BACKGROUND Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radio-graphically and with the use of current laboratory diagnostic tests are needed. METHODS We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among adults 18 years of age or older in five hospitals in Chicago and Nashville. Patients with recent hospitalization or severe immunosuppression were excluded. Blood, urine, and respiratory specimens were systematically collected for culture, serologic testing, antigen detection, and molecular diagnostic testing. Study radiologists independently reviewed chest radiographs. We calculated population-based incidence rates of community-acquired pneumonia requiring hospitalization according to age and pathogen. RESULTS From January 2010 through June 2012, we enrolled 2488 of 3634 eligible adults (68%). Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. Among 2259 patients who had radio-graphic evidence of pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 853 (38%): one or more viruses in 530 (23%), bacteria in 247 (11%), bacterial and viral pathogens in 59 (3%), and a fungal or mycobacterial pathogen in 17 (1%). The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%). The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). For each pathogen, the incidence increased with age. CONCLUSIONS The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults. Despite current diagnostic tests, no pathogen was detected in the majority of patients. Respiratory viruses were detected more frequently than bacteria. (Funded by the Influenza Division of the National Center for Immunizations and Respiratory Diseases.)

Background U.S. incidence estimates of pediatric community-acquired pneumonia hospitalizations based on prospective data collection are limited. Updated estimates with radiographic confirmation and current laboratory diagnostics are needed. Methods We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children <18 years in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization and severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection by multiple modalities. Chest radiographs were independently reviewed by study radiologists. We calculated population-based incidence rates of community-acquired pneumonia hospitalizations, overall and by age and pathogen. Results From January 2010-June 2012, we enrolled 2638 (69%) of 3803 eligible children; 2358 (89%) had radiographic pneumonia. Median age was 2 years (interquartile range 1-6); 497 (21%) children required intensive care, and three (<1%) died. Among 2222 children with radiographic pneumonia and specimens available for both bacterial and viral testing, a viral and/or bacterial pathogen was detected in 1802 (81%); ≥1 virus in 1472 (66%), bacteria in 175 (8%), and bacterial-viral co-detection in 155 (7%). Annual pneumonia incidence was 15.7/10,000 children [95% confidence interval (CI) 14.9-16.5], with highest rates among children <2 years [62.2/10,000 (CI 57.6-67.1)]. Respiratory syncytial virus (37% vs. 8%), adenovirus (15% vs. 3%), and human metapneumovirus (15% vs. 8%) were more commonly detected in children <5 years compared with older children; Mycoplasma pneumoniae (19% vs. 3%) was more common in children ≥5 years. Conclusions Pediatric community-acquired pneumonia hospitalization burden was highest among the very young, with respiratory viruses most commonly detected.

Purpose The addition of immunotherapy, including a combination of anti-GD2 monoclonal antibody (mAb), ch14.18, and cytokines, improves outcome for patients with high-risk neuroblastoma. However, this therapy is limited by ch14.18-related toxicities that may be partially mediated by complement activation. We report the results of a phase I trial to determine the maximum-tolerated dose (MTD), safety profile, and pharmacokinetics of hu14.18K322A, a humanized anti-GD2 mAb with a single point mutation (K322A) that reduces complement-dependent lysis. Patients and Methods Eligible patients with refractory or recurrent neuroblastoma received escalating doses of hu14.18K322A ranging from 2 to 70 mg/m2 per day for 4 consecutive days every 28 days (one course). Results Thirty-eight patients (23 males; median age, 7.2 years) received a median of two courses (range, one to 15). Dose-limiting grade 3 or 4 toxicities occurred in four of 36 evaluable patients and were characterized by cough, asthenia, sensory neuropathy, anorexia, serum sickness, and hypertensive encephalopathy. The most common non–dose-limiting grade 3 or 4 toxicities during course one were pain (68%) and fever (21%). Six of 31 patients evaluable for response by iodine-123 metaiodobenzylguanidine score had objective responses (four complete responses; two partial responses). The first-course pharmacokinetics of hu14.18K322A were best described by a two-compartment linear model. Median hu14.18K322A α (initial phase) and β (terminal phase) half-lives were 1.74 and 21.1 days, respectively. Conclusion The MTD, and recommended phase II dose, of hu14.18K322A is 60 mg/m2 per day for 4 days. Adverse effects, predominately pain, were manageable and improved with subsequent courses.