Pneumococcal Community-acquired Pneumonia Research Articles

A genome-wide association study of adults with community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS).MethodsWe performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted.ResultsSix independent sentinel variants reached the genome-wide significance (p < 5 × 10-8), three on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Only one variant at 6p21.32 was validated in independent GWAS of bacterial and pneumococcal pneumonia. Our analyses prioritized C4orf33 on 4q28.2, TAPBP on 6p21.32, and ZNF341 on 20q11.22. Interestingly, genetic defects of TAPBP and ZNF341 are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus and Haemophilus influenzae. Associations were all non-significant for the classical HLA alleles.ConclusionsWe completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility.

Pneumococcal infection in children with recurrent respiratory diseases

In frequently ill children with recurrent respiratory diseases (RRD), violations of local immunity and microbiocenosis of the mucous membranes can contribute to the development of acute and chronic bronchopulmonary diseases. Vaccination against major pathogens, including S. pneumoniae, can help prevent respiratory infections in children.Objective: to study the microbiocenosis and local immunological factors of the nasopharyngeal mucosa in children with RRD, the serotype composition of S. pneumoniae in children with community-acquired pneumococcal pneumonia (CAP) and pneumococcal carriers, as well as the correspondence of the serotype landscape to the composition of modern pneumococcal vaccines.Materials and methods: The study included 150 patients (104 children with RRD and 46 patients with CAP). To assess the condition of the nasopharyngeal mucosa cultural methods, morphofunctional, immunological and capsule PCR typing of S. pneumoniae isolates were performed. Statistical analysis was performed using the Statistica 10.0 package.Results: The age structure was dominated by children aged 3 to 6 years (36%). The majority of patients with RRD had pronounced nasopharyngeal mucosal dysbiosis (n=60), as well as destruction of epithelial cells (n=97). These factors may predispose to the development of bronchopulmonary diseases, including community-acquired pneumonia (CAP). Capsule PCR typing of S. pneumoniae isolates from the nasopharynx was performed in 46 patients. It has been established that in the structure of nasopharyngeal carrier S. pneumoniae in children with CAP, serotypes “3” and 19F prevailed, which were also the main pathogens in pneumococcal CAP. In nasopharyngeal pneumococcal carrier, the thirteen–valent pneumococcal conjugate vaccine (PCV13) overlapped 39.6% (95%CI 27.6–53.1%) of serotypes, in pneumococcal VP – 57.2% (95% CI 36.5-75.5%), while PCV20 overlapped 22.6% more S. pneumoniae serotypes in children with CAP.Conclusion: The strategy for the prevention of acute respiratory infections in children is immunization against pneumococcal infection, which should be carried out taking into account the regional prevalence of S. pneumoniae serotypes.

Carriage of Streptococcus pneumoniae in adults hospitalised with community-acquired pneumonia

We aimed to determine the prevalence of and risk factors for nasopharyngeal and oral pneumococcal carriage in adults with community-acquired pneumonia (CAP), and the relationship between carried and disease-causing serotypes. Between 2016 and 2018, nasopharyngeal swabs, oral-fluid, and urine were collected from hospitalised adults recruited into a prospective cohort study of CAP. Pneumococcal carriage was detected by semi-quantitative real-time PCR of direct and culture-enriched nasopharyngeal swabs and culture-enriched oral-fluid. LytA and piaB positive/indeterminate samples underwent semi-quantitative serotype/serogroup-specific real-time-PCR. Serotypes in urine were identified using a 24-valent serotype-specific urinary-antigen assay. We included 465 CAP patients. Nasopharyngeal carriage was detected in 34/103 (33.0%) swabbed pneumococcal pneumonia patients and oral carriage in 18/155 (12%) of sampled pneumococcal pneumonia patients. Concordance between nasopharyngeal/urine serotypes and oral/urine serotypes was 70.6% and 50% respectively. Serotypes 3 (26%, 22.2%), 8 (19.7%, 19.4%), non-typeable (11.6%, 13.9%) and 19A/F (7.5%, 8.3%) were most prevalent in urine and nasopharyngeal swabs respectively, with non-typeable (35%) and 15A/F (17%) most prevalent in oral-fluid. Pneumococcal carriage was significantly associated with pneumococcal pneumonia (nasopharyngeal adjusted odds ratio [aOR] 8.1, 95% confidence interval [CI] 3.8-17.2; oral aOR 5.5, 95% CI 2.1-13.3). All-cause CAP patients ≥65 years had lower odds of nasopharyngeal carriage (aOR 0.47, 95% CI 0.24-0.91) and current smokers had higher odds of oral carriage (aOR 2.69, 95% CI 1.10-6.60). The association between nasopharyngeal carriage and pneumococcal CAP was strong. Adult carriage and disease from serotypes 8 and 19A may support direct protection of adults with PCV vaccines.

Role of CD64 ratio determination in pneumococcal versus Legionella community-acquired pneumonia

Community-Acquired Pneumonia (CAP) poses a major clinical challenge, with atypical pathogens contributing to a notable percentage of cases. Early identification of Legionella is essential for prompt therapeutic intervention. The Urinary Antigen Test (UAT), which targets Legionella pneumophila serogroup 1, stands out as a widely used and advantageous method for Legionella diagnosis due to its simplicity and ability to detect the pathogen even after antibiotic therapy.

Meningitis in critically ill patients admitted to intensive care unit for severe community-acquired pneumococcal pneumonia

BackgroundAlthough it has been reported that patients with pneumococcal pneumonia may develop meningitis, lumbar puncture is not systematically recommended in these patients, even in patients with associated bacteremia or invasive pneumococcal disease. The aim of this study was to determine the characteristics and outcomes of patients admitted to intensive care unit (ICU) for pneumococcal community-acquired pneumonia who developed meningitis.MethodsWe retrospectively included all consecutive patients admitted to our ICU from January 2006 to December 2020 for severe pneumococcal community-acquired pneumonia according to American Thoracic Society criteria. Meningitis was defined as pleocytosis > 5 cells/mm3 or a positive culture of cerebrospinal fluid for Streptococcus pneumoniae in lumbar puncture. The primary endpoint was the proportion of patients with meningitis during their ICU stay.ResultsOverall, 262 patients [64(52–75) years old] were included: 154(59%) were male, 80(30%) had chronic respiratory disease, 105(39%) were immunocompromised and 6(2%) were vaccinated against S. pneumoniae. A lumbar puncture was performed in 88(34%) patients with a delay from ICU admission to puncture lumbar of 10.5 (2.8–24.1) h and after the initiation of pneumococcal antibiotherapy in 81(92%) patients. Meningitis was diagnosed in 14 patients: 16% of patients with lumbar puncture and 5% of patients in the whole population. Patients with meningitis had more frequently human immunodeficiency virus positive status (29 vs. 5%, p = 0.02), neurological deficits on ICU admission (43 vs. 16%, p = 0.03) and pneumococcal bacteremia (71 vs. 30%, p < 0.01) than those without. The ICU mortality rate (14 vs. 13%, p = 0.73) and the mortality rate at Day-90 (21 vs. 15%, p = 0.83) did not differ between patients with and without meningitis. The proportion of patients with neurological disorders at ICU discharge was higher in patients with meningitis (64 vs. 23%, p < 0.001) than in those without. The other outcomes did not differ at ICU discharge, Day-30 and Day-90 between the two groups of patients.ConclusionMeningitis was diagnosed in 16% of patients with severe pneumococcal community-acquired pneumonia in whom a lumbar puncture was performed, was more frequent in patients with pneumococcal bacteremia and was associated with more frequent neurological disorders at ICU discharge. Further studies are needed to confirm these results.

Pneumococcal serotypes and risk factors in adult community acquired pneumonia 2018–20: a multicentre UK cohort study

BackgroundHigher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. MethodsWe conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. FindingsOf 1921 adults hospitalised with CAP, 781 (40·7%, 95% confidence intervals (CI) 38·5-42·9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31·0%, 95% CI 27·8-34·3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70·7%, 95% CI 64·5-76·0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2·8-5·6%), and PCV20-non13-serotypes in 192 (24·6%), with serotype 8 most prevalent (123/192, 64·1%, 95% CI 57·1-70·5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p<0·001) and less likely to be male (44% versus 61%, p=0·01). PPV23-non13-serotypes were found in 252 (32·3%, 95% CI 29·1-35·6%) pneumococcal CAP patients. InterpretationDespite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. FundingUnrestricted investigator-initiated research grant from Pfizer; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.

Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016-2020: The CAPA Study.

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

Cost-effectiveness of use of 20-valent pneumococcal conjugate vaccine among adults in Germany

ABSTRACTObjectivesDespite national recommendations for use of pneumococcal vaccines, rates of community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) remain high in Germany. New pneumococcal conjugate vaccines (PCVs) with expanded coverage have the potential to reduce the pneumococcal disease burden among adults.MethodsUsing a Markov model, we evaluated the lifetime outcomes/costs comparing 20-valent PCV (PCV20) with standard of care (SC) vaccinations for prevention of CAP and IPD among adults aged ≥60 years and at-risk adults aged 18–59 years in Germany. PCV20 also was compared with sequential vaccination with 15-valent PCV (PCV15) followed by PPSV23 in a scenario analysis.ResultsOver the course of a lifetime (82 years), use of PCV20vs. SC would prevent 54,333 hospitalizations, 26368 outpatient CAP cases, 10946 disease-related deaths yield 74,694 additional life-years (LYs), while lowering total medical costs by 363.2 M €. PCV20 remained cost saving (i.e. dominant) versus SC even in numerous sensitivity analyses, including a sensitivity analysis assuming moderate effectiveness of the SC pneumococcal polysaccharide vaccine against noninvasive pneumococcal CAP. In several scenario analyses and a probabilistic sensitivity analysis, PCV20 was also cost-saving compared toPCV15 PPSV23 vaccination.ConclusionsOne dose of PCV20 among adults aged ≥60 years and adults aged 18–59 years with moderate- and high-risk conditions wouldsubstantially reduce pneumococcal disease, save lives, and be cost saving compared with SC.

Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

Nausea Predicts Bacteremia in Immunocompetent Patients with Pneumococcal Community-Acquired Pneumonia: Secondary Data Analysis from a Prospective Cohort.

In pneumococcal community-acquired pneumonia (CAP), bacteremia is associated with increased mortality, but initial clinical severity scores frequently fail to identify bacteremic patients at risk. We have previously shown that gastrointestinal symptoms are common among patients admitted to the hospital with pneumococcal bacteremia. The aim of this study was to examine gastrointestinal symptoms and inflammatory responses in bacteremic and non-bacteremic pneumococcal CAP in a prospective cohort of immunocompromised and immunocompetent patients hospitalized with CAP. Logistic regression analysis was used to estimate the predictive value of gastrointestinal symptoms for pneumococcal bacteremia in patients with CAP. The Mann-Whitney test was used to compare inflammatory responses in patients with bacteremic vs. non-bacteremic pneumococcal CAP. Eighty-one patients with pneumococcal CAP were included, of whom 21 (26%) had bacteremia. Immunocompetent patients with pneumococcal CAP had an odds ratio of 16.5 (95% CI 3.0-90.9, p = 0.001) for bacteremia if nausea was present, whereas no such association was found in the immunocompromised patients (OR 0.22, 95% CI 0.02-2.05, p = 0.18). The serum levels of C-reactive protein, procalcitonin and interleukin 6 were significantly higher in the patients with bacteremic pneumococcal CAP compared to non-bacteremic pneumococcal CAP patients (p < 0.001, p = 0.005, and p = 0.019, respectively). In immunocompetent patients hospitalized with pneumococcal CAP, nausea may be a predictor of bacteremia. Bacteremic pneumococcal CAP patients display an increased inflammatory response compared to non-bacteremic pneumococcal CAP patients.

HTA49 Cost-Utility Analysis of Pneumococcal Vaccines for Older Adults Available in El Salvador

In El Salvador, the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) are available to prevent invasive pneumococcal disease (IPD) such as meningitis, bacteremia, as well as community-acquired pneumococcal pneumonia (CAP) caused by serotypes contained in these vaccines. This analysis estimated the clinical and economic values of PCV13 and PPSV23 from the public healthcare perspective.

HTA31 Cost-Utility Analysis of Pneumococcal Vaccines for Older Adults Available in Costa Rica

In Costa Rica, 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) are available to prevent invasive pneumococcal disease (IPD) such as meningitis, bacteremia, as well as community-acquired pneumococcal pneumonia (CAP) caused by serotypes contained in these vaccines. This analysis estimated the clinical and economic values of PCV13 and PPSV23 from the public healthcare perspective.

Short- and long-term prognosis of patients with community-acquired Legionella or pneumococcal pneumonia diagnosed by urinary antigen testing

ObjectivesTo analyze the differences in short- and long-term prognosis and the predictors of survival between patients with community-acquired Legionella and Streptococcus pneumoniae pneumonia, diagnosed early by urinary antigen testing (UAT). MethodsProspective multicenter study conducted in immunocompetent patients hospitalized with community-acquired Legionella or pneumococcal pneumonia (L-CAP or P-CAP) between 2002-2020. All cases were diagnosed based on positive UAT. ResultsWe included 1452 patients, 260 with community-acquired Legionella pneumonia (L-CAP) and 1192 with community-acquired pneumococcal pneumonia (P-CAP). The 30-day mortality was higher for L-CAP (6.2%) than for P-CAP (5%). After discharge and during the median follow-up durations of 11.4 and 8.43 years, 32.4% and 47.9% of patients with L-CAP and P-CAP died, and 82.3% and 97.4% died earlier than expected, respectively. The independent risk factors for shorter long-term survival were age >65 years, chronic obstructive pulmonary disease, cardiac arrhythmia, and congestive heart failure in L-CAP and the same first three factors plus nursing home residence, cancer, diabetes mellitus, cerebrovascular disease, altered mental status, blood urea nitrogen ≥30 mg/dl, and congestive heart failure as a cardiac complication during hospitalization in P-CAP. ConclusionIn patients diagnosed early by UAT, the long-term survival after L-CAP or P-CAP was shorter (particularly after P-CAP) than expected, and this shorter survival was mainly associated with age and comorbidities.

EE96 Budget Impact Analysis of Pneumococcal Vaccines for Older Adults Available in Costa Rica

In Costa Rica, the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) are available to prevent invasive pneumococcal disease (IPD) such as meningitis, bacteremia, as well as community-acquired pneumococcal pneumonia (CAP) caused by serotypes contained in these vaccines. We aim to estimate these vaccines' budget impact (BI) on Costa Rica's public health system.

CARDIOVASCULAR DISEASE AFTER PNEUMOCOCCAL PNEUMONIA

Objective: The purpose of this study was to assess the impact of arterial hypertension (AH) and dyslipidemia on the severity, cardiovascular events and death in patients hospitalized for pneumococcal community acquired pneumonia (CAP). Design and method: Retrospective, cohort, multicenter, epidemiologic study. All adult inpatients of 4 different centres in Portugal, with microbiological and clinical documented pneumococcal CAP were included. Demographic data, comorbidities, antibiotic therapy, hospital length of stay, need for ICU admission, invasive mechanical ventilation (IMV) and renal replacement therapy (RRT) were collected. All patients were monitored until death or 1-year of follow up. Risk factors for short- and long-term all-cause mortality, including cardiovascular events, were computed. Patients were divided into 3 groups: H) with isolated AH; HD) with both AH and dyslipidemia; Control) without AH or dyslipidemia. The significance level was defined as p &lt;0.05. Results: 797 patients were included in this study, 53.6% male, mean age 72.4±16.5 years. Comparing the 3 groups, females were prevalent in H and HD groups (52% and 54.3% vs 40.6% Control; p&lt;0.002). Mean age was higher in H and HD (78.2±12.6 and 78.4±10.7 years; vs Control 67.5±18.2 years, ANOVA p&lt;0.001). 18.8% patients required ICU admission, 6.7% IMV and 13.1% RRT. H required more IMV (7.5%, p = 0,5) and HD more RRT (16.6%, p = 0.2). The overall in-hospital mortality was 17.8%. During the follow up, H and HD groups were more readmitted to the emergency department due to cardiovascular events than Control group (11.7% and 13.4% vs. 6.5%, OR 1,91 p = 0.04 and OR 2.26 p = 0.016, respectively); also required more hospitalization for cardiovascular events than Control group (14.4% e 12.6% vs. 6.2%; OR 2.49, p = 0.002; and OR 1.99, p = 0.02, respectively). One-year all-cause mortality was higher in H group (39.2%; p = 0.026). Conclusions: Prevalence of arterial hypertension was 47.4%, higher than the national rate. H group resorted, with or without dyslipidemia, more often to the emergency department, requiring more hospitalization and with higher mortality rates, without difference in hospital mortality. It's crucial to control cardiovascular risk factors, providing greater cardiovascular protection to reduce the risk of long-term mortality.

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Management of Pediatric Community-Acquired Pneumonia in the Era of Widespread Vaccination against Streptococcus Pneumoniae at a First-Level Hospital

Community-acquired pneumonia (CAP) is a common and potentially severe infection affecting children. A retrospective study was carried out at our Institution between November 2022 and January 2023. Twenty-eight patients under 14 years of age were diagnosed and treated accordingly. Median age was 35 months, half of the patients were males. The most detected pathogen was S. pneumoniae (in 36% of all patients). Other pathogens detected were RSV in 3 patients (11%), influenza B virus in two patients (7%), adenovirus in two patients (7%), and M. pneumoniae in one patient (4%). Fourteen children (50% of the total number) developed a respiratory failure that required supplemental oxygen. Among these, 8 children (57% of all children receiving oxygen supplementation) required low-flow oxygen delivery, four children (29%) required high-flow oxygen delivery, and one child (7%) required invasive ventilation. Five children (55% of children with a bacterial CAP) received intravenous antibiotics, while 44% of patients received oral antibiotics. First-line intravenous antibiotics consisted of a third-generation cephalosporin for infants and children older than 1 month, and ampicillin/sulbactam with gentamicin for newborns. Amoxy-clavulanic acid was the first-line oral antibiotic for pneumococcal CAP, while oral clarithromycin was the first line antimicrobic for CAP caused by M. pneumoniae.&#x0D; Twenty-one children (75% of total patients) were fully vaccinated, three children (11%) had received two doses because of age. Regarding the 10 children with a pneumococcal CAP, seven (70%) were fully vaccinated, one had received two-doses of pneumococcal conjugate vaccine (PCV), and two were unvaccinated.

Amoxicillin and penicillin G dosing in pediatric community-acquired pneumococcal pneumonia in the era of conjugate pneumococcal vaccines.

Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data. Using NONMEM v7.3, Monte Carlo simulations (N=10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%-50% of the dosing interval. In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard-dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high-dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%-50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens. Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.

Community-Acquired Pneumococcal Pneumonia in Highly Vaccinated Population: Analysis by Serotypes, Vaccination Status, and Underlying Medical Conditions.

Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961). Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.