Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.

Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN. Black and tan, brachyuric obese/obese mice were randomized into 4 interventions groups: Active NBD peptide (10 and 6 µg/g body weight); Inactive mutant peptide (10 µg/g); and vehicle control. In vivo/ex vivo fluorescence imaging revealed efficient delivery of NBD peptide, systemic biodistribution and selective renal metabolization. In vivo administration of active NBD peptide improved albuminuria (>40% reduction on average) and kidney damage, decreased podocyte loss and basement membrane thickness, and modulated the expression of proinflammatory and oxidative stress markers. In vitro, NBD blocked IKK-mediated NF-κB induction and target gene expression in mesangial cells exposed to diabetic-like milieu. These results constitute the first nephroprotective effect of NBD peptide in a T2D mouse model that recapitulates the kidney lesions observed in DN patients. Targeting IKK-dependent NF-κB activation could be a therapeutic strategy to combat kidney inflammation in DN.

Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

Chronic kidney disease has become a major medical issue in recent years due to its high prevalence worldwide, its association with premature mortality, and its social and economic implications. A number of patients gradually progress to end-stage renal disease (ESRD), requiring then dialysis and kidney transplantation. Currently, approximately 40% of patients with diabetes develop kidney disease, making it the most prevalent cause of ESRD. Thus, more effective therapies for diabetic nephropathy are needed. In preclinical studies of diabetes, anti-inflammatory therapeutic strategies have been used to protect the kidneys. Recent evidence supports that immune cells play an active role in the pathogenesis of diabetic nephropathy. Th17 immune cells and their effector cytokine IL-17A have recently emerged as promising targets in several clinical conditions, including renal diseases. Here, we review current knowledge regarding the involvement of Th17/IL-17A in the genesis of diabetic renal injury, as well as the rationale behind targeting IL-17A as an additional therapy in patients with diabetic nephropathy.

VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy.

The absence of optimal treatments for Diabetic Nephropathy (DN) highlights the importance of the search for novel therapeutic targets. The vascular endothelial growth factor receptor 2 (VEGFR2) pathway is activated in experimental and human DN, but the effects of its blockade in experimental models of DN is still controversial. Here, we test the effects of a therapeutic anti-VEGFR2 treatment, using a VEGFR2 kinase inhibitor, on the progression of renal damage in the BTBR ob/ob (leptin deficiency mutation) mice. This experimental diabetic model develops histological characteristics mimicking the key features of advanced human DN. A VEGFR2 pathway-activation blockade using the VEGFR2 kinase inhibitor SU5416, starting after kidney disease development, improves renal function, glomerular damage (mesangial matrix expansion and basement membrane thickening), tubulointerstitial inflammation and tubular atrophy, compared to untreated diabetic mice. The downstream mechanisms involved in these beneficial effects of VEGFR2 blockade include gene expression restoration of podocyte markers and downregulation of renal injury biomarkers and pro-inflammatory mediators. Several ligands can activate VEGFR2, including the canonical ligands VEGFs and GREMLIN. Activation of a GREMLIN/VEGFR2 pathway, but not other ligands, is correlated with renal damage progression in BTBR ob/ob diabetic mice. RNA sequencing analysis of GREMLIN-regulated genes confirm the modulation of proinflammatory genes and related-molecular pathways. Overall, these data show that a GREMLIN/VEGFR2 pathway activation is involved in diabetic kidney disease and could potentially be a novel therapeutic target in this clinical condition.

Gremlin, A Potential Urinary Biomarker of Anca-Associated Crescentic Glomerulonephritis.

Gremlin renal overexpression has been reported in diabetic nephropathy, pauci-immune crescentic glomerulonephritis and chronic allograft nephropathy and has been implicated in the pathophysiology of the progression of renal damage. However, it is unknown whether urinary Gremlin can be associated with renal functional status, renal biopsy findings and outcome. To examine these associations we studied 20 patients with ANCA+ renal vasculitis and very high urinary Gremlin (354 ± 76 ug/gCr), 86 patients with other glomerular diseases and moderately elevated urinary Gremlin (83 ± 14 ug/gCr) and 11 healthy controls (urinary Gremlin 11.3 ± 2.4 ug/gCr). Urinary Gremlin was significantly correlated with renal expression of Gremlin (r = 0.64, p = 0.013) observed in cellular glomerular crescents, tubular epithelial cells and interstitial inflammatory cells. Moreover, urinary Gremlin levels were correlated with the number of glomerular crescents (r = 0.53; p < 0.001), renal CD68 positive cells (r = 0.71; p < 0.005), tubulointerstitial fibrosis (r = 0.50; p < 0.05), and serum creatinine levels (r = 0.60; p < 0.001). Interestingly, Gremlin expression was colocalized with CD68, CD163 (monocyte/macrophage markers) and CCL18 positive cells. ROC curve analysis showed that the cutoff value of urinary Gremlin in glomerular diseases as 43 ug/gCr with 72% of sensitivity and 100% of specificity [AUC: 0.96 (CI 95% 0.92-0.99] (p < 0.001). For ANCA+ renal vasculitis the value of urinary Gremlin of 241 ug/gCr had 55% of sensitivity and 100% of specificity [AUC: 0.81 (CI 95% 0.68-0.94) (p < 0.001]. Based on these results we propose that urinary Gremlin represents a non-invasive biomarker in ANCA+ renal vasculitis, and suggest a role of Gremlin in the formation of crescents.

Gremlin activates the Notch pathway linked to renal inflammation.

Preclinical studies suggest that Gremlin participates in renal damage and could be a potential therapeutic target for human chronic kidney diseases. Inflammation is a common characteristic of progressive renal disease, and therefore novel anti-inflammatory therapeutic targets should be investigated. The Notch signaling pathway is involved in kidney development and is activated in human chronic kidney disease, but whether Gremlin regulates the Notch pathway has not been investigated. In cultured tubular cells, Gremlin up-regulated gene expression of several Notch pathway components, increased the production of the canonical ligand Jagged-1, and caused the nuclear translocation of active Notch-1 (N1ICD). In vivo administration of Gremlin into murine kidneys elicited Jagged-1 production, increased N1ICD nuclear levels, and up-regulated the gene expression of the Notch effectors hes-1 and hey-1 All these data clearly demonstrate that Gremlin activates the Notch pathway in the kidney. Notch inhibition using the γ-secretase inhibitor DAPT impaired renal inflammatory cell infiltration and proinflammatory cytokines overexpression in Gremlin-injected mice and in experimental models of renal injury. Moreover, Notch inhibition blocked Gremlin-induced activation of the canonical and noncanonical nuclear factor-κB (NF-κB) pathway, identifying an important mechanism involved in the anti-inflammatory actions of Notch inhibition. In conclusion, Gremlin activates the Notch pathway in the kidney and this is linked to NF-κB-mediated inflammation, supporting the hypothesis that Notch inhibition could be a potential anti-inflammatory strategy for renal diseases.

Gremlin and renal diseases: ready to jump the fence to clinical utility?

The current therapeutic strategy for the treatment of chronic kidney diseases only ameliorates disease progression. During renal injury, developmental genes are re-expressed and could be potential therapeutic targets. Among those genes reactivated in the adult damaged kidney, Gremlin is of particular relevance since recent data suggest that it could be a mediator of diabetic nephropathy and other progressive renal diseases. Earlier studies have shown that Gremlin is upregulated in trans-differentiated renal proximal tubular cells and in several chronic kidney diseases associated with fibrosis. However, not much was known about the mechanisms by which Gremlin acts in renal pathophysiology. The role of Gremlin as a bone morphogenetic protein antagonist has clearly been demonstrated in organogenesis and in fibrotic-related disorders. Gremlin binds to vascular endothelial growth factor receptor 2 (VEGFR2) in endothelial and tubular epithelial cells. Activation of the Gremlin-VEGFR2 axis was found in several human nephropathies. We have recently described that Gremlin activates the VEGFR2 signaling pathway in the kidney, eliciting a downstream mechanism linked to renal inflammatory response. Gremlin deletion improves experimental renal damage, diminishing fibrosis. Overall, the available data identify the Gremlin-VEGFR2 axis as a novel therapeutic target for kidney inflammation and fibrosis and provide a rationale for unveiling new concepts to investigate in several clinical conditions.

Rapidly progressive glomerulonephritis associated to afebrile endocarditis and anti-proteinasa 3 anca / Glomerulonefritis rápidamente progresiva asociada a endocarditis afebril y anca anti-proteinasa 3

Absctrat Endocarditis associated with antiPR3 ANCA and acute kidney injure generates a challenge in its diagnosis and treatment. In order to make a review about that combination, we presented a patient with necrotizing glomerulonephritis produced by a Enterococcus faecalis's subacute endocarditis and antiPR3 ANCA positive. Differential diagnosis is made between an acute kidney failure produced by ANCA's vasculitis vs necrotizing glomerulonephritis by endocarditis. Frequently it is necessary to make a biopsy to get a diagnosis. Negative immunofluorescence will guide to vasculitis associated ANCA, while positive immune complexes will guide to poststreptococcal glomerulonephritis. Other challenge that generates the association of acute kidney disease, endocarditis and antiPR3 ANCA is the treatment. ANCA positive can prompt to start immunosuppressant treatments. However, in the context of endocarditis, it could be inadvisable and even dangerous to use it. For this reason, it is controversial the use of immunosuppressant in combination with antibiotics in the acute process, in contrast with the use of only antibiotics. In the current paper we collect the 19 reports in the literature about endocarditis associated with antiPR3 ANCA, the treatment and the renal evolution of each patient. We concluded, generally, a better improvement of kidney function in patients treated with only antibiotics than those patients treated with the combination of antibiotics and corticoids. However, there are so few reports that we can't consider significant the different between both treatment groups.

Resumen La endocarditis asociada a ANCA anti-PR3 e insuficiencia renal plantea un dilema tanto en su diagnóstico como tratamiento. Para abordar una revisión de dicho tema, se presenta el caso de un paciente con glomerulonefritis rápidamente progresiva secundaria a endocarditis subaguda por Enterococcus faecalis y positividad para ANCA anti-PR3. El diagnóstico diferencial principal se establecería entre una afectación renal de una vasculitis asociada a ANCA no diagnosticada previamente vs una glomerulonefritis postinfecciosa secundaria a la endocarditis. En muchos casos es necesario disponer de una biopsia renal que esclarezca el diagnóstico, ya que una inmunofluorescencia negativa orientará hacia una vasculitis, mientras que una positividad para inmunocomplejos iría a favor de una glomerulonefritis postestreptocócica. El tratamiento a seguir es otro reto que se plantea en la coexistencia de insuficiencia renal aguda, endocarditis y ANCA anti-PR3 positivo. La positividad de ANCAs induce a valorar iniciar tratamiento con inmunosupresores, no obstante, en el lecho de una endocarditis puede resultar desaconsejado e incluso poner en riesgo la vida del paciente someterlo a un estado de inmunosupresión. Es, por tanto, controvertido el uso de inmunosupresión en combinación con antibioterapia en el proceso agudo en contraposición al uso de antibioterapia exclusivamente. En el actual artículo se recogen los 19 casos publicados en la literatura de endocarditis asociados a ANCA anti-PR3, así como el tratamiento que se realizó en cada uno de los casos y la evolución en la función renal de cada paciente, concluyendo, en general, una mejor recuperación de la función renal en los pacientes tratados con antibioterapia en exclusiva que en aquellos tratados con la combinación antibiótico-corticoides. Sin embargo, dado el pequeño tamaño muestral, no se puede considerar significativa la diferencia entre ambos tratamientos.

Bisphenol (A) uremic toxin to take into account in the Renal disease in Hemodialysis / Bisfenol (A) una toxina a tener en cuenta en el enfermo renal en hemodiálisis

Abstract Introduction: Most uremic toxins are by-products of protein metabolism by action of intestinal flora. The metabolism of aromatic amino acids originates phenolic type residues. The most studied is p-cresol that is associated with renal function and vascular damage. Bisphenol A (BPA) is an exogenous molecule with characteristics similar to these aromatic uremic toxins. BPA is an estrogenic endocrine disruptor, found in tin cans, plastic bottles, epoxy resins and in some dialyzers. This molecule accumulates in patients who have impaired renal function. Observational studies have shown that exposure of BPA is linked to renal and cardiovascular injury, among many others in humans, and in animal studies a causal link has been described. Kidneys with normal renal function rapidly excrete BPA, but insufficient excretion in patients with CKD results in accumulation of BPA in the body.

Resumen Muchas toxinas urémicas son originadas como consecuencia del catabolismo proteico por la flora intestinal. El metabolismo de aminoácidos aromáticos origina residuos de tipo fenólico. De estas toxinas, la más estudiada es el p-cresol, que se asocia a la función renal y daño vascular. El Bisfenol A (BPA) es una molécula exógena de características semejantes a estas toxinas urémicas aromáticas. El BPA es un disruptor endocrino estrogénico que se encuentra en latas de conserva, botellas de plástico, resinas epoxi y en algunos dializadores. Esta molécula se acumula en pacientes que tienen deteriorada la función renal. Estudios observacionales han demostrado que una exposición a BPA está vinculada, entre otras muchas, a lesión renal y cardiovascular en los seres humanos; en estudios en animales se ha descrito un vínculo causal. Los riñones con función renal normal excretan rápidamente BPA, pero una excreción insuficiente en pacientes con ERC da lugar a la acumulación del BPA en el organismo.

Tubular overexpression of gremlin induces renal damage susceptibility in mice.

A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-ß. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1) specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-ß and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage progression. This transgenic mouse model could be used as a new tool for enhancing the knowledge of renal disease progression.

Expression of gremlin, a bone morphogenetic protein antagonist, in glomerular crescents of pauci-immune glomerulonephritis.

BACKGROUND: Recent evidence in vitro and in vivo suggests that gremlin, a bone morphogenetic protein antagonist, is participating in tubular epithelial mesenchymal transition (EMT) in diabetic nephropathy as a downstream mediator of TGF-beta. Since EMT also occurs in parietal epithelial glomerular cells (PECs) leading to crescent formation, we hypothesized that gremlin could participate in this process. With this aim we studied its expression in 30 renal biopsies of patients with pauci-immune crescentic nephritis. METHODS: Gremlin was detected by in situ hybridization (ISH) and immunohistochemistry (IMH) and TGF-beta by ISH and Smads by southwestern histochemistry (SWH). Phosphorylated Smad2, CTGF, BMP-7, PCNA, alpha-SMA, synaptopodin, CD-68, and phenotypic markers of PECs (cytokeratin, E-cadherin), were detected by IMH. In cultured human monocytes, gremlin and CTGF induction by TGF-beta was studied by western blot. RESULTS: We observed strong expression of gremlin mRNA and protein in cellular and fibrocellular crescents corresponding to proliferating PECs and monocytes, in co-localization with TGF-beta. A marked over-expression of gremlin was also observed in tubular and infiltrating interstitial cells, correlating with tubulointerstitial fibrosis (r=0.59; P<0.01). A nuclear Smad activation in the same tubular cells, that are expressing TGF-beta and gremlin, was detected. In human cultured monocytes, TGF-beta induced gremlin production while CTGF expression was not detected. CONCLUSION: We postulate that gremlin may play a role in the fibrous process in crescentic nephritis, both in glomerular crescentic and tubular epithelial cells. The co-localization of gremlin and TGF-beta expression found in glomeruli and tubular cells suggest that gremlin may be important in mediating some of the pathological effects of TGF-beta.

NF-kappaB activation and overexpression of regulated genes in human diabetic nephropathy.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) regulates genes involved in renal disease progression, such as the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES. NF-kappaB is activated in experimental models of renal injury, and in vitro studies also suggest that proteinuria and angiotensin II could be important NF-kappaB activators. It has been proposed that locally produced MCP-1 may be involved in the development of diabetic nephropathy (DN). We examined the hypothesis that NF-kappaB could be an indicator of renal damage progression in DN. METHODS: Biopsy specimens from 11 patients with type 2 diabeties and overt nephropathy were studied by southwestern histochemistry for the in situ detection of activated NF-kappaB. In addition, by immunohistochemistry and/or in situ hybridization, we studied the expression of MCP-1 and RANTES, whose genes are regulated by NF-kappaB. RESULTS: NF-kappaB was detected mainly in cortical tubular epithelial cells and, to a lesser extent, in some glomerular and interstitial cells. A strong upregulation of MCP-1 and RANTES was observed in all the cases, mainly in tubular cells, and there was a strong correlation between the expression of these chemokines and NF-kappaB activation in the same cells, as observed in serial sections (r = 0.7; P = 0.01). In addition, the tubular expression of these chemokines was correlated mainly with the magnitude of the proteinuria (P = 0.002) and with interstitial cell infiltration (P<0.05). CONCLUSIONS: The activation of NF-kappaB and the transcription of certain pro-inflammatory chemokines in tubular epithelial cells are markers of progressive DN. Proteinuria might be one of the main factors inducing the observed pro-inflammatory phenotype.

Preliminary study of community-acquired Staphylococcus aureus infection in Manaus Hospital, Amazonia Region, Brazil

Methicillin resistant Staphylococcus aureus is considered a public health problem with a strong potential for dissemination and high rates of morbidity and mortality. In this study we describe bacteriological and epidemiological characteristics of Staphylococcus aureus in Manaus (Amazon region). During the one-year study period (2000-2001), sixteen cases of acute pyogenic multiple abscess were evaluated. Community-acquired S. aureus was identified as causative agent in 10 (62.5 percent) patients. The strains tested with antimicrobials by discs diffusion method, exhibited a high rate of sensitivity to cephalexin (100 percent), erythromycin (90 percent). Oxacillin-susceptible Staphylococcus aureus was 90 percent. No isolate was resistant to Vancomycin. To our knowledge, no series of community-acquired Staphylococcus aureus in Manaus hospital has been published. Our partial results showed a high rate of antimicrobial sensitivity among community-acquired Staphylococcus aureus in the hospital of Tropical Medicine Institute of Manaus, Amazon Region.

Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy.

BACKGROUND: The molecular mechanisms of renal injury and fibrosis in proteinuric nephropathies are not completely elucidated but the renin-angiotensin system (RAS) is involved. Idiopathic membranous nephropathy (MN), a proteinuric disease, may progress to renal failure. Our aim was to investigate the localization of RAS components in MN and their correlation with profibrotic parameters and renal injury. METHODS: Renal biopsies from 20 patients with MN (11 with progressive disease) were studied for the expression of RAS components [angiotensin-converting enzyme (ACE) and angiotensin II (Ang II)] by immunohistochemistry. Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF)-BB were studied by by in situ hybridization, and myofibroblast transdifferentiation by alpha-smooth muscle actin (alpha-SMA) staining. RESULTS: ACE immunostaining was elevated in tubular cells and appeared in interstitial cells colocalized in alpha-actin-positive cells in progressive disease. Elevated levels of Ang II were observed in tubules and infiltrating interstitial cells. TGF-beta and PDGF mRNAs were up-regulated mainly in cortical tubular epithelial cells in progressive disease (P < 0.01) and correlated with the myofibroblast transdifferentiation (r = 0.8, P < 0.01 for TGF-beta; r = 0.6, P < 0.01 for PDGF). Moreover, in serial sections of progressive cases, the ACE and Ang II over-expression was associated with the tubular expression of these pro-fibrogenic factors, and with the interstitial infiltration and myofibroblast activation. CONCLUSION: Intrarenal RAS is selectively activated in progressive MN. De novo expression of ACE at sites of tubulointerstitial injury suggests that the in situ Ang II generation could participate in tubular TGF-beta up-regulation, epithelial-myofibroblast transdifferentiation, and disease progression. These results suggest a novel role of Ang II in human tubulointerstitial injury.

Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy.

BACKGROUND: The molecular mechanisms of renal injury in diabetic nephropathy (DN) are not completely understood, although inflammatory cells play a key role. The renin-angiotensin system (RAS) is involved in kidney damage; however, few studies have examined the localization of RAS components in human DN. Our aim was to investigate in renal biopsies the expression of RAS and their correlation with proinflammatory parameters and renal injury. METHODS: The biopsies from 10 patients with type 2 diabetes mellitus and overt nephropathy were studied for the expression of RAS components by immunohistochemistry (IH). In addition, by Southwestern histochemistry we studied the in situ detection of the activated nuclear factor kappa B (NFkappaB), and by IH and/or in situ hybridization (ISH), the expression of monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES), whose genes are regulated by NFkappaB. RESULTS: Angiotensin-converting enzyme (ACE) immunostaining was elevated in tubular cells and appeared in interstitial cells. Elevated levels of angiotensin II (Ang II) immunostaining were observed in tubular and infiltrating interstitial cells. There was also a down-regulation of AT1 and up-regulation of AT2 receptors. An activation of NFkappaB and a marked up-regulation of NFkappaB-dependent chemokines mainly in tubular cells was observed. Elevated levels of NFkappaB, chemokines, and Ang II in tubules were correlated with proteinuria and interstitial cell infiltration. CONCLUSIONS: Our results show that in human DN, RAS components are modified in renal compartments, showing elevated local Ang II production, activation of tubular cells, and induction of proinflammatory parameters. These data suggest that Ang II contributes to the renal inflammatory process, and may explain the molecular mechanisms of the beneficial effect of RAS blockade.

Preliminary study of community-acquired Staphylococcus aureus infection in Manaus Hospital, Amazonia Region, Brazil.

Methicillin resistant Staphylococcus aureus is considered a public health problem with a strong potential for dissemination and high rates of morbidity and mortality. In this study we describe bacteriological and epidemiological characteristics of Staphylococcus aureus in Manaus (Amazon region). During the one-year study period (2000-2001), sixteen cases of acute pyogenic multiple abscess were evaluated. Community-acquired S. aureus was identified as causative agent in 10 (62.5%) patients. The strains tested with antimicrobials by discs diffusion method, exhibited a high rate of sensitivity to cephalexin (100%), erythromycin (90%). Oxacillin-susceptible Staphylococcus aureus was 90%. No isolate was resistant to Vancomycin. To our knowledge, no series of community-acquired Staphylococcus aureus in Manaus hospital has been published. Our partial results showed a high rate of antimicrobial sensitivity among community-acquired Staphylococcus aureus in the hospital of Tropical Medicine Institute of Manaus, Amazon Region.