Antibiotic susceptibility in Endophthalmitis Management Study and intravitreal antibiotic practice trend in India-EMS Report #5.

AIM: Analyze antibiotic susceptibility in the Endophthalmitis Management Study (EMS) and compare it with the current intravitreal antibiotic practice trend of members of the Vitreoretinal Society of India (VRSI) practicing in India. METHODS: The microbiology work-up of undiluted vitreous included microscopy, culture-susceptibility, polymerase chain reaction (PCR), and next-generation sequencing (NGS). VRSI members were invited to the survey. The EMS conventional culture-susceptibility (PCR and NGS excluded) results were compared vis-a-vis gram-positive cocci (GPC), gram-negative bacilli (GNB), and less commonly used antibiotics with the current recommended intravitreal antibiotics. p < 0.05 was considered significant. RESULTS: Culture and positivity (culture + PCR/NGS) positivity was 28.8% and 56.1%, respectively. GPC was most susceptible to cefazolin, linezolid, and vancomycin; GNB was most susceptible to amikacin, ceftazidime, colistin, and imipenem. There was no susceptibility difference between cefazolin and vancomycin (p = 0.999) and between ceftazidime and imipenem (p = 1.0). Colistin was superior to ceftazidime (p = 0.047) against GNB. The GNB resistant to amikacin (n = 14) were equally susceptible to ceftazidime and colistin; resistant to ceftazidime (n = 16) were susceptible to colistin; and resistant to colistin (n = 7) were susceptible to ceftazidime. The preference of VRSI members (n = 231) practicing in India was a vancomycin-ceftazidime combination (82%), vancomycin for GPC (94%), ceftazidime for GNB (61%), and voriconazole for fungi (74%). CONCLUSION: In EMS, GPC had good susceptibility to vancomycin; GNB had good susceptibility to ceftazidime and colistin. Given the lower resistance of colistin, a vancomycin-colistin combination could be an alternative empiric treatment in post-cataract endophthalmitis in India.

PRESENTATIONS AND FACTORS AFFECTING OUTCOME OF RHEGMATOGENOUS RETINAL DETACHMENT WITH CHOROIDAL DETACHMENT: An Indo-Taiwanese Study.

PURPOSE: To report the clinical settings, management, and factors associated with outcomes of rhegmatogenous retinal detachment with concurrent choroidal detachment. METHODS: Retrospective, consecutive, multicenter case series from January 2014 to January 2021 were included. Cases were from a tertiary eye care center in India and Taiwan. RESULTS: Overall 303 eyes were included. Mean age was 43.72 ± 20.64 years (median 46). Best-corrected presenting visual acuity was 1.79 ± 0.92 logMAR (median 2.10) (Snellen 20/1,233). Forty-four patients (17.91%) received preoperative steroids. Final visual acuity was 1.33 ± 0.94 logMAR (median 1.10) (Snellen 20/427). Favorable anatomic outcome was seen in 200/303 (66%), whereas favorable functional outcome was seen in 128/303 (42.20%). Factors predicting favorable anatomic outcome were absence of phakic lens status (odds ratio [OR] 2.76), absence of proliferative vitreoretinopathy worse than Grade A (OR 7.69), use of preoperative steroids (OR 4.50), and use of an encircling band (3.85). Factors predicting favorable functional outcome were better presenting visual acuity (OR 3.03), absence of phakic lens status (OR 4.93), absence of proliferative vitreoretinopathy worse than Grade A (OR 10.41), and use of preoperative steroids (OR 7.24). CONCLUSION: Administration of preoperative steroids, use of an encircling band during surgery, and pseudophakic status of the eye were found to have better outcomes in rhegmatogenous retinal detachment with concurrent choroidal detachment.

Green synthesized cobalt nanoparticles from Trianthema portulacastrum L. as a novel antimicrobials and antioxidants.

Trianthema portulacastrum is a dietary and medicinal plant that has gained substantial importance due to its pharmacological properties. This plant was used for its various healing properties since the ancient period in ayurvedic system of medicine. The green synthesis technique is an eco-friendly as well as cost effective technique which can produce more biocompatible nanoparticles when compared with those fabricated by physio-chemical methods. Therefore, nanoparticles produced by green synthesis are credible alternatives to those which are produced by conventional synthesis techniques. This research mainly aims to produce nanoparticles with the methanolic leaf extract of T. portulacastrum. The optimized nanoparticles were further analyzed for anti-fungal, anti-bacterial and antioxidant properties. Disk diffusion assay was used for the determination of the antimicrobial property and on the other hand, DPPH radical scavenging assay as well as hydrogen peroxide scavenging activity proved the antioxidant property of the formulation. The study revealed that Escherichia coli (gram negative strain) shows greater zone of inhibition when compared with Bacillus subtilis (gram positive bacteria). The nanoparticles have also been reported to show significant anti-fungal activity against the strains of Aspergillus niger and Fusarium oxysporum which proves its desirability for its further use against both bacterial as well as fungal infections. The novel formulation can be explored dually as antimicrobial and antioxidant agent.

Clinical Presentations, Management, and Factors Affecting Outcomes in Posterior Segment Open Globe Injuries: An Analysis of 2,360 Eyes.

INTRODUCTION: The aim of the study was to report the clinical presentations, management, and factors affecting the outcomes of posterior segment open globe injuries in 2,360 consecutive eyes. METHODS: This was a retrospective, consecutive, non-comparative interventional case series. All cases with scleral and corneoscleral wounds presenting to these centers from January 2014 to January 2021 were included. The cases were defined according to the Birmingham Eye Traumatology Terminology system (BETTs) classification. The Ocular Trauma Score (OTS) was applied to the dataset. RESULTS: Mean age of presentation was 36.63 ± 19.92 years (median 35 years). Penetrating trauma accounted for 70.92%, rupture for 18.6%, perforation for 4.60%, and IOFB in 5.88% eyes. In 76.60%, the location of injury involved zone 1 extending till zone 2, while in 23.40% it involved zone 2 and/or zone 3. Vision at presentation was logMAR 3.03 ± 0.99 and at the last visit was logMAR 2.47 ± 1.42 (p < 0.0001). Time interval between presentation to the treatment center and globe repair was 13.93 ± 19.56 h (median 7.60 h). Favorable functional outcomes were seen in 29.20% eyes and favorable anatomic outcomes in 66.90%. Decreasing age at presentation, penetrating injury instead of rupture or perforating injury, a higher OTS, absence of corneal involvement, absence of retinal detachment at presentation, and absence of concurrent orbital fracture were associated with a favorable functional outcome (>20/200). Final visual acuity in logMAR correlated with the OTS value calculated at presentation. CONCLUSIONS: In the absence of retinal detachment and orbital fracture, posterior open globe injuries typically have a favorable functional outcome. OTS correlated with the final visual acuity.

COVID-19 reduced scleral buckling training in fellows and shifted young ophthalmologists' preference toward vitrectomy: An Asia-Pacific survey.

BACKGROUND: To assess rhegmatogenous retinal detachment (RRD) surgery trends and training among young ophthalmologists (YOs, vitreoretinal fellows or attendings/consultants with ≤10 years of independent practice) and the impact of the COVID-19 pandemic. METHODS: An anonymous online survey was completed by 117 YOs in the Asia-Pacific regarding their RRD surgery experiences in 2021-2022. RESULTS: To achieve a 90% probability of surgical competency, 91 vitrectomy and 34 scleral buckling (SB) completions during fellowship were needed. In total, 49 (41.9%) YOs had fellowship affected by COVID-19. In the COVID versus pre-COVID era, however, the volume of SB completions per fellowship year decreased significantly (median [IQR] 3.3 [1.5, 9] vs. 13 [6.5, 23]; p < 0.001) and was lower than the required volume to achieve competency. YOs were less confident in conducting SB versus vitrectomy (3.5 ± 1.1 vs. 4.2 ± 0.8, p < 0.001), and they reported a decrease in the proportion of SB (-3.1%, p = 0.047) and an increase in the proportion of vitrectomy (+4.8%, p < 0.001) after the pandemic outbreak. Apart from RRD clinical characteristics, surgical confidence is among the main factors that affect surgical method decisions. During the pandemic, more YOs may have avoided SB due to the need for general anaesthesia, leading to longer surgical time and risk of viral transmission during intubation/extubation. CONCLUSIONS: SB surgical exposure is suboptimal in most fellowship programs in the 11 Asia-Pacific countries/regions we surveyed and further declined during the COVID-19 pandemic. YOs are less confident in performing SB, leading to a trend toward primary vitrectomy since the COVID-19 outbreak.

CLINICAL PRESENTATIONS, MICROBIOLOGY, AND FACTORS AFFECTING MANAGEMENT OUTCOMES IN LENS ABSCESS WITH CONCURRENT ENDOPHTHALMITIS.

PURPOSE: To describe the clinical presentations, microbiology, and factors affecting management outcomes in lens abscess with concurrent endophthalmitis. MATERIALS: A retrospective, consecutive, noncomparative series including cases of endophthalmitis with concurrent lens abscess from January 2017 to May 2021. RESULTS: This study included 102 eyes, predominantly male (71.6%). All cases were posttrauma. The mean age noted was 30.47 ± 19.51 years. Presenting vision was logMAR 3.02 ± 0.74 (median 3.5, Snellen 20/63245). A favorable anatomical outcome was seen in 63 eyes (61.8%), while a final favorable functional outcome was seen in 51 eyes (50%). The mean follow-up duration was 10.04 ± 10.87 months (median 4.5). Final vision was logMAR 2.13 ± 1.32 (median 2.7, Snellen 20/10023) (P < 0.0001). The mean follow-up duration was 10.04 ± 10.87 months (median 4.5). Increasing age (OR 1.04, P = 0.02), female sex (OR 7.91, P = 0.007), initial intervention of vitrectomy instead of limited vitreous biopsy (OR 11.72, P = 0.009), and a negative vitreous culture (OR 14.28, P = 0.0004) predicted a favorable anatomical outcome. Absence of a corneal infiltrate (OR 11.11, P = 0.003) and initial intervention of vitrectomy instead of a limited vitreous biopsy (OR 21.96, P < 0.0001) predicted a favorable functional outcome. Culture positivity was seen in 56.9% of the cases. Gram-positive organisms were predominant (n = 41) followed by Gram-negative organisms (n = 12) and fungi (n = 10). CONCLUSION: Lens abscess can present concurrently with traumatic endophthalmitis. Management should involve the complete removal of the crystalline lens along with a pars plana vitrectomy for optimal outcomes.

CULTURE POSITIVITY RATES OF DEEP VITREOUS BIOPSY UNDER AIR VIS-À-VIS CONVENTIONAL ANTERIOR VITREOUS BIOPSY IN ENDOGENOUS ENDOPHTHALMITIS.

PURPOSE: To describe the comparison of the culture positivity rates of deep vitreous biopsy under air and conventional anterior vitreous biopsy in endogenous endophthalmitis. MATERIALS: A retrospective, consecutive, comparative series including cases of endogenous endophthalmitis from January 2014 to January 2021. They were divided into those where conventional anterior vitreous biopsy was taken and those where a deep biopsy was taken under air (DBA group). The culture positivity rate among the two groups was compared, and factors affecting the same were analyzed by a regression analysis. RESULTS: There were 140 eyes in the conventional anterior vitreous biopsy group and 44 eyes in the DBA group. Sex, age, duration of symptoms, underlying systemic illness, presenting vision in logMAR, and total number of vitreous interventions were comparable between the two groups. Visual outcome was better in patients undergoing DBA as compared with those who underwent conventional anterior vitreous biopsy , (1.28 ± 1.01 logMAR, 20/380 vs. 1.88 ± 1.33 logMAR, 20/1,500, P = 0.03). No case in the DBA group developed retinal detachment or any complication attributable to the technique. In the conventional anterior vitreous biopsy group, the culture positivity was seen in 43/140 samples (30.71%), and in the DBA group, it was noted in 29/44 samples (65.9%). Taking a DBA was the only factor that was significant both in bivariate (odds ratio 4.36, 95% confidence interval 2.12-8.95, P < 0.0001) and multivariate analysis (odds ratio 4.02, 95% confidence interval 3.1-7.43, P < 0.0001). CONCLUSION: Vitreous sampling can be performed from the deep vitreous cavity in endogenous endophthalmitis safely and effectively under air infusion, improving the culture positivity rates.

Choroidal vascularity index in thyroid eye disease: comparison with controls and application in diagnosing non-inflammatory active disease.

PURPOSE: To report the differences in choroidal vascularity index (CVI) in thyroid eye disease (TED) and normals and its discriminatory value for differentiating various stages of TED. METHODS: Prospective, cross-sectional, non-interventional imaging study. Ninety-four eyes of 54 patients were included and divided into 5 groups - normal controls (C), inactive TED (I), active TED (A), non-inflammatory active TED (NIA) and systemic hyperthyroid disorder but no TED (SYS). Choroidal images were acquired using the swept-source optical coherence tomography and the choroid was binarized to calculate the CVI. RESULTS: Ninety-four eyes were included. Mean age was 44.52 ± 10.02 years (median 46 years, range 19-65 years). Mean IOP was 16.1 ± 3.37 mm Hg (median 16 mm Hg, range 16-24 mm Hg). Mean Spherical equivalent (SE) was -0.08 ± 1.86 diopters (median 0, range -2.5 to +2.25). Intra-rater agreement was 0.84 (p < 0.001). Inter-rater agreement was noted to be 0.85 (p < 0.001) for consistency and 0.77 (p < 0.001) for absolute agreement. CVI in the A group was 70.11 ± 3.38% and in the NIA group was 69.32 ± 3.5%. Both were comparable to each other and significantly higher than the C, I and SYS groups (p < 0.001). Multiple regression showed that the Clinical Activity Score (CAS) had a positive effect and spheroequivalent had a negative effect on the CVI. At CVI of 66.83%, active TED can be diagnosed with sensitivity of 91.67% and specificity of 82.14%                 . CONCLUSIONS: CVI is significantly higher in active TED and NIA TED compared to other groups. It has a good value in differentiating the non-inflammatory active TED eyes from the inactive eyes.

Retinal vascularity, nerve fiber, and ganglion cell layer thickness in thyroid eye disease on optical coherence tomography angiography.

PURPOSE: To compare the retinal vascularity, peripapillary vascularity, nerve fiber layer thickness and ganglion cell layer thickness between active, inactive thyroid eye disease (TED) and healthy eyes. METHODS: Retrospective comparative cross-sectional cohort study. Patients with TED, active and inactive on the VISA score, and healthy eyes were included. All patients underwent optical coherence tomography angiography with detailed demographic and clinical data capture. Using automated software, retinal and peripapillary vascularity index, nerve fiber layer thickness, and ganglion cell layer thickness were calculated and were compared between the groups. RESULTS: Twenty-four eyes with active TED, 102 eyes with inactive TED and 52 healthy eyes were included. Independent sample t test was used to compare parametric data and Mann-Whitney test to compare non-parametric data. The age and gender were comparable across groups. The peripapillary vascularity index (26.82 ± 4.13 versus 34.92 ± 5.08, p = .002) and the macular vascularity index (20.32 ± 2.5 versus 31.21 ± 3.89, p < .0001) were reduced in active TED eyes versus inactive eyes. Macular vascularity index was comparable in the inactive versus the healthy eyes. The RNFL thickness was increased in the active TED eyes versus the inactive eyes (45.11 ± 18.3 versus 35.55 ± 7, p = .03) and active versus healthy eyes (45.11 ± 18.3 versus 36.28 ± 7.89, p = .03). Ganglion cell layer thickness between all three groups was comparable. CONCLUSION: Decrease in peripapillary and macular vascular density and increase in RNFL thickness are seen in active TED compared to inactive TED and healthy eyes. In disease inactivity, these parameters are comparable to healthy eyes.

Antidepressant activity of Spathodea campanulata in mice and predictive affinity of spatheosides towards type A monoamine oxidase.

The antidepressant activity of Spathodea campanulata flowers was evaluated in mice and in silico. When tested at doses of 200 and 400 mg/kg, the methanol extract of S. campanulata (MESC) showed dose-dependent antidepressant activity in the force swim test (FST), tail suspension test (TST), lithium chloride-induced twitches test and the open field test. In FST and TST, animals treated with MESC demonstrated a significant decrease in the immobility period compared to the control group. The lithium chloride-induced head twitches were significantly reduced following administration of MESC. The latter, at the dose of 400 mg/kg, also significantly reduced locomotor activity. Following administration of MESC, changes in the levels of serum corticosterone, and of norepinephrine, dopamine, serotonin, 4-hydroxy-3-methoxyphenylglycol (MHPG), 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in different brain regions using HPLC. The presence of spatheoside A (m/z 541) and spatheoside B (m/z 559) in MESC was detected using HPLC/ESI-MS. These two iridoids demonstrated a high predictive binding affinity for the active site of the type A monoamine oxidase (MAO-A) enzyme with scores of 99.40 and 93.54, respectively.  These data suggest that S. campanulata flowers warrants further investigation as a source of novel templates for antidepressive drugs.

Management of Endophthalmitis with and without Topical Antibiotics: A Case-Control Study.

PURPOSE: The aim of this study was to compare the management outcome of endophthalmitis with and without the use of topical antibiotics. METHODS: A retrospective comparative chart review of 2 cohorts of endophthalmitis (other than those associated with open-globe injury, keratitis, or wound site infection), one managed with topical antibiotics (TA group) and one without (NTA group), was performed. RESULTS: The study included a total of 270 eyes of 270 patients. Of these, 169 eyes were in the TA group and 101 were in the NTA group. Post-cataract surgery was the most common etiology, accounting for 81.06 and 78.2% of cases, respectively (p = 0.57). A favorable functional outcome at the last visit was seen in 37.5 and 39.6% of eyes (p = 0.73), and a favorable anatomic outcome was noted in 61.2 and 49.5% of eyes (p = 0.06), respectively. The median follow-up was 3.5 and 9 months, respectively (p < 0.0001). Susceptibilities to the common antibiotics used (vancomycin, ceftazidime, and amikacin) were comparable, with the exception of imipenem, for which the susceptibility noted was 95 and 66%, respectively (p = 0.01). Culture positivity in the TA group was seen in 72 out of 169 eyes (42.6%), while in the NTA group it was seen in 98 out of 101 eyes (97.02%; p < 0.0001). CONCLUSION: Topical antibiotics do not give any added advantage in the management of endophthalmitis otherwise being treated with intravitreal antibiotics and standard vitrectomy techniques.

Evaluation of vitreous Procalcitonin as a diagnostic biomarker in infectious endophthalmitis.

BACKGROUND: Endophthalmitis is a potentially blinding intraocular infection following intraocular surgery or trauma. Prompt diagnosis and treatment are important in preventing devastating visual complications. Procalcitonin (PCT) is a promising biomarker for diagnosing bacterial infections. The aim of the study was to measure vitreous PCT in infectious endophthalmitis and assess its utility as a biomarker. METHODS: In this prospective study, vitreous was collected from patients with non-infectious retinal disorders and infectious endophthalmitis. PCT was measured using the Human Procalcitonin ELISA Kit. The diagnostic performance of PCT was calculated via receiver operating characteristic curves. RESULTS: The study included three groups: patients with non-infectious retinal conditions, culture-positive endophthalmitis, and culture-negative endophthalmitis. The average PCT was 75.74 ± 26.8 pg mL-1, 100.24 ± 12.9 pg mL-1, and 126.41 ± 26.47 pg mL-1 in control, culture-negative, and culture-positive endophthalmitis, respectively. There was a significant difference in the vitreous PCT in the study and control groups (p = 0.04), but not between culture-positive and culture-negative endophthalmitis (p = 0.65). The sensitivity (66.7%) and specificity (65%) for PCT with a cut-off of ≤ 54.88 pg mL-1(p = 0.31) implied that its diagnostic accuracy was not significant. But there was a significant difference in gram-negative (68.2 ± 16.5 pg mL-1) and gram-positive (175.09 ± 45 pg mL-1) (p = 0.02) bacterial infections; the sensitivity and specificity were 70%, with a cut-off of ≤ 82.3 pg mL-1. CONCLUSIONS: This study showed that vitreous procalcitonin concentration might not be a suitable biomarker for diagnosing culture-negative endophthalmitis though it could help distinguish between gram-positive and gram-negative infections.

Comparing clinical outcomes of macular hole surgeries performed by trainee surgeons using a 3D heads-up display viewing system versus a standard operating microscope.

PURPOSE: To compare the surgical outcomes of macular hole (MH) surgery performed by trainee surgeons using a three-dimensional heads-up display (3D HUD) versus a standard operating microscope (SOM). MATERIALS AND METHODS: A retrospective review of all consecutive medical records patients operated on for MHs by a trainee surgeon between 2017 and 2020 using either 3D HUD or SOM was performed. Minimum hole diameter, maximum hole diameter, total surgical time, and MH closure rates were compared between the two groups. MH retinal detachments, traumatic MHs, and MHs for which inverted internal limiting membrane flaps were used were excluded from the study. RESULTS: Trainee surgeons operated on 51 patients using 3D HUD and 63 patients using SOM. Age at presentation, intraocular pressure (IOP) at diagnosis, maximum hole diameter, minimum hole diameter, surgical time, duration between diagnosis and surgery were comparable between both groups. MH closure rate was significantly (p < 0.004) higher in the 3D HUD group (n = 44, 86.3%) than that of the SOM group (n = 38, 60.3%). There were no postoperative adverse events such as glaucoma or retinal detachment in either group. Other than the viewing technique, there were no significant variables associated with MH closure in the two groups. CONCLUSION: Surgeries conducted by trainee surgeons using 3D HUD had higher MH closure rates than those using SOM.

CLINICAL PRESENTATIONS, DIAGNOSIS, AND MANAGEMENT OUTCOMES OF CURVULARIA ENDOPHTHALMITIS AND A REVIEW OF LITERATURE.

PURPOSE: To describe the clinical presentation and management of Curvularia endophthalmitis and compare with previous published literature. METHODS: Retrospective interventional comparative case series and literature review. Eight cases with culture-proven Curvularia endophthalmitis from January 2000 to March 2018 underwent vitrectomy/vitreous biopsy, intravitreal antibiotic with or without additional procedures as appropriate. The undiluted vitreous biopsy was subjected to microbiologic evaluation. Pre-existing literature was reviewed, and the current outcomes were compared with them. The mean age at presentation, etiology, number of interventions, interval between inciting event and presentation, type of intravitreal antifungal used, anatomical, and the functional outcomes were reported and compared with pre-existing literature. A favorable anatomical outcome was defined as preservation of the globe, absence of hypotony, attached retina, and absence of active inflammation at the last visit. RESULTS: In the current series, there were 4 men and 4 women. Mean age at presentation was 34.5 ± 13.51 years (median 30 years). Inciting event was open-globe injury in five cases and cataract surgery, trabeculectomy, and endogenous cause in one case each. Presenting visual acuity was ≥20/400 in 3 cases at presentation and 5 cases at the last visit. One case with staphyloma and endophthalmitis underwent evisceration for a painful blind eye. The patients in the current series were much younger than those described previously. CONCLUSION: Presentation and diagnosis of Curvularia can be delayed especially in postoperative cases. Early and appropriate management with multiple interventions can result in an acceptable visual and anatomical outcome.

ENTEROCOCCUS ENDOPHTHALMITIS: Clinical Settings, Antimicrobial Susceptibility, and Management Outcomes.

PURPOSE: To report the clinical presentation and management outcome of patients with endophthalmitis caused by Enterococcus species and to report the susceptibility profile of the isolates. METHODS: Twenty-nine cases with culture-proven Enterococcus endophthalmitis from January 2005 to May 2018 underwent vitrectomy/vitreous biopsy, intravitreal antibiotic with or without additional procedures. The undiluted vitreous was subjected to microbiologic evaluation. A favorable anatomical outcome was defined as preservation of the globe, absence of hypotony, attached retina, and absence of active inflammation at the last visit. Favorable visual outcome was final visual acuity ≥20/400. RESULTS: There were 24 men (82.8%). Mean age at presentation was 32.89 ± 25.25 years (median 24 years). Inciting event was open globe injury in 18 (62%), endogenous in 5 (17.24%), postcataract surgery in 3 (10.34%), postscleral buckling in 2 (6.89%), and postkeratoplasty in 1 (3.44%). Enterococcus casseliflavus was the commonest species isolated (14/29, 48.27%) followed by E. faecalis (9/29, 31%). Susceptibility to vancomycin was seen in 27/29 isolates (93%). Visual acuity was ≤20/400 in all eyes at presentation and ≥20/400 in 10/29 cases (34.48%) at final visit. Anatomical success was seen in 18/29 eyes (62%). Corneal involvement was high at 24/29 eyes (82.75%). CONCLUSION: Enterococcus is not an uncommon organism in the setting of endophthalmitis after open globe injury. Resistance to vancomycin is rare. Multidrug resistance pattern is restricted to E. faecalis. Visual outcome is poor despite early and appropriate therapy due to inherent organism virulence.

Physical Barrier Type Abuse-Deterrent Formulations: Mechanistic Understanding of Sintering-Induced Microstructural Changes in Polyethylene Oxide Placebo Tablets.

The main goal of the presented work was to understand changes in the microstructure of tablets, as well as the properties of its main component viz. polyethylene oxide (PEO) as a function of sintering. Key polymer variables and sintering conditions were investigated, and sintering-induced increase in tablet tensile strength was evaluated. For the current study, binary-component placebo tablets comprised of varying ratios of PEO and anhydrous dibasic calcium phosphate (DCP) were prepared at two levels of tablet solid fraction. The prepared tablets were sintered in an oven at 80°C at different time points ranging from 10 to 900 min and were evaluated for pore size, tablet expansion (%), and PEO crystallinity. The results showed that for efficient sintering and a significant increase in the tablet tensile strength, a minimum of 50% w/w PEO was required. Moreover, all microstructural changes in tablets were found to occur within 60 min of sintering, with no significant changes occurring thereafter. Sintering also resulted in a decrease in PEO crystallinity, causing changes in polymer ductility. These changes in PEO ductility resulted in tablets with higher tensile strength. Formulation variables such as PEO level and PEO particle size distribution were found to be important influencers of the sintering process. Additionally, tablets with high initial solid fraction and sintering duration of 60 min were found to be optimal conditions for efficient sintering of PEO-based compacts. Finally, prolonged sintering times were not found to provide any additional benefits in terms of abuse-deterrent properties.

MicroRNA amplification and detection technologies: opportunities and challenges for point of care diagnostics.

The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC. However, the most widely used methods for analyzing miRNAs, including Northern blot-based platforms, in situ hybridization, reverse transcription qPCR, microarray, and next-generation sequencing, are still far from being used as ideal POC diagnostic tools, due to considerable time, expertize required for sample preparation, and in terms of miniaturizations making them suitable platforms for centralized labs. In this review, we highlight various existing and upcoming technologies for miRNA amplification and detection with a particular emphasis on the POC testing industries. The review summarizes different miRNA targets and signals amplification-based assays, from conventional methods to alternative technologies, such as isothermal amplification, paper-based, oligonucleotide-templated reaction, nanobead-based, electrochemical signaling- based, and microfluidic chip-based strategies. Based on critical analysis of these technologies, the possibilities and feasibilities for further development of POC testing for miRNA diagnostics are addressed and discussed.

Flurbiprofen loaded ethosomes - transdermal delivery of anti-inflammatory effect in rat model.

BACKGROUND: Ethosomes have been widely used in Transdermal Drug Delivery System (TDDS) as they increase the permeation of drug across the skin. METHODS: Flurbiprofen loaded vesicular ethosomes were formulated, optimized and characterized for particle size, entrapment efficiency, poly dispersive index (PDI), microscopy using Atomic force microscopy (AFM), Scanning electron microscope (SEM) and Transmission electron microscopy (TEM) and Interaction of drug and excipients were studied using Fourier transform infra-red (FTIR) spectroscopy, Differential scanning colorimetry (DSC), Thermo gravimetric analysis (TGA). Further, ethosomal formulations of flurbiprofen were evaluated for stability study of three months and in vitro drug permeation study was carried out using albino rat skin. In addition, skin irritation test was evaluated by Draize test and in vivo study of prepared formulation was examined through paw edema assay by inducing carrageenan and cold plate method. RESULTS: Amongst all formulations, EF5 formulation exhibited ideal surface morphology, with maximum entrapment efficiency (95%) with optimal excipient concentration i.e. 200 mg phospholipid and 35% ethanol. The ideal vesicle size was achieved as 162.2 ± 2 nm, with zeta potential - 48.14 ± 1.4 mV with the PDI of 0.341. In-vitro permeation study shows a release of 82.56 ± 2.11 g/cm2 in 24 h and transdermal flux was found as 226.1 µg/cm2/h. Cold plate test indicates that the formulation EF5 showed a marked analgesic activity and Carrageenan induced paw edema test indicates that the formulation EF5 inhibits the increase in paw edema. Ethosomal suspension at 4 °C showed maximum stability. CONCLUSIONS: The overall study concluded that this ethosomal approach offers a new delivery system for sustained and targeted delivery for flurbiprofen.

Influence of punch geometry (head-flat diameter) and tooling type ('B' or 'D') on the physical-mechanical properties of formulation tablets.

The presented study assessed the influence of punch geometry (head-flat [HF] diameter) and tooling type ('B' or 'D') on the physical-mechanical properties of tablets prepared by direct-compression of two guaifenesin (25% or 40% w/w) formulations. Tablets of both formulations were prepared on instrumented, single-layer, rotary tablet press using 10 mm, flat-faced, 'B' or 'D'-type tooling with different HF diameters, and compression forces (CF) ranging from 5 to 25 kN with 5 kN increments. The tablets were evaluated for dimensions, weight variation, tensile strength (TS), friability, and capping index. In general, tablets prepared using 'D' tooling showed a significantly (p < 0.05) higher TS compared to those prepared using 'B' tooling, likely due to higher dwell-times associated with 'D' tooling. Formulations containing 25% w/w guaifenesin showed a significantly (p < 0.05) higher TS compared to those containing 40% w/w guaifenesin, at given compression CF, punch geometry, or tooling type. This could be due to the higher ratio of Prosolv® SMCC contributing to the compressibility. For both formulations compressed using 'B' tooling, differences in TS profiles were observed between different HF tooling. The TS of these tablets increased significantly with increasing HF diameter. For formulations compressed using 'D' tooling, this trend was observed only up to a CF of 15 kN, beyond which the TS plateaued, possibly due to work-hardening of the formulation at higher CF. These formulations also exhibited capping at CF above 15 kN and with higher HF diameters. The study showed a significant influence of punch geometry and tooling type on the physical properties of tablets.

PEG-PLGA- hybrid nanoparticles loaded with etoricoxib - phospholipid complex for effective treatment of inflammation in rat model.

The aim of the present study was to increase the bioavailability of the etoricoxib by making PEG-PLGA-Hybrid nanoparticles using emulsion solvent evaporation method. Then the prepared nanoparticles were further characterised using TEM, particle size, PDI, zeta potential, encapsulation efficiency and drug release study. Lipid (Phospholipon 90-G) and drug thermal behaviour were studied using DSC, TGA. The results of optimised formulation of Particle size, PDI and zeta potential was found 216.6 ± 4.0 nm, 0.24 ± 0.19 and +36.3 ± 1.9 mV. Encapsulation efficiency was found in the range of 77.15% w/v to 93.88% w/v. In-vivo study shows that the optimised formulation at a particular dose decreases the swelling index and number of writhes. Stability study indicated that the nanoparticles can be stored at a temperature of 4 ± 2 °C/60 ± 5% RH in well-closed container, away from heat and damp places. The prepared formulation has significantly increased the bioavailability of etoricoxib via oral administration.