Variability of pharmacokinetic parameters in patients receiving different dosages of daptomycin: is therapeutic drug monitoring necessary?

Falcone, Marco; Russo, Alessandro; Cassetta, Maria Iris; Lappa, A.; Tritapepe, Luigi; d’Ettorre, Gabriella; Fallani, Stefania; Novelli, Andréa; Venditti, Mario

doi:10.1007/s10156-013-0559-z

Cited by 75 publications

(59 citation statements)

References 21 publications

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“…On the other hand, 2 patients in this study exhibited low C trough and C peak levels despite receiving high‐dose treatments (> 9 mg/kg). The unexpected variability or low levels of daptomycin in blood were also reported in another study . Therefore, the monitoring of serum levels of daptomycin may be useful to detect and prevent the occurrence of subtherapeutic serum levels.…”

Section: Discussionsupporting

confidence: 65%

Observational retrospective single‐centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation

et al. 2019

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What is known and objective Daptomycin‐induced creatinine phosphokinase (CPK) elevation is reported to be associated with its trough level (Ctrough; breakpoint of 24.3 μg/mL). However, even with high‐dose treatment (ie, > 8 mg/kg), the safety of daptomycin treatment is widely demonstrated with low or no significant incidence of CPK elevation or other adverse effects, despite the possibility of Ctrough above 24.3 μg/mL. Therefore, we questioned the clinical significance of Ctrough levels of 24.3 μg/mL. In this study, we retrospectively evaluated the significance of Ctrough in the clinical setting, in addition to completing a retrospective safety assessment of daptomycin utilizing electronic health records. Methods Patients who had received daptomycin treatment for > 4 days from July 2011 to June 2015 were enrolled. Serum daptomycin levels, including Ctrough and peak (Cpeak), were measured by high‐performance liquid chromatography equipped with a photodiode array. To evaluate the safety, patients’ characteristics and relevant laboratory test values were reviewed retrospectively using an electronic medical record system. Results and discussion A total of 52 therapeutic cases for 46 patients were identified; of these, Ctrough and Cpeak levels were measured in 27 and 28 cases, respectively, and 6 patients received multiple courses of daptomycin treatment. The median age of the 52 patients was 68 years (range: 19‐88 years), and 14 patients initially had an estimated creatinine clearance of less than 30 mL/min. Seven cases indicated a Ctrough of above 24.3 μg/mL; however, none of these presented CPK elevation, which meets with the study definition for abnormality. Furthermore, of the two patients with abnormal CPK elevations, only one patient had a measured Ctrough (of 10.9 μg/mL). Their CPK abnormalities were temporal and did not result in treatment discontinuation. The other four patients discontinued daptomycin treatment due to suspicions of adverse effects. Of the discontinued patients, two had measured Ctrough levels; these were 8.6 and 8.1 μg/mL. All patients with abnormal CPK elevation or treatment discontinuation exhibited Ctrough levels lower than 24.3 μg/mL. In this study, two patients receiving high‐dose daptomycin (ie, 9.4 and 10.0 mg/kg) had observed Ctrough levels similar to patients who received doses of daptomycin < 9 mg/kg. What is new and conclusions The safety of daptomycin treatment was suggested in this study. Ctrough level of 24.3 μg/mL was not suggested as a significant clinical index for the incidence of CPK elevation, adverse effects or treatment discontinuation. Thus, acceptable tolerability towards higher Ctrough levels than 24.3 μg/mL was also suggested, though further studies are required. On the other hand, low levels of daptomycin in blood were unexpectedly observed in two cases, despite the high‐dose treatments. Accordingly, the monitoring of serum daptomycin levels may also be useful to assess cases in which subtherapeutic levels were achieved.

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Section: Discussionsupporting

confidence: 65%

Observational retrospective single‐centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation

et al. 2019

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“…From a previous study report, it is important to indicate that DAP AUC/MIC <666 in infectious patients is a risk factor associated with a poor outcome [3]. Another study suggested that the AUC free /MIC required for static effects with MRSA was 12-36, but that 99% of maximal kill was achieved at ratios of 171-442 [4].…”

Section: Discussionmentioning

confidence: 99%

“…DAP is approved at a dose of 4 mg/kg for the treatment of complicated skin and soft tissue infections, and 6 mg/kg for the treatment of right-sided infective endocarditis and bacteremia. Its therapeutic efficacy is directly related to an adequate concentration in the blood [3]. As key pharmacodynamics parameters, the ratio of the area under the unbound concentration-time curve to the minimum inhibitory concentration (MIC) (AUC free /MIC) has been shown to be the best for predicting bacterial killing by DAP [4].…”

Section: Introductionmentioning

confidence: 99%

Considerations about the Use of a Loading Dose of Daptomycin in a Neutropenic Murine Thigh Infection Model with Methicillin-Resistant Staphylococcus aureus Infection

Kato

Hagihara²,

Murakami³

et al. 2017

Chemotherapy

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Previous clinical studies have showed the clinical benefits of the initiation of treatment with a daptomycin (DAP) loading dose, but only a few studies have evaluated its antimicrobial benefits. We evaluated the efficacy of a DAP loading dose against methicillin-resistant Staphylococcus aureus (MRSA) infections in a neutropenic murine thigh infection model. Three MRSA isolates (DAP MIC: 0.5, 1, and 2 mg/L) were tested. Four DAP regimens simulating human concentration-time profiles, i.e., (i) day 1: 8 mg/kg and day 2: 6 mg/kg, (ii) days 1 and 2: 6 mg/kg/day, (iii) day 1: 8 mg/kg and day 2: 4 mg/kg, and (iv) days 1 and 2: 4 mg/kg/day, were administered to the mice. Efficacy was calculated as the change in bacterial density. DAP loading-dose regimen iii showed greater antimicrobial activity against MRSA with MIC 1 mg/L than nonloading regimen iv (-3.10 ± 0.63 vs. -0.71 ± 0.34 log₁₀ CFU; p < 0.01). Loading-dose regimen iii achieved greater log₁₀ CFU changes than nonloading regimen ii, while the total DAP dose for 2 days was the same (-3.10 ± 0.63 vs. -1.46 ± 0.48 log₁₀ CFU; p < 0.05). DAP loading-dose regimen iii showed enhanced antimicrobial activity against MRSA with DAP MIC 0.5 mg/L when compared with nonloading regimen iv. However, loading-dose regimens i and iii did not reduce bacterial density for MRSA with DAP MIC 2 mg/L. Our data suggest that a DAP loading-dose regimen would be an advantageous procedure for patients infected with MRSA with DAP MIC ≤1 mg/L.

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“…In our patient, usual-dose DAP (350 mg/day, approximately 7 mg/kg) was initially administered for two weeks; however, the treatment failed. Falcone et al reported that the pharmacokinetics of DAP can significantly change in patients with sepsis; its clearance is increased and the level of DAP exposure is lower (34). The authors suggested that a minimum of 500 mg or 750 mg of DAP is required to achieve the target concentration (11).…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Persistent MRSA Bacteremia using High-dose Daptomycin Combined with Rifampicin

et al. 2014

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We herein report a case of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that was successfully treated with combination therapy consisting of high-dose daptomycin (DAP, 10 mg/kg) and rifampicin. The patient's condition was complicated with multiple infectious foci, including an iliopsoas abscess and epidural abscess, as well as discitis and spondylitis at the cervical, thoracic and lumbar levels. Monotherapy treatments with vancomycin, linezolid and usual-dose DAP were all ineffective. It has been shown that usual-dose DAP administration may result in the emergence of a resistant strain and treatment failure. We would like to emphasize the importance of high-dose DAP therapy for MRSA bacteremia, a condition with a potentially high mortality rate.

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Variability of pharmacokinetic parameters in patients receiving different dosages of daptomycin: is therapeutic drug monitoring necessary?

Cited by 75 publications

References 21 publications

Observational retrospective single‐centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation

Observational retrospective single‐centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation

Considerations about the Use of a Loading Dose of Daptomycin in a Neutropenic Murine Thigh Infection Model with Methicillin-Resistant Staphylococcus aureus Infection

Successful Treatment of Persistent MRSA Bacteremia using High-dose Daptomycin Combined with Rifampicin

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