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Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain. In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days. Antibiotic selection, dosing, and route were at the discretion of the treating team. We excluded patients with severe immunosuppression, foci requiring prolonged treatment, single cultures with possible contaminants, or cultures yielding . The primary outcome was death from any cause by 90 days after diagnosis of the bloodstream infection, with a noninferiority margin of 4 percentage points. Across 74 hospitals in seven countries, 3608 patients underwent randomization and were included in the intention-to-treat analysis; 1814 patients were assigned to 7 days of antibiotic treatment, and 1794 to 14 days. At enrollment, 55.0% of patients were in the ICU and 45.0% were on hospital wards. Infections were acquired in the community (75.4%), hospital wards (13.4%) and ICUs (11.2%). Bacteremia most commonly originated from the urinary tract (42.2%), abdomen (18.8%), lung (13.0%), vascular catheters (6.3%), and skin or soft tissue (5.2%). By 90 days, 261 patients (14.5%) receiving antibiotics for 7 days had died and 286 patients (16.1%) receiving antibiotics for 14 days had died (difference, -1.6 percentage points [95.7% confidence interval {CI}, -4.0 to 0.8]), which showed the noninferiority of the shorter treatment duration. Patients were treated for longer than the assigned duration in 23.1% of the patients in the 7-day group and in 10.7% of the patients in the 14-day group. A per-protocol analysis also showed noninferiority (difference, -2.0 percentage points [95% CI, -4.5 to 0.6]). These findings were generally consistent across secondary clinical outcomes and across prespecified subgroups defined according to patient, pathogen, and syndrome characteristics. Among hospitalized patients with bloodstream infection, antibiotic treatment for 7 days was noninferior to treatment for 14 days. (Funded by the Canadian Institutes of Health Research and others; BALANCE ClinicalTrials.gov number, NCT03005145.).

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus ) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus , compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae , Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.

Clinical decision making relative to community-acquired pneumonia (CAP) diagnosis is difficult. Chest radiograph is key in establishing parenchymal lung involvement. However, radiologic performance may lead to misdiagnosis, rendering questionable the use of chest computed tomography (CT) scan in patients with clinically suspected CAP. To assess whether early multidetector chest CT scan affects diagnosis and management of patients visiting the emergency department with suspected CAP. A total of 319 prospectively enrolled patients with clinically suspected CAP underwent multidetector chest CT scan within 4 hours. CAP diagnosis probability (definite, probable, possible, or excluded) and therapeutic plans (antibiotic initiation/discontinuation, hospitalization/discharge) were established by emergency physicians before and after CT scan results. The adjudication committee established the final CAP classification on Day 28. Chest radiograph revealed a parenchymal infiltrate in 188 patients. CAP was initially classified as definite in 143 patients (44.8%), probable or possible in 172 (53.8%), and excluded in 4 (1.2%). CT scan revealed a parenchymal infiltrate in 40 (33%) of the patients without infiltrate on chest radiograph and excluded CAP in 56 (29.8%) of the 188 with parenchymal infiltrate on radiograph. CT scan modified classification in 187 (58.6%; 95% confidence interval, 53.2-64.0), leading to 50.8% definite CAP and 28.8% excluded CAP, and 80% of modifications were in accordance with adjudication committee classification. Because of CT scan, antibiotics were initiated in 51 (16%) and discontinued in 29 (9%), and hospitalization was decided in 22 and discharge in 23. In CAP-suspected patients visiting the emergency unit, early CT scan findings complementary to chest radiograph markedly affect both diagnosis and clinical management. Clinical trial registered with www.clinicaltrials.gov (NCT 01574066).

Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Abstract Rationale To identify pathogens that require different treatments in community-acquired pneumonia (CAP), we propose an acronym, “PES” (P  seudomonas aeruginosa, E  nterobacteriaceae extended-spectrum β-lactamase–positive, and methicillin-resistant S  taphylococcus aureus). Objectives To compare the clinical characteristics and outcomes between patients with CAP caused by PES versus other pathogens, and to identify the risk factors associated with infection caused by PES. Methods We conducted an observational prospective study evaluating only immunocompetent patients with CAP and an established etiological diagnosis. We included patients from nursing homes. We computed a score to identify patients at risk of PES pathogens. Measurement and Main Results: Of the 4,549 patients evaluated, we analyzed 1,597 who presented an etiological diagnosis. Pneumonia caused by PES was identified in 94 (6%) patients, with 108 PES pathogens isolated (n = 72 P. aeruginosa, n = 15 E  nterobacteriaceae extended-spectrum β-lactamase positive, and n = 21 methicillin-resistant S  taphylococcus aureus). These patients were older (P = 0.001), had received prior antibiotic treatment more frequently (P < 0.001), and frequently presented with acute renal failure (P = 0.004). PES pathogens were independently associated with increased risk of 30-day mortality (adjusted odds ratio = 2.51; 95% confidence interval = 1.20–5.25; P = 0.015). The area under the curve for the score we computed was 0.759 (95% confidence interval, 0.713–0.806; P < 0.001). Conclusions PES pathogens are responsible for a small proportion of CAP, resulting in high mortality. These pathogens require a different antibiotic treatment, and identification of specific risk factors could help to identify these microbial etiologies.

Background. Prevalence of Staphylococcus aureus community-acquired pneumonia (CAP) and its clinical features remain incompletely understood, complicating empirical selection of antibiotics. Methods. Using a multicenter, prospective surveillance study of adults hospitalized with CAP, we calculated the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) among all CAP episodes. We compared the epidemiologic, radiographic, and clinical characteristics of S. aureus CAP (per respiratory or blood culture) with those of pneumococcal (per respiratory or blood culture or urine antigen) and all-cause non-S. aureus CAP using descriptive statistics. Results. Among 2259 adults hospitalized for CAP, 37 (1.6%) had S. aureus identified, including 15 (0.7%) with MRSA and 22 (1.0%) with MSSA; 115 (5.1%) had Streptococcus pneumoniae. Vancomycin or linezolid was administered to 674 (29.8%) patients within the first 3 days of hospitalization. Chronic hemodialysis use was more common among patients with MRSA (20.0%) than pneumococcal (2.6%) and all-cause non-S. aureus (3.7%) CAP. Otherwise, clinical features at admission were similar, including concurrent influenza infection, hemoptysis, multilobar infiltrates, and prehospital antibiotics. Patients with MRSA CAP had more severe clinical outcomes than those with pneumococcal CAP, including intensive care unit admission (86.7% vs 34.8%) and in-patient mortality (13.3% vs 4.4%). Conclusions. Despite very low prevalence of S. aureus and, specifically, MRSA, nearly one-third of adults hospitalized with CAP received anti-MRSA antibiotics. The clinical presentation of MRSA CAP overlapped substantially with pneumococcal CAP, highlighting the challenge of accurately targeting empirical anti-MRSA antibiotics with currently available clinical tools and the need for new diagnostic strategies.

Background. Previous reports suggest that community-acquired pneumonia (CAP) is associated with an enhanced risk of cardiovascular complications. However, a contemporary and comprehensive characterization of this association is lacking. Methods. In this multicenter study, 1182 patients hospitalized for CAP were prospectively followed for up to 30 days after their hospitalization for this infection. Study endpoints included myocardial infarction, new or worsening heart failure, atrial fibrillation, stroke, deep venous thrombosis, cardiovascular death, and total mortality. Results. Three hundred eighty (32.2%) patients experienced intrahospital cardiovascular events (CVEs) including 281 (23.8%) with heart failure, 109 (9.2%) with atrial fibrillation, 89 (8%) with myocardial infarction, 11 (0.9%) with ischemic stroke, and 1 (0.1%) with deep venous thrombosis; 28 patients (2.4%) died for cardiovascular causes. Multivariable Cox regression analysis showed that intrahospital Pneumonia Severity Index (PSI) class (hazard ratio [HR], 2.45, P = .027; HR, 4.23, P < .001; HR, 5.96, P < .001, for classes III, IV, and V vs II, respectively), age (HR, 1.02, P = .001), and preexisting heart failure (HR, 1.85, P < .001) independently predicted CVEs. One hundred three (8.7%) patients died by day 30 postadmission. Thirty-day mortality was significantly higher in patients who developed CVEs compared with those who did not (17.6% vs 4.5%, P < .001). Multivariable Cox regression analysis showed that intrahospital CVEs (HR, 5.49, P < .001) independently predicted 30-day mortality (after adjustment for age, PSI score, and preexisting comorbid conditions). Conclusions. CVEs, mainly those confined to the heart, complicate the course of almost one-third of patients hospitalized for CAP. More importantly, the occurrence of CVEs is associated with a 5-fold increase in CAP-associated 30-day mortality.

In Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador. This observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2-59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction. Risk factors for specific respiratory pathogens were also evaluated. Among 406 children tested, 159 (39.2%) had respiratory syncytial virus (RSV), 71 (17.5%) had human metapneumovirus (hMPV), and 62 (15.3%) had adenovirus. Streptococcus pneumoniae was identified in 37 (9.2%) samples and Mycoplasma pneumoniae in three (0.74%) samples. The yearly circulation pattern of RSV (P = 0.0003) overlapped with S. pneumoniae, (P = 0.03) with most cases occurring in the rainy season. In multivariable analysis, risk factors for RSV included younger age (adjusted odds ratio [aOR] = 1.9, P = 0.01) and being underweight (aOR = 1.8, P = 0.04). Maternal education (aOR = 0.82, P = 0.003), pulse oximetry (aOR = 0.93, P = 0.005), and rales (aOR = 0.25, P = 0.007) were associated with influenza A. Younger age (aOR = 3.5, P = 0.007) and elevated baseline respiratory rate were associated with HPIV-3 infection (aOR = 0.94, P = 0.03). These results indicate the importance of RSV and influenza, and potentially modifiable risk factors including undernutrition and future use of a RSV vaccine, when an effective vaccine becomes available. ClinicalTrials.gov NCT 00513929.

We assessed whether multiplex real-time PCR plus conventional microbiological testing is safe and more effective than conventional microbiological testing alone for reducing antibiotic use in community-acquired pneumonia (CAP). In this randomised trial, we recruited adults hospitalised with CAP at four Spanish hospitals. Patients were randomly assigned (1:1) to undergo either multiplex real-time PCR in non-invasive respiratory samples plus conventional microbiological testing or conventional microbiological testing alone. The primary endpoint was antibiotic use measured by days of antibiotic therapy (DOT). Between February 20, 2020, and April 24, 2023, 242 patients were enrolled; 119 were randomly assigned to multiplex real-time PCR plus conventional microbiological testing and 123 to conventional microbiological testing alone. All but one of the patients allocated to multiplex real-time PCR plus conventional microbiological testing underwent PCR, which was performed in sputum samples in 77 patients (65.2%) and in nasopharyngeal swabs in 41 (34.7%). The median DOT was 10.04 (IQR 7.98, 12.94) in the multiplex PCR plus conventional microbiological testing group and 11.33 (IQR 8.15, 16.16) in the conventional microbiological testing alone group (difference −1.04; 95% CI, −2.42 to 0.17; p  = 0.093). No differences were observed in adverse events and 30-day mortality. Our findings do not support the routine implementation of multiplex real-time PCR in the initial microbiological testing in hospitalised patients with CAP. Clinicaltrials.gov registration: NCT04158492. Here, the authors report the results of a randomised trial assessing whether adding multiplex real-time PCR to conventional testing reduces antibiotic use in community-acquired pneumonia and observe no significant reduction in days of antibiotic therapy or in 30-day mortality.

Community-acquired pneumonia is not usually considered a high-priority problem by the public, although it is responsible for substantial mortality, with a third of patients dying within 1 year after being discharged from hospital for pneumoniae. Although up to 18% of patients with community-acquired pneumonia who were hospitalised (admitted to hospital and treated there) have at least one risk factor for immunosuppression worldwide, strong evidence on community-acquired pneumonia management in this population is scarce. Several features of clinical management for community-acquired pneumonia should be addressed to reduce mortality, morbidity, and complications related to community-acquired pneumonia in patients who are immunocompetent and patients who are immunocompromised. These features include rapid diagnosis, microbiological investigation, prevention and management of complications (eg, respiratory failure, sepsis, and multiorgan failure), empirical antibiotic therapy in accordance with patient's risk factors and local microbiological epidemiology, individualised antibiotic therapy according to microbiological data, appropriate outcomes for therapeutic switch from parenteral to oral antibiotics, discharge planning, and long-term follow-up. This Seminar offers an updated view on community-acquired pneumonia in adults, with suggestions for clinical and translational research.