Serum human epididymis secretory protein 4 correlates with sepsis-associated acute respiratory distress syndrome and 28-day mortality in critically ill patients.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. METHODS: One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman's correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. RESULTS: Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all p < 0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cut-off value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5 pmol/L. CONCLUSIONS: The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.

Disseminated Human Parvovirus B19 Infection Induced Multiple Organ Dysfunction Syndrome in an Adult Patient With Alcoholic Hepatitis Complicated by Hemolytic Anemia: A Case Report and Literature Review.

Background: Human parvovirus B19 (B19) can cause acute hepatitis and is attributed to the high mortality of alcoholic hepatitis (AH). B19 infection is generally self-healing in previously healthy people, but it can cause fatal effects in some high-risk groups and increase its virulence and infectivity. Disseminated B19 infection-induced multiple organ dysfunction syndrome (MODS) in patients with AH has not been reported yet. Here, we described B19 viremia in an adult patient with AH accompanied by hemolytic anemia (HA), leading to disseminated infection and secondary MODS, as well as self-limiting B19 infections in seven nurses caring for him. Meanwhile, we reviewed the literature on AH and B19 infection. Case Presentation: A 43-year-old male patient with AH accompanied by HA was transferred to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, on March 31, 2021. After supportive treatment, his transaminase and bilirubin levels were reduced, but his anemia worsened. He received a red blood cell (RBC) infusion on April 9 for hemoglobin (Hb) lower than 6 g/dl. On April 13, he suddenly had a high fever. Under empirical anti-infection, his high fever dropped and maintained at a low fever level; however, his anemia worsened. On April 25, he was transferred to the medical intensive care unit (MICU) due to severe pneumonia, acute respiratory distress syndrome (ARDS), acute aplastic crisis (AAC), and hemophagocytic syndrome (HPS), which were subsequently confirmed to be related to B19 infection. After methylprednisolone, intravenous immunoglobulin (IVIG), empirical anti-infection, and supportive treatment, the lung infection improved, but hematopoietic and liver abnormalities aggravated, and systemic B19 infection occurred. Finally, the patient developed a refractory arrhythmia, heart failure, and shock and was referred to a local hospital by his family on May 8, 2021. Unfortunately, he died the next day. Fourteen days after he was transferred to MICU, seven nurses caring for him in his first two days in the MICU developed self-limiting erythema infectiosum (EI). Conclusions: B19 infection is self-limiting in healthy people, with low virulence and infectivity; however, in AH patients with HA, it can lead to fatal consequences and high contagion.

Disseminated Tuberculosis Associated Hemophagocytic Lymphohistiocytosis in a Pregnant Woman With Evans syndrome: A Case Report and Literature Review.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review. Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis (M. tuberculosis) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT. Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome.

Cytomegalovirus Infection in an Adult Patient With Neuromyelitis Optica and Acute Hemorrhagic Rectal Ulcer: Case Report and Literature Review.

Background: Previous infectious or inflammatory events may be involved in the pathogenesis of neuromyelitis optica (NMO), potentially by triggering an autoimmune response. Cytomegalovirus (CMV)-related NMO (CMV-NMO) is rarely reported. Acute hemorrhagic rectal ulcer (AHRU) is a rare disease with a largely unknown pathogenesis. Herein, we reported a co-NMO and AHRU case associated with CMV infection. In addition, we review previously reported cases of CMV-NMO and CMV-AHRU. Case presentation: A 40-year-old female diagnosed with aquaporin4 (AQP4)-IgG+ NMO and a poor response to high-dose intravenous methylprednisolone and immunoglobulin, followed by three rounds of plasma exchange was transferred to Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. She developed repeated acute lower gastrointestinal hemorrhage from the third day of admission. Abdominal computed tomography angiography (CTA) and interventional angiography did not detect any bleeding vessel. Bedside colonoscopy revealed a large ulcer-like lesion at 10 cm above the anus. Rectal biopsy pathology confirmed a CMV infection on day 23 post-admission, and cerebrospinal fluid (CSF) pathogen gene sequencing detected CMV gene copies on day 25 post-admission. After 2 weeks of treatment with ganciclovir and sodium phosphinate, the patient's lower gastrointestinal bleeding stopped, and her limb muscle strength and visual acuity gradually improved. After 4 weeks of antiviral therapy, colonoscopy showed that the intestinal wall of the original lesion was smooth. Hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) of a biopsy specimen was negative for CMV, her right eye vision was normal, and limb muscle strength had recovered. Serum AQP4-IgG was negative, and lesions on brain magnetic resonance imaging (MRI) manifested shrinkage. Conclusions: The benefits of antiviral therapy remain unclear; however, clinicians should be aware of the possibility of CMV-related NMO, if NMO was refractory to high-dose intravenous methylprednisolone, immunoglobulin, and plasma exchange. Moreover, clinicians should consider the possibility of CMV-related AHRU when recurrent acute lower gastrointestinal bleeding occurs in a patient.

Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.

Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis.

BACKGROUND: Human epididymis protein 4 (HE4) has been recognized as a biomarker which elevated in various diseases. The aim of this study was to evaluate the value of serum HE4 in pulmonary tuberculosis (PTB). METHODS: Serum HE4 concentrations were determined in 127 PTB, 88 chronic bronchitis (CHB), and 105 healthy control subjects by chemiluminescent microparticle immunoassay. Receiver operating characteristic (ROC) curves and Spearman's correlation analysis were performed for investigating value of HE4. RESULTS: Serum HE4 concentrations were significantly increased in PTB (62.8 pmol/L, IQR 45.8-90.7), compared with that of CHB (50.2 pmol/L, IQR 42.3-64.3, P = 0.0002) and normal control (35.4 pmol/L, IQR 31.1-42.9, P < 0.0001). ROC curve suggested that the AUC of HE4 used to discriminate PTB from CHB was 0.647 (95% CI, 0.574-0.719), with the cutoff value, sensitivity, specificity, PPV, and NPV at 71.9 pmol/L, 0.417, 0.852, 0.672 and 0.543, respectively. Meanwhile, compared with mild to moderated PTB, the levels of HE4 in advanced PTB were significantly elevated (75.8 vs. 57.7 pmol/L, P = 0.0052). What's more, the levels of HE4 in PTB were found to be significantly associated with the albumin, CRP, and cavity (r = -0.2996, P = 0.0006, r = 0.265, P = 0.0026, r = 0.4699, P < 0.0001, respectively). CONCLUSIONS: Elevated serum HE4 concentration could be used as a biomarker for the diagnosis and assessment of disease severity in PTB.

Metastatic infection caused by hypervirulent Klebsiella pneumonia and co-infection with Cryptococcus meningitis: A case report.

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) used to affect mainly people with compromised immunity or weakened by other infections, but recent emergence of hypervirulent strains has increased infections even in healthy individuals. These infections include liver abscess, pneumonia, bacteremia, meningitis, necrotizing fasciitis, and endophthalmitis. Although metastatic infection by hypervirulent K. pneumoniae (hvKP) is increasingly recognized, co-infection with Cryptococcus neoformans (C. neoformans) meningitis in immunocompetent hosts is rare but fatal. So, it is necessary to determine the risk factors, complications, and comorbidity of this disease. CASE SUMMARY: This report describes a 58-year-old man with hvKP pulmonary abscess, bacteremia, and meningitis, accompanied by fatal Cryptococcus meningitis. This patient presented with fever for 1 wk and drowsiness for 3 d. Laboratory findings revealed pulmonary abscess and bacteremia of K. pneumoniae. He was given intravenous antibiotic therapy, and the infection was under control for about 1 wk. However, his condition deteriorated rapidly because of metastatic purulent meningitis. Although hvKP and C. neoformans were isolated and confirmed, the patient died of spontaneous respiratory and cardiac arrest caused by cerebral hernia. CONCLUSION: HvKP has emerged as a cause of metastatic infections in immunocompetent hosts. polymicrobial co-infections should be taken into consideration when metastatic infection is present.

Therapeutic plasma exchange and continuous renal replacement therapy for severe hyperthyroidism and multi-organ failure: A case report.

BACKGROUND: Severe hyperthyroidism is a life-threatening exacerbation of thyrotoxicosis, characterized by high fever and multiorgan failure. The most common medical treatments are administration of antithyroid drugs and radioactive iodine, and thyroidectomy. In some patients, antithyroid therapy is limited due to serious adverse effects or failure to control disease progression. In some extreme cases, such as thyroid storm, conventional therapy alone does not yield effective and rapid improvement before the development of multiorgan failure. CASE SUMMARY: This report describes a Chinese patient with severe hyperthyroidism accompanied by multiorgan failure, who was transferred to the medical intensive care unit of our hospital. The patient presented with palpitations, vomiting, diarrhea, and shortness of breath for a week. Laboratory tests showed elevation of thyroid hormones. Hepatic failure occurred with high aminotransferase levels and jaundice. Given her abnormal liver function and medication history, we could not exclude diagnosis of propylthiouracil-induced hepatic failure. Moreover, she also suffered from heart failure. Therapeutic plasma exchange (commonly known as TPE) and continuous renal replacement therapy (commonly known as CRRT) were used as life-saving therapy, which resulted in notable improvement of clinical symptoms and laboratory tests. CONCLUSION: Combined TPE and CRRT are safe and effective for patients with hyperthyroidism and multiorgan failure.

Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients.

BACKGROUND: Renal fibrosis remains an important cause of kidney allograft failure. The objective of this study was to evaluate the performance of serum human epididymis secretory protein 4 (HE4) as a biomarker for renal fibrosis in kidney transplant recipients. METHODS: A total of 103 kidney transplantation patients were enrolled in this study, and serum HE4 concentrations were detected using the chemiluminescent microparticle immunoassay. Renal biopsy was carried out, and histological findings were assessed by immunohistochemistry. RESULTS: Median serum HE4 concentrations were significantly increased in kidney transplant recipients (186.2 pmol/l, interquartile range [IQR] 125.6-300.2) compared with control subjects (34.3 pmol/l, IQR 30.4-42.3, p < 0.0001). Meanwhile, serum HE4 concentrations were significantly increased along with disease severity (p < 0.0001). In addition, we found serum HE4 concentrations to be strongly correlated with the severity of fibrosis (IF/TA 0, 1, 2, and 3: 114.3, 179.0, 197.8, and 467.8 pmol/l, respectively; p < 0.0001) and serum HE4 concentrations significantly correlated with HE4 tissue expression concentrations in renal biopsy. CONCLUSIONS: Serum HE4 was increased in kidney transplant recipients with decreased kidney function and renal fibrosis and was correlated with the severity of the disease, suggesting that HE4 has the potential to be used as a novel clinical biomarker for evaluating kidney function and predicting renal fibrosis in kidney transplant recipients.

Regulatory effects of miR-155 and miR-146a on repolarization and inflammatory cytokine secretion in human alveolar macrophages in vitro.

Macrophages play an important role in inflammatory responses; however, miRNA-mediated repolarization of macrophages is essential for fulfilling this function. To clarify a series of changes at the RNA level in alveolar macrophages under normal and inflammatory conditions, bronchial alveolar lavage liquid (BALF) was collected from healthy volunteers or patients with pneumonia. This approach, which differs from that used in previously, provides more accurate information about the states of macrophages in different lung microenvironments. In this study, the density plots of macrophage subtypes (M1 and M2) in the BALF of healthy volunteers differed from that of the patients with pneumonia. The M2 subtype dominated in healthy volunteers and was rapidly repolarized to M1 in response to miRNA-mediated gene regulation. Differential miRNA expression in the two macrophage subtypes revealed lower expression of miR-155 and MIR-146a in patients with pneumonia compared with healthy volunteers; this may be related to inflammation and the use of anti-inflammatory drugs. We also found increased TNF-α and IL-6 expression at the RNA level, while macrophage galactose-type C-type lectin 1 (MGL-1) expression decreased with downregulation of miR-155 and miR-146a expression. These results indicate that the gene regulation mediated by miR-155 and miR-146a contributes to human alveolar macrophage phenotype repolarization, thus leading to an early switch from pro-inflammatory to anti-inflammatory cytokine production.

Protective effects of caffeoylxanthiazonoside isolated from fruits of Xanthium strumarium on sepsis mice.

CONTEXT: The fruit of Xanthium strumarium L. (Asteraceae) has been used for the treatment of various inflammatory diseases. OBJECTIVE: This study investigates the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of X. strumarium on sepsis mice in vitro and in vivo. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) operation was used to establish the sepsis mice model, and sham mice were also performed. CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2 mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then mice were sacrificed, and serum levels of TNF-α and IL-6 were determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was measured by using the LAL test, and expressions of TNF-α, IL-6 were determined by using real-time fluorogenic PCR. RESULTS: Results indicated that CYXD significantly elevated survival rates of sepsis mice induced by CLP (p < 0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD (10, 20, and 40 mg/kg) can not only significantly decrease TNF-α and IL-6 levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 cells at doses of 20, 40, and 80 µg/mL (p < 0.05). CONCLUSION: Our study demonstrated that CYXD has significant protective effects on sepsis mice.

Continuous venovenous hemodiafiltration for hyperlactatemia caused by telbivudine in a patient with chronic hepatitis B: a case report and update review.

Although there have been reports on telbivudine-induced myopathy and creatine kinase (CK) elevation, few reports focus on its effect on hyperlactatemia in patients with chronic hepatitis B (CHB). Here we reported a case of hyperlactatemia during telbivudine treatment. A 26-year-old Chinese man had been receiving telbivudine for CHB since July 2011, with a CK level of 68 U/L before the antiviral therapy. After 3 months he felt muscular weakness in both upper and lower extremities. A check in the local clinic found his CK level was increased to 222 U/L (upper limit of normal 170 U/L). However, he did not visit his doctor or stop the telbivudine treatment until he felt myalgia throughout his body. By this time his CK level had increased to 4151 U/L. Even after the withdrawal of telbivudine, his myalgia was exacerbated and his CK level was decreased extremely slowly. His constant myolysis developed into hyperlactatemia and he finally recovered after successful venovenous hemodiafiltration. The findings in this patient suggest that telbivudine may lead to high CK levels and hyperlactatemia may occur if telbivudine is not discontinued immediately when CK levels are clearly increased. Moreover, we emphasized that serum CK and lactate levels should be monitored closely during treatment with telbivudine in patients with CHB.

Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages.

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-1ß), 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.

Inhibitory effects of lipoteichoic acid from Staphylococcus aureus on platelet function and platelet-monocyte aggregation.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Factors associated with the outcome of life-threatening necrotizing pneumonia due to community-acquired Staphylococcus aureus in adult and adolescent patients.

BACKGROUND: 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. OBJECTIVES: 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. RESULTS: 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). CONCLUSIONS: 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.

[Analysis of risk factors related to mortality of patients with community-acquired pneumonia due to methicillin-resistant Staphylococcus aureus].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Pulmonary nocardiosis in immunocompromised host: report of 2 cases and review of the literature].

OBJECTIVE: To investigate the clinical, imaging and pathogenic features of pulmonary nocardiosis and the drug resistance of Nocardia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[The effect of recombinant panton-valentine leukocidin on the production of cytokines by human alveolar macrophages].

OBJECTIVE: To investigate the effect of recombinant panton-valentine leukocidin (rPVL) on the regulation of human alveolar macrophage CD14 and IL-10 and TNF-alpha. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Clinical analysis of community-acquired pneumonia in the elderly].

OBJECTIVES: To evaluate the clinical features, etiology, and outcome of patients over 65 years old hospitalized for community-acquired pneumonia (CAP). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Study on the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamase-producing clinical isolates].

OBJECTIVE: To investigate the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamases (ESBLs) producing isolates. METHODS: 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. RESULTS: 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. CONCLUSION: 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.