Comprehensive Guidance for Antibiotic Dosing in Obese Adults

Aim: Vancomycin guidelines for therapeutic drug monitoring (TDM) aim to maximise efficacy while minimising toxicity and resistance. Vancomycin is effective against Staphylococcus aureus when it achieves area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) > 400. Studies in children have shown that target trough concentrations poorly correlate to AUC/MIC > 400; however, they are used in practice for clinical convenience. This review in paediatric inpatients aims to audit performance against TDM guidelines and consider what changes are needed to optimise vancomycin monitoring. Methods: Vancomycin prescriptions in patients younger than 18 years old were collected over a 15-month period. Primary outcome measures were vancomycin initial dose (mg/kg/day) and the timing and result of first trough concentration (mg/L). Secondary outcome measures were the numbers achieving recommended targets and whether appropriate dose adjustments were made in response to TDM. Results: A total of 133 courses reached the time when TDM should occur. Average patient age was 6.5 years, and the average initial dose was 52.55 mg/kg/day (range 19.05-86.54 mg/kg). Only 25% of courses (n = 34) had a trough concentration measured at the recommended time. The mean trough concentration was 11.6 mg/L (range < 2.0-39.7). Of 40 patients with a low trough concentration, 50% continued without dose adjustment. Conclusion: As shown in the literature, there is a poor correlation between the vancomycin dose given and the trough concentration achieved. Given that recommendations for trough concentration monitoring are designed to simplify the process yet are poorly adhered to, a strategic plan to address these issues is needed.

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“…Recent guidelines by Meng et al . favour Bayesian forecasting over the traditional trough measurements in adult obese patients …”

Section: Introductionmentioning

confidence: 99%

Vancomycin therapeutic drug monitoring in paediatrics

Patel

Lucas

Ryan

et al. 2019

J Paediatrics Child Health

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“…Obese patients are another population where under-dosing may occur if dose adjustments are not implemented. A recent review of literature concluded that 23/34 (68%) of antibiotics were recommended for obesity-specific dosing (Meng et al, 2017). These problems may be further unknowingly amplified by the disposal of a residual volume of antibiotic within the administration set.…”

Section: Discussionmentioning

confidence: 99%

Non-flushing of IV administration sets: an under-recognised under-dosing risk

2018

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Background: intravenous (IV) drugs are administered widely and under-dosing can result in therapy failure. The aim of this study was to quantify frequency, volume and dose of drug discarded within administration sets in the clinical setting. Methods: residual volume for 24 different administration sets was measured under controlled conditions in a laboratory. Clinical assessment of current practice regarding post-infusion flushing occurred in 6 departments of one teaching hospital in the UK over 7 days. Details of drug last infused, (concentration, diluent and volume) and type and brand of administration set were collected. Results: 74% of administration sets were not flushed. Nonflushing exceeded 90% and 61% for gravity and pump infusions respectively (p<0.001) in all areas excluding oncology. Oncology was the only area where flushing was standard practice for all infusions (p<0.001). Mean residual volume of the administration sets was 13.1 ml and 16.7 ml for gravity and pump sets respectively. Antibiotics were commonly infused and up to 21% of antibiotic dose was frequently discarded. Conclusions: the findings suggest disposal of substantial volumes of drugs occurs frequently in general hospital areas. Without clear national and local policies this unrecognised underdosing will continue.

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“…Therefore, adequate antibiotic therapy with sufficient effective concentrations is particularly important for obese patients. However, guideline recommendations for linezolid suggest weight-independent dosing [16]. The plasma volume does not differ between non-obese and obese patients nearly as much as the volume of soft tissue [17].…”

Section: Introductionmentioning

confidence: 99%

Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study

Simon

Busse

Petroff

et al. 2020

JCM

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Background: Linezolid is used for the treatment of soft tissue infections in critically ill patients. However, data for characterizing the pharmacokinetics (PK) and assessing whether effective concentrations are reached at the target site are lacking. We hypothesized that current dosing regimens do not lead to effective concentrations in the plasma and interstitial fluid (ISF) of subcutaneous tissue in obese patients. Methods: As a controlled clinical model, critically ill obese and non-obese patients undergoing intra-abdominal surgery received 600 mg linezolid as a single infusion. Concentrations in the plasma and microdialysate from the ISF of subcutaneous tissue were determined up to 8 h after dosing. Pharmacokinetic analysis was performed by non-compartmental methods. As a therapeutic target, we used f AUC/MIC > 80. Results: Fifteen obese (BMI: 48.7 ± 11.2 kg/m 2 ) and 15 non-obese (23.9 ± 2.1 kg/m 2 ) patients were analyzed. AUC 0-8 in ISF decreased by −1.69 mg*h/L (95% CI: −2.59 to −0.79, p < 0.001) for every 10 kg increase in weight. PK in obese patients were characterized by lower maximal plasma concentrations (median 3.8 vs. 8.3 mg/L, p < 0.001) and a higher volume of distribution (41.0 vs. 30.8 L, p < 0.001), and the therapeutic target was not reached for MIC ≥ 1 mg/L in ISF and ≥ 2 mg/L in plasma. Conclusions: Increasing the weight led to a decrease of linezolid concentrations in the plasma and subcutaneous tissue. The current dosing regimen does not seem to produce sufficient concentrations to kill bacteria with MIC ≥ 2 mg/L, especially as empirical antimicrobial therapy in critically ill obese patients.

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Comprehensive Guidance for Antibiotic Dosing in Obese Adults

Cited by 122 publications

References 75 publications

Vancomycin therapeutic drug monitoring in paediatrics

Vancomycin therapeutic drug monitoring in paediatrics

Non-flushing of IV administration sets: an under-recognised under-dosing risk

Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study

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