Ioannis Pneumatikos

Ventilator-associated Pneumonia or Endotracheal Tube-associated Pneumonia?An Approach to the Pathogenesis and Preventive Strategies Emphasizing the Importance of Endotracheal Tube

Ventilator-associated pneumonia is the most common nosocomial infection in the intensive care unit, and it is associated with prolonged hospitalization, increased health care costs, and high attributable mortality. During the past several decades, numerous studies focused on the crucial role of the endotracheal tube (ETT) in the pathogenesis of ventilator-associated pneumonia. Tracheal intubation thwarts the cough reflex, compromises mucocilliary clearance, injures the tracheal epithelial surface, provides a direct conduit for rapid access of bacteria from upper into the lower respiratory tract, and allows the formation of biofilm on the ETT surface. The combination of these factors puts the mechanically ventilated patient at great jeopardy of developing ventilator-associated pneumonia. Many preventive strategies have arisen from this understanding: control of intracuff pressure, aspiration of subglottic secretions, decontamination of subglottic area, use of antiseptic impregnated ETTs, and elimination or prevention of the ETT biofilm formation. The authors review the role of ETT management for the prevention of the ventilator-associated pneumonia.

Autophagy mediates the delivery of thrombogenic tissue factor to neutrophil extracellular traps in human sepsis.

Background Sepsis is associated with systemic inflammatory responses and induction of coagulation system. Neutrophil extracellular traps (NETs) constitute an antimicrobial mechanism, recently implicated in thrombosis via platelet entrapment and aggregation. Methodology/Principal Findings In this study, we demonstrate for the first time the localization of thrombogenic tissue factor (TF) in NETs released by neutrophils derived from patients with gram-negative sepsis and normal neutrophils treated with either serum from septic patients or inflammatory mediators involved in the pathogenesis of sepsis. Localization of TF in acidified autophagosomes was observed during this process, as indicated by positive LC3B and LysoTracker staining. Moreover, phosphatidylinositol 3-kinase inhibition with 3-MA or inhibition of endosomal acidification with bafilomycin A1 hindered the release of TF-bearing NETs. TF present in NETs induced thrombin generation in culture supernatants, which further resulted in protease activated receptor-1 signaling. Conclusions/Significance This study demonstrates the involvement of autophagic machinery in the extracellular delivery of TF in NETs and the subsequent activation of coagulation cascade, providing evidence for the implication of this process in coagulopathy and inflammatory response in sepsis.

C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is characterized by the presence of fibrin-rich inflammatory exudates in the intra-alveolar spaces and the extensive migration of neutrophils into alveoli of the lungs. Tissue factor (TF)-dependent procoagulant properties of bronchoalveaolar lavage fluid (BALF) obtained from ARDS patients favor fibrin deposition, and are likely the result of cross-talk between inflammatory mediators and hemostatic mechanisms. However, the regulation of these interactions remains elusive. Prompted by previous findings suggesting that neutrophils, under certain inflammatory conditions, can express functional TF, we investigated the contribution of intra-alveolar neutrophils to the procoagulant properties of BALF from patients with ARDS. Our results confirm that the procoagulant properties of BALF from ARDS patients are the result of TF induction, and further indicate that BALF neutrophils are a main source of TF in intra-alveolar fluid. We also found that BALF neutrophils in these patients express significantly higher levels of TF than peripheral blood neutrophils. These results suggest that the alveolar microenvironment contributes to TF induction in ARDS. Additional experiments indicated that the ability of BALF to induce TF expression in neutrophils from healthy donors can be abolished by inhibiting C5a or TNF-α signaling, suggesting a primary role for these inflammatory mediators in the up-regulation of TF in alveolar neutrophils in ARDS. This cross-talk between inflammatory mediators and the induction of TF expression in intra-alveolar neutrophils may be a potential target for novel therapeutic strategies to limit ARDS-associated disturbances of coagulation.

Short- vs Long-Duration Antibiotic Regimens for Ventilator-Associated Pneumonia: A Systematic Review and Meta-analysis

BACKGROUND We performed a systematic review and meta-analysis of short- vs long-duration antibiotic regimens for ventilator-associated pneumonia (VAP). METHODS We searched PubMed and Cochrane Central Registry of Controlled Trials. Four randomized controlled trials (RCTs) comparing short (7-8 days) with long (10-15 days) regimens were identified. Primary outcomes included mortality, antibiotic-free days, and clinical and microbiologic relapses. Secondary outcomes included mechanical ventilation-free days, duration of mechanical ventilation, and length of ICU stay. RESULTS All RCTs included mortality data, whereas data on relapse and antibiotic-free days were provided in three and two out of four RCTs, respectively. No difference in mortality was found between the compared arms (fixed effect model [FEM]: OR = 1.20; 95% CI, 0.84-1.72; P = .32). There was an increase in antibiotic-free days in favor of the short-course treatment with a pooled weighted mean difference of 3.40 days (random effects model: 95% CI, 1.43-5.37; P < .001). There was no difference in relapses between the compared arms, although a strong trend to lower relapses in the long-course treatment was observed (FEM: OR = 1.67; 95% CI, 0.99-2.83; P = .06). No difference was found between the two arms regarding the remaining outcomes. Sensitivity analyses yielded similar results. CONCLUSIONS Short-course treatment of VAP was associated with more antibiotic-free days. No difference was found regarding mortality and relapses; however, a strong trend for fewer relapses was observed in favor of the long-course treatment, being mostly driven by one study in which the observed relapses were probably more microbiologic than clinical. Additional research is required to elucidate the issue.

Original ResearchCritical CareFeaturedShort- vs Long-Duration Antibiotic Regimens for Ventilator-Associated Pneumonia: A Systematic Review and Meta-analysis

BACKGROUND We performed a systematic review and meta-analysis of short- vs long-duration antibiotic regimens for ventilator-associated pneumonia (VAP). METHODS We searched PubMed and Cochrane Central Registry of Controlled Trials. Four randomized controlled trials (RCTs) comparing short (7-8 days) with long (10-15 days) regimens were identified. Primary outcomes included mortality, antibiotic-free days, and clinical and microbiologic relapses. Secondary outcomes included mechanical ventilation-free days, duration of mechanical ventilation, and length of ICU stay. RESULTS All RCTs included mortality data, whereas data on relapse and antibiotic-free days were provided in three and two out of four RCTs, respectively. No difference in mortality was found between the compared arms (fixed effect model [FEM]: OR = 1.20; 95% CI, 0.84-1.72; P = .32). There was an increase in antibiotic-free days in favor of the short-course treatment with a pooled weighted mean difference of 3.40 days (random effects model: 95% CI, 1.43-5.37; P < .001). There was no difference in relapses between the compared arms, although a strong trend to lower relapses in the long-course treatment was observed (FEM: OR = 1.67; 95% CI, 0.99-2.83; P = .06). No difference was found between the two arms regarding the remaining outcomes. Sensitivity analyses yielded similar results. CONCLUSIONS Short-course treatment of VAP was associated with more antibiotic-free days. No difference was found regarding mortality and relapses; however, a strong trend for fewer relapses was observed in favor of the long-course treatment, being mostly driven by one study in which the observed relapses were probably more microbiologic than clinical. Additional research is required to elucidate the issue.

A prospective study of the diagnostic utility of sputum Gram stain in pneumonia

INTRODUCTION Sputum Gram stain and culture have been said to be unreliable indicators of the microbiological diagnosis of bacterial pneumonia. The etiological diagnosis of pneumonia is surrounded by great degree of uncertainty. This uncertainty should be and can be calculated and incorporated in the diagnosis and treatment. STUDY OBJECTIVES To determine the diagnostic accuracy and diagnostic value of sputum Gram stain in etiological diagnosis and initial selection of antimicrobial therapy of bacterial community acquired pneumonia (CAP). DESIGN-METHOD: Prospective study of 1390 patients with CAP admitted January 2002-June 2008, to our institutions. Of the 1390 patients, 178 (12.8%) fulfilled the criteria for inclusion into this study (good-quality sputa and presence of the same microorganism in blood and sputum cultures which was used as gold standard for assessing the diagnostic accuracy and diagnostic value of sputum Gram stain). RESULTS The sensitivity of sputum Gram stain was 0.82 for Pneumococcal pneumonia, 0.76 for Staphylococcal pneumonia, 0.79 for Haemophilus influenzae pneumonia and 0.78 for Gram-negative bacilli pneumonia. The specificity of sputum Gram stain was 0.93 for Pneumococcal pneumonia, 0.96 for Staphylococcal pneumonia, 0.96 for H. influenzae pneumonia and 0.95 for Gram-negative bacilli pneumonia. The positive likelihood ratio (LR+) was 11.58 for Pneumococcal pneumonia, 19.38 for Staphylococcal pneumonia, 16.84 for H. influenzae pneumonia, 14.26 for Gram-negative bacilli pneumonia. The negative likelihood ratio (LR-) was 0.20 for Pneumococcal pneumonia, 0.25 for Staphylococcal pneumonia, 0.22 for H. influenzae pneumonia, and 0.23 for Gram-negative bacilli pneumonia. CONCLUSIONS Sputum Gram stain is a dependable diagnostic test for the early etiological diagnosis of bacterial CAP that helps in choosing orthological and appropriate initial antimicrobial therapy.

Pleural Involvement in Systemic Autoimmune Disorders

Systemic autoimmune diseases, a heterogeneous group of immunologically mediated inflammatory disorders including multiorgan involvement, can affect the pleura with various frequencies, either as a single presenting feature or as part of multisystem involvement. Rheumatoid arthritis and systemic lupus erythematosus represent the most common immunological diseases that affect the pleural cavity; however, there is considerable variation regarding the reported prevalence, natural history and prognosis of pleural involvement in both conditions. The definition of pleural disease in the remaining systemic autoimmune disorders is unquestionably imprecise and assumptive, since it is risky to support premises based on single case reports or retrospective data from very small series. In this article, we will review the manifestations of pleural disease caused by rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis/dermatomyositis, mixed connective tissue disease, ankylosing spondylitis, Sjögren’s syndrome and Wegener’s granulomatosis.

The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome

BackgroundThe predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS).MethodsWe measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C).ResultsAn excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively).ConclusionsBALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS.

Saccharomyces boulardii fungaemia in an intensive care unit patient treated with caspofungin.

We describe a case of Saccharomyces boulardii fugaemia in a critically ill patient with septic shock treated with a probiotic agent containing this yeast. We attributed this fugaemia to gut translocation. Our use of caspofugin yielded excellent results.

Relation of heart rate variability to serum levels of C-reactive protein, interleukin 6, and 10 in patients with sepsis and septic shock

PURPOSE The aim of the study was to investigate possible associations between different heart rate variability (HRV) indices and various biomarkers of inflammation in 45 septic patients. MATERIALS AND METHODS We daily assessed HRV in the time domain (SD of RR intervals [SDNN]), frequency domain (low [LF], high frequency [HF], LF/HF as an indicator of sympathovagal balance); the 2 values of SD (SD1, SD2) from the Poincaré plot; and measured C-reactive protein, interleukin 6, and interleukin 10 serum levels in patients with sepsis and mean Sequential Organ Failure Assessment score (SOFA) 10 or lower (n = 25) and septic shock (SOFA > 10, n = 20) for 6 days. RESULTS C-reactive protein exhibited significant negative correlations with LF (r = -0.78), LF/HF (r = -0.61), and SDNN (r = -0.79) and positive correlations with HF (r = 0.80) and SD1/SD2 (r = 0.66), whereas interleukin 10 was positively correlated with HF (r = 0.71) and negatively with LF (r = -0.89) and LF/HF (r = -0.66) in septic shock patients (P < .05 for all comparisons). Standard deviation of RR intervals and HF proved to be independent predictors of the severity of disease (beta slope [B] = -1.091; P = .013; 95% confidence interval [CI], -1.43 to -0.74, and B = 0.78; P = .022; 95% CI, 0.21-1.35, respectively). CONCLUSIONS Our data suggest that low HRV and sympathovagal balance during septic shock are associated with both an increased hyperinflammatory and antiinflammatory response.