scholarly journals Evaluation of linezolid pharmacokinetics in critically-ill obese patients with severe skin and soft tissue infections

2020 ◽  
Author(s):  
Alison L. Blackman ◽  
Praneeth Jarugula ◽  
David P. Nicolau ◽  
Sai Ho Chui ◽  
Manjari Joshi ◽  
...  
Keyword(s):  
Critically Ill ◽  
Total Body Weight ◽  
Compartment Model ◽  
Sepsis Syndrome ◽  
Obese Patients ◽  
Target Attainment ◽  
Post Infusion ◽  
Cirrhotic Patients ◽  
Total Body ◽  
Higher Doses

Background: Linezolid standard dosing is fixed at 600 mg q12h for adults. Literature suggests critically-ill, obese patients require higher doses. The study aim is two-fold: (i) to describe linezolid PK and (ii) to evaluate if PK/PD target attainment is achieved with standard dosing in critically-ill, obese patients with severe SSTIs. Methods: Adult patients with a body mass index (BMI) ≥ 30 kg/m2 and receiving IV linezolid from August 2018 to April 2019 were eligible for consent in this prospective study. Severe SSTIs were defined as necrotizing fasciitis, myonecrosis, or SSTI with sepsis syndrome. Four blood samples were collected at steady state at 1, 3, 5 hours post-infusion and as a trough. Target attainment was defined as achieving AUC0-24h/MIC ≥ 100 hr*mg/L. Monte Carlo simulations were used to determine probability of target attainment (PTA). Results: Eleven patients were included in the study. The median BMI was 45.7 kg/m2 and median total body weight (TBW) was 136.0 kg. Seven patients received standard linezolid doses and four received 600 mg q8h. A one-compartment model described linezolid PK. Based on AUC0-24h/MIC targets, for non-cirrhotic patients at 140 kg, PTA with standard linezolid doses was 100%, 98.8%, 34.1%, and 0% for MICs 0.5, 1, 2, and 4 mg/L, respectively. Conclusion: Target attainment ≥ 90% is not achieved with standard linezolid doses for non-cirrhotic patients ≥ 140 kg with MICs ≥ 2 mg/L. This study adds to accumulating evidence that standard linezolid doses may not be adequate for all patients.

scholarly journals Evaluation of Total Body Weight versus Adjusted Body Weight Liposomal Amphotericin B Dosing in Obese Patients

2021 ◽  
Author(s):  
Michelle H. Ting ◽  
Andrej Spec ◽  
Scott T. Micek ◽  
David J. Ritchie ◽  
Tamara Krekel
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Critically Ill ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Total Body Weight ◽  
Liposomal Amphotericin B ◽  
Obese Patients ◽  
Definitive Therapy ◽  
Total Body

Liposomal amphotericin B (LAmB) is used for various fungal infections, but it is unclear which dosing weight to use in obese patients. The purpose of this study was to compare clinical outcomes of adjusted body weight (adjBW) versus total body weight (TBW) dosing of LAmB. This single-center, retrospective cohort study included patients who received LAmB for definitive therapy, whose TBW exceeded 120% of their ideal body weight (IBW). Analyses were conducted for 3 mg/kg adjBW versus TBW, and 5 mg/kg adjBW versus TBW. A total of 238 patients were included. For the 68 patients who received LAmB 3 mg/kg, there were no differences in safety or efficacy outcomes. For the 170 patients who received LAmB 5 mg/kg, significantly more patients in the TBW group experienced the primary outcome of nephrotoxicity (57% vs. 35%, p-value 0.016), and had significantly higher rates of early discontinuation of LAmB due to toxicity (33% vs. 17%, p = 0.030). There was a trend towards increased 90-day mortality in the adjBW group (60% vs. 45%, p = 0.079); however, adjBW dosing was not associated with increased mortality in an adjusted model. Given lower rates of nephrotoxicity but a possible trend towards increased mortality, in patients whose TBW exceeds 120% of IBW, dosing LAmB by adjBW may be reasonable in patients who are not critically ill and who have lower risk infections. In critically ill patients or those with fungal pathogens or sites of infection associated with higher mortality risk, dosing by TBW can be considered.

scholarly journals Population Pharmacokinetics and Probability of Target Attainment of Different Dosing Regimens of Ceftazidime in Critically Ill Patients with a Proven or Suspected Pseudomonas aeruginosa Infection

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 612
Author(s):  
Annabel Werumeus Buning ◽  
Caspar J. Hodiamont ◽  
Natalia M. Lechner ◽  
Margriet Schokkin ◽  
Paul W. G. Elbers ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Hematologic Malignancy ◽  
Compartment Model ◽  
Target Attainment ◽  
Worst Case ◽  
Optimal Dosing ◽  
Population Pk ◽  
Pseudomonas Aeruginosa Infection

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected Pseudomonas aeruginosa infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement. A population PK model was constructed, and probability of target attainment (PTA) was assessed for targets 100% T > MIC and 100% T > 4 × MIC in the first 24 h. Ninety-six patients yielded 368 ceftazidime concentrations. In a one-compartment model, variability in ceftazidime clearance (CL) showed association with CVVH. For patients not receiving CVVH, variability in ceftazidime CL was 103.4% and showed positive associations with creatinine clearance and with the comorbidities hematologic malignancy, trauma or head injury, explaining 65.2% of variability. For patients treated for at least 24 h and assuming a worst-case MIC of 8 mg/L, PTA was 77% for 100% T > MIC and 14% for 100% T > 4 × MIC. Patients receiving loading doses before continuous infusion demonstrated higher PTA than patients who did not (100% T > MIC: 95% (n = 65) vs. 13% (n = 15); p < 0.001 and 100% T > 4 × MIC: 20% vs. 0%; p = 0.058). The considerable IIV in ceftazidime PK in ICU patients could largely be explained by renal function, CVVH use and several comorbidities. Critically ill patients are at risk for underexposure to ceftazidime when empirically aiming for the breakpoint MIC for P. aeruginosa. A loading dose is recommended.

Population pharmacokinetic modeling and dosing simulations of tobramycin in pediatric patients with cystic fibrosis

2021 ◽  
Author(s):  
Antonin Praet ◽  
Laurent Bourguignon ◽  
Florence Vetele ◽  
Valentine Breant ◽  
Charlotte Genestet ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Dose Adjustment ◽  
Total Body Weight ◽  
Compartment Model ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Population Pharmacokinetic Modeling ◽  
Two Compartment Model ◽  
Total Body

Initial dosing and dose adjustment of intravenous tobramycin in cystic fibrosis children is challenging. The objectives of this study were to develop nonparametric population pharmacokinetic (PK) models of tobramycin in children with CF to be used for dosage design and model-guided therapeutic drug monitoring. We performed a retrospective analysis of tobramycin PK data in our CF children center. The Pmetrics package was used for nonparametric population PK analysis and dosing simulations. Both the maximal concentration over the MIC (Cmax/MIC) and daily area under the concentration-time curve to the MIC (AUC 24 /MIC) ratios were considered as efficacy target. Trough concentration (Cmin) was considered as the safety target. A total of 2884 tobramycin concentrations collected in 195 patients over 9 years were analyzed. A two-compartment model including total body weight, body surface area and creatinine clearance as covariates best described the data. A simpler model was also derived for implementation into the BestDose software to perform Bayesian dose adjustment. Both models were externally validated. PK/PD simulations with the final model suggest that an initial dose of tobramycin of 15 to 17.5 mg/kg/day was necessary to achieve Cmax/MIC ≥ 10 values for MIC values up to 2 mg/L in most patients. The AUC 24 /MIC target was associated with larger dosage requirements and higher Cmin. A daily dose of 12.5 mg/kg would optimize both efficacy and safety target attainment. We recommend to perform tobramycin TDM, model-based dose adjustment, and MIC determination to individualize intravenous tobramycin therapy in children with CF.

P0264ASSESSMENT OF GFR IN MORBIDLY OBESE PATIENTS USING DIFFERENT EQUATIONS: WHICH IS THE BEST?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alaa Sabry ◽  
Amir Basiony ◽  
Mohamed Kamal
Keyword(s):  
Body Weight ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Total Body Weight ◽  
Lean Body Weight ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Morbidly Obese Patient ◽  
Gault Formula ◽  
Total Body

Abstract Background and Aims Obesity is a potent risk factor for the development of kidney disease. The prevalence of abdominal obesity in Egyptians based upon the European cut-off points was 30.2% for men and 70.9% for women. To detect the best formula for estimation of glomerular filtration rates in morbidly obese individuals. Method: In this prospective study 82 morbidly obese patients were included, Age: 15 to 65 years, Morbidly obese patient (BMI &gt; 40 Kg/m2), Creatinine clearance calculated from a 24-h urine was done, Estimated glomerular filtration rate (eGFR): It was assessed to be correlated with creatinine clearance and detect the most suitable formula for morbidly obese patients. Cockcroft-Gault formula:  Cockcroft-Gault formula (for total body weight): ockcroft-Gault formula (for adjusted body weight): Cockcroft-Gault formula (for lean body weight), MDRD-eGFR (Modification of Diet in Renal Disease equation) (Shahbaz & Gupta, 2019), CKD-epidemiology (CKD-EPI): (Levey, et al, 2009) Results Demogrphic criteria of the studdied patients Conclusion: The equations that had the nearest values to creatinine clearance were CG-TBW-GFR and CGAjBW- GFR, both of them had a moderate reliability with more agreement for the CG-TBW-GFR equation . The CG-TBW-GFR formula was the most reliable one to measure GFR, followed by the CG-AjBW-GFR formula, while the CG-IBW, CG-LBW, MDRD-GFR and CKD-EPI-GFR formulae were not reliable at all .

scholarly journals 1381. Impact of Total Body Weight on Efficacy of Ceftriaxone in Obese Patients

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S423-S423
Author(s):  
Jamie L Wagner ◽  
J Taylor Loper ◽  
Austin R Morrison ◽  
Kayla R Stover ◽  
Katie E Barber
Keyword(s):  
Treatment Failure ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Source Control ◽  
Causative Organism ◽  
Obese Patients ◽  
Discharge Disposition ◽  
Single Temperature ◽  
Total Body ◽  
Nonobese Patients

Abstract Background Ceftriaxone (CRO), while highly protein bound, retains a small volume of distribution. Obese patients have larger volumes of distributions and higher clearance than nonobese patients. The effect of these differences on the pharmacokinetics and efficacy of CRO remain unclear. Methods This retrospective cohort study included adult in-patients who received CRO for ≥72 hours as definitive monotherapy from July 2015 to July 2017. Patients were excluded if there was a lack of adequate source control at 72 hours or if there was a polymicrobial infection requiring multiple antibiotics. Obesity was defined as BMI ≥30 kg/m2. The primary outcome was clinical treatment failure, defined as changing therapy at &gt;72 hours due to clinical worsening, leukocytosis (WBC &gt; 10 × 109/L), fever (single temperature &gt;100.9°F) for &gt;72 hours, or readmission to the hospital within 30 days for re-infection. Secondary outcomes included discharge disposition and 30-day readmission. Results One hundred one patients were included: 39 obese patients and 62 nonobese patients. Median [IQR] age was 62 [51–70] years; 55% males. Median weight was 103 [95–120] kg in obese patients vs. 66 [58–77] kg in nonobese patients (P &lt; 0.001). There were no differences in comorbidities (Charlson 3[1–5] obese vs. 2[1–4] nonobese; P = 0.293). Infection sources were similar: urinary tract (54% obese vs. 52% nonobese; P = 0.827), respiratory (28% obese vs. 23% nonobese; P = 0.524), bloodstream (20% obese vs. 23% nonobese; P = 0.806). The most common causative organism was E. coli (48%). There were no differences in CRO regimen between groups (1g q24h: obese 54% vs. nonobese 69%; P = 0.115). Treatment failure occurred in 24 (61%) obese patients compared with 25(40%) nonobese patients (P = 0.038). Obese patients had delayed resolution of leukocytosis (54% vs. 29%, P = 0.013). Eight patients died (13% obese vs. 5% nonobese; P = 0.255); 82% of patients were not readmitted within 30 days. Conclusion Obese patients treated with ceftriaxone had higher rates of treatment failure compared with nonobese patients. While not statistically significant, there was numerically higher mortality in obese patients compared with nonobese patients. Obese patients may be slow to recover from infection when treated with CRO. Disclosures All authors: No reported disclosures.

scholarly journals Suture pattern does not influence outcomes of endoscopic sleeve gastroplasty in obese patients

2020 ◽  
Vol 08 (10) ◽  
pp. E1349-E1358
Author(s):  
E. Espinet-Coll ◽  
J. Nebreda-Durán ◽  
M. Galvao-Neto ◽  
C. Bautista-Altamirano ◽  
P. Diaz-Galán ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight Loss ◽  
Total Body Weight ◽  
Obese Patients ◽  
Serious Adverse Events ◽  
Comparative Review ◽  
Sleeve Gastroplasty ◽  
Total Body ◽  
Suture Patterns ◽  
Comorbidity Resolution

Abstract Background and study aims ESG is an effective and safe medium-term procedure for obesity treatment. A variety of suture patterns have been reported. We aimed to compare whether there are differences in efficacy depending on suture pattern used. Patients and methods Retrospective and comparative review of 5 years of prospectively collected data, including consecutive obese patients undergoing ESG at two collaborative centers. Primary outcomes included weight loss (mainly % total body weight loss [TBWL] and % exces weight loss [EWL]) at 12 months and safety profile. We compared them according to three suture patterns (transverse bilinear [TBp], longitudinal [Lp] and transverse monolinear [TMp]), and number of sutures (4 – 7) and stitches (< 25, 25 to 30 and > 30) applied. Evolution of major obesity-associated morbidities (hypertension, dyslipidemia, Type 2 diabetes mellitus (T2DM), sleep obstructive apnea syndrome, and arthropathy) were also described. Results 88 patients (mean age 46.1±12.3 years, 69.3 % female) underwent ESG. Mean body mass index (BMI) at baseline was 39.40 ± 4.69 kg/m². At 1 year, %TBWL was 17.36 ± 6.09 % (%EWL 46.41±20.6 %) with TBWL > 10 % in 95.5 % of patients (EWL > 25 % in 94.3 % of patients). According to pattern, there were no differences in %TBWL but there were in %EWL (43.7 ± 20.4 %, 59.8 ± 18.9 % and 45.4 ± 14.9 % in TBp, Lp and TMp patterns, respectively) (P = 0.034). No differences were found related to number of sutures (mean 5.2 ± 0.73, r = 4 – 7) or stitches (mean 27.4 ± 6.50, r = 18 – 50) applied. Forty-three of 72 (59.7 %) major comorbidities were resolved. No serious adverse events were observed with any pattern. Conclusions ESG is an effective procedure at 12-month follow-up for weight loss and comorbidity resolution. All three analyzed patterns are safe and effective without differences in %TBWL, but there was a slight increase in %EWL in Lp, regardless of the number of sutures or stitches applied.

Estimation of Total Body Weight in Obese Patients

2009 ◽  
Vol 28 (3) ◽  
pp. 139-145 ◽  
Author(s):  
Cameron S. Crandall ◽  
Stephanie Gardner ◽  
Darren A. Braude
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Obese Patients ◽  
Total Body

scholarly journals An Investigation of 2′-Deoxyribonucleoside Cyanoboranes in Mice for Therapeutic Safety

1994 ◽  
Vol 1 (1) ◽  
pp. 19-30
Author(s):  
Iris H. Hall ◽  
Bruce S. Burnham ◽  
K. G. Rajendran ◽  
J.-J. Chang ◽  
Anup Sood ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
White Blood Cells ◽  
Total Body Weight ◽  
Cell Counts ◽  
Daily Food ◽  
Organ Specific ◽  
Total Body ◽  
Higher Doses ◽  
Therapeutic Safety

A standard acute toxicity study was undertaken to assess 2′-deoxyribonucleoside cyanoboranes for therapeutic safety. 2′-Deoxyribonucleoside cyanoboranes and related derivatives were nontoxic at doses required for anti-neoplastic and hypolipidemic activities. At higher doses (50 and 100 mg/kg/day IP for 7 days), all treated animals survived with slight reductions in total body weight and small decrements in daily food consumption. No clinical chemistry value was elevated to a magnitude suggesting onset of organ specific toxicity. However, agents appeared to modulate subpopulations of white blood cells, i.e.¯, more lymphocytes than PMNs were present in blood from treated animals as determined by differential cell counts. This modulation is correlated with increases in granulomatous foci in the spleen and mesentery of treated animals after 7 days. The kidney was damaged only by Compound 5¯ at 50 and 100 mg/kg/day; Compound 5¯ had the most potent anti-neoplastic activity. The compounds demonstrated no in vitro¯ toxicity against human HCT-8 ileum cells. LD50 values were greater than 1000 mg/kg, IP, for all compounds.

scholarly journals Population Pharmacokinetics of Anidulafungin in Critically Ill Patients

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
S. Luque ◽  
W. Hope ◽  
N. Campillo ◽  
R. Muñoz-Bermúdez ◽  
L. Sorli ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Model ◽  
Candida Glabrata ◽  
Total Body Weight ◽  
Content Type ◽  
Final Population ◽  
Dosage Escalation ◽  
Optimal Drug ◽  
Total Body

ABSTRACT A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.

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