Background
Despite the high mortality of patients with sepsis and carbapenem-resistant bacteria infection, appropriate antimicrobial therapies are yet to be established. Here, we have reported the case of a patient with pneumonia that subsequently developed by carbapenem-resistant
Pseudomonas aeruginosa
infection and was treated with a continuous high-dose infusion of doripenem.
Case presentation
We started a continuous intravenous infusion of doripenem 3 g/day although the 59-year-old woman (body weight, 45 kg) had developed septic acute kidney injury, followed by continuous renal replacement therapy (the effluent flow rate was 650 mL/h). The minimum inhibitory concentration (MIC) of doripenem was 8 mg/L. The concentration of unbound doripenem in the serum was measured by using high-performance liquid chromatography. Twenty hours after the initial dose, the patient’s serum level of doripenem was 47.8 μg/mL; the level decreased to 33.6 μg/mL at 111 h after initial dosing. The unbound doripenem concentration in the serum was maintained four times above the MIC throughout the treatment. After the completion of 11 days of dosing, the patient was discharged from the intensive care unit. During the treatment period, the MIC remained at 8 mg/L.
Conclusions
A continuous high-dose infusion of doripenem is a potentially efficient strategy for the treatment of antimicrobial-resistant bacteria. Moreover, therapeutic drug monitoring may be useful for patients displaying variable pharmacokinetics, because the MIC is generally high in resistant bacteria.
Background
Therapeutic drug monitoring for voriconazole is recommended for its optimum pharmacotherapy. Although the feedback of the measurement result of serum voriconazole concentration by outsourcing needs a certain time (days within a 1 week), there was no medical equipment for the measurement available in clinical practice. Recently, a medical equipment based on high performance liquid chromatography, named LM1010, has been developed and authorized for clinical use. In this study, to validate the clinical performance of LM1010, we compared the measured serum voriconazole concentrations by LM1010 with those by outsourcing measurement using liquid chromatography-tandem mass spectrometry.
Methods
We conducted the observational study approved by the institutional review board of Kumamoto University Hospital (No. 1786). Residual serum samples harvested for therapeutic drug monitoring were separated. Measured concentrations by LM1010 by the standard filter method (needs serum volume of > 400 μL) or the dilute method (needs serum volume of 150 μL) were compared with those by outsourcing, respectively. Acceptable measurement error range of 0.72–1.33 was considered. There were 69 serum samples, where the 35 or 34 samples were employed for evaluation of the standard filter method or the dilute method, respectively.
Results
The measured concentration using the standard filter method/outsourcing was 2.22/2.10 μg/mL as the median, 1.57–3.40/1.53–3.62 as the interquartile range, < 0.2–10.76/< 0.2–11.46 μg/mL as the range, while those using the dilute method/outsourcing was 2.36/2.29 μg/mL as the median, 1.08–2.94/1.03–3.06 as the interquartile range, 0.24–10.00/< 0.2–10.85 μg/mL as the range. The regression line for the standard filter method or the dilute method were y = 0.935x + 0.154 or y = 0.933x + 0.162, respectively. The standard filter method or the dilute method showed 11.4% samples (4/35, 95%CI 3.2–26.7%) or 8.8% samples (3/34, 95%CI 1.9–23.7%) out of the acceptable measurement error range, respectively.
Conclusion
Measurement of serum voriconazole concentration by LM1010 can be acceptable in clinical TDM practice.
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