Continuous high-dose infusion of doripenem in a pneumonia patient infected by carbapenem-resistant Pseudomonas aeruginosa: a case report

Abstract

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.

A Systematic Review of the Effect of Therapeutic Drug Monitoring on Patient Health Outcomes during Treatment with Carbapenems

“…The included studies are summarised in Table S3 [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. Best practice for carbapenem TDM is not known, which has led to differences in the way it is carried out, particularly concerning pharmacological targets, dose-adjustment protocols, and frequency of antibiotic concentration measurement.…”

Anti-Mutant Efficacy of Combination Therapy with Doripenem and Levofloxacin: <i>In Vitro</i> Model Studies with <i>Pseudomonas Aeruginosa</i>

“…Одними из основных антисинегнойных препаратов, применяемых для терапии инфекций, вызванных псевдомонадами, являются карбапенемный антибиотик дорипенем и антибиотик группы фторхинолонов левофлоксацин [8,9]. Несмотря на исходно высокую активность указанных антибиотиков в отношении P.aeruginosa [10][11][12][13][14], клинические штаммы псевдомонад, резистентные к этим препаратам, имеют широкое распространение [15][16][17][18][19].…”