RESUMO
Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.
Assuntos
Artrite , Micoses , Osteomielite , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/epidemiologia , Fungos , Aspergillus , Artrite/tratamento farmacológico , Osteomielite/tratamento farmacológico , Antifúngicos/uso terapêuticoRESUMO
Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is known about its epidemiology, clinical manifestations, laboratory features, treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the English literature from 1967 through 2015 for variables of arthritis with Aspergillus spp. recovered from joint and/or adjacent bone, underlying conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging, management, and outcome. Among 31 evaluable cases, 87% were males and 13% pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were immunosuppressed with such conditions as hematological malignancies (26%), corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%) of patients had hematogenous seeding of the joint, and more than 80% had de novo infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints) occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical manifestations included pain (87%), edema (26%), and limited function (23%), with knees (35%), intervertebral discs (26%), and hips (16%) being most commonly infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus flavus in 13%, Aspergillus niger in 3%, and not specified in 7%. Median ESR was 90 mm/hr and median CRP was 3.6 mg/dl. Median synovial fluid WBC was 17,200/µL (7,300-128,000) with 72% PMNs (range 61-92). Osteolysis occurred in 35%, and soft-tissue extension 47%. Nineteen patients (61%) were managed with combined medical and surgical therapy, 10 (32%) with medical therapy only, and 2 (6%) surgery only. Amphotericin B and itraconazole were the most frequently used agents with median duration of therapy of 219 days (range 30-545). Surgical interventions included debridement in 61%, drainage 19%, and amputation 6%. Complete or partial response was achieved in 71% and relapse occurred in 16%. Medical therapy was reinstituted with successful outcome in these patients. Overall survival was 65%. Aspergillus arthritis mainly develops as a de novo infection involving knees and intervertebral disks in immunocompromised patients with localizing symptoms. Contiguous osteomyelitis is frequently observed. Diagnosis is established by synovial fluid culture. Aspergillus arthritis is therapeutically challenging with most patients undergoing surgery and protracted antifungal therapy.
Assuntos
Artrite/patologia , Artrite/terapia , Aspergilose/patologia , Aspergilose/terapia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Artrite/diagnóstico , Artrite/epidemiologia , Aspergilose/diagnóstico , Aspergilose/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Operatórios , Resultado do Tratamento , Adulto JovemRESUMO
Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014. Among 34 patients with median age 41 (0.5-73 years), 24 (71%) were males. While 12 (35%) were immunocompromised patients, 14 (41%) had prior surgery, and seven (21%) suffered trauma. Other underlying conditions included diabetes mellitus, hematological malignancies, transplantation, and corticosteroid therapy. The median diagnostic delay from onset of symptoms and signs was 60 (10-180) days. The principal mechanism of the infection was direct inoculation (n = 19; 56%), and in immunocompromised patients was usually hematogenous disseminated. The long bones were infected by trauma or surgery, while a wide variety of bones were involved by hematogenous dissemination. Combined surgery and amphotericin B treatment were implemented in 28 (82%) and eight (23%) had an unfavorable outcome. Osteoarticular mucormycosis occurs most frequently after trauma or surgical procedures. These infections are progressively destructive and more virulent in individuals with impaired immune systems. Early diagnosis, timely administration of amphotericin B, control of underlying conditions, and surgical debridement of infected tissue are critical for successful management of osteoarticular mucormycosis.
Assuntos
Artrite/diagnóstico , Artrite/epidemiologia , Mucorales/isolamento & purificação , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Osteomielite/diagnóstico , Osteomielite/epidemiologia , Adolescente , Adulto , Idoso , Antifúngicos/uso terapêutico , Artrite/patologia , Artrite/terapia , Criança , Pré-Escolar , Desbridamento , Diagnóstico Precoce , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mucormicose/patologia , Mucormicose/terapia , Osteomielite/patologia , Osteomielite/terapia , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/patologia , Infecção da Ferida Cirúrgica/terapia , Ferimentos e Lesões/complicações , Adulto JovemRESUMO
BACKGROUND: As more is understood regarding the human microbiome, it is increasingly important for nurse scientists and healthcare practitioners to analyze these microbial communities and their role in health and disease. 16S rRNA sequencing is a key methodology in identifying these bacterial populations that has recently transitioned from use primarily in research to having increased utility in clinical settings. OBJECTIVES: The objectives of this review are to (a) describe 16S rRNA sequencing and its role in answering research questions important to nursing science; (b) provide an overview of the oral, lung, and gut microbiomes and relevant research; and (c) identify future implications for microbiome research and 16S sequencing in translational nursing science. DISCUSSION: Sequencing using the 16S rRNA gene has revolutionized research and allowed scientists to easily and reliably characterize complex bacterial communities. This type of research has recently entered the clinical setting, one of the best examples involving the use of 16S sequencing to identify resistant pathogens, thereby improving the accuracy of bacterial identification in infection control. Clinical microbiota research and related requisite methods are of particular relevance to nurse scientists-individuals uniquely positioned to utilize these techniques in future studies in clinical settings.
Assuntos
Infecções Bacterianas/genética , Microbiota/genética , RNA Ribossômico 16S/genética , Infecções Bacterianas/enfermagem , Humanos , Controle de Infecções/métodos , Pesquisa Metodológica em Enfermagem , Reação em Cadeia da PolimeraseRESUMO
The mortality rate of alveolar hemorrhage (AH) after allogeneic hematopoietic stem cell transplantation is greater than 60% with supportive care and high-dose steroid therapy. We performed a retrospective cohort analysis to assess the benefits and risks of recombinant human factor VIIa (rFVIIa) as a therapeutic adjunct for AH. Between 2005 and 2012, 57 episodes of AH occurred in 37 patients. Fourteen episodes (in 14 patients) were treated with steroids alone, and 43 episodes (in 23 patients) were treated with steroids and rFVIIa. The median steroid dose was 1.9 mg/kg/d (interquartile range [IQR], 0.8 to 3.5 mg/kg/d; methylprednisolone equivalents) and did not differ statistically between the 2 groups. The median rFVIIa dose was 41 µg/kg (IQR, 39 to 62 µg/kg), and a median of 3 doses (IQR, 2 to 17) was administered per episode. Concurrent infection was diagnosed in 65% of the episodes. Patients had moderately severe hypoxia (median PaO2/FiO2, 193 [IQR, 141 to 262]); 72% required mechanical ventilation, and 42% survived to extubation. The addition of rFVIIa did not alter time to resolution of AH (P = .50), duration of mechanical ventilation (P = .89), duration of oxygen supplementation (P = .55), or hospital mortality (P = .27). Four possible thrombotic events (9% of 43 episodes) occurred with rFVIIa. rFVIIa in combination with corticosteroids did not confer clear clinical advantages compared with corticosteroids alone. In patients with AH following hematopoietic stem cell transplantation, clinical factors (ie, worsening infection, multiple organ failure, or recrudescence of primary disease) may be more important than the benefit of enhanced hemostasis from rFVIIa.
Assuntos
Fator VIIa/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Pneumopatias/tratamento farmacológico , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Pneumopatias/etiologia , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/patologia , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Transplante Homólogo , Adulto JovemRESUMO
Candidemia and other forms of invasive candidiasis are important causes of morbidity and mortality. The evolving challenge of antimicrobial resistance among fungal pathogens continues to highlight the need for potent, new antifungal agents. MEDLINE, EMBASE, Scopus and Web of Science searches (up to January 2014) of the English-language literature were performed with the keywords 'Candida' or 'Candidemia' or 'Candidiasis' and terms describing investigational drugs with activity against Candida spp. Conference abstracts and the bibliographies of pertinent articles were also reviewed for relevant reports. ClinicalTrials.gov was searched for relevant clinical trials. Currently available antifungal agents for the treatment of candidemia are summarised. Investigational antifungal agents with potential activity against Candida bloodstream infections and other forms of invasive candidiasis and vaccines for prevention of Candida infections are also reviewed as are selected antifungal agents no longer in development. Antifungal agents currently in clinical trials include isavuconazole, albaconazole, SCY-078, VT-1161 and T-2307. Further data are needed to determine the role of these compounds in the treatment of candidemia and other forms of invasive candidiasis. The progressive reduction in antimicrobial drug development may result in a decline in antifungal drug discovery. Still, there remains a critical need for new antifungal agents to treat and prevent invasive candidiasis and other life-threatening mycoses.
Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/prevenção & controle , Vacinas Fúngicas/imunologia , Vacinas Fúngicas/isolamento & purificação , Ensaios Clínicos como Assunto , Descoberta de Drogas/tendências , Drogas em Investigação , HumanosRESUMO
BACKGROUND: The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood. METHODS: Cases of Candida osteomyelitis from 1970 through 2011 were reviewed. Underlying conditions, microbiology, mechanisms of infection, clinical manifestations, antifungal therapy, and outcome were studied in 207 evaluable cases. RESULTS: Median age was 30 years (range, ≤ 1 month to 88 years) with a >2:1 male:female ratio. Most patients (90%) were not neutropenic. Localizing pain, tenderness, and/or edema were present in 90% of patients. Mechanisms of bone infection followed a pattern of hematogenous dissemination (67%), direct inoculation (25%), and contiguous infection (9%). Coinciding with hematogenous infection, most patients had ≥2 infected bones. When analyzed by age, the most common distribution of infected sites for adults was vertebra (odds ratio [OR], 0.09; 95% confidence interval [CI], .04-.25), rib, and sternum; for pediatric patients (≤18 years) the pattern was femur (OR, 20.6; 95% CI, 8.4-48.1), humerus, then vertebra/ribs. Non-albicans Candida species caused 35% of cases. Bacteria were recovered concomitantly from 12% of cases, underscoring the need for biopsy and/or culture. Candida septic arthritis occurred concomitantly in 21%. Combined surgery and antifungal therapy were used in 48% of cases. The overall complete response rate of Candida osteomyelitis of 32% reflects the difficulty in treating this infection. Relapsed infection, possibly related to inadequate duration of therapy, occurred among 32% who ultimately achieved complete response. CONCLUSIONS: Candida osteomyelitis is being reported with increasing frequency. Localizing symptoms are usually present. Vertebrae are the most common sites in adults vs femora in children. Timely diagnosis of Candida osteomyelitis with extended courses of 6-12 months of antifungal therapy, and surgical intervention, when indicated, may improve outcome.
Assuntos
Candidíase/epidemiologia , Osteomielite/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Osso e Ossos/microbiologia , Candida , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Criança , Pré-Escolar , Feminino , Histocitoquímica , Humanos , Lactente , Inflamação/microbiologia , Articulações/microbiologia , Masculino , Pessoa de Meia-Idade , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Triazole and imidazole antifungal agents inhibit metabolism of vincristine, leading to excess vinca alkaloid exposure and severe neurotoxicity. Recent reports of debilitating interactions between vincristine and itraconazole, as well as posaconazole, voriconazole and ketoconazole underscore the need to improve medical awareness of this adverse combination. We, therefore, undertook a comprehensive analysis of reports of adverse drug interactions (ADIs) with the combination of vincristine and azole antifungal agents, established a new classification, and provided a detailed summary of these toxicities. In patients who had sufficient data for analysis, 47 individuals were identified who had an ADI with the combination of vincristine and antifungal azoles. Median age was 8 years (1.3-68 years) with 33(70%) having a diagnosis of acute lymphoblastic leukaemia. Median time to ADI with vincristine was 9.5 days with itraconazole, 13.5 days posaconazole and 30 days voriconazole. The median number of vincristine doses preceding the ADI was 2 doses with itraconazole, 3 doses posaconazole and 2 doses voriconazole. The most common severe ADIs included gastrointestinal toxicity, peripheral neuropathy, hyponatremia/SIADH, autonomic neuropathy and seizures. Recovery from these ADIs occurred in 80.6% of patients. We recommend using alternative antifungal agents if possible in patients receiving vincristine to avoid this serious and potentially life-threatening drug interaction.
Assuntos
Antifúngicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Azóis/efeitos adversos , Vincristina/efeitos adversos , Adolescente , Antifúngicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Azóis/uso terapêutico , Criança , Pré-Escolar , Interações Medicamentosas , Feminino , Humanos , Lactente , Masculino , Vincristina/uso terapêutico , Adulto JovemRESUMO
Candida empyema is a serious complication of disseminated candidiasis. However, little is known about the intrapleural pharmacokinetics of echinocandins. We report the penetration of anidulafungin into the pleural fluid of a patient with Candida tropicalis empyema. The anidulafungin ratio for the area under the concentration-time curve from 0 h to the last measurement between pleural fluid and serum values was only 0.125 (12.5%), with pleural fluid concentrations ranging between 0.67 and 0.88 µg/ml.
Assuntos
Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candida/patogenicidade , Equinocandinas/farmacocinética , Equinocandinas/uso terapêutico , Empiema/tratamento farmacológico , Empiema/microbiologia , Adulto , Anidulafungina , Empiema Pleural/tratamento farmacológico , Empiema Pleural/microbiologia , Humanos , MasculinoRESUMO
We report the penetration of liposomal amphotericin B into the pleural fluid of a patient with pulmonary zygomycosis and empyema. The ratio of area under the concentration-versus-time curve in pleural fluid (AUC(pleural fluid)) to that in serum (AUC(serum)) for liposomal amphotericin B over 24 h was 9.4%, with pleural fluid concentrations of 2.12 to 4.91 microg/ml. Given the relatively low level of intrapleural penetration of liposomal amphotericin B, chest tube drainage may be warranted for successful treatment of zygomycotic empyema.
Assuntos
Anfotericina B/farmacocinética , Antifúngicos/farmacocinética , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/metabolismo , Mucormicose/tratamento farmacológico , Mucormicose/metabolismo , Derrame Pleural/metabolismo , Anfotericina B/administração & dosagem , Anfotericina B/sangue , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Empiema Pleural/tratamento farmacológico , Empiema Pleural/metabolismo , Feminino , Humanos , Lipossomos , Pneumopatias Fúngicas/sangue , Pessoa de Meia-Idade , Mucormicose/sangue , Derrame Pleural/tratamento farmacológicoRESUMO
OBJECTIVE: To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. CASE SUMMARY: Continuous infusion ceftazidime or aztreonam was administered to achieve target drug concentrations at or above the minimum inhibitory concentration, when possible, in 3 patients with P. aeruginosa infections. The maximal calculated target drug concentration was 100 mg/L. In the first patient, with primary immunodeficiency, neutropenia, and aggressive cutaneous T-cell lymphoma/leukemia, continuous infusion ceftazidime (6.5-9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient, with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient, with severe aplastic anemia, continuous infusion ceftazidime (7-16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. DISCUSSION: Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy, when no other options are available, is the continuous infusion of existing beta-lactam antibiotics to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in 3 chronically immunocompromised patients. CONCLUSIONS: Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients.
Assuntos
Antibacterianos/uso terapêutico , Hospedeiro Imunocomprometido , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamas/uso terapêutico , Adolescente , Adulto , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Masculino , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Resultado do Tratamento , beta-Lactamas/administração & dosagemRESUMO
Acute kidney injury (AKI) and cardiorenal syndrome (CRS) are increasingly prevalent in hospitalized patients with cardiovascular disease and remain associated with poor short- and long-term outcomes. There are no specific therapies to reduce mortality related to either AKI or CRS, apart from supportive care and volume status management. Acute renal replacement therapies (RRTs), including ultrafiltration, intermittent hemodialysis, and continuous RRT are used to manage complications of medically refractory AKI and CRS and may restore normal electrolyte, acid-base, and fluid balance before renal recovery. Patients who require acute RRT have a significant risk of mortality and long-term dialysis dependence, emphasizing the importance of appropriate patient selection. Despite the growing use of RRT in the cardiac intensive care unit, there are few resources for the cardiovascular specialist that integrate the epidemiology, diagnostic workup, and medical management of AKI and CRS with an overview of indications, multidisciplinary team management, and transition off of RRT.
Assuntos
Injúria Renal Aguda/terapia , Síndrome Cardiorrenal/terapia , Gerenciamento Clínico , Terapia de Substituição Renal/normas , Índice de Gravidade de Doença , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Síndrome Cardiorrenal/epidemiologia , Síndrome Cardiorrenal/fisiopatologia , Cardiologia/métodos , Cardiologia/normas , Hemofiltração/métodos , Hemofiltração/normas , Humanos , Diálise Renal/métodos , Diálise Renal/normas , Terapia de Substituição Renal/métodos , Estados Unidos/epidemiologia , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
We report a case of accelerated metabolism of voriconazole during therapy for invasive pulmonary aspergillosis, resulting in subtherapeutic levels. Target voriconazole levels were restored with high dosages of voriconazole (up to 40 mg/kg of body weight/day) and the addition of cimetidine as a cytochrome P450 enzyme inhibitor.
Assuntos
Antifúngicos/metabolismo , Cimetidina/farmacologia , Pirimidinas/metabolismo , Triazóis/metabolismo , Citocromo P-450 CYP3A/biossíntese , Interações Medicamentosas , Hemofiltração , Humanos , Masculino , Pessoa de Meia-Idade , VoriconazolRESUMO
OBJECTIVE: To describe the rationale, principles, and dosage calculations for continuous-infusion beta-lactam antibiotics to treat multidrug-resistant bacteria in patients undergoing continuous venovenous hemofiltration (CVVH). DATA SOURCES: A MEDLINE search (1968-November 2008) of the English-language literature was performed using the terms continuous infusion and Pseudomonas or Acinetobacter; hemofiltration or CVVH or hemodiafiltration or CVVHDF or continuous renal replacement therapy or pharmacokinetics; and terms describing different beta-lactam antibiotics. STUDY SELECTION AND DATA EXTRACTION: In vitro, in vivo, and human studies were evaluated that used continuous-infusion beta-lactam antibiotics to treat Pseudomonas aeruginosa and Acinetobacter baumannii infections. Studies were reviewed that described the pharmacokinetics of beta-lactam antibiotics during CVVH as well as other modalities of continuous renal replacement therapy. DATA SYNTHESIS: Continuous infusion of beta-lactam antibiotics, maintaining drug concentrations 4-5 times higher than the minimum inhibitory concentration, is a promising approach for managing infections caused by P. aeruginosa and A. baumannii. Safe yet effective continuous infusion therapy is made difficult by the occurrence of acute renal failure and the need for renal replacement therapy. Case series and pharmacokinetic properties indicate that several beta-lactam antimicrobials that have been studied for continuous infusion, such as cefepime, ceftazidime, piperacillin, ticarcillin, clavulanic acid, and tazobactam, are significantly cleared by hemofiltration. Methodology and formulas are provided that allow practitioners to calculate dosage regimens and reach target drug concentrations for continuous beta-lactam antibiotic infusions during CVVH based on a literature review, pharmacokinetic principles, and our experience at the National Institutes of Health Clinical Center. CONCLUSIONS: Continuous infusion of beta-lactam antibiotics may be a useful treatment strategy for multidrug-resistant gram-negative infections in the intensive care unit. Well-established pharmacokinetic and pharmacodynamic principles can be used to safely reach and maintain steady-state target concentrations of beta-lactam antibiotics in critical illness complicated by acute renal failure requiring CVVH.
Assuntos
Antibacterianos/administração & dosagem , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hemofiltração , beta-Lactamas/administração & dosagem , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Ensaios Clínicos como Assunto , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Infusões Intravenosas , Testes de Sensibilidade Microbiana , beta-Lactamas/efeitos adversos , beta-Lactamas/farmacocinéticaRESUMO
In March 2015, the extended-spectrum triazole antifungal isavuconazole was granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. Isavuconaozle has activity against a broad range of yeasts, dimorphic fungi, and molds and is associated with fewer toxicities than voriconazole. It also has predictable pharmacokinetics in adults, fewer drug-drug interactions than many existing antifungal agents, and is available in both oral and ß-cyclodextrin-free intravenous formulations. In this review, we explore what is known about the pharmacokinetics and pharmacodynamics of isavuconazole and look ahead to its expanding applications in clinical practice.
Assuntos
Antifúngicos/administração & dosagem , Infecções Fúngicas Invasivas/tratamento farmacológico , Nitrilas/administração & dosagem , Piridinas/administração & dosagem , Triazóis/administração & dosagem , Adulto , Animais , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Aspergilose/tratamento farmacológico , Interações Medicamentosas , Humanos , Infecções Fúngicas Invasivas/microbiologia , Mucormicose/tratamento farmacológico , Nitrilas/farmacocinética , Nitrilas/farmacologia , Piridinas/farmacocinética , Piridinas/farmacologia , Triazóis/farmacocinética , Triazóis/farmacologiaRESUMO
Contemporary cardiac intensive care units (CICUs) provide care for an aging and increasingly complex patient population. The medical complexity of this population is partly driven by an increased proportion of patients with respiratory failure needing noninvasive or invasive positive pressure ventilation (PPV). PPV often plays an important role in the management of patients with cardiogenic pulmonary edema, cardiogenic shock, or cardiac arrest, and those undergoing mechanical circulatory support. Noninvasive PPV, when appropriately applied to selected patients, may reduce the need for invasive mechanical PPV and improve survival. Invasive PPV can be lifesaving, but has both favorable and unfavorable interactions with left and right ventricular physiology and carries a risk of complications that influence CICU mortality. Effective implementation of PPV requires an understanding of the underlying cardiac and pulmonary pathophysiology. Cardiologists who practice in the CICU should be proficient with the indications, appropriate selection, potential cardiopulmonary interactions, and complications of PPV.
Assuntos
Respiração com Pressão Positiva , Algoritmos , Débito Cardíaco/fisiologia , Unidades de Cuidados Coronarianos , Circulação Coronária/fisiologia , Insuficiência Cardíaca/terapia , Hemodinâmica/fisiologia , Humanos , Hipóxia/terapia , Respiração , Choque Cardiogênico/terapia , Desmame do Respirador , Função Ventricular/fisiologiaRESUMO
PURPOSE: Results of an assessment of the chemical stability of isoniazid injection in 0.9% sodium chloride injection and 5% dextrose injection are reported. METHODS: Triplicate solutions of isoniazid (0.5 and 6.0 mg/mL) in the 2 diluents were prepared in ethylene and propylene copolymer i.v. containers and stored under light protection at room temperature (20-25 °C) or under refrigeration (2-8 °C). Standard aliquots were removed from each solution at time points up to 72 hours and analyzed via high-performance liquid chromatography (HPLC). Stability was defined as retention of >90% of the initial isoniazid concentration; pH, osmolality, and visual appearance were assessed. RESULTS: Isoniazid 0.5- and 6.0-mg/mL solutions in 0.9% sodium chloride injection were stable for up to 72 hours at room temperature or under refrigeration. HPLC analysis of isoniazid 0.5-mg/mL solutions in 5% dextrose injection revealed a decrease to less than 90% of the initial concentration at 8 hours at room temperature and at 30 hours under refrigeration. Isoniazid 6.0-mg/mL solutions in 5% dextrose injection were stable for 24 hours at room temperature and for 48 hours under refrigeration. The pH, osmolality, and visual appearance of the solutions were not affected. CONCLUSION: Isoniazid solutions of 0.5 and 6.0 mg/mL in 0.9% sodium chloride injection were stable under light protection for up to 72 hours when stored at room temperature or under refrigeration. Isoniazid injection was less stable in 5% dextrose injection, especially at a concentration of 0.5 mg/mL at room temperature.
Assuntos
Antituberculosos/administração & dosagem , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Isoniazida/administração & dosagem , Antituberculosos/química , Cromatografia Líquida de Alta Pressão , Embalagem de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Glucose/química , Injeções , Isoniazida/química , Veículos Farmacêuticos/química , Refrigeração , Cloreto de Sódio/química , Temperatura , Fatores de TempoRESUMO
BACKGROUND: Music listening may reduce the physiological, emotional, and mental effects of distress and anxiety. It is unclear whether music listening may reduce the amount of opioids used for pain management in critical care, postoperative patients or whether music may improve patient experience in the intensive care unit (ICU). METHODS: A total of 41 surgical patients were randomized to either music listening or controlled non-music listening groups on ICU admission. Approximately 50-minute music listening interventions were offered 4 times per day (every 4-6 hours) during the 48 hours of patients' ICU stays. Pain, distress, and anxiety scores were measured immediately before and after music listening or controlled resting periods. Total opioid intake was recorded every 24 hours and during each intervention. RESULTS: There was no significant difference in pain, opioid intake, distress, or anxiety scores between the control and music listening groups during the first 4 time points of the study. However, a mixed modeling analysis examining the pre- and post-intervention scores at the first time point revealed a significant interaction in the Numeric Rating Scale (NRS) for pain between the music and the control groups (P = .037). The Numeric Rating Score decreased in the music group but remained stable in the control group. Following discharge from the ICU, the music group's interviews were analyzed for themes. CONCLUSIONS: Despite the limited sample size, this study identified music listening as an appropriate intervention that improved patients' post-intervention experience, according to patients' self-report. Future mixed methods studies are needed to examine both qualitative patient perspectives and methodology to improve music listening in critical care units.
Assuntos
Antifúngicos/farmacocinética , Antineoplásicos/farmacocinética , Hidrocarboneto de Aril Hidroxilases/genética , Pirimidinas/farmacocinética , Triazóis/farmacocinética , Vincristina/farmacocinética , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Citocromo P-450 CYP2C19 , Interações Medicamentosas , Genótipo , Meia-Vida , Humanos , Masculino , Taxa de Depuração Metabólica , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , VoriconazolRESUMO
Background. Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods. Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results. Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1-84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10-141) and C reactive protein 26 mg/dL (0.5-95). Synovial fluid median white blood cell count was 27 500/µL (range, 100-220 000/µL) with 90% polymorphonuclear neutrophils (range, 24-98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion. Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy.