Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.316
Filtrar
1.
BMC Infect Dis ; 20(1): 167, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087689

RESUMO

BACKGROUND: Even though enterococci can cause serious infections in multiple sites, they are a rare cause of pneumonia. We reported a uremic patient with vancomycin-resistant E. faecium (VRE-fm) pneumonia, possibly related to epileptic seizures. CASE PRESENTATION: A 57-year old man with uremia on hemodialysis was admitted to the hospital with complaint of recurrent epileptic seizures, followed by a two-week history of recurrent fever and cough with purulent sputum. Chest CT demonstrated multiple exudation of both lungs. He was diagnosed as community acquired pneumonia. Despite antibiotic combination therapy, abnormal chest shadows aggravated. Sputum and blood cultures were initially negative, but later blood culture grew VRE-fm. We suspected aspiration of gastrointestinal content induced by epilepsy as the most likely mechanism. The patient was successfully treated with a four-week course of linezolid according to the antibiotic susceptibility testing. CONCLUSIONS: Physicians should consider multi-drug resistant organisms such as VRE in uremic patients with pneumonia that fails to resolve with broad-spectrum antibiotics, especially in the cases with aspiration induced by epilepsy, immunocompromised conditions, and repeated or prolonged hospitalizations.


Assuntos
Antibacterianos/uso terapêutico , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Linezolida/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Resistência a Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Vancomicina/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Diálise Renal , Resultado do Tratamento , Uremia/terapia , Vancomicina/efeitos adversos
2.
J Agric Food Chem ; 68(10): 3112-3120, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046486

RESUMO

Maternal gut dysbiosis affects the development of the offspring immune system. Our previous study has indicated that microbial metabolite butyrate directly shapes pancreatic immune tolerance and dampens type 1 diabetes (T1D) progression. Therefore, maternal butyrate intervention may protect their offspring from maternal gut dysbiosis-accelerated T1D. To test this, pregnant nonobese diabetic (NOD) mice were treated with vancomycin in drinking water with or without a butyrate-supplemented diet during gestation and nursing (oral vancomycin is used to induce maternal gut dysbiosis). Three weeks after delivery, T1D-associated innate and adaptive immune cells were detected to investigate the effects of butyrate on the vancomycin-exacerbated pancreatic immune disorder in dams and pups. The results showed that butyrate inhibited maternal vancomycin-exacerbated secretion of proinflammation cytokines (interferon γ and interleukin-1ß) and maternal vancomycin-exacerbated recruitment of interferon γ+ T cells (cytotoxic T lymphocytes 1 cells and T helper type 1 cells) in the pancreas of the female offspring, thus dampening T1D development. The protection may be due to butyrate inhibiting the activation of pancreatic dendritic cells (DCs). Our data thus demonstrate that maternal gut dysbiosis can exacerbate pancreatic-directed autoimmunity in the female offspring through T cell- and DC-associated mechanisms that are inhibited by butyrate.


Assuntos
Antibacterianos/efeitos adversos , Butiratos/administração & dosagem , Diabetes Mellitus Tipo 1/tratamento farmacológico , Vancomicina/efeitos adversos , Animais , Células Dendríticas/imunologia , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Feminino , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
3.
World Neurosurg ; 136: 136-139, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954899

RESUMO

BACKGROUND: Encephalopathy is reported to have affected 250,000 people in the United States over the last decade, with considerable morbidity and mortality. Baclofen, a gamma-aminobutyric acid-B agonist that acts on the central nervous system, is the drug most widely used to treat spasticity. Baclofen overdose is a potentially deadly condition that can cause encephalopathy and can result from multiple etiologies. Renal disease can contribute to baclofen overdose and encephalopathy, and there are currently no dosing recommendations for patient's on baclofen with renal impairment. CASE DESCRIPTION: We report an unusual case of a man aged 35 years who presented with persistent fevers, seizures, and normal mentation. The patient presented with intrathecal baclofen use and prior exposure to West Nile Virus. He developed acute kidney injury at hospital secondary to vancomycin use, and mental status declined. CONCLUSIONS: This case highlights that patients with baclofen overdose can initially appear to have serious brain injury, however, full patient recovery can occur in <72 hours. This case provides additional insight into the guidelines for the treatment and management for unknown cause encephalopathy. This case also highlights the link between renal disease, baclofen, and encephalopathy through a review of the literature.


Assuntos
Baclofeno/efeitos adversos , Encefalopatias/induzido quimicamente , Agonistas dos Receptores de GABA-B/efeitos adversos , Espasmo/tratamento farmacológico , Lesão Renal Aguda/induzido quimicamente , Adulto , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Baclofeno/administração & dosagem , Encefalopatias/complicações , Encefalopatias/fisiopatologia , Eletroencefalografia , Febre/etiologia , Febre/fisiopatologia , Agonistas dos Receptores de GABA-B/administração & dosagem , Humanos , Bombas de Infusão Implantáveis , Infusão Espinal , Masculino , Meropeném/uso terapêutico , Paraplegia/complicações , Convulsões/etiologia , Convulsões/fisiopatologia , Espasmo/etiologia , Traumatismos da Medula Espinal/complicações , Vancomicina/efeitos adversos
5.
Yakugaku Zasshi ; 139(12): 1609-1614, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787651

RESUMO

It has been reported that the risk of acute kidney injury (AKI) is higher during treatment with vancomycin and piperacillin/tazobactam compared to use of vancomycin and cefepim or meropenem. We investigated the risk of AKI in patients receiving vancomycin and piperacillin/tazobactam versus those receiving vancomycin and meropenem or doripenem. The subjects were patients over 18 years old who received either vancomycin and piperacillin/tazobactam (V+P/T therapy) or vancomycin and carbapenems (meropenem or doripenem) (V+C therapy) for at least 48 h between 1 May 2013 and 28 February 2019. The primary endpoint was the incidence of AKI in patients receiving V+P/T or V+C therapy, while the secondary outcome was the timing of AKI in each group. The incidence of AKI was 33.3% (9/27) in patients receiving V+P/T therapy versus 9.1% (5/55) in those receiving V+C therapy, and its incidence was significantly higher with the former regimen (χ2=5.90, p=0.015). Multiple logistic regression analysis confirmed that V+P/T therapy was associated with an increased risk of AKI compared to V+C therapy (adjusted odds ratio: 5.05, 95% confidence interval: 1.46-17.5, p=0.01). The time to onset of AKI after initiation of treatment was not significantly different between patients receiving V+T/P or V+C therapy [median (interquartile range): 4 d (2-6 d) versus 7 d (3-10 d); p=0.282]. V+P/T therapy was associated with a significantly higher incidence of AKI than alternative regimens, suggesting that it should be avoided. When broad spectrum antibacterial therapy is required, V+C therapy should be considered instead.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Doripenem/efeitos adversos , Meropeném/efeitos adversos , Combinação Piperacilina e Tazobactam/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Estudos de Coortes , Doripenem/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Meropeném/administração & dosagem , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam/administração & dosagem , Estudos Retrospectivos , Risco , Vancomicina/administração & dosagem
6.
Crit Care Resusc ; 21(4): 265-73, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31778633

RESUMO

OBJECTIVE: To determine the prevalence and impact of patient-reported antibiotic allergies in the intensive care unit (ICU), which are currently poorly defined. Antibiotic allergy labels (AALs) are associated with inappropriate antibiotic prescribing and with inferior patient, microbiological and hospital outcomes. DESIGN: Prospective, single-centre case-control study. SETTING: Mixed ICU, Austin Hospital, Melbourne. PARTICIPANTS: All adults (≥ 18 years old) admitted to the ICU who received at least two doses of systemic antibiotics between 12 February and 20 April 2018. MAIN OUTCOME MEASURES: Demographic data, infection and allergy history, antibiotic prescriptions and ICU interventions and outcomes. RESULTS: Of the 247 patients (79.9%) who received systemic antibiotics, 43 patients (17.4%) had an AAL and 204 (82.6%) did not. A higher proportion of patients with AAL were female (P = 0.032) and received vancomycin (37.2% AAL v 18.6% no antibiotic allergies [NAAL]; P = 0.014), and a lower proportion of patients received narrow spectrum ß-lactams (39.5% AAL v 58.8% NAAL; P = 0.028). On multivariable logistic regression, the AAL cohort had twice higher odds of receiving vancomycin (odds ratio [OR], 2.04; 95% CI, 1.07-3.86; P = 0.029) and half the odds of receiving a narrow spectrum ß-lactam (OR, 0.52; 95% CI, 0.29-0.94; P = 0.03). AAL distribution on the electronic medical record included 17% type A (predictable), 13% type B-I (immediate), 2% type B-IV (delayed), 35% type B (unspecified), and 32% unknown. An interview clarifying allergy phenotype found that 59.5% of AALs matched their documented description. CONCLUSION: Patients with AALs had twice the odds of receiving intravenous vancomycin and half the odds of receiving narrow spectrum ß-lactams, which highlights the continued need for antimicrobial stewardship initiatives.


Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Adolescente , Adulto , Antibacterianos/imunologia , Antibacterianos/uso terapêutico , Austrália , Estudos de Casos e Controles , Hipersensibilidade a Drogas/etiologia , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Vancomicina/efeitos adversos , beta-Lactamas/efeitos adversos
7.
Am J Case Rep ; 20: 1440-1445, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31564716

RESUMO

BACKGROUND Herein, we describe a case of eosinophilic pneumonia that was likely to have been induced by vancomycin. CASE REPORT A 65-year-old man on maintenance hemodialysis presented with chest pain and dyspnea. He subsequently developed methicillin-resistant Staphylococcus aureus-positive acute pleural empyema in an evacuated right-sided pneumothorax. Surgical thoracoscopic curettage was ultimately performed, but dyspnea recurred postoperatively. Computed tomography depicted widespread reticular shadowing of the left lung, and peripheral eosinophilia was detected. The proportion of eosinophils found in bronchoalveolar lavage fluid was also remarkable (43%). All symptoms and the results of laboratory tests immediately improved after the discontinuation of vancomycin and initiation of prednisolone therapy. CONCLUSIONS We attribute this case of eosinophilic pneumonia to vancomycin, because all other candidate causes were ruled out, and only vancomycin fulfilled the criteria of both drug-induced eosinophilic pneumonia and drug-induced lung injury. If confirmed, this constitutes the first reported case of vancomycin-induced eosinophilic pneumonia.


Assuntos
Antibacterianos/efeitos adversos , Eosinofilia Pulmonar/induzido quimicamente , Vancomicina/efeitos adversos , Idoso , Líquido da Lavagem Broncoalveolar/citologia , Eosinófilos/metabolismo , Humanos , Masculino
8.
BMJ Case Rep ; 12(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527200

RESUMO

A 57-year-old man presented for an elective pacemaker upgrade, complicated by the discovery of device infection. He had a background of complex congenital heart disease, including replacement of heart valves, and was treated for presumed infective endocarditis that was later confirmed by echocardiography. Antibiotic treatment, with intravenous vancomycin, was given as per the tissue sample sensitivities. On day 24 of treatment he deteriorated clinically, with the evolution of recurrent fever, epigastric pain, diarrhoea, widespread pruritic rash, lymphadenopathy and severe hypoxia over the subsequent 7-10 days. Blood tests revealed development of a marked eosinophilia, transaminitis and rising inflammatory markers. Further radiological imaging was non-diagnostic. On the basis of these clinical and biochemical features a diagnosis of drug reaction with eosinophilia and systemic symptoms syndrome was made. This led to the cessation of vancomycin, the offending agent and the referral for specialist immunology advice. He was subsequently treated with oral prednisolone and made a full recovery.


Assuntos
Endocardite Bacteriana/tratamento farmacológico , Eosinofilia/induzido quimicamente , Doenças das Valvas Cardíacas/tratamento farmacológico , Marca-Passo Artificial/efeitos adversos , Vancomicina/efeitos adversos , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Infecções Relacionadas à Prótese/tratamento farmacológico , Valva Tricúspide/microbiologia , Vancomicina/uso terapêutico
9.
Am J Health Syst Pharm ; 76(16): 1204-1210, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369115

RESUMO

PURPOSE: Results of a study of rates of acute kidney injury (AKI) in pediatric patients treated with vancomycin plus piperacillin-tazobactam or vancomycin plus alternative antipseudomonal ß-lactams (APBLs) are reported. METHODS: A retrospective, single-center cohort study was performed. Pediatric patients were included in the study cohort if they received combination therapy for at least 48 hours, had documented baseline and follow-up serum creatinine levels, and had a documented serum vancomycin trough concentration. The primary outcome was the frequency of AKI, defined as a 50% or greater increase in serum creatinine concentration from baseline or an increase of at least 0.5 mg/dL from baseline. The secondary outcome was time to AKI onset. RESULTS: A total of 474 patients were included. Among 100 patients who received vancomycin plus piperacillin-tazobactam, the rate of AKI was higher than the rate in the group treated with vancomycin plus alternative APBLs (27% versus 7%, p < 0.0001). The median time to AKI onset was shorter in the piperacillin-tazobactam group versus the alternative APBL group (3.8 versus 7.9 days, p = 0.0065). Patients who were administered piperacillin-tazobactam were almost 6 times as likely to develop AKI (odds ratio [OR], 5.955; 95% confidence interval [CI], 2.774-12.784), and patients who had a maximum vancomycin trough concentration greater than 20 mg/L were 7.5 times as likely to develop AKI (OR, 7.552; 95% CI, 3.625-15.734). CONCLUSION: Pediatric patients treated with concomitant vancomycin and piperacillin-tazobactam had a higher rate of AKI, with faster AKI onset, than those who received vancomycin in combination with other APBLs.


Assuntos
Lesão Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Combinação Piperacilina e Tazobactam/efeitos adversos , Sepse/tratamento farmacológico , Vancomicina/efeitos adversos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/induzido quimicamente , Antibacterianos/administração & dosagem , Criança , Creatinina/sangue , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Combinação Piperacilina e Tazobactam/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Vancomicina/administração & dosagem
10.
Am J Health Syst Pharm ; 76(16): 1211-1217, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369116

RESUMO

PURPOSE: Results of a study to determine whether obesity is associated with acute kidney injury (AKI) among patients receiving combination therapy with piperacillin-tazobactam and vancomycin are reported. METHODS: A retrospective, single-center cohort study of patients who received combination therapy for at least 48 hours was conducted using data from the University of Kentucky Center for Clinical and Translational Science's Enterprise Data Trust. Patients with chronic kidney disease, baseline creatinine clearance of less than 30 mL/min, cystic fibrosis, or missing height or weight information were excluded. RESULTS: A total of 8,125 patients were included in the cohort. Among the variables evaluated, total body weight of 91 kg or more was the variable most predictive of AKI. Patients with a weight of 91 kg or higher were more likely than lower-weight patients to have diabetes (39% versus 21%, p < 0.00001), hypertension (64% versus 47%, p < 0.00001), and heart failure (15% versus 13%, p = 0.007). The median daily vancomcyin dose was lower in patients with a weight of less than 91 kg (2,000 mg versus 3,000 mg, p < 0.00001); however, weight-based doses were lower in patients weighing 91 kg or more (25.5 mg/kg/day versus 27.9 mg/kg/day, p < 0.00001). AKI was more common in patients weighing 91 kg or more (24% versus 18%, p < 0.00001; adjusted odds ratio, 1.46 [95% confidence interval, 1.28-1.66]). CONCLUSION: Increased total body weight increased the rate of AKI among patients concurrently treated with piperacillin-tazobactam and vancomycin independent of clinically important confounders, with an important breakpoint occurring at 91 kg.


Assuntos
Lesão Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Obesidade/epidemiologia , Combinação Piperacilina e Tazobactam/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Kentucky/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Curr Drug Metab ; 20(8): 656-664, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296157

RESUMO

BACKGROUND: Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. METHODS: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. RESULTS: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. CONCLUSION: Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/urina , Adulto , Idoso , Aminoglicosídeos/efeitos adversos , Anfotericina B/efeitos adversos , Biomarcadores/urina , Inibidores de Calcineurina/efeitos adversos , Quimiocina CCL2/urina , Clusterina/urina , Ciclosporina/efeitos adversos , Cistatina C/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Masculino , Pessoa de Meia-Idade , Tacrolimo/efeitos adversos , Vancomicina/efeitos adversos , Microglobulina beta-2/urina
12.
ACS Appl Mater Interfaces ; 11(30): 26711-26721, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31287648

RESUMO

The fact that increasing antibiotic resistance of pathogenic bacteria and a lack of new potent broad-spectrum antibiotics call for the development of alternative approaches for treating infectious diseases. With the merits of great efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents an attractive modality for this purpose. Here, we report that the newly fabricated photodynamic chitosan nano-assembly, designated CS-Ce6, could synergistically kill antibiotic-resistant bacteria with superior potency to vancomycin. CS-Ce6 nano-assembly, obtained from covalent conjugate of chlorin e6 (Ce6) with chitosan, exhibited strong association with bacteria, thus altering their morphologies and mediating great delivery efficiency of Ce6. Upon light irradiation, localized generation of singlet oxygen by CS-Ce6 nano-assembly has a remarkable bactericidal effect toward both drug-resistance Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Acinetobacter baumannii, which was greater than that the free Ce6 and antibiotics had. We also confirmed that APDT-treated MRSA neither developed resistance to APDT nor altered their resistance to methicillin. Our in vivo studies demonstrated that the CS-Ce6 nano-assembly had comparable therapeutic efficacy with vancomycin in MRSA-infected mice. These results suggest that APDT by photodynamic chitosan nano-assembly hold great potential in combating antibiotic-resistant bacteria and hopefully in reducing the need of antibiotics in the future.


Assuntos
Infecções Bacterianas/terapia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Nanopartículas/química , Fotoquimioterapia , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Infecções Bacterianas/patologia , Quitosana/química , Quitosana/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Oxigênio Singlete/química , Vancomicina/efeitos adversos , Vancomicina/farmacologia
13.
Phytother Res ; 33(8): 2056-2063, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209949

RESUMO

Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the development of effective nephroprotective agents remains a priority in antimicrobial chemotherapy. In this study, we investigated the cell protective effects of the flavonol glycoside rutin against vancomycin-induced toxicity. Vancomycin added to porcine renal tubular LLC-PK1 cells caused an increase of production of intracellular reactive oxygen species and subsequent apoptotic cell death. Pretreatment of LLC-PK1 cells with rutin at 5, 10, and 20 µM for 2 hr prior to 2-mM vancomycin exposure for 24 hr significantly decreased intracellular reactive oxygen species and increased superoxide dismutase and catalase activities. Rutin pretreatment also protected cells from vancomycin-induced caspase activation, mitochondrial membrane depolarization, and subsequent apoptosis. This study demonstrates a protective effect of rutin and suggests that rutin coadministration is an alternative therapy for treatment of vancomycin-induced nephrotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Rutina/uso terapêutico , Vancomicina/efeitos adversos , Animais , Rutina/farmacologia , Suínos , Vancomicina/farmacologia
14.
J Clin Pharm Ther ; 44(5): 750-759, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228353

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high-strength and long-term vancomycin therapy might have unstable and time-varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (PK) modeling and model-based estimation of vancomycin pharmacokinetics. While Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for renal function estimation has been widely integrated into clinical practice, a population PK model including CKD-EPI has not been established. The study was aimed at developing a new population PK model for optimal vancomycin prediction in patients with time-varying and variable renal function to evaluate the interchangeability of estimation methods. METHODS: The most suitable population PK model was explored and evaluated using non-linear mixed-effect modelling for the best fit of vancomycin concentrations from patients who needed to maintain high trough vancomycin concentrations of >10 mg/L or >15 mg/L. Renal function was estimated using the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations. NONMEM 7.4 was used to develop the population PK model. RESULTS: A total of 328 vancomycin concentrations in 99 patients were used to develop the population PK model. Vancomycin pharmacokinetics was best described by a two-compartment model. The CKD-EPI equation for vancomycin clearance was included in the final model among the estimation methods of renal function. A new covariate model, including extended covariate parameters that explain changes in renal function from the population-predicted value and individual dosing time, provided the best explanation for vancomycin pharmacokinetics among the various models tested. WHAT IS NEW AND CONCLUSION: A new extended covariate model for vancomycin using the CKD-EPI method may afford suitable dose adjustment for high-strength and long-term vancomycin therapy that results in unstable renal function.


Assuntos
Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Renal Crônica/induzido quimicamente , Vancomicina/efeitos adversos , Vancomicina/farmacocinética , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Vancomicina/administração & dosagem
16.
Intern Med ; 58(18): 2621-2625, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31118388

RESUMO

Objective The importance of antimicrobial stewardship is increasingly highlighted in this age of antimicrobial resistance. A better comprehension of adverse drug events (ADEs) can promote the appropriate use of antibiotics. We aimed to quantify the incidence of ADEs associated with broad-spectrum systemic antibiotics in a hospital setting. Methods We conducted a six-month prospective, observational study at Osaka University Hospital to describe the incidence of ADEs in patients hospitalized in general wards undergoing treatment with broad-spectrum antibiotics [carbapenems, piperacillin/tazobactam (PIPC/TAZ), and anti-methicillin-resistant Staphylococcus aureus agents]. The occurrence of ADE was defined as any cardiac, gastrointestinal, hepatobiliary, renal, neurologic, hematologic, dermatologic, or musculoskeletal manifestation after 48 hours or more of systemic antibiotic therapy. Results The 3 most frequently prescribed antibiotics were PIPC/TAZ (242 cases), meropenem (181 cases), and vancomycin (92 cases). Of 689 patients, 118 (17.1%) experienced ADEs, including gastrointestinal (6.4%), hepatobiliary (4.2%), dermatologic (2.5%), and renal (2.3%) manifestations. Patients treated with PIPC/TAZ, meropenem, doripenem, vancomycin, daptomycin, and teicoplanin developed ADEs at rates of 20.7%, 16.0%, 15.4%, 19.6%, 11.8%, and 10.9%, respectively. Conclusion Our study provides a quantitative value for the incidence of ADEs associated with broad-spectrum antibiotics in clinical practice. To optimize patient safety, clinicians need to be aware of the risks associated with antibiotic administration.


Assuntos
Antibacterianos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Carbapenêmicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Incidência , Masculino , Meropeném/efeitos adversos , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam/efeitos adversos , Estudos Prospectivos , Vancomicina/efeitos adversos , Adulto Jovem
17.
BMC Infect Dis ; 19(1): 438, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109283

RESUMO

BACKGROUND: Gram-positive organisms are a leading cause of infection in cardiovascular surgery. Furthermore, these patients have a high risk of developing postoperative renal failure in intensive care unit (ICU). Some antibiotic drugs are known to impair renal function. The aim of the study was to evaluate whether patients treated for Gram-positive cardiovascular infection with daptomycin (DAP) experienced a lower incidence of acute kidney injury (AKI) when compared to patients treated with vancomycin (VAN), with comparable efficacy. METHODS: ICU patients who received either DAP or VAN, prior to or after cardiovascular surgery or mechanical circulatory support, from January 2010 to December 2012, were included in this observational retrospective cohort study. We excluded patients with end stage renal disease and antibiotic prophylaxis. The primary endpoint was the incidence of AKI within the first week of treatment. Secondary endpoints were the incidence of AKI within the first 14 days of treatment, the severity of AKI including renal replacement therapy (RRT), the rates of clinical failure (unsuccessful infection treatment) and of premature discontinuation and mortality. To minimize selection bias, we used a propensity score to compare the 2 groups. Univariate and multivariate analysis were performed to determine factors associated with AKI. RESULTS: Seventy two patients, treated for infective endocarditis, cardiovascular foreign body infection, or surgical site infection were included (DAP, n = 28 and VAN, n = 44). AKI at day 7 was observed in 28 (64%) versus 6 (21%) of the VAN and DAP patients, respectively (p = 0.001). In the multivariate analysis adjusted to the propensity score, vancomycin treatment was the only factor associated with AKI (Odds Ratio 4.42; 95% CI: 1.39-15.34; p = 0.014). RRT was required for 2 (7%) DAP patients and 13 (30%) VAN patients, p = 0.035. Premature discontinuation and clinical failure occurred more frequently in VAN group than in DAP group (25% versus 4%, p = 0.022 and 42% versus 12%, respectively, p = 0.027). CONCLUSIONS: Daptomycin appears to be safer than vancomycin in terms of AKI risk in ICU patients treated for cardiovascular procedure-related infection. Daptomycin could be considered as a first line treatment to prevent AKI in high-risk patients.


Assuntos
Lesão Renal Aguda/etiologia , Daptomicina/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/epidemiologia , Idoso , Antibacterianos/uso terapêutico , Doenças Cardiovasculares/cirurgia , Estado Terminal , Daptomicina/uso terapêutico , Endocardite/tratamento farmacológico , Endocardite/epidemiologia , Endocardite/etiologia , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pontuação de Propensão , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Vancomicina/uso terapêutico
18.
Knee Surg Sports Traumatol Arthrosc ; 27(7): 2322-2327, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968239

RESUMO

PURPOSE: A frequent reason for revision surgery after total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) is periprosthetic joint infection (PJI). The efficacy of intrawound VP in preventing PJI after primary TKA or UKA is rarely reported. The purpose of this study was to investigate the efficacy and side effects of local high-dose VP application to the joint to prevent PJI in TKA and UKA. METHODS: From 2010 to 2017, 166 consecutive patients that underwent primary TKA or UKA were enrolled. Seventy-five patients (92 knees) did not receive VP (control group), while 90 patients (110 knees, VP group) received VP (intrawound, 1 g) before capsule closure during TKA and UKA. Aseptic wound complications, such as skin erosion, wound dehiscence, and prolonged wound healing, were evaluated within 3 months post-operatively. PJI was assessed within a year post-operatively. RESULTS: Seven patients (7.6%) in the control group and five patients (4.5%) in the VP group had PJI. No significant differences existed in the PJI rates between the groups. Aseptic operative wound complications occurred in 4 patients (4.3%) and 13 patients (11.8%), whereas prolonged operative wound healing occurred in 3 patients (3.3%) and 14 patients (12.7%) of patients in the control and VP group, respectively. Operative wound complications were significantly frequent in the VP group. CONCLUSIONS: Intrawound VP administration does not decrease PJI occurrence in primary TKA and significantly causes aseptic wound complications. The use of intrawound VP for the prevention of PJI after primary TKA and UKA is not recommended. LEVEL OF EVIDENCE: Level II.


Assuntos
Antibacterianos/efeitos adversos , Artrite Infecciosa/prevenção & controle , Artroplastia do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Deiscência da Ferida Operatória/etiologia , Vancomicina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Artrite Infecciosa/etiologia , Feminino , Humanos , Joelho/cirurgia , Articulação do Joelho/cirurgia , Masculino , Período Pós-Operatório , Vancomicina/administração & dosagem
19.
Pediatr Blood Cancer ; 66(7): e27750, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30989780

RESUMO

There is mounting evidence that combination of antibiotic therapy with vancomycin and piperacillin/tazobactam (pip/tazo) is associated with acute kidney injury (AKI). To determine whether vancomycin plus pip/tazo is associated with higher rates of AKI compared to vancomycin plus cefepime among pediatric hematology/oncology (heme/onc) patients, we examined 121 heme/onc patients receiving at least two consecutive days of therapy with vancomycin and either pip/tazo or cefepime. Rate of AKI was higher in the pip/tazo than the cefepime group (4/27 [14.8%] vs 2/94 [2.1%], P = 0.022).


Assuntos
Lesão Renal Aguda , Cefepima/efeitos adversos , Neoplasias Hematológicas , Piperacilina/efeitos adversos , Tazobactam/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/epidemiologia , Adolescente , Cefepima/administração & dosagem , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Humanos , Masculino , Piperacilina/administração & dosagem , Estudos Retrospectivos , Tazobactam/administração & dosagem , Vancomicina/administração & dosagem
20.
Paediatr Drugs ; 21(2): 107-112, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30864056

RESUMO

BACKGROUND: Acute kidney injury (AKI) commonly occurs after cardiac arrest. Those subsequently treated with vancomycin are at additional risk for drug-induced kidney injury. OBJECTIVE: We aimed to determine whether opportunities exist for improved drug monitoring after cardiac arrest. METHODS: This was a retrospective cohort study of children aged 30 days-17 years treated after cardiac arrest in an intensive care unit from January 2010 to September 2014 who received vancomycin within 24 h of arrest. Vancomycin dosing and monitoring were compared between those with and without AKI, with AKI defined as pRIFLE (pediatric risk, injury, failure, loss, end-stage renal disease) stage 2-3 AKI at day 5 using Schwartz formula-calculated estimated glomerular filtration rate (eGFR). RESULTS: Of 43 children, 16 (37%) had AKI at day 5. Age, arrest duration, median time to first vancomycin dose, and the number of doses before and time to first vancomycin concentration measurement were similar between groups. Children with AKI had higher initial vancomycin concentrations than those without AKI (median 16 vs. 7 mg/L; p = 0.003). A concentration was not measured before the second dose in 44% of children with AKI. Initial eGFR predicted day 5 AKI. In children with AKI, the initial eGFR was lower in those with than those without a concentration measurement before the second dose (29 mL/min/1.73 m2 [interquartile range (IQR) 23-47] vs. 52 [IQR 50-57]; p = 0.03) but well below normal in both. CONCLUSIONS: In children with AKI after cardiac arrest, decreased vancomycin clearance was evident early, and early monitoring was not performed universally in those with low initial eGFR. Earlier vancomycin therapeutic drug monitoring is indicated in this high-risk population.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Parada Cardíaca/complicações , Vancomicina/efeitos adversos , Lesão Renal Aguda/diagnóstico , Adolescente , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Monitoramento de Medicamentos , Prescrições de Medicamentos , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Vancomicina/administração & dosagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA