Clostridioides difficile infection (CDI) is an urgent health threat being the most common healthcare‐associated infection, and its management is a clinical conundrum. Over 450 000 infections are seen ...in the United States with similar incidence seen in the rest of the developed world. The majority of infections seen are mild–moderate with fulminant disease and mortality being rare complications seen in the elderly and in those with comorbidities. The most common complication of CDI is recurrent infection with rates as high as 60% after three or more infections. A dilemma in the management of primary and recurrent CDI is testing due to the high sensitivity of the nucleic acid amplification tests such as the polymerase chain reaction, which leads to clinical false positives if patients are not chosen carefully (with symptoms) before testing. A newer testing regimen involving a 2‐step strategy is emerging using glutamate dehydrogenase as a screening strategy followed by enzyme immunoassay for the C. difficile toxin. Microbiota restoration therapies are the cornerstone of management of recurrent CDI to prevent future recurrences. The most common modality of microbiota restoration is faecal microbiota transplantation, which has been tainted with heterogeneity and adverse events such as serious infectious transmission. The success rates for recurrence prevention from microbiota restoration therapies are over 90% compared with less than 50% of recurrence prevention with courses of antibiotics. This has led to development and emergence of standardized microbiota restoration therapies in capsule and enema forms. Capsule‐based therapies include CP101 (positive phase II results), RBX7455 (positive phase I results), SER‐109 (positive phase III results) and VE303 (ongoing phase II trial). Enema‐based therapy includes RBX2660 (positive phase III data). This review summarizes the principles of management and diagnosis of CDI and focuses on emerging and existing data on faecal microbiota transplantation and standardized microbiota restoration therapies.
The physical and chemical properties of cluster systems at the subnano and nanoscale are often found to differ from those of the bulk and display a unique dependence on size, geometry, and ...composition. Indeed, most interesting are systems which have properties that vary discontinuously with the number of atoms and composition, rather than scale linearly with size. This realm of cluster science where “one atom makes a difference” is undergoing an explosive growth in activity, and as a result of extensive collaborative activities through theory at VCU and experiment at PSU, our groups are recognized as pioneers in this area in which we have been active for many years. Herein we provide an overview of the field with primary focus on our joint undertakings which have spawned the superatom concept, giving rise to a 3-D periodic table of cluster elements and the prospect of using these as building blocks of new nanoscale materials with tailored properties.
Background: Infection by Pseudomonas aeruginosa is common in the Intensive Care Unit (ICU), leading to increased morbidity and mortality. The organism is classified into various phenotypes based on ...the drug resistance pattern, namely, drug-resistant (DR), multi-DR (MDR), extensively DR (XDR), and pan-DR (PDR). We aim to study the incidence of P. aeruginosa phenotypes in a tertiary level ICU. Materials and Methods: We conducted this prospective, observational study for 2 years (January 2014-December 2015) and collected appropriate clinical samples (blood, urine, wound discharge, etc.,) from all the patients admitted to ICU. We excluded patients with known septicemia and P. aeruginosa infection. Group 1 comprised a total 1915 patient samples and Group 2 comprised 100 active surveillance samples, collected from the medical staff and the hospital environment. The data were analyzed using appropriate statistical methods, and a P < 0.05 was considered statistically significant. Results: We isolated 597 pathogenic bacteria out of 1915 specimens, giving a culture positivity rate of 31.2%. Klebsiella (43%), Acinetobacter (22%), and P. aeruginosa (15%) were the top three isolated bacteria. None of the surveillance samples grew P. aeruginosa. Antibiotic resistance studies revealed that 47.7% of P. aeruginosa isolates were DR, 50% were MDR, and 2.3% were XDR phenotype. None of the strains showed PDR phenotype. Conclusion: Our data revealed a high prevalence of DR phenotypes of P. aeruginosa in the ICU. Judicious use of antibiotics and strict infection control measures are essential to reduce the prevalence of drug resistance.
Summary
Background
Cytotoxic T‐lymphocyte‐associated protein‐4 (CTLA‐4) has an important role in T‐cell regulation, proliferation and tolerance. Anti‐CTLA‐4 agents, such as ipilimumab and ...tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune‐related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common.
Aims
To discuss the existing literature and summarise the epidemiology, pathogenesis and clinical features of anti‐CTLA‐4‐associated colitis, and to present a management algorithm for it.
Methods
We searched PubMed for studies published through October 2014 using the terms ‘anti‐CTLA,’ ‘ipilimumab,’ ‘tremelimumab,’ ‘colitis,’ ‘gastrointestinal,’ ‘immune‐related adverse effect,’ ‘immunotherapy,’ ‘melanoma,’ and ‘diarrhoea.’
Results
Watery diarrhoea is commonly associated with anti‐CTLA‐4 therapy (27–54%), and symptoms occur within a few days to weeks of therapy. Diffuse acute and chronic colitis are the most common findings on endoscopy (8–22%). Concomitant infectious causes of diarrhoea must be evaluated. Most cases may be successfully managed with discontinuation of anti‐CTLA‐4 and conservative therapy. Those with persistent grade 2 and grade 3/4 diarrhoea should undergo endoscopic evaluation and require corticosteroid therapy. Corticosteroid‐resistant cases may respond to anti‐tumour necrosis factor‐alpha therapy such as infliximab. Surgery is reserved for patients with bowel perforation or failure of medical therapy.
Conclusion
Given the increasing use of anti‐CTLA‐4 therapy, clinicians must be aware of related adverse events and their management.
Multidrug-resistant (MDR) microorganism development in the gut is frequently the result of inappropriate antibiotic use. Faecal microbiota transplantation (FMT) restores normal gut microbiota in ...patients with Clostridium difficile infection. We hypothesized that it may help in decolonizing MDR organisms (MDROs) and in preventing recurrent MDR infections.
To assess FMT efficacy (eradication rate) for decolonizing MDROs and preventing recurrent MDR infections.
Medline, Embase and Web of Science (inception through 11 February 2019).
Clinical trials, retrospective studies, case reports and case series.
Patients with MDR infections or MDRO colonization treated with FMT.
FMT.
Systematic review.
Twenty-one studies (one randomized clinical trial, seven uncontrolled clinical trials, two retrospective cohort studies, two case series, nine case reports) assessing 192 patients were included. Three studies assessed FMT efficacy in preventing MDR infections; 16 assessed its effect on MDRO colonization; two assessed both. Data from 151 patients were included in the final analyses. In studies with low to moderate risk of bias, the eradication rate was 37.5% to 87.5%. Efficacy was similar in studies looking at infection or colonization and did not differ by length of follow-up. No serious adverse events from FMT were reported. Seven patients died of other causes.
FMT could be used as a treatment for eradicating MDR colonization and possibly preventing recurrent MDR infections, once more supporting efficacy and safety data are available. Larger well-designed randomized controlled trials are needed to further explore this therapy.
The study evaluates the utility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) Vitek MS for identification of microorganisms in the routine clinical ...microbiology laboratory. From May 2013 to April 2014, microbial isolates recovered from various clinical samples were identified by Vitek MS. In case of failure to identify by Vitek MS, the isolate was identified using the Vitek 2 system (bioMerieux, France) and serotyping wherever applicable or otherwise by nucleic acid-mediated methods. All the moulds were identified by Lactophenol blue mounts, and mycobacterial isolates were identified by molecular identification systems including AccuProbe (bioMerieux, France) or GenoType Mycobacterium CM (Hain Lifescience, Germany). Out of the 12,003 isolates, the Vitek MS gave a good overall ID at the genus and or species level up to 97.7% for bacterial isolates, 92.8% for yeasts and 80% for filamentous fungi. Of the 26 mycobacteria tested, only 42.3% could be identified using the Saramis RUO (Research Use Only) database. VITEK MS could not identify 34 of the 35 yeast isolates identified as
C. haemulonii
by Vitek 2. Subsequently, 17 of these isolates were identified as
Candida auris
(not present in the Vitek MS database) by 18S rRNA sequencing. Using these strains, an in-house superspectrum of
C. auris
was created in the VITEK MS database. Use of MALDI-TOF MS allows a rapid identification of aerobic bacteria and yeasts in clinical practice. However, improved sample extraction protocols and database upgrades with inclusion of locally representative strains is required, especially for moulds.
Semiconductor lasers based on two-dimensional photonic crystals generally rely on an optically pumped central area, surrounded by un-pumped, and therefore absorbing, regions. This ideal configuration ...is lost when photonic-crystal lasers are electrically pumped, which is practically more attractive as an external laser source is not required. In this case, in order to avoid lateral spreading of the electrical current, the device active area must be physically defined by appropriate semiconductor processing. This creates an abrupt change in the complex dielectric constant at the device boundaries, especially in the case of lasers operating in the far-infrared, where the large emission wavelengths impose device thicknesses of several micrometres. Here we show that such abrupt boundary conditions can dramatically influence the operation of electrically pumped photonic-crystal lasers. By demonstrating a general technique to implement reflecting or absorbing boundaries, we produce evidence that whispering-gallery-like modes or true photonic-crystal states can be alternatively excited. We illustrate the power of this technique by fabricating photonic-crystal terahertz (THz) semiconductor lasers, where the photonic crystal is implemented via the sole patterning of the device top metallization. Single-mode laser action is obtained in the 2.55-2.88 THz range, and the emission far field exhibits a small angular divergence, thus providing a solution for the quasi-total lack of directionality typical of THz semiconductor lasers based on metal-metal waveguides.
Two classes of gas-phase aluminum-iodine clusters have been identified whose stability and reactivity can be understood in terms of the spherical shell jellium model. Experimental reactivity studies ...show that the$Al_{13}I_{x}^{-}$clusters exhibit pronounced stability for even numbers of I atoms. Theoretical investigations reveal that the enhanced stability is associated with complementary pairs of I atoms occupying the on-top sites on the opposing Al atoms of the$Al_{13}^-$core. We also report the existence of another series,$Al_{14}I_{x}^{-}$, that exhibits stability for odd numbers of I atoms. This series can be described as consisting of an$Al_{14}I_{3}^{-}$core upon which the I atoms occupy on-top locations around the Al atoms. The potential synthetic utility of superatom chemistry built upon these motifs is addressed.
PDF
