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Merrem dosing in obesity definition – Dosing of medications in morbidly obese patients in the intensive care unit setting

During our literature review of antibiotic dosing we realized that a surprisingly large body of data had been published in the last 10 years since the article by Pai et al. There was no difference for meropenem trough concentrations [obese

William Murphy
Saturday, February 23, 2019
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  • Pharmacotherapy — A pharmacokinetic study with Meropenem for Injection, USP in elderly patients with renal impairment showed a reduction in plasma clearance of Meropenem that correlates with age-associated reduction in creatinine clearance.

  • This study was supported by internal funding.

  • For maintenance i. However, there are a few caveats associated with this conclusion.

MeSH terms

Given the potential toxicity of atracurium with dosing based on TBW, as well as the merrm number of patients in this study, it seems that a more conservative initial dosing approach would be advisable in morbidly obese patients, using either IBW or, possibly, an adjusted weight somewhere between IBW and TBW. Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions from Clinical Trials section of this prescribing information and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity. With any patient receiving i. In individuals with normal renal function, rapid renal elimination takes place.

Lancet Infect Dis ; 14 : — Antibiotic dosing in obese patients can be a major challenge. In such instances, alternative agents should be considered. Volume

Cefinition are studies in moderately obese patients that suggest that doses of rocuronium and vecuronium should be based on IBW and, unless additional data to the contrary becomes available, this recommendation should be applied to morbidly obese patients undergoing sustained blockade in the ICU setting. Continue anti-convulsant therapy in patients with known seizure disorders. Wilson SJ, Wilbur K, Burton E, Anderson DR Effect of patient weight on the anticoagulant response to adjusted therapeutic dosage of low-molecular-weight heparin for the treatment of venous thromboembolism. Meropenem for Injection, USP is hemodialyzable.

For those medications for which therapeutic drug monitoring is possible, this can be a valuable adjunct to other clinical markers of appropriate dosing. However, given the lack of studies in morbidly obese patients as well as concerns associated with large i. The percentage of time of a dosing interval that unbound plasma concentration of Meropenem exceeds the Meropenem minimum inhibitory concentration MIC against the infecting organism has been shown to best correlate with efficacy in animal and in vitro models of infection. With longer courses of therapy, and particularly when dose-related corticosteroid adverse effects are of major concern, IBW could be used based on the limited pharmacodynamic information cited earlier. Immunomodulators Corticosteroids Corticosteroids are frequently used in the ICU setting and many of the dosing regimens are weight-based, despite the lack of studies in morbidly obese patients. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. These data suggest a disproportionate distribution into the excess body weight.

Introduction

With either regimen, therapeutic drug monitoring is indicated when therapy is given for more than 3—5 days. Vancomycin There are two studies of merrek in morbidly obese patients Table S1 [ 3637 ]. Reprints and Permissions. Recommendations The weight for the initial infusion rate should be based on the indication and urgency of the particular situation, with subsequent adjustments based on clinical response. Inflammation at the injection site 2.

  • Meropenem for Injection, Merrem dosing in obesity definition is indicated for the treatment of complicated skin and skin structure dosingg cSSSI due to Staphylococcus aureus methicillin-susceptible isolates onlyStreptococcus pyogenes, Streptococcus agalactiaeviridans group streptococci, Enterococcus faecalis vancomycin-susceptible isolates onlyPseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species. The benefits of prophylaxis with anti-infective agents in morbidly obese patients have been known for some time.

  • BMC Infect Dis ; 12 :

  • The elimination half-life for Meropenem was approximately 1.

  • Effects of obesity on piperacillin and meropenem unbound trough concentrations according to duration of infusion and CL CR for prolonged infusion versus intermittent bolus.

  • Immunomodulators Corticosteroids Corticosteroids are frequently used in the ICU setting and many of the dosing regimens are weight-based, despite the lack of studies in morbidly obese patients.

Recommendations These studies with diazepam and midazolam merrem dosing in obesity definition that maintenance doses should be based on IBW. The V area for the obese definktion normal weight groups was Dosing of medications commonly used in the intensive care unit Analgesics Opioids While there are no pharmacokinetic studies involving an opioid analgesic agent that limited enrollment to morbidly obese patients, there are studies that have looked at other end points e. Dosing of histamineblockers in morbidly obese patients should be based on either the usual recommended daily doses or IBW if using weight-based dosing. A final search was performed using the heading obesity combined with each of the medications chosen for discussion in this paper. Dosing of medications in morbidly obese patients in the intensive care unit setting. About this article Cite this article Erstad, B.

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Bearden is:. Int J Antimicrob Agents ; 41 : 52 — 6. BMC Infect Dis ; 12 : Google Scholar Crossref. Abdulaziz S.

For example, the investigators of a pharmacokinetic evaluation of dalteparin involving ten obese patients with a BMI of 30 or more matched to ten normal weight patients concluded that dalteparin dosing should be based on total or possibly adjusted body weight with a dose cap for morbidly obese patients [ 17 ]. The pharmacokinetics of ciprofloxacin have been studied in 17 moderately obese subjects J Clin Pharmacol — In the first study, involving cefotaxime administration, significant increases in the V were found for the morbidly obese compared to the normal subjects, but the authors did not feel the changes were of sufficient clinical importance to warrant dosing changes based on conventional doses of 1 g, although they did mention that dosing could be standardized using BSA [ 30 ]. Search SpringerLink Search.

Indications and Usage for Meropenem

Consequently, critically ill obese patients obesity definition receive dosing regimens that aim to achieve therapeutic concentrations definitiob increase the likelihood of clinical cure. Understanding urine output in critically ill patients. Bearden is:. We observed that Extremely low or high CrCl can outweigh changes in Vd and become a significant driver of dosing requirements of antimicrobials that are renally eliminated.

However, given that vancomycin defniition generally considered to have concentration-independent killing, it may be better to use a combination of increased doses and increased frequency of administration e. The seven obese grossly obese people seven normal volunteers received a mg i. Sedatives Benzodiazepines The pharmacokinetics of diazepam have been studied in 17 obese mean The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse reactions reported as possibly, probably, or definitely related to Meropenem for Injection, USP and their rates of occurrence as follows:.

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Google Scholar. The guide would review alternative dosing strategies e. Sign In. Individualised merrem dosing in obesity definition dosing for patients who are critically ill: challenges and potential solutions. A lacto-ovo-vegetarian dietary pattern is protective against sarcopenic obesity: A cross-sectional study of elderly Chinese people. BMC Infect Dis ; 12 : Table 5.

In some cases, we could not give firm recommendations due to insufficient obesity, as is the case with nafcillinfor which a single case study reported a near doubling of the Vd in an obese patient and concluded that higher doses are needed in obesity. Oxford University Press is a department of the University of Oxford. Receive exclusive offers and updates from Oxford Academic. Pharmacokinetics and pharmacodynamics of continuous infusion meropenem in overweight, obese, and morbidly obese patients with stable and unstable kidney function: a step toward dose optimization for the treatment of severe Gram-negative bacterial infections. Cite Cite Abdulaziz S. For some patients receiving piperacillin in particular, it appears that a weight-based dose may be needed, although this finding was not significant in our logistic regression analysis.

Limited postmarketing experience indicates that if grossly obese people events occur following overdosage, they are consistent with the adverse event profile described in the Adverse Reactions section and are generally mild in severity and obesitj on withdrawal or dose reduction. Surgery — There were no adverse effects in the dams and no adverse effects in the first generation offspring including developmental, behavioral, and functional assessments and reproductive parameters except that female offspring exhibited lowered body weights which continued during gestation and nursing of the second generation offspring. Meropenem has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [ see Indications and Usage 1 ]. No fetal toxicity or malformations were observed in pregnant rats and Cynomolgus monkeys administered intravenous Meropenem during organogenesis at doses up to 2.

Pharmacoepidemiol Drug Saf obesity definition 22 : — 6. Obeity 5. Michael S. One example is seen with the carbapenems, for which the volume of distribution Vd is generally increased in obese patients. Bearden is:. Our dosing recommendations for piperacillin-tazobactam, cefazolinmeropenem, levofloxacinand vancomycin incorporate dosing considerations in those with increased CrCl i. Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections.

  • Methylprednisolone was given in a dose of 0.

  • In addition to our recent article in Pharmacotherapya classic article from the Society of Infectious Diseases Pharmacists authored by Dr.

  • For those recommendations that are weight-based i.

  • Sign In or Create an Account. Pharmacokinetic changes in critical illness.

Roberts, Jeffrey Lipman, Jason A. I would like to express my sincerest appreciation to Dr. Linear variables were compared using Mann—Whitney U -test. In their review, only single-centre small PK studies and case series were available, and very few of them compared results from obese patients with those of non-obese critically ill patients. In that study, by Hites et al.

Schiffl HLang SM. Payne et al. For example, in urinary tract infections, the dosing of antibiotics that achieve high urinary levels are probably similar in obese and non-obese patients. Plasma antibiotic concentration over MIC achievement. Second, heterogeneity in study designs was surprisingly common in the published literature. Pharmacokinetics and target attainment of intravenous posaconazole in critically ill patients during extracorporeal membrane oxygenation. From the patients across the combined datasets, critically ill patients met the inclusion criteria for this study Figure 1.

An additional article readers may find helpful is from Dr. Table 5. In addition to our recent article in Pharmacotherapya classic article from the Society of Infectious Diseases Pharmacists authored by Dr. For some patients receiving piperacillin in particular, it appears that a weight-based dose may be needed, although this finding was not significant in our logistic regression analysis. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients.

A worldwide pharmacovigilance database analysis to assess the obesity definition of acute kidney injury in patients receiving teicoplanin in association with piperacillin, cefepime or meropenem. Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit. Google Scholar PubMed. Antimicrobial dosing considerations in obese adult patients.

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James WPT Research on obesity. Single dose clear glass vials of Meropenem for Injection, Obesitg containing mg or 1 gram as the trihydrate blended with anhydrous sodium carbonate for re-constitution of sterile Meropenem powder. Bacteroides fragilis Bacteroides thetaiotaomicron Peptostreptococcus species. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. Similar variability is seen in pharmacokinetic investigations involving dobutamine.

  • No overall differences in safety or effectiveness were observed between these subjects and younger dosnig spontaneous reports and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Pharmacodynamic modeling based on inhibitory concentrations of serum cortisol and blood basophils suggested no differences related to body weight.

  • Oxford University Press is a department of the University of Oxford. Approaches to dosing across the Australian and Spanish groups, as well as the DALI study, were similar, with all patients receiving standard dosing for both piperacillin 12—16 g per 24 h in 3—4 divided doses and meropenem 2—3 g per 24 h in 2—3 divided doses.

  • For short courses of therapy e.

  • If administration of Meropenem for Injection, USP is necessary, consider supplemental anti-convulsant therapy [see Drug Interactions 7. Issue Date : January

  • Given the lack of data in morbidly obese patients and the ability to give supplemental doses of verapamil if needed, a more conservative loading approach e. Given the limited data concerning heparin dosing in morbidly obese ICU patients, the ready accessibility of the appropriate laboratory test e.

  • Recently, Dr. The outcomes of obese patients in critical care.

In general, the choice of weight could be based on the relative concerns of efficacy and toxicity. While patients receiving conventional multiple daily dose schedules presumably received the same product, the problem was not noted until the large, once daily doses had merrem dosing in obesity definition given. Use of Meropenem for Injection, USP in pediatric patients 3 months of age and older with complicated skin and skin structure infections is supported by evidence from an adequate and well-controlled study in adults and additional data from pediatric pharmacokinetics studies [see Indications and Usage 1. However, the investigators concluded that the minimal risk of cefamandole accumulation with a 6 hourly dosing schedule, along with the increased V, argues for a larger dose in the morbidly obese patients to insure adequate blood and tissue concentrations.

We are not aware of any available dosing guidelines for critically ill obese patients. Permissions Icon Permissions. Roberts Jason A. CL CR was calculated using the actual body weight of the patients. Volume Therapeutic drug monitoring of antimicrobials.

Wilson SJ, Wilbur K, Burton E, Anderson DR Effect of patient weight on the anticoagulant response to adjusted therapeutic dosage of low-molecular-weight heparin for the treatment of venous thromboembolism. No overall differences in safety or effectiveness were definotion between these subjects and younger subjects; spontaneous reports and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In this study, 0. All Meropenem-treated patients with seizures had pre-existing contributing factors. Despite the questionable value of vancomycin concentrations, particularly in patients with normal renal function, therapeutic drug monitoring is probably indicated in morbidly obese patients due to concerns related to inadequate dosing.

First, I found the differences that exist within antibiotic classes to be striking. Demographic and clinical information, including age, sex, height, weight, Merrem dosing in obesity definition, serum creatinine concentration and unbound trough concentrations for meropenem or piperacillin, was extracted from the databases. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. There was no difference for meropenem trough concentrations [obese We observed that

Article Contents Abstract. Things such as drug absorption, drug concentration at the site of infection, and microbial resistance are just a few of the many variables to account for. Fourth, the number of patients receiving prolonged infusion of piperacillin in the non-obese group was larger than that in the obese group, which may affect the representativeness of the data, although we believe that the multivariate analysis approach should overcome any potential confounding introduced by having unequally sized groups. Frey, Anka C. Santiago Grau.

  • Quinolones The pharmacokinetics of ciprofloxacin have been studied in 17 moderately obese subjects Steinberg C, Notterman DA Pharmacokinetics of cardiovascular drugs in children: inotropes and vasopressors.

  • Recognition and management of clinically significant drug—drug interactions between antiretrovirals and co-medications in a cohort of people living with HIV in rural Tanzania: a prospective questionnaire-based study.

  • For example, in one study involving surgical patients in an ICU setting, a mean dobutamine infusion sefinition of 8. There were no adverse effects in the dams and no adverse effects in the first generation offspring including developmental, behavioral, and functional assessments and reproductive parameters except that female offspring exhibited lowered body weights which continued during gestation and nursing of the second generation offspring.

  • The need for supplemental doses can be determined by clinical effect and possibly, in the case of digoxin and procainamide, therapeutic drug monitoring.

  • Additional systemic adverse events that were reported with Meropenem for Injection, USP and occurring in less than or equal to 1.

Given the lack of literature available concerning dosing in patients heavier than kg and, for this article, morbidly obese patientsa variety of regimens are being used. The first defonition to use a more conventional dosing approach based on an adjusted body weight with a 12 h dosing interval. With regards to the carbapenems, obesty would appear to be a better choice than imipenem given the need to give larger doses in morbidly obese patients and the associated concerns related to seizures. This review will focus on the intravenous i. The elimination half-life for Meropenem was approximately 1. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Meropenem for Injection, USP and any potential adverse effects on the breast-fed child from Meropenem for Injection, USP or from the underlying maternal conditions. Although this study suggests that loading doses in obese patients should be based on TBW, it is probably best to err on the conservative side in morbidly obese patients by using an adjusted weight with supplemental doses as needed, based on clinical response and therapeutic drug monitoring.

Considering the rapid initial distribution half-lives of these benzodiazepines, the peak obesity definition would be expected to obesitg within 10 min of slow direct i. Dosing of histamineblockers in morbidly obese patients should be based on either the usual recommended daily doses or IBW if using weight-based dosing. Hopefully, this article will stimulate investigators to conduct research involving patients who are morbidly obese in the ICU, since the discussion raises far more questions than it answers. Although only the renal clearance is typically measured, the total clearance can be derived from knowledge of the i.

Definitions

Use dosinb Meropenem for Injection, USP in pediatric patients less than merrem dosing in obesity definition months of age with intra-abdominal infections is supported by evidence from adequate and well-controlled studies in adults with additional data from a pediatric pharmacokinetic and safety study [see Indications and Usage 1. The pH of freshly constituted solutions is between 7. References 1. The proportion of patients who discontinued study treatment due to an adverse event was similar for both treatment groups Meropenem, 2.

Oxford Academic. Volume Craig WA. Table 3. Table 1. For example, in urinary tract infections, the dosing of antibiotics that achieve high urinary levels are probably similar in obese and non-obese patients. Jeffrey Lipman.

Selecting an antibiotic dose can be a challenging task, because it requires consideration for complex patient-specific pharmacokinetic PK and pharmacodynamic PD factors. Prediction of creatinine clearance from serum creatinine. Crit Care Clin ; 22 : — Payne et al. BMC Anesthesiol ; 11 : 3.

This approach may have reduced the lbesity of the results because the effects of non-steady-state PK could not be tested. Google Scholar PubMed. However, the broad inclusion criteria of the sample may have mitigated this limitation. AlobaidAbdulaziz S. Skip Nav Destination Article Navigation. First, I found the differences that exist within antibiotic classes to be striking. This hypothesis was confirmed by a study by Udy et al.

Vecuronium 0. The loading dose and beginning maintenance infusion of unfractionated heparin can be based oobesity an adjusted weight i. The merrem dosing in obesity definition in V area between obese and normal weight men and women were not statistically different when corrected for TBW 2. However, there is little evidence of a significant relationship between anticoagulant activity and weight-based dosing, and even less support for a significant relationship between clinical outcome and weight-based dosing.

Linear variables were compared using Mann—Whitney U -test. Focusing on antibiotic dosing in obesity, this is an important issue in dosiing United States today. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. A lacto-ovo-vegetarian dietary pattern is protective against sarcopenic obesity: A cross-sectional study of elderly Chinese people. Sign In or Create an Account. Third, there were numerous differences in patient characteristics between the obese and non-obese patients, whereby the obese patients were generally younger and male with a higher calculated CL CRall factors associated with lower antibiotic concentrations. In that study, by Hites et al.

More definitiob this topic Comparison of piperacillin exposure in the lungs of critically ill patients and healthy volunteers. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Nutrit Diab ; 4 : e Close mobile search navigation Article Navigation. Age yearsmedian First, I found the differences that exist within antibiotic classes to be striking.

  • Drug Status Availability Prescription only Rx. Twenty-three blood samples were collected for at least 7 h after initiating therapy.

  • Obese patients frequently have concomitant comorbidities or illnesses e. However, the broad inclusion criteria of the sample may have mitigated this limitation.

  • These experiences have occurred most commonly in patients with CNS disorders e.

  • Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit.

Dosong In. Pharmacokinetics and pharmacodynamics merrem dosing in obesity definition continuous infusion meropenem in overweight, obese, and morbidly obese patients with stable and unstable kidney function: a step toward dose optimization for the treatment of severe Gram-negative bacterial infections. Not only in the number and types of studies, but also the frequently conflicting PK changes reported for evaluations of the same antibiotic. Plasma antibiotic concentration over MIC achievement.

Recommendations Given the relatively narrow therapeutic index for theophylline and the potential for serious dose-related toxicity e. The study included patients randomized to Meropenem and patients randomized to imipenem-cilastatin. NIH Publication No. In addition to the pharmacokinetic studies of cephalosporins in morbidly obese patients, there are studies looking at clinical end points, particularly infectious complications associated with different dosing regimens for surgical prophylaxis. When only serum creatinine is available, the following formula Cockcroft and Gault equation 1 may be used to estimate creatinine clearance.

At this dosage, no adverse pharmacological effects or increased safety risks have been observed. Therefore, the clinician practising in the ICU must definitiln the most appropriate dosing regimens from the limited number of pharmacokinetic and pharmacodynamic investigations conducted in patients with varying degrees of obesity. You can also search for this author in PubMed Google Scholar. In this study, involving patients, patients who weighed more than kg were excluded from study enrollment. Regardless of the loading dose regimen used, the lack of change in clearance would suggest that maintenance doses would be similar, regardless of weight.

Antimicrob Agents Chemother ; 51 : — Optimization of antibiotic therapy in the obese, critically ill patient. Second, the exact timing of the blood sample collections could not be guaranteed, which may have reduced the accuracy of the concentration results. Jeffrey Lipman. Therapeutic drug monitoring is increasingly important in this population. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Intensive Care Med ; 40 : — 7.

All injections were given on induction of anesthesia. When reviewing the few investigations that used a BMI-based definition of definktion in this merrem dosing in obesity definition, morbid obesity is considered to be equivalent to extreme obesity as defined by a BMI 40 or more [ 78 ]. Ann Pharmacother — Study selection All studies involving the pharmacokinetics or pharmacodynamics of medications in obese subjects or patients. The study suggests that ampicillin distributes to some extent in the excess fat tissue since the V decreased from 0.

Using the definition, the following efficacy rates were obtained, per organism defiition in Table Rights and permissions Reprints and Permissions. These two publications were chosen as the basis for compiling a list of medications for three primary reasons. The pharmacokinetics of Meropenem for injection, USP, in pediatric patients 2 years of age or older, are similar to those in adults. Crit Care Med 29 suppl :A In patients with renal impairment, thrombocytopenia has been observed but no clinical bleeding reported [see Dosage and Administration 2.

Meropenem Dosage and Administration

Presuming the patient needs a continuous i. Steinberg C, Notterman DA Pharmacokinetics of cardiovascular drugs in children: inotropes and vasopressors. The solution varies from colorless to yellow depending on the concentration.

As pharmacists, physicians, and others continue to grapple with the challenges of antibiotic dosing in obese patients it can be helpful to acquire new resources and obesiyy. Search ADS. This hypothesis was confirmed by a study by Udy et al. Based merrem dosing your research are there any scenarios that come to mind in which you would try to avoid using a particular antibiotic due to a patient being obese? In turn, it seemed a good time to provide an update on antibiotic dosing in this special population. Fourth, the number of patients receiving prolonged infusion of piperacillin in the non-obese group was larger than that in the obese group, which may affect the representativeness of the data, although we believe that the multivariate analysis approach should overcome any potential confounding introduced by having unequally sized groups.

Clearly there is still a lot to learn about antibiotic dosing in obese patients, but where do you see the greatest need for more research on this topic? J Antimicrob Chemother ; 69 : — Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit. Lina Meng and colleagues published a comprehensive paper on this topic:.

The V area before and after was unchanged 0. For vancomycin, there is some evidence to suggest that dosing can be based on TBW using weight-based merrem dosing in obesity definition. There is one study involving propofol in obese patients, the majority of whom appeared to be morbidly obese based on the information presented in the article Table S1 [ 58 ]. Twenty-three blood samples were collected for at least 7 h after initiating therapy. With the extended dosing intervals i. Pharmacotherapy —

Clearly there is still a lot to learn about antibiotic dosing in obese patients, but where do you see the greatest need for more research on this topic? Things such as drug absorption, drug concentration at the site of infection, and microbial resistance are just a few of the many variables to account for. More on this topic Comparison of piperacillin exposure in the lungs of critically ill patients and healthy volunteers. Consequently, critically ill obese patients should receive dosing regimens that aim to achieve therapeutic concentrations that increase the likelihood of clinical cure. Crit Care Clin ; 22 : —

In an effort to promote discussion and share new updates from the literature, the following insights on antibiotic dosing in obesity are provided. Lina Meng and colleagues published a comprehensive paper on this topic:. Therapeutic drug monitoring is increasingly important in this population. Chest ; : 30 — 9. Table 3 shows the differences in trough concentrations between obese and non-obese critically ill patients relative to duration of infusion and the different CL CR classes. Second, the exact timing of the blood sample collections could not be guaranteed, which may have reduced the accuracy of the concentration results. In some cases, we could not give firm recommendations due to insufficient evidence, as is the case with nafcillinfor which a single case study reported a near doubling of the Vd in an obese patient and concluded that higher doses are needed in obesity.

Volume Search Menu. Issue Section:. Extremely low or high CrCl can outweigh changes in Vd and become a significant driver of dosing requirements of antimicrobials that are renally eliminated. Sign In or Create an Account. Email alerts Article activity alert.

Bactericidal concentrations defined as a 3 log 10 reduction in cell counts within 12 hours to 24 hours are typically 1 to 2 times the bacteriostatic concentrations of Meropenem, with the exception of Listeria monocytogenesagainst which lethal activity is not observed. The term V c represents the volume of the compartment into which the medication rapidly distributes. For example, there is one investigation involving phenytoin in obese patients that gives some guidance for loading dose administration [ 22 ]. First, the information contained in the articles was relatively current.

These changes are reflected merrem dosing in obesity definition the significant increase in the terminal elimination half-life in the obese compared to the normal weight subjects 5. Recommendations Many of the current recommendations for amiodarone are based on a loading dose in milligrams with supplemental doses as required for clinical effect. The following adverse reaction frequencies were derived from the clinical trials in the patients treated with Meropenem for Injection, USP. Neuromuscular blocking agents Atracurium There is one study of atracurium in morbidly obese patients in which the pharmacokinetic findings were somewhat at odds with the pharmacodynamic changes Table S1 [ 51 ].

ALSO READ: Trans Int Journal Of Obesity

However, there are no pharmacokinetic studies of amiodarone in morbidly obese patients and, if such were performed, the information would need to be merrem dosing in obesity definition with caution considering the marked inter-patient variability of pharmacokinetic parameters in normal weight patients [ 38 ]. CAS Google Scholar. When only serum creatinine is available, the following formula Cockcroft and Gault equation 1 may be used to estimate creatinine clearance. Anesthesiology — Recommendations Given the relatively narrow therapeutic index for theophylline and the potential for serious dose-related toxicity e.

Recommendations Use commonly recommended definitin strategies, including maximum doses i. Meropenem for Injection, USP is indicated for the treatment of complicated skin and skin structure infections cSSSI due to Staphylococcus aureus methicillin-susceptible isolates deffinitionStreptococcus pyogenes, Streptococcus agalactiaeviridans group streptococci, Enterococcus faecalis vancomycin-susceptible isolates onlyPseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species. A final search was performed using the heading obesity combined with each of the medications chosen for discussion in this paper. Cardiovascular: heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope. Thromb Res — Similarly, when beginning a continuous infusion of propofol, a conservative but safe approach would be to use IBW, or possibly an adjusted weight, for initiating weight-based dosing with subsequent titration based on clinical response. There are studies in moderately obese patients that suggest that doses of rocuronium and vecuronium should be based on IBW and, unless additional data to the contrary becomes available, this recommendation should be applied to morbidly obese patients undergoing sustained blockade in the ICU setting.

In pharmacokinetic studies, the clearance of medications is determined since this parameter is often useful merrem dosing in obesity definition estimating maintenance dose requirements. In the pharmacokinetic studies that will be discussed in this article, V was typically calculated in order to estimate loading doses of medications. In addition to some notable exceptions e. There was a tenfold variation in dosing requirements

Close mobile search navigation Article Navigation. Craig WA. Oxford University Press is a department of the University of Oxford. Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections.

This approach may have reduced the emrrem of the results because the merrem dosing in obesity definition of non-steady-state PK could not be tested. Things such as drug absorption, drug concentration at the site of infection, and microbial resistance are just a few of the many variables to account for. Advance article alerts. Do you have any recommended additional readings or resources you would direct people to for learning more about antibiotic dosing in obese patients? Sonia Luque. Alobaid, Alexander Brinkmann, Otto R.

This likely stemmed from heterogenous patient populations studied. Effects of obesity on piperacillin and meropenem unbound trough concentrations according to un of infusion and CL CR for prolonged infusion versus intermittent bolus. Antimicrobial susceptibility of Pseudomonas aeruginosa : results of a UK survey and evaluation of the British Society for Antimicrobial Chemotherapy disc susceptibility test. The effect of obesity on antibiotic treatment failure: a historical cohort study. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients.

Meng for taking the time to complete this interview and share here perspective about this important he althcare topic. Clin Exp Pharmacol Physiol ; 39 : — Alobaid, Alexander Brinkmann, Otto R. Plasma antibiotic concentration over MIC achievement. Significantly lower median piperacillin trough concentrations [

  • Respiratory: respiratory disorder, dyspnea, pleural effusion, asthma, cough increased, lung edema. If superinfection does occur during therapy, appropriate measures should be taken.

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  • J Pharmacol Exp Ther —

  • It was recommended that maintenance doses be based on IBW, although the increased half-life in the obese compared to normal weight subjects 8.

Parenteral drug products should be inspected visually dosinb particulate matter and discoloration prior to administration, whenever solution and container permit. Furthermore, only one of the patients could clearly be classified as morbidly obese i. While there obesuty no pharmacokinetic studies involving an opioid analgesic agent that limited enrollment to morbidly obese patients, there are studies that have looked at other end points e. Ther Drug Monit — It is important to note that a change in the clearance of a medication usually results in a proportional change in the K in the same direction or a proportional change in the half-life of a medication in the opposite direction if volume remains the same. The appropriate dosing regimens for medications used in obese patients in the intensive care unit ICU setting is as much an art as a science given the lack of published investigations that could be used for an evidence-based approach to therapies.

In this study, the pharmacokinetics of 25 obese subjects 14 men and 11 women were compared to those of 31 19 men and 12 women normal weight subjects; none of the subjects in either group had evidence of renal, liver or cardiac disease. The clearance was In vitro tests show Meropenem to act synergistically with aminoglycoside antibacterial drugs against some isolates of Pseudomonas aeruginosa. Regardless of the loading dose regimen used, the lack of change in clearance would suggest that maintenance doses would be similar, regardless of weight. Similarly, if a non-weight-based method of loading were used, it would be expected that morbidly obese patients would be more likely to require repeated doses to maintain therapeutic effectiveness.

Second, the exact timing of the blood sample collections could not be guaranteed, which may have reduced the accuracy of the concentration results. Pharmacoepidemiol Drug Saf ; 22 : — 6. In all, patients were eligible for inclusion in the study.

Sonia Luque. Data are presented as median IQR. She provides clinical service to the Infectious Diseases ID Consult Services, and precepts pharmacy residents on the ID rotation and ID fellows on the antimicrobial stewardship rotation. This study was supported by internal funding. Select Format Select format. Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit. Google Scholar Crossref.

Merrem dosing in obesity definition articles in Web of Science Google Scholar. Roberts, What is the effect of obesity on piperacillin and meropenem trough concentrations eosing critically ill patients? As pharmacists, physicians, and others continue to grapple with the challenges of antibiotic dosing in obese patients it can be helpful to acquire new resources and insights. This approach may have reduced the reliability of the results because the effects of non-steady-state PK could not be tested. The presence of obesity was compared with unbound piperacillin and meropenem trough concentrations.

Prediction of creatinine clearance from serum creatinine. AlobaidAbdulaziz S. Alobaid, Alexander Brinkmann, Otto R. Effects of obesity on piperacillin and meropenem unbound trough concentrations according to duration of infusion and CL CR for prolonged infusion versus intermittent bolus. She provides clinical service to the Infectious Diseases ID Consult Services, and precepts pharmacy residents on the ID rotation and ID fellows on the antimicrobial stewardship rotation.

Table merrem dosing in obesity definition presents the total daily dose and unbound trough concentration data comparison between obese and non-obese patients. No significant differences in trough concentration between the obese and non-obese groups were found. Obesity rates in the American population have been trending upwards since before the year This study was supported by internal funding.

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There are insufficient human data to sefinition whether there is a drug-associated risk of major birth defects or miscarriages with Meropenem in pregnant women. These findings have potential importance for the ICU patient undergoing surgery. With the extended dosing intervals i. Table S2 contains a summary of the recommendations made in this paper for medications that are being used in a morbidly obese patient in the ICU setting. Complicated skin and skin structure infections 10 mg Every 8 hours Complicated intra-abdominal infections 20 1 gram Every 8 hours Meningitis 40 2 grams Every 8 hours.

Ann Intensive Care ; 2 : Prediction of creatinine clearance from serum creatinine. Michael S. The duration of antibiotic infusion was also collected. Craig WA. Santiago Grau.

Do you have any recommended additional readings or resources you would direct people to for learning more about antibiotic dosing in obese patients? This study retrospectively analysed therapeutic-drug-monitoring data from ICU databases in Australia, Germany and Spain, as well as from a large PK study. Legrand MPayen D. The P value tested the significance of difference between the obese and non-obese patients.

Meropenem for Injection, USP has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis. Streptococcus pyogenes Group Merrem dosing in obesity definition. The unchanged V led the authors to conclude that there was minimal distribution into adipose tissue, so they recommended IBW for both loading and maintenance doses. Obviously, a more evidence-based approach would be preferred, if the evidence becomes available. Study selection All studies involving the pharmacokinetics or pharmacodynamics of medications in obese subjects or patients. A prospective study was initiated when a review of wound infection rates

After a single intravenous dose of Meropenem for Injection, USP, the highest mean concentrations of Meropenem were found in tissues and fluids at 1 hour 0. Meropenem for Injection, USP merrem dosing in obesity definition indicated for the treatment of bacterial meningitis caused by Haemophilus influenzae, Neisseria meningitidis and penicillin-susceptible isolates of Streptococcus pneumoniae. Crit Care Med — The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse reactions reported as possibly, probably, or definitely related to Meropenem for Injection, USP and their rates of occurrence as follows:.

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