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Background.  Antibiotic use predisposes patients to Clostridium difficile infections (CDI), and approximately 32% of these infections are community-associated (CA) CDI. The population-level impact of antibiotic use on adult CA-CDI rates is not well describ

BACKGROUND: Clostridium difficile infection (CDI) is no longer restricted to hospital settings, and population-based incidence measures are needed. Understanding the determinants of CDI incidence will allow for more meaningful comparisons of rates and accu

Objectives: Introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine has resulted in a dramatic reduction of Hib disease in the U.S. and an increase in the relative importance of infections caused by nontypeable strains. The current project describes the characteristics and clinical outcomes of pediatric and adult patients with invasive H. influenzae (HI) and, through multivariable analysis, identifies risk factors for in-hospital mortality.Methods: HI cases were identified during 1999-2008 through active surveillance as part of active bacterial core surveillance (ABCs). Multivariable analysis was performed with logistic regression to identify factors predictive of in-hospital death.Results: 4839 cases of HI were identified from 1999-2008. Children accounted for 17.1% of cases and adults 82.9%. Underlying conditions were present in 20.7% of children and 74.8% of adults. In-hospital mortality was highest in cases ≥65 years (21.9%) and <3 months (16.2%). The risk of in-hospital death in children <1 year was higher among those who were prematurely-born (<28 weeks, OR 7.1, 95% CI 3.2-15.6; 28-36 weeks OR 2.1, 95% CI 0.9-4.8) and, among children aged 1-17 years, higher in those with healthcare-associated onset and dialysis (OR 5.66, 95% CI 1.84-17.39; OR 18.11, 95% CI 2.77-118.65). In adults, age ≥40 was associated with death in nontypeable, but not encapsulated, infections. Infections with nontypeable strains increased the risk of death in cases ≥65 years (OR 1.81, 95% CI 1.31-2.52). Healthcare-associated HI, bacteremia without identifiable focus, bacteremic pneumonia, associated cirrhosis, cerebrovascular accident, dialysis, heart failure, and non-hematologic malignancy also increased the risk of death in adults.Conclusion: Prematurity in infants, advanced age and certain chronic diseases in adults were associated with an increased risk of in-hospital death. Nontypeable HI was associated with higher mortality in the elderly. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examined epidemiologic factors affecting mortality from pneumococcal pneumonia in 1995 through 1997. METHODS: Persons residing in a surveillance area who had community-acquired pneumonia requiring hospitalization and Streptococcus pneumoniae isolated from a sterile site were included in the analysis. Factors affecting mortality were evaluated in univariate and multivariate analyses. The number of deaths from pneumococcal pneumonia requiring hospitalization in the United States in 1996 was estimated. RESULTS: Of 5837 cases, 12% were fatal. Increased mortality was associated with older age, underlying disease. Asian race, and residence in Toronto/Peel, Ontario. When these factors were controlled for, increased mortality was not associated with resistance to penicillin or cefotaxime. However, when deaths during the first 4 hospital days were excluded, mortality was significantly associated with penicillin minimum inhibitory concentrations of 4.0 or higher and cefotaxime minimum inhibitory concentrations of 2.0 or higher. In 1996, about 7000 to 12,500 deaths occurred in the United States from pneumococcal pneumonia requiring hospitalization. CONCLUSIONS: Older age and underlying disease remain the most important factors influencing death from pneumococcal pneumonia. Mortality was not elevated in most infections with beta-lactam-resistant pneumococci. [ABSTRACT FROM AUTHOR]

With resistance on the rise among pneumococcal pathogens, prudent use of antibiotics--and reliance on the narrowest-spectrum agent likely to work--must be accompanied by wider use of the vaccine. Are you doing all you can? [ABSTRACT FROM AUTHOR]

Group B streptococci (GBS) cause invasive disease in neonates, pregnant adults, and nonpregnant adults with underlying or chronic disease. Previous studies found capsular serotypes Ia, Ib, II, and III cause invasive disease. Prospective population-based surveillance of invasive GBS disease was done from June 1992 to June 1993 in metropolitan Atlanta: 279 patients had invasive disease. Of these, 43% were < or = 6 months old, and 57% were adults. The incidence among all adults was 7.7/100,000/year, 33% higher than in 1989-1990 (P < .01). The incidence in nonpregnant adults was 5.9/100,000/year, 37% higher than in 1989-1990 (P < .02). Serotyping of 178 patient isolates revealed that 34% had GBS serotype Ia or Ia/c, 8% had Ib/c, 6% had II or II/c, 29% had III, 0% had IV, 21% had V, and 2% were nontypeable. Serotype V was recovered from all groups and was the most common serotype from nonpregnant adults. Serotype V isolates appeared to be highly related genetically. The increasing incidence of GBS disease in adults, the changing distribution of serotypes, and the emergence of serotype V will impact vaccine strategies. [ABSTRACT FROM AUTHOR]

Background: Five of seven serotypes in the pneumococcal conjugate vaccine, introduced for infants in the United States in 2000, are responsible for most penicillin-resistant infections. We examined the effect of this vaccine on invasive disease caused by resistant strains.Methods: We used laboratory-based data from Active Bacterial Core surveillance to measure disease caused by antibiotic-nonsusceptible pneumococci from 1996 through 2004. Cases of invasive disease, defined as disease caused by pneumococci isolated from a normally sterile site, were identified in eight surveillance areas. Isolates underwent serotyping and susceptibility testing.Results: Rates of invasive disease caused by penicillin-nonsusceptible strains and strains not susceptible to multiple antibiotics peaked in 1999 and decreased by 2004, from 6.3 to 2.7 cases per 100,000 (a decline of 57 percent; 95 percent confidence interval, 55 to 58 percent) and from 4.1 to 1.7 cases per 100,000 (a decline of 59 percent; 95 percent confidence interval, 58 to 60 percent), respectively. Among children under two years of age, disease caused by penicillin-nonsusceptible strains decreased from 70.3 to 13.1 cases per 100,000 (a decline of 81 percent; 95 percent confidence interval, 80 to 82 percent). Among persons 65 years of age or older, disease caused by penicillin-nonsusceptible strains decreased from 16.4 to 8.4 cases per 100,000 (a decline of 49 percent). Rates of resistant disease caused by vaccine serotypes fell 87 percent. An increase was seen in disease caused by serotype 19A, a serotype not included in the vaccine (from 2.0 to 8.3 per 100,000 among children under two years of age).Conclusions: The rate of antibiotic-resistant invasive pneumococcal infections decreased in young children and older persons after the introduction of the conjugate vaccine. There was an increase in infections caused by serotypes not included in the vaccine. [ABSTRACT FROM AUTHOR]

Stress signaling is important for determining the fates of neurons following axonal insults. Previously we showed that the stress-responsive kinase PERK contributes to injury-induced neurodegeneration (Larhammar et al., 2017). Here we show that PERK acts primarily through Activating Transcription Factor-4 (ATF4) to stimulate not only pro-apoptotic but also pro-regenerative responses following optic nerve damage. Using conditional knockout mice, we find an extensive PERK/ATF4-dependent transcriptional response that includes canonical ATF4 target genes and modest contributions by C/EBP Homologous Protein (CHOP). Overlap with c-Jun-dependent transcription suggests interplay with a parallel stress pathway that orchestrates regenerative and apoptotic responses. Accordingly, neuronal knockout of ATF4 recapitulates the neuroprotection afforded by PERK deficiency, and PERK or ATF4 knockout impairs optic axon regeneration enabled by disrupting the tumor suppressor PTEN. These findings reveal an integral role for PERK/ATF4 in coordinating neurodegenerative and regenerative responses to CNS axon injury.

Background: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes., Methods: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %)., Results: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively., Conclusions: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lee Harrison provides service on advisory boards (Pfizer, Sanofi, GSK) and a DSMB (Merck); while LH does not receive any fees for this work he is reimbursed for occasional travel. Tamara Pilishvili reports a relationship with GSK that includes: employment. During data collection, analysis, and write-up, TP was employed by CDC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention., Methods: Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data., Results: Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates ( P = .01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates., Conclusions: Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis . Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis ., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission , or acquired resistance. IMPORTANCE In our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo ., Competing Interests: The authors declare no conflict of interest.

Few data exist on asymptomatic carriage of Bordetella species among populations receiving acellular pertussis vaccine. We conducted a cross-sectional study among acellular-vaccinated children presenting to an emergency department (ED). Bordetella pertussis carriage prevalence was <1% in this population, a lower prevalence than that found in recent studies among whole-cell pertussis-vaccinated participants., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2023.)

Background: Nontypeable Haemophilus influenzae (NTHi) is the most common cause of invasive H. influenzae disease in the United States (US). We evaluated the epidemiology of invasive NTHi disease in the US, including among pregnant women, infants, and people with human immunodeficiency virus (PWH)., Methods: We used data from population- and laboratory-based surveillance for invasive H. influenzae disease conducted in 10 sites to estimate national incidence of NTHi, and to describe epidemiology in women of childbearing age, infants aged ≤30 days (neonates), and PWH living in the surveillance catchment areas. H. influenzae isolates were sent to the Centers for Disease Control and Prevention for species confirmation, serotyping, and whole genome sequencing of select isolates., Results: During 2008-⁠2019, average annual NTHi incidence in the US was 1.3/100 000 population overall, 5.8/100 000 among children aged <1 year, and 10.2/100 000 among adults aged ≥80 years. Among 225 reported neonates with NTHi, 92% had a positive culture within the first week of life and 72% were preterm. NTHi risk was 23 times higher among preterm compared to term neonates, and 5.6 times higher in pregnant/postpartum compared to nonpregnant women. More than half of pregnant women with invasive NTHi had loss of pregnancy postinfection. Incidence among PWH aged ≥13 years was 9.5 cases per 100 000, compared to 1.1 cases per 100 000 for non-PWH (rate ratio, 8.3 [95% confidence interval, 7.1-9.7]; P < .0001)., Conclusions: NTHi causes substantial invasive disease, especially among older adults, pregnant/postpartum women, and neonates. Enhanced surveillance and evaluation of targeted interventions to prevent perinatal NTHi infections may be warranted., Competing Interests: Potential conflicts of interest. L. H. H. has served as a member of data and safety monitoring boards for Merck and reports reimbursement for travel expenses from Merck and Pfizer. S. P. reports funding awarded by the Connecticut Department of Public Health by the CDC (Emerging Infections Cooperative Agreement). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the coronavirus disease 2019 (COVID-19) pandemic in the United States are limited., Methods: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as 1 March to 31 December 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014 to February 2020 trends. We conducted secondary analysis of a health care database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic., Results: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated nonpharmaceutical interventions (NPIs). Significant declines were observed across all age and race groups, and surveillance sites for S. pneumoniae and H. influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years., Conclusions: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing., Competing Interests: Presented in part: 12th International Symposium on Pneumococci and Pneumococcal Diseases, Toronto, Canada, 19-23 June., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Candidemia is a common healthcare-associated infection with high mortality. Estimates of recurrence range from 1% to 17%. Few studies have focused on those with recurrent candidemia, who often experience more severe illness and greater treatment failure. We describe recurrent candidemia trends and risk factors., Methods: We analyzed population-based candidemia surveillance data collected during 2011-2018. Persons with >1 episode (defined as the 30-day period after a positive Candida species) were classified as having recurrent candidemia. We compared factors during the initial episode between those who developed recurrent candidemia and those who did not., Results: Of the 5428 persons identified with candidemia, 326 (6%) had recurrent infection. Recurrent episodes occurred 1.0 month to 7.6 years after any previous episode. In multivariable logistic regression controlling for surveillance site and year, recurrent candidemia was associated with being 19-44 years old (vs ≥65 years; adjusted odds ratio [aOR], 3.05 [95% confidence interval {CI}, 2.10-4.44]), being discharged to a private residence (vs medical facility; aOR, 1.53 [95% CI, 1.12-2.08]), hospitalization in the 90 days prior to initial episode (aOR, 1.66 [95% CI, 1.27-2.18]), receipt of total parenteral nutrition (aOR, 2.08 [95% CI, 1.58-2.73]), and hepatitis C infection (aOR, 1.65 [95% CI, 1.12-2.43])., Conclusions: Candidemia recurrence >30 days after initial infection occurred in >1 in 20 persons with candidemia. Associations with younger age and hepatitis C suggest injection drug use may play a modifiable role. Prevention efforts targeting central line care and total parenteral nutrition use may help reduce the risk of recurrent candidemia., Competing Interests: Potential conflicts of interest. Monica M. Farley reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement, NIH grant to institution for the Infectious Diseases Clinical Research Consortium (IDCRC) Leadership Group (unrelated to this project), honoraria for Grand Rounds presentation at NYU in January 2022 (unrelated to this project), and serves in a leadership role on the National Foundation for Medical Research Finance Committee (unrelated to this project). Lee H. Harrison reports support for attending meetings and/or travel from GSK and participation on a Data Safety Monitoring Board or Advisory Board (Merck). William Schaffner reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement and serves as Medical Director for National Foundation for Infectious Diseases outside the submitted work. Tiffanie M. Markus reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement. Rebecca A. Pierce reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program and Epidemiology and Laboratory Capacity cooperative agreements. All other authors report no conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: Disseminated gonococcal infections (DGIs) are thought to be uncommon; surveillance is limited, and case reports are analyzed retrospectively or in case clusters. We describe the population-level burden of culture-confirmed DGIs through the Active Bacterial Core surveillance (ABCs) system., Methods: During 2015-2016, retrospective surveillance was conducted among residents in 2 ABCs areas and prospectively in 3 ABCs areas during 2017-2019. A DGI case was defined as isolation of Neisseria gonorrhoeae from a normally sterile site. A case report form was completed for each case and antimicrobial susceptibility testing (AST) was performed on available isolates., Results: During 2015-2019, 77 DGI cases were identified (a rate of 0.13 cases per 100 000 population) and accounted for 0.06% of all reported gonorrhea cases in the 3 surveillance areas. Most DGI cases were male (64%), non-Hispanic Black (68%), and ranged from 16 to 67 years of age; blood (55%) and joint (40%) were the most common sterile sites. Among 29 isolates with AST results during 2017-2019, all were susceptible to ceftriaxone., Conclusions: DGI is an infrequent complication of N gonorrhoeae; because it can quickly develop antimicrobial resistance, continued DGI surveillance, including monitoring trends in antimicrobial susceptibility, could help inform DGI treatment recommendations., Competing Interests: Potential conflicts of interest. M. M. F. reports a National Institutes of Health grant unrelated to this article outside of the conduct of the study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press for the Infectious Diseases Society of America 2022.)

We evaluated healthcare facility use of International Classification of Diseases, Tenth Revision (ICD-10) codes for culture-confirmed candidemia cases detected by active public health surveillance during 2019-2020. Most cases (56%) did not receive a candidiasis code, suggesting that studies relying on ICD-10 codes likely underestimate disease burden., Competing Interests: Potential conflicts of interest. Christopher A. Czaja reports institutional support from Centers for Disease Control and Prevention cooperative agreements. Helen Johnston reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement. Paula Clogher reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement. Monica M. Farley reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement, NIH/DMID grant to institution (unrelated to this project) and Centers for Disease Control and Prevention Foundation Grant to institution (unrelated to this project). Lee H. Harrison reports support for attending meetings and/or travel from GSK, Sanofi, Merck, Pfizer and Participation on a Data Safety Monitoring Board or Advisory Board (Merck). Sarah Shrum Davis reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement. Erin C. Phipps reports institutional support from the Centers for Disease Control and Prevention. Brenda L. Tesini reports personal book writing honoraria from Merck. Rebecca Pierce reports institutional support from Centers for Disease Control and Prevention cooperative agreements. William Schaffner reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement, consulting fees from VBI Vaccines outside the submitted work, and serves as Medical Director for National Foundation for Infectious Diseases outside the submitted work. All other authors report no conflicts of interest. All authors have completed the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD., Methods: We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100 000 persons)., Results: From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, whereas incidence of nonvaccine type (NVT) NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-2018, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes., Conclusions: Nonsusceptible IPD incidence decreased after PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Disseminated gonococcal infection (DGI) is a rare complication caused by the systemic dissemination of Neisseria gonorrhoeae to normally sterile anatomical sites. Little is known about the genetic diversity of DGI gonococcal strains and how they relate to other gonococcal strains causing uncomplicated mucosal infections. We used whole genome sequencing to characterize DGI isolates (n = 30) collected from a surveillance system in Georgia, United States, during 2017-2020 to understand phylogenetic clustering among DGI as well as uncomplicated uro- and extragenital gonococcal infection (UGI) isolates (n = 110) collected in Fulton County, Georgia, during 2017-2019. We also investigated the presence or absence of genetic markers related to antimicrobial resistance (AMR) as well as surveyed the genomes for putative virulence genetic factors associated with normal human-serum (NHS) resistance that might facilitate DGI. We found that DGI strains demonstrated significant genetic variability similar to the population structure of isolates causing UGI, with sporadic incidences of geographically clustered DGI strains. DGI isolates contained various AMR markers and genetic mechanisms associated with NHS resistance. DGI isolates had a higher frequency of the porB1A allele compared with UGI (67% vs 9%, P  < .0001); however, no single NHS resistance marker was found in all DGI isolates. Continued DGI surveillance with genome-based characterization of DGI isolates is necessary to better understand specific factors that promote systemic dissemination., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older., Methods: We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs., Results: In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively., Conclusions: Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH., Competing Interests: W.S. served as a consultant for VBI Vaccines. L.H.H. served as a consultant for GSK, Merck, Pfizer, and Sanofi Pasteur. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system., Methods: During 2017-2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases., Results: Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n = 66 [63.5%]), mucormycosis (n = 8 [7.7%]), and fusariosis (n = 4 [3.8%]); the most frequently affected body sites were pulmonary (n = 66 [63.5%]), otorhinolaryngologic (n = 17 [16.3%]), and cutaneous/deep tissue (n = 9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit-level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients., Conclusions: IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis., Methods: We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention's Emerging Infections Program during April-August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher's exact tests., Results: Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit-level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%)., Conclusions: One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: Incidence of invasive disease due to Haemophilus influenzae serotype a (Hia) increased an average of 13% annually from 2002 through 2015. We describe clinical characteristics and adverse clinical outcomes of US invasive Hia cases detected through multistate surveillance during 2011-2015., Methods: Medical record data were abstracted for cases reported in 8 jurisdictions conducting active population- and laboratory-based surveillance for invasive Hia disease across the United States. Isolates from sterile sites were serotyped using real-time polymerase chain reaction. Adverse clinical outcomes were defined as any possible complication of meningitis, bacteremic pneumonia, or bacteremia (including hearing loss and developmental delay, but excluding death) and were assessed at hospital discharge and one-year post-disease onset., Results: During 2011-2015, 190 Hia cases were reported to the 8 participating sites; 169 (88.9%) had data abstracted. Many patients were aged <5 years (42.6%). Meningitis was the most common clinical presentation among those aged <1 year (71.4%); bacteremic pneumonia was the most common presentation among persons aged ≥50 years (78.7%). Overall, 95.9% of patients were hospitalized. Among those hospitalized, 47.5% were admitted to an intensive care unit and 6.2% died during hospitalization. At hospital discharge and one-year post-disease onset, adverse outcomes were identified in 17.7% and 17.8% of patients overall and in 43.9% and 48.5% of patients with meningitis (primarily children)., Conclusions: Hia infection can cause severe disease that requires hospitalization and may also cause short- and long-term adverse clinical outcomes, especially among children. Novel vaccines could prevent morbidity and mortality., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines., Methods: During 2017-2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures., Results: Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29-3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate., Conclusions: A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Automated identification systems may misidentify Brucella , the causative agent of brucellosis, which may be re-emerging in the United States as the result of an expanding feral swine population. We present a case of Brucella suis likely associated with feral swine exposure that was misidentified as Ochrobactrum anthropi , a phylogenetic relative., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Clinical trials of COVID-19 vaccines currently authorized for emergency use in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) indicate that these vaccines have high efficacy against symptomatic disease, including moderate to severe illness (1-3). In addition to clinical trials, real-world assessments of COVID-19 vaccine effectiveness are critical in guiding vaccine policy and building vaccine confidence, particularly among populations at higher risk for more severe illness from COVID-19, including older adults. To determine the real-world effectiveness of the three currently authorized COVID-19 vaccines among persons aged ≥65 years during February 1-April 30, 2021, data on 7,280 patients from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed with vaccination coverage data from state immunization information systems (IISs) for the COVID-NET catchment area (approximately 4.8 million persons). Among adults aged 65-74 years, effectiveness of full vaccination in preventing COVID-19-associated hospitalization was 96% (95% confidence interval [CI] = 94%-98%) for Pfizer-BioNTech, 96% (95% CI = 95%-98%) for Moderna, and 84% (95% CI = 64%-93%) for Janssen vaccine products. Effectiveness of full vaccination in preventing COVID-19-associated hospitalization among adults aged ≥75 years was 91% (95% CI = 87%-94%) for Pfizer-BioNTech, 96% (95% CI = 93%-98%) for Moderna, and 85% (95% CI = 72%-92%) for Janssen vaccine products. COVID-19 vaccines currently authorized in the United States are highly effective in preventing COVID-19-associated hospitalizations in older adults. In light of real-world data demonstrating high effectiveness of COVID-19 vaccines among older adults, efforts to increase vaccination coverage in this age group are critical to reducing the risk for COVID-19-related hospitalization., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Evan J. Anderson reports grants from Pfizer, Merck, PaxVax, Micron, Sanofi-Pasteur, Janssen, MedImmune, and GSK; personal fees from Sanofi-Pasteur, Pfizer, Medscape, Kentucky Bioprocessing, Inc, Janssen, outside the submitted work; and his institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. Sue Kim reports grants from Michigan Department of Health and Human Services, during the conduct of the study. William Schaffner reports personal fees from VBI Vaccines, outside the submitted work. Jessica Shiltz reports grants from Council for State and Territorial Epidemiologists during the conduct of the study. No other potential conflicts of interest were disclosed.

Objective: To describe the epidemiology of carbapenem-resistant Enterobacterales (CRE) bacteriuria and to determine whether urinary catheters increase the risk of subsequent CRE bacteremia., Design: Using active population- and laboratory-based surveillance we described a cohort of patients with incident CRE bacteriuria and identified risk factors for developing CRE bacteremia within 1 year., Setting: The study was conducted among the 8 counties of Georgia Health District 3 (HD3) in Atlanta, Georgia., Patients: Residents of HD3 with CRE first identified in urine between 2012 and 2017., Results: We identified 464 patients with CRE bacteriuria (mean yearly incidence, 1.96 cases per 100,000 population). Of 425 with chart review, most had a urinary catheter (56%), and many resided in long-term care facilities (48%), had a Charlson comorbidity index >3 (38%) or a decubitus ulcer (37%). 21 patients (5%) developed CRE bacteremia with the same organism within 1 year. Risk factors for subsequent bacteremia included presence of a urinary catheter (odds ratio [OR], 8.0; 95% confidence interval [CI], 1.8-34.9), central venous catheter (OR, 4.3; 95% CI, 1.7-10.6) or another indwelling device (OR, 4.3; 95% CI, 1.6-11.4), urine culture obtained as an inpatient (OR, 5.7; 95% CI, 1.3-25.9), and being in the ICU in the week prior to urine culture (OR, 2.9; 95% CI, 1.1-7.8). In a multivariable analysis, urinary catheter increased the risk of CRE bacteremia (OR, 5.3; 95% CI, 1.2-23.6)., Conclusions: In patients with CRE bacteriuria, urinary catheters increase the risk of CRE bacteremia. Future interventions should aim to reduce inappropriate insertion and early removal of urinary catheters.

Background: Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008-2017., Methods: Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated., Results: From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN., Conclusions: Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: The mechanisms by which Neisseria meningitidis cause persistent human carriage and transition from carriage to invasive disease have not been fully elucidated., Methods: Georgia and Maryland high school students were sampled for pharyngeal carriage of N. meningitidis during the 2006-2007 school year. A total of 321 isolates from 188 carriers and all 67 invasive disease isolates collected during the same time and from the same geographic region underwent whole-genome sequencing. Core-genome multilocus sequence typing was used to compare allelic profiles, and direct read mapping was used to study strain evolution., Results: Among 188 N. meningitidis culture-positive students, 98 (52.1%) were N. meningitidis culture positive at 2 or 3 samplings. Most students who were positive at >1 sampling (98%) had persistence of a single strain. More than a third of students carried isolates that were highly genetically related to isolates from other students in the same school, and occasional transmission within the same county was also evident. The major pilin subunit gene, pilE, was the most variable gene, and no carrier had identical pilE sequences at different time points., Conclusion: We found strong evidence of local meningococcal transmission at both the school and county levels. Allelic variation within genes encoding bacterial surface structures, particularly pilE, was common., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Hyperinflammation is associated with increased mortality in coronavirus disease 2019 (COVID-19). In this retrospective, uncontrolled patient cohort with moderate -severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized, controlled clinical trials., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development., Methods: Using whole genome sequencing, a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6340 invasive GBS isolates recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in 8 states., Results: Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in 11 clonal complexes (CCs) comprised of multilocus sequence types identical or closely related to sequence types 1, 8, 12, 17, 19, 22, 23, 28, 88, 452, and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with nonsusceptibility to 1 or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin nonsusceptible (minimum inhibitory concentration = 2 µg/mL). Nearly all isolates possessed capsule genes, 1-2 of the 3 main pilus gene clusters, and 1 of 4 homologous alpha/Rib family determinants. Presence of the hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed., Conclusions: This first comprehensive, population-based quantitation of strain features in the United States suggests that current vaccine candidates should have good coverage. The β-lactams remain appropriate for first-line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States. IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States., (Copyright © 2021 Band et al.)

Background: Invasive group B Streptococcus (iGBS) isolates with mutations in the pbp2x gene that encodes penicillin binding protein 2x can have reduced beta-lactam susceptibility (RBLS) when susceptible by Clinical and Laboratory Standards Institute (CLSI) criteria. We assessed the emergence and characteristics of RBLS strains in US iGBS isolates., Methods: We analyzed iGBS isolates from 8 multistate population-based surveillance sites from 1998 to 2018. During 1998-2014, phenotypic antimicrobial susceptibility was determined by broth microdilution; criteria for 6 antibiotics were used to identify RBLS, followed by whole-genome sequencing (WGS). WGS for all isolates was added in 2015; we used phenotypic and genotypic results of >2000 isolates to validate phenotypic RBLS criteria and genotypic predictions. Since 2016, WGS has been used to screen for RBLS with broth microdilution confirmation of predicted RBLS isolates., Results: Of 28 269 iGBS isolates, 28 (0.1%) were nonsusceptible by CLSI criteria; 137 (0.5%) met RBLS criteria. RBLS isolates were detected in all Active Bacterial Core surveillance sites. The RBLS proportion increased, especially since 2013 (odds ratio, 1.17; 95% CI, 1.03-1.32); the proportion that were nonsusceptible remained stable., Conclusions: The RBSL proportion was low but increasing among US iGBS isolates. Ongoing monitoring is needed to detect emerging threats to prevention and treatment of GBS infections., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)

Background: Candidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States (US)., Methods: In 2017, the Centers for Disease Control and Prevention conducted active population-based surveillance for candidemia through the Emerging Infections Program in 45 counties in 9 states encompassing approximately 17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida, and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality were estimated by extrapolating surveillance area cases to national numbers using 2017 national census data., Results: We identified 1226 candidemia cases across 9 surveillance sites in 2017. Based on this, we estimated that 22 660 (95% confidence interval [CI], 20 210-25 110) cases of candidemia occurred in the US in 2017. Overall estimated incidence was 7.0 cases per 100 000 persons, with highest rates in adults aged ≥ 65 years (20.1/100 000), males (7.9/100 000), and those of black race (12.3/100 000). An estimated 3380 (95% CI, 1318-5442) deaths occurred within 7 days of a positive Candida blood culture, and 5628 (95% CI, 2465-8791) deaths occurred during the hospitalization with candidemia., Conclusions: Our analysis highlights the substantial burden of candidemia in the US. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Colistin is an important last-line antibiotic to treat highly resistant Enterobacter infections. Resistance to colistin has emerged among clinical isolates but has been associated with a significant growth defect. Here, we describe a clinical Enterobacter isolate with a deletion of mgrB , a regulator of colistin resistance, leading to high-level resistance in the absence of a growth defect. The identification of a path to resistance unrestrained by growth defects suggests colistin resistance could become more common in Enterobacter .

Background: Injection drug use (IDU) is a known, but infrequent risk factor on candidemia; however, the opioid epidemic and increases in IDU may be changing the epidemiology of candidemia., Methods: Active population-based surveillance for candidemia was conducted in selected US counties. Cases of candidemia were categorized as IDU cases if IDU was indicated in the medical records in the 12 months prior to the date of initial culture., Results: During 2017, 1191 candidemia cases were identified in patients aged >12 years (incidence: 6.9 per 100 000 population); 128 (10.7%) had IDU history, and this proportion was especially high (34.6%) in patients with candidemia aged 19-44. Patients with candidemia and IDU history were younger than those without (median age, 35 vs 63 years; P < .001). Candidemia cases involving recent IDU were less likely to have typical risk factors including malignancy (7.0% vs 29.4%; relative risk [RR], 0.2 [95% confidence interval {CI}, .1-.5]), abdominal surgery (3.9% vs 17.5%; RR, 0.2 [95% CI, .09-.5]), and total parenteral nutrition (3.9% vs 22.5%; RR, 0.2 [95% CI, .07-.4]). Candidemia cases with IDU occurred more commonly in smokers (68.8% vs 18.5%; RR, 3.7 [95% CI, 3.1-4.4]), those with hepatitis C (54.7% vs 6.4%; RR, 8.5 [95% CI, 6.5-11.3]), and in people who were homeless (13.3% vs 0.8%; RR, 15.7 [95% CI, 7.1-34.5])., Conclusions: Clinicians should consider injection drug use as a risk factor in patients with candidemia who lack typical candidemia risk factors, especially in those with who are 19-44 years of age and have community-associated candidemia., (© Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

We assessed viral co-infections in 155 patients with community-associated Clostridioides difficile infection in five U.S. sites during December 2012-February 2013. Eighteen patients (12%) tested positive for norovirus (n = 10), adenovirus (n = 4), rotavirus (n = 3), or sapovirus (n = 1). Co-infected patients were more likely than non-co-infected patients to have nausea or vomiting (56% vs 31%; p = 0.04), suggesting that viral co-pathogens contributed to symptoms in some patients. There were no significant differences in prior healthcare or medication exposures or in CDI complications., Competing Interests: No authors have competing interests.

Background: Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-IC adults., Methods: We identified adults hospitalized with laboratory-confirmed influenza during 2011-2015 seasons through CDC's Influenza Hospitalization Surveillance Network. IC patients had human immunodefiency virus (HIV)/AIDS, cancer, stem cell or organ transplantation, nonsteroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and/or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics. Multivariable logistic regression and Cox proportional hazards models controlled for confounding by patient demographic characteristics, pre-existing medical conditions, influenza vaccination, and other factors., Results: Among 35 348 adults, 3633 (10%) were IC; cancer (44%), nonsteroid immunosuppressive therapy (44%), and HIV (18%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs 46%; P < .001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.20-1.76). Intensive care was more likely among IC patients 65-79 years (aOR, 1.25; 95% CI, 1.06-1.48) and those >80 years (aOR, 1.35; 95% CI, 1.06-1.73) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge, 0.86; 95% CI, .83-.88) and more likely to require mechanical ventilation (aOR, 1.19; 95% CI, 1.05-1.36)., Conclusions: Substantial morbidity and mortality occurred among IC adults hospitalized with influenza. Influenza vaccination and antiviral administration could be increased in both IC and non-IC adults., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)