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.

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.

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.IMPORTANCEIn 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.

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. B. pertussis carriage prevalence was <1% in this population, a lower prevalence than that found in recent studies among whole-cell pertussis-vaccinated participants.

BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) is the most common cause of invasive H. influenzae disease in the United States. We evaluated the epidemiology of invasive NTHi disease in the United States, including among pregnant women, infants, and people with HIV (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 United States 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 non-pregnant women. Over half of pregnant women with invasive NTHi had loss of pregnancy post-infection. Incidence among PWH aged ≥13 years was 9.5 cases per 100,000, compared to 1.1 cases per 100,000 for non-PWH (RR=8.3; 95% CI=7.1-9.7; p<0.0001). CONCLUSION: 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.

BACKGROUND: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the 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 March 1-December 31, 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014-February 2020 trends. We conducted secondary analysis of a healthcare 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 non-pharmaceutical-interventions (NPIs). Significant declines were observed across all age, 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.

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.

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.

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.

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.

BACKGROUND: Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States following 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, while incidence of 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 2014-18, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes. CONCLUSIONS: NS-IPD incidence decreased following 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.

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.

BACKGROUND: Disseminated gonococcal infections (DGI) 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 DGI through the Active Bacterial Core surveillance (ABCs) system. METHODS: During 2015-2016, retrospective surveillance was conducted among residents in two ABCs areas and prospectively in three ABCs areas during 2017-2019. A DGI case was defined as isolation of Neisseria gonorrhoeae (Ng) 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 three surveillance areas. Most DGI cases were male (64%), non-Hispanic Black (68%), and ranged from 16-67 years; 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 Ng; since Ng can quickly develop antimicrobial resistance, continued DGI surveillance, including monitoring trends in antimicrobial susceptibility, could help inform DGI treatment recommendations.

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.

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 co-infection 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 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 co-infection, 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 two 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.

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 nine U.S. 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 1,835 patients who received antifungal treatment, 1,258 (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). Over 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 non-adherence to IDSA guidelines should be evaluated, and clinician education is needed.

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.

BACKGROUND: The mechanisms by which Neisseria meningitidis (Nm) 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 Nm during the 2006-2007 school year. 321 isolates from 188 carriers and all 67 invasive isolates collected during the same time and from the same geographic region underwent whole genome sequencing. Core-genome MLST (cgMLST) was used to compare allelic profiles, and direct read mapping was employed to study strain evolution. RESULTS: Among 188 Nm culture-positive students, 98 (52.1%) were Nm culture-positive at two or three samplings. Most students who were positive at more than one sampling (98%) had persistence of a single strain. Over 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 level. Allelic variation within genes encoding bacterial surface structures, particularly pilE, was common.

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.

BACKGROUND: Incidence of invasive disease due to H. influenzae serotype a (Hia) increased an average of 13% annually from 2002-2015. We described clinical characteristics and adverse clinical outcomes of U.S. invasive Hia cases detected through multi-state surveillance during 2011-2015. METHODS: Medical record data were abstracted for cases reported in eight jurisdictions conducting active population- and laboratory-based surveillance for invasive Hia disease across the United States. Isolates from sterile sites were serotyped by real-time polymerase chain reaction. Adverse clinical outcomes were defined as any possible complication of meningitis, bacteremic pneumonia, or bacteremia (including hearing loss, developmental delay, and speech 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 eight participating sites; 169 (88.9%) had data abstracted. Many patients were aged <5 years (42.6%) or >/=65 years (20.7%). Meningitis was the most common clinical presentation among <1 year olds (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 requiring hospitalization and may also cause short- and long-term adverse clinical outcomes, especially among children. Novel vaccines could prevent morbidity and mortality.

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 2008-2017, 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, incidence was 17 times higher among American Indians 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 U.S. 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.

BACKGROUND: Efforts to prevent Clostridioides difficile infection continue to expand across the health care spectrum in the United States. Whether these efforts are reducing the national burden of C. difficile infection is unclear. METHODS: The Emerging Infections Program identified cases of C. difficile infection (stool specimens positive for C. difficile in a person >/=1 year of age with no positive test in the previous 8 weeks) in 10 U.S. sites. We used case and census sampling weights to estimate the national burden of C. difficile infection, first recurrences, hospitalizations, and in-hospital deaths from 2011 through 2017. Health care-associated infections were defined as those with onset in a health care facility or associated with recent admission to a health care facility; all others were classified as community-associated infections. For trend analyses, we used weighted random-intercept models with negative binomial distribution and logistic-regression models to adjust for the higher sensitivity of nucleic acid amplification tests (NAATs) as compared with other test types. RESULTS: The number of cases of C. difficile infection in the 10 U.S. sites was 15,461 in 2011 (10,177 health care-associated and 5284 community-associated cases) and 15,512 in 2017 (7973 health care-associated and 7539 community-associated cases). The estimated national burden of C. difficile infection was 476,400 cases (95% confidence interval [CI], 419,900 to 532,900) in 2011 and 462,100 cases (95% CI, 428,600 to 495,600) in 2017. With accounting for NAAT use, the adjusted estimate of the total burden of C. difficile infection decreased by 24% (95% CI, 6 to 36) from 2011 through 2017; the adjusted estimate of the national burden of health care-associated C. difficile infection decreased by 36% (95% CI, 24 to 54), whereas the adjusted estimate of the national burden of community-associated C. difficile infection was unchanged. The adjusted estimate of the burden of hospitalizations for C. difficile infection decreased by 24% (95% CI, 0 to 48), whereas the adjusted estimates of the burden of first recurrences and in-hospital deaths did not change significantly. CONCLUSIONS: The estimated national burden of C. difficile infection and associated hospitalizations decreased from 2011 through 2017, owing to a decline in health care-associated infections. (Funded by the Centers for Disease Control and Prevention.).

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. METHODS: In 2017, the Centers for Disease Control and Prevention (CDC) conducted active population-based surveillance for candidemia through the Emerging Infections Program (EIP) in 45 counties in nine states encompassing ~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 was estimated by extrapolating surveillance area cases to national numbers using 2017 national census data. RESULTS: We identified 1,226 candidemia cases across nine surveillance sites in 2017. Based on this, we estimated 22,660 (95% confidence interval [CI]: 20,210-25,110) cases of candidemia occurred in the United States in 2017. Overall estimated incidence was 7.0 cases per 100,000 persons, with highest rates in adults >/=65 years (20.1/100,000), males (7.9/100,000), and those of black race (12.3/100,000). An estimated 3,380 (95% CI: 1,318-5,442) deaths occurred within seven days of a positive Candida blood culture and 5,628 (95% CI: 2,465-8,791) deaths occurred during the hospitalization with candidemia. CONCLUSIONS: Our analysis highlights the substantial burden of candidemia in the U.S. 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.

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 (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight 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 eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more beta-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 (MIC 2microg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of 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 current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

Importance: Invasive nontypeable Haemophilus influenzae (NTHi) infection among adults is typically associated with bacteremic pneumonia. Nontypeable H influenzae is genetically diverse and clusters of infection are uncommon. Objective: To evaluate an increase in invasive NTHi infection from 2017-2018 among HIV-infected men who have sex with men in metropolitan Atlanta, Georgia. Design, Setting, and Participants: A population-based surveillance study with a cohort substudy and descriptive epidemiological analysis identified adults aged 18 years or older with invasive NTHi infection (isolation of NTHi from a normally sterile site) between January 1, 2008, and December 31, 2018 (final date of follow-up). Exposures: Time period, HIV status, and genetic relatedness (ie, cluster status) of available NTHi isolates. Main Outcomes and Measures: The primary outcome was incidence of invasive NTHi infection (from 2008-2016 and 2017-2018) among persons with HIV and compared with NTHi infection from 2008-2018 among those without HIV. The secondary outcomes were assessed among those aged 18 to 55 years with invasive NTHi infection and included epidemiological, clinical, and geographic comparisons by cluster status. Results: Among 553 adults with invasive NTHi infection (median age, 66 years [Q1-Q3, 48-78 years]; 52% male; and 38% black), 60 cases occurred among persons with HIV. Incidence of invasive NTHi infection from 2017-2018 among persons with HIV (41.7 cases per 100000) was significantly greater than from 2008-2016 among those with HIV (9.6 per 100000; P < .001) and from 2008-2018 among those without HIV (1.1 per 100000; P < .001). Among adults aged 18 to 55 years with invasive NTHi infections from 2017-2018 (n = 179), persons with HIV (n = 31) were significantly more likely than those from 2008-2018 without HIV (n = 124) to be male (94% vs 49%, respectively; P < .001), black (100% vs 53%; P < .001), and have septic arthritis (35% vs 1%; P < .001). Persons with HIV who had invasive NTHi infection from 2017-2018 (n = 31) were more likely than persons with HIV who had invasive NTHi infection from 2008-2016 (n = 24) to have septic arthritis (35% vs 4%, respectively; P = .01). Pulsed-field gel electrophoresis of 174 of 179 NTHi isolates from 18- to 55-year-olds identified 2 genetically distinct clonal groups: cluster 1 (C1; n = 24) and cluster 2 (C2; n = 23). Whole-genome sequencing confirmed 2 clonal lineages of NTHi infection and revealed all C1 isolates (but none of the C2 isolates) carried IS1016 (an insertion sequence associated with H influenzae capsule genes). Persons with HIV were significantly more likely to have C1 or C2 invasive NTHi infection from 2017-2018 (28/31 [90%]) compared with from 2008-2016 among persons with HIV (10/24 [42%]; P < .001) and compared with from 2008-2018 among those without HIV (9/119 [8%]; P < .001). Among persons with C1 or C2 invasive NTHi infection who had HIV (n = 38) (median age, 34.5 years; 100% male; 100% black; 82% men who have sex with men), 32 (84%) lived in 2 urban counties and an area of significant spatial aggregation was identified compared with those without C1 or C2 invasive NTHi infection. Conclusions and Relevance: Among persons with HIV in Atlanta, the incidence of invasive nontypeable H influenzae infection increased significantly from 2017-2018 compared with 2008-2016. Two unique but genetically related clonal strains were identified and were associated with septic arthritis among black men who have sex with men and who lived in geographic proximity.

BACKGROUND: Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines describe recommended therapy for Clostridioides difficile infection (CDI). OBJECTIVE: To describe CDI treatment and, among those with severe CDI, determine predictors of adherence to the 2010 IDSA/SHEA treatment guidelines. DESIGN: We analyzed 2013-2015 CDI treatment data collected through the Centers for Disease Control and Prevention's Emerging Infections Program. Generalized linear mixed models were used to identify predictors of guideline-adherent therapy. PATIENTS: A CDI case was defined as a positive stool specimen in a person aged >/= 18 years without a positive test in the prior 8 weeks; severe CDI cases were defined as having a white blood cell count >/= 15,000 cells/mul. MAIN MEASURES: Prescribing and predictors of guideline-adherent CDI therapy for severe disease. KEY RESULTS: Of 18,243 cases, 14,257 (78%) were treated with metronidazole, 7683 (42%) with vancomycin, and 313 (2%) with fidaxomicin. The median duration of therapy was 14 (interquartile range, 11-15) days. Severe CDI was identified in 3250 (18%) cases; of 3121 with treatment data available, 1480 (47%) were prescribed guideline-adherent therapy. Among severe CDI cases, hospital admission (adjusted odds ratio [aOR] 2.48; 95% confidence interval [CI] 1.90, 3.24), age >/= 65 years (aOR 1.37; 95% CI 1.10, 1.71), Charlson comorbidity index >/= 3 (aOR 1.27; 95% CI 1.04, 1.55), immunosuppressive therapy (aOR 1.21; 95% CI 1.02, 1.42), and inflammatory bowel disease (aOR 1.56; 95% CI 1.13, 2.17) were associated with being prescribed guideline-adherent therapy. CONCLUSIONS: Provider adherence to the 2010 treatment guidelines for severe CDI was low. Although the updated 2017 CDI guidelines, which expand the use of oral vancomycin for all CDI, might improve adherence by removing the need to apply severity criteria, other efforts to improve adherence are likely needed, including educating providers and addressing barriers to prescribing guideline-adherent therapy, particularly in outpatient settings.

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 over the age of 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 years. Candidemia patients with IDU history were younger than those without (median age: 35 vs 63 years, p<0.001). 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): 0.1-0.5), abdominal surgery (3.9% vs 17.5%, RR: 0.2, CI: 0.09-0.5), and total parenteral nutrition (3.9% vs 22.5%, RR: 0.2, CI: 0.07-0.4). Candidemia cases with IDU occurred more commonly in smokers (68.8% vs 18.5%, RR: 3.7, CI: 3.1-4.4), those with hepatitis C (54.7% vs 6.4%, RR: 8.5, CI: 6.5-11.3), and in people who were homeless (13.3% vs 0.8%, RR: 15.7; CI: 7.1-34.5). CONCLUSION: Clinicians should consider screening for candidemia in people who inject drugs and IDU in patients with candidemia who lack typical candidemia risk factors, especially in those with who are 19-44 years, and have community-associated candidemia.

PROBLEM/CONDITION: Candidemia is a bloodstream infection (BSI) caused by yeasts in the genus Candida. Candidemia is one of the most common health care-associated BSIs in the United States, with all-cause in-hospital mortality of up to 30%. PERIOD COVERED: 2012-2016. DESCRIPTION OF SYSTEM: CDC's Emerging Infections Program (EIP), a collaboration among CDC, state health departments, and academic partners that was established in 1995, was used to conduct active, population-based laboratory surveillance for candidemia in 22 counties in four states (Georgia, Maryland, Oregon, and Tennessee) with a combined population of approximately 8 million persons. Laboratories serving the catchment areas were recruited to report candidemia cases to the local EIP program staff. A case was defined as a blood culture that was positive for a Candida species collected from a surveillance area resident during 2012-2016. Isolates were sent to CDC for species confirmation and antifungal susceptibility testing. Any subsequent blood cultures with Candida within 30 days of the initial positive culture in the same patient were considered part of the same case. Trained surveillance officers collected clinical information from the medical chart for all cases, and isolates were sent to CDC for species confirmation and antifungal susceptibility testing. RESULTS: Across all sites and surveillance years (2012-2016), 3,492 cases of candidemia were identified. The crude candidemia incidence averaged across sites and years during 2012-2016 was 8.7 per 100,000 population; important differences in incidence were found by site, age group, sex, and race. The crude annual incidence was the highest in Maryland (14.1 per 100,000 population) and lowest in Oregon (4.0 per 100,000 population). The crude annual incidence of candidemia was highest among adults aged >/=65 years (25.5 per 100,000 population) followed by infants aged <1 year (15.8). The crude annual incidence was higher among males (9.4) than among females (8.0) and was approximately 2 times greater among blacks than among nonblacks (13.7 versus 5.8). Ninety-six percent of cases occurred in patients who were hospitalized at the time of or during the week after having a positive culture. One third of cases occurred in patients who had undergone a surgical procedure in the 90 days before the candidemia diagnosis, 77% occurred in patients who had received systemic antibiotics in the 14 days before the diagnosis, and 73% occurred in patients who had had a central venous catheter (CVC) in place within 2 days before the diagnosis. Ten percent were in patients who had used injection drugs in the past 12 months. The median time from admission to candidemia diagnosis was 5 days (interquartile range [IQR]: 0-16 days). Among 2,662 cases that were treated in adults aged >18 years, 34% were treated with fluconazole alone, 30% with echinocandins alone, and 34% with both. The all-cause, in-hospital case-fatality ratio was 25% for any time after admission; the all-cause in-hospital case-fatality ratio was 8% for <48 hours after a positive culture for Candida species. Candida albicans accounted for 39% of cases, followed by Candida glabrata (28%) and Candida parapsilosis (15%). Overall, 7% of isolates were resistant to fluconazole and 1.6% were resistant to echinocandins, with no clear trends in resistance over the 5-year surveillance period. INTERPRETATION: Approximately nine out of 100,000 persons developed culture-positive candidemia annually in four U.S. sites. The youngest and oldest persons, men, and blacks had the highest incidences of candidemia. Patients with candidemia identified in the surveillance program had many of the typical risk factors for candidemia, including recent surgery, exposure to broad-spectrum antibiotics, and presence of a CVC. However, an unexpectedly high proportion of candidemia cases (10%) occurred in patients with a history of injection drug use (IDU), suggesting that IDU has become a common risk factor for candidemia. Deaths associated with candidemia remain high, with one in four cases resulting in death during hospitalization. PUBLIC HEALTH ACTION: Active surveillance for candidemia yielded important information about the disease incidence and death rate and persons at greatest risk. The surveillance was expanded to nine sites in 2017, which will improve understanding of the geographic variability in candidemia incidence and associated clinical and demographic features. This surveillance will help monitor incidence trends, track emergence of resistance and species distribution, monitor changes in underlying conditions and predisposing factors, assess trends in antifungal treatment and outcomes, and be helpful for those developing prevention efforts. IDU has emerged as an important risk factor for candidemia, and interventions to prevent invasive fungal infections in this population are needed. Surveillance data documenting that approximately two thirds of candidemia cases were caused by species other than C. albicans, which are generally associated with greater antifungal resistance than C. albicans, and the presence of substantial fluconazole resistance supports 2016 clinical guidelines recommending a switch from fluconazole to echinocandins as the initial treatment for candidemia in most patients.

BACKGROUND: Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-immunocompromised adults. METHODS: We identified adults (>/=18 years) hospitalized with laboratory-confirmed influenza during 2011-2015 seasons through CDC's Influenza Hospitalization Surveillance Network. IC patients had >/=1: HIV/AIDS, cancer, stem cell or organ transplantation, non-steroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics and used multivariable logistic regression and Cox proportional hazards models to control 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%), non-steroid immunosuppressive therapy (44%), and HIV (17%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs. 46%; p<0.001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.46 [1.20-1.76]). Intensive care was more likely among IC patients 65-79 years (aOR [95% CI]: 1.25 [1.06-1.48]) and >80 years (aOR [95% CI]: 1.35 [1.06-1.73]) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge [95% CI]: 0.86 [0.83-0.88]) and were more likely to require mechanical ventilation (aOR [95% CI] 1.19 [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.

We characterized 22 meningococcal disease cases due to nongroupable Neisseria meningitidis, a rare cause of invasive disease. Disease presentation and severity were similar to those for serogroupable meningococcal disease. However, 7 (32%) patients had complement deficiency or abnormal complement testing results, highlighting the importance of complement testing for nongroupable cases.