Nonbacteremic Pneumonia Research Articles

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine in Argentinean Adults.

In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

Cost-effectiveness of the 20-valent pneumococcal conjugate vaccine versus the 23-valent pneumococcal polysaccharide vaccine for older adults in South Korea

BackgroundDespite the demonstrated immunogenicity and safety of the 20-valent pneumococcal conjugate vaccine (PCV20) in older adults, the cost-effectiveness of the PCV20 was not examined compared to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in South Korea. Therefore, this study aimed to evaluate the cost-effectiveness of PCV20 compared with PPSV23 in adults aged 65 years and older in South Korea. MethodsWe constructed a Markov model that included susceptible states, invasive pneumococcal disease (IPD), non-bacteremic pneumonia (NBP), and death. The population was categorized by disease risk status (low risk, moderate risk, and high risk) and age group (65–74/75–84/85–99 years) at model entry. The annual incidence and mortality of IPD and NBP associated with PCV20 and PPSV23 were estimated based on serotype coverage, vaccine coverage, and vaccine effectiveness. The disease costs and utilities were obtained from previous studies. The incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness within the threshold of 16,824 USD per quality-adjusted life-year (QALY). ResultsAmong the total population (n = 8,843,072), PCV20 prevented 1941 and 50,575 cases of IPDs and NBPs, respectively, and 898 and 8593 deaths due to IPDs and NBPs compared to PPSV23. The total medical cost per person was 12.11 USD higher in PCV20, with a gain of 0.0053 LYs and 0.0045 QALYs per person. The ICER for PCV20 and PPSV23 was 2270 USD/LY and 2677 USD/QALY. ConclusionsIn South Korea, PCV20 is a cost-effective option compared with PPSV23 for adults aged 65 years and older. These cost-effectiveness results provide evidence for decision-making regarding the approval and National Immunization Program implementation of PCV20.

Health and economic outcomes of 20-valent pneumococcal conjugate vaccine compared to 15-valent pneumococcal conjugate vaccine strategies for adults in Greece.

Higher valency pneumococcal conjugate vaccines (PCVs) are expected to improve protection against pneumococcal disease through coverage of additional serotypes. The aim of the present study was to evaluate the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to 15-valent pneumococcal conjugate vaccine (PCV15) alone or followed by 23-valent polysaccharide vaccine (PPV23) for adults in Greece. A published Markov model was adapted to simulate lifetime risk of clinical and economic outcomes from the public payer's perspective. The model population was stratified based on age and risk profile (i.e., low, moderate, or high-risk of developing pneumococcal disease). Epidemiologic parameters, serotype coverage and vaccines' effectiveness were based on published literature, while direct medical costs (prices €, 2022) were obtained from official sources. Main model outcomes were projected number of invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP) cases and attributable deaths, costs and quality-adjusted life-years (QALY) for each vaccination strategy. Sensitivity analyses were performed to ascertain the robustness of model results. Over the modeled time horizon, vaccination with PCV20 compared to PCV15 alone or PCV15 followed by PPV23 prevents an additional 747 and 646 cases of IPD, 10,334 and 10,342 cases of NBP and 468 and 455 deaths respectively, resulting in incremental gain of 1,594 and 1,536 QALYs and cost savings of €11,183 and €48,858, respectively. PSA revealed that the probability of PCV20 being cost-effective at the predetermined threshold of €34,000 per QALY gained was 100% compared to either PCV15 alone or the combination of PCV15 followed by PPV23. PCV20 is estimated to improve public health by averting additional pneumococcal disease cases and deaths relative to PCV15 alone or followed by PPV23, and therefore translates to cost-savings for the public payer. Overall results showed that vaccination with PCV20 was estimated to be a dominant vaccination strategy (improved health outcomes with reduced costs) over PCV15 alone or followed by PPV23 for prevention of pneumococcal disease in adults in Greece.

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

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

Outcomes among Thai children with risk conditions hospitalized for pneumococcal disease (invasive or non-bacteraemic pneumonia): A multi-centre, observational study

The objective of this study was to describe the risk condition status and clinical outcomes among Thai children hospitalized with pneumococcal disease. In this retrospective analysis, pediatric patients with invasive pneumococcal disease (IPD) or X-ray confirmed non-bacteremic pneumococcal pneumonia (NBPP) were identified from nine hospitals from 2010-2019 in Thailand. Data on risk factors and outcomes were extracted from medical records. In total, 413 cases were identified, 319 IPD and 94 NBPP. Overall, 133 (32.2%) patients were admitted to the intensive care unit and 11/406 (2.7%) died. Twenty-seven percent of IPD cases had at-risk conditions; 15% had high-risk conditions. Most IPD cases (32.9%) occurred in children aged 2-4 years and most NBPP cases (28.7%) occurred in infants aged 0-11 months. Of 51 Streptococcus pneumoniae isolates collected, 41 (80%) were PCV13 serotypes. Only 5.1% of children had received a pneumococcal vaccine. Most children with IPD and NBPP had no risk condition, while 42% of the children had at-risk or high-risk conditions for pneumococcal disease. Very few children in the cohort had received any type of pneumococcal vaccine. Increasing the availability of pneumococcal conjugate vaccines should be considered to reduce the burden of pneumococcal disease among children in Thailand.

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

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

Budgetary Impact of 20-Valent Pneumococcal Conjugate Vaccine Use for Adult Expatriates Living in Dubai

Dubai Health Authority currently recommends sequential administration of 13-valent pneumococcal conjugate vaccine (PCV13) followed by (→) 23-valent pneumococcal polysaccharide vaccine (PPV23) to prevent pneumococcal disease among adults at elevated risk of illness. Despite recommendations, disease burden and associated costs remain substantial. A new 20-valent pneumococcal conjugate vaccine (PCV20) recently received regulatory approval in the United Arab Emirates and has the potential to further reduce burden of pneumococcal disease. To evaluate budget impact of use of novel PCV20 compared with current recommendations (ie, PCV13→PPV23) among expatriates in Dubai aged 50 to 99 years and those aged 19 to 49 years with risk factors. A deterministic model depicted 5-year risks and costs of invasive pneumococcal disease and all-cause nonbacteremic pneumonia. Each year of the modeling horizon, persons could be vaccinated with either PCV20 or PCV13→PPV23 or remain unvaccinated; persons vaccinated during the modeling horizon were not eligible for vaccination in subsequent years. Annual vaccine uptake was assumed to be 5% in base cases analyses; higher uptake was considered in scenario analyses. Costs were discounted at 3.5% annually and reported in US dollars. In base case, use of PCV20 alone would prevent an additional 13 cases of invasive pneumococcal disease, 31 cases of inpatient all-cause nonbacteremic pneumonia, 139 cases of outpatient all-cause nonbacteremic pneumonia, and 5 disease-related deaths compared with PCV13→PPV23. Medical care costs would be reduced by $354,000, and total vaccination costs would decrease by $4.4 million. PCV20 would therefore yield net budgetary impact of -$4.8 million, resulting in savings of $2.47 per-person per-year over 5 years. In scenarios with higher vaccine uptake, PCV20 prevented more cases and deaths and yielded greater budget savings (vs PCV13→PPV23). PCV20 would reduce burden and economic costs of pneumococcal disease among expatriates in Dubai compared with PCV13→PPV23 and would therefore be budget saving for private health insurers who cover the majority of this population.

Cost-Effectiveness of Vaccination with the 20-Valent Pneumococcal Conjugate Vaccine in the Italian Adult Population.

The availability of a new 20-valent pneumococcal conjugate vaccine (PCV) makes it appropriate to assess its cost-effectiveness. This was evaluated by adopting the Italian National Health Service perspective, using a cost consequences Markovian model. The expected effects of vaccination with 20-valent PCV were compared with the administration of 13-valent PCV and 15-valent PCV. Assuming a 100% vaccination of cohorts aged 65-74 years, in the (lifetime) comparison between 20-valent PCV and 13-valent PCV, the former is dominant (lower cost for a better health outcome). A reduction in disease events was estimated: -1208 deaths; -1171 cases of bacteraemia; -227 of meningitis; -9845 hospitalised all-cause nonbacteremic pneumonia cases (NBP) and -21,058 non-hospitalised. Overall, in the Italian population, a total gain of 6581.6 life years and of 4734.0 QALY was estimated. On the cost side, against an increase in vaccinations costs (EUR +40.568 million), other direct health costs are reduced by EUR 48.032 million, with a net saving of EUR +7.464 million. The comparison between 20-valent PCV and 15-valent PCV results in an Incremental Cost-Effectiveness Ratio (ICER) of EUR 66 per life year gained and EUR 91 per QALY gained. The sensitivity analyses confirm the robustness of the results. We can conclude that the switch to 20-valent PCV is a sustainable and efficient investment.

Cost-effectiveness analyses of 15- and 20-valent pneumococcal conjugate vaccines for Japanese elderly

BackgroundDespite the 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination programme implementation, pneumococcal disease (PD) remains an important cause of morbidity and mortality among the elderly in Japan, particularly since childhood pneumococcal conjugate vaccine (PCV) vaccination programme continues to alter the serotype PD distribution among the elderly. Recently, in the United States, PCV15/PCV20 were recommended for adults aged ≥ 65 years and those aged 19–64 years with certain underlying conditions. In Japan, PCV15 is under the approval application process and PCV20 undergoing clinical trials, which has warranted the need in evaluating their value for money. MethodsWe conducted cost-effectiveness analyses with Markov model and calculated incremental cost-effectiveness ratios of PCV15/PCV20 vaccination programme compared to status quo from payers’ perspective. Transition probabilities and utility weights in estimating quality-adjusted life-year (QALY), and disease treatment costs were either estimated or obtained from literature. To reflect the situation of COVID-19 pandemic, epidemiological data from 2020 and beyond were used. ResultsCompared to the current vaccination programme, PCV20 vaccination programme gained more QALYs with less cost, while PCV15 vaccination programme cost ¥35,020 (US$318, US$1 = ¥110) to gain an additional QALY. Replacing PPSV23 vaccination programme with PCV20 vaccination programme is cost-saving. One-way sensitivity analyses revealed that lower VE limits of PCVs against non-bacteremic pneumonia (NBP) have large impact to change the result from PCV20 vaccination programme dominated PPSV23 vaccination programme to PPSV23 vaccination programme dominated PCV20 vaccination programme. ConclusionIn the COVID-19 era, replacing current PPSV23 with a single-dose PCV15- or PCV20 immunisation programme for 65-year-old adults in Japan is highly cost-effective, while the PCV 20 vaccination programme was observed to be more favourable.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Medically Attended Lower Respiratory Tract Infection and Pneumonia Among Older Adults.

Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. Among 42700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, -.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.

Streptococcus-Pneumoniae Diseases

Streptococcus pneumoniae is a Gram-positive encapsulated diplococcus. The capsule determines the ≥100 serotypes, is the relevant vaccine antigen and the main pathogenicity factor. Children <5 years are the main reservoir and often spread S. pneumoniae to the elderly. Presence of an acute viral respiratory tract infection (ARI) may favor the development of mucosal pneumococcal infections, as theoretical, experimental, epidemiological, and clinical data indicate viral-bacterial synergy. Many risk factors like anatomical and immunological factors, underlying diseases, and environmental/behavioral factors favor development of invasive pneumococcal disease (IPD). Pneumococcal diseases can be treated with different groups of antibiotics, depending on the local resistance situation. Polysaccharide and polysaccharide-conjugate vaccines are used for pneumococcal disease prevention. The disadvantages of 23-valent pneumococcal polysaccharide vaccine (Pneumovax®) are: lack of memory cell induction, and thus no booster response, no reduction of carriage, and thus no herd protection, lack of IgG immune response in children <2 years, only short-term and moderate protection rates in subjects ≥65 years against bacteremic pneumonia only. In contrast, pneumococcal conjugate vaccines (PCVs): generate a memory response in all ages, can reduce pneumococcal acquisition/colonization, reduce mucosal diseases (otitis media, non-bacteremic pneumonia, IPD), and there is long-term protection. Currently licensed and marketed PCVs are PCV10 (Synflorix®, not licensed in the USA; indicated only for children), PCV13 (Prevenar 13® [Europe]; Prevnar 13® [USA]) and PCV15 (Vaxneuvance®) which are both licensed in EU and USA for adults and children, and PCV20 (Prevnar 20® [USA]; Apexxnar® [Europe]) which is currently only licensed for use in adults.

Health and economic burden of invasive pneumococcal disease associated with 15-valent pneumococcal conjugate vaccine serotypes in children across eight European countries

Aims V114, a 15-valent pneumococcal conjugate vaccine (PCV15) currently approved in adults in the US, contains the 13 S. pneumoniae serotypes in PCV13 and two additional serotypes, 22 F and 33 F, which are important contributors to residual PD. This study quantified the health and economic burden of pediatric invasive pneumococcal disease (IPD) associated with V114 serotypes in eight countries in Europe. Materials and methods A Markov model estimated V114-type IPD cases and costs in hypothetical unvaccinated birth cohorts from Denmark, France, Germany, Italy, Norway, Spain, Switzerland, and the UK over 20 years. Inputs were obtained from published literature. IPD cases and costs were calculated for three time periods using time-specific epidemiological data: (a) pre-PCV7; (b) pre-PCV13; and (c) post-PCV13. Costs were estimated from a societal perspective (2018 Euros) and discounted at 3%. Results The model estimated that 4,649 IPD cases in the pre-PCV7 period, 3,248 cases in the pre-PCV13 period, and 958 cases in the post-PCV13 period were attributable to V114 serotypes. Total discounted costs associated with V114 serotypes were €109.1 million (pre-PCV7 period), €65.7 million (pre-PCV13 period), and €18.7 million (post-PCV13 period). Limitations Post-meningitis sequelae, acute otitis media, and non-bacteremic pneumonia were not considered. Direct non-medical costs were not included. Conclusions on effectiveness of V114 or added value over existing infant vaccination programs cannot be drawn. Conclusions IPD cases and costs were estimated in hypothetical birth cohorts in eight European countries followed for 20 years during three time periods. Serotypes included in V114 were associated with significant morbidity and costs in pre-PCV7, pre-PCV13, and post-PCV13 periods. Future pediatric pneumococcal vaccines should maintain protection against serotypes in licensed vaccines while extending coverage to additional serotypes to ensure reductions in IPD burden are maintained.

Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States

Aims V114 is an investigational 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 Streptococcus pneumoniae serotypes in 13-valent PCV (PCV13) plus two additional serotypes. This study quantified the health and economic burden of invasive pneumococcal disease (IPD) and acute otitis media (AOM) caused by V114 types among children in the United States. Materials and methods A Markov model estimated the number of V114-type IPD and AOM cases and costs in a hypothetical, unvaccinated US birth cohort over 20 years. Three time periods were analyzed using time-specific epidemiological data to determine the number of IPD and AOM cases associated with all 15 serotypes in V114. The time periods were: (1) pre-PCV7 (1999); (2) pre-PCV13 (2009); (3) post-PCV13 (2017). Costs were estimated from a societal perspective (2018 US dollars) and discounted at 3%. Results The model estimated 18,983 IPD cases and 5.4 million AOM cases associated with V114 serotypes pre-PCV7, 4,697 IPD cases and 3.0 million AOM cases pre-PCV13, and 948 IPD cases and 0.2 million AOM cases post-PCV13. Total discounted costs associated with V114 serotypes were $1.7 billion pre-PCV7, $730 million pre-PCV13, and $75 million US dollars post-PCV13. Limitations Post-meningitis sequelae, cases of non-bacteremic pneumonia, and direct non-medical costs were not included. Conclusions IPD and AOM cases and costs were estimated in a hypothetical US birth cohort followed for 20 years at three time periods. In all three periods, the serotypes targeted by V114 contributed to significant morbidity and costs. New pediatric pneumococcal vaccines must continue to retain serotypes in licensed vaccines to maintain disease reduction while extending coverage to non-vaccine serotypes.

Qualification and Clinical Validation of an Immunodiagnostic Assay for Detecting 11 Additional Streptococcus pneumoniae Serotype-specific Polysaccharides in Human Urine.

BackgroundIdentifying Streptococcus pneumoniae serotypes by urinary antigen detection (UAD) assay is the most sensitive way to evaluate the epidemiology of nonbacteremic community-acquired pneumonia (CAP). We first described a UAD assay to detect the S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, covered by the licensed 13-valent S. pneumoniae conjugate vaccine. To assess the substantial remaining pneumococcal disease burden after introduction of several pneumococcal vaccines, a UAD-2 assay was developed to detect 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F) in individuals with radiographically confirmed CAP.MethodsThe specificity of the UAD-2 assay was achieved by capturing pneumococcal polysaccharides with serotype-specific monoclonal antibodies, using Luminex technology. Assay qualification was used to assess accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by nonparametric statistical evaluation of urine samples from individuals without pneumococcal disease. The sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation, using urine samples obtained from a large study that measured the proportion of radiographically confirmed CAP caused by S. pneumoniae serotypes in hospitalized US adults.ResultsThe UAD-2 assay was shown to be specific and reproducible. Clinical validation demonstrated assay sensitivity and specificity of 92.2% and 95.9% against a reference standard of bacteremic pneumonia. In addition, the UAD-2 assay identified a S. pneumoniae serotype in 3.72% of nonbacteremic CAP cases obtained from hospitalized US adults. When combined with bacteremic CAP cases, the proportion of pneumonias with a UAD-2 serotype was 4.33%.ConclusionsThe qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic S. pneumoniae CAP and for assessing the efficacy of future pneumococcal conjugate vaccines that are under development.

Rate and Predictors of Bacteremia in Afebrile Community-Acquired Pneumonia

Although blood cultures (BCs) are the "gold standard" for detecting bacteremia, the utility of BCs in patients with community-acquired pneumonia (CAP) is controversial. This study describes the proportion of patients with CAP and afebrile bacteremia and identifies the clinical characteristics predicting the necessity for BCs in patients who are afebrile. Bacteremia rates were determined in 4,349 patients with CAP enrolled in the multinational cohort study The Competence Network of Community-Acquired Pneumonia (CAPNETZ) and stratified by presence of fever at first patient contact. Independent predictors of bacteremia in patients who were afebrile were determined using logistic regression analysis. Bacteremic pneumonia was present in 190 of 2,116 patients who were febrile (8.9%), 101 of 2,149 patients who were afebrile (4.7%), and one of 23 patients with hypothermia (4.3%). Bacteremia rates increased with the CURB-65 score from 3.5%in patients with CURB-65 score of 0 to 17.1%in patients with CURB-65 score of 4. Patients with afebrile bacteremia exhibited the highest 28-day mortality rate (9.9%). Positive pneumococcal urinary antigen test (adjusted OR [AOR], 4.6; 95%CI, 2.6-8.2), C-reactive protein level > 200mg/L (AOR, 3.1; 95%CI, 1.9-5.2), and BUN level≥ 30mg/dL (AOR, 3.1; 95%CI, 1.9-5.3) were independent positive predictors, and antibiotic pretreatment (AOR, 0.3; 95%CI, 0.1-0.6) was an independent negative predictor of bacteremia in patients who were afebrile. A relevant proportion of patients with bacteremic CAP was afebrile. These patients had an increased mortality rate compared with patients with febrile bacteremia or nonbacteremic pneumonia. Therefore, the relevance of fever as an indicator for BC necessity merits reconsideration.

Antibiotic de-escalation therapy in patients with community-acquired nonbacteremic pneumococcal pneumonia.

Background De-escalation therapy is recommended as an effective antibiotic treatment strategy for several infectious diseases. While there is limited evidence supporting its clinical and cost-effective outcomes in patients with community-acquired bacteremic pneumonia, there is no evidence in patients with nonbacteremic pneumonia. Objective This study aimed to evaluate the antibiotic costs in patients who did and did not receive de-escalation therapy, based on the 2017 Japanese guidelines for the management of community-acquired nonbacteremic pneumococcal pneumonia of the Japanese Respiratory Society (JRS). Setting Kobeuniversity hospital, Japan. Methods A retrospective case series review including antibiotic use and length of hospital stay was conducted using the medical records from April 2008 to May 2019 at a university hospital in Japan. Main outcome measure Impact of antibiotic de-escalation therapy on the antibiotic costs. Results Among 55 patients who were eligible, the treating physicians de-escalated antibiotics in 28 (51%). The differences in the median length of hospital stay and the incidence of adverse drug reactions between the two groups were not statistically significant (p = 0.67 and 1.0, respectively). However, the median total antibiotic cost per infected patient in the de-escalated group was significantly lower than that in the non-de-escalated group [$269.8 ($195-$389) vs. $420.5 ($221-$799), p = 0.048]. Conclusion Antibiotic de-escalation based on the 2017 JRS guidelines leads to a reduction in total antibiotic costs for the management of community-acquired nonbacteremic pneumococcal pneumonia.

244. Development, Qualification, and Clinical Validation of an Immunodiagnostic assay for the Detection of 11 Additional S. pneumoniae Serotype-Specific Polysaccharides in Human Urine

BackgroundIdentifying Streptococcus pneumoniae (Sp) serotypes by urinary antigen detection assay (UAD) is the most sensitive and specific way to evaluate the changing epidemiology of non-bacteremic community-acquired pneumonia (CAP) and efficacy of pneumococcal vaccines. We first described an UAD to detect the Sp serotypes 1,-3,-4,-5,-6A,-6B,-7F,-9V,-14,-18C,-19A,-19F,-23F covered by the 13-valent Sp conjugate vaccine PCV13. To assess the pneumococcal disease burden of additional serotypes, a UAD-2 assay was developed to diagnose 11 additional Sp serotypes (-2,-8,-9N,-10A,-11A,-12F,-15B,-17F,-20,-22F,-33F).MethodsUAD-2 specificity was achieved by capturing highly purified pneumococcal polysaccharides with serotype-specific monoclonal antibodies using Luminex technology. Assay qualification assessed accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by non-parametric statistical evaluation of urine samples from individuals without pneumococcal disease. Clinical sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation.ResultsThe UAD-2 was shown to be specific and reproducible. Clinical validation using urine samples from invasive disease patients demonstrated assay sensitivity and specificity of 92.2% and 95.9%, respectively compared with a gold standard of isolating and typing (by Quellung) Sp bacteria from patient samples. Analysis of 11,087 CAP patients showed a UAD-2 and UAD-1 serotype prevalence of 4.33% and 4.60%, respectively (bacteremic and non-bacteremic CAP combined).ConclusionThe qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic Sp CAP as well as assessing vaccine efficacy of future pneumococcal conjugate vaccines.Disclosures All authors: No reported disclosures.

Racial Disparities in Adult Pneumococcal Vaccination Indications and Pneumococcal Hospitalizations in the U.S.

BackgroundRacial disparities in U.S. adult pneumococcal vaccination rates persist despite reduced barriers to access. Consequently, racial and ethnic minorities experience pneumococcal disease at higher rates than whites. This study examined prevalence of high-risk conditions and pneumococcal hospitalizations among U.S. black and non-black populations aged ≥50 years. MethodsNational Health Interview Survey, National Center for Health Statistics and National Inpatient Sample data were used to create black and non-black population cohorts, determine risk factors for pneumococcal disease (pneumococcal vaccine indications) and assess the impact of pneumococcal hospitalization. Each racial cohort was segmented into groups based on the presence of immunocompromising or other pneumococcal high-risk conditions. Persons without those conditions were separated into smokers (also a pneumococcal vaccine indication) and nonsmokers. Mortality was estimated from NCHS life table data. NIS data provided length of stay and costs (calculated from cost to charge ratios) for admissions related to pneumococcal disease including bacteremia, meningitis and nonbacteremic pneumonia. ResultsThere were similar proportions of immunocompromised (<5%) and smokers (14%) in both racial cohorts. Likelihood of non-immunocompromising pneumococcal high-risk conditions was higher for blacks than non-blacks at age 65, but higher for non-blacks than blacks at age 80 years (P < 0.001). Age-specific relative likelihood of mortality was 1.1%–12% higher in blacks than non-blacks (P < 0.001). Length of stay was significantly longer for blacks than non-blacks in all age and discharge status groups for non-bacteremic pneumonia and for blacks discharged alive with invasive pneumococcal disease. Costs were higher for blacks 65 years or older with invasive pneumococcal disease. ConclusionMarked differences exist between U.S. black and non-black populations in likelihood of conditions conferring a high-risk of pneumococcal disease, and for length of stay and costs of pneumococcal disease hospitalizations. Further research is recommended to identify cost-effective policies or interventions to increase vaccine uptake in higher risk populations.

Relationship Between the Quorum Network (Sensing/Quenching) and Clinical Features of Pneumonia and Bacteraemia Caused by A. baumannii.

Acinetobacter baumannii (Ab) is one of the most important pathogens associated with nosocomial infections, especially pneumonia. Interest in the Quorum network, i.e., Quorum Sensing (QS)/Quorum Quenching (QQ), in this pathogen has grown in recent years. The Quorum network plays an important role in regulating diverse virulence factors such as surface motility and bacterial competition through the type VI secretion system (T6SS), which is associated with bacterial invasiveness. In the present study, we investigated 30 clinical strains of A. baumannii isolated in the “II Spanish Study of A. baumannii GEIH-REIPI 2000-2010” (Genbank Umbrella Bioproject PRJNA422585), a multicentre study describing the relationship between the Quorum network in A. baumannii and the development of pneumonia and associated bacteraemia. Expression of the aidA gene (encoding the AidA protein, QQ enzyme) was lower (P < 0.001) in strains of A. baumannii isolated from patients with bacteraemic pneumonia than in strains isolated from patients with non-bacteraemic pneumonia. Moreover, aidA expression in the first type of strain was not regulated in the presence of environmental stress factors such as the 3-oxo-C12-HSL molecule (substrate of AidA protein, QQ activation) or H2O2 (inhibitor of AidA protein, QS activation). However, in the A. baumannii strains isolated from patients with non-bacteraemic pneumonia, aidA gene expression was regulated by stressors such as 3-oxo-C12-HSL and H2O2. In an in vivo Galleria mellonella model of A. baumannii infection, the A. baumannii ATCC 17978 strain was associated with higher mortality (100% at 24 h) than the mutant, abaI-deficient, strain (carrying a synthetase enzyme of Acyl homoserine lactone molecules) (70% at 24 h). These data suggest that the QS (abaR and abaI genes)/QQ (aidA gene) network affects the development of secondary bacteraemia in pneumonia patients and also the virulence of A. baumannii.

Treatment outcomes of patients with non-bacteremic pneumonia caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolates

Few therapeutic options exist for various infections caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex isolates, including pneumonia. This study investigated the clinical efficacy between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day) treatment alone or in combination with standard-dose tigecycline (TGC) in patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors influencing patients’ 30-day mortality.A 1:1 case (n = 106; receiving TGC plus AS-CMS) control (receiving AS-CMS alone with matching scores) observational study was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia in a Taiwanese medical center from January 2014 through December 2016. The clinically relevant data were retrospectively recorded. The primary endpoint was 30-day case fatality. Secondary endpoints investigated that if the co-morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors, or airway colonization with colistin-resistant Acb negatively influenced the 14-day clinical condition of enrolled patients.A higher 30-day mortality rate was noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17). The ≥7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156]) patients were colonized with colistin-resistant Acb isolates. After the conditional factors were adjusted by multivariate logistic analysis, the only factor independently predicting the 30-day case-fatality was the failure of treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95% confidence interval [CI] = 9.96–142.29; P < .001). Cox proportional regression analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard ratio [aHR] = 2.08; 95% CI = 1.05–4.10; P = .035), chronic renal failure (aHR = 3.00; 95% CI = 1.52–5.90; P = .002), non-invasive ventilation use (aHR = 2.68; 95% CI = 1.37–5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27–1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely, the emergence of colistin-resistant Acb isolates in the follow-up sputum samples was not statistically significantly associated with curing or improving XDR-Acb pneumonia.In conclusion, aggressive pulmonary hygiene care, the addition of TGC, and corticosteroid dose tapering were beneficial in improving the 14-day patients’ outcomes.