Daptomycin dosing in obese patients: analysis of the use of adjusted body weight <i>versus</i> actual body weight

Fox, Ashley N.; Smith, W. L.; Kupiec, Katherine; Harding, Stephanie J; Resman-Targoff, Beth H.; Neely, Stephen; White, Bryan P.; Owens, Ryan E.

doi:10.1177/2049936118820230

Cited by 11 publications

(11 citation statements)

References 24 publications

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“…[97] Thus, dosing regimens, either fixed (500 mg/day), based on ideal body weight or based on adjusted body weight (calculated according to a function depending on actual and ideal body weights), have been proposed. [96,[98][99][100] Although it appears that the administration of fixed doses is most likely to lead to comparable exposures between obese and non-obese patients, this approach needs to be better evaluated and the determination of fixed doses to achieve effective exposure in obese patients remains to be done. [96] Furthermore, in order to make dose recommendations in obese patients, it seems important to measure the free fraction in this population.…”

Section: Pk In Special Populationsmentioning

confidence: 99%

Clinical Pharmacokinetics of Daptomycin

Grégoire¹,

Chauzy²,

Buyck³

et al. 2020

Clin Pharmacokinet

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Due to the low level of resistance observed with daptomycin, this antibiotic has an important place in the treatment of severe Gram-positive infections. It is the first in class of the group of calcium-dependent, membrane binding lipopeptide. It is a cyclic peptide constituted of 13 amino acids and a n-decanoyl fatty acid chain. The antibacterial action of daptomycin requires its complexation with calcium.Daptomycin is not absorbed from the gastrointestinal tract and needs to be administered parenterally. The distribution of daptomycin is limited (volume of distribution of 0.1 L/kg in healthy volunteers) due to its negative charge at physiological pH and its high binding to plasma proteins (about 90%). Its elimination is mainly renal, with about 50% of the dose excreted unchanged in the urine, justifying dosage adjustment for patients with renal insufficiency. Pharmacokinetics of daptomycin is altered under certain pathophysiological conditions, resulting in high inter-individual variability. As a result, therapeutic drug monitoring (TDM) of daptomycin may be of interest for certain patients such as intensive care unit (ICU) patients, patients with renal or hepatic insufficiency, dialysis patients, obese patients or children. A target for the ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC) greater than 666 is usually recommended for clinical efficacy, whereas in order to limit the risk of undesirable muscular effects the residual concentration (Cmin) should not exceed 24.3 mg/L.

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Section: Pk In Special Populationsmentioning

confidence: 99%

Clinical Pharmacokinetics of Daptomycin

Grégoire¹,

Chauzy²,

Buyck³

et al. 2020

Clin Pharmacokinet

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“…Two small retrospective studies observed similar treatment outcomes in obese patients with resistant gram-positive infections dosed on adjusted body weight (ABW) versus TBW. 28,29 Another retrospective analysis described similar clinical and microbiological outcomes in obese patients with gram-positive infections prescribed daptomycin dosed using ideal body weight (IBW) versus TBW. 30 Despite this, PK-PD analyses suggest that IBW-based dosing in obese patients results in suboptimal exposures compared with TBW-based dosing, whereas ABW (with a correction factor of 0.4) generated exposures only 6.6% higher than TBW-based dosing.…”

Section: Discussionmentioning

confidence: 99%

A Pharmacokinetic-Pharmacodynamic Analysis to Dose Optimize Daptomycin in Vancomycin-Resistant Enterococcus faecium: Is the Answer Fixed Dosing or Lowering Breakpoints?

Butterfield-Cowper¹

2020

Ann Pharmacother

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Background: The optimal daptomycin dose for vancomycin-resistant Enterococcus faecium remains unclear. Dosing of 8 to 12 mg/kg/d has been recommended to improve outcomes, but literature suggests fixed dosing may improve methicillin-resistant Staphylococcus aureus bacteremia pharmacodynamic (PD) targets. Objective: This study sought to evaluate weight-based versus fixed dosing of daptomycin based on pharmacokinetic and PD (PK-PD) targets in vancomycin-resistant E faecium bacteremia. Methods: PK-PD analyses were conducted using previously published PK models for daptomycin. Probability of target attainment (PTA) was assessed for 8 to 12 mg/kg/d and various fixed doses. The percentage of simulated participants who achieved a free area under the concentration-time curve from 0 to 24 hours to minimum inhibitory concentration ratio ( fAUC0-24/MIC) >27.43 for susceptible dose-dependent (SDD) MICs and the probability of a minimum concentration ( Cmin) > 24.3 mg/L were calculated. Results: At MICs ≤2 mg/L, fixed doses had the best overall PTA. At the SDD breakpoint of 4 mg/L, all weight-based doses had <60% PTA. A fixed dose of 1500 mg/d was necessary for >/= 90% PTA at higher MICs considered SDD; however, this dose had elevated risks of Cmin ≥24.3 mg/L. Conclusion and Relevance: Fixed doses were more likely to achieve a fAUC/MIC of 27.43 than weight-based doses up to 12 mg/kg/d. However, fixed doses necessary for 90% PTA against SDD isolates with higher MICs were associated with elevated risks of toxicity. A reevaluation of Clinical Laboratory Standards Institute breakpoints may need to be considered, with an emphasis on lowering the SDD breakpoint to 1 mg/L.

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“…Dosing of daptomycin in patients with weight >100 kg has not been clearly established and can vary by site of infection, indication, and clinical pharmacist. In comparing adjusted with actual body weight dosing of daptomycin, there was no difference in clinical outcomes or CPK elevations in a retrospective review [ 9 ]. Our site changed from actual to adjusted body weight in our period of review, which impacted our ability to determine the effect of elevated BMI on eosinophilia.…”

Section: Discussionmentioning

confidence: 99%

“…Also, factors associated with the causes of eosinophilia (obesity and daptomycin dosing) have been inferred from case reports, but not clearly demonstrated [ 6 , 7 ]. With increased dosing of daptomycin to 8 mg/kg recommended for S. aureus infections, there has been no guidance on whether this should be on actual body weight (as recommended by the Food and Drug Administration [FDA]) or adjusted body weight, making it complicated for dosing in morbidly obese patients [ 8 , 9 ].…”

mentioning

confidence: 99%

Eosinophilic Syndromes Associated With Daptomycin Use: Re-exposure Hypersensitivity Pneumonitis and Prior Peripheral Eosinophilia

West

Sheeti

Mackay

et al. 2022

Open Forum Infectious Diseases

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Background Daptomycin pulmonary eosinophilia (DPE) has been well described in case reports and reporting from the Food and Drug Administration. We report 3 eosinophilic syndromes associated with daptomycin use. Methods This is a retrospective review of all patients who received daptomycin (inpatient or outpatient) from 2010 to 2020 at the Veterans Affairs Portland Healthcare System. Patients who developed DPE while receiving daptomycin were evaluated to determine risk factors. Data collected included daptomycin dose and duration, body mass index, creatinine clearance, and peripheral eosinophilia. Results Of 330 patients who received daptomycin, 81.5% developed a peripheral eosinophilia, with 109 (33%) developing peripheral eosinophilia ≥5%. Fifty-one (16%) met criteria for DPE. Primary DPE occurred in 38 of the 51 patients with a median 26 days of treatment, and 49% had peripheral eosinophilia ≥5%. Re-exposure DPE occurred in the other 13 patients and occurred a median of 3 days after initiation of daptomycin. The presence of an elevated peripheral eosinophilia of ≥5% during daptomycin usage was significantly associated with primary (odds ratio [OR], 2.23; 95% CI, 1.2–4.09; P = .008) and re-exposure DPE (OR, 12; 95% CI, 1.6–103; P = .003). All patients recovered after withdrawal of daptomycin without complications. Conclusions There are 3 daptomycin eosinophilic syndromes: peripheral eosinophilia, primary DPE occurring about 4 weeks into therapy, and re-exposure DPE. Elevated peripheral eosinophilia ≥5% was a risk factor for both primary and re-exposure DPE, but still identified about half the cases. Peripheral eosinophilia should be carefully monitored during daptomycin treatment, and clinicians should be aware that prior eosinophilia may predict an acute pulmonary reaction upon daptomycin re-exposure.

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Daptomycin dosing in obese patients: analysis of the use of adjusted body weight versus actual body weight

Cited by 11 publications

References 24 publications

Clinical Pharmacokinetics of Daptomycin

Clinical Pharmacokinetics of Daptomycin

A Pharmacokinetic-Pharmacodynamic Analysis to Dose Optimize Daptomycin in Vancomycin-Resistant Enterococcus faecium: Is the Answer Fixed Dosing or Lowering Breakpoints?

Eosinophilic Syndromes Associated With Daptomycin Use: Re-exposure Hypersensitivity Pneumonitis and Prior Peripheral Eosinophilia

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