Invasive Pneumococcal Disease Patients 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.

Mortality of Invasive Pneumococcal Disease following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Greenland.

Before the incorporation of the 13-valent pneumococcal conjugate vaccine (PCV13) into the childhood vaccination regimen in Greenland in 2010, Inuit populations experienced a substantial prevalence of invasive pneumococcal disease (IPD). The PCV13 introduction has been shown to markedly reduce the incidence of IPD. This current study estimated the impact of PCV13 introduction on IPD mortality in Greenland. This was a nationwide register-based study using all available data on IPD cases 1995-2020 in Greenland. Thirty-one-day IPD case fatality rates (CFR), and all-cause and mortality rates associated with IPD during the period before the introduction of PCV13 (January 1995 to September 2010) were compared with those observed in the post-PCV13 era (September 2010 to October 2020). Standardized mortality ratios (SMRs) expressed differences in mortality by sex, age, region, ethnicity, comorbidity, and serotype. IPD CFR decreased with 24.5% from the pre- to the post-PCV13 period. SMR in IPD patients decreased by 57% (95% CI, 36-75%), and a reduction occurred in all age groups. While SMR in IPD persons ≥60 years remained virtually unchanged, there were no IPD-related deaths in persons ≤39 years in the post-PCV13 period. In conclusion, IPD-related mortality has decreased in Greenland following PCV13 introduction in 2010 in the country.

Molecular characterization of invasive Streptococcus pneumoniae clinical isolates from a tertiary children's hospital in eastern China.

Streptococcus pneumoniae is a common opportunistic pathogen that causes invasive pneumococcal disease (IPD), especially in children. This study aimed to determine the prevalence and molecular characteristics of S. pneumoniae isolated from children with IPD. A total of 78 S. pneumoniae isolates from aseptic body fluids of 70 IPD patients were collected at the Children's Hospital of Nanjing Medical University (Jiangsu Province, China) during 2017-2021. Whole-genome sequencing technology was used to analyze the serotype, sequence type (ST), virulence, and antibiotic resistance of the 78 invasive S. pneumoniae clinical isolates. Our results showed that the pneumococcal infection rate declined after the COVID-19 outbreak in 2019. Serotypes 19F, 14, 6A, 23F, 19A, and 6B were the most common strains. The pneumococcal conjugate vaccine (PCV) 13 serotype coverage rate was 87.1%. All isolates were classified by multi-locus sequence typing (MLST) analysis into 27 different STs, including 3 novel STs (ST17941, ST17942, and ST17944) and 1 novel allele [recP (558)]. The most predominant ST was ST271, followed by ST320 and ST876. All isolates carried the following virulence genes: cbpG, lytB, lytC, pce (cbpE), pavA, slrA, plr (gapA), hysA, nanA, eno, piuA, psaA, cppA, iga, htrA (degP), tig (ropA), zmpB, and ply. All isolates were multidrug resistant and had high levels of resistance to macrolides, tetracyclines, and sulfonamides. Taken together, this study revealed extensive genetic diversity among S. pneumoniae isolates from a single Chinese hospital. Wearing masks, universal infant vaccination with PCV13, and the launch of recombinant protein vaccine development programs could reduce the burden of IPD in children. IMPORTANCE Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae in children remains a global burden and should be given more attention due to the fact that the pneumococcal vaccine is not fully covered globally. The molecular epidemiological characteristics of S. pneumoniae are not so clear, especially in these years of COVID-19. In this study, we collected S. pneumoniae isolates from the aseptic body fluid of children with IPD from 2017 to 2021 in a tertiary children's hospital in China and revealed the extensive genetic diversity of these isolates. Most importantly, we first found that the rate of pneumococcal infection has declined since the COVID-19 outbreak in 2019, which means that wearing masks could reduce the transmission of S. pneumoniae. In addition, it was shown that universal infant vaccination with PCV13 seems essential for reducing the burden of IPD in children.

Temporally Associated Invasive Pneumococcal Disease and SARS-CoV-2 Infection, Alaska, USA, 2020-2021.

Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020-December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p<0.01). IPD patients with SARS-CoV-2 were also more likely to be experiencing homelessness (adjusted OR 3.5; 95% CI 1.7-7.5). Our study highlights the risk for dual infection and ongoing benefits of pneumococcal and COVID-19 vaccination, especially among vulnerable populations.

Reduction in the incidence of invasive infections caused by encapsulated bacteria after the onset of the COVID-19 pandemic

Interaction between severe acute respiratory coronavirus 2 (SARS-CoV-2) and IIEB remains under investigation. Objective: to compare IIEB incidence before and during COVID-19 pandemic, and assess incidence of coinfection with COVID-19 and case fatality. A cross-sectional study was performed on data from a centralized microbiology laboratory serving a network of healthcare centers comprising 713 pediatric and adult inpatient beds, expanded by 20% during the pandemic. Three periods were evaluated: (1) pre-pandemic: March 1, 2019–February 29, 2020; (2) pandemic year 1: March 1, 2020–February 28, 2021; (3) pandemic year 2: March 1, 2021–July 31, 2021. Descriptive statistical analysis was performed. 56 502 samples (96% blood cultures) from 27224 patients were analyzed. Of these, 54 samples (from 54 patients) were positive for encapsulated bacteria. IIEB incidence was: 167.4, 32.6, and 50.4 per 100000 samples for periods 1, 2, and 3, respectively. Twelve IIEB episodes occurred during the pandemic period: 10 Streptococcus pneumoniae, and 2 Haemophilus influenzae, of which 7 were SARS-CoV-2/S. pneumoniae coinfections, with an incidence of 5.68 per 10000 COVID-19-related hospitalizations (0.056%). IIEB case fatality was 31%, 29%, and 60% for each period, respectively, 3/7 patients with coinfection died (43%). Case fatality for invasive pneumococcal disease (IPD) in patients without COVID-19, was 32.5%. Significant reduction in IIEB incidence was observed during the pandemic, coinciding with implementation of containment measures. The incidence of SARS-CoV-2/S. pneumoniae coinfection was low, with higher case fatality than IPD patients without COVID-19.

Invasive pneumococcal disease in patients from a pediatric hospital in Peru, 2017-2020.

Motivation for the study: there are few reports describing cases of invasive pneumococcal disease after the introduction of the 13-valent conjugate vaccine in Peru. Main findings: cases of invasive pneumococcal disease are still reported in children, more frequently in children under five years of age. The most frequent clinical form was bacteremia and there was greater antibiotic resistance to erythromycin, trimethoprim-sulfamethoxazole, and penicillin. Implications: our findings suggest the need to maintain epidemiological surveillance of invasive pneumococcal disease and to measure the impact of vaccination against pneumococcus in children. This study aimed to describe the clinical characteristics, serotypes, and antibiotic susceptibility in patients with invasive pneumococcal disease (IPD). The medical records of patients with IPD who were hospitalized at the Instituto Nacional de Salud del Niño-Breña (Lima, Peru) were reviewed. We evaluated 29 patients. The median age was 1.9 years (interquartile range: 1 to 4 years). Of the sample, 51.7% were women and the most frequent clinical form of IPD was bacteremia in 18 (62.1%) patients; 65.5% had a complete vaccination schedule, according to the Peruvian Ministry of Health. Germ isolation was performed from blood samples in 82.8% of patients. Antibiotic resistance to erythromycin (55.2%) was the most frequent, followed by resistance to trimethoprim-sulfamethoxazole (48.3%) and penicillin (24.1%). The isolated serotypes were 6C, 19A, 23A and 24F. One patient died of meningitis. In conclusion, IPD was more frequent in children aged one to five years and the most frequent clinical form was bacteremia. Five serotypes reported in previous studies were found to be resistant to penicillin and erythromycin.

Clinical Characteristics of Pneumococcal Infections and Predictors of Invasive Pneumococcal Disease

Objectives: Streptococcus pneumoniae infections are an important cause of morbidity and mortality, especially among high-risk groups. Our country has limited data on the clinical findings of pneumococcal infections and invasive pneumococcal disease (IPD). Therefore, we aimed to evaluate patients’ demographic and clinical findings with pneumococcal infection. Methods: The data of the patients who were admitted to our hospital between January 2012 and December 2016 were analyzed retrospectively. Isolation of Streptococcus pneumoniae from sterile body sites was defined as invasive pneumococcal disease. Demographic data, clinical findings, laboratory values, and death rates of patients with the pneumococcal disease were analyzed statistically. Results: One hundred and fifty-four patients were included in the study. Of these patients, 106 (68.8%) were male, and the mean age was 65.3±15.6 (20-94). The diagnosis of the patients were pneumonia (79.2%), sepsis (10.4%), wound infection (3.2%), peritonitis (1.9%), epididymoorchitis (3.2%), pyelonephritis (3.2%), meningitis (1.3%), brain abscess (0.6%), arthritis (0.6%), endocarditis (0.6%) and pericarditis (0.6%). The mean follow-up period was 27.8±22.3 months. The overall mortality rate was 32.5% in all patients. Invasive pneumococcal disease was detected in 31 (20.1%) of all patients. C-reactive protein (CRP) levels (&gt;14.4 mg/dL), penicillin and ciprofloxacin sensitivity rates were significant parameters in invasive pneumococcal disease patients (p=0.039, p=0.028 and p=0.045). Pneumococcal strains obtained from patients with IPD were more susceptible to penicillin and ciprofloxacin than non-invasive pneumococcal strains (96.4% and 78.8%, p=0.028; 100%, and 42.9%, p=0.045). Conclusion: Knowledge of risk factors associated with pneumococcal infections in our country is crucial in supporting national immunization programs. CRP elevation, penicillin sensitivity, and fluoroquinolone sensitivity rates were significantly higher in patients with IPD. According to the results of our study, immunocompromised patients and patients with comorbidities have a higher risk for the development of invasive disease. Keywords: invasive, pneumococcus, risk factors, Streptococcus pneumonia

Invasive Pneumococcal Disease and Long-Term Mortality Rates in Adults, Alberta, Canada.

The relationship between increased short-term mortality rates after invasive pneumococcal disease (IPD) has been frequently studied. However, the relationship between IPD and long-term mortality rates is unknown. IPD patients in Alberta, Canada, had clinical data collected that were linked to administrative databases. We used Cox proportional hazards modeling, and the primary outcome was time to all-cause deaths. First IPD events were identified in 4,522 patients, who had a median follow-up of 3.2 years (interquartile range 0.8‒9.1 years). Overall all-cause mortality rates were consistently higher among cases than controls at 30 days (adjusted hazard ratio [aHR] 3.75, 95% CI 3.29–4.28), 30‒90 days (aHR 1.56, 95% CI 1.27‒1.93), and >90 days (aHR 1.43, 95% CI 1.33–1.54). IPD increases risk for short, intermediate, and long-term mortality rates regardless of age, sex, or concurrent conditions. These findings can help clinicians focus on postdischarge patient plans to limit long-term effects after acute IPD infection.

Clinical characteristics, antimicrobial resistance, and risk factors for mortality in paediatric invasive pneumococcal disease in Beijing, 2012\u20132017

BackgroundTo analyse clinical characteristics, antibiotic susceptibility, and risk factors for mortality in paediatric invasive pneumococcal disease (IPD) in Beijing.MethodsPaediatric IPD patients in our hospital were retrospectively collected from 2012 to 2017. Clinical manifestations, laboratory tests, antimicrobial susceptibility and serotype of isolates, and risk factors for mortality of IPD were analysed.ResultsOverall, 186 IPD cases were enrolled. The major manifestations were meningitis (76), pneumonia with bacteraemia (60), bacteraemia without focus (21), and pneumonia with empyaema (22). Of 72 cases with underlying diseases, leukaemia (18.0%), congenital heart disease (15.3%), primary immunodeficiency disease (12.5%), nephrotic syndrome (12.5%), and cerebrospinal fluid leakage (12.5%) were most common. In total 96.9% of isolates would have been covered by the pneumococcal conjugate vaccine (PCV13), including 19F (32.8%), 19A (23.4%), 4 (17.2%), and 23F (9.4%). Nonsusceptibility rates of penicillin, cefotaxime, and cefepime among nonmeningitis patients increased between 2012 and 2017; The mortality rate was 21.5%. Meningitis, respiratory failure, multiple organ failure, and white blood cell count < 4000 cells/μL were independent risk factors for mortality.ConclusionMeningitis was the most common clinical manifestation of IPD, and was frequently associated with death. Strains in the PCV13 vaccine would cover most of the cases, and so wider use of PCV13 should be considered.

Streptococcus pneumoniae Serotypes Associated with Death, South Africa, 2012-2018.

The Streptococcus pneumoniae polysaccharide capsule plays a role in disease severity. We assessed the association of serotype with case-fatality ratio (CFR) in invasive pneumococcal disease (IPD) and meningitis in South Africa, 2012–2018 (vaccine era), using multivariable logistic regression by manual backward elimination. The most common serotypes causing IPD were 8 and 19A. In patients <15 years of age, serotypes associated with increased CFR in IPD, compared with serotype 8 and controlling for confounding factors, were 11A, 13, 19F, 15A, and 6A. None of these serotypes were associated with increased CFR in meningitis. Among IPD patients >15 years of age, serotype 15B/C was associated with increased CFR. Among meningitis patients of all ages, serotype 1 was associated with increased CFR. PCV13 serotypes 1, 3, 6A, 19A, and 19F should be monitored, and serotypes 8, 12F, 15A, and 15B/C should be considered for inclusion in vaccines to reduce deaths caused by S. pneumoniae.

Population-Based Surveillance of Pneumococcal Infections in Children with Sickle Cell Disease before and after Prevnar 7® and Prevnar 13® Licensure: Implications for Expanded Vaccination

Before prophylactic antibiotic use, approximately 1/10 children <5 years old with sickle cell disease (SCD) developed invasive pneumococcal disease (IPD) with a high risk of meningitis and death. Although the emergence of penicillin-resistance in IPD threatened benefits of penicillin prophylaxis, after licensure of the 7-valent pneumococcal polysaccharide vaccine (PCV7) in 2000, IPD rates in children with SCD decreased by over 2/3. In 2010, PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 18C, 23F) was licensed in children, and in 2021, two additional conjugated vaccines were approved for use in adults: PCV15 (VAXNEUVANCE®, PCV13+: 22F, 33F) and PCV20 (PREVNAR20®, PCV13+: 8, 10A, 11A, 12F, 15B, 22F, 33F). IPD rates in children with SCD over 24 years in Atlanta were evaluated to describe trends in age of infection, frequency of antibiotic resistance, non-vaccine IPD serotype distribution after vaccine licensures, and estimates for serotype coverage by newer vaccines. IPD among children with SCD, ages 0 to 4 years and 5 to 9 years, residing in the Metropolitan area of Atlanta, Georgia, USA, from 1/1/1994 through 7/31/2018, were compared to the general population. The Centers for Disease Control and Prevention (CDC)-funded Georgia Emerging Infections Program (GA EIP) Active Bacterial Core Surveillance network included initially 8 counties in 1994 and from 1997 onward, 20 counties (total populations of approximately 3.8 and 5.1 million, respectively). Two registries of patients with SCD seen at least once at one of 3 pediatric hospitals serving the region were merged and matched with GA EIP data. The serotyping and antibiotic susceptibility testing were conducted at the CDC. The study was approved by the Emory University Institutional Review Board. Data from 3 periods: pre PCV period (94-99), PCV7 period (00-09) and PCV13 period (10-18) were analyzed. Compared to the pre PCV period, overall, IPD rates decreased in children with SCD vs 91% in the RP for 0-4 years; and 80% in children with SCD vs 78% in the RP for 5-9 years (table1). The difference in IPD rates between patients with SCD and the general population increased over time: pre PCV period, relative risk (RR)=24.22 (95 % Confidence Interval [CI] 17.43,32.88), P<.001; PCV 7 period, RR=32.17 (95 %CI 22.17,45.37), P<.001; PCV 13 period, RR=39.18 (95 %CI 22.35,64.69) P<.001. Meningitis and deaths from IPD decreased significantly in all populations examined but remained significantly higher in patients with SCD compared to RP (table 2). The mean age at IPD diagnosis for the 3 periods examined increased both in SCD and in the RP. For those with SCD (n=50), pre-PCV7 period mean age was :2.7 standard deviation (+/-) 2.3 years; for the PCV 13 period: n=19; 3.7 years +/-2.2 years p= 0.0877; for the RP: Pre-PCV period: n=1025; 1.3 +/-1.6 years; PCV 13 period: n=213; 2.2 +/-2.3 years. Overall absolute IPD rates declined for all age groups examined (table 1). Prior to PCV7 licensure, IPD in patients with SCD were significantly less likely to be penicillin susceptible (MIC <0.06 µg/mL) compared to the RP: 41.9% (18/43) vs 60.0% (476/793) RR=0.70 (95% CI 0.49,1.00), p=0.025. This difference was no longer present after PCV licensure (PCV 13 period , SCD 52.9% [9/17], vs RP 48.6% [70/144]). Non PCV serotypes IPD rates increased after PCV7 licensure but remained stable after PCV13 licensure; 16% of non PCV13 serotypes during all time periods are included in PCV15, whereas PCV20 may cover between 29% and 50% depending on related serotypes cross protection (table3). Although significantly less frequent compared with pre-PCV-era, IPD can be severe in patients with SCD. Increase in IPD age was seen in both SCD and RP. Lower rates of penicillin non-susceptibility may may reflect lower exposure to penicillin prophylaxis. Newer vaccines may offer expanded coverage for children with SCD. Ongoing surveillance will help determine their effect. Vaccines that cover all serotypes are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Multiple comorbidities increase the risk of death from invasive pneumococcal disease under the age of 65 years

IntroductionRisk factors for death from invasive pneumococcal disease (IPD) have not been clearly established in patients aged under 65 years. We aimed to evaluate contributions of host and bacterial factors to the risk of death from IPD in patients aged under 65 years in Japan. MethodsIn this prospective, observational, multicenter cohort study, patients with IPD (n = 581) aged 6–64 years were enrolled between 2010 and 2017. We investigated the role of host and bacterial factors in 28-day mortality. ResultsThe mortality rate increased from 3.4% to 6.2% in patients aged 6–44 years to 15.5%–19.5% in those aged 45–64 years. Multivariable analysis identified the following risk factors for mortality: age 45–64 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6–6.8, p = 0.001), bacteremia with unknown focus (HR, 2.0; 95% CI, 1.1–3.7, p = 0.024), meningitis (HR, 2.1; 95% CI, 1.1–4.0, p = 0.019), underlying multiple non-immunocompromising conditions (HR, 2.6; 95% CI, 1.1–7.4, p = 0.023), and immunocompromising conditions related to malignancy (HR, 2.4; 95% CI, 1.0–5.2, p = 0.039). Pneumococcal serotype was not associated with poor outcomes. ConclusionsHost factors, including age of 45–64 years and underlying multiple non-immunocompromising conditions, are important for the prognosis of IPD. Our results will contribute to the development of targeted pneumococcal vaccination strategies in Japan.

176. Selected Impact of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) on Invasive Pneumococcal Disease (IPD) at Eight Children’s Hospitals in the United States. 2014–2019

BackgroundThe 2011 IDSA/PIDS Clinical Practice Guidelines for the Management of Community-acquired Pneumonia (CAP) in Children Older than 3 months recommended empiric treatment with either ampicillin/penicillin or ceftriaxone based on PCV13 vaccine status and the local antibiotic susceptibilities of IPD isolates. No study has addressed differences in antibiotic susceptibilities for isolates from children with pneumococcal pneumonia (PP) based on PCV13 status.MethodsInvestigators from 8 US children’s hospitals identified infants and children with IPD between 1/1/2014 and 12/31/2019. IPD was documented by positive cultures from a normally sterile site. PP diagnosis required an abnormal chest radiograph. Clinical data were recorded and isolates analyzed for serotype (ST) by the capsular swelling method and antimicrobial susceptibilities by standard methods. Administration of PCV7/13 was documented through the patient’s medical records, health care provider or a vaccine registry. Fisher Exact was performed; p< 0.05 was significant.Results690 IPD patients with isolates were available (0–18 y); 24% (166/690) of the isolates were PCV13 STs (ST3-75, ST19F-45, ST19A-36, ST7F-5, other STs-5). The most common non-PCV13 ST isolates were ST35B-60, ST23B-59, ST33F-47, ST22F-43, ST15C-35, ST23A-27, ST15B-26, ST10A-26, ST15A-23. Of non-PCV13 isolates, 41% (217/524) were among the 7 additional STs in PCV20. For children with PP (n=157), the distributions of penicillin (Table) (p=0.8) and ceftriaxone MICs were no different for isolates obtained from children regardless of prior PCV13 doses. Less than 7% of PP isolates were resistant to penicillin (MIC >2 µg/mL). Table. Minimal inhibitory concentrations (MIC) of pneumococcal isolates related to the number of PCV13 doses each patient received prior to pneumococcal pneumonia (PP).Number of PCV13 doses Penicillin MIC (µg/mL) 0 1 2 3 4 ≤ 0.125 26*1281743 0.25–0.5 42115 1 10031 2 40025 ≥4 12124*Number of pneumococcal pneumonia patients/isolates. 145/157 patients had immunization and isolate susceptibility data available for analysis.ConclusionPCV13 status should not modify empiric antibiotics for children with suspected pneumococcal CAP. 41% of non-PCV13 IPD isolates were among the 7 additional PCV20 STs.Disclosures Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support) Tina Q. Tan, MD, Pfizer (Grant/Research Support, Other Financial or Material Support, Chair, DMSB for PCV20 vaccine) Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member)

Impact of PCV-13 vaccine on invasive pneumococcal disease in hospitalised children: A multi-institutional analysis.

We aimed to describe changes in invasive pneumococcal disease (IPD) hospitalisations after introduction of the pneumococcal conjugate vaccine (PCV13). This was a retrospective analysis of the Pediatric Health Information System (PHIS) database, including children with IPD pre-PCV13 (2004-2009) and post-PCV13 (2012-2017). Healthy children and those with chronic conditions were analysed separately. The primary outcome was IPD incidence. Secondary outcomes included length of stay, intensive care unit (ICU) admission, mechanical ventilation and mortality. 9160 hospitalisations for IPD were included. The IPD rate per 100000 discharges was 180 pre-PVC13 and 150 post-PCV13 [17% decrease (P=0.085)]. The observed IPD rate in 2017 was 45.5% lower than the rate predicted by the pre-PCV13 trend (95% CI: 44%-46%). While a significant decrease in IPD (32%, P=0.026) was observed among healthy children, there was no change in those with chronic conditions (9%, P=0.24). In the post-PCV13 period, more IPD patients had chronic conditions, ICU admissions and longer ICU stays. Although there was no overall reduction in IPD after PCV13, we observed a significant decrease in IPD among healthy patients. Further research is needed to elucidate microbiology or other factors contributing to persistent IPD hospitalisations.

Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine against Invasive Pneumococcal Disease in Adults, Japan, 2013-2017.

The decline in the proportion of pneumococcal conjugate vaccine (PCV)–covered serotypes among adult invasive pneumococcal disease (IPD) patients might change the overall effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) because its effectiveness differs according to serotype. Using the indirect cohort method, we calculated the effectiveness of PPSV23 against IPD among adults in Japan to assess the impact of the national pediatric PCV program. Clinical and epidemiologic information and pneumococcal isolates were collected from IPD patients >20 years of age through enhanced IPD surveillance during April 2013–December 2017. Adjusted effectiveness against PPSV23-serotype IPD was 42.2%. Despite a substantial decline in the proportion of 13-valent PCV serotypes during the study period (45% to 31%), the change in effectiveness for PPSV23-serotype IPD was limited (47.1% to 39.3%) and only marginal in the elderly population (39.9% to 39.4%). The pediatric PCV program had limited impact on PPSV23 effectiveness against IPD in adults.

Molecular epidemiological characterization in mucoid-type Streptococcus pneumoniae isolates obtained from invasive pneumococcal disease patients in Japan

IntroductionStreptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era). MethodsA total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined. ResultsThe prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166). ConclusionsOur findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents.

Major Adverse Cardiovascular Events During Invasive Pneumococcal Disease Are Serotype Dependent.

Up to 30% of patients admitted to hospitals with invasive pneumococcal disease (IPD) experience major adverse cardiovascular event (MACE) including new/worsening heart failure, new/worsening arrhythmia, and/or myocardial infarction. Streptococcus pneumoniae (Spn) is the most frequently isolated bacterial pathogen among community-acquired pneumonia (CAP) patients and the only etiological agent linked independently to MACE. Nevertheless, no clinical data exist identifying which serotypes of Spn are principally responsible for MACE. This was an observational multicenter retrospective study conducted through the Public Health Secretary of Bogotá, Colombia. We included patients with a confirmed clinical diagnosis of IPD with record of pneumococcal serotyping and clinical information between 2012 and 2019. Spn were serotyped using the quellung method by the National Center of Microbiology. MACE were determined by a retrospective chart review. The prevalence of MACE was 23% (71/310) in IPD patients and 28% (53/181) in patients admitted for CAP. The most prevalent S. pneumoniae serotype identified in our study was the 19A, responsible for the 13% (42/310) of IPD in our cohort, of which 21% (9/42) presented MACE. Serotypes independently associated with MACE in IPD patients were serotype 3 (odds ratio [OR] 1, 48; 95% confidence interval [CI] [1.21-2.27]; P = .013) and serotype 9n (OR 1.29; 95% CI [1.08-2.24]; P = .020). Bacteremia occurred in 87% of patients with MACE. Moreover, serum concentrations of C-reactive protein were elevated in patients with MACE versus in non-MACE patients (mean [standard deviation], 138 [145] vs 73 [106], P = .01). MACE are common during IPD with serotype 3 and 9n independently of frequency.

Risk of invasive pneumococcal disease in patients with asplenia/hyposplenism: A nationwide population-based study in Korea, 2009–2018

ObjectivesWe aimed to determine the incidence and relative risk (RR) of invasive pneumococcal disease (IPD) in patients with asplenia/hyposplenism, using a nationwide population-based database. MethodsFrom 2009 to 2018, all claimed cases of newly diagnosed asplenia/hyposplenism in the National Health Insurance Service in South Korea were included. The incidence and RR of IPD in asplenia/hyposplenism patients were investigated using the Korean Center for Disease Control criteria. ResultsFifty-seven IPD cases were identified among 21,376 patients with 82,748 person-years of exposure. The cumulative 8-year IPD incidence was 0.5%; 45.6% of the infections occurred within two years after an asplenia/hyposplenism diagnosis. The age-standardised incidence rate was 104.5 per 100,000 person-years (95% confidence interval [CI], 103.6–105.4). Patients aged <5 years had a 15.1-times higher risk of IPD than those aged ≥60 years (95% CI: 5.8–39.5, p < 0.0001). The RR of IPD was 32.0 times higher in patients with asplenia/hyposplenism than in the general population (95% CI, 21.7–47.0); the standardized incidence ratio was 17.9(95% CI, 11.8–26.0). ConclusionsThis large population-based study highlights the high IPD incidence rate and RR in Korean patients with asplenia/hyposplenism. Increased awareness and effective prevention strategies are needed for these high-risk populations, especially children aged <5 years.

Gastrointestinal symptoms in invasive pneumococcal disease: a cohort study

BackgroundThe study aimed to assess whether gastrointestinal (GI) symptoms at admission are associated with increased short-term mortality in patients with invasive pneumococcal disease (IPD).MethodsWe included all patients with IPD at Aker University Hospital in Oslo, Norway, from 1993 to 2008. Clinical data were registered. Survival data were retrieved from official registries. We used Cox regression and Kaplan-Meier curve to compare mortality within 28 days of admission in patients with and without GI symptoms.ResultsFour hundred sixteen patients were included. Of these, 108 patients (26%) presented with GI symptoms, and 47 patients (11%) with GI symptoms only. Patients with GI symptoms were younger (p < 0.001) and had less cardiovascular disease (p < 0.001), pulmonary disease (p = 0.048), and cancer (p = 0.035) and received appropriate antibiotic treatment later. After adjusting for risk factors, we found an increased hazard ratio of 2.28 (95% CI 1.31–3.97) in patients presenting with GI symptoms. In patients with GI symptoms only there was an increased hazard ratio of 2.24 (95% CI 1.20–4.19) in univariate analysis, which increased to 4.20 (95% CI 2.11–8.39) after multivariate adjustment. Fewer patients with GI symptoms only received antibiotics upon admission.ConclusionsA large proportion of IPD patients present with GI symptoms only or in combination with other symptoms. GI symptoms in IPD are associated with increased short-term mortality.

Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study

BackgroundStreptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore.MethodsRetrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design.ResultsWe identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson’s score 1 (IQR 0–4), vs 3 (1–5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8–17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06–0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson’s score > 3.ConclusionPatients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.