RESUMO Klebsiella pneumoniae é um patógeno oportunista, responsável por diversos tipos de infecções nosocomiais, e é considerado um microrganismo multirresistente. Dados na literatura que forneçam informações a respeito da resistência desse microrganismo a antimicrobianos em amostras de animais são escassos. Dessa forma, o objetivo deste trabalho foi avaliar o perfil e o seu aumento das resistências a antimicrobianos dentro da medicina veterinária. Um total de 67 isolados de K. pneumoniae, provenientes de diferentes sítios de isolamento de animais domésticos (39/67) e silvestres (28/67), foi confirmado por sequenciamento do gene 16S rRNA. O maior percentual de isolamento de K. pneumoniae foi de amostras de urina, com 16% (11/67), fezes, com 15% (10/67), e pulmão, com 13,5% (09/67). No perfil de resistência, foram testadas 11 categorias de antibióticos, sendo a maior taxa de resistência ao metronidazol 97% (65/67), à ampicilina 94% (63/67), à amoxicilina 93% (62/67), às sulfonamidas 93% (62/67), à colistina 93% (62/67) e à nitrofurantoína 88% (59/67). Aqueles que apresentaram menor taxa de resistência foram: meropenem 3% (2/67), imipenem 6% (4/67) e amicacina 16% (11/67). Todos os isolados foram considerados bactérias multirresistentes (MRD), com o índice de resistência múltipla aos antibióticos (IRMA) variando de 0,15 a 0,85 e com 60 tipos de padrões de resistência. O resultado deste estudo reforça que os animais são reservatórios de K. pneumoniae multirresistentes.

Background Defective complement inhibition can lead to the formation of membrane attack complexes (MAC; C5b‐9) on the plasma membranes of vascular endothelial cells, resulting in injury that drives the progression of thrombotic microangiopathy (TMA), a key pathology in kidney disease. Objective/Methods We examined the response of human endothelial cells to complement‐mediated damage using blood outgrowth endothelial cells (BOECs) derived from healthy donors. BOECs were sensitized to complement factors present in normal human serum to induce the formation of C5b‐9 on their plasma membranes. Results This triggered an expected abrupt rise in intracellular Ca2+ reflecting membrane leakage. Remarkably, while intracellular Ca2+ remained elevated, membrane leakage ceased within 30 minutes, and cells did not show significant death. Extensive mobilization of Weibel‐Palade bodies (WPBs) was observed along with secretion of von Willebrand factor (VWF). The potential role of WPBs and VWF in mitigating complement‐mediated damage was examined by comparing the effects of C5b‐9 on BOECs derived from von Willebrand disease (VWD) patients expressing reduced amounts of VWF, lacking expression of functional VWF, or lacking both VWF and WPBs. BOECs lacking WPBs were not resistant to complement‐mediated damage, but became resistant when transfected to express VWF (and thus WPBs). Conclusion We conclude that BOECs exposed to C5b‐9 attack respond by mobilizing WPBs, which mitigate and repair damage by fusing with the plasma membrane. We propose that a similar cell‐specific response may protect the vascular endothelium from complement‐mediated damage in vivo.

Introduction Gordonia species, aerobic, weakly acid-fast, Gram-positive bacilli, are a rare cause of peritonitis in patients undergoing peritoneal dialysis (PD). We report the first pediatric case of PD-related peritonitis caused by Gordonia bronchialis . Case presentation A 13-year-old girl with chronic kidney disease (CKD) stage 5D, on continuous cycling PD (CCPD) for 8 years, presented with cloudy PD effluent, with no abdominal discomfort or fever. Intra-peritoneal (IP) loading doses of vancomycin and ceftazidime were started at home after obtaining a PD effluent sample, which showed WBC 2,340 × 10 /L (59% neutrophils) and Gram-positive bacilli. On admission, she was clinically well and afebrile, with no history of methicillin-resistant Staphylococcus aureus (MRSA) infection, so vancomycin was discontinued, and IP ceftazidime and cefazolin were started, following a loading dose of intravenous cefazolin. Gordonia species grew after 5 days of incubation and later identified as Gordonia bronchialis . IP vancomycin was restarted as monotherapy, empirically for a total of 3 weeks therapy. A 2-week course of oral ciprofloxacin was added, based on susceptibility testing. PD catheter replacement was advised due to the risk of recurrence but was refused. A relapse occurred 16 days after discontinuing antibiotics, successfully treated with a 2-week course of IP ceftazidime and vancomycin. The PD catheter was removed and hemodialysis initiated. She received a further 2-week course of oral ciprofloxacin and amoxicillin-clavulanate post PD catheter removal. Conclusions Gordonia bronchialis is an emerging pathogen in PD peritonitis and appears to be associated with a high risk of relapse. PD catheter replacement is strongly suggested.

Podocytes are differentiated epithelial cells which play an essential role to ensure a normal function of the glomerular filtration barrier (GFB). In addition to their adhesive properties in maintaining the integrity of the filtration barrier, they have other functions, such as synthesis of components of the glomerular basement membrane (GBM), production of vascular endothelial growth factor (VEGF), release of inflammatory proteins, and expression of complement components. They also participate in the glomerular crosstalk through multiple signalling pathways, including endothelin-1, VEGF, transforming growth factor β (TGFβ), bone morphogenetic protein 7 (BMP-7), latent transforming growth factor β-binding protein 1 (LTBP1), and extracellular vesicles.Growing literature suggests that podocytes share many properties of innate and adaptive immunity, supporting a multifunctional role ensuring a healthy glomerulus. As consequence, the “immune podocyte” dysfunction is thought to be involved in the pathogenesis of several glomerular diseases, referred to as “podocytopathies.” Multiple factors like mechanical, oxidative, and/or immunologic stressors can induce cell injury. The complement system, as part of both innate and adaptive immunity, can also define podocyte damage by several mechanisms, such as reactive oxygen species (ROS) generation, cytokine production, and endoplasmic reticulum stress, ultimately affecting the integrity of the cytoskeleton, with subsequent podocyte detachment from the GBM and onset of proteinuria.Interestingly, podocytes are found to be both source and target of complement-mediated injury. Podocytes express complement proteins which contribute to local complement activation. At the same time, they rely on several protective mechanisms to escape this damage. Podocytes express complement factor H (CFH), one of the main regulators of the complement cascade, as well as membrane-bound complement regulators like CD46 or membrane cofactor protein (MCP), CD55 or decay-accelerating factor (DAF), and CD59 or defensin. Further mechanisms, like autophagy or actin-based endocytosis, are also involved to ensure podocyte homeostasis and protection against injury.This review will provide an overview of the immune functions of podocytes and their response to immune-mediated injury, focusing on the pathogenic link between complement and podocyte damage.

The final version of this article unfortunately contained a mistake. During typesetting process, the magnitude of the WBC reported in the abstract was erroneously rendered as WBC 2,340 × 10 /L (59% neutrophils) and Gram-positive bacilli. The correct magnitude, however, is WBC 2,340 × 10 6 /L (59% neutrophils) and Gram-positive bacilli.

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Calcineurin inhibitor (CNI) use significantly reduced acute rejection rates and revolutionized early allograft and patient outcomes post-transplantation. However, known nephro-and vascular toxicity preclude its use and contribute to chronic allograft injury, negatively impacting longer term outcomes. Evolving evidence suggest a role for complement dysregulation in the pathogenesis of CNI-induced endothelial injury. In an in vitro model using Blood Outgrowth Endothelial Cells (BOEC) isolated from healthy donors and a donor with a pathogenic MCP/CD46 variant, we showed that cyclosporine resulted in a dose and time dependent increase in complement deposition, enhanced by anti-CD59 sensitization. We showed for the first time that MCP/CD46 deficient BOECs were genetically predisposed to be more susceptible to cyclosporine-induced complement deposition (multiple-hit hypothesis). We found complement factor H surface dysregulation to play a key role in cyclosporine-induced complement activation on BOEC surfaces, with glycocalyx abolishment possibly being the key mechanism leading to alternative pathway dysregulation.iii