We performed a meta-analysis of randomised clinical studies in which the efficacy and toxicity of the same total daily dose of aminoglycosides administered once-daily was compared with multiple divided daily dosing for treating human infections. Of twenty-eight publications identified from a literature search using Medline 19 publications of 20 study comparisons involving 2881 patients met the criteria for analysis. Netilmicin was investigated in 11 studies, amikacin in seven studies and gentamicin in two studies but no studies of tobramycin met the inclusion criteria. The meta-analysis showed that there was a small, statistically significant difference in clinical efficacy of 3.5% (95% confidence intervals 0.5% to 6.5%, P = 0.027) in favour of once-daily administration but no significant differences in bacteriological efficacy or nephrotoxicity were detected. Auditory and vestibular toxicity rates were low for all agents and no differences in these toxicities were identified between once-daily or multiple-dose administration regimens either clinically or by audiometry or electronystagmography. Aminoglycosides can be given once-daily without loss of efficacy or increased toxicity offering greater simplicity and potentially improved cost-effectiveness than can be achieved by giving these drugs in divided doses.
Objective: To assess the practicality, safety, cost effectiveness and outcome of receiving intravenous antibiotics at home. Methods: Patients with serious bacterial infections requiring parenteral antibiotic therapy were enrolled in a pilot program to receive treatment at home. Antibiotics were premixed in the hospital pharmacy and administered by the Royal District Nursing Service, and medical back‐up was provided. Results: Twenty patients (mean age, 58 years; range, 19–84 years) received 21 courses of intravenous antibiotics at home (mean duration ± SD, 26 ± 9 days; range, 11–44 days). Conditions treated included osteomyelitis (10 patients), endocarditis (5), vascular graft and pacemaker sepsis (4), and chronic cellulitis (1). Treatment at home was well tolerated with no significant complications, and cure was achieved in 18 of the 20 patients. It was both efficient and cost effective, with a mean benefit in treatment costs between home and the equivalent inpatient therapy of at least $112 per day for the 538 days that home therapy was provided. Moreover, the reduced bed use could allow an additional hospital throughput of between 86 and 107 patients annually. Conclusions: Home intravenous antibiotic therapy is safe, effective and well tolerated. It allows more efficient inpatient care and reduces total treatment costs in an important subpopulation of patients.
Objective To assess the clinical outcome and pharmacokinetics of therapy with cefazolin for patients with cellulitis in a hospital‐in‐the‐home (HIH) program. Design Observational study with outcome data compared with previously published reports of therapy for cellulitis. Setting: A university teaching hospital and HIH unit, July 1996 – December 1997. Participants Patients with cellulitis were eligible for inclusion provided their medical condition was stable, they did not require surgical intervention, and their social circumstances allowed home‐based therapy. Intervention Cefazolin 2g intravenously twice daily, with regular nursing and medical assessment. Main outcome measures Clinical efficacy; peak and trough serum concentrations of cefazolin. Results Fifty‐seven patients (37 were men) with a mean age of 48 years (range, 18–90 years) had 61 episodes of moderate to severe cellulitis (41, lower limb; 17, upper limb; and three, face). They received a median of 11 doses of cefazolin (range, 3–27 doses). Clinical outcomes were: cure in 54, improvement in one, treatment failure in three, and in the remaining three episodes the outcome was indeterminate. Cefazolin concentrations were measured in 27 patients. All peak concentrations were more than 40μg/mL, while trough concentrations were all above the MIC90 of the expected pathogens: median, 3.2μg/mL (range: 0.4–18.5 μg/mL). Cefazolin was well tolerated. Conclusions Twice‐daily cefazolin 2g intravenously is a convenient and effective option for home‐based treatment of patients with cellulitis. Its clinical efficacy is comparable with other treatment regimens.
30Alcohol-based hand rubs are international pillars of hospital infection control, restricting 31 transmission of pathogens such as Staphylococcus aureus. Despite this success, health care 32 infections caused by Enterococcus faecium (Efm) -another multidrug resistant pathogen -are 33 increasing. We tested alcohol tolerance of 139 hospital Efm isolates, obtained between 1997 and 34 2015 and found Efm post-2010 were 10-fold more tolerant to alcohol killing than older isolates. 35 Using a mouse infection control model, we then showed that alcohol tolerant Efm resisted standard 36 70% isopropanol surface disinfection and led to gastrointestinal colonization significantly more 37 often than alcohol sensitive Efm. We next looked for bacterial genomic signatures of adaptation. 38 Tolerant Efm have independently accumulated mutations modifying genes involved in carbohydrate 39 uptake and metabolism. Mutagenesis confirmed their roles in isopropanol tolerance. These findings 40 suggest bacterial adaptation and complicate infection control recommendations. Additional policies 41 and procedures to prevent Efm spread are required. 42 [146 words] 43 44 3
Background-Influences of female hormones on the occurrence of allergic disorders have been suggested. Age at menarche may be a marker of endogenous oestrogen levels. Data from a Finnish birth cohort followed to adulthood were analysed to determine whether there is any association between maternal age at menarche and the occurrence of atopy among oVspring. Methods-The study was conducted in 5188 subjects born in northern Finland for whom data collections were started during pregnancy and a follow up examination was completed at the age of 31 years. Atopy was determined by skin prick tests with cat, birch, grass, and mite extracts, and doctor diagnosed asthma was ascertained by questionnaire at follow up. Maternal age at menarche was obtained from perinatal data. Logistic regression models were used to adjust for maternal age, parity, smoking, season of birth, parental allergy, and measures of adiposity and socioeconomic status. Results-The prevalence of atopy at the age of 31 years was lower in children whose mothers reached menarche at a later age, especially after age 15. Compared with children whose mothers started menarche at the age of 16 or over, the adjusted odds ratios of being atopic for children whose mothers started menarche younger than or at 12, 13, 14 and 15 years were 1.43 (95% CI 1.12 to 1.83), 1.29 (95% CI 1.03 to 1.60), 1.15 (95% CI 0.93 to 1.42), and 1.19 (95% CI 0.95 to 1.48), respectively. Among girls, the oVspring's own age at menarche was not significantly associated with atopy. Conclusion-Our results encourage further evaluation of the potential eVect of maternal age at menarche on the later development of atopy and possible biological mechanisms.
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