Pharmacokinetic/pharmacodynamic analysis of vancomycin in patients with Enterococcus faecium bacteraemia: a retrospective cohort study.

OBJECTIVES: The trough concentration of vancomycin and the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus. However, the use of similar pharmacokinetic principles in determining antibiotic efficacy against other gram-positive cocci is lacking. We performed a pharmacokinetic/pharmacodynamic analysis (association of target trough concentration values and AUC/MIC with therapeutic outcome) of vancomycin in patients with Enterococcus faecium bacteraemia. METHODS: Between January 2014 and December 2021 we performed a retrospective cohort study of patients with E. faecium bacteraemia treated with vancomycin. Patients who received renal replacement therapy or had chronic kidney disease were excluded. Clinical failure, the primary outcome, was defined as a composite of 30-day all-cause mortality, vancomycin-susceptible infection requiring change of treatment, and/or recurrence. AUC24 was estimated using a Bayesian estimation approach based on an individual vancomycin trough concentration. The MIC for vancomycin was determined using a standardised agar dilution method. Additionally, classification was used to identify the vancomycin AUC24/MIC ratio associated with clinical failure. RESULTS: Of the 151 patients identified, 69 were enrolled. All MICs of vancomycin for E. faecium were ≤1.0 µg/mL. The AUC24 and AUC24/MIC ratio were not significantly different between the clinical failure group and the clinical success group (432±123 µg/mL/hour vs 488±92 µg/mL/hour; p=0.075). However, 7 of 12 patients (58.3%) in the clinical failure group and 49 of 57 patients (86.0%) in the clinical success group had a vancomycin AUC24/MIC ratio ≥389 (p=0.041). No significant association between trough concentration or AUC24 ≥600 µg/mL×hour and acute kidney injury was observed (p=0.365 and p=0.487, respectively). CONCLUSION: The AUC24/MIC ratio is associated with the clinical outcome of vancomycin administration in E. faecium bacteraemia. In Japan, where vancomycin-resistant enterococcal infection is rare, empirical therapy with a target AUC24 ≥389 should be recommended.

Increased Arbekacin Clearance in Patients With Febrile Neutropenia.

BACKGROUND: Arbekacin (ABK) is used to treat infections caused by methicillin-resistant Staphylococcus aureus and is used widely for the treatment of febrile neutropenia (FN). As ABK has a narrow therapeutic concentration window, the dosage must be adjusted via therapeutic drug monitoring. However, the influence of the physiology of patients with FN on the pharmacokinetic (PK) parameters of ABK remains unclear. Therefore, we examined this influence on ABK PK parameters. METHOD: We performed a retrospective cohort study using data from patients with a hematologic malignancy who were ≥18 years and had been administered ABK. We excluded patients who did not receive therapeutic drug monitoring and had an estimated glomerular filtration rate (eGFR) of <30 mL/min, because clinically sufficient data would not be available. RESULT: Of the 99 enrolled patients, 25 did not have FN and 74 had FN. Arbekacin clearance (CLabk) was shown to correlate with eGFR in patients with FN (r = 0.32, P = 0.0062) and without FN (r = 0.50, P = 0.01). CLabk was higher in patients with FN than in those without FN. In addition, in the eGFR of <100 mL/min group (normal renal function), CLabk and CLabk/eGFR were also higher in patients with FN than in those without FN. CONCLUSIONS: CLabk was increased in patients with FN and normal renal function; therefore, we propose an increased ABK dose for patients with FN and normal renal function.

Relationship between hemoglobin levels and vancomycin clearance in patients with sepsis.

PURPOSE: It is important to accurately estimate accurate vancomycin (VCM) clearance (CLvcm) for appropriate VCM dosing in the treatment of patients with sepsis. However, the pathophysiology of sepsis can make CLvcm prediction less accurate. Clearance of hydrophilic antibiotics is disturbed by organ dysfunction, and hemoglobin levels are negatively correlated with sequential organ function assessment scores. We investigated whether hemoglobin levels are associated with CLvcm in sepsis patients. METHODS: We performed a retrospective cohort study of patients treated with VCM in the Emergency and Critical Care Center of Nihon University Itabashi Hospital between 2005 and 2015. We enrolled 72 patients after exclusion of patients who received renal replacement therapy or surgery, had a change in hemoglobin levels more than 2 g/dL or received an erythrocyte infusion during the interval between initial VCM administration and measurement of initial trough levels, had a serum baseline creatinine level of ≥ 2 mg/dL, or were under 18 years old. RESULTS: Enrolled patients consisted of 13 non-sepsis patients and 59 sepsis patients. In sepsis patients, although CLvcm was correlated with CrCl in HGB ≥ 9 group as well as in non-sepsis patients, its correlation was not observed in HGB < 9 group. Hemoglobin levels were correlated with CLvcm in sepsis patients but not in non-sepsis patient. Multiple linear regression analysis also indicated that lower CLvcm was associated with lower hemoglobin and CrCl. CONCLUSION: Lower hemoglobin levels influence a relationship between CLvcm and CrCl in sepsis patients. We propose that VCM dosing should be adjusted for hemoglobin levels in sepsis patients.