Bacteremic Pneumococcal Pneumonia Research Articles

Unveiling the role of preceding seasonal influenza in the development of bacteremic pneumococcal pneumonia in older adults before the COVID-19 pandemic in Japan

We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan. Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022). The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza. Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults.

Impact of the new membrane-targeting lipoglycopeptide antibiotic MCC5145 on the treatment of bacteremic pneumococcal pneumonia in mice.

Bacteremic Streptococcus pneumoniae pneumonia is one of the most severe forms of invasive pneumococcal disease (IPD) and with particularly high case-fatality rates among the elderly and individuals with comorbidities, exacerbated by rising antibiotic resistance and time to initiation of therapy. Here, we examined the efficacy of the preclinical "vancapticin" glycopeptide MCC5145 against fulminant infection by S. pneumoniae serotype 2 strain D39 in a bioluminescent, neutropenic mouse model of bacteremic pneumonia. MCC5145 is a semisynthetic vancomycin derivative chemically modified at the C-terminus with a membrane-targeting motif designed to preferentially bind the anionic bacterial surface. We show that similar to vancomycin, subcutaneous administration of MCC5145 to mice 1 day after intranasal infection with a bioluminescent derivative of S. pneumoniae D39 elicited time and concentration-dependent reduction in total flux in the lungs and blood. Together, our finding supports the further development of MCC5145 as a potential new treatment option for pneumonia and/or bacteremic pneumonia in clinical settings, particularly for immunocompromised individuals. IMPORTANCE S. pneumoniae (the pneumococcus) causes severe community acquired lung and blood infection, especially among the elderly and people with underlying medical conditions and/or weakened immune systems. The rising incidence of antibiotic resistance and delays between diagnosis of infection and commencement of effective therapy make treatment difficult and result in high mortality rates. In this work, we show that a new derivative (MCC5145) of an existing antibiotic (vancomycin) rapidly eradicated lethal pneumococcal challenge from the lungs and blood of mice with a suppressed immune system. Our findings support that MCC5145 is a promising option for the treatment of lung and blood infections caused by the pneumococcus at point-of-care settings, particularly for the elderly and individuals with a weakened immune system.

The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.

In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month. During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria. There was no funding for this study.

TNFR2+ regulatory Tcells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing γδ Tcells in the lung.

Streptococcus pneumoniae is a pathogen of global morbidity and mortality. Pneumococcal pneumonia can lead to systemic infections associated with high rates of mortality. We find that, upon pneumococcal infection, pulmonary Treg cells are activated and have upregulated TNFR2 expression. TNFR2-deficient mice have compromised Treg cell responses and highly activated IL-17A-producing γδ Tcell (γδT17) responses, resulting in significantly enhanced neutrophil infiltration, tissue damage, and rapid development of bacteremia, mirroring responses in Treg cell-depleted mice. Deletion of total Treg cells predominantly activate IFNγ-T cell responses, whereas adoptive transfer of TNFR2+ Treg cells specifically suppress the γδT17 response, suggesting a targeted control of γδT17 activation by TNFR2+ Treg cells. Blocking IL-17A at early stage of infection significantly reduces bacterial blood dissemination and improves survival in TNFR2-deficient mice. Our results demonstrate that TNFR2 is critical for Treg cell-mediated regulation of pulmonary γδT17-neutrophil axis, with impaired TNFR2+ Treg cell responses increasing susceptibility to disease.

2205. Potential Causative Association between Respiratory Viruses and Pneumococcus-Associated Disease in Young Children in Israel: Lessons from the COVID-19 Pandemic

Abstract Background During the early Covid-19 pandemic, we observed a close-to-full disappearance of the activity of 4 respiratory viruses (RSV, hMPV, influenza, and parainfluenza), followed by an off-season sequential re-emergence in 2021. Surprisingly, a striking similarity between the dynamics of pneumococcus-associated disease (PAD; namely community-acquired alveolar pneumonia [CAAP; often considered pneumococcal] and bacteremic-pneumococcal pneumonia [IPD-Pneumonia]), was also observed. In contrast, adenovirus and rhinovirus activities did not change during COVID-19. We examined the association between PAD and RSV, hMPV, influenza, and parainfluenza (PAD-viruses). Methods Surveillance of CAAP and IPD-Pneumonia incidences and viral activity in children &amp;lt; 5 years was described in detail previously [Danino D. et al. Clin Infect Dis. 2022, https://doi.org/10.1093/cid/ciab1014]. We extended the observations until December 2021, to capture the sequential re-emergence of the 4 PAD-viruses. A hierarchical linear regression model was used to quantify the association between PAD-viruses (each virus individually and combined), adenovirus and PAD. After fitting the models, the contribution of each virus was estimated. Results The Figure shows striking similarities in the dynamics of CAAP, IPD-Pneumonia, and PAD-viruses both before and during the COVID-19 pandemic. During the expected peak season (Oct 2020 – Apr 2021) PAD episodes were extremely low. However, off-season peaks were seen during May – Dec 2021. Overall, 78% and 25% of all CAAP and IPD-Pneumonia episodes, respectively, were attributable to these viruses in children &amp;lt; 5 (Table). In CAAP, cases were attributable to each of the 4 PAD-viruses individually throughout the first 5 years of life: RSV and hMPV combined contributed 80%, 63%, and 42% of all CAAP episodes in children aged &amp;lt; 1, 1, and 2-4 years, respectively. The respective figures for influenza and parainfluenza combined were 13%, 21%, and 22%. Only RSV significantly contributed to IPD-Pneumonia (19%). Adenovirus did not contribute to PAD episodes. Conclusion Our model suggests an important causative association between RSV, hMPV, influenza, and parainfluenza viruses and CAAP, and between RSV and IPD-Pneumonia. Disclosures All Authors: No reported disclosures.

The Effect of Macrolides on Mortality in Bacteremic Pneumococcal Pneumonia: A Retrospective, Nationwide Cohort Study, Israel, 2009-2017.

Previous cohort studies of pneumonia patients reported lower mortality with advanced macrolides. Our aim was to characterize antibiotic treatment patterns and assess the role of quinolones or macrolides in empirical therapy. An historical cohort, 1 July 2009 to 30 June 2017, included, through active surveillance, all culture-confirmed bacteremic pneumococcal pneumonia (BPP) among adults in Israel. Cases without information on antibiotic treatment were excluded. Logistic regression analysis was used to assess independent predictors of in-hospital mortality. A total of 2016 patients with BPP were identified. The median age was 67.2 years (interquartile range [IQR] 53.2-80.6); 55.1% were men. Lobar pneumonia was present in 1440 (71.4%), multi-lobar in 576 (28.6%). Median length of stay was 6 days (IQR 4-11). A total of 1921 cases (95.3%) received empiric antibiotics with anti-pneumococcal coverage: ceftriaxone, in 1267 (62.8%). Coverage for atypical bacteria was given to 1159 (57.5%), 64% of these, with macrolides. A total of 372 (18.5%) required mechanical ventilation, and 397 (19.7%) died. Independent predictors of mortality were age (odds ratio [OR] 1.051, 95% confidence interval [CI] 1.039, 1.063), being at high-risk for pneumococcal disease (OR 2.040, 95% CI 1.351, 3.083), multi-lobar pneumonia (OR 2.356, 95% CI 1.741, 3.189). Female sex and macrolide therapy were predictors of survival: (OR 0.702, 95% CI .516, .955; and OR 0.554, 95% CI .394, .779, respectively). Either azithromycin or roxithromycin treatment for as short as two days was predictor of survival. Quinolone therapy had no effect. Empirical therapy with macrolides reduced odds for mortality by 45%. This effect was evident with azithromycin and with roxithromycin. The effect did not require a full course of therapy.

Acetylsalicylic acid use is associated with improved survival in bacteremic pneumococcal pneumonia: A long-term nationwide study.

BackgroundPneumonia is commonly caused by Streptococcus pneumoniae (pneumococcus) and associated with subsequent cardiovascular complications and increased mortality. Potential short‐term survival benefits conferred by acetylsalicylic acid (ASA) use in pneumonia remain controversial, and long‐term outcomes have not been studied.ObjectivesTo evaluate the association between ASA use and survival for up to 1 year following bacteremic pneumococcal pneumonia.MethodsAll bacteremic pneumococcal episodes in Iceland from 1975 to 2019 were reviewed. The study cohort consisted of individuals at least 18 years of age with symptoms and imaging results consistent with pneumonia. Differences in survival were assessed at 30 days, 90 days and 1 year using propensity score weighting (inverse probability weighting). Splitting and stratifying on survival at 7 days was done for the 30‐day survival, because of nonproportionality.ResultsIn total, 815 bacteremic pneumococcal pneumonia episodes (median age 67 years, females 48%) were identified. Cox regression using propensity score weighting on the association of ASA with survival at 30 days showed an average hazard ratio (HR) of 0.60 (95% confidence interval [CI] 0.34–1.05). A significantly improved survival was observed within 7 days (HR = 0.42, 95% CI 0.19–0.92) but not during days 7–30 (HR = 1.08, 95% CI 0.46–2.55). ASA was associated with survival at 90 days (HR = 0.53, 95% CI 0.32–0.87) and 1 year (HR = 0.48, 95% CI 0.31–0.75).ConclusionUse of ASA upon admission for bacteremic pneumococcal pneumonia is associated with significantly reduced mortality for up to 1 year after diagnosis. ASA therapy in patients with pneumonia and other infectious syndromes warrants further study.

Clinical predictors and outcomes for Legionnaire's disease versus bacteremic pneumococcal pneumonia

BackgroundLegionnaires' disease (LD) is a serious sometimes fatal pneumonia caused by Legionella pneumophila. The clinical manifestations of LD may be similar to those by caused by Streptococcus pneumoniae. As both conditions can be serious illnesses but requiring different antimicrobial therapies, factors that can help differentiate these types of pneumonias can be helpful in the clinical management of hospitalized patients with bacterial pneumonia. This study aimed to compare clinical features and indicators of disease progression in hospitalized patients with community-acquired pneumonia caused by L. pneumophila and bacteremic S. pneumoniae. MethodsWe conducted a retrospective case comparison study of adult patients hospitalized with LD or S. pneumoniae. Data collected included demographic, clinical characteristics, and comorbidities, and outcomes. Data were analyzed using SPS vs 24.0. Multivariable analysis was done using logistic regression with a forward stepwise algorithm. ResultsA total of 106 patients met study criteria. The incidence of LD peaked in summer months and S. pneumoniae peaked in the winter quarter. From multivariable analysis predictors of LD were male gender (OR=21.6, p < 0.001), diarrhea (OR=4.5, p = 0.04), body mass index (BMI) (OR=1.13, p = 0.02), hyponatremia (OR=5.6, p = 0.03 and Charlson weighted index of comorbidity (CWIC) score (OR=0.61, p = 0.01). Patients with S. pneumoniae had higher rates of mechanical ventilation, septic shock, and death than those with LD. ConclusionsOur data suggests that variables that may distinguish LD from S. pneumoniae include male gender, diarrhea, hyponatremia, higher temperature on admission, higher BMI and fewer comorbidities. Bacteremic S. pneumoniae was associated with poorer outcomes than LD including higher rates of septic shock, mechanical ventilation, ICU admission, and death.

Decline in Pneumococcal Disease in Young Children During the Coronavirus Disease 2019 (COVID-19) Pandemic in Israel Associated With Suppression of Seasonal Respiratory Viruses, Despite Persistent Pneumococcal Carriage: A Prospective Cohort Study.

BackgroundThe incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis.MethodsThe first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared.ResultsCAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] .07 and .19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels.ConclusionsReductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density, but were strongly associated with the disappearance of specific respiratory viruses.

Bacteraemic pneumococcal pneumonia and SARS-CoV-2 pneumonia: differences and similarities

ObjectiveTo analyse differences in clinical presentation and outcome between bacteraemic pneumococcal community-acquired pneumonia (B-PCAP) and sSvere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pneumonia.MethodsThis observational multi-centre study was conducted on patients hospitalized with B-PCAP between 2000 and 2020 and SARS-CoV-2 pneumonia in 2020. Thirty-day survival, predictors of mortality, and intensive care unit (ICU) admission were compared.ResultsIn total, 663 patients with B-PCAP and 1561 patients with SARS-CoV-2 pneumonia were included in this study. Patients with B-PCAP had more severe disease, a higher ICU admission rate and more complications. Patients with SARS-CoV-2 pneumonia had higher in-hospital mortality (10.8% vs 6.8%; P=0.004). Among patients admitted to the ICU, the need for invasive mechanical ventilation (69.7% vs 36.2%; P<0.001) and mortality were higher in patients with SARS-CoV-2 pneumonia. In patients with B-PCAP, the predictive model found associations between mortality and systemic complications (hyponatraemia, septic shock and neurological complications), lower respiratory reserve and tachypnoea; chest pain and purulent sputum were protective factors in these patients. In patients with SARS-CoV-2 pneumonia, mortality was associated with previous liver and cardiac disease, advanced age, altered mental status, tachypnoea, hypoxaemia, bilateral involvement, pleural effusion, septic shock, neutrophilia and high blood urea nitrogen; in contrast, ≥7 days of symptoms was a protective factor in these patients. In-hospital mortality occurred earlier in patients with B-PCAP.ConclusionsAlthough B-PCAP was associated with more severe disease and a higher ICU admission rate, the mortality rate was higher for SARS-CoV-2 pneumonia and deaths occurred later. New prognostic scales and more effective treatments are needed for patients with SARS-CoV-2 pneumonia.

Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study

BackgroundThe presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP.MethodsThis was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients.ResultsAmong 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone.ConclusionBacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors.

Characteristics and outcomes of bacteremic pneumococcal pneumonia of patients with and without HIV infection in Argentina

Streptococcus pneumoniae is the main causative agent of pneumonia, with a 10 to 25 percent rate of isolation in blood cultures. Controversies exist regarding the prognostic impact of a history of human immunodeficiency virus (HIV) infection on community-acquired pneumonia. The aim of our work was to analyze and compare the clinical presentation, radiological findings and progression of pneumococcal pneumonia in patients infected with and not infected with HIV. We retrospectively analyzed adult patients with positive blood cultures for Streptococcus pneumoniae and clinical and radiological findings compatible with pneumonia in the period between January 2012 and May 2017. Age, sex, comorbidities, clinical and laboratory variables, radiological severity, progression and mortality were analyzed. Comparative analysis between HIV-positive and -negative patients was carried out. Receiver operating curves (ROC) for CURB-65 were performed to predict mortality in both groups. We included 107 patients (21 HIV-positive and 86 HIV-negative). HIV patients were on average younger (38 vs 58 years) with lower hematocrits (31.7 vs 36.5%) and fewer comorbidities (47 vs 72%). Overall mortality was 36 percent, and the area under the curve (AUC) of the CURB-65 ROC was 0.69 (95% confidence interval: 0.58–0.79) for all patients without differences between the two groups. Patients with a history of HIV infection had the same progression and mortality as the group of patients without that background.

Emergence of Streptococcus pneumoniae serotype 19A (Spn19A) in the pediatric population in Bogotá, Colombia as the main cause of invasive pneumococcal disease after the introduction of PCV10

ABSTRACT Introduction: With the use of pneumococcal conjugate vaccines(PCV), the behavior of invasive pneumococcal disease(IPD) has changed relative to serotype distribution. The introduction of these vaccines in national immunization programs has reduced the incidence of IPD, with a marked decrease in the circulation of the serotypes included in the vaccine used in each country. However, the subsequent emergence of other serotypes not included in the vaccine, such 19A in case of PCV7 and PCV10, has been documented. Materials and methods: This was case series study (2008–2017) in pediatric patients admitted to 10 hospitals in Bogota who were diagnosed with IPD. It was conducted during the transitional period of implementing the PCV10 vaccine in Colombia in 2012. Cases of bacteremic pneumococcal pneumonia, meningitis, primary bacteremia and osteoarticular infection were included. A descriptive analysis of the demographic, clinical and laboratory variables of patients with IPD by Spn19A, its trend over time, profiles of antimicrobial susceptibility and clinical outcomes was performed. Results: There were 463 cases of IPD, 315(68%) with known serotypes. The prevalence of IPD by Spn19A was 17.7%(56 cases), tending to increase over time. During 2008–2011, the prevalence was 4.4%, and during 2014–2017, it was 32.4%, The most frequent diagnosis was pneumonia(80.4%). In nonmeningeal isolates, 39.6% were not susceptible to penicillin. An increase in the resistance was observed over time. Conclusion: Spn19A is a prevalent cause of IPD in the pediatric population of the analyzed cohort, with an increasing trend of this serotype during the surveillance period after the introduction of PCV10, being the most common serotype identified in recent years.

Impact of Cefotaxime Non-susceptibility on the Clinical Outcomes of Bacteremic Pneumococcal Pneumonia.

Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses. Results: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate. Conclusion: Despite the prevalence of cefotaxime, non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.

Evolution of serotypes in bacteremic pneumococcal adult pneumonia in the period 2001–2014, after introduction of the pneumococcal conjugate vaccine in bizkaia (spain)

The introduction of pneumococcal conjugate vaccines (PCV7 and PCV13) in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease in adults. The aim of this study is to analyze the distribution of pneumococcal serotypes in adults with bacteremic pneumococcal community-acquired pneumonia (BPP) after the introduction of PCVs in childhood, and the impact of age and comorbidity on this distribution. We conducted an observational study of all adults hospitalized with BPP between 2001 and 2014, in two tertiary hospitals. Overall, we identified 451 cases of BPP (2001–2005: 194, 2006–2010: 134, 2011–2014: 123). The rate of appearance of new cases decreased over the study period. In 70% of the cases, the serotypes found were among those included in PCV13. The most prevalent serotypes were 3 (23.1%), 7F (14.6%), 19A (8.4%) and 1 (7.5%). There was a significant trend to decrease in the percentage of BPP cases due to PCV7 from period 2001–2005 to 2011–2014 (p = 0.0166) and a significant trend to increase in the six serotypes added to form PCV 13 (p = 0.0003). Serotype 3 was the most frequent in patients who developed complications during hospitalization. We did not detect a significant increase in cases caused by non-PCV13 serotypes. The most frequent non-PCV13 serotype was 22F. In conclusion, a significant proportion of adults continue to develop BPP with vaccine serotypes despite infant pneumococcal vaccination. There is a need for further strategies to reduce the current burden of this disease on adults.

Mortality and costs of pneumococcal pneumonia in adults: a cross-sectional study.

ABSTRACTObjectivePneumococcal pneumonia is a significant cause of morbidity and mortality among adults. The study’s main aim was to evaluate the in-hospital mortality and related costs of community-acquired pneumococcal pneumonia in adults.MethodsThis cross-sectional study used medical records of adult patients with pneumococcal pneumonia hospitalized in a university hospital in Brazil from October 2009 to April 2017. All patients aged ≥ 18 years diagnosed with pneumococcal pneumonia were included. Risk factors, intensive care unit admission, length of hospital stay, in-hospital mortality, and direct and indirect costs were analyzed.ResultsIn total, 186 patients were selected. The mean in-hospital mortality rate was 18% for adults aged < 65 years and 23% for the elderly (≥ 65 years). Bacteremic pneumococcal pneumonia affected 20% of patients in both groups, mainly through chronic respiratory disease (adjusted OR: 3.07, 95% CI: 1.23–7.65, p < 0.01). Over 7 years, annual total direct and indirect costs were USD 28,188 for adults < 65 years (USD 1,746 per capita) and USD 16,350 for the elderly (USD 2,119 per capita).ConclusionPneumococcal pneumonia remains an important cause of morbidity and mortality among adults, significantly affecting direct and indirect costs. These results suggest the need for prevention strategies for all adults, especially for patients with chronic respiratory diseases.

Effects of Anaerobic Culturing on Pathogenicity and Virulence-Related Gene Expression in Pneumococcal Pneumonia.

The pathogenicity of Streptococcus pneumoniae under anaerobic conditions remains largely unknown. We examined the pathogenicity of S. pneumoniae cultured under anaerobic conditions in a murine model of pneumococcal pneumonia. Mice were infected with S. pneumoniae grown under anaerobic or aerobic conditions. The pathogenic effects in vivo in the lower airway tract were then compared. The effect of anaerobic culture on lytA/ply transcript levels in vitro and in vivo were analyzed by quantitative real-time polymerase chain reaction. Mice inoculated with anaerobically cultured S. pneumoniae exhibited significantly lower survival rates and higher bacterial loads in the lungs and blood as compared to those infected with aerobically cultured S. pneumoniae. Aerobically cultured S. pneumoniae in the early log phase of growth was also able to induce severe pneumonia at levels equivalent to those of anaerobic S. pneumoniae. However, ply/gyrB transcript levels were significantly increased in the lungs of mice infected with anaerobically grown S. pneumoniae. In vitro, S. pneumoniae grown under anaerobic culture conditions demonstrated greater proliferation than S. pneumoniae grown under aerobic culture conditions, and bacterial concentrations were maintained for 24 hours without detectable upregulation of lytA messenger RNA. S. pneumoniae grown under anaerobic conditions had the potential to induce severe invasive bacteremic pneumococcal pneumonia in a manner different from that of S. pneumoniae grown under aerobic conditions.

327. Comparison of Clinical Outcome, Causative Serotypes, and Antimicrobial Susceptibilities Between Pneumococcal Meningitis and Pneumococcal Bacteremic Pneumonia in Adult Patients in the Republic of Korea

BackgroundPneumococcal meningitis (PM) is one of invasive pneumococcal disease (IPD) and is considered as a medical emergency with notable morbidity and mortality. This study was designed to characterize differences in clinical characteristics and outcomes, pneumococcal serotypes, and antimicrobial susceptibilities between PM and pneumococcal bacteremic pneumonia (PBP) in adult patients in the Republic of Korea (ROK) from a prospective observational cohort.MethodsAdult IPD cases (≥18 years) were prospectively collected from 20 hospitals participated in the pneumococcal surveillance program in the ROK from 2013 through 2015. Serotyping and antimicrobial susceptibility testing were performed by a multiplexed serotyping assay and Microscan system, respectively.ResultsDuring the study period, 30 cases of PM and 205 cases of PBP were compared. Serotypes 19A, 15B/15C, and 35B were the most prevalent among PM cases, whereas serotypes 3, 11A/D/F, and 19A were the most common serotypes in PBP. There were significant female predominance (46.7% vs. 2.3%, P = 0.022), younger age (56.7% vs. 36.1%, P = 0.031), less immunocompromised states (3.3% vs. 28.8%, P = 0.005), less underlying chronic lung diseases (3.3% vs. 16.6%, P = 0.04), and lower mortality rate (16.7% vs. 44.4%, P = 0.004) in PM, compared with PBP. However, PM cases showed higher penicillin resistance (76.7% vs. 19.2%, P < 0.001), and ceftriaxone resistance (53.3% vs. 13.4%, P < 0.001), consistent with higher MDR prevalence in PM cases (76.7% vs. 53.2 P = 0.016). All PM cases except for three cases received empiric or definite vancomycin treatment. Multiple logistic regression analysis showed that penicillin resistance (odds ratio [OR] 15.75, 95% confidence interval (CI) 3.82–64.72, P < 0.001) and survival (OR 20.73, 95% CI 3.1–136.74, P = 0.002) were significantly associated with PM.ConclusionThis study indicates that adult PM showed favorable clinical outcomes, compared with PBP, despite of differences in clinical characteristics.Disclosures All authors: No reported disclosures.

PIN44 - ECONOMIC EVALUATION OF 60+ YEARS ADULT VACCINATION STRATEGY USING PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN SPAIN

Invasive pneumococcal disease (IPD) and non bacteremic pneumococcal pneumonia (NBPP) represent an important health problem among older adult population. Currently, in Spain the use of PPV23 is recommended for all individuals above 65 years and for individuals with certain chronic diseases, and, in addition, the use of PCV13 is recommended for those with immunosuppression and with specific underlying conditions. This study was aiming to estimate the incremental cost-effectiveness ratio (ICER) of vaccinating immunocompetent adults aged 60+ with PPV23 compared to a sequential vaccination strategy (PCV13-PPV23). A Markov model was adapted to the Spanish healthcare setting to simulate incidence and consequences of NBPP and IPD. Parameters such as vaccine effectiveness, disease incidence, utilities, and costs were based on published data. The analysis was conducted from the perspective of the Spanish National Healthcare System (SNHS), with a lifetime horizon. Waning effect over time was considered for both vaccines’ effectiveness. Outcomes and costs were both discounted at 3% annually. Official list prices were used in the base case. Deterministic sensitivity analyses (DSA) were performed to explore the impact of parametric uncertainty. Additionally, the analysis assessed the ICER of starting vaccination at the age of 60 vs 65 with different strategies. The sequential vaccination strategy would prevent 3,340 cases of IPD, 14,451 cases of NBPP and 2,417 deaths related to pneumococcal disease compared to the PPV23 strategy. The sequential strategy presented a larger number of quality-adjusted life-years (QALYs) compared to PPV23 alone but also increased the total costs by more than €218 million, resulting an ICER of €42,259 per QALY gained. A sequential vaccination strategy of immunocompetent adults aged 60+ with PCV13-PPV23 would result in an improvement in health outcomes, but at a cost exceeding typical cost-effective benchmarks for Spain, compared to PPV23 alone.

Bacteremic pneumococcal pneumonia in adults admitted to a general hospital. Experience in 60 cases

Bacteremic pneumococcal pneumonia (BPP) is a preventable disease with high morbimortality. To evaluate clinical aspects and mortality on BPP patients admitted to a Chilean regional hospital. We looked for adult patients with Streptococcus pneumoniae isolated from blood cultures between 2010 and 2014 years and reviewed clinical records of those who were admitted with pneumonia. We identified 70 BPP patients: 58% were men, mean age was 56 years, 30% were > 65 years, 70% with basic public health insurance, 26% were alcoholics, 86% had comorbidities. Only two patients were vaccinated against S. pneumoniae. CURB-65 severity index for community acquired pneumonia was > 3 in 37% of patients. Twenty-four patients were admitted to ICU, twenty required mechanical ventilation and twenty-four died (34%). Mortality was associated with an age over 65 years, presence of comorbidities and complications of pneumonia. A total of 22 serotypes of S. pneumoniae were identified, five of them (1,3,7F,14 y 9V) were present in 57% of cases. Elevated mortality of our BNN patients was associated with comorbidities and possibly with socio economic factors, which conditioned a late access to medical care.