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.

No procalcitonin threshold perfectly discriminated between viral and bacterial pathogens, but higher procalcitonin strongly correlated with increased probability of bacterial pathogens, particularly typical bacteria.

SummaryHepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity, autoimmune phenomena and lymphomagenesis, supporting a role for lymphocyte dysregulation during persistent viral infection. We have shown that HCV core protein inhibits T-cell functions through interaction with a complement receptor, gC1qR. Here, we further report that B cells also express gC1qR that can be bound by HCV core protein. Importantly, using flow cytometry, we demonstrated differential regulation of B and T lymphocytes by the HCV core-gC1qR interaction, with down-regulation of CD69 activation in T cells but up-regulation of CD69 activation and cell proliferation in B cells. HCV core treatment led to decreased interferon-c production in CD8 + T cells but to increased immunoglobulin M and immunoglobulin G production as well as cell surface expression of costimulatory and chemokine receptors, including CD86 (B7-2), CD154 (CD40L) and CD195 (CCR5), in CD20 + B cells.Finally, we showed down-regulation of suppressor of cytokine signalling-1 (SOCS-1) using real-time reverse transcription-polymerase chain reaction, accompanied by up-regulation of signal transducer and activator of transcription-1 (STAT1) phosphorylation in B cells in response to HCV core protein, with the opposite pattern observed in HCV core-treated T cells. This study demonstrates differential regulation of B and T lymphocytes by HCV core and supports a mechanism by which lymphocyte dysregulation occurs in the course of persistent HCV infection.

New diagnostic platforms often use nasopharyngeal or oropharyngeal (NP/OP) swabs for pathogen detection for patients hospitalized with communityacquired pneumonia (CAP). We applied multipathogen testing to high-quality sputum specimens to determine if more pathogens can be identified relative to NP/OP swabs. Children (Ͻ18 years old) and adults hospitalized with CAP were enrolled over 2.5 years through the Etiology of Pneumonia in the Community (EPIC) study. NP/OP specimens with matching high-quality sputum (defined as Յ10 epithelial cells/lowpower field [lpf] and Ն25 white blood cells/lpf or a quality score [q-score] definition of 2ϩ) were tested by TaqMan array card (TAC), a multipathogen real-time PCR detection platform. Among 236 patients with matched specimens, a higher proportion of sputum specimens had Ն1 pathogen detected compared with NP/OP specimens in children (93% versus 68%; P Ͻ 0.0001) and adults (88% versus 61%; P Ͻ 0.0001); for each pathogen targeted, crossing threshold (C T ) values were earlier in sputum. Both bacterial (361 versus 294) and viral detections (245 versus 140) were more common in sputum versus NP/OP specimens, respectively, in both children and adults. When available, high-quality sputum may be useful for testing in hospitalized CAP patients.KEYWORDS community-acquired pneumonia, pneumonia, multipathogen, diagnostics, TaqMan array card, NP/OP, TAC, sputum A cute respiratory infections (ARI), especially lower respiratory tract (LRT) infections, including community-acquired pneumonia (CAP), are a significant cause of morbidity and mortality globally (1-3). Despite advances in diagnostic testing beyond culture-based methods, including molecular and antigen-based approaches, pneumonia etiology often remains undetermined even when systematic and comprehensive specimen collection and methods are employed, particularly in adults (1, 2); one reason for this is that specimens directly from the lungs are often not available. Upper respiratory tract specimens, such as nasopharyngeal and oropharyngeal (NP/OP) swabs, are often collected for molecular testing of respiratory pathogens due to the ease of collection. Some studies suggest that LRT specimens, such as sputum, endotracheal aspirates (ETA), and bronchoalveolar lavage (BAL) fluids, have improved sensitivity compared with NP/OP swabs; while issues of specificity needed to inform clinician