Incidence and risk factors for potentially suboptimal serum concentrations of vancomycin during cardiac surgery.

AIM: To investigate the incidence and risk factors for vancomycin concentrations less than 10 mg/L during cardiac surgery. METHODS: In this prospective study, patients undergoing cardiac surgery received a single dose of 1000 mg of vancomycin. Multiple arterial samples were drawn during surgery. Exclusion criteria were hepatic dysfunction; renal dysfunction; ongoing infectious diseases; solid or hematologic tumors; severe insulin-dependent diabetes; body mass index of < 17 or > 40 kg/m2; pregnancy or lactation; antibiotic, corticosteroid, or other immunosuppressive therapy; vancomycin or nonsteroidal anti-inflammatory drug therapy in the previous 2 wk; chemotherapy or radiation therapy in the previous 6 mo; allergy to vancomycin or cefazolin; drug abuse; cardiac surgery in the previous 6 mo; previous or scheduled organ transplantation; preoperative stay in the intensive care unit for more than 24 h; emergency procedure or lack of adequate preparation for surgery; and participation in another trial. RESULTS: Over a 1-year period, 236 patients were enrolled, and a total of 1682 serum vancomycin concentrations (median 7/patient) were measured. No vancomycin levels under 10 mg/L were recorded in 122 out of 236 patients (52%), and 114 out of 236 patients (48%) were found to have at least 1 serum sample with a vancomycin level < 10 mg/L; 54 out of 236 patients (22.9%) had at least 5 serum samples with a vancomycin level lower than 10 mg/L. Vancomycin infusion was administered for 60 min in 97 out of 236 patients (41%). In 47 patients (20%), the duration of infusion was longer than 60 min, and in 92 patients (39%) the duration of infusion was shorter than 60 min. The maximum concentration and area under the concentration-time curve were significantly higher in patients with no vancomycin levels less than 10 mg/L (P < 0.001). The multivariate analysis identified female gender, body mass index (BMI) > 25 kg/m2, and creatinine clearance above 70 mL/min as risk factors for vancomycin levels less than 10 mg/L. CONCLUSION: Results of this study identified female gender, BMI > 25 kg/m2, and creatinine clearance above 70 mL/min as risk factors for suboptimal vancomycin serum concentration during cardiac surgery; no relationship was found between infusion duration and vancomycin levels less than 10 mg/L. These findings call attention to the risk of facilitating the emergence of vancomycin-resistant methicillin-resistant Staphylococcus aureus strains.

Esquema posológico atualmente utilizado para vancomicina falha em obter níveis terapêuticos em 40% dos pacientes internados em unidade de terapia intensiva / Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients

RESUMO Objetivo: Avaliar se a posologia atualmente utilizada de vancomicina para tratamento de infecções bacterianas graves causadas por microrganismos Gram-positivos em pacientes admitidos à unidade de terapia intensiva proporcionam níveis plasmáticos de vale de vancomicina em nível terapêutico, e examinar possíveis fatores associados com níveis de vale de vancomicina adequados nesses pacientes. Métodos: Estudo prospectivo descritivo com amostra de conveniência. Os pacientes que cumpriam os critérios de inclusão tiveram seus dados coletados a partir das anotações da enfermagem e dos registros médicos entre setembro de 2013 e julho de 2014. Incluíram-se 83 pacientes. Os níveis plasmáticos de vale iniciais de vancomicina foram obtidos imediatamente antes da quarta dose de vancomicina. Definiu-se lesão renal aguda como um aumento de, pelo menos, 0,3mg/dL na creatinina sérica dentro de 48 horas. Resultados: Considerando os níveis de vale plasmáticos de vancomicina recomendados para o tratamento de infecções graves por Gram-positivos (15 - 20µg/mL), os pacientes foram categorizados em grupos como níveis de vale de vancomicina baixos, adequados e elevados, respectivamente divididos em 35 (42,2%), 18 (21,7%), e 30 (36,1%) pacientes. Os pacientes com lesão renal aguda tiveram níveis plasmáticos de vale de vancomicina significantemente mais elevados (p = 0,0055, com significância para tendência, p = 0,0023). Conclusão: Preocupantemente, mais de 40% dos pacientes não obtiveram níveis plasmáticos de vale de vancomicina considerados eficazes. São necessários estudos de farmacocinética e de regimes posológicos de vancomicina em pacientes admitidos em unidades de terapia intensiva, para contornar esta elevada proporção de falhas na obtenção de níveis de vale iniciais adequados de vancomicina. Deve ser desencorajado o uso de vancomicina sem monitoramento dos níveis de vale plasmáticos.

ABSTRACT Objective: This study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients. Methods: A prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours. Results: Considering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023). Conclusion: Surprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged.

Determination of vancomycin trough level in serum and cerebrospinal fluid of patients with acute community-acquired meningitis: a prospective study.

BACKGROUND: Penetration and concentration of vancomycin is still an elusive and complex issue particularly in Cerebrospinal Fluid (CSF). The aim of this study was to clarify the penetration of this antimicrobial agent in CSF during meningeal inflammation. METHODS: In a prospective study, adult patients, with clinical and CSF analysis compatible with acute meningitis, who received vancomycin (15 mg/kg loading and 30 mg/kg daily maintenance dose) with ceftriaxone (4 gr/daily) were enrolled. CSF analysis including vancomycin trough levels before the fourth maintenance dose and during the 8-10th days of treatment, and simultaneous serum levels were performed by High-Pressure Liquid Chromatography (HPLC). RESULTS: Twenty-seven patients (18 men, 9 women; mean age of 39.4 ± 14.7) were enrolled. The first serum trough level of vancomycin was 13.82 ± 1.28 mg/l. The mean of corresponding trough level in CSF was 11.2 ± 1.41 mg/l. The serum and CSF trough levels revealed positive linear correlation (r: 0.60) and was significant at the 0.01 level (P: 0.004). The penetration CSF/serum ratio was 0.811 ± 0.082 (coefficient of variation: 10.1%). The second trough levels of serum and CSF in (14 patients) vancomycin were 13.32 ± 1.02 and 10.64 ± 1.21, respectively. The serum and CSF trough levels revealed positive linear correlation (r: 0.71). The serum and CSF concentrations revealed no variation compared to the first trough levels. CONCLUSION: Vancomycin has appropriate concentration in CSF during the treatment of meningitis and do not decrease along with the alleviation of meningeal inflammation in spite of concerns in this regard.

Incremento da depuração renal em pacientes gravemente enfermos: incidência, fatores associados e efeitos no tratamento com vancomicina / Augmented renal clearance in critically ill patients: incidence, associated factors and effects on vancomycin treatment

Objetivo: Foi descrito um incremento da depuração renal em alguns grupos de pacientes gravemente enfermos, o qual pode induzir à eliminação de concentrações de fármacos por filtração glomerular aquém do ideal, principalmente no caso de antibióticos. Sua ocorrência e os fatores determinantes têm sido pouco estudados. Nossos objetivos foram determinar a incidência e os fatores associados ao incremento da depuração renal, bem como seus efeitos nas concentrações e na posologia de vancomicina em uma série de pacientes em unidade de terapia intensiva. Métodos: Estudamos, de forma prospectiva, 363 pacientes admitidos durante 1 ano em uma unidade de terapia intensiva clínico-cirúrgica. Foram excluídos pacientes que tivessem nível de creatinina sérica >1,3mg/dL. A depuração de creatinina foi calculada a partir da coleta de urina de 24 horas. Os pacientes foram agrupados segundo a presença de incremento da depuração renal (depuração de creatinina >120mL/min/1,73m2), e os possíveis fatores de risco foram analisados por meio de análise bivariada e logística. Em pacientes tratados com vancomicina, foram registradas a posologia e as concentrações plasmáticas. Resultados: O incremento da depuração renal esteve presente em 103 pacientes (28%), os quais eram mais jovens (48±15 versus 65±17 anos; p<0,0001), tinham mais frequentemente admissões obstétricas (16 versus 7%; p=0,0006) e por trauma (10 versus 3%; p=0,016), e menos comorbidades. Os únicos determinantes independentes para o desenvolvimento de incremento da depuração renal foram idade (OR=0,95; IC95%=0,93-0,96; p<0,0001;) e ausência de diabetes (OR 0,34; IC95% 0,12-0,92; p=0,03). Doze dos 46 pacientes que receberam vancomicina tinham ...

Objective: An augmented renal clearance has been described in some groups of critically ill patients, and it might induce sub-optimal concentrations of drugs eliminated by glomerular filtration, mainly antibiotics. Studies on its occurrence and determinants are lacking. Our goals were to determine the incidence and associated factors of augmented renal clearance and the effects on vancomycin concentrations and dosing in a series of intensive care unit patients. Methods: We prospectively studied 363 patients admitted during 1 year to a clinical-surgical intensive care unit. Patients with serum creatinine >1.3mg/dL were excluded. Creatinine clearance was calculated from a 24-hour urine collection. Patients were grouped according to the presence of augmented renal clearance (creatinine clearance >120mL/min/1.73m2), and possible risk factors were analyzed with bivariate and logistic regression analysis. In patients treated with vancomycin, dosage and plasma concentrations were registered. Results: Augmented renal clearance was present in 103 patients (28%); they were younger (48±15 versus 65±17 years, p<0.0001), had more frequent obstetric (16 versus 7%, p=0.0006) and trauma admissions (10 versus 3%, p=0.016) and fewer comorbidities. The only independent determinants for the development of augmented renal clearance were age (OR 0.95; p<0.0001; 95%CI 0.93-0.96) and absence of diabetes (OR 0.34; p=0.03; 95%CI 0.12-0.92). Twelve of the 46 patients who received vancomycin had augmented renal clearance and despite higher doses, had lower concentrations. Conclusions: In this cohort of critically ill patients, augmented renal clearance was a common finding. Age and absence of diabetes were the only independent determinants. Therefore, younger and previously healthy patients might require larger vancomycin dosing. .