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.     

Outcome of Judet's quadricepsplasty for knee contractures and the effect of local infiltration of epinephrine on reducing blood loss

Objective: To evaluate the effectiveness of Judet''s quadricepsplasty for treatment of knee contractures and to identify the effect of local infiltration of epinephrine on blood loss associated with this procedure. Methods: A retrospective cohort study was conducted in which all cases of knee contractures managed with Judet''s quadricepsplasty from 1st January 2009 to 31st December 2013 were included and were divided into two groups. The epinephrine group included patients who were infiltrated with diluted epinephrine (1:400,000) along with xylocaine, around the operative field 15 min prior to the incision time, while the control group did not receive any infiltration. Judet''s outcome, blood loss, drop in hemoglobin and required blood transfusion were noted for all patients and compared between both groups. Results: Most common preceding pathology identified for the development of knee contractures was periarticular fracture while ilizarov application was the most common etiology. Both groups were found similar in all preoperative characteristics except preoperative flexion contracture (p=0.02). All functional outcome measures including Judet''s outcome were similar in both groups. In contrast, duration of surgery (p=0.01), blood loss (p=0.02), drop in hemoglobin (p=0.01) and number of transfusions (p=0.03) were significantly reduced in epinephrine group. Conclusion: Judet''s quadricepsplasty is a useful procedure to increase the range of motion of rigid knees and local infiltration of epinephrine is effective in decreasing the amount of subsequent blood loss and transfusion requirements.     

Incorporating PROMIS Symptom Measures into Primary Care Practice—a Randomized Clinical Trial

Background

Symptoms account for more than 400 million clinic visits annually in the USA. The SPADE symptoms (sleep, pain, anxiety, depression, and low energy/fatigue) are particularly prevalent and undertreated.

Objective

To assess the effectiveness of providing PROMIS (Patient-Reported Outcome Measure Information System) symptom scores to clinicians on symptom outcomes.

Design

Randomized clinical trial conducted from March 2015 through May 2016 in general internal medicine and family practice clinics in an academic healthcare system.

Participants

Primary care patients who screened positive for at least one SPADE symptom.

Interventions

After completing the PROMIS symptom measures electronically immediately prior to their visit, the 300 study participants were randomized to a feedback group in which their clinician received a visual display of symptom scores or a control group in which scores were not provided to clinicians.

Main Measures

The primary outcome was the 3-month change in composite SPADE score. Secondary outcomes were individual symptom scores, symptom documentation in the clinic note, symptom-specific clinician actions, and patient satisfaction.

Key Results

Most patients (84%) had multiple clinically significant (T-score?≥?55) SPADE symptoms. Both groups demonstrated moderate symptom improvement with a non-significant trend favoring the feedback compared to control group (between-group difference in composite T-score improvement, 1.1; P?=?0.17). Symptoms present at baseline resolved at 3-month follow-up only one third of the time, and patients frequently still desired treatment. Except for pain, clinically significant symptoms were documented less than half the time. Neither symptom documentation, symptom-specific clinician actions, nor patient satisfaction differed between treatment arms. Predictors of greater symptom improvement included female sex, black race, fewer medical conditions, and receiving care in a family medicine clinic.

Conclusions

Simple feedback of symptom scores to primary care clinicians in the absence of additional systems support or incentives is not superior to usual care in improving symptom outcomes.

Trial Registration

clinicaltrials.gov identifier: NCT02383862.

     

Chronic endogenous fungal endophthalmitis: diagnostic and treatment challenges: A case report

Rationale:Endogenous fungal endophthalmitis (EFE) is a sight-threatening complication of systemic fungemia. As the prevalence rises, treatment remains a challenge especially when there is a failure in first-line treatment or drug-resistant fungus. This case report studies a case of chronic EFE, focusing on the diagnostic procedures, treatment options, monitoring parameters and the treatment outcomePatient concerns:A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks’ course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes.Diagnosis:He was diagnosed with EFE but the condition responded poorly with the medications.Interventions:He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed.Outcomes:At 3 months’ follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes.Lessons:Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.     

Hormetic effects of noncoplanar PCB exposed to human lung fibroblast cells (HELF) and possible role of oxidative stress

Hormesis, a biphasic dose–response phenomenon, which is characterized by stimulation of an end point at a low‐dose and inhibition at a high‐dose. In the present study we used human lungs fibroblast (HELF) cells as a test model to evaluate the role of oxidative stress (OS) in hormetic effects of non coplanar PCB 101. Results from 3‐(4,5‐dime‐thylthiazol‐2‐yl)‐2,5‐diphenyltetrazo‐lium bromide (MTT) assay indicated that PCB101 at lower concentrations (10^?5 to 10^?1 μg mL^?1) stimulated HELF cell proliferation and inhibited at high concentrations (1, 5, 10, and 20 μg mL^?1) in a dose‐ and time‐dependent manner. Reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) (except 48 h) showed a significant increase at higher concentrations of PCB 101 than those at the lower concentrations with the passage of time. Antioxidant enzymes such as glutathione peroxidase (GSH‐Px) exhibited decreasing trends in dose and time dependent manner. Lipid peroxidation assay resulted in a significant increase (P < 0.05) of MDA level in PCB 101‐treated HELF cells compared with controls, suggesting that OS plays a key role in PCB 101‐induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of PCB 101 exposure compared to lower concentrations. Overall, we found that HELF cell proliferation was higher at low ROS level and vice versa, which revealed activation of cell signaling‐mediated hormetic mechanisms. The results suggested that PCB 101 has hormetic effects to HELF cells and these were associated with oxidative stress. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1385–1392, 2015.