Sulbactam-Durlobactam, A Novel Drug for the Treatment of Multidrug-resistant Acinetobacter baumannii Infections - A Systematic Review.

BACKGROUND: Sulbactam-durlobactam (SUL-DUR) has been tested in vitro for its ability to gen- erate resistance in clinical isolates of Acinetobacter species. According to prior studies, combining durlobac- tam with sulbactam causes sulbactam-resistant isolates to become more active and revert to susceptibility. We aimed to conduct a systematic review of the in vitro activity of SUL-DUR on A. baumannii (Ab) iso- lates, including carbapenem-resistant A. baumannii (CRAb), to provide an overview for physicians dealing with Ab infections. METHODS: The following keywords were searched in the PubMed, Google Scholar, and EMBASE databases to look for eligible original works that have been published without restrictions till June 30, 2023: A. bau- mannii and sulbactam-durlobactam, SUL-DUR, durlobactam, and sulbactam-ETX2514. We also searched clinicaltrials.gov and the Clinical Trials Registry of India (CTRI) for clinical trials involving sulbactam- durlobactam and Acinetobacter. RESULTS: There were a total of 852 abstracts found. Among them, 633 articles with titles, abstracts, and key- words were reviewed, and 574 articles were removed after the initial screening. A total of 59 full-text eligi- ble articles were evaluated, and 51 of them were eliminated because they did not satisfy the criteria set for inclusion. The full texts of the final 8 in vitro studies on A. baumanii and sulbactam/durlobactam were fur- ther evaluated. There were 5 trials on A. baumanii and sulbactam/durlobactam found on clinicaltrials.gov and the Clinical Trial Registry of India (CTRI). CONCLUSION: The findings from the studies show that SUL-DUR might be a successful therapeutic option for multidrug-resistant-Ab infections. Future clinical trials will be required to validate the possibility of using this combination to treat multidrug-resistant A. baumannii infections.

Antimicrobial Stewardship Program: Time to be Focused in Speciality Settings of Leprosy Institute and Related Health Care Setup.

Leprosy, often known as Hansen's disease is a contagious chronic infectious disease caused by Mycobacterium leprae (M. leprae). Our methodology is easily repeatable in tertiary care settings with diagnostic accuracy resources and staff capable of building a stewardship team. Comprehensive antimicrobial policies and programmes are required to properly alleviate the initial issue.

Is Daclatasvir a suitable substitute for Amphotericin B in the treatment of Mucormycosis when Amphotericin B is scarce?

BACKGROUND: Mucormycosis has been infesting the universe for a while back, often with no prompt treatments. The disease devastation is spreading at an alarming rate. Many researchers are still hoping for a good potential drug that could help the healthcare system in this tussle. Molecular docking is an in silico tool that has gained popularity over the last few decades. Knowing the mechanism of enzymatic action is aided by imitating membrane protein actions in binding ligands. AIM: The aim of this perspective is to determine whether an existing drug, daclatasvir, has antifungal activity. OBJECTIVE: The primary objective of this in silico study was to investigate the potential effects of the binding affinity of daclatasvir with the crucial protein (1XFF) of mucormycosis, as well as the binding pattern of the active site amino acids with the drug molecule. MATERIALS AND METHODS: To calculate the binding affinity of daclatasvir to the fungal protein 1XFF, Auto Dock Vina was used for molecular docking studies. The CDOCKER protocol was used to determine the receptor-ligand interaction by configuring various parameters. RESULTS: The docking energy of the ligand (daclatasvir) on the protein (1XFF) was found to be -16.7216 kcal/mol, while the interaction energy was found to be - 42.1314 kcal/mol. CONCLUSION: The binding pattern completely alters the dynamics of the protein, resulting in the breakdown of the fungal wall. The vital protein (1XFF) of Rhizopus oryzae is proposed as a possible protein target for the non-structural protein 5A inhibitor/antiviral drug daclatasvir in this study.

A Change in the Trend of Quality Reporting in Leprosy Trials: A Systematic Review.

BACKGROUND: Leprosy is a communicable disease caused by bacteria Mycobacterium leprae. Despite all attempts, it has not been eradicated in several underdeveloped nations since the start of the antibiotic age. It's a social issue as well as a stigmatised disease. Due to these restrictions, randomised controlled trials in leprosy confront numerous obstacles, which are reflected in the quality of study reporting. OBJECTIVES: The objective of this study is to use the Consolidated Standard for Reporting Trials (CONSORT) 2010 checklist to assess the quality of leprosy trial reporting. METHODS: We assess the quality of reporting of randomised control trials on leprosy conducted after 2010 in the PubMed database, using the CONSORT checklist 2010. Second, we compare the quality of RCT reporting before and after the release of the CONSORT guidelines in 2010. RESULTS: A total of 19 full-text eligible articles were examined and included in the final list of articles, which were then evaluated further. 4 out of 19 trials had a compliance percentage of more than 75%. 6 out of 19 trials had compliance percentage of 50% to 75%. 9 trials had a compliance percentage of below 50%. Highest compliance was 86.48% and the lowest compliance was 32.43%. When compared with trials before 2010, we could see an improvement in some criteria showing a statistically significant rise in comparison with trials conducted before 2010. CONCLUSION: Leprosy is still a concern in developing countries, which have failed to eradicate the disease despite their best efforts and resources. The compliance of leprosy related RCTs has improved since the introduction of the CONSORT guidelines, but the quality of reporting still remains on the lower side.

Leprosy Reactions: Clinical Pharmacologist Perspective with Repurposed Medications.

The elimination of leprosy has been possible with the available anti-leprotic drugs. However, the lepra reactions usually occur months or years after multi-drug therapy completion, and continue to be a formidable challenge mainly owing to its role in causing nerve damage and disability. Corticosteroids are commonly used but they lead to systemic complications, and hence require dose reduction and adjunct therapy with a different target. Various drugs with different targets have been identified and are in practice to treat lepra reactions. The newer targets can include genetic and tissue targets in the skin and nerve. Thalidomide treatment reducing pentraxin-3, toll-like receptor antagonists, minocycline, apremilast, immunomodulators, and tenidap can be helpful in lepra reaction. Other modalities to manage lepra reactions include plasma exchange, intravenous immunoglobulins, and immunotherapy. Most of these treatments are based only on the pathological process of the reaction and tend to be incomplete leading to recurrence. Newer multimodal approaches are required based on various biomarkers (genetic, tissue, serological), which can be monitored to prevent the recurrence of reactions. Hence, there is a need for newer targets and drugs to be identified for the management of lepra reactions.

Efficacy and safety of sufentanil sublingual tablet system in postoperative pain management: a systematic review and meta-analysis.

BACKGROUND: Sufentanil sublingual tablet system (SSTS) is a recently approved formulation for postoperative pain management that has become popular due to its pharmacokinetic properties such as good bioavailability, rapid attainment of equilibrium and elimination without any metabolites, along with its pharmacodynamic properties such as rapid onset and effective pain reduction. It is also relatively well tolerated by patients. OBJECTIVE: This is a quantitative analysis of the efficacy and safety of SSTS in patients with moderate to severe postoperative pain. DESIGN: This is a systematic review and meta-analysis. Databases such as Cochrane Library, MEDLINE and EMBASE were searched for eligible articles. SETTINGS: Randomised controlled trials published after 2000 in English language and which assessed at least one of the outcome measures of interest with pain intensity difference between 12 hours and a maximum of 96 hours. PARTICIPANTS: Adults with moderate to severe postoperative pain and taking SSTS for pain management. METHODS: Data were analysed using Review Manager (RevMan) V.5.3. Risk of bias (RoB) assessment was done using RoB-2 scale, and overall grading of evidence of each outcome was done using GRADEpro Guideline Development Tool. RESULTS: Analysis of SSTS versus control indicates a statistically significant reduction in summed pain intensity difference at 12 hours (mean difference (MD)=-12.33 (95% CI -15.5 to -9.17), p<0.00001), summed pain intensity difference at 48 hours (MD=-43.57 (95% CI -58.65 to -28.48), p<0.00001), time-weighted total pain relief over 12 hours (MD=-4.77 (95% CI -6.28 to -3.27), p<0.00001) and pain intensity difference (MD=-0.73 (95% CI -1.00 to -0.46), p<0.00001) with SSTS, alongside high quality of evidence. Success of treatment as assessed by Patient Global Assessment (OR=4.01 (95% CI 2.74 to 5.89), p<0.00001) and Healthcare Professional Global Assessment (OR=4.46 (95% CI 3.03 to 6.56), p<0.00001) scoring at 72 hours was observed in a significantly high number of individuals using SSTS, with high quality of evidence. There was no difference in adverse events except for dizziness (RR=1.90, 95% CI 1.02 to 3.52). There was a significantly higher number of total adverse events in orthopaedic surgery in the SSTS group than in the comparator. CONCLUSION: SSTS is effective in postoperative pain management in patients with moderate to severe pain. It also has good tolerability and high patient satisfaction. PROSPERO REGISTRATION NUMBER: CRD42018115458.

Molecular Docking Analysis of Adhatoda vasica with Thromboxane A2 Receptor (TXA2R) (6IIU) and Antiviral Molecules for Possible Dengue Complications.

OBJECTIVE: The present study is an in silico model of platelet amplification potential of Adhatoda vasica, which can be used to treat thrombocytopenia in dengue complications. METHODS: Docking studies have proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In the present study, vasicine containing natural anti-dengue potential was subjected to docking studies using Schrodinger glides software (ver.11.1). The docking study was carried out to find out the potential molecular targets for selected protein. The docking was carried out on different ligands, like vasicine, ramatroban, chloroquine, celgosivir, and standard eltrombopag downloaded from PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Docking was performed using the ligand docking wizard of Glide-maestro 2018. RESULTS: The docking score of vasicine (-5.27) is nearly identical to the standard eltrombopag (-6.08), and both ligands bind with one hydrogen bond. The validation score of ramatroban is -12.39, binding with five hydrogen bonds, Celgosivir exhibited a docking score of -7.3 with three hydrogen bonds, and chloroquine displayed no hydrogen bond but had a docking score of -4.6. CONCLUSION: Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary, and it has been indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue; experimental evaluation will be carried out in the near future.

A Survey from a Tertiary Care Hospital in India on Pediatric Medication Re-Dosing Practices After Patient Vomiting.

OBJECTIVE: The study was started in our institution to analyze the clinical problem and identify the benefits and drawbacks of current practices associated with drug re-dosing after vomitting. Opinions and perspectives from health care professionals from various pediatric hospitals were also gathered to build an effective and systematic protocol. METHODS: Survey participants were recruited by using email distribution lists and forums catering to health care. Using this, 2 online surveys were carried out in the window period of 6 months. RESULTS: Of the 14 responses from the study hospitals that were suitable for analysis, 64.2% reported pediatric patients that vomited after being administered oral medications: 7.1% faced this daily, 35.7% weekly, and 21.4% monthly. When respondents were asked to rate the importance of 8 factors potentially affecting the decision to re-dose, more than half indicated that the patient's vitals and condition (stable, unstable, or critical) were most important (57.4%), followed by time after ingestion (50%), familiarity with medication (42.8%), and formulation of medication (42.8%). Of 43 respondents from other institutions, only 11.9% had a functioning guideline for re-dosing in their institution. CONCLUSIONS: Health care professional respondents to our surveys listed the time between ingestion and vomiting and the condition of the patient as the most important factors in their decision to re-dose the medication.

Information on migraine drugs in commonly available Indian drug information sources - Whether we satisfied the community needs?

Drug information can be obtained from various drug information sources that were available as government (National Formulary of India [NFI]; Central Drugs Standard Control Organization [CDSCO]), as well as commercial documents (Current Index of Medical Specialties [CIMS] and Monthly Index of Medical Specialties [MIMS]). Irrational drug usage may happen due to wide variation in the information available in these sources. In this study, we tried to assess these variations in a sample of drugs for the acute-specific management of migraine with ergot and Triptans antimigraine drugs in drug information sources such as NFI, CIMS, MIMS, and CDSCO. Scoring was done for various drug information based on the completeness of information about drugs used in acute-specific management of migraine. The scores for the completeness of drug information about the selected antimigraine drugs are 18.37% for CIMS (Ergotamine, Sumatriptan, Rizatriptan, and Zolmitriptan), 21.1% for NFI (Dihydroergotamine, Sumatriptan), 72.79% for MIMS (Ergotamine tartrate, Sumatriptan, Rizatriptan, Naratriptan, zolmitriptan, Almotriptan) and 21.77% for CDSCO (Ergotamine tartrate, Sumatriptan, Rizatriptan, Naratriptan, Zolmitriptan, eletriptan and almotriptan). The information for the antimigraine drugs available from various sources found to so much deficient. Necessary steps need to be taken in case of government public or hard documents to streamline drug information available with them as well the commercial documents as to provide reliable drug information uniformly for promoting rational use of the drug.

Vigilance Needed in Treating Leprosy Patients in Accordance with WHO's AWaRe.

BACKGROUND: Leprosy is a highly stigmatized disease that can range from a minor skin lesion to life-threatening conditions such as deformities and disability. The World Health Organization (WHO) has developed a tool called "Access, Watch, and Reserve" (AWaRe) to reduce antibiotic misuse and abuse. AIM: The purpose of this review is to determine whether the drugs used in the leprosy treatment regimen are complied with the AWaRe programme, in order to improve the quality of hospital antibiotic use and reduce the incidence of antimicrobial resistance (AMR). METHODS: We started by looking for antibiotics that are used in the treatment and chemoprophylaxis of leprosy, as defined by the WHO's AWaRe classification. Furthermore, we look for studies on antibiotics that showed sensitivity or less resistance after antimicrobial sensitivity testing (AST) on isolates from infected leprosy ulcers, as well as their AWaRe category. RESULTS: There were 32 studies found, but only 5 of them met the inclusion criteria. They consisted of four cross-sectional studies and one descriptive retrospective study. A total of 19 antibiotics were identified in 5 studies, with 9 (47.4%) antibiotics in the access category, 8 (42.1%) antibiotics in the watch group, and 2 (10.5%) antibiotics in the reserve group. CONCLUSION: As per our knowledge, this is the first study to explore antibiotics in leprosy treatment, chemoprophylaxis, and complications such as ulcer compliance with the AWaRe programme. Antimicrobial resistance is on the rise, which is a global issue that continues to pose challenges to clinical practices. This review may provide physicians with an overview of the current state of drug prescribing trends in leprosy, whether in accordance with the AWaRe classification in selecting the right drug when the use of antimicrobials is indicated and may also aid in rational drug prescribing.

The Role of Justicia adhatoda as Prophylaxis for COVID-19 - Analysis Based on Docking.

Coronavirus causes severe harm to the health of both humans as well as animals, creating a major global health problem affecting millions of populations. Considering the situational emergency of identifying novel targeted therapy, we have chosen the herbal compound Adhatoda Justicia/ vasica, which is a high potent olden vital compound having a key role in various respiratory conditions with multiple beneficial uses. Adhatoda is promoted and supported by the Ministry of AYUSH for symptomatic management of respiratory ailments in the case of COVID 19. In this study, we focused on the efficacy of Adathoda primary active alkaloid, vasicine against coronavirus infectious symptoms, evaluated by in silico screening studies on virus proteins ACE 2 Receptor, 3CL protease and Spike protein SARS HR1 motif using PyRx tool and AutoDoc 1.5.6. Based on PyRx results, Vasicine with ACE 2 Receptor showed a higher docking affinity score -7.1 K/cal respectively when compared to other virus proteins. AutoDoc 1.5.6 screening study report showed that vasicine promotes good inhibitory constant 486.54 mM on 3CL protease more than others. Results reveal that vasicine could be a potential target for the treatment of COVID 19. This study adds strong evidence to the claim by the advisory released by AYUSH. Based on the results with the available literature, Adhatoda could be a drug helpful in relieving symptoms in non-- COVID cases in those who were quarantined or in lockdown pace, thereby reducing pandemic panic in confirmed asymptomatic or mild cases. For usage in moderate to severe cases, this could be an add-on therapy with existing modern medical therapy.

Are We Jumping the Gun with Itolizumab in India? A Situational Analysis from the Pre-COVID Era.

Itolizumab, an anti-CD6 monoclonal antibody, has been recently approved for the off-label indication of cytokine release syndrome in the background of COVID-19, by the Drug Controller General of India. However, this drug has not been included in the National Clinical Management Protocol for COVID-19 yet. The limited-to-no experience of the Indian health workforce with the drug urged us to conduct a situational analysis in the pre-COVID era to analyse the degree of use of the drug and the indications for which it has been employed.

Role of Dupilumab in Approved Indications of COVID-19 Patient: an Efficacy-Based Nonsystematic Critical Analysis.

With many drugs being tried in the management and treatment of COVID-19, dupilumab is one such monoclonal antibody that has come under the limelight for its possible role as an adjunct therapy in COVID-19 position. There are isolated case reports and series that document a milder course of COVID-19 infection in patients who have already been on dupilumab therapy for treatment of conditions such as atopic dermatitis and chronic rhino-sinusitis with nasal polyp. There is also an ongoing debate regarding the continuation of biologicals in the COVID patient. In this article, a non-systematic critical analysis of dupilumab was performed to delve into this hypothesis further.

Rationale use of Thalidomide in erythema nodosum leprosum - A non-systematic critical analysis of published case reports.

INTRODUCTION: Thalidomide is an anti- tumor necrosis factor alpha (TNF-a) drug used mainly in the management of moderate to severe form of Erythema Nodosum Leprosum (ENL). Because of its teratogenic potential it has to be used under proper supervision. Our critical analysis tries to look into the rationale with which it has been used by means of case reports on lepra reaction. METHODS: We looked for the case reports between December 2005 to June 2019 in databases like Pubmed, Embase and other relevant resources. We used search words like "erythema nodosum leprosum(ENL)", "thalidomide", "case report" in different combinations to get relevant reports that focus on thalidomide usage atleast once at any time point during management. The information extracted were indication of thalidomide use, dose, response, outcome, complication if any, along with all the demographic details and geographical distribution. RESULTS: We found 41 case reports eligible for analysis.The information was critically evaluated. From the analysis it was found that 7 of the case report mentioned the exact indication, 4 case report showed irrational use of thalidomide in the case of neuritis without use of steroids, 7 showed proper use of Clofazimine prior to thalidomide initiation, 26 case report showed case report of rationale dose range and in 4 case reports clofazimine was used prior to thalidomide along with the rational dose of thalidomide. CONCLUSIONS: This analysis helps to guide the rationale use of thalidomide focussing on few important points that anyone should keep in mind while managing a case of ENL.