Treatment of bacterial infections in obese adult patients: how to appropriately manage antimicrobial dosage

Pai, Manjunath P.

doi:10.1016/j.coph.2015.06.004

Cited by 12 publications

(11 citation statements)

References 49 publications

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“…In support of this idea, the literature strongly supports dosing based on body weight or body surface area; drug pharmacokinetic parameters increase in proportion with increasing body size. 24 The BIA measurements regarding excessive body water (overhydration) showed an average 21% EBW, thus also supporting the different volume of distribution in our patient cohort. These data were used to format Figure 1 and Figure 2, which show strong correlations.…”

Section: Discussionsupporting

confidence: 84%

The need for a patient-tailored Helicobacter pylori eradication protocol prior to bariatric surgery

Pintar

Kaliterna²,

Carli

2018

J Int Med Res

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ObjectiveHigh-quality data indicating the advantages of preoperative Helicobacter pylori screening and eradication as well the clinical outcomes of patients with and without H. pylori after bariatric surgery are lacking.MethodsIn total, 96 morbidly obese patients with H. pylori preparing for bariatric surgery were retrospectively reviewed.ResultsOf 96 biopsy specimens, 73 (76%) were positive for H. pylori on initial Giemsa staining. These patients were treated with the standard 7-day antibiotic treatment protocol corrected by the individual patient’s creatinine clearance rate and body mass index and received a 30% higher dose because of their H. pylori positivity. A linear correlation was found between the effective antibiotic dose and the BMI with a recurrence rate of only 2.1% (2/96 patients). The preoperative percent estimated weight loss before surgery (17%) and in the first year of follow-up (68%–88%) was statistically equal between H. pylori-positive and -negative patients. Two early postoperative infectious complications and two postoperative surgical complications occurred in the preoperatively H. pylori-positive patients.ConclusionsA patient-tailored H. pylori eradication protocol prior to bariatric surgery is mandatory to improve the eradication rate and reduce the incidence of postoperative complications in mostly asymptomatic H. pylori-positive bariatric candidates.

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Section: Discussionsupporting

confidence: 84%

The need for a patient-tailored Helicobacter pylori eradication protocol prior to bariatric surgery

Pintar

Kaliterna²,

Carli

2018

J Int Med Res

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“…This point of an initial higher but standard maintenance regimen in obese patients is most applicable to agents such as linezolid. 16 Although not easy to visualize, the second point in this illustration is that all regimens achieve the same AUC over this period of time because the dose is identical in this simulation. The AUC is affected by the dose and clearance (CL) of the agent from systemic circulation.…”

Section: Pk-pd Considerationsmentioning

confidence: 98%

“…This is akin to the effects of obesity on the V d . 16 Larger adults typically have a larger V d that is noted by a lower systemic (plasma) C max concentration and may need a loading dose to achieve this. However, maintenance of this larger dose in obese patients may be unnecessary by the third dose for a time-dependent antimicrobial agent because all the illustrated regimens achieve similar T 4MIC values.…”

Section: Pk-pd Considerationsmentioning

confidence: 99%

Anti-infective Dosing for Obese Adult Patients: A Focus on Newer Drugs to Treat Methicillin-resistant Staphylococcus aureus Acute Bacterial Skin and Skin Structure Infections

Pai

2016

Clinical Therapeutics

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“…The findings from the population PK analyses had important implications for the iclaprim dosing regimen selected for the subsequent Monte Carlo simulation analyses. It is only necessary to dose a drug based on total body weight when key pharmacokinetic parameters, namely, drug clearance and volume of distribution, change proportionately with total body weight (14,15). The lack of association between weight and clearance allowed for the exploration of fixed iclaprim dosing regimens, as requested by the FDA, in Monte Carlo simulation analyses to maximize AUC, AUC/MIC, and T Ͼ MIC, the PD parameters associated with efficacy in animal infection models (8,9).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Analyses To Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Patients with Serious Infections Caused by Gram-Positive Pathogens

Lodise

Bosso

Kelly

et al. 2018

Antimicrob Agents Chemother

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Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection model studies suggest that the pharmacokinetic/pharmacodynamic (PK/PD) drivers for efficacy are area under the concentration-time curve from 0 to 24 h at steady state (AUC), AUC/MIC, and time above the MIC during the dosing interval ( > MIC), while QTc prolongation was associated with the maximal concentration at steady state () in a thorough QTc phase 1 study. Using PK data collected from 470 patients from the previously conducted phase 3 complicated skin and skin structure infection (cSSSI) trials, population PK modeling and Monte Carlo simulation (MCS) were used to identify a fixed iclaprim dosage regimen for the ongoing phase 3 ABSSSI studies that maximizes AUC, AUC/MIC, and > MIC while minimizing the probability of a of ≥800 ng/ml relative to the values for the previously employed cSSSI regimen of 0.8 mg/kg of body weight infused intravenously over 0.5 h every 12 h. The MCS analyses indicated that administration of 80 mg as a 2-h infusion every 12 h provides 28%, 28%, and 32% increases in AUC, AUC/MIC, and > MIC, respectively, compared to values for the 0.8-mg/kg cSSSI regimen, while decreasing the probability of a of ≥800 ng/ml, by 9%. Based on PK/PD analyses, 80 mg iclaprim administered over 2 h every 12 h was selected as the dosing scheme for subsequent phase 3 clinical trials.

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Treatment of bacterial infections in obese adult patients: how to appropriately manage antimicrobial dosage

Cited by 12 publications

References 49 publications

The need for a patient-tailored Helicobacter pylori eradication protocol prior to bariatric surgery

The need for a patient-tailored Helicobacter pylori eradication protocol prior to bariatric surgery

Anti-infective Dosing for Obese Adult Patients: A Focus on Newer Drugs to Treat Methicillin-resistant Staphylococcus aureus Acute Bacterial Skin and Skin Structure Infections

Pharmacokinetic and Pharmacodynamic Analyses To Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Patients with Serious Infections Caused by Gram-Positive Pathogens

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