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ABSTRACT: Staphylococcus aureus (S. aureus) is the most common bacterium in sepsis and pneumonia involving gram-positive bacteria. Lipoteichoic acid (LTA) is a cell wall component of gram-positive bacteria. It is a potent inducer of inflammatory mediators in human dendritic cells, human pulmonary epithelial cells, and murine macrophages. However, the effect of LTA on human alveolar macrophages (AMs) which are the major effector cells in host defense against respiratory tract infections has hardly been studied. Statins have anti-inflammatory, immunomodulatory, antioxidative, anticoagulant, and antibacterial activities. These effects may be contributed to reduce the markers of systemic inflammation. Emerging retrospective studies have demonstrated that statin use decreased the mortality of pneumonia. However, the precise mechanisms responsible for these effects are unclear. The purpose of this study is to define the role of S. aureus LTA in human AMs and the effects of simvastatin (SV) on LTA-stimulated human AMs. The results showed that LTA induced tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-8 mRNA expression, and suppressed IL-10 mRNA expression in human AMs. Simultaneously, LTA induced human AMs apoptosis. These effects were parallel with the up-regulation of the expression of NF-κB-P65 protein in the LTA-stimulated human AMs. The above effects of LTA on human AMs were inhibited significantly by SV. These data indicate that S. aureus LTA induces potent pro-inflammatory and pro-apoptotic effects on human AMs and statins exert anti-inflammatory effects by mediating inhibition of NF-κB activation and cytokine mRNA expression in human AMs. These results may explain, in part, the mechanisms responsible for favorable effects of statins on pneumonia.
Clinical and Experimental Medicine 03/2013; · 1.58 Impact Factor
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ABSTRACT: Lipoteichoic acid (LTA) from Staphylococcus aureus has been demonstrated to inhibit agonist-stimulated platelet aggregation. However, its effects on platelet inflammatory mediator release and platelet-monocyte aggregation are still unclear. In the present study, LTA is examined for its anti-inflammatory properties and effects on platelet-monocyte aggregation.
Blood samples were obtained from 5 healthy volunteers who had taken no medicine in the previous 2 weeks. Washed platelets were prepared and incubated with LTA (0.5-2.0 μg/mL), then platelet aggregation, P-selectin expression, and soluble CD40L (sCD40L) release were measured by light transmission aggregometry, flow cytometry and enzyme-linked immunoassays, respectively. Platelet-monocyte aggregate formation in whole blood was measured by flow cytometry. Thrombin was used as a stimulant.
LTA dose-dependently decreased platelet aggregation from 89.32 ± 10.24% to 36.28 ± 9.01% (P < 0.05), sCD40L release from 3.28 ± 0.76 to 1.13 ± 0.45 ng/mL (P < 0.05) and surface P-selectin expression from 82.01 ± 11.20 to 22.78 ± 6.42% (P < 0.05). In human whole blood, 1.0 μg/mL LTA inhibited platelet-monocyte aggregation from 78.19 ± 10.94 to 38.24 + 8.74% (P < 0.05).
These results indicate that LTA from S. aureus can inhibit platelet-dependent inflammatory mediator release and platelet-monocyte aggregation. These findings suggest that LTA-mediated functional alteration of platelets may contribute to immune evasion of S. aureus.
Agents and Actions 04/2011; 60(8):775-82. · 1.59 Impact Factor
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ABSTRACT: Although community-acquired Staphylococcus aureus pneumonia with highly virulent Panton-Valentine leukocidin (PVL)-positive strains, a severe disease with significant lethality, is rare, especially in adult and adolescent patients, recent reports highlight that these infections are on the rise.
To describe the demographic and clinical features of reported cases of life-threatening community-acquired S. aureus pneumonia with usually PVL-positive strains in adult and adolescent patients, to evaluate the variables related to death, and to select a more appropriate antimicrobial treatment for this potentially deadly disease. Methods: We summarized all of the 92 reported cases and our case. The effect of 5 variables on mortality was measured using logistic regression.
S. aureus community-acquired pneumonia (CAP) with usually PVL-positive strains is a severe disease with significant lethality, i.e. 42.9%; a short duration of the time from the onset of symptoms to death, i.e. 5.5 ± 10.1 days, and prolonged hospital admissions, i.e. 33.2 ± 29.5 days. Seventy-three cases have been tested for the gene for PVL, and 71 strains have been found to carry the PVL gene. Logistic regression analysis showed that leucopenia (p = 0.002), influenza-like symptoms or laboratory-confirmed influenza (p = 0.011), and hemoptysis (p = 0.024) were the factors associated with death. Antibiotic therapies inhibiting toxin production were associated with an improved outcome in these cases (p = 0.007).
Physicians should pay special attention to those patients who acquired severe CAP during influenza season and have flu-like symptoms, hemoptysis, and leucopenia, and they should consider S. aureus more frequently among the possible pathogens of severe CAP. Empiric therapy for severe CAP with this distinct clinical picture should include coverage for S. aureus. Targeted treatment with antimicrobials inhibiting toxin production appears to be a more appropriate selection.
Respiration 11/2010; 81(6):448-60. · 2.26 Impact Factor
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ABSTRACT: To describe the clinical features of reported cases of community-acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus (MRSA), and to evaluate the risk factors related to outcome.
A systematic search of databases from January 1995 to December 2009 was performed. Baseline characteristics of survivors and non-survivors in the hospital were compared with the chi2 test for categorical variables. Variables with P<0.2 were entered in Logistic regression. Survival analysis was estimated by the Kaplan-Meier method according to use of antimicrobials inhibiting toxin production.
Fifty-two articles were identified reporting data on 74 patients, with 41.1% of total mortality, short duration of symptom onset to death [(6.1+/-11.0) days], and prolonged hospital admissions [(28.6+/-29.1) days]. Logistic regression analysis showed that influenza like symptoms (P=0.04), hemoptysis (P<0.01), leucopenia (P<0.01) were the risk factors associated with death, and using clindamycin or linezolid which could inhibit the Panton-Valentine leukocidin (PLV, P<0.01) was the factor associated with survival. Kaplan-Meier analysis indicated that the antibiotic therapies inhibiting toxin production were associated with improved outcome in these cases (chi2=21.59, P<0.01).
CAP due to MRSA is a severe disease with significant lethality. Empiric therapy of severe CAP with flu-like symptoms, hemoptysis and leucopenia should include coverage for MRSA. Targeted treatment with antimicrobials inhibiting toxin production appear to be more appropriate selection.
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 08/2010; 22(8):459-64.
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ABSTRACT: To investigate the clinical, imaging and pathogenic features of pulmonary nocardiosis and the drug resistance of Nocardia.
The clinical and radiological data of 2 cases of pulmonary nocardiosis in this hospital were presented, and 32 cases reported in the Chinese literature since 1982 were reviewed.
Among the 34 cases of Nocardia infections, there were 26 cases of pulmonary nocardiosis, and 4 of whom died. Multiple organ infection occurred in 11 patients, including 7 with pulmonary and skin infections, 3 with pulmonary, skin and intracranial infections, and 1 with pulmonary and intracranial infections. All patients with pulmonary nocardiosis had cough. Of the 34 cases, 27 had fever, including intermittent fever in 5, and sustained fever in 22 cases. Of the 11 cases of pulmonary nocardiosis complicated with skin or intracranial dissemination, 8 patients were immunocompromised and 3 were immunocompetent (chi(2) = 2.08, P > 0.05). Three cases died in the immunocompromised group and 1 died in the immunocompetent group. Nocardia asteroides was identified in 14 cases, Nocardia brasiliensis in 4 cases, and the other 8 were not classified. In the patients with complicated skin or intracranial infections, 8 were caused by Nocardia asteroids, and 2 were caused by Nocardia brasiliensis. Chest X-ray or CT imaging of the lungs showed pleural effusion in 8, masses in 7, infiltrates in 6, cavities in 6, and nodular lesions in 5 cases. Antimicrobial susceptibility testing showed that Nocardia was sensitive to sulfonamide, amikacin, cefotaxime, ceftriaxone, minocycline, fluoroquinolones, and linezolid.
Immunosuppression is the most important predisposing factor for pulmonary nocardiosis. The most common pathogenic bacterium is Nocardia asteroids, which is frequently associated with disseminated lesions. The radiographic abnormalities of the lung show pleural effusion, masses, infiltration or cavity. With the increasing rate of resistance of Nocardia to the sulfonamide, the combination of antibiotic regimen according to susceptibility testing needs to be considered. Poor outcome is mostly found in immunocompromised hosts.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 08/2009; 32(8):593-7.
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ABSTRACT: To investigate the effect of recombinant panton-valentine leukocidin (rPVL) on the regulation of human alveolar macrophage CD14 and IL-10 and TNF-alpha.
Human alveolar macrophages (AM) were purified and cultured from bronchoalveolar lavage fluid. Each sample was divided into groups according to different concentrations and exposure times of rPVL. Semi-quantitative RT-PCR was used to evaluate the CD14 mRNA levels and Double-antibody-sandwich-ELISA was used to measure the IL-10 and TNF-alpha levels in AM cultures.
CD14 mRNA decreased after rPVL treatment in time-and concentration dependent manners. There were no statistically significant differences in CD14 mRNA among the blank control groups (F = 1.708, P > 0.05). CD14 mRNA in the T6N10 group and the T6N100 group( T = time in hours, N = concentration of rPVL/nmol/L) decreased as compared to the T6N0 group (t = 4.132, 6.818, both P < 0.001), and that in the T24N10 group and the T24N100 group also decreased as compared to the T24N0 group (t = 7.401, 11.415, both P < 0.001), indicating that the expression of CD14 was downregulated by rPVL treatment. There were also statistically significant differences in CD14 mRNA between T6N10 and T24N10 groups, T6N100 and T24N100 groups (t = 4.692, 6.019, both P < 0.001), T6N10 and T6N100 groups, T24N10 and T24N100 groups (t = 2.686, 4.014, P < 0.01 respectively), indicating that the expression of CD14 decreased as the treatment time and the concentration of rPVL increased. The IL-10 concentrations of the T24N10 and T24N100 groups increased as compared to the T24N0 group (t = 4.036, 3.941, both P < 0.01) in time-dependent and concentration-dependent manners with rPVL treatment. The TNF-alpha concentration of the T24N10 group decreased while that of the T24N100 group increased as compared to the T24N0 group (t = 2. 824, 8. 468, both P < 0.01, respectively), indicating that a lower concentration of rPVL inhibited TNF-alpha release while a higher concentration of rPVL induced release of TNF-alpha.
The results suggest that rPVL could reduce the expression of CD14 and induce disordered release of anti-inflammatory and proinflammatory cytokines by AMs, which may be one of the important mechanisms underlying the high mortality of infection with PVL-positive Staphylococcus aureus.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 07/2009; 32(7):503-7.
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ABSTRACT: To evaluate the clinical features, etiology, and outcome of patients over 65 years old hospitalized for community-acquired pneumonia (CAP).
A retrospective cohort analysis was performed for adult patients hospitalized with CAP in a 1000-bed teaching hospital between Jan 2002 and Jan 2006. Differences between < or = 65 yrs and > 65 yrs groups were calculated using chi(2) test.
A total of 302 patients (166 males), with a mean age of (68 +/- 21) yrs, were enrolled. Of the 216 elderly patients, 67.1% had comorbid conditions, mostly cardiovascular diseases and chronic obstructive lung disease. For the risk stratification, 175 patients were classified as IV - V according to Fine's index. The mean hospital stay was 12 days and in-hospital mortality was 12.0%. The most frequent pathogen was Streptococcus pneumoniae in elderly patients. As compared to 86 younger patients (< or = 65yrs), altered mental status, dyspnea, tachypnea and tachycardia on hospital admission were more frequent in the elderly. The etiological distribution was also different between the two groups.
CAP in elderly patients is a prevalent disease with high incidence of complications and mortality. More attention should be paid to the specific clinical manifestations of this patient population.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 11/2007; 46(10):810-4.
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ABSTRACT: To investigate the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamases (ESBLs) producing isolates.
Antibiotics susceptibility was tested by E-test method, and multi-resistance plasmids were screened and isolated by extracting transformant plasmids. Inserted gene Cassettes of class 1 integron were amplified and analyzed by polymerase chain reaction (PCR) and DNA sequencing.
Eight of the nine ESBL-producing plasmids were found to comprise class 1 integron sequence, of them 7 harbored 1 or 2 antibiotic resistant gene cassettes which encoding resistance to aminoglycosides (aacA4, aadA2 or aadA5), trimethoprim (dhfrA12 or dfrA17), rifampicin (arr-3) and chloramphenicol (cmlA6). The function of these gene cassettes corresponded to the resistance profiles of their electro-transformants.
Multi-resistance gene cassettes located on plasmids and mediated by class 1 integron may play an important role in causing the development and dissemination of multiple-antibiotic resistance in ESBL-producing clinical isolates.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 05/2003; 26(4):199-202.
