Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient?

ABSTRACTPractitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimation method. A two-compartment model with first-order elimination best described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for clearance and the volume of distribution, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volumes of distribution, and intercompartmental clearance were 3.06 liters/h, 14.4 liters, 17.1 liters, and 0.925 liters/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ from those in individuals without cystic fibrosis. However, further investigations are needed to confirm these results and, thus, the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish the optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.

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Population pharmacokinetics of vancomycin in critically ill adult patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01377-21 ◽

2021 ◽

Author(s):

Vesa Cheng ◽

Mohd H. Abdul-Aziz ◽

Fay Burrows ◽

Hergen Buscher ◽

Young-Jae Cho ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Population Pharmacokinetics ◽

Critically Ill ◽

Plasma Concentrations ◽

Total Body Weight ◽

Adult Patients ◽

Therapeutic Drug ◽

Membrane Oxygenation ◽

Dosing Regimens ◽

The Mean

Our study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analysed using a population PK approach on Pmetrics ®. The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC 0-24 ) of 400 – 700 mg·h/L at steady state. Twenty-two patients were enrolled, of which 11 patients received concomitant RRT. In the non-RRT patients, the median creatinine clearance (CrCL) was 75 mL/min and the mean daily dose of vancomycin was 25.5 mg/kg. Vancomycin was well described in a two-compartment model with CrCL, the presence of RRT and total body weight found as significant predictors of clearance and central volume of distribution (V c ). The mean vancomycin renal clearance and V c were 3.20 L/h and 29.7 L respectively, while the clearance for patients on RRT was 0.15 L/h. ECMO variables did not improve the final covariate model. We found that recommended dosing regimens for critically ill adult patients not on ECMO can be safely and effectively used in those on ECMO. Loading doses of at least 25 mg/kg followed by maintenance doses of 12.5 – 20 mg/kg 12-hourly are associated with a 97 – 98% probability of efficacy and 11 – 12% probability of toxicity, in patients with normal renal function. Therapeutic drug monitoring along with reductions in dosing are warranted for patients with renal impairment and those with concomitant RRT.

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Faculty Opinions recommendation of Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.716397814.793455523 ◽

2012 ◽

Author(s):

Marcio Nucci

Keyword(s):

Population Pharmacokinetics ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Adult Patients ◽

Efficacy And Safety ◽

Safety Population

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Ethionamide population pharmacokinetics/pharmacodynamics and therapeutic implications in South African adult patients with drug‐resistant tuberculosis

British Journal of Clinical Pharmacology ◽

10.1111/bcp.14795 ◽

2021 ◽

Author(s):

Pierre Mugabo ◽

Mwila Mulubwa

Keyword(s):

Population Pharmacokinetics ◽

South African ◽

Adult Patients ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Therapeutic Implications ◽

Resistant Tuberculosis

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Venoarterial extracorporeal membrane oxygenation as mechanical circulatory support in adult septic shock: a systematic review and meta-analysis with individual participant data meta-regression analysis

Critical Care ◽

10.1186/s13054-021-03668-5 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Ryan Ruiyang Ling ◽

Kollengode Ramanathan ◽

Wynne Hsing Poon ◽

Chuen Seng Tan ◽

Nicolas Brechot ◽

...

Keyword(s):

Septic Shock ◽

Extracorporeal Membrane Oxygenation ◽

Mechanical Circulatory Support ◽

Meta Analysis ◽

Left Ventricular ◽

Adult Patients ◽

Circulatory Support ◽

Venoarterial Extracorporeal Membrane Oxygenation ◽

Refractory Septic Shock ◽

Va Ecmo

Abstract Background While recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA ECMO, and identify factors associated with survival. Methods We searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st June 2021, and included all relevant publications reporting on > 5 adult patients requiring VA ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted. Data synthesis We included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI]: 23.6%–50.1%). Survival among patients with left ventricular ejection fraction (LVEF) < 20% (62.0%, 95%-CI: 51.6%–72.0%) was significantly higher than those with LVEF > 35% (32.1%, 95%-CI: 8.69%–60.7%, p = 0.05). Survival reported in studies from Asia (19.5%, 95%-CI: 13.0%–26.8%) was notably lower than those from Europe (61.0%, 95%-CI: 48.4%–73.0%) and North America (45.5%, 95%-CI: 16.7%–75.8%). GRADE assessment indicated high certainty of evidence for pooled survival. Conclusions When treated with VA ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock without severe left ventricular depression. VA ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.

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