Invasive Candidiasis in the Elderly: Considerations for Drug Therapy.

Candida infections in the elderly are an important and expanding clinical problem, with significantly higher mortality in this group than in younger patients. The increasing problem of invasive Candida infections may be related to higher prevalence of immunocompromised older people and the emergence of treatment resistance. Older people, especially the frail and critically ill, are at higher risk of medication-related harmful effects due to changes in pharmacokinetics and pharmacodynamics, which may be further complicated by organ dysfunction, diminished homeostatic control, co-morbidities and polypharmacy. Here, we review the available options for the treatment of Candida infections and provide insights into the challenges surrounding the optimal use of antifungal drugs in the elderly.

Pharmacokinetic Properties of Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis.

The estimated attributable mortality rate for invasive candidiasis (IC) in the intensive care unit (ICU) setting varies from 30 to 40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin, and therefore, dosing adjustments might be mandatory. The objective of this study was to determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment. Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin. MIC values for Candida isolates were determined to assess the probability of target attainment for patients. Data from 19 patients with suspected or proven invasive candidiasis were available for analysis. The median area under the concentration-time curve from 0 to 24 h at steady state (AUC0-24) was 89.6 mg · h/liter (interquartile range [IQR], 75.4 to 113.6 mg · h/liter); this was significantly lower than the median micafungin AUC0-24 values of 152.0 mg · h/liter (IQR, 136.0 to 162.0 mg · h/liter) and 134.0 mg · h/liter (IQR, 118.0 to 148.6 mg · h/liter) in healthy volunteers (P = <0.0001 and P = <0.001, respectively). All Candida isolates were susceptible to micafungin, with a median MIC of 0.016 mg/liter (IQR, 0.012 to 0.023 mg/liter). The median AUC0-24/MIC ratio was 5,684 (IQR, 4,325 to 7,578), and 3 of the 17 evaluable patients (17.6%) diagnosed with proven invasive candidiasis did not meet the AUC/MIC ratio target of 5,000. Micafungin exposure was lower in critically ill patients than in healthy volunteers. The variability in micafungin exposure in this ICU population could be explained by the patients' body weight. Our findings suggest that healthier patients (sequential organ failure assessment [SOFA] score of <10) weighing more than 100 kg and receiving 100 mg micafungin daily are at risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT01716988.).

Manual dexterity and keyboard use in spastic hemiparesis: a comparison between the impaired hand and the 'good' hand on a number of performance measures.

OBJECTIVE: To assess the functional deficits in tapping performance of subjects with spastic hemiparesis. DESIGN: In a pilot study, typing performance on a computer keyboard was examined on a number of performance measures. SETTING: Department of Research and Development at the Werkenrode Institute. SUBJECTS: Four subjects (mean age 16.4 years, standard deviation 1.8 years) with cerebral palsy and diagnosed as having spastic hemiparesis. INTERVENTIONS: Subjects had to type a sequence of one or more keys as quickly as possible within an 8 second period with the fingers of both hands separately. MAIN OUTCOME MEASURES: The average number of good and false responses were calculated. Within the false response category, four, mutually exclusive, types of errors were distinguished; wrong key, repetition, registrations under 75 ms and holding. Speed and regularity of the typing responses were also established. RESULTS: The 'good' hand outperformed the impaired hand on all performance measures except on the amount of repetition errors made. The holding error was only present for the impaired hand, and there was an increase in holding errors from the index to the little finger in this hand. In addition, the impaired hand performed the task with a slower speed and in a more irregular fashion. CONCLUSIONS: The results are discussed with reference to keyboard design. It is concluded that the standard 'QWERTY' keyboard hampers typing performance extensively, especially for subjects with left spastic hemiparesis. A learning method is presented in which the role of an external pacer (e.g. metronome) is discussed. This device can initially be used to decrease movement variability and, eventually, for increasing movement speed.