RESUMO
Introduction: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation. Methods: We examined complement activation throughout Staphylococcus epidermidis (S. epidermidis) central nervous system (CNS) catheter infection. In addition, based on accumulating evidence that C3 plays a role in synaptic pruning in other neuroinflammatory states we determined if C3 and downstream C5 led to alterations in synaptic protein levels. Using our murine model of S. epidermidis catheter infection we quantified levels of the complement components C1q, Factor B, MASP2, C3, and C5 over the course of infection along with bacterial burdens. Results: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and the wealth of information regarding the emerging roles of C1q in the CNS, this suggests functions beyond pathogen elimination during S. epidermidis CNS catheter infection. To identify if C3 impacted synaptic protein levels we performed synaptosome isolation and quantified levels of VGLUT1 and PSD95 as well as pre-, post- and total synaptic puncta in cortical layer V of C3 knockout (KO) and wild type mice. We also used C5 KO and wild type mice to determine if there was any difference in pre-, post- and total synaptic puncta. Discussion: Neither C3 nor C5 impacted synaptic protein abundance. These findings suggest that chronic elevations in C1q in the brain that persist once CNS catheter infection has resolved may be modulating disease sequalae.
Assuntos
Infecções Relacionadas a Cateter , Complemento C1q , Infecções Estafilocócicas , Staphylococcus epidermidis , Animais , Staphylococcus epidermidis/fisiologia , Camundongos , Complemento C1q/metabolismo , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/imunologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Masculino , Ativação do Complemento , Feminino , Doença Crônica , Camundongos KnockoutRESUMO
Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Biofilmes , Staphylococcus aureus/imunologia , Animais , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/terapia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estafilocócicas/microbiologia , Ácidos Teicoicos/imunologia , Ácidos Teicoicos/metabolismoRESUMO
Tsukamurella species are Gram-positive bacilli related to aerobic Actinomyces. Originally reported from the environment, Tsukamurella species have also been described in human infections, especially in bacteremia. A literature review analysis revealed that Tsukamurella spp. are often initially considered as contaminant microorganisms, especially due to bacterial identification issues. Here, we report a catheter-related bloodstream infection in an immunocompromised child caused by Tsukamurella pulmonis. Matrix-Assisted Laser Desorption/Ionization-Time Of Flight (MALDI-TOF) mass spectrometry allowed rapid genus-level identification and contributed to better patient care. However, accurate species-level identification required 16S rRNA gene sequencing and secA1 gene sequencing. Considering the increased number of Tsukamurella infections, the implementation of new Tsukamurella species in MALDI-TOF databases is required to be more discriminant.
Assuntos
Actinobacteria/isolamento & purificação , Bacteriemia/diagnóstico , Infecções Relacionadas a Cateter/diagnóstico , Hospedeiro Imunocomprometido , Actinobacteria/química , Actinobacteria/genética , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/imunologia , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Cateteres Venosos Centrais/efeitos adversos , DNA Bacteriano/genética , Feminino , Humanos , Lactente , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Resultado do TratamentoAssuntos
Bacteriemia/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Dermatite Atópica/imunologia , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Bacteriemia/imunologia , Bacteriemia/microbiologia , Bacteriemia/terapia , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/terapia , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Pele/imunologia , Pele/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento , Dispositivos de Acesso Vascular/efeitos adversosRESUMO
OBJECTIVE: Patients suffering from haemato-oncological diseases tend to have a weakened immune system after the end of their therapy. To avoid infections, patients are advised to limit contact with other people. This poses the question whether a stay at a rehabilitation facility can be recommended. METHODS: We report about 134 rehabilitation stays of patients. Premature discontinuation of the rehabilitation stay was selected as the criterion for a serious complication during the rehabilitation, and the underlying reasons were analysed. RESULTS: Compared to the discontinuation rates of patients suffering from solid tumours (2.4%), the percentage of haemato-oncological patients ending prematurely their rehabilitation stay (8.2%) is significantly increased. This rises to 17.1% for patients who have undergone an allogeneic stem cell transplantation. The analysis of the discontinuation reasons revealed that they were not directly connected to the rehabilitation. Apart from the already known risk factors for premature termination of the rehabilitation stay, we have identified the period (days) between the last therapy and the beginning of the rehabilitation stay as a risk factor. CONCLUSIONS: We show for the first time that a rehabilitation stay does not pose additional risks for patients suffering from haemato-oncological diseases.
Assuntos
Febre de Causa Desconhecida/epidemiologia , Neoplasias Hematológicas/reabilitação , Hospedeiro Imunocomprometido , Reinfecção/epidemiologia , Idoso , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/imunologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Neutropenia Febril/epidemiologia , Neutropenia Febril/imunologia , Feminino , Febre de Causa Desconhecida/imunologia , Alemanha/epidemiologia , Neoplasias Hematológicas/imunologia , Hospitais de Reabilitação , Humanos , Controle de Infecções , Masculino , Pessoa de Meia-Idade , Pancitopenia/epidemiologia , Pancitopenia/imunologia , Centros de Reabilitação , Reinfecção/imunologia , Estudos Retrospectivos , Risco , Transplante de Células-Tronco , Fatores de Tempo , Transplante HomólogoRESUMO
Urinary tract infections (UTIs) are one of the most common bacterial infections. Conventional approaches to diagnose these infections rely on microbial urine culture, urine sediment microscopy and basic molecular urinalysis tests, in combination with assessments of patient symptoms that are indicative of UTI. The last decade has seen a more widespread clinical use of standardized MALDI-TOF methods to identify UTI-causing microbial agents. Shotgun proteomics methods to determine the extent of inflammation and types of immune cell effectors in urine have not become part of routine clinical tests. However, such methods are useful to investigate UTI pathogenesis, identify difficult-to-culture pathogens and understand antimicrobial effector mechanisms. The present chapter describes these approaches in order to gain quantitative and qualitative insights into inflammation and immune responses in patients with UTI and simultaneously profile the causative agents. The methods are also applicable to examine catheter-associated UTIs and vaginal infections from urine samples. Protocols provided here pertain to direct analyses of clinical specimens including urine sediments and urethral catheter biofilms.
Assuntos
Infecções Relacionadas a Cateter/imunologia , Proteômica/métodos , Infecções Urinárias/imunologia , Infecções Relacionadas a Cateter/urina , Cromatografia Líquida , Feminino , Humanos , Masculino , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem , Urinálise , Infecções Urinárias/urinaRESUMO
BACKGROUND: Alcohol (EtOH) poses a challenge in traumatic brain injuries (TBIs) given its metabolic and neurologic impact. Studies have had opposing results regarding mortality and complication rates in the intoxicated TBI patient. We hypothesized that trauma mechanism, brain injury severity, and blood alcohol concentration (BAC) would influence the impact of EtOH on mortality in TBI. METHODS: We performed a single-institution retrospective review of consecutive adult trauma patients tested for EtOH and a diagnosis of TBI. The primary outcome was mortality, and secondary outcomes included infectious complications. The primary analysis included univariate and multivariate regression comparing mortality between intoxicated and sober patients, at different values of BAC, different brain injury severities, and among mechanisms of trauma. RESULTS: Admission EtOH was assessed in 583 patients with TBI, with 256 testing positive for EtOH and 327 testing negative. Overall, EtOH was associated with lower mortality on univariate analysis (4.7% versus 8.9%, P = 0.05) but not on multivariate analysis (P = 0.21). There was no effect of EtOH on mortality when patients were stratified by brain injury severity or among penetrating trauma victims. However, EtOH was associated with lower overall infectious complications on univariate and multivariate regression. Finally, EtOH was predictive of mortality with an area under the receiver operator characteristic curve of 0.83. CONCLUSIONS: We found that EtOH is not associated with mortality in the patient with TBI, suggesting no causative effect. However, EtOH showed some predictability of mortality based on a receiver operator characteristic analysis. Interestingly, EtOH was associated with lower infectious complications, suggesting an immunomodulatory effect of EtOH in TBI.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Concentração Alcoólica no Sangue , Lesões Encefálicas Traumáticas/mortalidade , Etanol/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/imunologia , Etanol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/imunologia , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/imunologia , Análise de Sobrevida , Infecções Urinárias/epidemiologia , Infecções Urinárias/imunologiaRESUMO
Social interactions play an increasingly recognized key role in bacterial physiology1. One of the best studied is quorum sensing (QS), a mechanism by which bacteria sense and respond to the status of cell density2. While QS is generally deemed crucial for bacterial survival, QS-dysfunctional mutants frequently arise in in vitro culture. This has been explained by the fitness cost an individual mutant, a 'quorum cheater', saves at the expense of the community3. QS mutants are also often isolated from biofilm-associated infections, including cystic fibrosis lung infection4, as well as medical device infection and associated bacteraemia5-7. However, despite the frequently proposed use of QS blockers to control virulence8, the mechanisms underlying QS dysfunctionality during infection have remained poorly understood. Here, we show that in the major human pathogen Staphylococcus aureus, quorum cheaters arise exclusively in biofilm infection, while in non-biofilm-associated infection there is a high selective pressure to maintain QS control. We demonstrate that this infection-type dependence is due to QS-dysfunctional bacteria having a significant survival advantage in biofilm infection because they form dense and enlarged biofilms that provide resistance to phagocyte attacks. Our results link the benefit of QS-dysfunctional mutants in vivo to biofilm-mediated immune evasion, thus to mechanisms that are specific to the in vivo setting. Our findings explain why QS mutants are frequently isolated from biofilm-associated infections and provide guidance for the therapeutic application of QS blockers.
Assuntos
Biofilmes/crescimento & desenvolvimento , Infecções Relacionadas a Cateter/microbiologia , Evasão da Resposta Imune , Leucócitos/imunologia , Percepção de Quorum/fisiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Animais , Proteínas de Bactérias/genética , Infecções Relacionadas a Cateter/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Camundongos Endogâmicos C57BL , Viabilidade Microbiana , Mutação , Percepção de Quorum/genética , Infecções Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia , Transativadores/genéticaRESUMO
INTRODUCTION: Staphylococcal infections can cause significant morbidity in patients undergoing dialysis. This study evaluated the effects of HIV infection on nasal carriage of Staphylococcus aureus, staphylococcal peritonitis, and catheter infection rates in patients with end-stage renal failure managed with continuous ambulatory peritoneal dialysis (CAPD). METHODS: Sixty HIV-positive and 59 HIV-negative CAPD patients were enrolled and followed up for up to 18 months. S. aureus nasal carriage (detected by nasal swab culture), Staphylococcal peritonitis (diagnosed by clinical presentation, and CAPD effluent Staphylococcal culture and white blood cell count ≥100 cells/µL), and catheter infections (including exit site and tunnel infections) were assessed monthly. RESULTS: At 18 months, S. aureus nasal carriage rates were 43.3% and 30.5% (p = 0.147) and the methicillin-resistant S. aureus (MRSA) nasal carriage rates were 31.7% and 13.6% (p = 0.018) for the HIV-positive and HIV-negative cohorts, respectively. The HIV-positive cohort was associated with increased hazards for staphylococcal peritonitis, (adjusted hazard ratio [AHR] 2.85, 95% confidence interval [CI] 1.19-6.84, p = 0.019) due to increased coagulase-negative staphylococcal (CNS) peritonitis rate in the HIV-positive cohort compared with the HIV-negative cohort (0.435 vs. 0.089 episodes/person-years; AHR 7.64, CI 2.18-26.82, p = 0.001). On multivariable analysis, CD4+ cell count <200 cells/µL, diabetes, and S. aureus nasal carriage were found to be independent predictors of S. aureus peritonitis. CONCLUSIONS: These findings suggest that HIV infection may be a risk factor for MRSA nasal colonization and may increase the risks of CNS peritonitis, while a CD4+ cell count <200 cells/µL and S. aureus nasal carriage may be important predictors of S. aureus peritonitis.
Assuntos
Portador Sadio/epidemiologia , Infecções por HIV/imunologia , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Adulto , Portador Sadio/imunologia , Portador Sadio/microbiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Cateteres de Demora/efeitos adversos , Cateteres de Demora/microbiologia , Feminino , Seguimentos , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Nariz/microbiologia , Diálise Peritoneal Ambulatorial Contínua/instrumentação , Peritonite/epidemiologia , Peritonite/imunologia , Peritonite/microbiologia , Estudos Prospectivos , Fatores de Risco , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologiaRESUMO
Microbacterium species are coryneform gram-positive rods that are widely distributed in the environment and have been recently recognized as rare pathogens in humans. However, information about the epidemiologic and clinical characteristics of Microbacterium species is scarce. We herein reported an 11-year-old girl with acute leukemia who was found to have catheter-related bloodstream infection in her neutropenic phase. Gram-positive bacilli repeatedly grew on the blood cultures and were later confirmed by 16S rRNA analysis as Microbacterium paraoxydans. A literature review found available clinical courses in 21 cases (7 pediatric cases) of Microbacterium spp. bacteremia. Our case and those in literature suggested that Microbacterium spp. bacteremia often occurs in patients with indwelling central venous catheters; the literature review further suggested that removal of central venous catheters is required in most cases and that 16S rRNA sequence was useful in identifying in detail the species of Microbacterium.
Assuntos
Actinobacteria/isolamento & purificação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bacteriemia/diagnóstico , Infecções Relacionadas a Cateter/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Actinobacteria/genética , Actinobacteria/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bacteriemia/imunologia , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateteres Venosos Centrais/efeitos adversos , Criança , DNA Bacteriano/isolamento & purificação , Feminino , Humanos , Hospedeiro Imunocomprometido , Microbacterium , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , RNA Ribossômico 16S/genéticaRESUMO
Malassezia are lipophilic and commensal yeasts capable of inducing skin disease among susceptible hosts. However, severely immunocompromised patients and preterm infants admitted to intensive care units are particularly at risk of developing Malassezia systemic infections. Patients often have central venous catheters which are usually the portal of entry for colonization and infection. In addition to the clinically non-specific findings, a delay in the laboratorial diagnosis may occur as there is often the need to add lipid supplementation to culture in order to support these organisms' growth. Herein, we report three unrelated cases of Malassezia bloodstream infection at a university hospital during a 2-year period, followed by a discussion of the clinical results and comparison with the most recently available published data on epidemiology and risk factors, pathogenesis, diagnosis, susceptibility profile and treatment.
Assuntos
Antifúngicos/uso terapêutico , Infecções Relacionadas a Cateter/microbiologia , Dermatomicoses/microbiologia , Infecções Fúngicas Invasivas/microbiologia , Malassezia/patogenicidade , Idoso , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/imunologia , Cateteres Venosos Centrais/microbiologia , Pré-Escolar , Dermatomicoses/diagnóstico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/imunologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Recém-Nascido , Recém-Nascido Prematuro , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/imunologia , Metabolismo dos Lipídeos , Malassezia/imunologia , Malassezia/isolamento & purificação , Malassezia/metabolismo , Masculino , Pessoa de Meia-Idade , Pele/imunologia , Pele/microbiologia , Resultado do TratamentoAssuntos
Bacteriemia/microbiologia , Infecções por Bordetella/diagnóstico , Bordetella , Hospedeiro Imunocomprometido , Idoso , Alcaligenes faecalis/isolamento & purificação , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/imunologia , Bordetella/isolamento & purificação , Infecções por Bordetella/tratamento farmacológico , Infecções por Bordetella/imunologia , Neoplasias da Mama/complicações , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Coinfecção , Feminino , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/imunologia , Humanos , Metástase Neoplásica , Combinação Piperacilina e Tazobactam/uso terapêuticoRESUMO
Candida biofilms are a major cause of nosocomial morbidity and mortality. The mechanism by which Candida biofilms evade the immune system remains unknown. In this perspective, we develop a theoretical framework of the three, not mutually exclusive, models, which could explain biofilm evasion of host immunity. First, biofilms may exhibit properties of immunological silence, preventing immune activation. Second, biofilms may produce immune-deviating factors, converting effective immunity into ineffective immunity. Third, biofilms may resist host immunity, which would otherwise be effective. Using a murine subcutaneous biofilm model, we found that mice infected with biofilms developed sterilizing immunity effective when challenged with yeast form Candida. Despite the induction of effective anti-Candida immunity, no spontaneous clearance of the biofilm was observed. These results support the immune resistance model of biofilm immune evasion and demonstrate an asymmetric relationship between the host and biofilms, with biofilms eliciting effective immune responses yet being resistant to immunological clearance.
Assuntos
Biofilmes , Candida albicans/fisiologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Animais , Infecções Relacionadas a Cateter/imunologia , Feminino , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: Concerns for infections resulting from antineoplastic therapy-associated immunosuppression may deter referral for symptom palliation with a tunneled pleural catheter (TPC) in patients with malignant/para-malignant pleural effusions (MPE/PMPE). While rates of TPC-related infections range from 1 to 21%, those in patients receiving antineoplastic therapy with correlation to immune status has not been established. We aimed to assess TPC-related infection rates in patients on antineoplastic therapy, determine relation to immune system competency, and assess impact on the patient. METHODS: Patients with a MPE/PMPE undergoing TPC management associated with antineoplastic therapy, from 2008 to 2016, were reviewed and categorized into those with an immunocompromised versus immunocompetent immune status. RESULTS: Of the 150 patients, a TPC-related infection developed in 13 (9%): pleural space in 11 (7%) and superficial in 2 (1%). Ninety-three percent (139/150) were identified to be immunocompromised during their antineoplastic therapy. No difference in TPC-related infections was seen in patients with an immunocompromised (9%, 12/139) versus immunocompetent status (9%, 1/11); p = 0.614. The presence of a catheter-related infection did not negatively impact overall survival over a median follow-up of 144 days (interquartile range 41-341); p = 0.740. CONCLUSIONS: These results suggest that antineoplastic therapy may not significantly increase the overall risk of TPC-related infections, as the rate remains low and comparable to rates in patients not undergoing antineoplastic therapy. Regardless of immune status, the presence of a catheter-related infection did not negatively impact overall survival. These results should reassure clinicians that the need to initiate antineoplastic therapy should not delay definitive pleural palliation with a TPC.
Assuntos
Infecções Relacionadas a Cateter/etiologia , Cateteres de Demora/efeitos adversos , Neoplasias/terapia , Derrame Pleural Maligno/terapia , Idoso , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Drenagem/efeitos adversos , Drenagem/instrumentação , Drenagem/métodos , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/microbiologia , Cuidados Paliativos , Derrame Pleural Maligno/imunologia , Derrame Pleural Maligno/microbiologia , Pleurodese/efeitos adversos , Pleurodese/instrumentação , Pleurodese/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The iron-regulatory hormone hepcidin is induced early in infection, causing iron sequestration in macrophages and decreased plasma iron; this is proposed to limit the replication of extracellular microbes, but could also promote infection with macrophage-tropic pathogens. The mechanisms by which hepcidin and hypoferremia modulate host defense, and the spectrum of microbes affected, are poorly understood. Using mouse models, we show that hepcidin was selectively protective against siderophilic extracellular pathogens (Yersinia enterocolitica O9) by controlling non-transferrin-bound iron (NTBI) rather than iron-transferrin concentration. NTBI promoted the rapid growth of siderophilic but not nonsiderophilic bacteria in mice with either genetic or iatrogenic iron overload and in human plasma. Hepcidin or iron loading did not affect other key components of innate immunity, did not indiscriminately promote intracellular infections (Mycobacterium tuberculosis), and had no effect on extracellular nonsiderophilic Y enterocolitica O8 or Staphylococcus aureus Hepcidin analogs may be useful for treatment of siderophilic infections.
Assuntos
Infecções Relacionadas a Cateter/imunologia , Hemocromatose/imunologia , Hepcidinas/imunologia , Sobrecarga de Ferro/imunologia , Ferro/metabolismo , Infecções Estafilocócicas/imunologia , Animais , Ligação Competitiva , Infecções Relacionadas a Cateter/metabolismo , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/mortalidade , Modelos Animais de Doenças , Resistência à Doença , Expressão Gênica , Hemocromatose/metabolismo , Hemocromatose/microbiologia , Hemocromatose/mortalidade , Hepcidinas/agonistas , Hepcidinas/deficiência , Hepcidinas/genética , Humanos , Ferro/imunologia , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/microbiologia , Sobrecarga de Ferro/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/metabolismo , Oligopeptídeos/farmacologia , Ligação Proteica , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus , Análise de Sobrevida , Transferrina/genética , Transferrina/metabolismo , Yersinia enterocolitica/efeitos dos fármacos , Yersinia enterocolitica/crescimento & desenvolvimento , Yersinia enterocolitica/metabolismoRESUMO
Infectious endocarditis (IE), a complication that is both cardiac and infectious, occurs frequently and is associated with a heavy burden of morbidity and mortality in chronic hemodialysis patients (CHD). About 2-6% of chronic hemodialysis patients develop IE and the incidence is 50-60 times higher among CHD patients than in the general population. The left heart is the most frequent location of IE in CHD and the different published series report a prevalence of left valve involvement varying from 80% to 100%. Valvular and perivalvular abnormalities, alteration of the immune system, and bacteremia associated with repeated manipulation of the vascular access, particularly central venous catheters, comprise the main factors explaining the left heart IE in CHD patients. While left-sided IE develops in altered valves in a high-pressure system, right-sided IE on the contrary, generally develops in healthy valves in a low-pressure system. Right-sided IE is rare, with its incidence varying from 0% to 26% depending on the study, and the tricuspid valve is the main location. Might the massive influx of pathogenic and virulent germs via the central venous catheter to the right heart, with the tricuspid being the first contact valve, have a role in the physiopathology of IE in CHD, thus facilitating bacterial adhesion? While the physiopathology of left-sided IE entails multiple and convincing mechanisms, it is not the case for right-sided IE, for which the physiopathological mechanism is only partially understood and remains shrouded in mystery.
Assuntos
Bacteriemia/fisiopatologia , Infecções Relacionadas a Cateter/fisiopatologia , Endocardite Bacteriana/fisiopatologia , Coração/fisiopatologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Bacteriemia/epidemiologia , Bacteriemia/imunologia , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Cateterismo/efeitos adversos , Ecocardiografia , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/imunologia , Endocardite Bacteriana/microbiologia , Coração/microbiologia , Humanos , Incidência , Falência Renal Crônica/complicações , Falência Renal Crônica/imunologia , Diálise Renal/métodos , Fatores de RiscoRESUMO
Inflammation is one of the well-recognized nontraditional risk factors that contributes to the excessive cardiovascular mortality in peritoneal dialysis (PD) patients. Serum C-reactive protein and interleukin-6 levels are common surrogate markers used to measure inflammatory burden and predict adverse clinical outcomes in PD patients. Causes of inflammation are complex and can be categorized into factors related to a decrease in renal function and factors related to dialysis. They interact with each other and finally result in systemic and intraperitoneal inflammation. This review discusses the various causes and clinical implications of inflammation in PD patients. More importantly, potential therapeutic options that target the underlying pathogenic mechanisms are explored.
Assuntos
Adipocinas/imunologia , Doenças Cardiovasculares/imunologia , Infecções Relacionadas a Cateter/imunologia , Inflamação/imunologia , Falência Renal Crônica/terapia , Estresse Oxidativo/imunologia , Diálise Peritoneal , Peritonite/imunologia , Proteína C-Reativa/imunologia , Doenças Cardiovasculares/mortalidade , Cateteres de Demora , Endotoxemia/imunologia , Corpos Estranhos/imunologia , Humanos , Infecções/imunologia , Interleucina-6/imunologia , Falência Renal Crônica/imunologia , PrognósticoRESUMO
Pseudomonas aeruginosa is a multifaceted pathogen causing a variety of biofilm-mediated infections, including catheter-associated urinary tract infections (CAUTIs). The high prevalence of CAUTIs in hospitals, their clinical manifestations, such as urethritis, cystitis, pyelonephritis, meningitis, urosepsis, and death, and the associated economic challenges underscore the need for management of these infections. Biomaterial modification of urinary catheters with two drugs seems an interesting approach to combat CAUTIs by inhibiting biofilm. Previously, we demonstrated the in vitro efficacy of urinary catheters impregnated with azithromycin (AZM) and ciprofloxacin (CIP) against P. aeruginosa Here, we report how these coated catheters impact the course of CAUTI induced by P. aeruginosa in a murine model. CAUTI was established in female LACA mice with uncoated or AZM-CIP-coated silicone implants in the bladder, followed by transurethral inoculation of 108 CFU/ml of biofilm cells of P. aeruginosa PAO1. AZM-CIP-coated implants (i) prevented biofilm formation on the implant's surface (P ≤ 0.01), (ii) restricted bacterial colonization in the bladder and kidney (P < 0.0001), (iii) averted bacteriuria (P < 0.0001), and (iv) exhibited no major histopathological changes for 28 days in comparison to uncoated implants, which showed persistent CAUTI. Antibiotic implants also overcame implant-mediated inflammation, as characterized by trivial levels of inflammatory markers such as malondialdehyde (P < 0.001), myeloperoxidase (P < 0.05), reactive oxygen species (P ≤ 0.001), and reactive nitrogen intermediates (P < 0.01) in comparison to those in uncoated implants. Further, AZM-CIP-coated implants showed immunomodulation by manipulating the release of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 to the benefit of the host. Overall, the study demonstrates long-term in vivo effectiveness of AZM-CIP-impregnated catheters, which may possibly be a key to success in preventing CAUTIs.
Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/prevenção & controle , Ciprofloxacina/farmacologia , Infecções por Pseudomonas/prevenção & controle , Infecções Urinárias/prevenção & controle , Animais , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Materiais Revestidos Biocompatíveis/farmacologia , Preparações de Ação Retardada , Modelos Animais de Doenças , Feminino , Corpos Estranhos/tratamento farmacológico , Corpos Estranhos/imunologia , Corpos Estranhos/microbiologia , Interleucina-10/biossíntese , Interleucina-10/metabolismo , Interleucina-6/biossíntese , Interleucina-6/metabolismo , Camundongos , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/metabolismo , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/microbiologia , Cateteres Urinários/microbiologia , Infecções Urinárias/imunologia , Infecções Urinárias/microbiologiaRESUMO
Biofilm-related infections have become an increasingly important clinical problem. Many of these infections occur in patients with multiple comorbidities or with impaired immunity. Echinocandins (caspofungin, micafungin, and anidulafungin) exert their fungicidal activity by inhibition of the synthesis of the (1â3)-ß-d-glucan. They are active among in vitro and in vivo model systems against a number of Candida species and filamentous fungi in their planktonic and biofilm phenotype. Their superior activity against biofilms poses them in an advantageous position among the antifungal armamentarium. However, additional studies are warranted to expand our knowledge on the role of echinocandins against biofilm-related infections.
Assuntos
Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/tratamento farmacológico , Equinocandinas/uso terapêutico , Fungos/efeitos dos fármacos , Mucosa/microbiologia , Micoses/tratamento farmacológico , Anidulafungina , Animais , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Infecções Relacionadas a Cateter/imunologia , Infecções Relacionadas a Cateter/microbiologia , Modelos Animais de Doenças , Equinocandinas/química , Equinocandinas/metabolismo , Humanos , Imunomodulação , Testes de Sensibilidade Microbiana , Micoses/imunologia , Micoses/microbiologiaRESUMO
Catheter-related bacteremias carry high mortality rates in hematological patients. When a multidrug-resistant microorganism is involved, the catheter should ideally be removed; however, this approach is not always possible. Tigecycline lock therapy was used in two pediatric oncohematological patients with intravascular catheter-related infection due to KPC-producing Klebsiella pneumoniae. The catheter was salvaged in both cases, and the patients were later discharged. Our experience suggests the usefulness of this approach in treating this type of infection.