Diabetic foot infection: Antibiotic therapy and good practice recommendations.

BACKGROUND: Healthcare events related to diabetic foot disease carry a burden of morbidity, mortality and economic cost. Prompt identification of clinical infection with appropriate tissue sampling limits use of broad spectrum empirical antibiotics and improves antibiotic stewardship. Staphylococcus aureus remains the commonest infecting organism and high-dose flucloxacillin remains the empirical antibiotic of choice for antibiotic naïve patients. Barriers to microbe-specific treatment include: adequate tissue sampling, delays in culture results, drug allergies and the emergence of multidrug-resistant organisms which can complicate the choice of targeted antibiotics. Even appropriate antibiotic treatment carries a risk of adverse events including the selection of resistant organisms. AIMS: Multidisciplinary clinical assessment of a diabetic foot infection is supported by the use of appropriate imaging modalities and deep tissue sampling, both of which are encouraged to enhance sampling accuracy. Narrow-spectrum, high dose, short duration antimicrobial therapy is ideal. Further clarity in these areas would be of benefit to clinicians involved in management of diabetic foot infections. METHODS: A combination of literature review with expert discussion was used to generate consensus on management of diabetic foot infection, with a specific focus on empirical antimicrobial therapy. RESULTS: Gram positive organisms represent the commonest pathogens in diabetic foot infection. However there are developing challenges in antimicrobial resistance and antibiotic availability. DISCUSSION: Recommendations for empirical therapy, including the choice of alternative oral agents and use of outpatient antibiotics would be of benefit to those involved in diabetic foot care. CONCLUSION: This paper provides advice on empirical antibiotic therapy that may be used as a framework for local guideline development to support clinicians in the management of diabetic foot infection.

Factors contributing to high levothyroxine doses in primary hypothyroidism: an interventional audit of a large community database.

BACKGROUND: While few hypothyroid patients require more than the expected weight-related dose of levothyroxine, the underlying causes of larger-than-expected dosing requirements have not been studied in a single cohort. Our aim was to determine and quantify the multiple factors contributing to high-dose levothyroxine requirements in a cohort of patients with hypothyroidism. METHODS: The Grampian Automated Follow-Up Register (GAFUR) monitors around 17,500 hypothyroid patients. In 2008, 190 (1%) patients took >225 µg of levothyroxine daily. A questionnaire was sent to 174 patients (16 were untraceable) to assess causes and to offer blood tests for endomysial, parietal cell (PCA), and thyroid peroxidase (TPO) autoantibodies. Primary care practices were contacted for medication details. All patients with positive endomysial autoantibodies were referred to a gastroenterologist. Thyroid function tests and levothyroxine doses were re-evaluated in 2011. RESULTS: A total of 125 questionnaires (72%) were returned. Mean levothyroxine dose was 248 µg daily. Twenty-six patients (20.8%) took medication known to interfere with levothyroxine absorption, and 21 patients (16.8%) admitted to compliance issues. Seven patients had positive anti-endomysial antibodies on initial screening, with four being new diagnoses of celiac disease, and PCA were positive in 27 (21.6%) patients. At follow-up in 2011, the mean levothyroxine dose had decreased in patients on interfering medications and in the four new cases of celiac disease. CONCLUSIONS: Causes of patients needing high-dose levothyroxine replacement include poor compliance, medication interference, PCA (as a marker of atrophic/autoimmune gastritis), and celiac disease. Doses can be decreased following advice regarding medication or after management of underlying conditions.

Adaptation to long-term cold-girdling in genotypes of common bean (Phaseolus vulgaris L.).

The effect of long-term cold-girdling on phloem transport and resource allocation in whole plants of common bean is described. Wide differences were found between genotypes, with some maintaining translocation when cold-girdled. This provides evidence to support passive phloem transport. The possibilities that cold-girdling may physically block transport and/or disrupt root-shoot signalling are discussed.

The DL gene system in common bean: a possible mechanism for control of root-shoot partitioning.

Crosses between certain genotypes of common bean result in dwarfing of F1 plants and lethal dwarfing in a proportion of the F2 population. This is under the control of the semi-dominant alleles, DL1 and DL2 at two complementary loci which are expressed in the root and shoot respectively. The various DL genotypes can be simulated by grafting. The graft combination DL1 DL1 dl2 dl2 /dl1 dl1 DL2 DL2 was found to have a significantly higher root dry matter fraction than either parent. Lethally dwarfed plants (DL1 DL1 DL2 DL2 ) and the analogous lethal graft combination (dl1 dl1 DL2 DL2 /DL1 DL1 dl2 dl2 ) exhibit failure of root growth and have very low root fractions. Hybrids or graft combinations with failed roots ceased growth and accumulated large amounts of starch throughout their hypocotyls. In sterile culture, both lethal dwarfs and lethal graft combinations were able to grow roots if sucrose was added to the growth medium. This indicates that a failure of sucrose translocation to the roots is probably responsible for failed root growth. Data from screening the DL genotypes of 49 cultivars could be fully explained using the DL system hypothesis, and grafting proved to be efficient for identifying DL genotype. The DL system might be of fundamental importance in root-shoot partitioning. Current evidence favours the hypothesis that failure of root growth is the outcome of excessively high sink strength of shoots compared to roots, which might arise from signalling incompatibilities between the genotypes.

Species-dependent induction of peroxisome proliferation by haloxyfop, an aryloxyphenoxy herbicide.

The potential of haloxyfop [2-(4-((3-chloro-5-(trifluoromethyl)-2- pyridinyl)oxy)phenoxy)propanoic acid; HAL] to induce the proliferation of hepatocellular peroxisomes (PP) was examined in rats, mice, dogs, and monkeys. Chemically induced PP is associated with the development of liver tumors in rodents via an apparent species-dependent, nongenotoxic mechanism of action. HAL is nongenotoxic yet has been shown to cause liver tumors in female B6C3F1 mice. Ingestion of HAL by rats and/or mice (0.1-14 mg/kg/day for 2 to 4 weeks) resulted in significant dose-related PP as evidenced by hepatocellular hypertrophy, increased peroxisome volume density (VD), and induction of peroxisomal enzymes and CYP4A1. Only a relatively weak induction of PP was noted at a carcinogenic dosage in female mice. In contrast to rodent species, ingestion of up to 20 mg/kg/day HAL by male and female Beagle dogs for 13 weeks failed to increase peroxisomal VD while causing only a slight increase in peroxisomal enzyme activity at the highest dosages. Oral administration of up to 30 mg/kg/day HAL by male and female Cynomolgus monkeys for 13 weeks failed to induce PP. While a direct relationship of PP with tumor formation, at least in mice, was not demonstrated, these data still support the concept that PP represents a potential marker of nongenotoxic tumorigenic activity, at some dosage, in rodents.