Pneumococcal Pneumonia: Epidemiology, Pathophysiology, Treatment and Vaccines

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 19244

Special Issue Editor

Institute for Infectious Diseases and Infection Control, Jena University Hospital / Friedrich-Schiller-University, Am Klinikum 1, 07747 Jena, Germany
Interests: pneumonia; sepsis; vaccines; antibiotic resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite antibiotics, community-acquired pneumonia remains a leading cause of death in the elderly, low-income countries, and infants. Streprococcus pneumonia is the leading cause of bacterial community-acquired pneumonia involving frequently mixed bacterial viral infections. Research on effective pneumococcal vaccines has been going on for decades and is challenged by the high degree of diversity in, and the poor immunogenicity of, pneumococcal polysccharid capsules and the genetic flexibility of the organism. This Special Issue will focus on the mechanism of action and coverage of different pneumococcal vaccination strategies and the dynamic adaption of pneumococcal species to vaccine-associated selective pressure. It will also cover a selection of novel treatment approaches to pneumococcal pneumonia.

Dr. Mathias W. Pletz
Guest Editor

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Keywords

  • Streptococcus pneumonia
  • vaccine
  • herd protection
  • invasive pneumococcal diseases
  • community-acquired pneumonia
  • mixed infection

Published Papers (9 papers)

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Research

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14 pages, 668 KiB  
Article
WGS-Based Phenotyping and Molecular Characterization of the Resistome, Virulome and Plasmid Replicons in Klebsiella pneumoniae Isolates from Powdered Milk Produced in Germany
by Gamal Wareth, Jörg Linde, Philipp Hammer, Mathias W. Pletz, Heinrich Neubauer and Lisa D. Sprague
Microorganisms 2022, 10(3), 564; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10030564 - 05 Mar 2022
Cited by 2 | Viewed by 2531
Abstract
The emergence of Klebsiella pneumoniae (K. pneumoniae) in German healthcare is worrying. It is not well-investigated in the veterinary world and food chains. In the current study, antibiotic susceptibility profiles of 24 K. pneumoniae strains isolated from powdered milk samples produced [...] Read more.
The emergence of Klebsiella pneumoniae (K. pneumoniae) in German healthcare is worrying. It is not well-investigated in the veterinary world and food chains. In the current study, antibiotic susceptibility profiles of 24 K. pneumoniae strains isolated from powdered milk samples produced in Germany were investigated by a microdilution test. Next-generation sequencing (NGS) was applied to identify genomic determinants for antimicrobial resistance (AMR), virulence-associated genes and plasmids replicons. All isolates were susceptible to the majority (14/18) of tested antibiotics. Resistance to colistin, fosfomycin, chloramphenicol and piperacillin was found. The ambler class A ß-lactamase, blaSHV variants were identified in all isolates, of which blaSHV-187 was most prevalent and found in 50% of isolates. Single-nucleotide-variants of oqxA and oqxB conferring resistance to phenicol/quinolone were found in all isolates, and the oqxB17 was the most prevalent found in 46% of isolates. 67% of isolates harbored fosA genes; however, only one was fosfomycin-resistant. Two isolates harbored genes conferring resistance to colistin, despite being susceptible. The majority of identified virulome genes were iron uptake siderophores. Two enterobactins (entB, fepC), six adherence-related genes belonging to E. coli common pilus (ECP) and one secretion system (ompA gene) were found in all isolates. In contrast, yersiniabactin was found in two isolates. One ST23 strain was susceptible to all tested antibiotics, and harbored determinants discriminatory for hypervirulent strains, e.g., aerobactin, salmochelin, yersiniabactin, enterobactin and regulator of mucoid phenotype A genes that are highly associated with hypervirulent K. pneumoniae. The IncF plasmid family was found in all strains, while almost half of the isolates harbored Col440I-type plasmids and nine isolates harbored various Inc-type plasmids. The presence of K. pneumoniae carrying different resistomes and major virulent specific virulomes in powdered milk samples is alarming. This could threaten public health, particularly of neonates and infants consuming dried milk. Full article
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10 pages, 429 KiB  
Article
23-Valent Pneumococcal Polysaccharide Vaccination Does Not Prevent Community-Acquired Pneumonia Hospitalizations Due to Vaccine-Type Streptococcus pneumoniae
by Thomas Chandler, Stephen Furmanek, Ruth Carrico, Dawn Balcom, Forest Arnold and Julio Ramirez
Microorganisms 2022, 10(3), 560; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10030560 - 04 Mar 2022
Cited by 15 | Viewed by 2488
Abstract
Controversy exists regarding the clinical effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the prevention of serotype-specific community-acquired pneumonia (CAP). The objective of this study was to define the effectiveness of PPSV23 for the prevention of CAP hospitalizations due to vaccine-contained serotypes. [...] Read more.
Controversy exists regarding the clinical effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the prevention of serotype-specific community-acquired pneumonia (CAP). The objective of this study was to define the effectiveness of PPSV23 for the prevention of CAP hospitalizations due to vaccine-contained serotypes. This secondary analysis was a nested case–control, test-negative study design of adult patients hospitalized for CAP between 1 June 2014 and 31 March 2017. Cases included patients with CAP due to a S. pneumoniae serotype contained in the PPSV23. Urinary antigen detection of the 23 serotypes was performed. In the study, PPSV23 vaccination alone and no other pneumococcal vaccination was the primary exposure of interest. Vaccine effectiveness was calculated as (1-OR) × 100. Adjusted estimates were obtained from a logistic regression model that controlled for confounding variables. A total of 3686 patients were included in the analysis. The PPSV23 vaccination was documented in 608 (16%) patients, and the PPSV23-serotype CAP was detected in 48 (8%) PPSV23-vaccinated patients and in 288 (9%) non-vaccinated patients. Unadjusted vaccine effectiveness for preventing PPSV23-serotype CAP was 17% (95% CI: −13% to 40%). Adjusted estimates for preventing PPSV23-serotype CAP was 14% (95% CI: −17% to 38%). In this study, PPSV23 vaccination offered no protection against PPSV23-serotype CAP hospitalization in adults. This is the first PPSV23 vaccine effectiveness study from United States that utilized a urinary antigen detection assay as the main method for S. pneumoniae serotyping. This study highlights the need for more effective vaccines in the prevention of hospitalization due to S. pneumoniae CAP. Full article
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13 pages, 1804 KiB  
Article
Molecular Epidemiology of Multidrug-Resistant Pneumococci among Ghanaian Children under Five Years Post PCV13 Using MLST
by Richael O. Mills, Mohammed R. Abdullah, Samuel A. Akwetey, Dorcas C. Sappor, Gustavo Gámez and Sven Hammerschmidt
Microorganisms 2022, 10(2), 469; https://doi.org/10.3390/microorganisms10020469 - 19 Feb 2022
Cited by 3 | Viewed by 1787
Abstract
Antibiotic resistance in pneumococci contributes to the high pneumococcal deaths in children. We assessed the molecular characteristics of multidrug-resistant (MDR) pneumococci isolated from healthy vaccinated children under five years of age in Cape Coast, Ghana. A total of 43 MDR isolates were selected [...] Read more.
Antibiotic resistance in pneumococci contributes to the high pneumococcal deaths in children. We assessed the molecular characteristics of multidrug-resistant (MDR) pneumococci isolated from healthy vaccinated children under five years of age in Cape Coast, Ghana. A total of 43 MDR isolates were selected from 151 pneumococcal strains obtained from nasopharyngeal carriage. All isolates were previously serotyped by multiplex PCR and Quellung reaction. Susceptibility testing was performed using either the E-test or disk diffusion method. Virulence and antibiotic resistance genes were identified by PCR. Molecular epidemiology was analyzed using multilocus sequence typing (MLST). Vaccine-serotypes 23F and 19F were predominant. The lytA and pavB virulence genes were present in all isolates, whiles 14–86% of the isolates carried pilus-islets 1 and 2, pcpA, and psrP genes. Penicillin, tetracycline, and cotrimoxazole resistance were evident in >90% of the isolates. The ermB, mefA, and tetM genes were detected in (n = 7, 16.3%), (n = 4, 9.3%) and (n = 43, 100%) of the isolates, respectively. However, >60% showed alteration in the pbp2b gene. MLST revealed five novel and six known sequence types (STs). ST156 (Spain9V-3) and ST802 were identified as international antibiotic-resistant clones. The emergence of international-MDR clones in Ghana requires continuous monitoring of the pneumococcus through a robust surveillance system. Full article
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10 pages, 4799 KiB  
Article
Clinical Outcomes of Immunocompromised Adults Hospitalized with Pneumococcal Pneumonia: A Case-Control Study
by Julio Ramirez, Thomas Chandler, Stephen Furmanek, Forest Arnold and Jose Bordon
Microorganisms 2021, 9(8), 1746; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9081746 - 16 Aug 2021
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Abstract
S. pneumoniae is a primary etiologic agent of CAP in immunocompromised adults (ICA). Data on clinical outcomes of ICA hospitalized with pneumococcal pneumonia (PP) is limited. The objectives of this study were (1) to define clinical presentation and outcomes of ICA hospitalized with [...] Read more.
S. pneumoniae is a primary etiologic agent of CAP in immunocompromised adults (ICA). Data on clinical outcomes of ICA hospitalized with pneumococcal pneumonia (PP) is limited. The objectives of this study were (1) to define clinical presentation and outcomes of ICA hospitalized with PP and (2) to compare the data to non-immunocompromised adults (non-ICA) hospitalized with PP. This was a case–control study of ICA hospitalized with PP (cases) and non-ICA hospitalized with PP (controls). Data were collected on clinical presentation, treatment, and outcomes. Evaluated clinical outcomes included time to clinical stability (TCS), length of hospitalization (LOH), clinical failure (CF), cardiovascular events (CE), and in-hospital mortality (IHM). One ICA was matched to two non-ICA through propensity score matching. A total of 93 ICA hospitalized with PP and 186 non-ICA hospitalized with PP were evaluated. Antibiotic therapy was appropriate in all patients. Clinical outcomes for ICA versus non-ICA were as follows: TCS 2 days vs. 2 days (p = 0.392); LOH 5 days vs. 5 days (p = 0.067); CF 4% vs. 6% (p = 0.618); CE 10% vs. 6% (p = 0.375); and IHM 5% vs. 3% (p = 0.296). In hospitalized patients with PP who are treated with appropriate antibiotic therapy, the presence of an abnormal immune system does influence clinical outcomes. Full article
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10 pages, 806 KiB  
Communication
An Observational Prospective Cohort Study of Incidence and Outcome of Streptococcus pneumoniae and Hemophilus influenzae Infections in Adult Solid Organ Transplant Recipients
by Omid Rezahosseini, Dina Leth Møller, Søren Schwartz Sørensen, Michael Perch, Finn Gustafsson, Marco Gelpi, Jenny Knudsen, Marie Helleberg, Allan Rasmussen, Susanne Dam Nielsen and Zitta Barrella Harboe
Microorganisms 2021, 9(7), 1371; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9071371 - 24 Jun 2021
Cited by 6 | Viewed by 1652
Abstract
Background: Streptococcus pneumoniae (S. pneumoniae) and Hemophilus influenzae (H. influenzae) are among the main vaccine-preventable bacterial infections in immunocompromised individuals including solid organ transplant (SOT) recipients. There is a lack of information about incidence and outcomes of these infections in SOT recipients. Methods: [...] Read more.
Background: Streptococcus pneumoniae (S. pneumoniae) and Hemophilus influenzae (H. influenzae) are among the main vaccine-preventable bacterial infections in immunocompromised individuals including solid organ transplant (SOT) recipients. There is a lack of information about incidence and outcomes of these infections in SOT recipients. Methods: We determined the incidence of S. pneumoniae and H. influenzae, the related hospitalization, and 30- and 180-days mortality in a large cohort of 1182 adult SOT recipients. We calculated 95% confidence intervals (CI) of incidence rate (IR) using Byar’s approximation to the Poisson distribution. Results: The overall IR of S. pneumoniae and H. influenzae were 1086 (95% CI, 796–1448) and 1293 (95% CI, 974–1687) per 100,000 person-years of follow-up (PYFU), respectively. The IR of invasive infections were 76 (95% CI, 21–202) and 25 (95% CI, 2.3–118) per 100,000 PYFU, respectively. Hospital admission was required in >50%, 30-days mortality was 0, and 180-days mortality was 8.8% and 4.5% after S. pneumoniae and H. influenzae infections, respectively. Conclusions: The IR of invasive S. pneumoniae and H. influenzae infections in SOT recipients were much higher than reports from the general population in Denmark. Furthermore, a large proportion of infected SOT recipients were hospitalized. These findings highlight the need for further studies to assess uptake and immunogenicity of vaccines against S. pneumoniae and H. influenzae in SOT recipients. Full article
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Review

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11 pages, 286 KiB  
Review
Cardiovascular Complications in Community-Acquired Pneumonia
by Antonio Desai, Stefano Aliberti, Francesco Amati, Anna Stainer and Antonio Voza
Microorganisms 2022, 10(11), 2177; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10112177 - 02 Nov 2022
Cited by 3 | Viewed by 2179
Abstract
Community-acquired pneumonia (CAP) is accountable for high mortality in both pediatric and adult populations worldwide, about one-third of hospitalized patients pass away within a year of being discharged from the facility. The high mortality and morbidity rates are closely related to cardiovascular complications [...] Read more.
Community-acquired pneumonia (CAP) is accountable for high mortality in both pediatric and adult populations worldwide, about one-third of hospitalized patients pass away within a year of being discharged from the facility. The high mortality and morbidity rates are closely related to cardiovascular complications that are consequent or concomitant to the acute episode of pneumonia. An updated perspective on the major pathophysiological mechanisms, prevalence, risk factors, outcomes, and relevant treatments of cardiovascular events in CAP patients is provided in the current study. It is possible to evaluate the pathophysiology of cardiac disease in this population based on plaque-related events, such as acute myocardial infarction, or events unrelated to plaque, such as arrhythmias and heart failure. With an absolute rate of cardiovascular problems ranging broadly from 10% to 30%, CAP raises the risk of both plaque-related and plaque-unrelated events. Both in- and out-patients may experience these issues at admission, throughout hospitalization, or even up to a year following discharge. At long-term follow-up, cardiac events account for more than 30% of deaths in CAP patients, making them a significant cause of mortality. If patients at risk for cardiac events are stratified, diagnostic tools, monitoring, and preventive measures may be applied to these patients. A prospective evaluation of cardioprotective treatments is urgently required from a research point of view. Full article
12 pages, 286 KiB  
Review
PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)
by Christian Theilacker, Mark A. Fletcher, Luis Jodar and Bradford D. Gessner
Microorganisms 2022, 10(1), 127; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010127 - 08 Jan 2022
Cited by 16 | Viewed by 3644 | Correction
Abstract
The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes [...] Read more.
The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination. Full article

Other

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4 pages, 206 KiB  
Comment
Comment on Chandler et al. 23-Valent Pneumococcal Polysaccharide Vaccination Does Not Prevent Community-Acquired Pneumonia Hospitalizations Due to Vaccine-Type Streptococcus pneumoniae. Microorganisms 2022, 10, 560
by Nicole Cossrow, Rennie Joshi, Kenneth Klinker and Ulrike K. Buchwald
Microorganisms 2022, 10(10), 1987; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10101987 - 08 Oct 2022
Viewed by 928
Abstract
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) targets 23 common serotypes and is recommended for use in adults in various countries to protect against pneumococcal infection. Test-negative design (TND) studies aim to include cases and controls from the same healthcare facilities; however, design choices [...] Read more.
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) targets 23 common serotypes and is recommended for use in adults in various countries to protect against pneumococcal infection. Test-negative design (TND) studies aim to include cases and controls from the same healthcare facilities; however, design choices or limitations associated with conducting real-world research can affect the study results. Here, we highlight how some methodological limitations may have affected results and conclusions of a published study described by Chandler et al. Full article
1 pages, 161 KiB  
Correction
Correction: Theilacker et al. PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Microorganisms 2022, 10, 127
by Christian Theilacker, Mark A. Fletcher, Luis Jodar and Bradford D. Gessner
Microorganisms 2022, 10(5), 1018; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10051018 - 12 May 2022
Cited by 2 | Viewed by 1110
Abstract
The authors wish to make the following corrections to this paper [...] Full article
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