Central nervous system infections requiring treatment with intraventricular (IVT) vancomycin are becoming increasingly common with advent of intracranial devices and increasing prevalence of multi-drug resistant and nosocomial organisms. Administering vancomycin via IVT route bypasses the blood-brain barrier to allow localized and controlled delivery directly to the desired site of action, achieving high concentrations for more reliable bactericidal action. This article systematically reviews current literature on IVT vancomycin in adults, compiles current knowledge, and integrates available evidence to serve as a practical reference.Medline (1946-July 2012), Embase (1974-July 2012), and International Pharmaceutical Abstracts (1970-July 2012) were searched using terms vancomycin, intraventricular, shunt infection, cerebrospinal fluid, and intraventriculitis. Seventeen articles were included in this review. Indications for IVT vancomycin included meningitis unresponsive to intravenous antibiotics, ventriculitis, and intracranial device infections. No serious adverse effects following IVT vancomycin have been reported. Dosages reported in literature ranged from 0.075-50 mg/day, with the most evidence for dosages of 5 to 20 mg/day. Duration of therapy most commonly ranged from 7 to 21 days. Therapeutic drug monitoring was reported in 11 studies, with CSF vancomycin levels varying widely from 1.1 to 812.6 mg/L, without clear relationships between CSF levels and efficacy or toxicity. Using IVT vancomycin to treat meningitis, ventriculitis, and CNS device-associated infections appears safe and effective based on current evidence. Optimal regimens are still unclear, and dosing of IVT vancomycin requires intricate consideration of patient specific factors and their impact on CNS pathophysiology. Higher-quality clinical trials are necessary to characterize the disposition of vancomycin within CNS, and to determine models for various pathophysiological conditions to facilitate better understanding of effects on pharmacokinetic and pharmacodynamic parameters.

Diabetic foot ulcers and infections are common and incur substantial economic burden for society, patients and families. We performed a comprehensive review, on a number of databases, of health economic evaluations of a variety of different prevention, diagnostic and treatment strategies in the area of diabetic foot ulcers and infections. We included English-language, peer-reviewed, cost-effectiveness, cost-minimization, cost-utility and cost-benefit studies that evaluated a treatment modality against placebo or comparator (i.e. drug, standard of care), regardless of year. Differences were settled through consensus. The search resulted in 1885 potential citations, of which 20 studies were retained for analysis (3 cost minimization, 13 cost effectiveness and 4 cost utility). Quality scores of studies ranged from 70.8% (fair) to 87.5% (good); mean = 78.4% +/- 5.33%.In diagnosing osteomyelitis in patients with diabetic foot infection, magnetic resonance imaging (MRI) showed 82% sensitivity and 80% specificity. MRI cost less than 3-phase bone scanning + Indium (In)-111/Gallium (Ga)-67; however, when compared with prolonged antibacterials, MRI cost $US120 (year 1993 value) more without additional quality-adjusted life-expectancy. Prevention strategies improved life expectancy and QALYs and reduced foot ulcer rates and amputations.Ampicillin/sulbactam and imipenem/cilastatin were both 80% successful in treating diabetic foot infections but the latter cost $US2924 more (year 1994 value). Linezolid cure rates were higher (97.7%) than vancomycin (86.0%) and cost $US873 less (year 2004 value). Ertapenem costs were significantly lower than piperacillin/tazobactam ($US356 vs $US503, respectively; year 2005 values). Becaplermin plus good wound care may be cost effective in specific populations. Bioengineered living-skin equivalents increased ulcer-free months and ulcers healed, but costs varied between countries. Promogran produced more ulcer-free months than wound care alone (3.75 vs 3.41 months, respectively). Treatment with cadexomer iodine resulted in higher rates of healed ulcer (29% vs 11%) and lower weekly treatment costs (Swedish krona [SEK]903 vs SEK1421; year 1993 values) than standard care. Filgrastim decreased hospital stays, time to resolution and costs (36% lower) compared with usual care. Adjunctive hyperbaric oxygen produced an incremental cost per QALY at year 1 of $US27 310 and $US2255 at year 12 (year 2001 values).Overall, preventive strategies were shown to be cost effective and potentially cost saving. Various antibacterial regimens are cost effective but empiric choices should be based on local resistance patterns. MRI was cost effective compared with three-phase bone scanning + In-111/Ga-67 but not against prolonged antibacterial therapy. Other innovations (becaplermin, bioengineered living-skin equivalents, filgrastim, cadexomer iodine ointment, hyperbaric oxygen, Promogran may be cost effective in this population but more studies are needed to confirm these findings.

Although women typically favor affirmative action, they do exhibit a range of reactions to affirmative action programs. To understand the diversity of reactions, the present study proposed an examination of various forms of affirmative action in the context of the discrimination problem such actions were designed to address. In Study 1, 60 female university students were presented with one of six scenarios describing a situation of discrimination against women, followed by a series of potential affirmative action response options which participants rated in terms of their level of endorsement. Analyses of variance showed that, despite the range of discrimination scenarios, some of which presented extreme cases of discrimination against women, respondents consistently endorsed nondiscrimination measures, and opposed affirmative action strategies involving preferential treatment. Study 2, which preselected 43 women who valued social equality, replicated this finding and found that these results were not due to women not perceiving the presence of collective discrimination. Study 3 examined the attitudes of women in a law and security police training stream (n = 19), whose vulnerability to employment discrimination, both as a group and personally, would be salient. The women in this study endorsed all forms of affirmative action, including explicit preferential treatment in the hiring of women police officers. The implications of these results for the consideration and implementation of affirmative action programs are discussed.

Due to increasing prevalence of intracranial device use and multidrug-resistant and nosocomial organisms, central nervous system (CNS) infections requiring treatment with intraventricular (IVT) aminoglycosides are becoming increasingly common. This article systematically reviews IVT aminoglycoside literature in adults and integrates available evidence to serve as a practical reference for clinicians. Medline (1946 to December 2015), Embase (1974 to December 2015), PubMed (1966 to December 2015), Google, and Google Scholar were searched using the term aminoglycoside combined individually with the terms IVT, meningitis, shunt infection, ventriculitis, and cerebral spinal fluid. Eighteen articles were included. IVT aminoglycosides were assessed in meningitis, ventriculitis, intracranial device infections and neurosurgery prophylaxis. No serious adverse effects following IVT aminoglycoside were reported. Dosages ranged from IVT gentamicin 4-10 mg daily, IVT tobramycin 5-10 mg daily, and IVT amikacin 5-50 mg daily. Duration of therapy should be individualized; however, continuing IVT antibiotics for 3 days and up to 21 days after cerebrospinal fluid (CSF) sterilization has been reported in literature. Most studies included concomitant intravenous antibiotic use. Therapeutic drug monitoring (TDM) was reported in five studies, with varying timing of CSF concentrations obtained. No clear relationship between CSF levels and efficacy or toxicity was evident. Based on current literature, IVT aminoglycosides for the treatment of sensitive gram-negative meningitis, ventriculitis, and CNS device-associated infections appear safe and effective. Optimal dosing regimens are unclear. It is reasonable to initiate IVT aminoglycoside at lowest dose in combination with IV therapy and continuing post CSF sterilization. Preservative-free formulations should be utilized to minimize adverse drug reactions. TDM should not be routinely utilized but reserved for more complicated patients. Further pharmacokinetic and clinical trials of IVT aminoglycosides are necessary to fill current therapeutic gaps. Due to the relatively limited cases of IVT aminoglycoside utilization, prospective, randomized, controlled trials are likely not feasible, and clinicians will have to rely on data from non-randomized and/or retrospective studies.

The available literature on prolonged and continuous infusions of cefepime demonstrated an improved achievement of pharmacodynamic targets; however, the effect on clinical outcomes is inconclusive. Well-designed prospective studies are required to determine optimal dosing and administration strategies.