Association of pneumococcal conjugate vaccination with SARS-CoV-2 infection among older adult recipients of COVID-19 vaccines: a longitudinal cohort study.

BACKGROUND: Pneumococcal carriage is associated with increased acquisition and duration of SARS-CoV-2 infection among adults. While pneumococcal conjugate vaccines (PCVs) prevent carriage of vaccine-serotype pneumococci, their potential impact on COVID-19 related outcomes remains poorly understood in populations with prevalent immunity against SARS-CoV-2. METHODS: We undertook a retrospective cohort study of adults aged ≥65 years in the Kaiser Permanente Southern California (KPSC) healthcare system who had received ≥2 COVID-19 vaccine doses, comparing risk of SARS-CoV-2 infection between 1 January, 2021 and 31 December, 2022 among recipients and non-recipients of PCV13. We estimated adjusted hazard ratios via Cox proportional hazards models, employing multiple strategies to mitigate bias from differential test-seeking behavior. RESULTS: The adjusted hazard ratio (aHR) of confirmed SARS-CoV-2 infection comparing PCV13 recipients to non-recipients was 0.92 (95% confidence interval: 0.90-0.95), corresponding to prevention of 3.9 (2.6-5.3) infections per 100 person-years. Following receipt of 2, 3, and ≥4 COVID-19 vaccine doses, aHRs were 0.85 (0.81-0.89), 0.94 (0.90-0.97), and 0.99 (0.93-1.04), respectively. The aHR for persons who had not received COVID-19 vaccination in the preceding 6 months was 0.90 (0.86-0.93), versus 0.94 (0.91-0.98) within 6 months after receipt of any dose. Similarly, the aHR was 0.92 (0.89-0.94) for persons without history of documented SARS-CoV-2 infection, versus 1.00 (0.90-1.12) for persons with documented prior infection. CONCLUSIONS: Among older adults who had received ≥2 COVID-19 vaccine doses, PCV13 was associated with modest protection against SARS-CoV-2 infection. Protective effects of PCV13 were greater among individuals expected to have weaker immune protection against SARS-CoV-2 infection.

Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13.

AIM: The US Food and Drug Administration approved the 20-valent pneumococcal conjugate vaccine (PCV20) to prevent pneumococcal disease. In the context of routine PCV20 vaccination, we evaluated the cost-effectiveness and public health and economic impact of a PCV20 catch-up program and estimated the number of antibiotic prescriptions and antibiotic-resistant infections averted. MATERIALS AND METHODS: A population-based, multi-cohort, decision-analytic Markov model was developed using parameters consistent with previous PCV20 cost-effectiveness analyses. In the intervention arm, children aged 14-59 months who previously completed PCV13 vaccination received a supplemental dose of PCV20. In the comparator arm, no catch-up PCV20 dose was given. The direct and indirect benefits of vaccination were captured over a 10-year time horizon. RESULTS: A PCV20 catch-up program would prevent 5,469 invasive pneumococcal disease cases, 50,286 hospitalized pneumonia cases, 218,240 outpatient pneumonia cases, 582,302 otitis media cases, and 1,800 deaths, representing a net gain of 30,014 life years and 55,583 quality-adjusted life years. Furthermore, 720,938 antibiotic prescriptions and 256,889 antibiotic-resistant infections would be averted. A catch-up program would result in cost savings of $800 million. These results were robust to sensitivity and scenario analyses. CONCLUSIONS: A PCV20 catch-up program could prevent pneumococcal infections, antibiotic prescriptions, and antimicrobial-resistant infections and would be cost-saving in the US.

Characterization of Streptococcus pneumoniae isolates obtained from the middle ear fluid of US children, 2011-2021.

Introduction: Pneumococcal conjugate vaccines (PCVs), including higher valency vaccines such as PCV20, have the potential to reduce pediatric otitis media. We assessed serotype distribution, potential PCV coverage, and antimicrobial susceptibility of Streptococcus pneumoniae isolates cultured from middle ear fluid (MEF) of US children age ≤5 years. Methods: S. pneumoniae isolates identified from US hospitals participating in the SENTRY Antimicrobial Surveillance program from 2011 to 2021 were included. Serotypes were determined by in silico analysis based on Pneumococcal Capsular Typing methodology. The percentage of isolates belonging to serotypes included in PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), PCV15 (PCV13 plus 22F, 33F), and PCV20 (PCV13 plus, 8, 10A, 11A, 12F, 15B, 22F and 33F) was calculated. Antimicrobial susceptibility testing was performed by broth microdilution and interpreted using CLSI criteria. Nonsusceptibility was defined as isolates that were intermediate or resistant to a selected antimicrobial. Results: Among the 199 S. pneumoniae isolates that were identified, 56.8% were from children age <2 years. Six serotypes accounted for around 60% of isolates: 35B (16.6%), 15B (14.6%), 15A (7.5%), 19A (7.5%), 19F (7.5%), and 3 (7.0%). Serotypes included in PCV13, PCV15, and PCV20 accounted for 23.1%, 30.2%, and 54.8% of isolates, respectively. Overall, 45.2% of isolates were penicillin non-susceptible, and 13.6% were MDR, of which 48% were serotype 19A. Seven serotypes (19A, 15A, 15B, 15C, 23A, 33F, and 35B) accounted for the majority of non-susceptible isolates. Discussion: PCVs, particularly PCV20, may prevent a substantial fraction of S. pneumoniae otitis media (OM), including OM due to non-susceptible serotypes. The addition of serotypes 15A, 23A, and 35B would improve coverage against susceptible and non-susceptible pneumococcal OM.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

INTRODUCTION: A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. METHODS: A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6 years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. RESULTS: Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6 years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. CONCLUSIONS: Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

The Cost of Seasonal Influenza: A Systematic Literature Review on the Humanistic and Economic Burden of Influenza in Older (≥ 65 Years Old) Adults.

INTRODUCTION: Adults aged ≥ 65 years contribute a large proportion of influenza-related hospitalizations and deaths due to increased risk of complications, which result in high medical costs and reduced health-related quality of life (HRQoL). Although seasonal influenza vaccines are recommended for older adults, the effectiveness of current vaccines is dependent on several factors including strain matching and recipient demographic factors. This systemic literature review aimed to explore the economic and humanistic burden of influenza in adults aged ≥ 65 years. METHODS: An electronic database search was conducted to identify studies assessing the economic and humanistic burden of influenza, including influenza symptoms that impact the HRQoL and patient-related outcomes in adults aged ≥ 65 years. Studies were to be published in English and conducted in Germany, France, Spain, and Italy, the UK, USA, Canada, China, Japan, Brazil, Saudi Arabia, and South Africa. RESULTS: Thirty-eight studies reported on the economic and humanistic burden of influenza in adults aged ≥ 65 years. Higher direct costs were reported for people at increased risk of influenza-related complications compared to those at low risk. Lower influenza-related total costs were found in those vaccinated with adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD). Older age was associated with an increased occurrence and longer duration of certain influenza symptoms. CONCLUSION: Despite the limited data identified, results show that influenza exerts a high humanistic and economic burden in older adults. Further research is required to confirm findings and to identify the unmet needs of current vaccines.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants.

BACKGROUND: As of June 2023, two pneumococcal conjugate vaccines, 20- (PCV20) and 15- (PCV15) valent formulations, are recommended for US infants under a 3 + 1 schedule. This study evaluated the health and economic impact of vaccinating US infants with a new expanded valency PCV20 formulation. METHODS: A population-based, multi cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of PCV20 from both societal and healthcare system perspectives over 10 years. Epidemiological data were based on published studies and unpublished Active Bacterial Core Surveillance System (ABCs) data. Vaccine effectiveness was based on PCV13 effectiveness and PCV7 efficacy studies. Indirect impact was based on observational studies. Costs and disutilities were based on published data. PCV20 was compared to both PCV13 and PCV15 in separate scenarios. RESULTS: Replacing PCV13 with PCV20 in infants has the potential to avert over 55,000 invasive pneumococcal disease (IPD) cases, 2.5 million pneumonia cases, 5.4 million otitis media (OM) cases, and 19,000 deaths across all ages over a 10-year time horizon, corresponding to net gains of 515,000 life years and 271,000 QALYs. Acquisition costs of PCV20 were offset by monetary savings from averted cases resulting in net savings of $20.6 billion. The same trend was observed when comparing PCV20 versus PCV15, with a net gain of 146,000 QALYs and $9.9 billion in net savings. A large proportion of the avoided costs and cases were attributable to indirect effects in unvaccinated adults and elderly. From a health-care perspective, PCV20 was also the dominant strategy compared to both PCV13 and PCV15. CONCLUSIONS: Infant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Estudio de las enfermedades respiratorias por virus Influenza A H1N1 (pH1N1) en niños internados durante el año de la pandemia: Experiencia de 34 centros en la Argentina / Study of respiratory influenza A H1N1 Virus (pH1N1) in hospitalized children in the pandemic year: Experience in 34 centers in Argentina

Introducción. En la Argentina, la pandemia de Influenza A pH1N1 de 2009 provocó cerca de 10 000 casos confirmados con alto impacto en pediatría. Objetivos. Describir las características clínico epidemiológicas y analizar los factores de riesgo de letalidad en niños hospitalizados con infección confirmada por pH1N1. Población y métodos. Se identificaron todas las fichas de casos sospechosos (según Ministerio de Salud) internados en 34 centros y se incluyeron todos los casos confirmados de 0-18 años desde el 1/4/09 al 31/8/09 en un estudio de cohorte retrospectivo. El diagnóstico viral se confirmó por método RT-PCR. Los datos se expresaron en porcentajes, media, mediana, desvío estándar e intervalo intercuartilo (IIC) según correspondiera; y como medida de asociación, Riesgo Relativo (RR), con Intervalo de Confianza 95% (IC95%). Se realizó regresión logística múltiple para determinar los predictores independientes. Resultados. Número total de casos sospechosos: 2367; se realizó PCR al 47,8% (n: 1131) siendo positivos para pH1N1 65,5% (n: 741/1131); 57,2% varones; 61,5% <24 meses, mediana de edad: 14 meses (IIC 6-46 meses); 45,1% con enfermedad subyacente; formas clínicas de presentación más frecuentes: neumonía 39,7% y bronquiolitis 25,8%; letalidad: 5,9% (44/741). Factores de riesgo de letalidad [RR (IC95%)]: enfermedad neurológica [5,00 (2,84-8,81)], enfermedad genética [3,67 (1,58-8,52)], desnutrición [3,07 (1,46-6,48)] y prematurez [2,28 (1,14-4,56)]. Predictor independiente de letalidad: enfermedad neurológica [3,84 (1,81-8,14)]. No se observó asociación significativa entre edad, enfermedad respiratoria crónica, inmunosupresión y coinfección viral con la letalidad. Conclusiones. Casi la mitad de los niños con infección por pH1N1 tenía enfermedad subyacente; la enfermedad neurológica fue un predictor independiente de letalidad.

Introduction. In Argentina, pandemic influenza pH1N1 caused nearly 10,000 confirmed cases with high impact in pediatrics. Objectives. To describe clinical and epidemiological characteristics and analyse the risk factor of lethality in children hospitalized with infection pH1N1 confirmed by PCR Population and methods. We identified all suspected cases (according to Ministry of health) in 34 centers and we included all the confirmed cases of 0-18 years from 1/4/09 to 31/8/09 in a retrospective cohort study. The viral diagnosis was confirmed by RT-PCR method. Data are expres sed in percentages, average, median, standard deviation, and range (IQR) as appropriate; and as a measure of association, relative risk (RR), with 95% confidence interval (95%CI). Multiple logistic regression was conducted to determine the independent risk predictors. Results. Total number of suspected cases were: 2367; PCR was performed to 47.8% (n: 1131) being positive for pH1N1 65.5% (n: 741/1131); 57.2% males; 61.5% <24 months, median age: 14 months (IQR 6-46 months); 45.1% with underlying disease; more frequent clinical pictures were: pneumonia (39,7%) and bronchiolitis 25.8%; Case-fatality rate: 5.9% (44/741). Mortality risk factors were [RR (95%CI)]: neurological disease [5.00 (2.84-8.81)], genetic disease [3.67 (1.58-8.52)], malnutrition [3,07 (1.46-6.48)] and prematurity [2.28 (1.14-4.56)]. Independent mortality predictor: neurological disease [3.84(1.81-8.14)]. No significant association between age, chronic respiratory disease, immunosuppression and viral co-infection with lethality was observed. Conclusions. Almost half of children with pH1N1 infection had underlying disease; the neurological condition was a separate CFR predictor.

Estudio de las enfermedades respiratorias por virus Influenza A H1N1 (pH1N1) en niños internados durante el año de la pandemia: experiencia de 34 centros en la Argentina / Study of respiratory influenza A H1N1 Virus (pH1N1) in hospitalized children in the pandemic year: experience in 34 centers in Argentina

Introducción. En la Argentina, la pandemia de InfluenzaA pH1N1 de 2009 provocó cerca de 10 000 casos confirmados con alto impacto en pediatría. Objetivos. Describir las características clínico epidemiológicas y analizar los factores de riesgo de letalidad en niños hospitalizados con infección confirmada por pH1N1.Población y métodos. Se identificaron todas las fichas de casos sospechosos (según Ministerio de Salud) internados en 34 centros y se incluyeron todos los casos confirmados de 0-18 años desde el 1/4/09 al 31/8/09 en un estudio de cohorte retrospectivo. El diagnóstico viral se confirmó por método RT-PCR. Los datos se expresaron en porcentajes, media, mediana, desvío estándare intervalo intercuartilo (IIC) según correspondiera; y como medida de asociación, Riesgo Relativo (RR), con Intervalo de Confianza 95 por ciento(IC95 por ciento). Se realizó regresión logística múltiple para determinar los predictores independientes. Resultados. Número total de casos sospechosos: 2367; se realizó PCR al 47,8 por ciento (n: 1131) siendo positivos para pH1N1 65,5 por ciento (n: 741/1131); 57,2 por cientovarones; 61,5 por ciento <24 meses, mediana de edad: 14 meses (IIC 6-46 meses); 45,1 por ciento con enfermedad subyacente; formas clínicas de presentación más frecuentes: neumonía 39,7 por ciento y bronquiolitis 25,8 por ciento; letalidad: 5,9 por ciento (44/741).Factores de riesgo de letalidad [RR (IC95 por ciento)]: enfermedad neurológica [5,00 (2,84-8,81)], enfermedad genética [3,67 (1,58-8,52)], desnutrición [3,07 (1,46-6,48)] y prematurez [2,28 (1,14-4,56)]. Predictor independiente de letalidad: enfermedad neurológica [3,84 (1,81-8,14)]. No se observó asociación significativa entre edad,enfermedad respiratoria crónica, inmunosupresión y coinfección viral con la letalidad. Conclusiones. Casi la mitad de los niños con infección por pH1N1 tenía enfermedad subyacente; la enfermedad neurológica fue un predictor independiente de letalidad.

Introduction. In Argentina, pandemic influenza pH1N1 caused nearly 10,000 confirmed cases with high impact in pediatrics. Objectives. To describe clinical and epidemiological characteristics and analyse the risk factor of lethality in children hospitalized with infectionpH1N1 confirmed by PCR Population and methods. We identified all suspectedcases (according to Ministry of health)in 34 centers and we included all the confirmed cases of 0-18 years from 1/4/09 to 31/8/09 in a retrospective cohort study. The viral diagnosis was confirmed by RT-PCR method. Data are expressed in percentages, average, median, standard deviation, and range (IQR) as appropriate; and as a measure of association, relative risk (RR), with 95% confidence interval (95%CI). Multiple logistic regression was conducted to determine the independent risk predictors. Results. Total number of suspected cases were: 2367; PCR was performed to 47.8% (n: 1131) beingpositive for pH1N1 65.5% (n:741/1131); 57.2% males; 61.5% <24 months, median age: 14 months(IQR 6-46 months); 45.1% with underlying disease; more frequent clinical pictures were: pneumonia (39,7%) and bronchiolitis 25.8%; Case-fatality rate: 5.9% (44/741). Mortality risk factors were [RR (95%CI)]: neurological disease [5.00 (2.84-8.81)], genetic disease [3.67 (1.58-8.52)], malnutrition [3,07 (1.46-6.48)] and prematurity [2.28 (1.14-4.56)]. Independent mortality predictor:neurological disease [3.84 (1.81-8.14)].No significant association between age, chronic respiratory disease, immunosuppression and viral co-infection with lethality was observed.Conclusions. Almost half of children with pH1N1 infection had underlying disease; the neurological condition was a separate CFR predictor.

Costo-efectividad de la vacunación universal antineumocócica en Uruguay / Cost-effectiveness of universal pneumococcal vaccination in Uruguay

OBJETIVO: Evaluar la relación costo-efectividad del programa de vacunación universal con la vacuna antineumocócica conjugada heptavalente (VCN7) en niños menores de 5 años en Uruguay. MÉTODOS: Se desarrolló un modelo Markov simulando una cohorte de 48 000 niños nacidos en 2007 y su evolución hasta los 76 años de edad. El caso base usó un esquema de tres dosis con una duración estimada de protección de cinco años. La presunción de eficacia y efectividad de la vacuna se realizó acorde con estudios realizados en Estados Unidos con ajuste a la prevalencia-incidencia de serotipos en Uruguay. Los resultados se expresaron como costo incremental por año de vida ganado (AVG) y por año de vida [ganado] ajustado por calidad (AVAC). RESULTADOS: Para el caso base, el costo incremental fue de US$ 7 334,6 por AVG y US$ 4 655,8 por AVAC, previniéndose 8 muertes y 4 882 casos de otitis, 56 bacteriemias-sepsis, 429 neumonías y 7 meningitis. El modelo muestra sensibilidad a variaciones en eficacia, costo de la vacuna y tasa de mortalidad por neumonía. CONCLUSIONES: El programa de vacunación universal con VCN7 en Uruguay es altamente costo-efectivo y, en consecuencia, recomendable para otros países con carga de enfermedad neumocócica y cobertura de serotipos similares a Uruguay.

OBJECTIVE: Evaluate the cost-effectiveness ratio of the program for universal vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) in children under 5 years of age in Uruguay. METHODS: A Markov model was developed that simulated a cohort of 48 000 children born in 2007 and their progress to age 76. The baseline case used a regimen of three doses with estimated protection for five years. The presumption of vaccine efficacy and effectiveness was based on studies conducted in the United States with adjustment for serotype prevalence-incidence in Uruguay. The results were expressed as the incremental cost per life year gained (LYG) and quality-adjusted life year (QALY) [gained]. RESULTS: For the baseline case, the incremental cost was US $7334.60 for each LYG and US $4655.80 for each QALY. Eight deaths and 4 882 cases of otitis, 56 cases of bacteremia-sepsis, 429 cases of pneumonia, and 7 cases of meningitis were prevented. The model shows sensitivity to variations in vaccine cost, efficacy, and pneumonia-related mortality. CONCLUSIONS: The universal vaccination program with PCV7 in Uruguay is highly cost-effective. Therefore, it is recommended for other countries with burden of pneumococcal disease and serotype coverage similar to those of Uruguay.

First clinical isolates of Cronobacter spp. (Enterobacter sakazakii) in Argentina: characterization and subtyping by pulsed-field gel electrophoresis / First clinical isolates of Cronobacter spp. (Enterobacter sakazakii) in Argentina: characterization and subtyping by pulsed-field gel electrophoresis.

Cronobacter species are opportunistic pathogens associated with severe infections in neonates and immunocompromised infants. From January 2009 through September 2010, two cases of neonatal infections associated with Cronobacter malonaticus and one case associated with Cronobacter sakazakii, two of them fatal, were reported in the same hospital. These are the first clinical isolates of Cronobacter spp. in Argentina. The objective of this work was to characterize and subtype clinical isolates of Cronobacter spp. in neonate patients, as well as to establish the genetic relationship between these isolates and the foodborne isolates previously identified in the country. Pulsed-field gel electrophoresis analysis showed a genetic relationship between the C. malonaticus isolates from two patients. Different results were found when the pulsed-field gel electrophoresis patterns of clinical isolates were compared with those deposited in the National Database of Cronobacter spp.

Indications of a new antibiotic in clinical practice: results of the tigecycline initial use registry

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22 percent) received tigecycline for approved indications, and 88 (78 percent) for "off label" indications (56 percent with scientific support and 22 percent with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93 percent). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50 percent of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76 percent). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.