Gentamicin Administration in Dialysis Patients:Before or After Hemodialysis?

BACKGROUND: Gentamicin is used to treat severe infections and has a small therapeutic window. This study aimed to optimize the dosing strategy of gentamicin in intermittently hemodialyzed patients by simulating concentration/time profiles during pre- and post-dialysis dosing, based on a published pharmacokinetic model.METHODS: Pharmacokinetic simulations were performed with virtual patients, including septic patients, who were treated with gentamicin and received weekly hemodialysis with an interval of 48h-48h-72h. The following dosing regimens were simulated: for non-septic patients, 5 mg/kg gentamicin was given 1h/2h before dialysis, or a starting dose of 2.5 mg/kg and a maintenance dose of 1.5 mg/kg immediately after dialysis; for septic patients, 6 mg/kg gentamicin was given 1h/2h before dialysis, or a starting dose of 3 mg/kg and a maintenance dose of 1.8 mg/kg immediately after dialysis. The mean Cmax, AUC24h, and target attainment (TA) of pharmacodynamic targets were calculated and compared. The following targets were adopted from literature: Cmax &gt;8 mg/L and &lt;20 mg/L and AUC24h &gt;70 mg·h/L and &lt;120 mg·h/L.RESULTS: In non-septic patients, postdialysis dosing resulted in a TA of 35% for Cmax &gt;8 mg/L, 100% for &lt;20 mg/L and AUC24h &gt;70 mg·h/L, and 45% for &lt;120 mg·h/L. Dosing 2h prior to dialysis resulted in a TA of 100% for Cmax&gt; 8 mg/L, 40% for &lt;20 mg/L, 65% for AUC24h &gt;70 mg·h/L, and 77% for &lt;120 mg·h/L. Simulations of septic patients resulted in comparable outcomes with higher TAs for Cmax &lt;20 mg/L (96%), AUC24h &gt;70 mg·h/L (90%), and &lt;120 mg·h/L (53%) for dosing 1h prior to dialysis.CONCLUSIONS: Postdialysis dosing resulted in a low TA of Cmax &gt;8 mg/L; however, predialysis dosing ensured a high TA of Cmax &gt;8 mg/L and acceptable TA of Cmax &lt;20 mg/L, AUC24h &gt;70 mg·h/L, and &lt;120 mg·h/L, which could increase the efficacy of gentamicin. Therefore, clinicians should consider predialysis dosing of gentamicin in patients undergoing intermittent hemodialysis.</p

Shedding a Light on Acyclovir Pharmacodynamics: A Retrospective Analysis on Pharmacokinetic/Pharmacodynamic Modelling of Acyclovir for the Treatment of Varicella Zoster Virus Infection in Immunocompromised Patients: A Pilot Study

BackgroundAcyclovir and valacyclovir are used for the treatment and prophylaxis of infections with herpes simplex virus (HSV) and varicella zoster virus (VZV). The aim of this study is to provide insight into the pharmacodynamics (PD) of (val)acyclovir.MethodsPatients were retrospectively selected, based on therapeutic drug monitoring for acyclovir, to create a population pharmacokinetic (PK) model in Pmetrics. This PK model was used to develop a PK/PD model to study the effect of acyclovir levels on VZV viral load in plasma in immunocompromised patients.ResultsImmunocompromised patients with known VZV viral loads in plasma were included for PK/PD modelling (N = 4, with 23 measure points); they were part of the population of 43 patients used for PK model building. The PK/PD model described the data well (r2 = 0.83). This is a hopeful first step in clarifying the pharmacodynamics of acyclovir; however, the data in this study are limited.ConclusionsOur preliminary PK/PD model can be used in further research to determine the effect of acyclovir levels on VZV viral load

Diagnosis and treatment of vascular graft and endograft infections:a structured clinical approach

A vascular graft or endograft infection (VGEI) is a severe complication that can occur after vascular graft or endograft surgery and is associated with high morbidity and mortality rates. A multidisciplinary approach, consisting of a team of vascular surgeons, infectious diseases specialists, medical microbiologists, radiologists, nuclear medicine specialists, and hospital pharmacists, is needed to adequately diagnose and treat VGEI. A structured diagnostic, antibiotic, and surgical treatment algorithm helps clinical decision making and ultimately aims to improve the clinical outcome of patients with a VGEI

Efficacy of a Standardized Oral Vitamin D Dosing Regimen in Nursing Home Residents

BACKGROUND: The prevalence of vitamin D deficiency in nursing home residents ranges from 79% to 98%. OBJECTIVES: The aim of this cross-sectional observational study in somatic and psychogeriatric nursing home residents was to determine the efficacy of a standardized oral vitamin D dosing regimen (VDDR) consisting of a loading dose (LD) of cholecalciferol 200,000 IU followed by a maintenance dose (MD) of 100,000 IU every 13 weeks in obtaining and maintaining an adequate and safe vitamin D trough level (VDTL), defined as 75-220 nmol/L (reference range). METHODS: Blood samples of nursing home residents who had received the LD followed by at least one MD were analyzed for VDTL, calcium, parathyroid hormone, and creatinine. Data on age, sex, race, body weight and height, co-morbidity, co-medication, number of MDs, calcium supplementation, smoking, and use of alcohol were obtained from patient charts. The primary outcome for the efficacy of the VDDR was the percentage of nursing home residents with a VDTL 75-220 nmol/L, with a target percentage of 85% for the dosing regimen to be considered efficacious. RESULTS: In 91 (58%; 95% confidence interval [CI] 50-66) of 156 included nursing home residents, a VDTL within the reference range was measured (mean [standard deviation] 81 [28] nmol/L, range 13-150 nmol/L). The only variable that was identified as a significant risk indicator for obtaining a VDTL ≥ 75 nmol/L was the number of MDs being four or more (≥ 4 vs. < 4; odds ratio 2.7; 95% CI 1.4-5.3). CONCLUSION: This standardized VDDR was not efficacious in obtaining and maintaining an adequate VDTL in this nursing home resident population. CLINICAL TRIALS REGISTRATION NUMBER: NTR6029 (The Netherlands National Trial Register)

Shedding a Light on Acyclovir Pharmacodynamics: A Retrospective Analysis on Pharmacokinetic/Pharmacodynamic Modelling of Acyclovir for the Treatment of Varicella Zoster Virus Infection in Immunocompromised Patients: A Pilot Study

Background: Acyclovir and valacyclovir are used for the treatment and prophylaxis of infections with herpes simplex virus (HSV) and varicella zoster virus (VZV). The aim of this study is to provide insight into the pharmacodynamics (PD) of (val)acyclovir. Methods: Patients were retrospectively selected, based on therapeutic drug monitoring for acyclovir, to create a population pharmacokinetic (PK) model in Pmetrics. This PK model was used to develop a PK/PD model to study the effect of acyclovir levels on VZV viral load in plasma in immunocompromised patients. Results: Immunocompromised patients with known VZV viral loads in plasma were included for PK/PD modelling (N = 4, with 23 measure points); they were part of the population of 43 patients used for PK model building. The PK/PD model described the data well (r2 = 0.83). This is a hopeful first step in clarifying the pharmacodynamics of acyclovir; however, the data in this study are limited. Conclusions: Our preliminary PK/PD model can be used in further research to determine the effect of acyclovir levels on VZV viral load

Subtherapeutic Exposure of Ganciclovir in Children Despite Appropriate Dosing: A Short Communication

Therapeutic drug monitoring (TDM) results for ganciclovir in 12 different treatment episodes showed large intraindividual and interindividual variabilities in the trough concentration and area under the 24-hour concentration-time curve (AUC24). Despite adequate valganciclovir dosing, subtherapeutic concentrations were found in 30% of the treatment episodes. A decrease in viral load was observed regardless of subtherapeutic exposure. These findings show the need for target concentration evaluation and assessment of the applicability of ganciclovir TDM in children

Diagnosis and treatment of vascular graft and endograft infections: a structured clinical approach

A vascular graft or endograft infection (VGEI) is a severe complication that can occur after vascular graft or endograft surgery and is associated with high morbidity and mortality rates. A multidisciplinary approach, consisting of a team of vascular surgeons, infectious diseases specialists, medical microbiologists, radiologists, nuclear medicine specialists, and hospital pharmacists, is needed to adequately diagnose and treat VGEI. A structured diagnostic, antibiotic, and surgical treatment algorithm helps clinical decision making and ultimately aims to improve the clinical outcome of patients with a VGEI