Infections by multidrug-resistant Gram-negative Bacteria: What's new in our arsenal and what's in the pipeline?

The spread of multidrug-resistant bacteria is an ever-growing concern, particularly among Gram-negative bacteria because of their intrinsic resistance and how quickly they acquire and spread new resistance mechanisms. Treating infections caused by Gram-negative bacteria is a challenge for medical practitioners and increases patient mortality and cost of care globally. This vulnerability, along with strategies to tackle antimicrobial resistance development, prompts the development of new antibiotic agents and exploration of alternative treatment options. This article summarises the new antibiotics that have recently been approved for Gram-negative bacterial infections, looks down the pipeline at promising agents currently in phase I, II, or III clinical trials, and introduces new alternative avenues that show potential in combating multidrug-resistant Gram-negative bacteria.     

Pharmacotherapeutic strategies for castrate-resistant prostate cancer

ABSTRACT

Introduction

Metastatic castration-resistant prostate cancer (CRPC) is a potentially symptomatic disease with an eventual lethal outcome. Novel pharmaceutical agents are continuously studied with encouraging results in CRPC.     

Biomechanical evaluation of plating techniques for fixing mandibular angle fractures: the introduction of a new 3D plate approach

Purpose

The aim of this study was to comparatively evaluate the use of a three-dimensional (3D) square-shaped plate for the treatment of mandibular angle fractures.

Materials and methods

Synthetic mandible replicas were used to evaluate the effectiveness of the 3D square plate along with three other mandibular angle plating techniques. The plating techniques consisted of: (1) a 3D miniplate (2?×?2 holes, square, 2 mm); (2) a 3D miniplate (6?×?2 holes, curved, 2 mm); (3) two miniplates (four holes, straight, 2 mm and 1.6 mm); and (4) one single miniplate (four holes, straight, 2 mm). Each group was subjected to incisal and homolateral molar region loading by a tensile materials testing machine (Monsanto Tensometer 20). Load stiffness values and peak measurements of the fracture gap distraction at the superior aspect of the mandible were measured. The mean values (±standard deviation) were derived and compared using one-way analysis of variance, with statistical significance set at p?<?0.05.

Results

For homolateral molar loading, statistically significant differences existed within groups (p?<?0.05). For incisal edge loading, no statistically significant differences were found for stiffness among the fixation methods tested. Gap distraction at the superior aspect of the mandible was limited for three of the groups tested.

Conclusion

Under the conditions tested, the 3D square plate system provided the most favorable mechanical behavior.     

The association of diabetic microvascular and macrovascular disease with cutaneous circulation in patients with type 2 diabetes mellitus

Aims

To study the impact of diabetic neuropathy, both peripheral sensorimotor (DPN) and cardiac autonomic neuropathy (CAN), on transcutaneous oxygen tension (TcPO₂) in patients with type 2 diabetes mellitus (T2DM).

Nutritional Surveillance of Christian Orthodox Minority Adolescents in Istanbul

Previous studies have shown that the diets of migrant populations are of poor quality; however, studies on populations remaining in one geographical region as a minority after an acute population movement are scarce. Therefore, the aim of the present study was to assess dietary intake and growth of Greek minority adolescents in Turkey. Anthropometric measurements and dietary assessment were performed in 103 Greek Orthodox students (aged 10–19 years old) of three minority schools in Istanbul. Prevalence of overweight and obesity according to the WHO growth charts was 39.8 %. Accordingly, 40 % of the sample exhibited excess body fat. Dietary intakes of protein, carbohydrate, fiber, vitamins E and D, folic acid and calcium were inadequate, while energy, total fat and iron intakes were considered adequate. Our results indicate that Greek minority adolescents living in Turkey have similar weight status compared to their counterparts in Greece, but greater body fat than Turkish coevals, while being at risk of several nutrient inadequacies.     

Eleven Patients With Testicular Leydig Cell Tumors

We present the sonographic and magnetic resonance imaging findings of Leydig cell tumors in a series of patients, along with a brief review of the literature. We evaluated the sonographic features of 11 cases of Leydig cell tumors, including echogenicity, size, margins, and patterns of vascularity. The magnetic resonance imaging characteristics of 9 patients were also assessed, with special attention to the appearance of the tumors on T2-weighted imaging and postcontrast T1-weighted imaging. Seven tumors were hypoechoic, and 4 were almost isoechoic. Ten patients showed various patterns of hypervascularity in the tumors, combined in some cases with feeding vessels. One case presented with a single feeding vessel. The tumors showed homogeneous or heterogeneous low signal intensity on T2-weighted imaging and marked enhancement on postcontrast T1-weighted imaging. The small size of these tumors, the various patterns of vascularity on color and power Doppler sonography, and the marked enhancement on postcontrast T1-weighted imaging are considered valuable but generally nonspecific for identification of these tumors.     

Intravenous fosfomycin for the treatment of multidrug-resistant pathogens: what is the evidence on dosing regimens?

Introduction: The intravenous (IV) formulation of fosfomycin has been re-introduced in clinical practice mainly to overcome treatment failures against multidrug-resistant (MDR) bacteria. Appropriate dosing schedules of the IV formulation have not yet been established.

Areas covered: The mechanism of action and resistance development, commercial IV formulations, pharmacokinetic/pharmacodynamic (PK/PD) properties, IV dosing regimens for the treatment of MDR infections along with efficacy and safety issues were reviewed. Data regarding specific MDR pathogens, daily doses and patients’ outcomes, gaps in the current literature, and in progress research agenda are presented.

Expert opinion: The doses of fosfomycin IV range between 12 and 24 grams/day depending on the severity of infection. The efficacy and safety of the commonly administered doses have been shown mainly in observational non-comparative trials. The optimal dose ensuring maximal efficacy with minimal toxicity along with the most appropriate co-administered antibiotic(s) need further evaluation. The pharmacokinetic/pharmacodynamic parameter associated with maximum efficacy has not yet been established, although, the ratio of the area under the concentration-time curve (AUC) for the free unbound fraction of fosfomycin versus the MIC (fAUC/MIC) may be linked to optimal treatment. RCTs and other comparative studies are underway to address gaps of knowledge in adult patients and neonates.