Potential new fluoroquinolone treatments for suspected bacterial keratitis.

Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use. For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae and several of the Enterobacteriaceae However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. The purpose of this review is to compare the pharmacokinetics and pharmacodynamics of the FQs licensed for topical ophthalmic use with the same parameters for new generation FQs. We performed a literature review of the FQs approved for topical treatment and the new generation FQs licensed to treat systemic infections. We then compared the minimum inhibitory concentrations (MIC) of bacterial isolates and the published concentrations that FQs achieved in the cornea and aqueous. We also considered the potential suitability of new generation FQs for topical use based on their medicinal properties. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to continue with the prescribed antimicrobial, increase the frequency of application, use a combination of antimicrobials or change treatment.

Postnatal head growth in preterm infants: a randomized controlled parenteral nutrition study.

BACKGROUND: Early postnatal head growth failure is well recognized in very preterm infants (VPIs). This coincides with the characteristic nutritional deficits that occur in these parenteral nutrition (PN) dependent infants in the first month of life. Head circumference (HC) is correlated with brain volume and later neurodevelopmental outcome. We hypothesized that a Standardized, Concentrated With Added Macronutrients Parenteral (SCAMP) nutrition regimen would improve early head growth. The aim was to compare the change in HC (ΔHC) and HC SD score (ΔSDS) achieved at day 28 in VPIs randomly assigned to receive SCAMP nutrition or a control standardized, concentrated PN regimen. METHODS: Control PN (10% glucose, 2.8 g/kg per day protein/lipid) was started within 6 hours of birth. VPIs (birth weight <1200 g; gestation <29 weeks) were randomly assigned to either start SCAMP (12% glucose, 3.8 g/kg per day protein/lipid) or remain on the control regimen. HC was measured weekly. Actual daily nutritional intake data were collected for days 1 to 28. RESULTS: There were no differences in demographic data between SCAMP (n = 74) and control (n = 76) groups. Comparing cumulative 28-day intakes, the SCAMP group received 11% more protein and 7% more energy. The SCAMP group had a greater ΔHC at 28 days (P < .001). The difference between the means (95% confidence interval) for ΔHC was 5 mm (2 to 8), and ΔSDS was 0.37 (0.17 to 0.58). HC differences are still apparent at 36 weeks' corrected gestational age. CONCLUSIONS: Early postnatal head growth failure in VPIs can be ameliorated by optimizing PN.

SCAMP: standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care.

BACKGROUND: Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake. METHODS: We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age. TRIAL REGISTRATION: Current controlled trials: ISRCTN76597892; EudraCT Number: 2008-008899-14.