Susceptibility of Rickettsia rickettsii to Tigecycline in a Cell Culture Assay and Animal Model for Rocky Mountain Spotted Fever.

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is a severe tick-borne infection endemic to the Americas. Oral doxycycline is effective, but during severe life-threatening disease, intravenous therapy is recommended. Unfortunately, intravenous formulations of doxycycline are not always available. Therefore, we aimed to determine the susceptibility of R. rickettsii to an alternative parenteral agent, tigecycline, in vitro and in vivo. To determine the minimum inhibitory concentration of tigecycline, R. rickettsii-inoculated Vero cells were incubated with medium containing tigecycline. At various time points, monolayers were collected and R. rickettsii was quantified via real-time polymerase chain reaction (PCR). The growth of R. rickettsii was inhibited in the presence of ≥ 0.5 µg/mL of tigecycline. To determine the effectiveness of tigecycline in vivo, guinea pigs were inoculated with R. rickettsii. Five days after inoculation, they were treated twice daily with subcutaneous tigecycline 3.75 mg/kg or subcutaneous doxycycline 5 mg/kg. Treated animals improved, whereas untreated controls remained ill. Tissues were collected for quantitative PCR-determined bacterial loads on day 8. Median bacterial loads in the tigecycline group were less than those in untreated animals: liver (0 versus 2.9 × 104 copies/mg), lung (0 versus 8.3 × 103 copies/mg), skin (2.6 × 102 versus 2.2 × 105 copies/mg), spleen (0 versus 1.3 × 104 copies/mg), and testes (0 versus 1.0 × 105 copies/mg, respectively). There were no significant differences in the bacterial loads between doxycycline-treated versus tigecycline-treated guinea pigs. These data indicate that tigecycline is effective against R. rickettsii in cell culture and in an animal model of RMSF.

Statin Use and 25-Hydroxyvitamin D Blood Level Response to Vitamin D Treatment of Older Adults.

OBJECTIVES: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. DESIGN: Pooled analysis. SETTING: Three double-blind randomized controlled trials that tested different doses of vitamin D. PARTICIPANTS: Participants of three trials (N = 646; mean age 76.3 ± 8.4, 65% female). MEASUREMENTS: In all three trials, 25(OH)D status and statin use were assessed repeatedly over time (baseline, 6 and 12 months). Repeated-measures analysis was used to compare 25(OH)D response to vitamin D treatment at baseline and 6 and 12 months of statin users and nonusers, controlling for age, sex, body mass index, Charlson Comorbidity Index, vitamin D dose, trial, and season. RESULTS: At baseline, 17.5% were statin users, and 65% were vitamin D deficient (25(OH)D < 20 ng/mL). Baseline 25(OH)D levels did not differ significantly between groups at baseline (18.8 for statin users, 17.2 ng/mL for nonusers, P = .07), but according to the longitudinal analyses, the total increase over 12 months in 25(OH)D concentration was significantly lower in statin users (13.1 ng/L) than nonusers (15.9 ng/mL; 21.4% difference; P = .009). CONCLUSION: Of persons aged 60 and older at high risk of vitamin D deficiency, statin users had a 21.4% smaller increase in 25(OH)D serum concentrations over time than nonusers, independent of vitamin D dose and other covariates.

Associations between drug burden index and mortality in older people in residential aged care facilities.

BACKGROUND: The Drug Burden Index (DBI), a measure of an individual's exposure to anticholinergic and sedative medications, is associated with functional impairment in community-dwelling, older people. In people from residential aged care facilities (RACFs), DBI score does not appear to be associated with functional impairment, but is associated with an increased risk of falls. OBJECTIVE: We investigated the associations between increasing DBI score and mortality in older adults living in RACFs. METHODS: Study participants (n = 602; 70.9% female), recruited from 51 RACFs in Sydney, Australia, had a mean ± standard deviation (SD) age of 85.7 ± 6.4 years and a mean ± SD DBI score of 0.58 ± 0.64. RESULTS: Exposure to anticholinergic medication was 33.6% and sedative medications 41.9%. All-cause mortality after a variable follow-up time (774-1269 days) was 36.2% (n = 218), with the leading causes of death classified as stroke (n = 46; 21.1%), ischaemic heart disease/cardiovascular system (n = 44; 20.2%) and pneumonia (n = 31; 14.2%). One-year mortality multivariate models showed that the DBI categories low (n = 260; hazard ratio [HR] 1.13; 95% CI 0.82, 1.57) and high (n = 153; HR 1.19; 95% CI 0.82, 1.74) were not associated with mortality. This lack of a significant association remained after dichotomization into the anticholinergic and sedative components of the DBI. CONCLUSIONS: We found that with high exposure to anticholinergic and sedative medications, there was no significant association between increasing DBI score and all-cause mortality in old individuals living in RACFs. Further research into the adverse effects of medication use on the mortality of institutionalized older individuals is needed.

Associations between drug burden index and falls in older people in residential aged care.

OBJECTIVES: To evaluate the association between the Drug Burden Index (DBI), a measure of a person's total exposure to anticholinergic and sedative medications that includes principles of dose-response and maximal effect and is associated with impaired physical function in community-dwelling older people, and falls in residents of residential aged care facilities (RACFs). DESIGN: Data were drawn from participants in a randomized controlled trial that investigated falls and fractures. SETTING: RACFs in Sydney, Australia. PARTICIPANTS: Study participants (N=602; 70.9% female) were recruited from 51 RACFs. Mean age was 85.7 ± 6.4, and mean DBI was 0.60 ± 0.66. MEASUREMENTS: Medication history was obtained on each participant. Drugs were classified as anticholinergic or sedative and a DBI was calculated. Falls were measured over a 12-month period. Comorbidity, cognitive impairment (Mini-Mental State Examination) and depression (Geriatric Depression Scale) were determined. RESULTS: There were 998 falls in 330 individuals during a follow-up period of 574.2 person-years, equating to an average rate of 1.74 falls per person-year. The univariate negative binomial regression model for falls showed incidence rate ratios of 1.69 (95% confidence interval (CI)=1.22-2.34) for low DBI (<1) and 2.11 (95% CI=1.47-3.04) for high DBI (≥1) when compared with those who had a DBI of 0. After adjusting for age, sex, history of falling, cognitive impairment, depression, use of a walking aid, comorbidities, polypharmacy, and incontinence, incident rate ratios of 1.61 (95% CI=1.17-2.23) for low DBI and 1.90 (95% CI=1.30-2.78) for high DBI were obtained. CONCLUSION: DBI is significantly and independently associated with falls in older people living in RACFs. Interventional studies designed for this population are needed to determine whether reducing DBI, through dose reduction or cessation of anticholinergic and sedative drugs, can prevent falls.

Medication safety in residential aged-care facilities: a perspective.

Medication safety must be tailored to the distinctive issues in residential aged-care facilities (RACFs). The health and functional characteristics of their residents are different to those of hospital inpatients and community-dwelling older adults, and there are unique staffing and management issues. Understanding the aetiology and epidemiology of drug-related problems is vital in developing methods to improve patient safety. In this perspective review, we discuss tools that are used to quantify exposure to 'high-risk' medications and their evaluation in residential aged-care settings. Drug withdrawal interventions are described as a potential way to reduce adverse drug events in RACFs. Multidisciplinary professional interventions, education programs and improved communication between health professionals have been shown to improve medication safety in RACFs. Technological advances and other administrative strategies may also improve resident safety. This perspective addresses issues in medication safety facing RACFs and methods to improve the safety of medicines for their residents.