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Background. Persons with human immunodeficiency virus (HIV) infection are at increased risk of pneumococcal disease. We evaluated the safety and immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) in this population. Methods. HIV-infected persons ≥18 years of age who were previously vaccinated with ≥1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and had CD4 cell counts ≥200 cells/mm3 and HIV viral loads <50 000 copies/mL were enrolled in this 3-dose PCV13 open-label study. Results. A total of 329 subjects received ≥1 dose, and 279 received 3 doses administered at 6-month intervals. Increases in anticapsular polysaccharide immunoglobulin G concentrations and opsonophagocytic antibody titers were demonstrated 1 month after each of the 3 doses of PCV13. Antibody levels were generally similar after each dose. The responses were similar whether subjects had previously received 1 or ≥2 doses of PPSV23. Pain at the injection-site was the most common local reaction. Severe injection site or systemic events were uncommon. Conclusions. Vaccination with PCV13 induces anticapsular immunoglobulin G and opsonophagocytic antibody responses in HIV-infected adults with prior PPSV23 vaccination and CD4 cell counts ≥200 cells/mm3. The observations support the use of PCV13 in this population. [ABSTRACT FROM AUTHOR]

Twenty-seven episodes of Pseudomonas aeruginosa bacteremia in 21 patients with AIDS were evaluated at the Mount Sinai Medical Center in 1987–1992. Of 21 primary episodes, 12 were acquired in the community, 8 were nosocomial, and one was acquired in a nursing home. Sources of bacteremia (i.e., sites of infection; n = 30) included the lungs (12 cases) an indwelling vascular catheter (9), and the upper respiratory tract (5, including 2 cases of sinusitis, 2 cases of malignant external otitis, and 1 case of epiglottitis/pharyngeal cellulitis); in 4 cases the source was unknown. White blood cell counts ranged from 0.1 to 26.2 (mean, 4.32) × 103/mm3; in 19 of 26 cases, the absolute neutrophil count was >1 × 103/mm3. With the exclusion of primary episodes of bacteremia that resulted in death, the rate of relapse was 33.3% (5 of 15 cases). Mortality for the 25 evaluable episodes of bacteremia was 40% (32% for primary infection and 80% for relapse; P = .06); 52.6% of evaluable patients (10 of 19) ultimately died of P. aeruginosa bacteremia. The institution of appropriate therapy at presentation did not positively affect outcome. Rates of response were higher among episodes treated with a drug combination (an antipseudomonal β-lactam or monobactam antibiotic plus an aminoglycoside) than among those treated with a single agent (P = .036). [ABSTRACT FROM PUBLISHER]

Background Staphylococcus aureus causes serious health care– and community-associated disease, requiring improved preventive measures such as vaccines. The investigational S. aureus 4-antigen vaccine (SA4Ag), comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant mutant clumping factor A (r m ClfA), and recombinant manganese transporter protein C (rP305A or rMntC), was well tolerated, inducing robust functional immune responses to all 4 antigens through 12 months postvaccination. This is a serological extension study through 36 months postvaccination. Methods In 2 previous studies, healthy adults received SA4Ag, SA3Ag (without rMntC), or placebo; serology was also assessed at ~24 and ~36 months postvaccination. Functional immune responses (antibody responses that facilitate killing of S. aureus or neutralize S. aureus virulence mechanisms) were assessed with opsonophagocytic activity killing assays (CP5 or CP8) and a fibrinogen-binding inhibition assay (ClfA). A competitive Luminex immunoassay assessed ClfA and rMntC responses. Adverse events within 48 hours of blood draw were recorded. Results Four hundred forty subjects (18–64 years old, 255; 65–85 years old, 185) were enrolled. At 24 and 36 months postvaccination, subjects receiving SA4Ag had substantially higher geometric mean titers (GMTs) for CP5, CP8, and ClfA vs baseline; geometric mean fold rises (GMFRs) from baseline to month 36 were 2.7–8.1. For rMntC, 36-month GMTs declined from peak levels but remained above baseline for all SA4Ag groups; GMFRs from baseline to month 36 were 1.8 and 1.5 in the younger and older cohorts, respectively. Conclusions Persistent functional immune responses to S. aureus antigens were observed through 36 months in healthy adults. ClinicalTrials.gov NCT01643941 and NCT01364571. [ABSTRACT FROM AUTHOR]

The article discusses safety findings from the associated phase 2-3 clinical trial that were provided to the Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration (FDA) to support the emergency use authorization (EUA) of the BNT162b2 vaccine in children. Topics include safety data are presented according to protocol-defined end points; and the protocol defined end point was evaluated after the administration of dose the protocol-defined end point.

Background Vaccination effectively reduces invasive disease and pneumonia caused by Streptococcus pneumoniae . However, waning antibody titers and the ability of revaccination to boost titers in older adults have been concerns. A study to describe antibody persistence after vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) and response to revaccination 5 years after the initial dose was conducted. Methods Pneumococcal vaccine–naive subjects aged 50–59 years were randomized and vaccinated with PCV13 plus trivalent inactivated influenza vaccine concomitantly or 1 month apart, then revaccinated with PCV13 five years later. Antipneumococcal polysaccharide opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) were determined before and approximately 1 month after each vaccination. Targeted local reactions and systemic events were collected for 14 days, adverse events (AEs) for 1 month, and serious AEs (SAEs) for 6 months after each vaccination. Results Of 1116 randomized subjects, 727 were revaccinated at year 5. Between the time of initial vaccination and revaccination, OPA GMTs and IgG GMCs declined but remained higher than levels before initial vaccination for 12 of the 13 vaccine serotypes. One month after revaccination, OPA GMTs and IgG GMCs were comparable with, or higher than, levels observed 1 month after initial vaccination for most vaccine serotypes. Local reactions were mostly mild. AEs were reported by <5% and SAEs by <1% of subjects at 1 and 6 months after revaccination, respectively. No SAEs were vaccine-related. Conclusions Revaccination of adults ≥50 years with PCV13 five years after primary vaccination was safe and immunogenic. Additionally, antibody titers were maintained for at least 5 years after vaccination. The vaccine stimulated a memory response as shown by enhanced responses that were maintained or enhanced by revaccination. ClinicalTrials.gov registration NCT00521586. [ABSTRACT FROM AUTHOR]

The article reports that use ofSGLT2 inhibitors in the Prospective ARNI versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events after Myocardial Infarction. Topics include meta-analysis, Fang and colleagues pool data from three trials, including ours, which provide support for the safety and efficacy of two different mRNA Covid-19 vaccines; and age of participants in the trial populations and the differences in vaccines and vaccine dosages.

Background: Older individuals and adults with certain chronic or immunocompromising health conditions are at increased risk of severe RSV disease., Methods: In this phase 3 randomized trial of RSVpreF safety and immunogenicity in 18-59-year-olds at high-risk of severe RSV disease, participants were randomized 2:1 to 1 RSVpreF (120 µg) or placebo dose. Primary safety endpoints included reactogenicity events and adverse events (AEs) through 7 days and 1 month after vaccination, respectively, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) throughout the study. In primary analyses, immunogenicity elicited 1 month after RSVpreF was bridged to a randomly selected subset of ≥60-year-olds receiving RSVpreF from the immunogenicity subset in the pivotal phase 3 RENOIR trial, which demonstrated RSVpreF efficacy. Noninferiority was declared if 95% CI lower bounds were >0.667 (neutralizing titer adjusted geometric mean ratios) and >-10% (seroresponse rate differences) for RSV-A and RSV-B., Results: Overall, 678 participants received RSVpreF (n=453) or placebo (n=225). Most reactogenicity events were mild/moderate; severe events occurred in ≤2.0% of participants overall. AE frequencies were similar in RSVpreF (7.1%) and placebo recipients (7.6%). No vaccine-related SAEs or NDCMCs were reported. One month after RSVpreF administration, noninferiority criteria were met in 18-59-year-olds versus ≥60-year-olds for RSV-A and RSV-B neutralizing titers and seroresponse rates., Conclusion: RSVpreF was well tolerated with no safety concerns and demonstrated immunobridging to efficacy in 18-59-year-olds at high-risk of severe RSV disease versus ≥60-year-olds in whom efficacy was previously demonstrated, supporting use of RSVpreF to prevent RSV-associated disease in this population. NCT05842967., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Staphylococcus aureus is a global pathogen that is frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S. aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S. aureus infection is critically needed. We evaluated the efficacy and safety of an investigational 4-antigen S. aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation., Methods: In this multicenter, site-level, randomized, double-blind trial, patients aged 18-85 years received a single dose of SA4Ag or placebo 10-60 days before surgery. SA4Ag efficacy in preventing postoperative S. aureus bloodstream infection and/or deep incisional or organ/space SSIs was the primary end point. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed., Results: Study enrollment was halted when a prespecified interim efficacy analysis met predefined futility criteria. SA4Ag showed no efficacy (0.0%) in preventing postoperative S. aureus infection (14 cases in each group through postoperative day 90), despite inducing robust functional immune responses to each antigen compared with placebo. Colonization rates across groups were similar through postoperative day 180. Local reactions and systemic events were mostly mild or moderate in severity, with AEs reported at similar frequencies across groups., Conclusions: In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe and well tolerated but, despite eliciting substantial antibody responses that blocked key S. aureus virulence mechanisms, was not efficacious in preventing S. aureus infection. Clinical Trials Registration. NCT02388165., Competing Interests: Potential conflicts of interest. H. H. is a consultant for Medtronic, DePuy, Nuvasive, and Orthofix; has obtained research support from Orthofix, Nuvasive, Medtronic, SKK, and Pfizer; has taught/spoken for Nuvasive, Medtronic, Orthofix, and Globus; has received payment for expert testimony from the Expert Institute; has participated on an advisory board for MTF; and reports stock or stock options with Nuvasive and 4Web. V. P. is a consultant for Medtronic; has obtained research support from Pfizer, Orthofix, Medicrea, Mainstay Medical, SI Bone, and Premia Spine; reports grants or contracts from Spinal Kinetics; reports consulting fees from DePuy Synthes, J&J SI-BONE, Mainstay Medical, Zimmer, Baxter, Stryker, and Aesculap; has filed multiple patents with the university office; and receives royalties from Stryker and Aesculap. H. K. has served as a consultant for Pfizer. D. N. is a consultant for Stryker. J. B., E. B., C. S., I. M., D. C., D. R., A. J., M. P., W. C. G., K. U. J., A. S. A., and A. G. are current employees of Pfizer and may hold stock or stock options. A. J. reports support for attending meetings as part of duties as a Pfizer employee and STRIVE team member. J. C. reports grants or contracts from the Canadian Institutes for Health Research and from Alberta Innovates; has received accommodations and airfare to attend and speak at a symposium from bioMerieux Canada; and is a member and chair of the World Health Organization (WHO) and a member of the WHO Health Emergencies Programme Ad-hoc COVID-19 IPC Guidance Development Group, both of which provide multidisciplinary advice to the WHO, for which no funding is received and from which no funding recommendations are made for any WHO contracts or grants; and works as an infectious diseases consultant at Alberta Health Services. K. J. reports consulting fees from and patents with Pfizer. M. W. reports royalties or licenses from Depuy-Synthes Spine; consulting fees from Depuy-Synthes Spine, Pacira, Stryker, NuVasive, Spineology, and Surgalign; and stock or stock options from Innovasive Surgical Devices, Kinesiomerics, and Medical Device Partners. 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., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Post-surgical invasive Staphylococcus aureus infections among spinal fusion patients are serious complications that can worsen clinical outcomes and increase healthcare utilization. Risk of such infections at the population level remains unknown. This study assessed the post-surgical risk of invasive Staphylococcus aureus infections among patients undergoing elective posterior instrumented spinal fusion surgeries in 129 U.S. hospitals. Patients and Methods: This retrospective cohort study analyzed adult patients ≥18 years of age who underwent thoracolumbar/lumbar and cervical fusion surgeries during 2010 - 2014 using the Premier Healthcare Database, the largest hospital discharge database in the United States. Risks of blood stream infection (BSI), deep or organ/space surgical site infections (SSI) caused by Staphylococcus aureus during 90 and 180 days post-index surgery were estimated. Infections were identified based on positive culture results, related International Classification of Diseases, Ninth Revision (ICD-9) procedure codes, and specific claims information. Results: Among 11,236 patients with thoracolumbar/lumbar fusion, 90- and 180-day BSI/SSI infection risks were higher for multilevel than single level fusion (90-day, 1.52% vs. 1.07%, p = 0.05; 180-day, 1.66% vs. 1.07%, p = 0.014). Among 1,641 patients with cervical fusion, 90- and 180-day BSI/SSI infection risks were also higher in multilevel fusions but not statistically significant (90-day, 1.66% vs. 0.52%, p = 0.350; 180-day, 1.80% vs. 0.51%, p = 0.241). The risk for SSI/BSI was more than twice as high among multilevel thoracolumbar/lumbar fusion patients with more than two comorbidities than those with no comorbidity at both 90-day (2.78% vs. 1.00%, p < 0.05) and 180-day (3.01% vs. 1.10%, p < 0.05). Similar trend without statistical significance was seen in multilevel cervical fusion cohort (90-day, 2.91% vs. 1.25%, p > 0.05; 180-day, 3.88% vs. 1.41%, p > 0.05). Conclusions: The risk of BSI/SSI infection for elective posterior instrumented spinal fusions ranged between 0.5% and 2%. Higher risk was observed in multilevel thoracolumbar/lumbar surgery, with infection risk greatest in patients with more than two comorbidities. These real-world findings highlight the need for additional measures, in addition to antibiotic prophylaxis, to reduce invasive Staphylococcus aureus infections in this setting.

Background: 7-Valent pneumococcal conjugate vaccine (PCV7 [Prevnar, Wyeth Pharmaceuticals Inc, Philadelphia, PA], serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) is effective in preventing vaccine-serotype pneumococcal disease. 13-Valent pneumococcal conjugate vaccine (PCV13) (PCV7 serotypes plus 1, 3, 5, 6A, 7F, and 19A) was designed to provide broader pneumococcal disease coverage. We evaluated the immunogenicity and safety of PCV13 compared with PCV7., Methods: Infants received PCV13 or PCV7 at ages 2, 4, 6, and 12 to 15 months with routine pediatric vaccinations. Pneumococcal anticapsular polysaccharide-binding immunoglobulin G responses and functional antipneumococcal opsonophagocytic activity were assessed 1 month after dose 3, before the toddler dose, and 1 month after the toddler dose. Safety and tolerability were also assessed., Results: For the 7 common serotypes, PCV13-elicited immunoglobulin G titers were noninferior to those elicited by PCV7, although PCV13 responses were generally somewhat lower. PCV13 also elicited functional opsonophagocytic activity comparable with that elicited by PCV7. For the 6 additional serotypes in PCV13, PCV13 elicited binding and functional antibody levels notably greater than those in PCV7 recipients. After PCV13 immunization, concordance between antipolysaccharide and opsonophagocytic responses was noted for all 13 serotypes. The PCV13 toddler dose resulted in higher immune responses compared with infant-series doses. Safety and tolerability were comparable; reactogenicity was generally mild., Conclusions: PCV13 will be as effective as PCV7 in the prevention of pneumococcal disease caused by the 7 common serotypes and could provide expanded protection against the 6 additional serotypes. The PCV13 safety profile was comparable to that of PCV7.

Occupational exposure to Hepatitis C virus is an area of growing concern due to a lack of prophylaxis and limited knowledge regarding prevalence in hospital environment. Between 1999 and 2003, a total of 128 occupational exposures to this virus were registered in Diego Paroissien Hospital, eight of which led to hepatitis (6.3%) and one case to serum conversion (0.8%). Currently there is no preventive therapy and great interest is focused on acute infection therapy the effectiveness of which is still controversial. This study reinforces the fact that adherence to the Universal Precautions is still the most important preventive measure for health care workers, and the most cost beneficial.