Evaluating the measures taken to contain a Candida auris outbreak in a tertiary care hospital in South India: an outbreak investigational study.

BACKGROUND: Candida auris infections are an emerging global threat with poor clinical outcome, high mortality rate, high transmission rate and outbreak potential. The objective of this work is to describe a multidisciplinary approach towards the investigation and containment of a Candida auris outbreak and the preventive measures adopted in a resource limited setting. METHODS: This outbreak investigational study was conducted at a 1300-bedded tertiary care academic hospital in South India. The study included 15 adult inpatients with laboratory confirmed Candida auris isolates. The outbreak cluster was identified in adult patients admitted from September 2017 to 2019. The system response consisted of a critical alert system for laboratory confirmed Candida auris infection and multidisciplinary 'Candida auris care team' for patient management. The team implemented stringent Infection Prevention and Control (IPC) measures including patient cohorting, standardized therapy and decolonization, staff training, prospective surveillance and introduction of Candida auris specific care bundle. RESULTS: Two outbreak clusters were identified; first cluster occurring between October and November 2017 and the second cluster in May 2018. The cohorts consisted of 7 and 8 Candida auris positive patients in the first and second waves of the outbreak respectively with a total survival rate of 93% (14/15). Deployment of containment measures led to gradual decline in the incidence of adult Candida auris positive cases and prevented further cluster formation. CONCLUSIONS: The sustained implementation of guideline and evidence-based IPC measures and training of healthcare workers for improving awareness on systematically following standardized protocols of Candida auris related IPC practices successfully contained Candida auris outbreaks at our hospital. This demonstrates the feasibility of establishing a multidisciplinary model and bundling of practices for preventing Candida auris outbreaks in a Low- and Middle-income country.

A Green Approach to the Synthesis of α-Amino Phosphonate in Water Medium: Carbene Insertion into the N-H Bond by Cu(I) Catalyst.

Synthesis of amino phosphonates is more important owing to their significant applications in the biological systems. There are few methods already known in the literature to make these molecules; however, known methods have their own disadvantages. In this regard, synthesis of different kinds of amino phosphonates have been achieved via phosphonate substituted carbene insertion into the N-H bond of aniline catalyzed by readily available copper salt under mild reaction conditions in water. In order to find an efficient catalyst for carbene insertion reaction in neat water, a large number of transition metal catalysts were screened, and we found that the [Cu(CH3CN)4]ClO4 was the best catalyst under employed reaction conditions. Using this environmentally benign methodology (copper catalyzed reaction in water), a large number of biologically important amino phosphonates have been synthesized, isolated (37 examples), and characterized using standard analytical and spectroscopic techniques.

Syntheses, structural, photophysical and theoretical studies of heteroleptic cycloplatinated guanidinate(1-) complexes bearing acetylacetonate and picolinate ancillary ligands.

Cycloplatination of symmetrical N,N',N''-triarylguanidines, (ArNH)2C[double bond, length as m-dash]NAr with cis-[Pt(TFA)2(S(O)Me2)2] in toluene afforded cis-[Pt(TAG)(TFA)(S(O)Me2)] (TAG = triarylguanidinate(1-)-κC,κN; TFA = OC(O)CF3; 6-9) in 75-82% yields. The reactions of 6-9 and the previously known cis-[Pt(TAG)X(S(O)Me2)] (X = Cl (1) and TFA (2-5)) with acetylacetone (acacH) or 2-picolinic acid (picH) in the presence of a base afforded [Pt(TAG)(acac)] (acac = acetylacetonate-κ2O,O'; 10-18) and [Pt(TAG)(pic)] (pic = 2-picolinate-κN,κO; 19) in high yields. The new complexes were characterised by analytical, IR and multinuclear NMR spectroscopies. Further, molecular structures of 11, 12, 13·0.5 toluene and 14-19 were determined by single crystal X-ray diffraction. Absorption spectra of 10-19 in solution and their emission spectra in crystalline form were measured. Platinacycles 10-19 are bluish green light emitter in the crystalline form, and emit in the λPL = 488-529 nm range (11 and 13-19) while 12 emits at λPL = 570 nm. Unlike other platinacycles, the emission band of 12 is broad, red shifted, and this pattern is ascribed to the presence of an intermolecular N-H⋯Pt interaction involving the endocyclic amino unit of the six-membered [Pt(TAG)] ring and the Pt(ii) atom in the adjacent molecule in an asymmetric unit of the crystal lattice. Lifetime measurements were carried out for all platinacycles in crystalline form, which revealed lifetime in the order of nanoseconds. The origin of absorption and emission properties of 11, 15, 18 and 19 were studied by TD-DFT calculations.

Study of Non-Covalent Interactions Present in the Tapinarof-Ethanol System with Special Emphasis on Hydrogen-Bonding Interactions.

In this study, the effect of non-covalent interaction in the tapinarof-EtOH systems is evaluated, particularly the hydrogen-bonding interaction using density functional theory in a gas phase. From the optimization results and the binding energy calculated thereafter, it is concluded that interaction in the employed system occurs between the O-H groups on tapinarof and the oxygen atom of EtOH molecules existing in the vicinity of the O-H group. These interactions were concluded to be those of the weak hydrogen bonds by carrying out the reduced gradient approach and QTAIM analysis, which are basically electron-density-based topological analyses. The charge localization between the donor-acceptor moieties was analyzed using the NBO analysis. Using the LED analysis, the binding energy between the tapinarof and EtOH was partitioned into different energy terms centered on a domain-based local pair natural orbital coupled cluster method. Thus, the electronic environment of the tapinarof-EtOH systems is evaluated.

Investigating the structure, bonding, and energy decomposition analysis of group 10 transition metal carbonyls with substituted terminal germanium chalcogenides [M(CO)3GeX] (M = Ni, Pd, and Pt; X = O, S, Se, and Te) complexes: insight from first-principles calculations.

CONTEXT: This research focused on the theoretical investigation of transition metal carbonyls [M(CO)4] coordinated with terminal germanium chalcogenides complexes [M(CO)3GeX], where M represents Ni, Pd, and Pt and X represents O, S, Se, and Te labeled 1-15. While the notable complexes M(CO)4 (where M = Ni, Pd, Pt) numbered 1, 6, and 11 are of significance, substituting one of the CO ligands in 1, 6, and 11 with a GeX ligand (where X = O, S, Se, or Te) result in substituted complexes (2-5, 7-10, and 11-15). Substituting of the CO ligand slightly alters these bond angles. Specifically, the ∠CMC bond angles for [Ni] complexes range from 111.9° to 112.2°, for [Pd] complexes from 111.4° to 111.7°, and for [Pt] complexes from 112.4° to 112.8°. These findings indicate a minor deviation from the tetrahedral geometry due to the influence of the new GeX ligand. Similarly, there is a slight change in the geometry of the metal complexes, where the ∠GeMC angles for [Ni] complexes are between 106.7° and 106.9°, for [Pd] complexes between 107.2° and 107.5°, and for [Pt] complexes between 105.9° and 106.4°. Comparing among the substituted GeX complexes, those containing GeTe exhibit a higher natural bond orbital (NBO) contribution from the Ge atom compared to the M atom. Consequently, based on the above observations, it can be inferred that GeX acts as an effective sigma donor in contrast to carbonyl compounds. Results of energy decomposition analysis (EDA) for the M-CO bond in 1, 6, and 11 and for the M-GeX bond in the other [M(CO)3(GeX)] complexes where M = Ni, Pd and Pt. The percentage contribution of ΔEelstat and ΔEorb shows a relatively identical behavior for all ligands in case of each metal complexes. METHODS: Density functional theory (DFT) calculations were conducted using the B3LYP/gen/6-31G*/LanL2DZ level of theory to examine transition metal carbonyls [M(CO)4] coordinated with terminal germanium chalcogenides complexes [M(CO)3GeX], where M represents Ni, Pd, and Pt, and X represents O, S, Se, and Te labeled 1-15 utilized through the use of Gaussian 09W and GaussView 6.0.16 software packages. Post-processing computational code such as multi-wave function was employed for results analysis and visualization.

Repurposing synthetic and natural derivatives induces apoptosis in an orthotopic glioma-induced xenograft model by modulating WNT/ß-catenin signaling.

BACKGROUND: Glioblastomas arise from multistep tumorigenesis of the glial cells. Despite the current state-of-art treatment, tumor recurrence is inevitable. Among the innovations blooming up against glioblastoma, drug repurposing could provide profound premises for treatment enhancement. While considering this strategy, the efficacy of the repurposed drugs as monotherapies were not up to par; hence, the focus has now shifted to investigate the multidrug combinations. AIM: To investigate the efficacy of a quadruple-combinatorial treatment comprising temozolomide along with chloroquine, naringenin, and phloroglucinol in an orthotopic glioma-induced xenograft model. METHODS: Antiproliferative effect of the drugs was assessed by immunostaining. The expression profiles of WNT/ß-catenin and apoptotic markers were evaluated by qRT-PCR, immunoblotting, and ELISA. Patterns of mitochondrial depolarization was determined by flow cytometry. TUNEL assay was performed to affirm apoptosis induction. In vivo drug detection study was carried out by ESI-Q-TOF MS analysis. RESULTS: The quadruple-drug treatment had significantly hampered glioma proliferation and had induced apoptosis by modulating the WNT/ß-catenin signaling. Interestingly, the induction of apoptosis was associated with mitochondrial depolarization. The quadruple-drug cocktail had breached the blood-brain barrier and was detected in the brain tissue and plasma samples. CONCLUSION: The quadruple-drug combination served as a promising adjuvant therapy to combat glioblastoma lethality in vivo and can be probed for translation from bench to bedside.

A quality improvement initiative to improve the appropriateness of candidemia management by the implementation of a comprehensive candidemia care bundle at a tertiary care hospital in South India: Results of a quasi-experimental study.

ABSTRACT: Management of candidemia in developing countries like India encounters laxity in appropriate clinical management and challenges in terms of healthcare capacity, despite its association with high morbidity and mortality. Our study aims to evaluate the impact of a comprehensive candidemia care bundle implementation on appropriateness of therapy and major clinical outcomes.The single-center, quasi-experimental study conducted at a south Indian tertiary care center included adult patients diagnosed with candidemia. Following a retrospective review of candidemia patients of the pre-implementation period (January 2013-December 2015), the hospital antifungal stewardship team instituted a clinical pharmacist driven comprehensive candidemia care bundle for candidemia patients during the post-implementation period (October 2017-2019) and its impact on appropriateness of antifungal prescriptions and inpatient mortality was evaluated.The study included 175 patients with candidemia, comprising of 103 patients in the pre-implementation period and 72 patients in the post-implementation period. Appropriateness of antifungal prescriptions rose to 65% during post-implementation period from 30% observed in pre-implementation phase (P = .0005). The inhospital mortality rate reduced from 40% in the pre-implementation phase to 36% in the post-implementation phase, recording a 10% reduction over 2 years post-implementation (P = .26). No significant difference was observed in terms length of stay (P = .17).Our study demonstrates the successful implementation of an antifungal stewardship led comprehensive care bundle in a low middle income countries setting. The results of our study will have profound implications in improving the appropriateness of management of candidemia and feasibility of scaling up to wider settings could be explored.

Antimicrobial Stewardship and Its Impact on the Changing Epidemiology of Polymyxin Use in a South Indian Healthcare Setting.

Polymyxins being last resort drugs to treat infections triggered by multidrug-resistant pathogens necessitates the implementation of antimicrobial stewardship program (ASP) initiatives to support its rational prescription across healthcare settings. Our study aims to describe the change in the epidemiology of polymyxins and patient outcomes following the implementation of ASP at our institution. The antimicrobial stewardship program initiated in February 2016 at our 1300 bed tertiary care center involved post-prescriptive audits tracking polymyxin consumption and evaluating prescription appropriateness in terms of the right indication, right frequency, right drug, right duration of therapy and administration of the right loading dose (LD) and maintenance dose (MD). Among the 2442 polymyxin prescriptions tracked over the entire study period ranging from February 2016 to January 2020, the number of prescriptions dropped from 772 prescriptions in the pre-implementation period to an average of 417 per year during the post-implementation period, recording a 45% reduction. The quarterly patient survival rates had a significant positive correlation with the quarterly prescription appropriateness rates (r = 0.4774, p = 0.02), right loading dose (r = 0.5228, p = 0.015) and right duration (r = 0.4361, p = 0.04). Our study on the epidemiology of polymyxin use demonstrated favorable effects on the appropriateness of prescriptions and mortality benefits after successful implementation of antimicrobial stewardship in a real-world setting.

Awareness, Prevalence and Factors Associated with Respiratory Morbidities Among Selected Petrol Pump Workers in Bengaluru City?

INTRODUCTION: Petrol pump workers are exposed to fumes emanated during petrol filling and vehicular exhaust thus falling prey to several respiratory diseases. OBJECTIVES: To assess the awareness and prevalence of respiratory morbidities among petrol pump workers of selected petrol pumps in Bangalore. METHODOLOGY: This cross-sectional study was conducted among 158 petrol pump workers from 11 selected pumps in Bengaluru. Following IEC approval, the baseline socio-demographic data, knowledge regarding respiratory morbidities and current morbidity pattern were ascertained. Medical examination and Peak Expiratory Flow rate (PEFR) was estimated. RESULTS: The 158 workers were all male, mostly between 18-27 years (65.19%) and high school educated (49.37%). Knowledge regarding respiratory morbidities was 56%, while prevalence of respiratory morbidity was 61%. Those workers who had completed their higher education (>10th standard), earning monthly income (>Rs. 5000) had better knowledge regarding respiratory morbidities. RECOMMENDATION: Pre-employment and regular medical examination including lung function tests and promotion of use of PPEs to be implemented.

Factors associated with completion of pre-kidney transplant evaluations.

This study sought to examine various factors that may prevent transplant candidates from completing their transplant workup prior to listing. We reviewed the records of 170 subjects (cases = 100, controls 70) who were either on dialysis or had less than 20 mL/min creatinine clearance and were therefore candidates for preemptive transplantation. Approximately, 56% of preemptive patients completed their workup, while only 36% of patients on dialysis completed their workup. Our data revealed that factors contributing toward completion of workup included intrinsic motivation (four times more likely), lack of specific medical comorbidities (three times more likely), and preemptive status (two times more likely). Among patients on dialysis, intrinsic motivation (five times more likely) and absence of cardiovascular complications (four times more likely) were associated with completion. When comparing patients on dialysis to patients not on dialysis, there were significant differences between the two groups in distance from home to the transplant center, level of education, and presence of medical comorbidities. We believe that targeted interventions such as timely referral, providing appropriate educational resources, and development of adequate support systems, have the potential to improve workup compliance of patients with advanced chronic kidney disease, including those on dialysis.