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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by collagen deposition within the lung interstitium. Bacterial infection is associated with increased morbidity and more rapid mortality in IPF patient populations, and pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are commonly isolated from the lungs of hospitalized patients with IPF. Despite this, the effects of fibrotic lung injury on critical immune responses to infection remain unknown. In the present study, we show that, like humans with IPF, fibrotic mice infected with MRSA exhibit increased morbidity and mortality compared with uninfected fibrotic mice. We determine that fibrosis conferred a defect in MRSA clearance compared with nonfibrotic mice, resulting from blunted innate immune responses. We show that fibrosis inhibited neutrophil intracellular killing of MRSA through impaired neutrophil elastase release and oxidative radical production. Additionally, we demonstrate that lung macrophages from fibrotic mice have impaired phagocytosis of MRSA. Our study describes potentially novel impairments of antimicrobial responses upon pulmonary fibrosis development, and our findings suggest a possible mechanism for why patients with IPF are at greater risk of morbidity and mortality related to infection.

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

Acute chest syndrome (ACS) is the most serious complication of sickle cell disease. The pathophysiology of ACS may involve lower respiratory tract infection (LRTI), alveolar hypoventilation and atelectasis, bone infarcts-driven fat embolism, and in situ pulmonary artery thrombosis. One of the most challenging issues for the physicians is to diagnose LRTI as the cause of ACS. The use of a respiratory multiplex PCR (mPCR) for the diagnosis of LRTI has not been assessed in sickle-cell adult patients with ACS. To describe the spectrum of infectious aetiologies of severe ACS, using a diagnostic approach combining conventional tests and mPCR. A non-interventional monocenter prospective study involving all the consecutive sickle-cell adult patients with ACS admitted to the intensive care unit (ICU). Microbiological investigation included conventional tests and a nasopharyngeal swab for mPCR. Altogether, 36 patients were enrolled, of whom 30 (83%) had complete microbiological investigations. A bacterial microorganism, mostly Staphylococcus aureus (n = 8), was identified in 11 patients. There was no pneumonia-associated intracellular bacterial pathogen. A respiratory virus was identified in six patients. Using both conventional tests and nasopharyngeal mPCR, a microbiological documentation was obtained in half of adult ACS patients admitted to the ICU. Pyogenic bacteria, especially S. aureus, predominated.

Background: The 2019 community-acquired pneumonia guidelines recommend using recent respiratory cultures and locally validated epidemiology plus risk factor assessment to determine empirical coverage of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa ., Objective: To develop a methodology for evaluating local epidemiology and validating local risk factors for P aeruginosa and MRSA., Methods: This multicenter, retrospective cohort evaluated adult patients admitted for pneumonia. Risk factors for MRSA and P aeruginosa were evaluated using multivariable logistic regression and reported as adjusted odds ratios (aORs)., Results: There were 10 723 cases evaluated. Lung abscess/empyema had the highest odds associated with MRSA (aOR = 4.24; P < 0.0001), followed by influenza (aOR = 2.34; P = 0.01), end-stage renal disease (ESRD; aOR = 2.09; P = 0.006), illicit substance use (aOR = 1.7; P = 0.007), and chronic obstructive pulmonary disease (COPD; aOR = 1.26; P = 0.04). For P aeruginosa, the highest odds were in bronchiectasis (aOR = 6.13; P < 0.0001), lung abscess/empyema (aOR = 3.36; P = 0.005), and COPD (aOR = 1.84; P < 0.0001). Isolated COPD without other risk factors did not pose an increased risk of either organism., Conclusion and Relevance: Influenza, ESRD, lung abscess/empyema, and illicit substance use were local risk factors for MRSA. Bronchiectasis and lung abscess/empyema were risk factors for Pseudomonas . COPD was associated with MRSA and Pseudomonas . However, isolated COPD had similar rates of MRSA and Pseudomonas pneumonia compared with the total population. This study established a feasible methodology for evaluating local risk factors.

COVID-19 is a new disease with many undescribed clinical manifestations. We report herein a case of severe immune thrombocytopenic purpura (ITP) in a critical COVID-19 patient. A patient presented a severe episode of immune thrombocytopenia (< 10 × 10 9 /L) 20 days after admission for a critical COVID-19. This thrombocytopenia was associated with a life-threatening bleeding. Response to first-line therapies was delayed as it took up to 13 days after initiation of intravenous immunoglobulin and high-dose dexamethasone to observe an increase in platelet count. COVID-19 may be associated with late presenting severe ITP. Such ITP may also be relatively resistant to first-line agents. Hematological manifestations of COVID-19, such as the ones associated with life-threatening bleeding, must be recognized.

Objectives: Secondary bacterial pneumonia is common following influenza infection. However, it remains unclear about the underlying molecular mechanisms., Materials and Methods: We established a mouse model of post-influenza S aureus pneumonia using conditional Shp2 knockout mice (LysM Cre/+ :Shp2 flox/flox ). The survival, bacterial clearance, pulmonary histology, phenotype of macrophages, and expression of type I interferons and chemokines were assessed between SHP2 deletion and control mice (Shp2 flox/flox ). We infused additional KC and MIP-2 to examine the reconstitution of antibacterial immune response in LysM Cre/+ :Shp2 flox/flox mice. The effect of SHP2 on signal molecules including MAPKs (JNK, p38 and Erk1/2), NF-κB p65 and IRF3 was further detected., Results: LysM Cre/+ :Shp2 flox/flox mice displayed impaired antibacterial immunity and high mortality compared with control mice in post-influenza S aureus pneumonia. The attenuated antibacterial ability was associated with the induction of type I interferon and suppression of chemo-attractants KC and MIP-2, which reduced the infiltration of neutrophils into the lung upon secondary bacterial invasion. In additional, Shp2 knockout mice displayed enhanced polarization to alternatively activated macrophages (M2 phenotype). Further in vitro analyses consistently demonstrated that SHP2-deficient macrophages were skewed towards an M2 phenotype and had a decreased antibacterial capacity. Moreover, SHP2 modulated the inflammatory response to secondary bacterial infection via interfering with NF-κB and IRF3 signalling in macrophages., Conclusions: Our findings reveal that the SHP2 expression enhances the host immune response and prompts bacterial clearance in post-influenza S aureus pneumonia., (© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Common variable immunodeficiency (CVID) refers to a group of disorders where differentiation and maturation of B cells into plasma cells are affected, leading to decreased or defective immunoglobulin production and subsequent immunodeficiency. Symptoms may present at any age between 5 and 72 years, although more severe forms often manifest earlier in life. Milder forms may not be detected. We present an intriguing case of a 69-year-old man presenting with recurrent pneumonia caused by a rare organism Staphylococcus lugdunensis , eventually determined to be caused by CVID. The patient had a good clinical outcome after receiving immunoglobulin replacement therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in cystic fibrosis (CF), with increasing incidence in recent years. We examined the association between bacterial colonization in the sputum (MRSA with or without pseudomonas (PA)) and computed tomography (CT) scores in CF patients., Methods: MRSA patients were divided according to PA status based on at least three consecutive sputum cultures; controls were patients without MRSA (with or without PA), matched for gender and age at CT. Clinical data and CT scores were compared between groups., Results: Of 33 patients with MRSA, 14 had no PA (MRSA + PA-) and 19 had also PA (MRSA + PA+). MRSA + PA- and MRSA + PA+ patients had CT scores similar to their controls PA+ (38.25 ± 20.18 vs. 32.22 ± 18.74, P = .4, and 41.88 ± 18.18 vs. 45.33 ± 11.5, P = .4, respectively). Although MRSA + PA- had worse CT scores than their matched PA- controls, their mean FEV1 values were similar., Conclusions: Colonization with MRSA in CF is associated with structural CT changes at least similar to those in PA. A cause and effect relationship cannot be established. The current findings call for a larger study assessing longitudinally the impact of MRSA acquisition and eradication protocols., (© 2016 John Wiley & Sons Ltd.)

Mitochondrial damage is often overlooked in acute lung injury (ALI), yet most of the lung's physiological processes, such as airway tone, mucociliary clearance, ventilation-perfusion (Va/Q) matching, and immune surveillance require aerobic energy provision. Because the cell's mitochondrial quality control (QC) process regulates the elimination and replacement of damaged mitochondria to maintain cell survival, we serially evaluated mitochondrial biogenesis and mitophagy in the alveolar regions of mice in a validated Staphylococcus aureus pneumonia model. We report that apart from cell lysis by direct contact with microbes, modest epithelial cell death was detected despite significant mitochondrial damage. Cell death by TdT-mediated dUTP nick-end labeling staining occurred on days 1 and 2 postinoculation: apoptosis shown by caspase-3 cleavage was present on days 1 and 2, while necroptosis shown by increased levels of phospho- mixed lineage kinase domain-like protein (MLKL) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was present on day 1 Cell death in alveolar type I (AT 1 ) cells assessed by bronchoalveolar lavage fluid receptor for advanced glycation end points (RAGE) levels was high, yet AT 2 cell death was limited while both mitochondrial biogenesis and mitophagy were induced. These mitochondrial QC mechanisms were evaluated mainly in AT 2 cells by localizing increases in citrate synthase content, increases in nuclear mitochondrial biogenesis regulators nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and increases in light chain 3B protein (LC3-I)/LC3II ratios. Concomitant changes in p62, Pink 1, and Parkin protein levels indicated activation of mitophagy. By confocal microscopy, mitochondrial biogenesis and mitophagy were often observed on day 1 within the same AT 2 cells. These findings imply that mitochondrial QC activation in pneumonia-damaged AT 2 cells promotes cell survival in support of alveolar function., (Copyright © 2017 the American Physiological Society.)

Background: Nosocomial pneumonias are common in trauma patients and so interventions to prevent and treat nosocomial pneumonia may improve outcomes. Our prior work strongly suggests that tissue injury predisposes to infections like nosocomial pneumonia because mitochondrial debris originating from injured cells contains damage-associated molecular patterns that can reduce neutrophil (PMN) migration into the airway and diminish PMN function in response to bacterial inoculation of the airway. This suggested that putting exogenous "normal" PMN into the airway might be beneficial., Methods: Postinjury pneumonia (PNA) commonly arises in two groups, early, community-acquired PNA (CAP) and later hospital-acquired PNA (HAP). Posttraumatic early-onset CAP and late-onset HAP were modeled in CD-1 mice using Staphylococcus aureus or Pseudomonas aeruginosa instilled intratracheal (i.t.) at clinically relevant times with or without extrapulmonary injuries mimicked by an intraperitoneal application of mitochondrial damage-associated molecular patterns. We applied bone marrow-derived PMN (BM-PMN) intratracheally to assess their effect on bacterial clearance in the lung., Results: BM-PMN instillation i.t. had no untoward clinical effects on recipient animals. In both the early/CAP and late/HAP models, clearance of the bacterial inoculum from the lung was suppressed by mitochondrial debris and restored to uninjured levels by i.t. instillation of exogenous BM-PMN. Furthermore, PMN instillation cleared the inoculum of P. aeruginosa that could not be cleared by uninjured mice. Instillation of PMN into the lung, even across strains (CD-1 vs. C57BL/6) had no injurious effect., Conclusion: These initial studies suggest PMN instillation (i.t.) is worthy of further study as a potential adjunctive therapy aimed at decreasing the morbidity of lung infections in trauma patients. Moreover, PMN instillation (i.t.) may represent a unique means of preventing or treating pneumonia after serious injury that is completely independent of the need for antibiotic use.

Congenital pulmonary airway malformation (CPAM) is a rare congenital abnormality with unknown exact aetiology or clear genetic association. It is characterised by a failure of bronchial development and localised glandular overgrowth. Typically, it is diagnosed on prenatal ultrasound, only infrequently in children, and even less commonly in adults. We present a case of a 25-year-old man, with no previous lung diseases who presented with right-sided chest pain, fever and cough suggestive of pulmonary infection. Chest imaging, including CT scan, showed a large focal cystic mass within the right lower lobe along with ground glass opacities suggestive of CPAM. He was started on intravenous antibiotics. Bronchoscopy showed a large amount of pus in the right lung and bronchoalveolar lavage confirmed the microbiological diagnosis of methicillin-resistant Staphylococcus aureus. He improved with antibiotic treatment. He was discharged with 6-week course of antibiotics and follow-up afterward., (2016 BMJ Publishing Group Ltd.)

Unlabelled: Staphylococcus aureus is a ubiquitous opportunistic human pathogen and a major health concern worldwide, causing a wide variety of diseases from mild skin infections to systemic disease. S. aureus is a major source of severe secondary bacterial pneumonia after influenza A virus infection, which causes widespread morbidity and mortality. While the phenomenon of secondary bacterial pneumonia is well established, the mechanisms behind the transition from asymptomatic colonization to invasive staphylococcal disease following viral infection remains unknown. In this report, we have shown that S. aureus biofilms, grown on an upper respiratory epithelial substratum, disperse in response to host physiologic changes related to viral infection, such as febrile range temperatures, exogenous ATP, norepinephrine, and increased glucose. Mice that were colonized with S. aureus and subsequently exposed to these physiologic stimuli or influenza A virus coinfection developed pronounced pneumonia. This study provides novel insight into the transition from colonization to invasive disease, providing a better understanding of the events involved in the pathogenesis of secondary staphylococcal pneumonia., Importance: In this study, we have determined that host physiologic changes related to influenza A virus infection causes S. aureus to disperse from a biofilm state. Additionally, we report that these same host physiologic changes promote S. aureus dissemination from the nasal tissue to the lungs in an animal model. Furthermore, this study identifies important aspects involved in the transition of S. aureus from asymptomatic colonization to pneumonia., (Copyright © 2016 Reddinger et al.)

Background: The risk factors for Staphylococcus aureus (S. aureus) pneumonia are not fully identified. The aim of this work was to find out the clinical characteristics associated with S. aureus infection in patients with healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), which may be applicable for more appropriate selection of empiric antibiotic therapy., Methods: From July 2007 to June 2010, patients who were admitted to the intensive care unit with severe HCAP/HAP and severe sepsis were enrolled in this study. Lower respiratory tract sample was semiquantitatively cultured. Initial broad-spectrum antibiotics were chosen by Taiwan or American guidelines for pneumonia management. Standard bundle therapies were provided to all patients according to the guidelines of the Surviving Sepsis Campaign., Results: The most frequently isolated pathogens were Pseudomonas aeruginosa, S. aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Patients with positive isolation of S. aureus in culture had significantly higher history of liver cirrhosis and diabetes mellitus, with odds ratios of 3.098 and 1.899, respectively. The S. aureus pneumonia was not correlated with history of chronic obstructive pulmonary disease, hypertension, and hemodialysis., Conclusion: Liver cirrhosis and diabetes mellitus may be risk factors for S. aureus infection in patients with severe HCAP or HAP.

While visiting Malaysia, a 22-year-old previously healthy Japanese man developed myalgia, headache, and fever, leading to a diagnosis of classical dengue fever. After improvement and returning to Japan after a five day hospitalization, he developed productive cough several days after defervescing from dengue. Computed tomography (CT) thorax scan showed multiple lung cavities. A sputum smear revealed leukocytes with phagocytized gram-positive cocci in clusters, and grew an isolate Staphylococcus aureus sensitive to semi-synthetic penicillin; he was treated successfully with ceftriaxone and cephalexin. This second reported case of pneumonia due to S. aureus occurring after dengue fever, was associated both with nosocomial exposure and might have been associated with dengue-associated immunosuppression. Clinicians should pay systematic attention to bacterial pneumonia following dengue fever to establish whether such a connection is causally associated., (© The American Society of Tropical Medicine and Hygiene.)

Colonization with Staphylococcal aureus is markedly more frequent in individuals with atopic dermatitis (AD) than in unaffected individuals. Chronic scratching leads to worsening of an existing defect in the epidermal barrier, which can allow S. aureus invasion into the bloodstream and subsequent systemic infections. We report two unusual cases of systemic illness in individuals with AD. One developed infective endocarditis followed by a stroke and the other developed septic arthritis and osteomyelitis. We performed an extensive literature review of reported systemic complications caused by S. aureus in patients with AD. Although reports are rare, practitioners should be aware of these important, albeit unlikely, complications of staphylococcal superinfections in individuals with AD., (© 2015 Wiley Periodicals, Inc.)

Background: Increasing evidence has indicated that Staphylococcus aureus pneumonia complicated with influenza virus infection is often fatal. In these cases, disease severity is typically determined by susceptibility to antimicrobial agents and the presence of high-virulence factors that are produced by Staphylococcus aureus, such as Panton-Valentine leukocidin (PVL)., Case Report: We describe a rare case of fatal community-acquired pneumonia caused by methicillin-sensitive Staphylococcus aureus (MSSA), which did not secrete major high-virulence factors and coexisted with influenza type B infection. The 32-year-old previously healthy male patient presented with dyspnea, high fever, and cough. His roommate had been diagnosed with influenza B virus infection 3 days earlier. Gram-positive clusters of cocci were detected in the patient's sputum; therefore, he was diagnosed with severe pneumonia and septic shock, and was admitted to the intensive care unit. Despite intensive antibiotic and antiviral treatment, he died of multiple organ failure 5 days after admission. His blood culture from the admission was positive for MSSA, and further analysis revealed that the strain was negative for major high-virulence factors, including PVL and enterotoxins, although influenza B virus RNA was detected by PCR., Conclusions: Physicians should pay special attention to patients with pneumonia following influenza and Staphylococcus aureus infection, as it may be fatal, even if the Staphylococcus aureus strain is PVL-negative and sensitive to antimicrobial agents.

Nosocomial pneumonia (NP; encompassing hospital-acquired, health care-associated and ventilator-associated pneumonia) is one of the most common nosocomial infections and is associated with a mortality rate of 18.7%-40.8% in Asian countries. The burden of methicillin-resistant Staphylococcus aureus (MRSA) infections in Asia is high, and approximately 13% of NP cases in Asia are caused by this pathogen. Evidence regarding optimal management of MRSA NP continues to evolve and is complicated by the fact that a significant proportion of cases are likely to be caused by isolates with reduced susceptibility to the main therapeutic agent, vancomycin. The Asian Consensus Taskforce on MRSA Nosocomial Pneumonia has developed this statement to provide consensus points on diagnosis, antimicrobial treatment and prevention strategies for MRSA NP in the Asian context, based on our review of Asian data, previous international guidelines and recent scientific evidence., (© 2014 John Wiley & Sons Ltd.)

Postinfluenza bacterial pneumonia is a leading cause of influenza-associated death, and Staphylococcus aureus and Streptococcus pneumoniae have been important pathogens that have caused pneumonia since the influenza pandemic in 1919. Emergence of novel influenza A (H1N1) pdm09 and the concomitant global spread of community-associated methicillin-resistant S. aureus (CA-MRSA) have led to increasing prevalence of CA-MRSA pneumonia following influenza infection. Such an epidemiologic change poses a therapeutic challenge due to a high risk of inappropriate empiric antimicrobial therapy and poor clinical outcomes. Early diagnosis and initiation of appropriate antimicrobial therapy for post-influenza bacterial pneumonia have become even more important in the era of CA-MRSA. Therefore, novel molecular diagnostic techniques should be applied to more readily diagnose MRSA pneumonia.

Objective: Describe the epidemiology of healthcare-related (ie, healthcare-associated and hospital-acquired) pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) among hospitalized patients in community hospitals., Design: Retrospective cohort study., Setting: Twenty-four community hospitals in the southeastern United States affiliated with the Duke Infection Control Outreach Network (median size, 211 beds; range, 103-658 beds)., Methods: Adult patients with healthcare-related MRSA pneumonia admitted to study hospitals from January 1, 2008, to December 31, 2012, were identified using surveillance data. Seasonal and annual incidence rates (cases per 100,000 patient-days) were estimated using generalized estimating equation models. Characteristics of community-onset and hospital-onset cases were compared., Results: A total of 1,048 cases of healthcare-related pneumonia due to MRSA were observed during 5,863,941 patient-days. The annual incidence rate of healthcare-related MRSA pneumonia increased from 11.3 cases per 100,000 patient-days (95% confidence interval [CI], 6.8-18.7) in 2008 to 15.5 cases per 100,000 patient-days (95% CI, 8.4-28.5) in 2012 (P = .055). The incidence rate was highest in winter months and lowest in summer months (15.4 vs 11.1 cases per 100,000 patient-days; incidence rate ratio, 1.39 [95% CI, 1.06-1.82]; P = .016). A total of 814 cases (77.7%) were community-onset healthcare-associated pneumonia cases; only 49 cases (4.7%) were ventilator-associated cases. Of 811 patients whose disposition was known, 240 (29.6%) died during hospitalization or were discharged to hospice., Conclusions: From 2008 through 2012, the incidence of healthcare-related MRSA pneumonia among patients who were admitted to a large network of community hospitals increased, despite the decreasing incidence of invasive MRSA infections nationwide. Additional study is warranted to evaluate trends in this important and potentially modifiable public health problem.

Objectives: Community-acquired Staphylococcus aureus necrotizing pneumonia is a life-threatening disease. Panton Valentine Leukocidin (PVL) has been associated with necrotizing pneumonia. PVL triggers inflammasome activation in human macrophages leading to IL-1β release. IL-1β activates lung epithelial cells to release IL-8. This study aimed to assess the relevance of this inflammatory cascade in vivo and to test the potential of an IL-1 receptor antagonist (IL-1Ra/Kineret) to decrease inflammation-mediated lung injury., Methods: We used the sequential instillation of Heat-killed S. aureus and PVL or S. aureus infection to trigger necrotizing pneumonia in rabbits. In these models, we investigated inflammation in the presence or absence of IL-1Ra/Kineret., Results: We demonstrated that the presence of PVL was associated with IL-1β and IL-8 release in the lung. During PVL-mediated sterile pneumonia, Kineret/IL-1Ra reduced IL-8 production indicating the relevance of the PVL/IL-1/IL-8 cascade in vivo and the potential of Kineret/IL-1Ra to reduce lung inflammation. However, Kineret/IL-1Ra was ineffective in blocking IL-8 production during infection with S. aureus. Furthermore, treatment with Kineret increased the bacterial burden in the lung., Conclusions: Our data demonstrate PVL-dependent inflammasome activation during S.aureus pneumonia, indicate that IL-1 signaling controls bacterial burden in the lung and suggest that therapy aimed at targeting this pathway might be deleterious during pneumonia.

We describe a case of Staphylococcus aureus sepsis after acupuncture for chronic fatigue syndrome (CFS). Sepsis is a rare, but potentially fatal complication of acupuncture. The most common cause of bacterial infection after acupuncture is S. aureus. The effectiveness of acupuncture for the treatment of CFS is not proven, therefore the potential benefits should be weighed against the risks.

A chest X-ray of a young healthy African-American man with acute respiratory failure revealed bilateral multiple nodular shadows in the lungs, while community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was detected in blood and sputum cultures. Magnetic resonance imaging showed osteomyelitis of the left thigh, and computed tomography revealed bilateral cavitary lesions in the chest, indicating necrotizing pneumonia with pulmonary embolism caused by osteomyelitis as a result of infection with CA-MRSA. CA-MRSA should be suspected as a causative agent of severe community-acquired pneumonia, even in Japan, among patients who belong to communities at high risk of CA-MRSA infection.

Objectives: To determine primarily (1) the incidence of ventilator-associated pneumonia (VAP) among ventilated patients aged 1 month to 12 years and secondarily (2) the risk factors for VAP and (3) common organisms causing VAP., Study Design and Setting: Prospective study in a tertiary care center in India. Consecutive ventilated patients aged ≥1 month and ≤12 years and requiring mechanical ventilation (MV) for ≥48 hours were included after written informed parental consent. For the diagnosis of VAP, National Nosocomial Infections Surveillance System criteria of 1996 were used., Results: Incidence of VAP among patients aged 1 month to 12 years was 36.2% (38/105; 95% confidence interval [CI]: 27, 46). In unconditional logistic regression analysis controlling for the presence of underlying illnesses, risk factor for VAP was >4 days of MV (adjusted odds ratio, 3.76; 95% CI: 1.41, 10.02; P = 0.008). Reintubation within 72 hours of extubation and more than two attendants at the time of recruitment showed increased tendency for the development of VAP but did not reach statistical significance. Endotracheal and endobronchial aspirates were positive for organism in 19.05% (20/105) and 37.14% (39/105) of patients, respectively., Conclusion: Almost one-third of ventilated patients develop VAP. Vigilance for the development of VAP has to be kept on those requiring >4 days of MV. Klebsiella and Staphylococcus aureus were common bacterial isolates in such patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most successful community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA has been predominant in Korea, and there has been no report of infections by the USA300 strain except only one case report of perianal infection. Here, we describe the first case of pneumonia caused by the USA300 strain following pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever and cough and chest radiograph showed pneumonic consolidation at the right lower lung zone. He received a ventilator support because of respiratory failure. PCR for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE patterns showed that this isolate was the same pulsotype as the USA300 strain.

Background and Objective: To include a specific antibiotic in the empiric therapy, it is necessary to predict when a nosocomial pneumonia (NP) is caused by methicillin-resistant Staphylococcus aureus (MRSA). We have developed a model for the prediction of the probability of a NP being caused by MRSA, when the carrier status and the microbiological diagnosis are unknown., Patients and Methods: A retrospective case-control study (1999-2005) was designed. A univariate and multivariate logistic regression was performed to identify the risk factors for suffering a NP due to MRSA. Demographic factors, related to hospitalization, immunosuppression or neutropenia, to medication and severity were included., Results: Three hundred and sixty three patients (121 cases and 242 controls) were studied. The final model of multivariate logistic regression included an age>14 years (OR 7.4, CI 95% 1.5-37.4, P<.015), NP appearance>6 days after admittance (OR 4.1, CI 95% 2.4-7,1, P<.001), NP development excluding summers (OR 2.5, CI 95% 1.2-5.2, P<.015), respiratory diseases (OR 4.9, CI 95% 1.5-15.8, P<.007) and multilobar involvement (OR 4, CI 95% 2.3-7.2, P<.001).The probability of developing a pneumonia due to MRSA was studied for each of the possible combinations and subsequently classified in minor and major criteria., Conclusions: MRSA coverage should be included in the empirical treatment of NP when: a) an adult patient (>14 years old) presents, at least, 2 major criteria or 1 major criterion together with 2 minor criteria, and b) a patient <14 years-old has 2 major criteria as well as 2 minor criteria., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

We herein report a case of toxic shock syndrome (TSS) associated with the 2009 pandemic H1N1 (pH1N1) influenza virus and a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in a 16-year-old Vietnamese girl. Staphylococcal enterotoxin B (SEB) was detected in the patient's serum, and the level of anti-SEB antibodies was found to be elevated. A flow cytometric analysis showed evidence of activated SEB-reactive Vβ3+ and Vβ12+ T cells. These data suggest that the CA-MRSA-induced activation of SEB-reactive T cells may cause TSS in patients with pH1N1 virus infection. Moreover, this is the first report describing immunological confirmation of SEB contributing directly to TSS in a patient fulfilling the diagnostic criteria of TSS.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is epidemic in the United States, even rivaling HIV/AIDS in its public health impact. The pandemic clone USA300, like other CA-MRSA strains, expresses Panton-Valentine leukocidin (PVL), a pore-forming toxin that targets polymorphonuclear leukocytes (PMNs). PVL is thought to play a key role in the pathogenesis of necrotizing pneumonia, but data from rodent infection models are inconclusive. Rodent PMNs are less susceptible than human PMNs to PVL-induced cytolysis, whereas rabbit PMNs, like those of humans, are highly susceptible to PVL-induced cytolysis. This difference in target cell susceptibility could affect results of experimental models. Therefore, we developed a rabbit model of necrotizing pneumonia to compare the virulence of a USA300 wild-type strain with that of isogenic PVL-deletion mutant and -complemented strains. PVL enhanced the capacity of USA300 to cause severe lung necrosis, pulmonary edema, alveolar hemorrhage, hemoptysis, and death, hallmark clinical features of fatal human necrotizing pneumonia. Purified PVL instilled directly into the lung caused lung inflammation and injury by recruiting and lysing PMNs, which damage the lung by releasing cytotoxic granule contents. These findings provide insights into the mechanism of PVL-induced lung injury and inflammation and demonstrate the utility of the rabbit for studying PVL-mediated pathogenesis.

Hyper-immunoglobulin E syndromes (HIES) including compound primary immunodeficiency and nonimmunological abnormalities are characterized by extremely high serum IgE levels, eosinophilia, eczema, susceptibility to infections, distinctive facial appearance, retention of deciduous teeth, cyst-forming pneumonias, and skeletal abnormalities. Itis reported that some cases of familial HIES are relative to autosomal dominant or recessive inheritance, but most cases are sporadic, and result from mutations in the human signal transducer and activator of transcription 3 (STAT3) gene. In this paper, we firstly report a young man diagnosed of Hyper-IgE syndrome with STAT3 mutation in Mainland China, and investigate the autosomal dominant trait of his family members.

Introduction: Pneumonia in patients with head trauma occurs commonly; however, few data are available to evaluate the effects of the infection on the prognosis., Objective: The incidence and microbiological findings were described, and the associated risk factors were established with the appearance of pneumonia in patients with severe brain trauma., Materials and Methods: A prospective cohort study was conducted that included 39 patients with severe brain trauma and who required mechanical ventilation; initially, none had pneumonia. These patients were observed during a 24-month period in an attempt to discern the principal risk factors associated with the onset of pneumonia., Results: Pneumonia occurred in 31 (80%) of the 39 patients, and 28 of these presented early pneumonia. The most frequent germ in patients with pneumonia was Staphylococcus aureus with a percentage of the 42.4%. In the multivariate analysis, the single statistically significant risk factor was the presence of hypotension and vasopressor support with a RR = 27.9 (95% CI = 1.0-749.9, p < 0.05). No significant differences in the days of mechanical ventilation or mortality in both groups. The major mortality-associated risk factor in patients with pneumonia was a low Glasgow score at admittance with an OR = 2.19 (95% CI 1.03 - 4.65), p < 0.05., Conclusions: The incidence of pneumonia in patients with severe brain trauma is high; however, its appearance does not affect the prognosis. The single significant risk factor was the presence of hypotension and vasopressor support.

A 30-year-old man presented with community-acquired pneumonia (CAP), directly following influenza. Sputum Gram stain confirmed Staphylococcus aureus pneumonia. Initial empirical antimicrobial therapy did not cover S. aureus. The isolated S. aureus strain contained genes encoding exotoxins, such as Panton-Valentine leukocidin (PVL). This exotoxin is associated with high mortality and methicillin resistance, but in this patient the strain was susceptible to methicillin. The patient died. In the Netherlands the risk of methicillin resistance in PVL-positive S. aureus CAP is low but real. This should be taken into account when selecting empirical treatment, which can include the combination of flucloxacillin and rifampicin. This case report illustrates the difficulty in predicting the causative agent in CAP and highlights the usefulness of the sputum Gram stain. Moreover, clinical awareness and recognition of S. aureus CAP remains essential to the early initiation of directed therapy.

The authors describe a one-year-old girl with a fronto-ethmoidal encephalomeningocele who developed wound infection, purulent meningitis and septic shock 5 hours after operation. The patient was treated with intravenous ceftazidime and vancomycin empirically. The cerebrospinal fluid (CSF) and eye discharge grew Streptococcus pneumoniae (S. pneumoniae). The minimal inhibitory concentration (MIC) by E-test of penicillin and cefotaxime were 1.0 and 0.38 ug/ml respectively so the antibiotics were switched to cefotaxime 300 mg/kg/day. She recovered completely after appropriate treatment. Penicillin-non-susceptible S. pneumoniae should be considered as one of the causes of post-operative serious infection of the face and neck in the era of increasing prevalence of penicillin-resistant S. pneumoniae.

We report cases of immunocompetent patients showing multiple abscesses by a Panton-Valentine leukocidin (PVL) positive Staphylococcus aureus. PVL is considered to be an important virulence factor. The most common manifestations by this pathogen are recurrent or multiple abscesses of the skin. Seldom necrotizing pneumonia with high mortality occurs. Even methicillin-resistant PVL positive isolates have been identified in Germany. Only appropriate infection control measures in combination with antimicrobial therapy resulted in successful eradication of this pathogen. Dermatologists should be informed about this specific type of infection and about the appropriate infection control measures.

We describe 3 patients with methicillin-resistant Staphylococcus aureus, hospital-acquired pneumonia who demonstrated a microbiological and clinical failure with vancomycin despite adequate trough levels. All 3 patients were cured with linezolid.

Pulmonary infections are a significant cause of morbidity and mortality after liver transplantation. Infections with methicillin-resistant Staphylococcus aureus (MRSA) have increased in the last 10 years. Mortality may exceed 80% in liver transplant recipients who develop MRSA pneumonia. A 57-year-old male following living-donor liver transplantation developed a right-sided MRSA pneumonia 6 weeks after transplantation, which required artificial ventilation for 14 weeks. Initially, pneumonia was treated with linezolid. However, after 12 days under current therapy, the infection spread out to both lungs. At that time. we initiated the treatment with tigecycline. Under this therapy, the patient could be cured from MRSA pneumonia and was extubated. We detected no tigecycline related hepatotoxic effect. In conclusion, this case suggests that tigecycline may be useful in the salvage therapy of pneumonia due to MRSA after linezolid failure., ((c) 2006 AASLD)

Hospital-acquired pneumonia is a common nosocomial infection, with significant morbidity and mortality, and represents a major therapeutic challenge to clinicians. The therapeutic approach must be patient-oriented and institution-specific. The specific risk factors of each patient, such as previous antibiotic exposure, underlying diseases, length of hospital stay and the local patterns of antimicrobial resistance, should guide physicians in their decision of the initial optimal empirical therapy. Delays in the initiation or inappropriate/inadequate initial therapy are related to increased mortality and worse outcomes. In responding patients, as soon as culture data are available, efforts should be made to change the initial broad spectrum antibiotic regimen to a more targeted one (de-escalation). The optimal duration of treatment is a matter of debate, but courses longer than 1 week are rarely justified.

The recent worldwide surge in the incidence of fatal pneumonia caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has generated renewed interest in this well-known organism. We describe two cases of fulminant bacteraemic pneumonia due to CA-MRSA at the National University Hospital in Singapore and provide further epidemiological descriptors of this potentially-deadly disease. The first patient was an 83-year-old woman while the second was a 71-year-old man, none of whom had risk factors for hospital-acquired MRSA colonisation. Clinicians should be aware of the possibility of severe community-acquired pneumonia caused by this organism. Adequate empirical antimicrobial coverage for this important pathogen should be considered.

A young woman presented with pneumonia of a 3-month duration with predominantly nodular pulmonary infiltrates. Methicillin-resistant Staphylococcus aureus was identified in multiple cultures of sputum specimens. According to findings of pulsed-field gel electrophoresis, the isolate was identical to USA 300 and carried a type IV Staphylococcus cassette chromosome mec type IV gene and the genes for Panton-Valentine leukocidin.

Estimating the consequences and the cost of methicillin resistance is a difficult challenge. Patients who develop methicillin-resistant ventilator-associated pneumonia (VAP) are very different from those who develop methicillin-sensitive VAP, and biased estimates are frequent. We reviewed some important confounding factors of which the reader should be aware.

Objective: To determine the incidence, risk factors, associated pathogens, and outcome of ventilator-associated pneumonia (VAP) in patients admitted to a coronary care unit (CCU)., Patients and Methods: This retrospective cohort study was performed in the CCU of a single tertiary medical center. Patients who were admitted to the CCU between March 23, 2002, and May 25, 2003, and who required invasive mechanical ventilation for more than 48 hours were included., Results: Of the 92 patients who met the study criteria, 17 (18.5%; 95% confidence interval, 11.9%-27.6%) developed VAP. The incidence of VAP was 36.3 (95% confidence interval, 21.1-58.1) per 1000 days of mechanical ventilation. There were no statistically significant differences in demographics, presence of chronic obstructive pulmonary disease, or use of continuous intravenous sedatives or neuromuscular blockers between patients with and without VAP. The most commonly isolated organisms were methicillin-sensitive Staphylococcus aureus, Sphingomonas paucimobilis, and Stenotrophomonas maltophilia. The median length of stay in the CCU for patients with VAP was 10 days compared to 6 days for patients without VAP (P < .01). Eight (47%) of the 17 patients with VAP died compared to 29 (39%) of 75 patients without VAP (P = .52)., Conclusions: The incidence of VAP in the CCU is similar to or higher than that reported in other intensive care units. The development of VAP in CCU patients is associated with a prolonged CCU stay but not with an increased hospital mortality.

Background: Excess mortality associated with methicillin resistance in patients with Staphylococcus aureus ventilator-associated pneumonia (SA-VAP), taking into account such confounders as treatment adequacy and time in the intensive care unit (ICU), have not been adequately estimated., Methods: One hundred thirty-four episodes of SA-VAP entered in the Outcomerea database were studied. Patients from whom methicillin-resistant S. aureus (MRSA) was recovered were compared with those from whom methicillin-susceptible S. aureus (MSSA) was recovered, stratified for duration of stay in the ICU at the time of VAP diagnosis and adjusted for confounders (severity at admission, characteristics at VAP diagnosis, and treatment adequacy)., Results: Treatment was adequate within 24 h after VAP diagnosis for 86% of the 65 MSSA-infected patients and 77% of the 69 MRSA-infected patients (P = .2). Polymicrobial VAP was more commonly associated with MSSA than with MRSA (49.2% vs. 25.7%; P = .01). MRSA infection was associated with a lower prevalence of coma at hospital admission and a higher rate of use of central venous lines and fluoroquinolones during the first 48 h of the ICU stay. The rates of shock, recurrence, and superinfection were similar in both groups. The crude hospital mortality rate was higher for MRSA-infected patients than for MSSA-infected patients (59.4% vs. 40%; P = .024). This difference disappeared after controlling for time in the ICU before VAP and parameters imbalanced at ICU admission (odds ratio [OR], 1.23; 95% confidence interval [CI], 0.49-3.12; P = .7) and remained unchanged after further adjustments for initial treatment adequacy and polymicrobial VAP (OR, 0.98; 95% CI, 0.36-2.66)., Conclusions: Differences in patient characteristics, initial ICU treatment, and time in the ICU confounded estimates of excess death due to MRSA VAP. After careful adjustment, methicillin resistance did not affect ICU or hospital mortality rates.

A 39-year old female patient who was kidney transplanted three years ago was admitted to hospital with fever of unknown origin for several days. Blood samples revealed decreased renal function and increased inflammation parameters. Chest X-ray and CT scan showed multiple cavernous structures, some with liquid. Staphylococcus aureus was detected in blood culture samples. With the aid of these results Staphylococcus pneumonia with multiple abscesses was diagnosed. The treatment consisted of removal of the infectious focus and a systemic antibiotic therapy corresponding to the microbiologic results. We describe a case of Staphylococcus pneumonia caused by a infected vascular prosthesis under consideration of immunosuppression in a renal transplanted patient.

Mortality from influenza is high in the elderly. Deaths are mainly due to secondary complications, including Staphylococcus aureus (SA) infections. Vitamin E (E) supplementation reduces influenza in aged mice. This study determined the efficacy of E supplementation on secondary bacterial infections after influenza in young and old mice. C57BL/6 mice were fed diets containing 30 or 500 ppm E for 4 weeks. Priming with influenza significantly increased SA in the lungs of infected mice fed control diet. Age did not have a significant effect on SA infection alone or SA infection after influenza infection. E supplementation did not have a significant effect on SA infection alone. However, E supplementation abolished the priming effect of influenza on SA.

The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was appropriate for every patient. Patients with methicillin-resistant Staphylococcus aureus VAP were older, had higher disease-severity scores, and had been on mechanical ventilation longer at onset of VAP. Factors associated with 28-day mortality retained by multivariate logistic regression analysis were: age (odds ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1 organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p = 0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22). The percentages of infection relapse or superinfection did not differ significantly between the two patient groups. In conclusion, after controlling for clinical and physiologic heterogeneity between groups, methicillin resistance did not significantly affect 28-day mortality of patients with Staphylococcus aureus VAP receiving appropriate antibiotics.