RESUMO
Morbidity and mortality related to ventriculitis in neurocritical care patients remain high. Antibiotic dose optimization may improve therapeutic outcomes. In this study, a population pharmacokinetic model of meropenem in infected critically ill patients was developed. We applied the final model to determine optimal meropenem dosing regimens required to achieve targeted cerebrospinal fluid exposures. Neurocritical care patients receiving meropenem and with a diagnosis of ventriculitis or extracranial infection were recruited from two centers to this study. Serial plasma and cerebrospinal fluid samples were collected and assayed. Population pharmacokinetic modeling and Monte Carlo dosing simulations were performed using Pmetrics. We sought to determine optimized dosing regimens that achieved meropenem cerebrospinal fluid concentrations above pathogen MICs for 40% of the dosing interval, or a higher target ratio of meropenem cerebrospinal fluid trough concentrations to pathogen MIC of ≥1. In total, 53 plasma and 34 cerebrospinal fluid samples were obtained from eight patients. Meropenem pharmacokinetics were appropriately described using a three-compartment model with linear plasma clearance scaled for creatinine clearance and cerebrospinal fluid penetration scaled for patient age. Considerable interindividual pharmacokinetic variability was apparent, particularly in the cerebrospinal fluid. Percent coefficients of variation for meropenem clearance from plasma and cerebrospinal fluid were 41.7% and 89.6%, respectively; for meropenem, the volume of distribution in plasma and cerebrospinal fluid values were 63.4% and 58.3%, respectively. High doses (up to 8 to 10 g/day) improved attainment of meropenem cerebrospinal fluid target exposures, particularly for less susceptible organisms (MICs, ≥0.25 mg/L). Standard meropenem doses of 2 g every 8 h may not achieve effective concentrations in cerebrospinal fluid in all critically ill patients. Higher doses, or alternative dosing methods (e.g., loading dose followed by continuous infusion) may be required to optimize cerebrospinal fluid exposures. Doses of up to 8 to 10 g/day either as intermittent boluses or continuous infusion would be suitable for patients with augmented renal clearance; lower doses may be considered for patients with impaired renal function as empirical suggestions. Ongoing dosing should be tailored to the individual patient circumstances. Notably, the study population was small and dosing recommendations may not be generalizable to all critically ill patients.
Assuntos
Ventriculite Cerebral , Insuficiência Renal , Antibacterianos , Estado Terminal , Humanos , Meropeném/farmacocinética , Estudos Prospectivos , TienamicinasRESUMO
OBJECTIVES: To evaluate the circulation lifespan of forks and teaspoons in an institutional tearoom. DESIGN: Longitudinal quality improvement study, based on prospective tracking of marked teaspoons and forks. SETTING: Staff tearoom in a public teaching and research hospital, Brisbane. PARTICIPANTS: Tearoom patrons blinded to the purposes of the study. INTERVENTION: Stainless steel forks and teaspoons (18 each) were marked with red spots and introduced alongside existing cutlery (81 items) in the tearoom. MAIN OUTCOME MEASURES: Twice weekly count of marked forks and teaspoons for seven weeks; baseline and end of study count of all utensils on day 45. RESULTS: The loss of marked teaspoons (six of 18) was greater than that of forks (one of 18) by the conclusion of the study period (P = 0.038). The overall rate of utensil loss was 2.2 per 100 days for teaspoons and spoons, and -2.2 per 100 days for forks and knives. CONCLUSIONS: Teaspoon disappearance is a more substantial problem than fork migration in a multidisciplinary staff tearoom, and may reflect different kleptomaniacal or individual appropriation tendencies. If giving cutlery this Christmas, give teaspoons, not forks. The symbolism of fork rebirth or resurrection is appropriate for both Christmas and Easter, and forks are also mighty useful implements for eating cake!
Assuntos
Senso de Humor e Humor como Assunto , Utensílios de Alimentação e Culinária/estatística & dados numéricos , Férias e Feriados , Hospitais de Ensino , Humanos , Estudos Longitudinais , Recursos Humanos em Hospital , Melhoria de QualidadeRESUMO
Extra-corporeal membrane oxygenation (ECMO) therapy could affect effective drug concentrations via adsorption onto the oxygenator or associated circuit. We describe a case of a 25-year-old female who required a veno-arterial ECMO therapy for refractory cardiac arrest due to massive pulmonary embolism. She had mild renal dysfunction as a result of the cardiac arrest. A total of 2 g of intravenous cefazolin 8-hourly was administered. Pre- and post-oxygenator blood samples were collected at 0, 1, 4, and 8 h post antibiotic administration. Samples were analyzed for total and unbound cefazolin concentrations. Protein binding was â¼60%. Clearance was reduced due to impaired renal function. The pharmacokinetics of cefazolin appear to not be affected by ECMO therapy and dosing adjustment may not be required.
Assuntos
Cefazolina/administração & dosagem , Oxigenação por Membrana Extracorpórea , Adulto , Área Sob a Curva , Cefazolina/sangue , Cefazolina/metabolismo , Feminino , Meia-Vida , Parada Cardíaca/complicações , Parada Cardíaca/diagnóstico , Humanos , Ligação Proteica , Embolia Pulmonar/complicações , Embolia Pulmonar/patologia , Curva ROCRESUMO
Dosing of amoxicillin-clavulanic acid in critical illness is difficult as ß-lactam pharmacokinetics are altered by physiological changes and therapies initiated in the intensive care unit such as renal replacement therapy (RRT). Successful treatment relies on sustaining a free antibiotic concentration above the minimum inhibitory concentration of the target pathogen (fT>MIC). We present a case of a patient treated with amoxicillin-clavulanic acid (1.2 g for 8 h) for an aspiration pneumonia. Dosing in this case was complicated by the necessity for RRT to treat a drug overdose with carbamazepine, despite normal native renal function. Antibiotic concentrations taken at steady state revealed a clearance of 14.6 L/h and a low fT>MIC (<40%). Analysis of the urine drug concentration suggested that 48% of clearance was via the native kidneys. This case illustrates that careful consideration of antibiotic dose and frequency is required in critically ill patients receiving RRT and highlights the need for further research in this patient group. In future similar cases, we would consider a dose of 2.2 g 6- or 8-hourly with early therapeutic drug monitoring.
Assuntos
Amoxicilina/uso terapêutico , Ácido Clavulânico/uso terapêutico , Hemodiafiltração , Pneumonia/tratamento farmacológico , Adulto , Consumo de Bebidas Alcoólicas , Amoxicilina/sangue , Cromatografia Líquida de Alta Pressão , Meia-Vida , Humanos , Unidades de Terapia Intensiva , Rim/fisiologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Espectrometria de Massas , Polimedicação , Escarro/microbiologia , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Extracorporeal membrane oxygenation (ECMO) can affect antimicrobial pharmacokinetics. This case report describes a 33-year-old male with newly diagnosed acquired immunodeficiency syndrome presenting in acute severe type 1 respiratory failure. On investigation, the patient had positive cultures for Candida albicans from respiratory specimens and high blood cytomegalovirus titres, and required venovenous ECMO therapy for refractory respiratory failure. Intravenous fluconazole (6 mg/kg, 24-h) and ganciclovir (5 mg/kg, 12-h) was commenced. Pre-oxygenator, post-oxygenator and arterial blood samples were collected after antibiotic administration, and were analysed for total fluconazole and ganciclovir concentrations. Although there was a 40% increase in the volume of distribution for fluconazole relative to healthy volunteers, the pharmacodynamic targets for prophylaxis were still met. The area under the curve exposure of ganciclovir (50.78 mgâ¢h/L) achieved target thresholds. The ECMO circuit had no appreciable effect on achievement of therapeutic exposures of fluconazole and ganciclovir.
Assuntos
Candidíase/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Oxigenação por Membrana Extracorpórea/efeitos adversos , Fluconazol/farmacocinética , Ganciclovir/farmacocinética , Insuficiência Respiratória/terapia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/microbiologia , Adulto , Antifúngicos/uso terapêutico , Antivirais/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/isolamento & purificação , Quimioterapia Combinada , Fluconazol/uso terapêutico , Ganciclovir/uso terapêutico , Humanos , MasculinoRESUMO
BACKGROUND AND OBJECTIVE: Patients with severe trauma exhibit augmented renal clearance, which can alter the dosing requirement of renally eliminated drugs. This study aimed to develop a population pharmacokinetic model for levetiracetam in patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage, and use it to describe optimal dosing regimens. METHODS: This was a prospective open-label observational study. Critically ill adult patients with severe traumatic brain injury or aneurysmal subarachnoid hemorrhage without renal dysfunction and receiving levetiracetam were eligible. Serial levetiracetam plasma concentrations were analyzed to develop a population pharmacokinetic model and perform dosing simulations. RESULTS: A two-compartment model best described the concentration-time data from 30 patients. The mean ± standard deviation parameter estimates were bioavailability (F) of 0.8 ± 0.2, absorption rate constant of 2.4 ± 2 h-1, clearance 2.5 ± 1.1 L/h, central volume of distribution 8.9 ± 3.0 L/h, and transfer rate constraints of 1.8 ± 1.1 h-1 from central to peripheral compartments and 0.7 ± 0.3 h-1 from peripheral to central compartments. For the simulated intermittent dosing regimens, on average, the median trough concentration reduced by 50% for every 40-mL/min/1.73 m2 increase in urinary creatinine clearance. Simulated doses of at least 6 g/day were required for some levels of augmented renal clearance. CONCLUSIONS: Patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage with augmented renal clearance are at risk of not achieving target levetiracetam plasma concentrations. We suggest dose titration guided by measured creatinine clearance, and/or, therapeutic drug monitoring if available, to minimize the risk of seizures.
Assuntos
Lesões Encefálicas Traumáticas , Insuficiência Renal , Hemorragia Subaracnóidea , Adulto , Antibacterianos/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Estado Terminal , Humanos , Levetiracetam , Estudos Prospectivos , Hemorragia Subaracnóidea/tratamento farmacológicoRESUMO
Extracorporeal membrane oxygenation (ECMO) therapy could affect drug concentrations via adsorption onto the oxygenator and/or associated circuit. We describe a case of a 33-year-old man with severe respiratory failure due to Pneumocystis jirovecii infection on a background of recently diagnosed human immunodeficiency virus infection. He required venovenous ECMO therapy for refractory respiratory failure. Intravenous sulfamethoxazole-trimethoprim (100 and 20 mg/kg/day) was administered in a dosing regimen every 6 hours. Pre-oxygenator, post-oxygenator, and arterial blood samples were collected after antibiotic administration and were analyzed for total sulfamethoxazole and trimethoprim concentrations. The peak sulfamethoxazole and trimethoprim concentrations were 122 mg/L and 5.3 mg/L, respectively. The volume of distribution for sulfamethoxazole was 0.37 and 2.30 L/kg for trimethoprim. The clearance for sulfamethoxazole was 0.35 ml/minute/kg and for trimethoprim was 1.64 ml/minute/kg. The pharmacokinetics of sulfamethoxazole and trimethoprim appear not to be affected by ECMO therapy, and dosing adjustment may not be required.