BACKGROUND: Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years. METHODS: We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression. RESULTS: We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines. CONCLUSIONS: HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

This report updates the 2020-21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021-22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4).The 2021-22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html. Recommendations for the use of COVID-19 vaccines are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html, and additional clinical guidance is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.Updates described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021-22 season are expected to be quadrivalent. Second, the composition of 2021-22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture-based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture-based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4. This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021-22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu); vaccination and health care providers should check this site periodically for additional information.

INTRODUCTION: The 2016-2017 and 2017-2018 influenza seasons were notable for high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match. METHODS: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by RT-PCR for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees. RESULTS: A total of 6,129 adults were enrolled from ten hospitals. Adjusted VE against A(H3N2) was 22.8% (95% C.I. 8.3%, 35.0%), pooled across both years and 49.4% (95% C.I. 34.3%, 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% C.I. -36.3%, 76.1%; 56 vaccine recipients) compared to 24.0% (95% C.I. 3.9%, 39.9%) for egg based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals. CONCLUSIONS: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE.

This report updates the 2019-20 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2019;68[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Most influenza vaccines available for the 2020-21 season will be quadrivalent, with the exception of MF59-adjuvanted IIV, which is expected to be available in both quadrivalent and trivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 23, 2019; February 26, 2020; and June 24, 2020. Primary updates to this report include the following two items. First, the composition of 2020-21 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Victoria lineage components. Second, recent licensures of two new influenza vaccines, Fluzone High-Dose Quadrivalent and Fluad Quadrivalent, are discussed. Both new vaccines are licensed for persons aged ≥65 years. Additional changes include updated discussion of contraindications and precautions to influenza vaccination and the accompanying Table, updated discussion concerning use of LAIV4 in the setting of influenza antiviral medication use, and updated recommendations concerning vaccination of persons with egg allergy who receive either cell culture-based IIV4 (ccIIV4) or RIV4.The 2020-21 influenza season will coincide with the continued or recurrent circulation of SARS-CoV-2 (the novel coronavirus associated with coronavirus disease 2019 [COVID-19]). Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient illnesses, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html.This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2020-21 season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration (FDA)-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

BACKGROUND: Antibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation. METHODS: Electronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments. RESULTS: We identified 14 Verona integron-encoded metallo-ss-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment. CONCLUSIONS: This investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.

BACKGROUND: Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged >/=65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. METHODS: Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at eight hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015-2016 and 2016-2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. RESULTS: Among 1487 enrolled patients aged >/=65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] -42%, 38%) and that of HD-IIV was 32% (95%CI -3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95%CI -1%, 48%). CONCLUSIONS: During two U.S. influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged >/=65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

This report updates the 2018-19 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2018;67[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged >/=6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV), and live attenuated influenza vaccine (LAIV) are expected to be available for the 2019-20 season. Standard-dose, unadjuvanted, inactivated influenza vaccines will be available in quadrivalent formulations (IIV4s). High-dose (HD-IIV3) and adjuvanted (aIIV3) inactivated influenza vaccines will be available in trivalent formulations. Recombinant (RIV4) and live attenuated influenza vaccine (LAIV4) will be available in quadrivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 25, 2018; February 27, 2019; and June 27, 2019. Primary updates in this report include the following two items. First, 2019-20 U.S. trivalent influenza vaccines will contain hemagglutinin (HA) derived from an A/Brisbane/02/2018 (H1N1)pdm09-like virus, an A/Kansas/14/2017 (H3N2)-like virus, and a B/Colorado/06/2017-like virus (Victoria lineage). Quadrivalent influenza vaccines will contain HA derived from these three viruses, and a B/Phuket/3073/2013-like virus (Yamagata lineage). Second, recent labeling changes for two IIV4s, Afluria Quadrivalent and Fluzone Quadrivalent, are discussed. The age indication for Afluria Quadrivalent has been expanded from >/=5 years to >/=6 months. The dose volume for Afluria Quadrivalent is 0.25 mL for children aged 6 through 35 months and 0.5 mL for all persons aged >/=36 months (>/=3 years). The dose volume for Fluzone Quadrivalent for children aged 6 through 35 months, which was previously 0.25 mL, is now either 0.25 mL or 0.5 mL. The dose volume for Fluzone Quadrivalent is 0.5 mL for all persons aged >/=36 months (>/=3 years).This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2019-20 season in the United States. A brief summary of these recommendations and a Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

BACKGROUND: Recent studies of influenza vaccine effectiveness (VE) observed lower effectiveness with increasing time since vaccination, raising the question of optimal vaccination timing. We sought to evaluate the estimated number of influenza-associated hospitalizations among older adults due to potential changes in vaccination timing. METHODS: Using empirical data and a health state transition model, we estimated change in influenza-associated hospitalizations predicted to occur among the U.S. population aged >/=65 years if vaccination were delayed until October 1. We assumed the vaccination timing, coverage, and effectiveness observed in 2012-13 as a prototypical influenza season, ~7% monthly waning of VE, and that between 0% and 50% of individuals who usually get vaccinated earlier than October failed to get vaccinated. We also assessed change in influenza-associated hospitalizations if vaccination uptake shifted substantially toward August and September. RESULTS: In a typical season, delaying vaccination until October increased influenza hospitalizations if more than 14% of older adults usually vaccinated in August and September failed to get vaccinated. The consequences of delayed vaccination depended heavily on influenza season timing, rate of waning, and overall VE. A shift toward vaccination in August and September led to, on average, an increase in influenza-associated hospitalizations, but this result was also sensitive to influenza season timing. CONCLUSIONS: Consequences of delayed vaccination varied widely. Uncertainties about vaccine waning and effects of a delay on vaccine coverage suggest it is premature to change current vaccine recommendations, although it may be prudent to prevent a substantial shift toward early vaccination.

Background: Evidence establishing effectiveness of influenza vaccination for prevention of severe illness is limited. The US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) is a multi-year test-negative case-control study initiated in 2015-16 to estimate effectiveness of vaccine in preventing influenza hospitalization among adults. Methods: Adults aged >/=18 years admitted to eight US hospitals with acute respiratory illness and testing positive for influenza by PCR were cases; those testing negative were controls. VE was estimated with logistic regression adjusting for age, comorbidities and other confounding factors and stratified by frailty, two-year vaccination history, and clinical presentation. Results: We analyzed data from 236 cases and 1231 controls; mean age was 58 years. Over 90% of patients had >/=1 comorbidity elevating risk of influenza complications. Fifty percent of cases and 70% of controls were vaccinated. Vaccination was 51% (95%CI 29, 65) and 53% (95%CI 11, 76) effective in preventing hospitalization due to influenza A(H1N1)pdm09 and influenza B virus infection, respectively. Vaccine was protective for all age groups. Conclusions: During the 2015-16 US influenza A(H1N1)pdm09-predominant season, we found that vaccination halved the risk of influenza-association hospitalization among adults, most of whom were at increased risk of serious influenza complications due to comorbidity or age.

Mycobacterium chimaera is a nontuberculous mycobacterium species commonly found in the environment. Here, we report the first complete genome sequence of a strain from the investigation of invasive infections following open-heart surgeries that used contaminated LivaNova Sorin Stockert 3T heater-cooler devices.

Eighty Gram-negative bacilli (54 Enterobacteriaceae and 26 non-fermenting Gram-negative bacilli), obtained from multiple institutions in the United States were distributed in a blinded manner to seven testing laboratories to compare the performance of a test for detection of carbapenemase production, the Carba NP test. The Carba NP test was performed by all laboratories, following the Clinical and Laboratory Standards Institute (CLSI) procedure. Site-versus-site comparisons demonstrated a high level of consistency for the Carba NP assay with just 3/21 site comparisons yielding a difference in sensitivity (p<0.05). Previously described limitations with blaOXA-48-like carbapenemases and blaOXA carbapenemases associated with Acinetobacter baumannii were noted. Based on these data, we demonstrate that the Carba NP test, when implemented with the standardized CLSI methodology, provides reproducible results across multiple sites for detection of carbapenemases.