Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

HBP/O-GlcNAcylation Metabolic Axis Regulates Bone Resorption Outcome.

Osteoclasts play a key role in the regulation of bone mass and are highly active metabolically. Here we show that a metabolic reprogramming toward the hexosamine biosynthetic pathway (HBP) is required not only for osteoclast differentiation but also to determine the bone resorption mode during physiological and pathological bone remodeling. We found that pharmacological inhibition of O-GlcNAc transferase (OGT) significantly reduced protein O-GlcNAcylation and osteoclast differentiation. Accordingly, genetic deletion of OGT also inhibited osteoclast formation and downregulated critical markers related to osteoclasts differentiation and function (NFATc1, αvintegrin, cathepsin K). Indeed, cells treated with OSMI-1, an OGT inhibitor, also reduced nuclear translocation of NFATc1. Furthermore, the addition of exogenous N-acetylglucosamine (GlcNAc) strongly increased osteoclast formation and demineralization ability. Strikingly, our data show for the first time that O-GlcNAcylation facilitates an aggressive trench resorption mode in human cells. The incubation of osteoclasts with exogenous GlcNAc increases the percentage of erosion by trench while having no effect on pit resorption mode. Through time-lapse recording, we documented that osteoclasts making trenches moving across the bone surface are sensitive to GlcNAcylation. Finally, osteoclast-specific Ogt-deficient mice show increased bone density and reduced inflammation-induced bone loss during apical periodontitis model. We show that osteoclast-specific Ogt-deficient mice are less susceptible to develop bacterial-induced periapical lesion. Consistent with this, Ogt-deleted mice showed a decreased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site. In summary, here we describe a hitherto undiscovered role of the HBP/O-GlcNAcylation axis tuning resorption mode and dictating bone resorption outcome.

Riboflavin did not provide anti-inflammatory or antioxidant effects in an experimental model of sepsis.

We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.

Riboflavin did not provide anti-inflammatory or antioxidant effects in an experimental model of sepsis

We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.

Pitavastatin ameliorates autoimmune neuroinflammation by regulating the Treg/Th17 cell balance through inhibition of mevalonate metabolism.

While Treg cells are responsible for self-tolerance and immune homeostasis, pathogenic autoreactive Th17 cells produce pro-inflammatory cytokines that lead to tissue damage associated with autoimmunity, as observed in multiple sclerosis. Therefore, the immunological balance between Th17 and Treg cells may represent a promising option for immune therapy. Statin drugs are used to treat dyslipidemia; however, besides their effects on preventing cardiovascular diseases, statins also have anti-inflammatory effects. Here, we investigated the role of pitavastatin on experimental autoimmune encephalomyelitis (EAE) and the differentiation of Treg and Th17 cells. EAE was induced by immunizing C57BL/6 mice with MOG35-55. EAE severity was determined by analyzing the clinical score and inflammatory parameters in the spinal cord. Naive CD4 T cells were cultured under Treg and Th17-skewing conditions in vitro in the presence of pitavastatin. We found that pitavastatin decreased EAE development, which was accompanied by a reduction of all parameters investigated. Pitavastatin also reduced the expression of IBA1 and pSTAT3 (Y705 and S727) in the spinal cords of EAE mice. Interestingly, the reduction of Th17 cell frequency in the draining lymph nodes of EAE mice treated with pitavastatin was followed by an increase of Treg cells. Indeed, pitavastatin directly affects T cell differentiation in vitro by decreasing Th17 and increasing Treg cell differentiation. Mechanistically, pitavastatin effects are dependent on mevalonate synthesis. Thus, our data show the potential anti-inflammatory effect of pitavastatin on the pathogenesis of the experimental neuroinflammation by modulating the Th17/Treg axis.

Fructose 1,6-bisphosphate inhibits osteoclastogenesis by attenuating RANKL-induced NF-κB/NFATc-1.

BACKGROUND: Although some glycolytic intermediates have been shown to modulate several cell type formation and activation, the functional role of fructose 1,6-bisphosphate (FBP) on osteoclastogenesis is still unknown. METHODS: Osteoclastogenesis was evaluated on bone marrow preosteoclasts cultured with M-CSF - 30 ng/ml, RANKL - 10 ng/ml, and two concentrations of FBP (100 and 300 µM). TRAP-positive stained cells were counted, and osteoclastogenic marker genes expression were evaluated by qPCR. Osteoclasts resorption capacity was evaluated by the expression of specific enzymes and capacity to resorb a mineralized matrix. The NF-κB activation was detected using RAW 264.7, stably expressing luciferase on the NF-κB responsive promoter. RESULTS: We show that FBP, the product of the first stage of glycolysis, inhibited RANKL-induced osteoclasts differentiation and TRAP activity. The treatment of preosteoclasts with FBP attenuated osteoclast fusion and formation, without affecting cell viability. Moreover, the inhibition of several osteoclastogenic marker genes expression (TRAP, OSCAR, DC-STAMP, Integrin αv, NFATc1) by FBP correlates with a reduction of mineralized matrix resorption capacity. The mechanism underlying FBP-inhibition of osteoclastogenesis involves NF-κB/NFATc1 signaling pathway inhibition. CONCLUSION: Altogether these data show a protective role of a natural glycolytic intermediate in bone homeostasis that may have therapeutic benefit for osteolytic diseases.

M2 macrophages or IL-33 treatment attenuate ongoing Mycobacterium tuberculosis infection.

The protective effects of mycobacterial infections on lung allergy are well documented. However, the inverse relationship between tuberculosis and type 2 immunity is still elusive. Although type 1 immunity is essential to protection against Mycobacterium tuberculosis it might be also detrimental to the host due to the induction of extensive tissue damage. Here, we determined whether lung type 2 immunity induced by allergen sensitization and challenge could affect the outcome of M. tuberculosis infection. We used two different protocols in which sensitization and allergen challenge were performed before or after M. tuberculosis infection. We found an increased resistance to M. tuberculosis only when allergen exposure was given after, but not before infection. Infected mice exposed to allergen exhibited lower bacterial load and cellular infiltrates in the lungs. Enhanced resistance to infection after allergen challenge was associated with increased gene expression of alternatively activated macrophages (M2 macrophages) and IL-33 levels. Accordingly, either adoptive transfer of M2 macrophages or systemic IL-33 treatment was effective in attenuating M. tuberculosis infection. Notably, the enhanced resistance induced by allergen exposure was dependent on IL-33 receptor ST2. Our work indicates that IL-33 might be an alternative therapeutic treatment for severe tuberculosis.

An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice.

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors.

An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors.

IL-33/ST2 signalling contributes to carrageenin-induced innate inflammation and inflammatory pain: role of cytokines, endothelin-1 and prostaglandin E2.

BACKGROUND AND PURPOSE: IL-33 signals through ST2 receptors and induces adaptive and innate inflammation. IL-33/ST2 is involved in adaptive inflammation-induced pain. Here, we have investigated the contribution of IL-33/ST2-triggered mechanisms to carrageenin-induced innate inflammation. EXPERIMENTAL APPROACH: Carrageenin- and IL-33-induced inflammatory responses were assessed in BALB/c- (WT) and ST2-deficient ((-/-) ) mice as follows: oedema (plethysmometer), myeloperoxidase activity (colorimetric assay), mechanical hyperalgesia (electronic version of von Frey filaments), cytokine levels (ELISA), PGE2 (RIA), mRNA expression (quantitative PCR), drug treatments targeting leukocyte recruitment (fucoidin), TNF-α (infliximab), CXCL1 (antibody to CXCL1), IL-1 (IL-1ra), endothelin ETA (clazosentan) and ETB (BQ788) receptors and COX (indomethacin). KEY RESULTS: Carrageenin injection increased ST2 and IL-33 mRNA expression and IL-33 production in paw skin samples. Carrageenin-induced paw oedema, hyperalgesia and myeloperoxidase activity were reduced in ST2(-/-) compared with WT mice, effects mimicked by IL-33 injection in the paw. Furthermore, IL-33-induced hyperalgesia was reduced by fucoidin suggesting a role for recruited leukocytes in its hyperalgesic effect. IL-33-induced hyperalgesia in naïve mice was reduced by treatments targeting TNF, CXCL1, IL-1, endothelin receptors and COX while carrageenin-induced ST2-dependent TNF-α, CXCL1, IL-1ß, IL-10 and PGE2 production and preproET-1 mRNA expression. Combining IL-33 and carrageenin at doses that were ineffective as single treatment induced significant hyperalgesia, oedema, myeloperoxidase activity and cytokine production in a ST2-dependent manner. CONCLUSIONS AND IMPLICATIONS: IL-33/ST2 signalling triggers the production of inflammatory mediators contributing to carrageenin-induced inflammation. These data reinforces the importance of IL-33/ST2 signalling as a target in innate inflammation and inflammatory pain.

Fructose-1,6-bisphosphate reduces inflammatory pain-like behaviour in mice: role of adenosine acting on A1 receptors.

BACKGROUND AND PURPOSE: D-Fructose-1,6-bisphosphate (FBP) is an intermediate in the glycolytic pathway, exerting pharmacological actions on inflammation by inhibiting cytokine production or interfering with adenosine production. Here, the possible antinociceptive effect of FBP and its mechanism of action in the carrageenin paw inflammation model in mice were addressed, focusing on the two mechanisms described above. EXPERIMENTAL APPROACH: Mechanical hyperalgesia (decrease in the nociceptive threshold) was evaluated by the electronic pressure-metre test; cytokine levels were measured by elisa and adenosine was determined by high performance liquid chromatography. KEY RESULTS: Pretreatment of mice with FBP reduced hyperalgesia induced by intraplantar injection of carrageenin (up to 54%), tumour necrosis factor alpha (40%), interleukin-1 beta (46%), CXCL1 (33%), prostaglandin E(2) (41%) or dopamine (55%). However, FBP treatment did not alter carrageenin-induced cytokine (tumour necrosis factor alpha and interleukin-1 beta) or chemokine (CXCL1) production. On the other hand, the antinociceptive effect of FBP was prevented by systemic and intraplantar treatment with an adenosine A(1) receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine), suggesting that the FBP effect is mediated by peripheral adenosine acting on A(1) receptors. Giving FBP to mice increased adenosine levels in plasma, and adenosine treatment of paw inflammation presented a similar antinociceptive mechanism to that of FBP. CONCLUSIONS AND IMPLICATIONS: In addition to anti-inflammatory action, FBP also presents an antinociceptive effect upon inflammatory hyperalgesia. Its mechanism of action seems dependent on adenosine production but not on modulation of hyperalgesic cytokine/chemokine production. In turn, adenosine acts peripherally on its A(1) receptor inhibiting hyperalgesia. FBP may have possible therapeutic applications in reducing inflammatory pain.

Peroxynitrite mediates the failure of neutrophil migration in severe polymicrobial sepsis in mice.

BACKGROUND AND PURPOSE: Sepsis is a systemic inflammatory response resulting from the inability of the host to restrict local infection. The failure of neutrophil migration to the infection site is one of the mechanisms involved in this process. Recently, it was demonstrated that this event is mediated by nitric oxide (NO). The present study addresses the possibility that peroxynitrite (ONOO(-)), a NO-derived powerful oxidizing and nitrating compound, could also be involved in neutrophil migration failure. EXPERIMENTAL APPROACH: Male C57Bl/6 mice were subjected to moderate (MSI) or severe (SSI) septic injury, both induced by cecal ligation and puncture (CLP). The leukocyte rolling and adhesion in the mesentery was evaluated by intravital microscopy. Cytokines (TNF-alpha and MIP-1alpha) were measured by ELISA and 3-nitrotyrosine (3-NT) by immunofluorescence. KEY RESULTS: Compared with saline pretreatment of SSI mice, pre-treatment with uric acid, a ONOO(-) scavenger, partially restored the failure of neutrophil rolling, adhesion and migration to the site of infection. These mice also presented low circulating bacterial counts and diminished systemic inflammatory response. Pretreatment with uric acid reduced 3-NT labelling in leukocytes in mesenteric tissues and in neutrophils obtained from peritoneal exudates. Finally, uric acid pretreatment enhanced significantly the survival rate in the SSI mice. Similarly, treatment with FeTPPs, a more specific ONOO(-) scavenger, re-established neutrophil migration and increased mice survival rate. CONCLUSIONS AND IMPLICATIONS: These results indicate that ONOO(-) contributed to the reduction of neutrophil/endothelium interaction and the consequent failure of neutrophil migration into infection foci and hence susceptibility to severe sepsis.

The effects of fructose-1,6-bisphosphate and dexamethasone on acute inflammation and T-cell proliferation.

OBJECTIVE AND DESIGN: Chronic glucocorticoid treatment is associated with pharmacological resistance. We investigated the auxiliary effects of fructose-1,6-bisphosphate (FBP) on dexamethasone (DEX)-related modulation of inflammation and T-cell proliferation. METHODS: Acute inflammation (pleurisy) was induced by injection of carrageenan into the pleural cavity of rats that were treated in vivo with DEX s. c. and FBP i. p. Peripheral blood mononuclear cells were isolated and T-cell sensitivity to FBP and DEX was evaluated in vitro. RESULTS: FBP and DEX reduced the exudate volume, protein concentration and neutrophils in the pleural cavity. However no synergistic effects were observed when these compounds were tested simultaneously. In contrast, both compounds dose-dependently and synergistically suppressed T-cell proliferation. CONCLUSION: These data suggest that FBP may be beneficial as auxiliary drug for the treatment of patients with acquired glucocorticoid resistance.

Heme oxygenase/carbon monoxide-biliverdin pathway down regulates neutrophil rolling, adhesion and migration in acute inflammation.

BACKGROUND AND PURPOSE: Heme oxygenase (HO) activity is known to down-regulate inflammatory events. Here, we address the role of HO and its metabolites, carbon monoxide (CO) and biliverdin (BVD), in leukocyte rolling, adhesion and neutrophil migration during inflammatory processes. EXPERIMENTAL APPROACH: Intravital microscopy was used to evaluate leukocyte rolling and adhesion in the mesenteric microcirculation of mice. TNFalpha and IL-1beta were determined by ELISA and HO-1 protein expression by Western blot. KEY RESULTS: Intraperitoneal challenge with carrageenan enhanced HO-1 protein expression in mesentery and bilirubin concentration in peritoneal exudates. Pretreatment of mice with a non-specific inhibitor of HO (ZnDPBG) or with a HO-1 specific inhibitor (ZnPP IX) enhanced neutrophil migration, rolling and adhesion on endothelium induced by carrageenan. In contrast, HO substrate (hemin), CO donor (DMDC) or BVD reduced these parameters. The reduction of neutrophil recruitment promoted by HO metabolites was independent of the production of chemotactic cytokines. Inhibitory effects of CO, but not of BVD, were counteracted by treatment with a soluble guanylate cyclase (sGC) inhibitor, ODQ. Furthermore, inhibition of HO prevented the inhibitory effect of a nitric oxide (NO) donor (SNAP) upon neutrophil migration, while the blockade of NO synthase (NOS) activity by aminoguanidine did not affect the CO or BVD effects. CONCLUSIONS AND IMPLICATIONS: Metabolites of HO decreased leukocyte rolling, adhesion and neutrophil migration to the inflammatory site by a mechanism partially dependent on sGC. Moreover, inhibition by NO of neutrophil migration was dependent on HO activity.

Neutrophil function in severe sepsis.

Sepsis and septic shock continue to be a major cause of morbidity and mortality in critically ill patients. During the onset of sepsis, several inflammatory mediators, including cytokines, chemokines and nitric oxide are released systemically and mediate most of the pathophysiological events present in sepsis and septic shock, such as cardiovascular dysfunction and target-organ lesions. Polymorphonuclear leukocytes are critical effector cells during the inflammatory process and their migration to the infection focus is extremely important for the local control of bacterial growth and consequently for the prevention of bacterial dissemination. In experimental models and in human sepsis a profound failure of neutrophil migration to the infection focus is observed. It seems that the failure of neutrophil migration is dependent on toll-like receptor 4 (TLR4) and mediated by cytokines and chemokines, which induce the production of nitric oxide that inhibits neutrophil adhesion to venular endothelium and also the neutrophil chemotactic ability.

Effect of fructose-1,6-bisphosphate in the cold storage solution after 12 and 36 hours of rat liver preservation.

Fructose-1,6-bisphosphate (FBP) has been reported to have a protective effect on liver injury following ischemic/reperfusion periods because it maintains ATP levels during cold preservation. In the present study, we evaluated the effects of addition of FBP to storage solutions for cold liver preservation during 12 or 36 hours. Adult male Wistar rats were randomly divided into three experimental groups. The hepatic perfusion and preservation were performed with these solutions: UW; UW plus 10 mmol/L FBP; and FBP 10 mmol/L (FBPS) alone. The biochemical measurements of AST and ALT were performed on samples of the cold storage solution after 12- or 36-hour preservation. UW and FBPS solutions showed similar preservation grades at 12 hours. Addition of 10 mmol/L of FBP to UW solution induced liver injury and a poor preservation grade during 12 or 36 hours. UW solution was better than FBPS after 36 hours preservation. UW solution continues to offer a superior performance for liver preservation during long times; however, FBPS may be an alternative for short cold preservation times.

Protective effect of fructose-1,6-bisphosphate in the cold storage solution for liver preservation in rat hepatic transplantation.

Fructose-1,6-bisphosphate (FBP) has been reported to have a protective effect on liver injury following ischemic/reperfusion periods. FBP maintains ATP levels and thereby cellular energy metabolism, which is important to the liver during cold preservation. In the present study, we evaluated the effects of FBP on the composition of storage solutions for cold liver preservation. Adult male Wistar rats were randomly divided into three experimental groups. Hepatic perfusion and preservation were performed with UW, UW plus 10 mmol/L FBP (UWM), and FBP 10 mmol/L (FBPS) alone solutions. Biochemical measurements of AST, ALT, and TBARS were performed on samples of the cold storage solution at 0, 12, 18, and 24 hours preservation. FBPS and UW solutions showed similar preservation grades during 18 hours. Addition of 10 mmol/L of FBP to UW solution induced liver injury and a poor preservation grade. FBP appears to protect the liver from injury caused by free radicals when the preservation time is less than 18 hours. Therefore, FBP may exert a protective effect for the preservation of livers during cold storage, and could represent an important component of new cold storage solutions.

Sepse relacionada ao uso de cateter intravascular / Intravascular catheter - related sepsis

O objetivo deste trabalho foi relacionar de forma retrospectiva, o uso de cateteres intravasculares em pacientes hospitalizados em Unidades de Tratamento Intensivo (UTIs) com a incidência de bacteremia e sepse. Os cateteres (n = 250) foram semeados em ágar suplementado com 5% de sangue de carneiro. A cultura foi semi-quantitativa e, considerada positiva, quando encontrou-se o crescimento de 15 ou mais colônias em placa de agar. As hemoculturas foram incubadas e monitoradas pelo sistema Bact Alert (Organon Teknika). A identificação microbiana foi realizada através de provas convencionais ou sistemas automatizados. Do total de 250 cateteres, 12,4% tiveram cultura positiva (31/250), com maior frequência para Staphylococcus sp. coagulase negativa (49%). Foram realizadas hemoculturas de 13 pacientes que tiveram cultura positiva para o cateter intracath, sendo que 7 (58,8%) foram positivas e 4 dessas hemoculturas apresentaram o mesmo microorganismo encontrado no cateter, sinalizando uma bacteremia devida ao cateter (30,7%). Dos 7 pacientes, 4 (57%) evoluíram clinicamente para sepse e chegaram ao óbito. Esse achado, demonstra uma relação importante entre a implantação de cateteres intravasculares e o desenvolvimento de bacteremia e sepse.

The aim of this paper was to analyze a retrospective way from the use of catheters in patient hospitalized in Intensive Care Units, with bacteraemia incidence and sepsis. The catheters (n=250) were sowed in agar blood (5% of sheep blood). The culture was semi-quantitative and considered positive, when were found the growth 15 or more colonies in agar plate...