Insights and Opinions of Critical Care Healthcare Professionals in the Management of Carbapenem-resistant Enterobacteriaceae Cases and Antibiotic-Resistant Infections in the Intensive Care Unit Setting: A Survey-Based Approach.

INTRODUCTION: A survey-based approach to managing antibiotic-resistant infections in the intensive care unit (ICU) setting, with a focus on carbapenem-resistant Enterobacteriaceae (CRE) cases, was conducted. Among CRE, New Delhi metallo-ß-lactamase 1 (NDM-1) is a carbapenemase that is resistant to ß-lactam antibiotics and has a broader spectrum of antimicrobial resistance than other carbapenemase types. The article explains that healthcare-associated infections (HAIs) are a significant problem, particularly in low- and middle-income countries, and that carbapenem in combination with other antibiotics are the most potent class of antimicrobial agents effective in treating life-threatening bacterial infections, including those caused by resistant strains. AIM: The survey aimed to gather critical care healthcare professionals (HCPs') opinions on their current practices in managing infections acquired in the hospital and ICU settings, with a focus on CRE cases, specifically NDM-1 and other antibiotic-resistant infections. METHODS: Responses from critical care healthcare professionals, including online surveys and in-person interviews, to gain insights into the management of infections caused by multidrug-resistant bacteria. The findings related to the insights on the prevalence of bacterial flora, clinical experiences on efficacy and safety of meropenem sulbactam ethylenediaminetetraacetic acid (EDTA) (MSE) in CRE cases, and various combination therapies of antibiotics used to treat antibiotic-resistant infections in ICU setting were evaluated. RESULTS: Klebsiella pneumoniae bacteria were the most common bacteria in cultures, followed by Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. NDM-1 was the type of carbapenemase found in around 50% of CRE patients. MSE is among the most preferred antibiotics besides colistin, polymyxin B, and ceftazidime avibactum for CRE cases and specifically for NDM-1 cases due to its high rate of efficacy and safety. CONCLUSION: The article concludes with a discussion on the antibiotics used in response to CRE cases, reporting that critical care HCP considers MSE with high efficacy and safe antibiotic combination and was used as both monotherapy and in combination with other antibiotics. The survey highlights the need for exploring and better understanding the role of MSE in the management of CRE infections, especially in NDM-1.

Safety and efficacy of a Siddha Medicine fixed regimen for the treatment of asymptomatic and mild COVID-19 patients.

Background: The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive threat to public health worldwide. Siddha system of medicine is one of the traditional medicines of South India. The recommended formulations in Siddha Sasthric Medicines- Fixed Regimen (SSM-FiRe) are Amukkura tablets, Kaba Sura Kudineer (KSK) for asymptomatic COVID-19 positive (RT-PCR) patients, and Athimathuram tablets, Adathodai Manappagu syrup, Thippili Rasayanam, Brahmananda Bairavam tablet, and Notchi Kudineer for mild symptomatic patients. The core objective of the trial was to document the efficacy of SSM-FiRe in the prevention of asymptomatic and mild COVID-19 disease progression to the next level of severity, reduce the severity of symptoms and revert to RT-PCR Negative. Methods: An exploratory, prospective, open-labeled, single-arm, non-randomized trial was designed as per GCP guidelines to assess the efficacy of SSM-FiRe. Sixty RT-PCR positive participants who were asymptomatic or with mild COVID-19 symptoms were recruited for the study at the Siddha COVID Care Centre, Vyasarpadi, Chennai from June to August 2020. Nasal and oropharyngeal swab tests were performed on the 0, 7th, and 14th days. All participants were treated with SSM - FiRe regimen. All the participants were also assessed based on Siddha Yakkkaiyin Ilakkanam, which included Clinical symptoms and vitals. Laboratory investigations such as Haemogram, Liver Function Test, Renal Function Test, HbA1C, Electrolytes, Inflammatory markers, Cardiac profile, Immunoglobulins, and anti-SARS-CoV-2 antibody tests were performed. Results: 83% of COVID-19 patients turned RT-PCR negative on the 7th day and in most of the cases, symptoms were reduced within the first 5 days of admission. The RT-PCR cycle threshold (ct) value increased significantly (<0.001) after treatment and all the participants were RT-PCR negative, except one, who was positive even after 14 days. Anti-SARS-CoV-2 antibodies developed significantly (p-value - 0.006). LFT, RFT, CBC, Total proteins, and electrolytes continued to be in the normal range after treatment, indicating the safety of the intervention. Conclusion: Asymptomatic and mild COVID-19 disease can be well managed by SSM - FiRe treatment, Further studies could be taken up to strengthen the findings.

Long-term Outcome of Lupus Nephritis: A Single Center Study.

INTRODUCTION: There is paucity of data on long-term outcome of lupus nephritis (LN) from south India. Our study looks at long term outcomes in patients with biopsy proven LN with terms of response to therapy, flare, mortality, treatment-related complications, outcome and post flare analysis. We also analyzed the factors which predicted the outcome. METHODS: A retrospective observational study was conducted from 2005 to 2012 at St. John's Medical college and hospital, Bangalore. Patients received treatment as per NIH protocol. Patients of LN who regularly visited OPD were included. Statistical analysis was done by using SPSS 19 software. RESULTS: At end of 84 ± 6 months (N = 59), 38 subjects showed complete remission (CR), 6 partial remission (PR), 3 developed chronic kidney disease, 2 developed end-stage kidney disease (ESKD), and 10 died. In outcome of flare (N = 15), 7 had nephrotic flare, 3 had refractory flare, 3 showed nephritic flare with 2 developing ESKD. Change of LN class was 3 subjects had changed to class II from class IV, 1 to class II from class V, 7 to class III from class IV, 2 to class IV from class V, and 2 to class IV from class VI. Factors predicting poor outcomes were serum creatinine, hypertension at presentation, and failure to achieve remission in 1 year. 7 subjects conceived, of which 4 of them were treated with azathioprine (AZA) and 3 of them who were on mycophenolate mofetil and was changed to AZA. 4 subjects had successful pregnancy outcome, 2 had preeclampsia, and 1 subject had missed abortion. CONCLUSION: At end of 84 ± 6 months, patient survival rate was 84%.

Analysis of AYUSH studies registered in clinical trials registry of India from 2009 to 2020.

BACKGROUND: The Clinical Trials Registry-India (CTRI) is an initiative of the Indian Council of Medical Research, New Delhi, India (ICMR) and monitored by the ICMR-National Institute of Medical Statistics (NIMS) since July 20, 2007. Randomized clinical trials are considered as the gold standard in evidence-based medicine. Registration of clinical trials enables disseminating evidence among clinicians, researchers, and patients. It promotes transparency and avoids duplication. The registration process is mandatory for AYUSH clinical trials also. OBJECTIVES: This analysis is aimed to determine the different characteristics of registered AYUSH clinical trials in CTRI from 2009 to 2020. MATERIALS AND METHODS: A cross-sectional retrospective analysis was conducted. The information on registered clinical trials about AYUSH was obtained from the website www.ctri.nic.in from 2009 to 2020 (n = 3632; last accessed on July 30 2020). Data analysis considered the following factors for analysis using descriptive statistics. The number of clinical trials registered in AYUSH stream were classified according to registration type (retrospective/prospective), postgraduate dissertations (yes/no), primary sponsor, type of trial (interventional/observational), study design, health condition and State-wise distribution of sites of studies. RESULTS: The number of clinical trial registrations among AYUSH streams (3632) descends from Ayurveda (2054), followed by Siddha (635), Yoga (408), Unani (366) and Homoeopathy (169). Interventional studies dominate observational studies among all AYUSH registered trials. AYUSH streams took four years to register in CTRI due to an increase in reporting trials from 2013. Significant number of trials were registered retrospectively. The order of closure of retrospective registration has influenced an increase in prospective enrolment between 2017-2019. CONCLUSION: Registration of clinical trials in the CTRI should be encouraged. Randomized controlled trials (RCTs) occupy a rear seat which exposes an opportunity for trials and alarms about weak trials. Non-communicable diseases (NCDs) are registered more comparatively, which reflects the strength of AYUSH in NCDs. Most of the trials fall under phase 2, which seems to have an increasing opportunity for more trials. Certain visible flaws like registering Phase 2 trials as Phase 3 or 4 and domestic trials as international trials reflect human resources crunch in ICMR-CTRI in Issuing Certificates. These errors should be rectified by training the stakeholders effectively.

Performance Parameters and Characterizations of Nanocrystals: A Brief Review.

Poor bioavailability of drugs associated with their poor solubility limits the clinical effectiveness of almost 40% of the newly discovered drug moieties. Low solubility, coupled with a high log p value, high melting point and high dose necessitates exploration of alternative formulation strategies for such drugs. One such novel approach is formulation of the drugs as "Nanocrystals". Nanocrystals are primarily comprised of drug and surfactants/stabilizers and are manufactured by "top-down" or "bottom-up" methods. Nanocrystals aid the clinical efficacy of drugs by various means such as enhancement of bioavailability, lowering of dose requirement, and facilitating sustained release of the drug. This effect is dependent on the various characteristics of nanocrystals (particle size, saturation solubility, dissolution velocity), which have an impact on the improved performance of the nanocrystals. Various sophisticated techniques have been developed to evaluate these characteristics. This article describes in detail the various characterization techniques along with a brief review of the significance of the various parameters on the performance of nanocrystals.

Management of incidentally detected gallbladder carcinomas in a high prevalence area of gallbladder cancer.

BACKGROUND: There is an increasing incidence of advanced unresectable gallbladder cancer even in patients who undergo re-exploration and these cases are marked by poor survival even after undergoing curative resection and adjuvant chemotherapy. Lack of suspicion during primary surgery, unavailability of frozen section facilities and delayed referrals are believed to contribute to this high incidence. AIM: Our aim was to evaluate the results of re-surgery in incidental gallbladder cancers detected after open or laparoscopic cholecystectomy and to assess the outcome in patients who underwent complete radical cholecystectomy and adjuvant therapy. METHOD: We retrospectively analyzed the data from a prospectively maintained computerized database of all patients with incidentally detected gallbladder cancers operated in the Department of Surgical Oncology, from June 2006 to January 2013. RESULTS: Forty-two patients with incidental gallbladder cancer were re-explored. The median time of re-exploration after initial surgery was 65 days. Eighteen (43%) patients were found inoperable due to locally advanced unresectable or metastatic disease. Among the 24 (57%) patients who underwent completion radical cholecystectomy, 11 developed recurrence over a median time of 11 months. CONCLUSION: Despite the dismal prognosis, more than half of the incidentally detected gallbladder carcinoma patients could receive curative treatment. Identification of patients with incidentally discovered gallbladder cancer and early referral to an oncology center may ensure these patients receive curative resection thereby increasing their chances for long-term disease free survival.

Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride.

Lercanidipine hydrochloride is a calcium channel blocker used in the treatment of hypertension. It is a poor water soluble drug with absolute bioavailability of 10%. The aim of this study was to design lercanidipine hydrochloride-loaded nanostructured lipid carriers to investigate whether the bioavailability of the same can be improved by oral delivery. Lercanidipine hydrochloride nanostructured lipid carriers were prepared by the method of solvent evaporation at a high temperature and solidification by freeze drying. The nanostructured lipid carriers were evaluated for particle size analysis, zeta potential, entrapment efficiency, in vitro drug diffusion, ex vivo permeation studies and pharmacodynamic study. The resultant nanostructured lipid carriers had a mean size of 214.97 nm and a zeta potential of -31.6 ± 1.5 mV. More than 70% lercanidipine hydrochloride was entrapped in the NLCs. The SEM studies indicated the formation of type 2 nanostructured lipid carriers. The in vitro release studies demonstrated 19.36% release in acidic buffer pH 1.2 indicating that the drug entrapped in the nanostructured lipid carriers remains entrapped at acidic pH. The ex vivo studies indicated that the drug release was enhanced from 10% to 60.54% at blood pH in 24h. The in vivo pharmacodynamic study showed that NLCs released lercanidipine hydrochloride in a controlled manner for a prolonged period of time as compared to plain drug. These results clearly indicate that nanostructured lipid carriers are a potential controlled release formulation for lercanidipine hydrochloride and may be a promising drug delivery system for the treatment of hypertension.

Cancer chemotherapeutic agents as human teratogens.

BACKGROUND: Cancer is the second leading cause of death among women of reproductive age. Although the coincidence of pregnancy and cancer is rare and treatment may sometimes be safely delayed, the use of chemotherapeutic agents in pregnancy is sometimes unavoidable or inadvertent. METHODS: We review the literature for the use of antineoplastic agents in single-agent and combination therapy from 1951 through June 2012. We also summarize the evidence relating to teratogenicity of disorder-specific combination chemotherapy treatments for those malignancies frequently encountered in women of childbearing age. Major endpoints were called "adverse pregnancy outcomes" (APOs), to include structural anomalies (congenital malformations), functional defects, blood or electrolyte abnormalities, stillbirths, spontaneous abortions (miscarriages), and fetal, neonatal, or maternal deaths. RESULTS: The registry totals 863 cases. Rates of APOs (and congenital malformations) after any exposure were 33% (16%), 27% (8%), and 25% (6%), for first, second, and third trimesters. Among the groups of cancer drugs, antimetabolites and alkylating agents have the highest rates of APOs. Mitotic inhibitors and antibiotics seem more benign. Mixed results were observed from single-agent exposure, often because of small numbers of exposures. As a whole, the alkylating agents and antimetabolites are more harmful when given as a single agent rather than as part of a regimen. First-trimester exposure poses a more permanent risk to the fetus. CONCLUSIONS: Systematic ascertainment of women early in pregnancy, preferably in a population base, is needed for assessment of true risks. Long-term follow-up is needed to rule out neurobehavioral effects.

Isolation of 1,4-naphthalenedione, an antibacterial principle from the leaves of Holoptelea integrifolia and its activity against beta-lactam resistant Staphylococcus aureus.

Antimicrobials derived from plants have been receiving increasing attention in recent years. Antimicrobial activities of a number of phytochemicals have been reported. Many present day antibiotics are ineffective against several pathogenic organisms. About 90% of Staphylococcus aureus isolates from clinical specimens is reported to have resistance against beta-lactam antibiotics. In the present study, the effect of hexane, diethyl ether, acetone and water extracts of leaves of a medicinal plant Holoptelea integrifolia has been tested against beta-lactam resistant strain of S. aureus in presence of antibiotics such as ampicillin, amoxicillin, cefotaxime and ceftriaxone. The diethyl ether extract has shown the maximum antibacterial activity and the active principle is found to be 1,4-naphthalenedione which is characterized by GC-MS and FTIR spectroscopy. The minimum inhibitory concentration (MIC) of the compound is found to be 4 mg/ml. Structural similarity of this compound with a functional group of a beta-lactamase-resistant antibiotic indicates that 1,4-naphthlenedione may be acting as an inhibitor to beta-lactamase.

Inhibition of beta-lactamase by 1,4-naphthalenedione from the plant Holoptelea integrifolia.

The most important mechanism of the beta-lactam antibiotic resistance is the destruction of the antibiotics by the enzyme beta-lactamase. Use of beta-lactamase inhibitors in combination with antibiotics is one of the successful antibacterial strategies. The inhibitory effect of a phytochemical, 1,4-naphthalenedione, isolated from the plant Holoptelea integrifolia on beta-lactamase is reported here. This compound was found to have a synergistic effect with the antibiotic amoxicillin against a resistant strain of Staphylococcus aureus. The enzyme was purified from the organism and incubated with the compound. An assay showed that the compound can inhibit the enzymatic activity of beta-lactamase. Modeling and molecular docking studies indicated that the compound can fit into the active site of beta-lactamase. Hence, the compound can serve as a potential lead compound for the development of effective beta-lactamase inhibitor that can be used against beta-lactam-resistant microbial strains.

Pattern of breakdown of laminar flow into turbulent spots.

The breakdown into turbulent spots is the least understood stage of the laminar-turbulent transition process. With cellular-automaton stochastic simulations and stability analysis, we show that the pattern of breakdown in boundary-layer flow bears a connection to laminar instability and may be reconstructed using macroscopic properties of the transition zone, such as persistence times and transitional intermittency. We propose experimental tests of our ideas.

Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency: the case for screening all newborns.

Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency is the most common inborn error of fatty acid oxidation with a frequency of 1 in 12,000, an estimated four new cases in the state of Oklahoma each year. The first clinical manifestation is a hypoglycemic episode any time between the newborn period to adulthood. Largely due to failure of diagnosis, the first episode can be lethal, with a frequency of early mortality of 25%. We report a child with MCAD deficiency admitted to the OU Medical Center-Children's Hospital to illustrate the molecular basis, clinical features, and management of the disorder and to present the pros and cons of instituting newborn screening in our state. Such screening is already part of routine newborn metabolic screening in four states. In Oklahoma and elsewhere, there is current discussion, which we summarize, on whether or not to include MCAD deficiency in the routine neonatal screening program. We suggest the evidence says, "Start now."