were to describe the minimal inhibitory concentrations (MICs) of the outbreak strain for various antibiotics and the successful treatment of two patients using imipenem-cilastatin, a drug not traditionally used to treat Campylobacter infections. METHODS: We used whole genome multi-locus sequence typing (wgMLST) to determine the genetic relatedness of Campylobacter isolates collected from two human patients' stool samples with the outbreak strain. We performed extended antimicrobial susceptibility testing on 14 outbreak isolates and 6 control strains to determine MICs for 30 antibiotics from 14 classes. RESULTS: Isolates from both patients were found to be highly related to the outbreak strain by wgMLST. MICs indicated resistance of outbreak strain to most antibiotic classes; exceptions included phenicols, glycylcyclines, and carbapenems. Due to potential side effects of phenicols and safety issues precluding use of glycylcyclines like tigecycline when alternatives agents are available, we used carbapenems to treat patients who got severely ill from the outbreak strain infections. CONCLUSIONS: Stewardship and clinical vigilance are warranted when deciding whether and how to treat patients with suspected C. jejuni diarrhea with antibiotics. Clinicians should maintain a high index of suspicion for XDR Campylobacter when patients fail to improve and consider use of carbapenems in such settings.

Extended-spectrum beta-lactamases (ESBLs) confer resistance to clinically important third-generation cephalosporins, which are often used to treat invasive salmonellosis. In the United States, ESBLs are rarely found in Salmonella. However, in 2014, the US Food and Drug Administration found blaCTX-M-65 ESBL-producing Salmonella enterica serotype Infantis in retail chicken meat. The isolate had a rare pulsed-field gel electrophoresis pattern. To clarify the sources and potential effects on human health, we examined isolates with this pattern obtained from human surveillance and associated metadata. Using broth microdilution for antimicrobial susceptibility testing and whole-genome sequencing, we characterized the isolates. Of 34 isolates, 29 carried the blaCTX-M-65 gene with <9 additional resistance genes on 1 plasmid. Of 19 patients with travel information available, 12 (63%) reported recent travel to South America. Genetically, isolates from travelers, nontravelers, and retail chicken meat were similar. Expanded surveillance is needed to determine domestic sources and potentially prevent spread of this ESBL-containing plasmid.