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.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.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.
The combined use of vancomycin (VCM) and tazobactam/piperacillin (TAZ/PIPC) is a major risk factor for nephrotoxicity. We sought to evaluate interventions against the combined use of VCM and TAZ/PIPC. This retrospective cohort study involved patients who considered the combined use of VCM and TAZ/PIPC as a treatment. Patients that had either or both antimicrobials replaced were assigned to the intervention group, whereas those who were continued on combination therapy were assigned to the comparison group. The primary endpoint was the incidence of acute kidney injury (AKI). The survival rate of patients on day 30 was evaluated as the secondary endpoint. The comparison and intervention groups were composed of 65 and 68 patients, respectively, and the incidence rates of AKI were 44.6% and 17.6%, respectively. Cox proportional hazard analysis identified the intervention as the only independent factor against AKI development, with a hazard ratio of 0.282 (95% confidence interval [CI], 0.141 to 0.565). For the incidence of AKI of grade greater than 1, the hazard ratio was 0.114 (95% CI, 0.025 to 0.497). The survival rates on day 30 in the comparison and intervention groups were 92.3% and 91.2%, respectively, with a relative risk of 0.988 (95% CI, 0.892 to 1.094). The trough VCM concentration was not associated with the incidence of AKI in patients receiving the combination therapy. This study demonstrated that intervention against the combined use of VCM and TAZ/PIPC can lower the risk of nephrotoxicity. IMPORTANCE The combined use of vancomycin (VCM) and tazobactam/piperacillin (TAZ/PIPC) is a major risk factor for nephrotoxicity. We retrospectively evaluated interventions against the combined use of VCM and TAZ/PIPC. Patients for whom either or both antimicrobials were replaced were assigned to the intervention group (65 patients), whereas those who were continued on combination therapy were assigned to the comparison group (68 patients). The primary endpoint was the incidence of acute kidney injury (AKI). The incidence rates of AKI in the intervention and comparison groups were 44.6% and 17.6%, respectively. Cox proportional hazard analysis identified intervention as the only independent factor against AKI development, with a hazard ratio of 0.282 (95% confidence interval [CI], 0.141 to 0.565). In conclusion, this study demonstrated that intervention against the combined use of VCM and TAZ/PIPC can lower the risk of nephrotoxicity.
