Validation of Drug Resistance in Pneumonia (DRIP) Score as Empirical Antibiotic Failure Predictor in Community-Acquired Pneumonia Patients in Cipto Mangunkusumo Hospital.

BACKGROUND: The incidence of CAP due to Drug-Resistant Pathogen (DRP) requires broad-spectrum antibiotic therapy, Drugs Resistance in Pneumonia (DRIP) score can predict these cases. The use of the DRIP score can prevent antibiotic failure and long hospitalization, but validation is needed so that the DRIP score can be used according to the local community at Cipto Mangunkusumo National Central Public Hospital. METHODS: This research is a retrospective cohort study in CAP patients who were hospitalized during the period January 2019 to June 2020. Data were taken from medical records. Failure of empiric antibiotics occurs when one of these criteria is found: patient mortality, ICU transfer, and escalation of antibiotics as well as length of stay. RESULTS: 480 patients met the criteria. There were 331 patients (69%) with a DRIP score of <4 and 149 patients (31%) with a DRIP score of≥4. A total of 283 patients (59%) of antibiotic failures were detailed in 174 patients with a DRIP score <4 and 109 patients DRIP score ≥4. DRIP calibration using the Hosmer-Lemeshow test obtained p-value= 0.667 (p>0.05). AUC observations on the ROC curve obtained 0.651 (95% CI; 0.601-0.700). CONCLUSION: The DRIP score has low accuracy performance and calibration value in predicting empirical antibiotic failure and poor discriminatory value.

Prior pneumococcal vaccination improves in-hospital mortality among elderly population hospitalized due to community-acquired pneumonia.

BACKGROUND: Pneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients. METHODS: The data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown. RESULTS: A total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 [71.0;82.0], 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P < 0.001), and showed higher in-hospital improvement (97.6 vs. 95.0%; P < 0.001) and lower 30-day mortality (2.6 vs. 5.3%; P < 0.001). After adjusting confounding factors such as age, gender, CURB score and CCI score, the vaccinated group demonstrated a significant reduction in 30-day mortality (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81; P < 0.01) and in-hospital mortality (HR 0.53, 95% CI0.37-0.78; P < 0.001) compared to the unvaccinated group in multivariate analysis. Vaccinated group showed better 30-day survival than those in non-vaccinated group (log-rank test < 0.05). CONCLUSIONS: Among elderly hospitalized CAP patients, prior pneumococcal vaccination was associated with improved in-hospital mortality and 30-day mortality.

Optimizing Diagnosis and Management of Community-acquired Pneumonia in the Emergency Department.

Pneumonia is split into 3 diagnostic categories: community-acquired pneumonia (CAP), health care-associated pneumonia, and ventilator-associated pneumonia. This classification scheme is driven not only by the location of infection onset but also by the predominant associated causal microorganisms. Pneumonia is diagnosed in over 1.5 million US emergency department visits annually (1.2% of all visits), and most pneumonia diagnosed by emergency physicians is CAP.

Severe Community-Acquired Pneumonia: Noninvasive Mechanical Ventilation, Intubation, and HFNT.

Severe acute respiratory failure (ARF) is a major issue in patients with severe community-acquired pneumonia (CAP). Standard oxygen therapy is the first-line therapy for ARF in the less severe cases. However, respiratory supports may be delivered in more severe clinical condition. In cases with life-threatening ARF, invasive mechanical ventilation (IMV) will be required. Noninvasive strategies such as high-flow nasal therapy (HFNT) or noninvasive ventilation (NIV) by either face mask or helmet might cover the gap between standard oxygen and IMV. The objective of all the supporting measures for ARF is to gain time for the antimicrobial treatment to cure the pneumonia. There is uncertainty regarding which patients with severe CAP are most likely to benefit from each noninvasive support strategy. HFNT may be the first-line approach in the majority of patients. While NIV may be relatively contraindicated in patients with excessive secretions, facial hair/structure resulting in air leaks or poor compliance, NIV may be preferable in those with increased work of breathing, respiratory muscle fatigue, and congestive heart failure, in which the positive pressure of NIV may positively impact hemodynamics. A trial of NIV might be considered for select patients with hypoxemic ARF if there are no contraindications, with close monitoring by an experienced clinical team who can intubate patients promptly if they deteriorate. In such cases, individual clinician judgement is key to choose NIV, interface, and settings. Due to the paucity of studies addressing IMV in this population, the protective mechanical ventilation strategies recommended by guidelines for acute respiratory distress syndrome can be reasonably applied in patients with severe CAP.

Retrospective study on the health and economic burden of hospitalized patients due to pneumonia and invasive pneumococcal infections in Belgium settings.

INTRODUCTION: pneumococcal infections are associated with high morbidity, hospitalisation and mortality. The objective of this study was to investigate the health and economic burden of all-cause pneumonia and invasive pneumococcal disease in Belgian hospital settings, by patient's age and risk profile. METHODS: This descriptive retrospective study was conducted in 17 Belgian hospitals. Univariate and multivariate logistic linear regression models were performed. The Health Insurance and patient's cost perspectives were considered because a few studies report these costs. RESULTS: The analysis has included 4,712 hospital admissions over the year 2018. Median hospitalization costs were higher for invasive pneumococcal infection diagnosis than for all-cause pneumonia (p < 0,001), respectively 4,051€ and 3,362€. Other factors associated with higher hospitalization cost were patient's high-risk profile, admission to emergency unit, transfer from nursing home, admission to intensive care unit and length of stay. CONCLUSION: Streptococcus pneumoniae infections remain a public health problem with significant cost for the Health Insurance and poor prognosis. Invasive pneumococcal infections are associated with longer hospital stays and required more intensive care than all other causes of pneumonia, in addition to be more costly, which justifies more attention for vaccination. This study also suggests an increase of economic and health burden with age and presence of underlying conditions.

A hypervirulent Acinetobacter baumannii strain has robust anti-phagocytosis ability.

BACKGROUND: Acinetobacter baumannii (A. baumannii) is associated with both hospital-acquired infections (HAP) and community-acquired pneumonia (CAP). In this study, we present a novel CAP-associated A. baumannii (CAP-AB) strain causing severe pneumonia in an afore healthy male patient without underlying conditions. Subsequently, we investigated the pathogenicity and immunogenicity of this CAP-AB strain using a mice pneumonia model. RESULTS: A 58-year-old male patient with no underlying conditions experienced worsening symptoms of a productive cough, sputum, and fever that developed acutely, in just 24 h. The diagnosis was severe community-acquired pneumonia (CAP) and type-1 respiratory failure. An A. baumannii strain was isolated from his sputum and blood cultures. To gain a deeper understanding of the rapid progression of its pathology, we utilized the CAP-associated A. baumannii strain YC128, a previously obtained hospital-acquired pneumonia A. baumannii (HAP-AB) strain YC156, and a highly virulent A. baumannii control strain LAC-4 to construct a mouse pneumonia model, and subsequently compared the mortality rate of the three groups. Following inoculation with 107 CFU of A. baumannii, the mortality rate for the YC128, LAC-4, and YC156 groups was 60% (6/10), 30% (3/10), and 0%, respectively. The bacterial burden within the pulmonary, liver, and spleen tissues of mice in the YC128 group was significantly higher than that of the YC156 group, and slightly higher than that of the LAC-4 group. Pathological analysis of lung tissue using HE-staining revealed that the inflammatory pathological changes in mice from the YC128 group were significantly more severe than those in the YC156 group. Additionally, CT scan images displayed more pronounced inflammation in the lungs of mice from the YC128 group compared to the YC156 group. Local levels of cytokines/chemokines such as IL-1ß, IL-6, TNF-α, and CXCL1 were assessed via RT-qPCR in lung tissues. In comparison with the YC156 strain, the highly virulent YC128 strain induced the expression of proinflammatory cytokines more rapidly and severely. Furthermore, we examined the in vitro anti-phagocytosis ability of YC128 and YC156 strains against mice peritoneal macrophages, revealing that the highly virulent YC128 isolate displayed greater resistance to macrophage uptake in contrast to YC156. Results from Whole Genome Sequencing (WGS) indicated that YC128 harbored a complete type VI secretion system (T6SS) gene cluster, while YC156 lacked the majority of genes within the T6SS gene cluster. The other virulence-related genes exhibited minimal differences between YC128 and YC156. Drawing from previous studies, we postulated that the T6SS is linked to the hypervirulence and robust anti-phagocytic ability of YC128. CONCLUSIONS: This article reports on the isolation of a novel hypervirulent CAP-AB strain, YC128, from a severe CAP patient. The results demonstrate that this CAP-AB strain, YC128, is capable of inducing fatal pneumonia and extrapulmonary dissemination in a mouse pneumonia model. Moreover, this highly virulent CAP-AB strain exhibits significantly stronger anti-phagocytic abilities compared to the HAP-AB YC156 strain. Genome sequencing comparisons reveal that the heightened hypervirulence and enhanced anti-phagocytosis abilities observed in YC128 may be attributed to the presence of the T6SS.

Relapsing bronchopneumonia due to community-associated methicillin-resistant Staphylococcus aureus: a case report.

BACKGROUND: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased the incidence of community-onset MRSA infection. Respiratory tract infections caused by MRSA has been noted for their severity; however, repeated relapses that require extended antibiotic therapy are rare. CASE PRESENTATION: We report a case of relapsing bronchopneumonia caused by CA-MRSA in a 56-year-old man. The patient responded to antibiotics, but repeatedly relapsed after stopping treatment. MRSA was consistently isolated from airway specimens during each relapse. Extended oral antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for 6 months achieved infection control. Whole-genome sequencing of the isolated strain revealed that the causative agent was sequence type (ST)1/staphylococcal cassette chromosome mec (SCCmec) type IVa, a clone that is rapidly increasing in Japan. DISCUSSION AND CONCLUSIONS: This patient had an unusual course of MRSA bronchopneumonia with repeated relapses. Although the choice of antibiotics for long-term use in MRSA respiratory tract infections has not been well established, TMP/SMX was effective and well tolerated for long-term therapy in this case. The clinical course of infections related to the rapid emerging clone, ST1/SCCmec type IVa warrants further attention.

Alveolar-arterial oxygen gradient: An early marker to predict the severity of community-acquired pneumonia in children.

To study the clinical significance of alveolar-arterial oxygen gradient (PA-aO2) for children with community-acquired pneumonia (CAP). A prospective study was carried out from January 2020 to June 2023, Overall, 100 patients were included in the study, 35 had severe pneumonia, whereas, 65 had non-severe pneumonia. Clinical and laboratory data were retrospectively collected at the time of hospital admission and during hospitalization. Patients were divided into severe and non-severe groups. PA-aO2 was significantly higher among children with severe pneumonia, as determined by WHO, PRESS (P < .001). PA-aO2 was significantly higher among children with mechanical ventilation, shock, sepsis, and mortality. Receiver operating characteristic curve (ROC) analysis for PA-aO2 showed that the area under the curve was 0.76 (P value < .05), with a sensitivity of 84.3% and a specificity of 67.9%. Our study suggests that PA-aO2 level has a predictive value for detecting community-acquired pneumonia severity in children.

The prevalence of acute kidney injury in patients with community-acquired pneumonia who required mechanical ventilation.

BACKGROUND: Community-acquired pneumonia (CAP) is a common reason for intensive care unit (ICU) admission and sepsis. Acute kidney injury (AKI) is a frequent complication of community-acquired pneumonia and is associated with increased short- and long-term morbidity and mortality and healthcare costs. OBJECTIVE: Describe the prevalence of AKI in patients with CAP requiring mechanical ventilation and evaluate its association with inhospital mortality. DESIGN: Retrospective cohort. SETTING: Intensive care unit. PATIENTS AND METHODS: We included patients with CAP on mechanical ventilation. Patients were categorized according to the development of AKI in the first 24 hours of ICU admission using the Kidney Disease Improving Global Outcomes (KDIGO) classification from no AKI, stage 1 AKI, stage 2 AKI, and stage 3 AKI. MAIN OUTCOME MEASURES: The primary outcome was hospital mortality. Secondary outcomes were ICU mortality, hospital and ICU length of stay, ventilation duration, tracheostomy, and renal replacement therapy requirement. RESULTS: Of 1536 patients included in the study, 829 patients (54%) had no AKI while 707 (46%) developed AKI. In-hospital mortality was 288/829 (34.8%) for patients with no AKI, 43/111 (38.7%) for stage 1 AKI, 86/216 (40%) for stage 2 AKI, and 196/380 (51.7%) for stage 3 AKI (P<.0001). Multivariate analysis revealed that stages 1, 2, or 3 AKI compared to no AKI were not independently associated with in-hospital mortality. Older age, vasopressor use; decreased Glasgow coma scale, PaO2/Fio2 ratio and platelet count, increased bilirubin, lactic acid and INR were associated with increased mortality while female sex was associated with reduced mortality. CONCLUSION: Among mechanically ventilated patients with CAP, AKI was common and was associated with higher crude mortality. The higher mortality could not be attributed alone to AKI, but rather appeared to be related to multi-organ dysfunction. LIMITATIONS: Single-center retrospective study with no data on baseline serum creatinine and the use of estimated baseline creatinine distributions based on the MDRD (Modification of Diet in Renal Disease)equation which may lead to an overestimation of AKI. Second, we did not have data on the microbiology of pneumonia, appropriateness of antibiotic therapy or the administration of other medications that have been demonstrated to be associated with AKI.

Novel Variant and Known Mutation in 23S rRNA Gene of Mycoplasma pneumoniae, Northern Vietnam, 2023.

During a 2023 outbreak of Mycoplasma pneumoniae-associated community-acquired pneumonia among children in northern Vietnam, we analyzed M. pneumoniae isolated from nasopharyngeal samples. In almost half (6 of 13) of samples tested, we found known A2063G mutations (macrolide resistance) and a novel C2353T variant on the 23S rRNA gene.

Oral versus intravenous antibiotic treatment of moderate-to-severe community-acquired pneumonia: a propensity score matched study.

Community-acquired Pneumonia (CAP) guidelines generally recommend to admit patients with moderate-to-severe CAP and start treatment with intravenous antibiotics. This study aims to explore the clinical outcomes of oral antibiotics in patients with moderate-to-severe CAP. We performed a nested cohort study of an observational study including all adult patients presenting to the emergency department of the Haga Teaching Hospital, the Netherlands, between April 2019 and May 2020, who had a blood culture drawn. We conducted propensity score matching with logistic and linear regression analysis to compare patients with moderate-to-severe CAP (Pneumonia Severity Index class III-V) treated with oral antibiotics to patients treated with intravenous antibiotics. Outcomes were 30-day mortality, intensive care unit admission, readmission, length of stay (LOS) and length of antibiotic treatment. Of the original 314 patients, 71 orally treated patients were matched with 102 intravenously treated patients. The mean age was 73 years and 58% were male. We found no significant differences in outcomes between the oral and intravenous group, except for an increased LOS of + 2.6 days (95% confidence interval 1.2-4.0, p value < 0.001) in those treated intravenously. We conclude that oral antibiotics might be a safe and effective treatment for moderate-to-severe CAP for selected patients based on the clinical judgement of the attending physician.

Comparison of outcomes and characteristics of patients admitted to the ICU with COVID-19 and other community-acquired pneumonia based on propensity score matching.

OBJECTIVE: To compare the similarities and differences between patients with Coronavirus Disease 2019 (COVID-19) and those with other community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), utilizing propensity score matching (PSM), regarding hospitalization expenses, treatment options, and prognostic outcomes, aiming to inform the diagnosis and treatment of COVID-19. METHODS: Patients admitted to the ICU of the Third People's Hospital of Datong City, diagnosed with COVID-19 from December 2022 to February 2023, constituted the observation group, while those with other CAP admitted from January to November 2022 formed the control group. Basic information, clinical data at admission, and time from symptom onset to admission were matched using PSM. RESULTS: A total of 70 patients were included in the COVID-19 group and 119 in the CAP group. The patients were matched by the propensity matching method, and 37 patients were included in each of the last two groups. After matching, COVID-19 had a higher failure rate than CAP, but the difference was not statistically significant (73% vs. 51%, p = 0.055). The utilization rate of antiviral drugs (40% vs. 11%, p = 0.003), γ-globulin (19% vs. 0%, p = 0.011) and prone position ventilation (PPV) (27% vs. 0%, p < 0.001) in patients with COVID-19 were higher than those in the CAP, and the differences were statistically significant. The total hospitalization cost of COVID-19 patients was lower than that of CAP patients, and the difference was statistically significant (27889.5 vs. 50175.9, p = 0.007). The hospital stay for COVID-19 patients was shorter than for CAP patients, but the difference was not statistically significant (10.9 vs. 16.6, p = 0.071). CONCLUSION: Our findings suggest that limited medical resources influenced patient outcomes during the COVID-19 pandemic. Addressing substantial demands for ICU capacity and medications during this period could have potentially reduced the mortality rate among COVID-19 patients.

Population-based retrospective cohort study on community-acquired pneumonia hospitalization in children with a ventricular septal defect.

The cohort consisted of 9400 exposed children diagnosed with ventricular septal defect (VSD). The risk of community-acquired pneumonia (CAP) or asthma with VSD was assessed using the Cox proportional hazard model with an inverse probability of treatment weighting. During a mean follow-up of 6.67 years (starting from 12 months after birth), there were 2100 CAP admission cases among exposed patients (incidence rate: 33.2 per 1000 person-years) and 20,109 CAP admission cases among unexposed children (incidence rate: 29.6 per 1000 person-years), with hazard ration of 1.09 (95% CI 1.04-1.14).

Predictive Value of Lysophosphatidylcholine for Determining the Disease Severity and Prognosis of Elderly Patients with Community-Acquired Pneumonia.

Purpose: To investigate the clinical value of serum lysophosphatidylcholine (LPC) as a predictive biomarker for determining disease severity and mortality risk in hospitalized elderly patients with community-acquired pneumonia (CAP). Methods: This prospective, single-center study enrolled 208 elderly patients, including 67 patients with severe CAP (SCAP) and 141 with non-SCAP between November 1st, 2020, and November 30th, 2021 at the Qingdao Municipal Hospital, Shandong Province, China. The demographic and clinical parameters were recorded for all the included patients. Serum LPC levels were measured on day 1 and 6 after admission using ELISA. Propensity score matching (PSM) was used to balance the baseline variables between SCAP and non-SCAP patient groups. Receiver operative characteristic (ROC) curve analysis was used to compare the predictive performances of LPC and other clinical parameters in discriminating between SCAP and non-SCAP patients and determining the 30-day mortality risk of the hospitalized CAP patients. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors associated with SCAP. Cox proportional hazard regression analysis was used to determine if serum LPC was an independent risk factor for the 30-day mortality of CAP patients. Results: The serum LPC levels at admission were significantly higher in the non-SCAP patients than in the SCAP patients (P = 0.011). Serum LPC level <24.36 ng/mL, and PSI score were independent risk factors for the 30-day mortality in the elderly patients with CAP. The risk of 30-day mortality in the elderly CAP patients with low serum LPC levels (< 24.36ng/mL) was >5-fold higher than in the patients with high serum LPC levels (≥ 24.36ng/mL). Conclusion: Low serum LPC levels were associated with significantly higher disease severity and 30-day mortality in the elderly patients with CAP. Therefore, serum LPC is a promising predictive biomarker for the early identification of elderly CAP patients with poor prognosis.

Diagnostic and Prognostic Value of Peripheral Neutrophil CD64 Index in Elderly Patients with Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in the elderly. The peripheral blood neutrophil CD64 (nCD64) index is increasingly recognized for its association with poor pneumonia prognosis. A comprehensive investigation involving 128 elderly patients diagnosed with CAP, including 96 with non-severe CAP and 32 with severe CAP, from January 2020 to January 2021 was performed. The nCD64 index, CD4+, CD8+, C-reactive protein (CRP), white blood cell (WBC) count, procalcitonin (PCT), neutrophil (NEUT), and B lymphocyte count were determined using flow cytometry. Our findings reveal that patients with severe CAP exhibited significantly higher levels of nCD64 index, NEUT, WBC, CRP, and PCT. Intriguingly, lower CRP, nCD64 index, CURB-65 score, and PCT were associated with a higher survival rate. Notably, the nCD64 index demonstrated remarkable predictive efficiency for 28-d survival in CAP patients [area under the curve (AUC) = 0.907], surpassing other markers and even showing enhanced predictive power when combined with the CURB-65 score (AUC = 0.905). Furthermore, a negative association was observed between the nCD64 index and both CD4+, CD4+/CD8+ ratios, and B lymphocytes, highlighting its potential role in immune dysregulation. These findings underscore the critical importance of the nCD64 index in the early diagnosis, risk stratification, and prognostic evaluation of infections and immune responses in elderly CAP patients.

Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing: A Randomized Clinical Trial.

Importance: Lower respiratory tract (LRT) infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. Molecular tests have the potential to optimize treatment decisions and management of CAP, but limited evidence exists to support their routine use. Objective: To determine whether the judicious use of a syndromic polymerase chain reaction (PCR)-based panel for rapid testing of CAP in the emergency department (ED) leads to faster, more accurate microbiological test result-based treatment. Design, Setting, and Participants: This parallel-arm, single-blinded, single-center, randomized clinical superiority trial was conducted between September 25, 2020, and June 21, 2022, in the ED of Haukeland University Hospital, a large tertiary care hospital in Bergen, Norway. Adult patients who presented to the ED with suspected CAP were recruited. Participants were randomized 1:1 to either the intervention arm or standard-of-care arm. The primary outcomes were analyzed according to the intention-to-treat principle. Intervention: Patients randomized to the intervention arm received rapid syndromic PCR testing (BioFire FilmArray Pneumonia plus Panel; bioMérieux) of LRT samples and standard of care. Patients randomized to the standard-of-care arm received standard microbiological diagnostics alone. Main Outcomes and Measures: The 2 primary outcomes were the provision of pathogen-directed treatment based on a microbiological test result and the time to provision of pathogen-directed treatment (within 48 hours after randomization). Results: There were 374 patients (221 males [59.1%]; median (IQR) age, 72 [60-79] years) included in the trial, with 187 in each treatment arm. Analysis of primary outcomes showed that 66 patients (35.3%) in the intervention arm and 25 (13.4%) in the standard-of-care arm received pathogen-directed treatment, corresponding to a reduction in absolute risk of 21.9 (95% CI, 13.5-30.3) percentage points and an odds ratio for the intervention arm of 3.53 (95% CI, 2.13-6.02; P < .001). The median (IQR) time to provision of pathogen-directed treatment within 48 hours was 34.5 (31.6-37.3) hours in the intervention arm and 43.8 (42.0-45.6) hours in the standard-of-care arm (mean difference, -9.4 hours; 95% CI, -12.7 to -6.0 hours; P < .001). The corresponding hazard ratio for intervention compared with standard of care was 3.08 (95% CI, 1.95-4.89). Findings remained significant after adjustment for season. Conclusions and Relevance: Results of this randomized clinical trial indicated that routine deployment of PCR testing for LRT pathogens led to faster and more targeted microbial treatment for patients with suspected CAP. Rapid molecular testing could complement or replace selected standard, time-consuming, laboratory-based diagnostics. Trial Registration: ClinicalTrials.gov Identifier: NCT04660084.

Lymphopenia is associated with broad host response aberrations in community-acquired pneumonia.

OBJECTIVES: Lymphopenia at hospital admission occurs in over one-third of patients with community-acquired pneumonia (CAP), yet its clinical relevance and pathophysiological implications remain underexplored. We evaluated outcomes and immune features of patients with lymphopenic CAP (L-CAP), a previously described immunophenotype characterized by admission lymphocyte count <0.724 × 109 cells/L. METHODS: Observational study in 149 patients admitted to a general ward for CAP. We measured 34 plasma biomarkers reflective of inflammation, endothelial cell responses, coagulation, and immune checkpoints. We characterized lymphocyte phenotypes in 29 patients using spectral flow cytometry. RESULTS: L-CAP occurred in 45 patients (30.2%) and was associated with prolonged time-to-clinical-stability (median 5 versus 3 days), also when we accounted for competing events for reaching clinical stability and adjusted for baseline covariates (subdistribution hazard ratio 0.63; 95% confidence interval 0.45-0.88). L-CAP patients demonstrated a proportional depletion of CD4 T follicular helper cells, CD4 T effector memory cells, naïve CD8 T cells and IgG+ B cells. Plasma biomarker analyses indicated increased activation of the cytokine network and the vascular endothelium in L-CAP. CONCLUSIONS: L-CAP patients have a protracted clinical recovery course and a more broadly dysregulated host response. These findings highlight the prognostic and pathophysiological relevance of admission lymphopenia in patients with CAP.

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.