Geriatric Fever Score: A New Decision Rule for Geriatric Care

Background

Evaluating geriatric patients with fever is time-consuming and challenging. We investigated independent mortality predictors of geriatric patients with fever and developed a prediction rule for emergency care, critical care, and geriatric care physicians to classify patients into mortality risk and disposition groups.

Materials and Methods

Consecutive geriatric patients (≥65 years old) visiting the emergency department (ED) of a university-affiliated medical center between June 1 and July 21, 2010, were enrolled when they met the criteria of fever: a tympanic temperature ≥37.2°C or a baseline temperature elevated ≥1.3°C. Thirty-day mortality was the primary endpoint. Internal validation with bootstrap re-sampling was done.

Results

Three hundred thirty geriatric patients were enrolled. We found three independent mortality predictors: Leukocytosis (WBC >12,000 cells/mm³), Severe coma (GCS ≤ 8), and Thrombocytopenia (platelets <150 10³/mm³) (LST). After assigning weights to each predictor, we developed a Geriatric Fever Score that stratifies patients into two mortality-risk and disposition groups: low (4.0%) (95% CI: 2.3–6.9%): a general ward or treatment in the ED then discharge and high (30.3%) (95% CI: 17.4–47.3%): consider the intensive care unit. The area under the curve for the rule was 0.73.

Conclusions

We found that the Geriatric Fever Score is a simple and rapid rule for predicting 30-day mortality and classifying mortality risk and disposition in geriatric patients with fever, although external validation should be performed to confirm its usefulness in other clinical settings. It might help preserve medical resources for patients in greater need.     

Antifungal Dosing Considerations in Patients Undergoing Continuous Renal Replacement Therapy

Purpose of Review

The incidence of systemic fungal infections is increasing among patients admitted to the intensive care unit (ICU). Acute kidney injury (AKI) occurs in one third of ICU patients and approximately 5% require renal replacement therapy (RRT). Among those requiring RRT, continuous RRT (CRRT) is used in more than 70% of cases. This review aims to summarize antifungal dosing management in ICU patients receiving CRRT.

Recent Findings

For most antifungal agents, including new azoles such as posaconazole and isavuconazole, CRRT does not significantly affect antifungal pharmacokinetics (PK) mainly due to drug liver elimination and high protein binding. For fluconazole, increased dose is recommended during CRRT taking into account the type of CRRT mode (CVVHF or CVVHDF), membrane surface, and effluent and dialysis flow rates. A dose increase for itraconazole seems also necessary during CRRT; a dose decrease for flucytosine is probably necessary but data are too scarce to give a strong recommendation.

Summary

In ICU patients receiving CRRT, no dosing adjustment is required for the majority of antifungal agents commonly used to treat invasive fungal infections (IFIs) excepted for fluconazole, itraconazole, and flucytosine. Due to high PK variability, therapeutic drug monitoring should be considered in ICU patients receiving CRRT.

     

Pharmacological and Host Considerations in the Selection of Dose and Duration of Azole Therapy for Adult Patients

Azole antifungals are used to treat a myriad of fungal infections in diverse patient populations. As a result, it becomes clear that use of one size fits all azole dosing regimens is illogical. Three general variable categories are essential to consider when developing an approach the management of fungal infections with the azoles. These categories are the pharmacological, microbiological, and host. In the clinical setting information regarding microbiological variables if often lacking; however, host and pharmacological data are abundant. Unfortunately, these available data are not always used to construct individualized dosing strategies. In this review, host and pharmacological factors that can influence azole activity will be presented. Additionally, recommendations will be provided to help the clinician optimize azole dosing regimens based on these variables.     

Pharmacological and Host Considerations Surrounding Dose Selection and Duration of Therapy with Echinocandins

Caspofungin, micafungin and anidulafungin are antifungal drugs with excellent safety profiles. Dosing regimens and treatment durations must be appropriate for optimal patient outcomes. Overall, factors that affect dosing of all three drugs are similar. Drug-specific properties, including in vitro concentration-dependent antifungal activity, activity against fungal biofilms, and pharmacokinetic and pharmacodynamic parameters influence dose selection and duration of therapy. Dosing strategies that provide “unbound” plasma drug concentrations exceeding the minimum inhibitory concentration (or minimum effective concentration) of the fungus are essential. Patient weight, age and illness severity are also important considerations for adequate exposure to drug: individuals >66 kg, pediatric patients and the critically-ill clear drug at higher rates although drug product information guidelines do not recommend for these populations to receive doses higher than those currently used. Clinical studies of treatment of, and prophylaxis against, Candida and Aspergillus infection indicate that currently recommended dosing regimens are adequate in most instances.