Management of bloodstream infections by infection specialists: an international ESCMID cross-sectional survey

Bloodstream infections (BSIs) are common, however international guidelines are available only for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and candidaemia. This international ESCMID cross-sectional survey, open from December 2016 to February 2017, explored the management of BSIs by infection specialists. All infection specialists (senior or trainees) giving at least weekly advice on positive blood cultures could participate. Their practices were evaluated using six clinical vignettes presenting uncomplicated BSI cases. A total of 616 professionals from 56 countries participated [333/616 (54%) infectious diseases specialists, 188/616 (31%) clinical microbiologists], of whom 76% (468/616) were members of an antimicrobial stewardship team. Large variations in practice were noted, in particular for the Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa vignettes. Echocardiography was considered standard of care by 81% (373/459) of participants for MRSA, 78% (400/510) for methicillin-susceptible S. aureus and 60% (236/395) for Candida albicans. Antimicrobial combination therapy was recommended by 2% (8/360) of respondents for C. albicans, 11% (43/378) for E. coli, 27% (114/420) for MRSA and 39% (155/393) for E. faecalis. Intravenous-to-oral switch was considered in 68% (285/418) for MRSA, 79% (306/388) for E. faecalis, 72% (264/366) for P. aeruginosa and 75% (270/362) for C. albicans. In multivariable analysis, IDSA guideline-compliant practice was more frequent among participants belonging to an antimicrobial stewardship team (aOR?=?1.7, P?=?0.018 for the MRSA vignette; and aOR?=?2.0, P?=?0.008 for the candidaemia vignette). This survey showed large variations in practice among infection specialists. International guidelines on management of BSI are urgently needed.     

Ranking Itraconazole Formulations Based on the Flux through Artificial Lipophilic Membrane

Purpose

The goal of the study was to evaluate a miniaturized dissolution-permeation apparatus (μFLUX? apparatus) for its ability to benchmark several itraconazole (ITZ) formulations for which in vivo PK data was available in the literature.

Method

Untreated and micronized powders of ITZ and various enabling formulations of ITZ (commercial Sporanox® solid dispersion, a Soluplus®-based solid dispersion and a nanosuspension) were introduced to the donor compartment of μFLUX? apparatus. Donor and acceptor chambers were divided from each other by a lipophilic membrane. In addition to the flux evaluations, changes in solid state as a function of time were investigated to gain further insight into the flux changes observed over time for the solid dispersion formulations.

Results

Initial flux values from Sporanox®, the nanosuspension and the micronized ITZ showed ratios of 52/4/1 with a decreasing flux from nanosuspension and both solid dispersions after 2.5–3 h. Although the initial flux from the Soluplus® formulation was 2.2 times lower than the one observed for Sporanox®, the decrease in flux observed was milder and became ~ 2 times higher than Sporanox® after approximately 2.5 h. The total amounts of ITZ in the receiver compartment after 240 min showed the same rank order as the rodent AUCs of these formulations reported in literature.

Conclusions

It was demonstrated that in vitro flux measurements using lipophilic artificial membranes could correctly reproduce the rank order of PK results for ITZ formulations. The drop in flux over time for solid dispersions could be backed by experimental indications of crystallization.

     

Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1α (p-IRE1α) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways

Context: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)].

Objective: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model.

Materials and methods: Sixty male rats were divided into five experimental groups: a normal control group (CTR?+?vehicle), a control group administered MOTILIPERM 200?mg/kg (CTR?+?M 200), a varicocele-induced control group (VC?+?vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC?+?M 100) or 200 (VC?+?M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG).

Results: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC?+?M 200 group compared with VC?+?vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio.

Discussion and conclusions: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.     

Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.     

The digastric muscle's anterior accessory belly: case report

Digastric muscle is characterized by presenting occasional variations. The suprahyoid region of an 83 year-old male cadaver was dissected and an anatomic variation of the digastric muscle was observed in its anterior belly. It consisted of an accessory bilateral anterior belly originating in the intermediate tendon and inserted into the mylohyoid raphe. The implications of this variation are discussed from a diagnostic and functional perspective.     

Breath sound distribution images of patients with pneumonia and pleural effusion

OBJECTIVE: To determine whether breath sound distribution maps can differentiate between patients with pneumonia or pleural effusion versus healthy controls. METHODS: We recorded breath sounds from 20 patients conventionally diagnosed as having pleural effusion, 20 patients conventionally diagnosed as having pneumonia, and 60 healthy controls, of whom 20 served as a learning sample. All subjects were examined with a computer-based multi-sensor breath sound mapping device that records, analyzes, and displays a dynamic map of breath sound distribution. The physicians who interpreted the breath sound images were first trained in identifying common characteristics of the images from the learning sample of normals. Then the images from the 40 patients and the 40 controls were interpreted as either normal or abnormal. RESULTS: In the normal images, the left and right lung images developed synchronously and had similar size, shape, and intensity. The sensitivity and specificity of blinded differentiation between normal and abnormal images when the physician interpreter did not know the patient's workup were 82.5% and 80%, respectively. The sensitivity and specificity of blinded detection of normal and abnormal images when the interpreter did know the patient' workup were 90% and 88%, respectively. CONCLUSIONS: Computerized dynamic imaging of breath sounds is a sensitive and specific tool for distinguishing pneumonia or pleural effusion from normal lungs. The role of computerized breath sound analysis for diagnosis and monitoring of lung diseases needs further evaluation.     

Foreign body reaction to calcium hydroxylapatite after lip augmentation

BACKGROUND: Dentists need to be aware of soft-tissue lesions resulting from cosmetic facial/lip procedures that involve the use of injectable materials. Common side effects detected on clinical examination may include edema, bruising and noninflammatory lip nodules. CASE DESCRIPTION: A 51-year-old woman visited a dental clinic with the chief complaint of a lump on the mucosal aspect of her lower lip. She reported having noted the lesion a few weeks before seeking care at the clinic. Several weeks later, the lesion persisted and new lesions were detected. The clinician excised the initial lesion only. CLINICAL IMPLICATIONS: The lip nodules were associated with a cosmetic procedure and were inflammatory in nature. This is the first granulomatous response reported as a result of injections with calcium hydroxylapatite (Radiesse, BioForm Medical, San Mateo, Calif.). Poor patient recollection of his or her medical history may result in confusion with pathological processes such as infection, neoplasia or malignancy.     

Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs

Recent studies have shown that ultrasound (US)-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to improve low-frequency (20 kHz) US methods for enhancing the transport of insulin in vitro across human skin. The feasibility of using US produced by small, lightweight novel transducers was explored for enhancing the transport of insulin across skin. Previous investigators have used US devices such as large, heavy sonicators or commercially obtained transducers for this type of research. The experiments carried out in this study used two low-profile novel US transducer arrays, the stack and standard array, for improved transport of insulin. The stack array generated a spatial peak temporal peak intensity (I(SPTP)) of 15.4 +/- 0.6 mW/cm(2) and the standard array had an I(SPTP) of 173.7 +/- 1.2 mW/cm(2). Spectrophotometeric absorption techniques were used for determining insulin transport in vitro across human skin. Compared with passive transmission (4.1 +/- 0.5 U) over an exposure period of 1 h, the standard array facilitated over a sevenfold increase in the noninvasive transdermal transport of Humulin R insulin (45.9 +/- 12.9 U). Using Humalog insulin with the standard array, there was a fourfold increase in the US-facilitated transmission over that in the control. These promising results indicate that low-frequency US can be used in a practical device for enhanced transport across the stratum corneum.