DONNELLY JP,BADDLEY JW,WANG HE.Antibiotic utilization for acute respiratory tract infections in U.S.emergency departments[J].Antimicrob Agents Chemother,2014,58(3):1451-1457.
Inappropriate use of antibiotics for acute respiratory tract infections (ARTIs) has decreased in many outpatient settings. For patients presenting to U.S. emergency departments (EDs) with ARTIs, antibiotic utilization patterns are unclear. We conducted a retrospective cohort study of ED patients from 2001 to 2010 using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). We identified patients presenting to U.S. EDs with ARTIs and calculated rates of antibiotic utilization. Diagnoses were classified as antibiotic appropriate (otitis media, sinusitis, pharyngitis, tonsillitis, and nonviral pneumonia) or antibiotic inappropriate (nasopharyngitis, unspecified upper respiratory tract infection, bronchitis or bronchiolitis, viral pneumonia, and influenza).There were 126 million ED visits with a diagnosis of ARTI, and antibiotics were prescribed in 61%. Between 2001 and 2010, antibiotic utilization decreased for patients aged<5 presenting with antibiotic-inappropriate ARTI (rate ratio [RR], 0.94; confidence interval [CI], 0.88 to 1.00). Utilization also decreased significantly for antibiotic-inappropriate ARTI patients aged 5 to 19 years (RR, 0.89; CI, 0.85 to 0.94). Utilization remained stable for antibiotic-inappropriate ARTI among adult patients aged 20 to 64 years (RR, 0.99; CI, 0.97 to 1.01). Among adults, rates of quinolone use for ARTI increased significantly from 83 per 1,000 visits in 2001 to 2002 to 105 per 1,000 in 2009 to 2010 (RR, 1.08; CI, 1.03 to 1.14). Although significant progress has been made toward reduction of antibiotic utilization for pediatric patients with ARTI, the proportion of adult ARTI patients receiving antibiotics in U.S. EDs is inappropriately high. Institution of measures to reduce inappropriate antibiotic use in the ED setting is warranted.
RICE TW,RUBINSONL,UYEKI TM,et al.Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States[J].Crit Care Med, 2012,40(5):1487-1498.
The contribution of bacterial coinfection to critical illness associated with 2009 influenza A virus infection remains uncertain. The objective of this study was to determine whether bacterial coinfection increased the morbidity and mortality of 2009 influenza A.Retrospective and prospective cohort study.Thirty-five adult U.S. intensive care units over the course of 1 yr.Six hundred eighty-three critically ill adults with confirmed or probable 2009 influenza A.None.A confirmed or probable case was defined as a positive 2009 influenza A test result or positive test for influenza A that was otherwise not subtyped. Bacterial coinfection was defined as documented bacteremia or any presumed bacterial pneumonia with or without positive respiratory tract culture within 72 hrs of intensive care unit admission. The mean age was 45卤16 yrs, mean body mass index was 32.5卤11.1 kg/m, and mean Acute Physiology and Chronic Health Examination II score was 21卤9, with 76% having at least one comorbidity. Of 207 (30.3%) patients with bacterial coinfection on intensive care unit admission, 154 had positive cultures with Staphylococcus aureus (n=57) and Streptococcus pneumoniae (n=19), the most commonly identified pathogens. Bacterial coinfected patients were more likely to present with shock (21% vs. 10%; p=.0001), require mechanical ventilation at the time of intensive care unit admission (63% vs. 52%; p=.005), and have longer duration of intensive care unit care (median, 7 vs. 6 days; p=.05). Hospital mortality was 23%; 31% in bacterial coinfected patients and 21% in patients without coinfection (p=.002). Immunosuppression (relative risk 1.57; 95% confidence interval 1.20 -2.06; p=.0009) and Staphylococcus aureus at admission (relative risk 2.82; 95% confidence interval 1.76-4.51; p<.0001) were independently associated with increased mortality.Among intensive care unit patients with 2009 influenza A, bacterial coinfection diagnosed within 72 hrs of admission, especially with Staphylococcus aureus, was associated with significantly higher morbidity and mortality.
FALSEY AR,BECKER KL,SWINBURNE AJ,et al.Bacterial complications of respiratory tract viral illness: a comprehensive evaluation[J].J Infect Dis,2013,208(3):432-441.
Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied.Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of 鈮 0.25 ng/mL on admission or day 2 of hospitalization.Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis.Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.
CHIRKOVAT,BOYOGLU-BARNUMS,GASTON KA,et al.Respiratory syncytial virus G protein CX3C motif impairs human airway epithelial and immune cell responses[J].J Virol,2013,87(24):13466-13479.
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory infection in infants and young children and causes disease in the elderly and persons with compromised cardiac, pulmonary, or immune systems. Despite the high morbidity rates of RSV infection, no highly effective treatment or vaccine is yet available. The RSV G protein is an important contributor to the disease process. A conserved CX3C chemokine-like motif in G likely contributes to the pathogenesis of disease. Through this motif, G protein binds to CX3CR1 present on various immune cells and affects immune responses to RSV, as has been shown in the mouse model of RSV infection. However, very little is known of the role of RSV CX3C-CX3CR1 interactions in human disease. In this study, we use an in vitro model of human RSV infection comprised of human peripheral blood mononuclear cells (PBMCs) separated by a permeable membrane from human airway epithelial cells (A549) infected with RSV with either an intact CX3C motif (CX3C) or a mutated motif (CX4C). We show that the CX4C virus induces higher levels of type I/III interferon (IFN) in A549 cells, increased IFN-伪 and tumor necrosis factor alpha (TNF-伪) production by human plasmacytoid dendritic cells (pDCs) and monocytes, and increased IFN-纬 production in effector/memory T cell subpopulations. Treatment of CX3C virus-infected cells with the F(ab')2 form of an anti-G monoclonal antibody (MAb) that blocks binding to CX3CR1 gave results similar to those with the CX4C virus. Our data suggest that the RSV G protein CX3C motif impairs innate and adaptive human immune responses and may be important to vaccine and antiviral drug development.
METZGER DW,SUNK.Immune dysfunction and bacterial coinfections following influenza[J].J Immunol,2013,191(5):2047-2052.
Secondary by encapsulated including and following represent a common and challenging clinical problem. The reasons for this polymicrobial synergy are still not completely understood, hampering of effective prophylactic and therapeutic interventions. Although it has been commonly thought that viral-induced epithelial cell damage allows bacterial invasiveness, recent studies by several groups have now implicated dysfunctional innate immune defenses following as the primary culprit for enhanced susceptibility to secondary . Understanding the immunological imbalances that are responsible for virus/synergy will ultimately allow the design of effective, broad-spectrum therapeutic approaches for prevention of enhanced susceptibility to these pathogens.
JAMIESON AM,YUS,ANNICELLI CH,et al.Influenza virus-induced glucocorticoids compromise innate host defense against a secondary bacterial infection[J].Cell Host Microbe, 2010,7(2):103-114.
Multicellular organisms are continuously exposed to many different pathogens. Because different classes of pathogens require different types of immune responses, understanding how an ongoing immune response to one type of infection affects the host's ability to respond to another pathogen is essential for a complete understanding of host-pathogen interactions. Here, we used a mouse model of coinfection to gain insight into the effect of respiratory influenza virus infection on a subsequent systemic bacterial infection. We found that influenza infection triggered a generalized stress response leading to a sustained increase in serum glucocorticoid levels, resulting in a systemic suppression of immune responses. However, virus-induced glucocorticoid production was necessary to control the inflammatory response and prevent lethal immunopathology during coinfection. This study demonstrates that activation of the hypothalamic-pituitary-adrenal axis controls the balance between immune defense and immunopathology and is an important component of the host response to coinfection.
ROBINSON KM,CHOI SM,MCHUGH KJ,et al.Influenza a exacerbates Staphylococcus aureus pneumonia by attenuating IL-1β production in mice[J].J Immunol,2013,191(10):5153-5159.
Pneumonia is a leading cause of death worldwide. Staphylococcal aureus can be a cause of severe pneumonia alone or a common pathogen in secondary pneumonia following influenza. Recently, we reported that preceding influenza attenuated the Type 17 pathway, increasing the lung's susceptibility to secondary infection. IL-1β is known to regulate host defense, including playing a role in Th17 polarization. We examined whether IL-1β signaling is required for S. aureus host defense and whether influenza infection impacted S. aureus-induced IL-1β production and subsequent Type 17 pathway activation. Mice were challenged with S. aureus (USA 300), with or without preceding Influenza A/PR/8/34 H1N1 infection. IL-1R1(-/-) mice had significantly higher S. aureus burden, increased mortality, and decreased Type 17 pathway activation following S. aureus challenge. Coinfected mice had significantly decreased IL-1β production versus S. aureus infection alone at early time points following bacterial challenge. Preceding influenza did not attenuate S. aureus-induced inflammasome activation, but there was early suppression of NF-κB activation, suggesting an inhibition of NF-κB-dependent transcription of pro-IL-1β. Furthermore, overexpression of IL-1β in influenza and S. aureus-coinfected mice rescued the induction of IL-17 and IL-22 by S. aureus and improved bacterial clearance. Finally, exogenous IL-1β did not significantly rescue S. aureus host defense during coinfection in IL-17RA(-/-) mice or in mice in which IL-17 and IL-22 activity were blocked. These data reveal a novel mechanism by which Influenza A inhibits S. aureus-induced IL-1β production, resulting in attenuation of Type 17 immunity and increased susceptibility to bacterial infection.
ALYMOVA IV,SAMARASINGHEA,VOGELP,et al.A novel cytotoxic sequence contributes to influenza a viral protein PB1-F2 pathogenicity and predisposition to secondary bacterial infection[J].J Virol,2014,88(1):503-515.
Enhancement of cell death is a distinguishing feature of H1N1 influenza virus A/Puerto Rico/8/34 protein PB1-F2. Comparing the sequences (amino acids [aa] 61 to 87 using PB1-F2 amino acid numbering) of the PB1-F2-derived C-terminal peptides from influenza A viruses inducing high or low levels of cell death, we identified a unique I68, L69, and V70 motif in A/Puerto Rico/8/34 PB1-F2 responsible for promotion of the peptide's cytotoxicity and permeabilization of the mitochondrial membrane. When administered to mice, a 27-mer PB1-F2-derived C-terminal peptide with this amino acid motif caused significantly greater weight loss and pulmonary inflammation than the peptide without it (due to I68T, L69Q, and V70G mutations). Similar to the wild-type peptide, A/Puerto Rico/8/34 elicited significantly higher levels of macrophages, neutrophils, and cytokines in the bronchoalveolar lavage fluid of mice than its mutant counterpart 7 days after infection. Additionally, infection of mice with A/Puerto Rico/8/34 significantly enhanced the levels of morphologically transformed epithelial and immune mononuclear cells recruited in the airways compared with the mutant virus. In the mouse bacterial superinfection model, both peptide and virus with the I68, L69, and V70 sequence accelerated development of pneumococcal pneumonia, as reflected by increased levels of viral and bacterial lung titers and by greater mortality. Here we provide evidence suggesting that the newly identified cytotoxic sequence I68, L69, and V70 of A/Puerto Rico/8/34 PB1-F2 contributes to the pathogenesis of both primary viral and secondary bacterial infections.
, 王世强
