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.

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.

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.

Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States.

BACKGROUND: Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. METHODS: We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. RESULTS: Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. CONCLUSIONS: Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.

Persistence of Pneumococcal Carriage among Older Adults in the Community despite COVID-19 Mitigation Measures.

Reported rates of invasive pneumococcal disease were markedly lower than normal during the 2020/2021 winter in the Northern Hemisphere, the first year after the start of the COVID-19 pandemic. However, little is known about rates of carriage of pneumococcus among adults during this period. Between October 2020-August 2021, couples in the Greater New Haven Area, USA, were enrolled if both individuals were aged 60 years and above and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social activities and contacts and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when Ct values for piaB were ≤40. Results. We collected 567 saliva samples from 95 individuals (47 household pairs and 1 singleton). Of those, 7.1% of samples tested positive for pneumococcus, representing 22/95 (23.2%) individuals and 16/48 (33.3%) households. Study participants attended few social events during this period. However, many participants continued to have regular contact with children. Individuals who had regular contact with preschool and school-aged children (i.e., 2 to 9 year olds) had a higher prevalence of carriage (15.9% versus 5.4%). Despite COVID-19-related disruptions, a large proportion of older adults continued to carry pneumococcus. Prevalence was particularly high among those who had contact with school-aged children, but carriage was not limited to this group. IMPORTANCE Carriage of Streptococcus pneumoniae (pneumococcus) in the upper respiratory tract is considered a prerequisite to invasive pneumococcal disease. During the first year of the COVID-19 pandemic, markedly lower rates of invasive pneumococcal disease were reported worldwide. Despite this, by testing saliva samples with PCR, we found that older adults continued to carry pneumococcus at pre-pandemic levels. Importantly, this study was conducted during a period when transmission mitigation measures related to the COVID-19 pandemic were in place. However, our observations are in line with reports from Israel and Belgium where carriage was also found to persist in children. In line with this, we observed that carriage prevalence was particularly high among the older adults in our study who maintained contact with school-aged children.

PCV13 Pediatric Routine Schedule Completion and Adherence Before and During the COVID-19 Pandemic in the United States.

INTRODUCTION: A 13-valent pneumococcal conjugate vaccine (PCV13) was licensed to protect against emerging Streptococcus pneumoniae serotypes. Healthcare services, including routine childhood immunizations, were disrupted as a result of coronavirus disease 2019 (COVID-19). This study compared PCV13 routine vaccination completion and adherence among US infants before and during the COVID-19 pandemic and the relationship between primary and booster dose completion and adherence. METHODS: Retrospective data from Optum's de-identified Clinformatics® Data Mart were used to create three cohorts using data collected between January 2017 and December 2020: cohort 1 (C1), pre-COVID; cohort 2 (C2), cross-COVID; and cohort 3 (C3), during COVID. Study endpoints were completion and adherence to the primary PCV13 series (analyzed using univariate logistic regression) and completion of and adherence to the booster dose (analyzed descriptively). RESULTS: The analysis included 142,853 infants in C1, 27,211 infants in C2, and 53,306 infants in C3. Among infants with at least 8 months of follow-up from birth, three-primary-dose completion (receipt of all three doses within 8 months after birth) and adherence (receipt of doses at recommended times) were significantly higher before (C1 and C2) versus during (C3) COVID-19 (odds ratio [OR] 1.12 [95% confidence interval [CI] 1.07, 1.16] and OR 1.10 [95% CI 1.05, 1.15], respectively). A significantly higher percentage of infants received a booster dose before versus during COVID-19 (83.2% vs. 80.2%; OR 1.23; 95% CI 1.17, 1.29); similarly, booster dose adherence was higher before than during COVID-19 (51.2% vs. 47.4%; OR 1.17; 95% CI 1.13, 1.21). The odds of booster dose completion were 8.26 (95% CI 7.92, 8.60) and 7.90 (95% CI 7.14, 8.74) times as likely in infants who completed all three primary doses than in infants who did not complete primary doses before COVID-19 and during COVID-19, respectively. CONCLUSIONS: PCV13 full completion was lower during the COVID-19 pandemic compared with pre-pandemic (79.0% vs. 77.1%).

Burden of pneumococcal disease due to serotypes covered by the 13-valent and new higher-valent pneumococcal conjugate vaccines in the United States.

The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.

Detection of pneumococcus during hospitalization for SARS-CoV-2.

Background: Infections with respiratory viruses [e.g. influenza and respiratory syncytial virus (RSV)] can increase the risk of severe pneumococcal infections. Likewise, pneumococcal coinfection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 coinfection and the role of coinfection in influencing COVID-19 severity. We, therefore, investigated the detection of pneumococcus in COVID-19 inpatients during the early pandemic period. Methods: The study included patients aged 18 years and older, admitted to the Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March-August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease). Results: Among 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; and 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 [OR: 2.20; 95% CI: (0.72, 7.48)]; however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died. Conclusions: Pneumococcal lower respiratory tract infection (LRTI), as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients.

One-Year Quality of Life Post-Pneumonia Diagnosis in Japanese Adults.

BACKGROUND: Pneumonia is a common, serious illness in the elderly, with a poorly characterized long-term impact on health-related quality of life (HRQoL). The Japanese Goto Epidemiology Study is a prospective, active, population-based surveillance study of adults with X-ray/CT scan-confirmed community-onset pneumonia, assessing the HRQoL outcome quality-adjusted life-years (QALYs). We report QALY scores and losses among a subset of participants in this study. METHODS: QALYs were derived from responses to the Japanese version of the EuroQol-5D-5L health-state classification instrument at days 0, 7, 15, 30, 90, 180, and 365 after pneumonia diagnosis from participants enrolled from June 2017 to May 2018. We used patients as their own controls, calculating comparison QALYs by extrapolating EuroQol-5D-5L scores for day -30, accounting for mortality and changes in scores with age. RESULTS: Of 405 participants, 85% were aged ≥65 years, 58% were male, and 69% were hospitalized for clinically and radiologically confirmed pneumonia. Compliance with interviews by patients or proxies was 100%. Adjusted EuroQol-5D-5L scores were 0.759, 0.561, 0.702, and 0.689 at days -30, 0 (diagnosis), 180, and 365, respectively. Average scores at all time points remained below the average day -30 scores (P ≤ .001). Pneumonia resulted in a 1-year adjusted loss of 0.13 QALYs (~47.5 quality-adjusted days) (P < .001). CONCLUSIONS: Substantial QALY losses were observed among Japanese adults following pneumonia diagnosis, and scores had not returned to prediagnosis levels at 1 year postdiagnosis. QALY scores and cumulative losses were comparable to those in US adults with chronic heart failure, stroke, or renal failure.

Streptococcus pneumoniae serotype distribution and antimicrobial nonsusceptibility trends among adults with pneumonia in the United States, 2009‒2017.

Background In the United States, the 13-valent pneumococcal conjugate vaccine has been recommended for children since 2010 and for adults aged ≥65 years since 2014. We assessed S. pneumoniae antimicrobial nonsusceptibility among adults with suspected pneumonia from hospital settings. Methods Isolates were collected from 105 US sites between 2009 and 2017 in the SENTRY Antimicrobial Surveillance Program. Clinical and Laboratory Standards Institute methods were used for susceptibility testing. Serotypes were determined by cpsB sequence obtained by PCR or whole genome sequencing, plus multiplex PCR and/or Neufeld Quellung reactions as needed. Findings Of 7254 S. pneumoniae isolates analyzed, 63.6% and 36.4% were from patients aged 18‒64 and ≥65 years, respectively. Among all isolates, penicillin and ceftriaxone nonsusceptibility declined by 72.3% and 73.8%, respectively, with smaller changes observed for other antibiotics. Nonsusceptibility patterns were serotype-specific; for example, nonsusceptibility was relatively stable for serotype 19A but declined for 19F. Simultaneously, the percentage of serotype 19A isolates decreased from 17.4% to 3.9%, whereas for serotype 19F this percentage increased from 2.8% to 5.0%. The percentage of serotype 3 isolates that were nonsusceptible increased for select antibiotic classes, and the percentage of serotype 3 among all isolates increased minimally from 10.2% to 11.8%. Interpretation Overall pneumococcal nonsusceptibility patterns were influenced by distinct patterns within serotypes, indicating the likelihood of serotype-specific resistance mechanisms. Serotype 19A observations were consistent with vaccine-induced reductions in circulation with no change in the organism susceptibility, whereas the nonsusceptibility increases for serotypes 3 and 19F may indicate circulation of more antibiotic-resistant clones.

Divergent serotype distribution between children with otitis media and those without in the pneumococcal conjugate vaccine era.

We investigated pneumococcal carriage between children ≦5 years old with otitis media (OM) and those without. Non-PCV13 serotypes were common in both groups; 19A remained the second most common serotype among children with OM despite high PCV13 coverage. This is important when considering a schedule with reduced vaccine doses or reduced valency, and the modification of pneumococcal immunization schedule should be followed up closely to monitor the result of protection against pneumococcal infections.

Upper respiratory tract colonization with Streptococcus pneumoniae in adults.

INTRODUCTION: Most of the current evidence regarding pneumococcal upper respiratory colonization in adults suggests that despite high disease burden, carriage prevalence is low. Contemporary studies on adult pneumococcal colonization have largely followed the pediatric approach by which samples are obtained mostly from the nasopharynx and bacterial detection is evaluated by routine culture alone. Recent evidence suggests that the 'pediatric approach' may be insufficient in adults and pneumococcal detection in this population may be improved by longitudinal studies that include samples from additional respiratory sites combined with more extensive laboratory testing. AREAS COVERED: In this article, relevant literature published in peer review journals on adult pneumococcal colonization, epidemiology, detection methods, and recommendations were reviewed. EXPERT OPINION: Respiratory carriage of Streptococcus pneumoniae has been underestimated in adults. Contemporary pneumococcal carriage studies in adults that collect samples from alternative respiratory sites such as the oropharynx, saliva, or nasal wash; are culture-enriched for pneumococcus; and use molecular diagnostic methods designed to target two pneumococcal DNA sequences should enhance pneumococcal detection in the adult respiratory tract. This finding may have implications for the interpretation of dynamics of pneumococcal transmission and vaccination.

Acute otitis media, antimicrobial prescriptions, and medical expenses among children in the United States during 2011-2016.

INTRODUCTION: We analyzed outpatient visits, incidence, antimicrobial prescriptions, and medical expenditures for acute otitis media (AOM) in the United States during 2011-2016. METHODS: Data sources included the National Disease and Therapeutic Index (NDTI™) projections by IQVIA (for AOM cases), The Medical Expenditure Panel Survey (for medical expenditures) and the US Census (for population estimates). Analyses focused on children aged ≤9 years between 2011 and 2016. We used the 2014 medical expenditure estimate per otitis media episode ($520) as proxy for all years. RESULTS: In 2011, there were an estimated 11.5 million AOM episodes in children aged 0-9 years in the US with AOM incidence rates (IR) of 476, 204, and 284 episodes per 1000 children aged 0-2, 3-9, and 0-9 years, respectively. All subsequent years had lower IRs, and by 2016, IR was 25.1% lower than in 2011 in children 0-9 years. In addition, there were estimates of 10.8 million and 9.2 million fewer cumulative AOM episodes and antimicrobial prescriptions for AOM nationwide between 2012 and 2016, compared to annual 2011 estimates, representing a ∼$5.6 billion decrease in direct medical expenditures. The average number of antibiotic prescriptions per AOM visit remained stable with 0.89 and 0.86 prescriptions per visit in 2011 and 2016, respectively. CONCLUSIONS: AOM incidence, antimicrobial prescriptions, and associated medical expenses decreased substantially between 2011 and 2016 in the United States. Antimicrobial prescribing practices remain unchanged. Additional studies are warranted to assess causality.

Streptococcus pneumoniae serotype 19A: worldwide epidemiology.

INTRODUCTION: Streptococcus pneumoniae causes mucosal and invasive diseases with high morbidity and mortality. Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into routine infant immunization programs worldwide resulted in serotype 19A becoming a leading cause of the remaining pneumococcal disease burden in vaccinated and nonvaccinated individuals. This article reviews the impact of the latest generation PCVs (10-valent PCV, PCV10, and 13-valent PCV, PCV13) on serotype 19A. Areas covered: This article covers immune responses elicited by PCV7, PCV10 and PCV13 against serotype 19A and their impact on nasopharyngeal (NP) carriage and disease in vaccinated and unvaccinated populations using data from surveillance systems, randomized controlled trials, and observational studies. Expert commentary: As expected from a PCV containing serotype 19A, PCV13 elicits significantly higher functional immune responses against serotype 19A than PCV7 and PCV10. Higher responses are likely to be linked to both direct impact in vaccinated populations and reductions in 19A NP carriage in children, thus inducing herd protection and reducing 19A invasive pneumococcal disease (IPD) in nonvaccinated children and adults. In contrast, PCV7 and PCV10 have shown mixed evidence of direct short-lived cross-protection and little to no impact on 19A carriage, resulting in continued transmission and disease.

Tick-borne encephalitis in China: A review of epidemiology and vaccines.

Tick-borne encephalitis (TBE) has been shown to be endemic in northern and western China, including the three mountain areas in Heilongjiang, Jilin, Inner Mongolia, and Xinjiang. In addition, serology evidence shows that there is human infection in south-west provinces of China, including Xizang (Tibet) and Yunnan. TBE in China is caused by the Far Eastern TBE virus subtype and there is no biphasic course for disease presentation. The majority of TBE cases in China have occurred in people who were living or working in forests. TBE vaccines became available in China soon after the virus was identified in the country and they have been used for more than 60years to date, with different vaccine types used in different periods. Currently, an inactivated and purified whole-virus vaccine produced in a primary hamster kidney (PHK) cell line is used. Clinical trials have shown this vaccine to have higher immunogenicity and fewer adverse reactions than previous TBE vaccines. This paper provides a review on the epidemiology of TBE and the history of TBE vaccination in China.

Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa Rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the National Immunization Program: acute otitis media microbiology in Costa Rican children.

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥ 2 PCV7 doses or ≥ 1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.

In vitro Activity of Cefditoren against Middle Ear Fluid Isolates from Costa Rican Children with Otitis Media.

Otitis media (OM) is one of the most common infections in children, Streptococcus pneumoniae and nontypable Haemophilus influenzae being the two most common pathogens isolated in the middle ear fluid (MEF) of children with OM. Cefditoren is a third-generation cephalosporin with broad-spectrum antibacterial activity, including activity against those pathogens commonly causing OM, with enhanced stability against common ß-lactamases. The main objective of this study was to evaluate the in vitro activity of cefditoren against pathogens collected from the MEF of Costa Rican children with OM between 2006 and 2011. A total of 715 samples were analyzed. Among the 89 S. pneumoniae strains that were penicillin-nonsusceptible, only 7% were cefditoren-resistant according to Spanish Regulatory Agency criteria; among the H. influenza and M. catarrhalis isolates obtained, 100 and 90% of the isolates, respectively, were cefditoren-susceptible. MIC50/90 against the 207 PCV-13 S. pneumoniae serotyped strains and the 79 serotypes not covered by PCV-13 for cefditoren were 0.03/1 and 0.03/0.12 mg/l, respectively. For both amoxicillin-susceptible and resistant H. influenzae strains, the MIC range against cefditoren was from ≤0.015 to 0.06 mg/l as well. In conclusion, the confirmation of the wide spectrum of activity of cefditoren and its intrinsic strength against resistant strains allows us to suggest that cefditoren might be included as one of the best choices among antibiotics that are widely used in empiric therapy for OM in pediatric patients.

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis.

BACKGROUND: The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. METHODS: We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. FINDINGS: We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3-13·9 million) episodes of severe and 3·0 million (2·1-4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265,000 (95% CI 160,000-450,000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. INTERPRETATION: Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. FUNDING: WHO.