Little information on the current burden of community-acquired pneumonia (CAP) in adults in Germany is available. We conducted a retrospective cohort study using a representative healthcare claims ...database of approx. 4 million adults to estimate the incidence rates (IR) and associated mortality of CAP in 2015. IR and mortality were stratified by treatment setting, age group, and risk group status. A pneumonia coded in the primary diagnosis position or in the second diagnosis position with another pneumonia-related condition coded in the primary position was used as the base cases definition for the study. Sensitivity analyses using broader and more restrictive case definitions were also performed. The overall IR of CAP in adults greater than or equal to18 years was 1,054 cases per 100,000 person-years of observation. In adults aged 16 to 59 years, IR for overall CAP, hospitalized CAP and outpatient CAP was 551, 96 and 466 (with a hospitalization rate of 17%). In adults aged greater than or equal to60 years, the respective IR were 2,032, 1,061 and 1,053 (with a hospitalization rate of 52%). If any pneumonia coded in the primary or secondary diagnosis position was considered for hospitalized patients, the IR increased 1.5-fold to 1,560 in the elderly greater than or equal to60 years. The incidence of CAP hospitalizations was substantially higher in adults greater than or equal to18 years with at-risk conditions and high-risk conditions (IR of 608 and 1,552, respectively), compared to adults without underlying risk conditions (IR 108). High mortality of hospitalized CAP in adults greater than or equal to18 was observed in-hospital (18.5%), at 30 days (22.9%) and at one-year (44.5%) after CAP onset. Mortality was more than double in older adults in comparison to younger patients. CAP burden in older adults and individuals with underlying risk conditions was high. Maximizing uptake of existing vaccines for respiratory diseases may help to mitigate the disease burden, especially in times of strained healthcare resources.
We review a previously published randomized clinical trial of 23-valent pneumococcal polysaccharide vaccine (PPSV23) that has been used extensively globally to support PPSV23 use among adults. We ...argue that serious issues with internal and external validity exist that affect the usefulness of these data when evaluating pneumococcal vaccines for the general adult population. As one example of internal data inconsistency, the values reported for the percent of all pneumonia cases due to pneumococcus and the vaccine efficacy (VE) for all cause pneumonia are mutually inconsistent, even based on unrealistically high values for PPSV23 VE against vaccine serotypes and the proportion of pneumococcal pneumonias due to vaccine serotypes.
Background. Recent population-based cohort studies have questioned the role of pneumococci as the most frequent pathogen causing severe infection in patients after splenectomy. The aim of the study ...was to define the causative pathogens and clinical presentation of patients with overwhelming postsplenectomy infection (OPSI). Methods. In a prospective cohort study in 173 German intensive care units, we searched for patients with and without asplenia and community-acquired severe sepsis/septic shock. Clinical and laboratory variables and survival of patients were assessed. Results. Fifty-two patients with severe sepsis or septic shock with asplenia and 52 without asplenia were included. OPSI patients more often had a history of malignancy (38% vs 17%; P= 0.16) and had a lower body mass index (24 kg/m2 vs 28 kg/m2; P= .004). Streptococcus pneumoniae was detected more frequently in OPSI patients (42% vs 12% without asplenia; P< .001) and more frequently manifested as bloodstream infection (31% vs 6%; P= .002). Gram-negative infection was similar in both groups (12% vs 19%; P = .157). Pneumococcal vaccine coverage of OPSI patients was low overall (42% vs 8% among patients without asplenia; P < .001). Purpura fulminans was a frequent complication, developing in 19% of OPSI patients vs 5% of patients without asplenia (P = .038). The interval between splenectomy and OPSI was 6 years (range, 1 month-50 years). On multivariable Poisson regression, asplenia was the only predictive variable independently associated with pneumococcal sepsis (adjusted relative risk, 2.53 95% confidence interval, 1.06-6.08). Conclusions. Pneumococcal infections remain the most important cause of severe sepsis and septic shock following splenectomy.
Two next-generation pneumococcal conjugate vaccines (PCVs), a 15- and a 20-valent PCV (PCV15 and PCV20), have recently been licensed for use in adults, and PCV15 has also been licensed in children. ...We developed a dynamic transmission model specific for Germany, with the aim to predict carriage prevalence and invasive pneumococcal disease (IPD) burden for serotypes included in these vaccines.
The model allows to follow serotype distributions longitudinally both in the absence and presence of PCV vaccinations. We considered eight age cohorts and seven serotype groups according to the composition of different pneumococcal vaccines. This comprises the additional serotypes contained in PCV15 and PCV20 but not in PCV13.
The model predicted that by continuing the current vaccine policy (standard vaccination with PCV13 in children and with PPSV23 in adults) until 2031, IPD case counts due to any serotype in children <2 years of age will remain unchanged. There will be a continuous decrease of IPD cases in adults aged 16-59y, but a 20% increase in adults ≥60y. Furthermore, there will be a steady decrease of the proportion of carriage and IPD due to serotypes included in PCV7 and PCV13 over the model horizon and a steady rise of non-PCV13 serotypes in carriage and IPD. The highest increase for both pneumococcal carriage and absolute IPD case counts was predicted for serotypes 22F and 33F (included in both PCV15 and PCV20) and serotypes 8, 10A, 11A, 12F, and 15B (included in PCV20 only), particularly in older adults. Between 2022 and 2031, serotypes included in PCV20 only are expected to cause 19.7-25.3% of IPD cases in adults ≥60y.
We conclude that introduction of next-generation PCVs for adults may prevent a substantial and increasing proportion of adult IPDs, with PCV20 having the potential to provide the broadest protection against pneumococcal disease.
BackgroundAlthough recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of coinfection with Streptococcus pneumoniae in patients with ...coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction may be explained by interactions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pneumococci in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses.MethodsHere, we investigated the relationship of these 2 respiratory pathogens in 2 distinct cohorts of health care workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and patients with moderate to severe disease who presented to the hospital. We assessed the effect of coinfection on host antibody, cellular, and inflammatory responses to the virus.ResultsIn both cohorts, pneumococcal colonization was associated with diminished antiviral immune responses, which primarily affected mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients.ConclusionOur findings suggest that S. pneumoniae impair host immunity to SARS-CoV-2 and raise the question of whether pneumococcal carriage also enables immune escape of other respiratory viruses and facilitates reinfection.Trial registrationISRCTN89159899 (FASTER study) and ClinicalTrials.gov NCT03502291 (LAIV study).
Data on the burden of community-acquired pneumonia (CAP) and health-care related costs in patients with cancer is scarce. We aimed to estimate the CAP incidence rate, mortality, and ...healthcare-related costs of CAP patients with different cancer subtypes in Germany.
We used German health claims data of a representative sample of 4 million subjects to conduct cohort studies in patients with a new diagnosis of lung, hematological, breast, gastro-intestinal tract and renal/urinary-tract cancer and a comparator cohort without cancer between 2011 and 2015. CAP cases were identified in both the hospital and ambulatory care setting. Crude and age- and sex-standardized incidence rates (sIR) of CAP and mortality after CAP were calculated. To compare the health care-related costs of cancer patients with and without a diagnosis of CAP, a propensity-score (PS) matched control group was created.
The study population comprised of 89,007 patients with cancer. In lung cancer patients, the sIR was increased 21-fold compared to the control cohort. For the other cancer subtypes, the sIR was increased 4.3-fold (hematological malignancies) to 1.7-fold (breast cancer) compared to the control cohort. The 30-day mortality in CAP cases was highest in lung cancer patients with 20.0% and ranged from 7.2 to 18.5% in CAP cases with other cancer subtypes. The highest costs were observed in CAP cases with hematological malignancies with 28,969 € (SD 37,142 €) and the lowest in patients with renal/urinary tract cancer with 17,432 € (SD 19,579 €). The absolute difference in the mean overall costs between CAP cases and controls without CAP ranged from 4,111€ to 9,826€, depending on the cancer type. CAP-related costs were predominantly triggered by substantially elevated hospital costs in CAP cases.
The incidence rate of CAP and related mortality is high in patients with cancer with strong variations by cancer subtype. Furthermore, CAP in cancer patients is associated with substantial direct excess costs.
OBJECTIVESDespite national recommendations for use of pneumococcal vaccines, rates of community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) remain high in Germany. New ...pneumococcal conjugate vaccines (PCVs) with expanded coverage have the potential to reduce the pneumococcal disease burden among adults.METHODSUsing a Markov model, we evaluated the lifetime outcomes/costs comparing 20-valent PCV (PCV20) with standard of care (SC) vaccinations for prevention of CAP and IPD among adults aged ≥60 years and at-risk adults aged 18-59 years in Germany. PCV20 also was compared with sequential vaccination with 15-valent PCV (PCV15) followed by PPSV23 in a scenario analysis.RESULTSOver the course of a lifetime (82 years), use of PCV20vs. SC would prevent 54,333 hospitalizations, 26368 outpatient CAP cases, 10946 disease-related deaths yield 74,694 additional life-years (LYs), while lowering total medical costs by 363.2 M €. PCV20 remained cost saving (i.e. dominant) versus SC even in numerous sensitivity analyses, including a sensitivity analysis assuming moderate effectiveness of the SC pneumococcal polysaccharide vaccine against noninvasive pneumococcal CAP. In several scenario analyses and a probabilistic sensitivity analysis, PCV20 was also cost-saving compared toPCV15 PPSV23 vaccination.CONCLUSIONSOne dose of PCV20 among adults aged ≥60 years and adults aged 18-59 years with moderate- and high-risk conditions wouldsubstantially reduce pneumococcal disease, save lives, and be cost saving compared with SC.
Enterococcus faecalis is among the predominant causes of nosocomial infections. Surface molecules like D-alanine lipoteichoic acid (LTA) perform several functions in gram-positive bacteria, such as ...maintenance of cationic homeostasis and modulation of autolytic activities. The aim of the present study was to evaluate the effect of D-alanine esters of teichoic acids on biofilm production and adhesion, autolysis, antimicrobial peptide sensitivity, and opsonic killing. A deletion mutant of the dltA gene was created in a clinical E. faecalis isolate. The absence of D-alanine in the LTA of the dltA deletion mutant was confirmed by nuclear magnetic resonance spectroscopy. The wild-type strain and the deletion mutant did not show any significant differences in growth curve, morphology, or autolysis. However, the mutant produced significantly less biofilm when grown in the presence of 1% glucose (51.1% compared to that of the wild type); adhesion to eukaryotic cells was diminished. The mutant absorbed 71.1% of the opsonic antibodies, while absorption with the wild type resulted in a 93.2% reduction in killing. Sensitivity to several cationic antimicrobial peptides (polymyxin B, colistin, and nisin) was considerably increased in the mutant strain, confirming similar results from other studies of gram-positive bacteria. Our data suggest that the absence of D-alanine in LTA plays a role in environmental interactions, probably by modulating the net negative charge of the bacterial cell surface, and therefore it may be involved in the pathogenesis of this organism.
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.
Introduction
Estimating the burden of lower respiratory tract infections (LRTIs) increasingly relies on administrative databases using International Classification of Diseases (ICD) codes, but no ...standard methodology exists. We defined best practices for ICD-based algorithms that estimate LRTI incidence in adults.
Methods
We conducted a systematic review of validation studies assessing the use of ICD code-based algorithms to identify hospitalized LRTIs in adults, published in Medline, EMBASE, and LILACS between January 1996 and January 2022, according to PRISMA guidelines. We assessed sensitivity, specificity, and other accuracy measures of different algorithms.
Results
We included 26 publications that used a variety of ICD code-based algorithms and gold standard criteria, and 18 reported sensitivity and/or specificity. Sensitivity was below 80% in 72% (38/53) of algorithms and specificity exceeded 90% in 77% (37/48). Algorithms for all-cause LRTI (
n
= 18) that included only pneumonia codes in primary position (
n
= 3) had specificity greater than 90% but low sensitivity (55–72%). Sensitivity increased by 5–15%, with minimal loss in specificity, with the addition of primary codes for severe pneumonia (e.g. sepsis) while pneumonia codes were in secondary position, and by 13% with codes from LRTI-related infections (e.g. viral) or other respiratory diseases (e.g. empyema). Sensitivity increased by 8% when pneumonia codes were in any position, but specificity was not reported. In hospital-acquired pneumonia and pneumococcal-specific pneumonia, algorithms containing only nosocomial- or pathogen-specific ICD codes had poor sensitivity, which improved when broader pneumonia codes were added, in particular codes for unspecified organisms.
Conclusion
Our systematic review highlights that most ICD code-based algorithms are relatively specific, but miss a substantial number of hospitalized LRTI adult cases. Best practices to estimate LRTI incidence in this population include the use of all pneumonia ICD codes for any LRTI outcome and, to a lesser extent, those for other LRTI-related infections or respiratory diseases.
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