Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .

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.

Staphylococcus aureus clinical isolates with vancomycin MICs of 2 μg/ml have been associated with vancomycin therapeutic failure and the heteroresistant vancomycin-intermediate S. aureus (hVISA) phenotype. A population analysis profile (PAP) with an area under the curve (AUC) ratio of ≥0.9 for the AUC of the clinical isolate versus the AUC for hVISA strain Mu3 is most often used for determining hVISA, but it is time-consuming and labor-intensive. A collection of 140 MRSA blood isolates with vancomycin MICs of 2 μg/ml by reference broth microdilution and screened for hVISA using PAP-AUC (21/140 [15%] hVISA) were tested by additional methods to detect hVISA. The methods included (i) Etest macromethod using vancomycin and teicoplanin test strips, brain heart infusion (BHI) agar, and a 2.0 McFarland inoculum; (ii) Etest glycopeptide resistance detection (GRD) using vancomycin-teicoplanin double-sided gradient test strips on Mueller-Hinton agar (MHA) with 5% sheep blood and a 0.5 McFarland inoculum; and (iii) BHI screen agar plates containing 4 μg/ml vancomycin and 16 g/liter casein using 0.5 and 2.0 McFarland inocula. Each method was evaluated using PAP-AUC as the reference method. The sensitivity of each method for detecting hVISA was higher when the results were read at 48 h. The Etest macromethod was 57% sensitive and 96% specific, Etest GRD was 57% sensitive and 97% specific, and BHI screen agar was 90% sensitive and 95% specific with a 0.5 McFarland inoculum and 100% sensitive and 68% specific with a 2.0 McFarland inoculum. BHI screen agar with 4 μg/ml vancomycin and casein and a 0.5 McFarland inoculum had the best sensitivity and specificity combination, was easy to perform, and may be useful for clinical detection of hVISA.

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.

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: 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.

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.

Nucleic acid amplification testing (NAAT) is increasingly being adopted for diagnosis of Clostridium difficile infection (CDI). Data from 3 states conducting population-based CDI surveillance showed increases ranging from 43% to 67% in CDI incidence attributable to changing from toxin enzyme immunoassays to NAAT. CDI surveillance requires adjustment for testing methods. © 2013 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Background: In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. Methods: We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. Findings: Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. We estimated that over 30 000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. Interpretation: PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations.

Several countries in Europe and Australia are reporting an increasing incidence of Neisseria meningitidis serogroup W (NmW) as a consequence of the rapid expansion of a single NmW clone belonging to clonal complex 11 (1-5). Because this clone is reported to be associated with more severe disease, unusual clinical presentations, and a high case fatality ratio (CFR), it is considered a hypervirulent strain (1,6). In the United States, NmW accounts for approximately 5% of meningococcal disease reported each year, and this proportion has remained stable for several years (7). However, localized increases in NmW have been reported, most notably in Florida during 2008-2009 (8). In Georgia, NmW accounted for only 3% of meningococcal disease cases reported during 2006-2013; however, between January 2014 and December 2016, 42% of all reported cases were NmW. Surveillance data from Georgia were analyzed to describe the epidemiology and clinical characteristics of NmW cases, and whole-genome sequencing of NmW isolates was performed for comparison with NmW strains circulating in the United States and worldwide. These data indicate that the U.S. NmW strains might have evolved from the same ancestor as the hypervirulent strain that is circulating globally. Genetic analysis demonstrates that these strains are closely related, which would suggest that genetic variation led to the rise of different strains from the same ancestor. Given the recent global expansion of this potentially hypervirulent NmW lineage, clinicians and public health officials need to remain vigilant in obtaining isolates to monitor changes in circulating strains.