Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Antibiotic Resistant Biofilms and the Quest for Novel Therapeutic Strategies.

Antimicrobial resistance (AMR) is one of the major leading causes of death around the globe. Present treatment pipelines are insufficient to overcome the critical situation. Prominent biofilm forming human pathogens which can thrive in infection sites using adaptive features results in biofilm persistence. Considering the present scenario, prudential investigations into the mechanisms of resistance target them to improve antibiotic efficacy is required. Regarding this, developing newer and effective treatment options using edge cutting technologies in medical research is the need of time. The reasons underlying the adaptive features in biofilm persistence have been centred on different metabolic and physiological aspects. The high tolerance levels against antibiotics direct researchers to search for novel bioactive molecules that can help combat the problem. In view of this, the present review outlines the focuses on an opportunity of different strategies which are in testing pipeline can thus be developed into products ready to use.

Effectiveness of prophylactic oral and/or vaginal probiotic supplementation in the prevention of recurrent urinary tract infections: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Widespread antibiotic resistance has sparked interest in the lookout for non-antibiotic strategies, particularly focusing on probiotics for the prevention of recurrent urinary tract infections (UTIs). We evaluated the effectiveness of prophylactic probiotic supplementation through oral and intravaginal routes in the prevention of recurrent UTIs. METHODS: This double-blind, placebo-controlled study enrolled 174 premenopausal women with a history of recurrent UTIs and randomized them to either of the four treatment groups, namely, Placebo (G1, oral placebo+vaginal placebo); Oral probiotic (G2, oral lactic acid bacteria and bifidobacteria+vaginal placebo); Vaginal probiotic (G3, oral placebo+vaginal lactobacilli); and Probiotic combination (oral lactic acid bacteria and bifidobacteria+vaginal lactobacilli), for 4 months. Participants were followed-up for symptomatic UTIs for one year. The primary endpoints were the number of symptomatic UTIs at 4 months, the proportion of subjects with at least one symptomatic UTI, and the time to the first symptomatic UTI. RESULTS: The incidence of UTI at 4 months in G1, G2, G3 and G4 was 70.4%, 61.3%, 40.9%, and 31.8%, respectively. The mean number of symptomatic UTI recurrence at 4 months was significantly lower (p<0.05) in G3 (1.06) and G4 (1.07) compared to G1 (2.1) and G2 (1.63). Further, the time to first symptomatic UTI (days) was significantly longer (p<0.05) in G3 (123.8) and G4 (141.8) compared to G1 (69.3) and G2 (71.9). Probiotic supplementations were well tolerated with no serious adverse events. CONCLUSION: Prophylactic supplementation with either vaginal probiotics or in combination with oral probiotics demonstrated effectiveness in preventing recurrent symptomatic UTI episodes.

The new Xpert Mycobacterium tuberculosis/rifampicin (MTB/Rif) Ultra assay in comparison to Xpert MTB/Rif assay for diagnosis of tuberculosis in children and adolescents.

BACKGROUND: Microbiological diagnosis of pediatric tuberculosis (TB) using conventional microbiological techniques has been challenging due to paucibacillary nature of the disease. Molecular methods using cartridge-based tests like Xpert, have immensely improved diagnosis. A novel next-generation cartridge test, Xpert Ultra, incorporates two additional molecular targets and claims to have much lower detection limit. We attempted to compare the two techniques in presumptive pediatric TB patients. OBJECTIVES: The aim of this study was to compare the diagnostic performance of Xpert MTB/Rif Ultra with Xpert MTB/Rif for the detection of pediatric TB. STUDY DESIGN: This is an observational comparative analytical study. METHODS: Children under 15 years of age with presumptive TB were enrolled. Appropriate specimens were obtained (sputum, induced sputum or gastric aspirate for suspected pulmonary TB, cerebrospinal fluid for suspected tubercular meningitis and pleural fluid for suspected tubercular pleural effusion), subjected to smear microscopy, mycobacterial culture, Xpert and Xpert ultra tests and other appropriate diagnostic investigations. RESULTS: Out of 130 enrolled patients, 70 were diagnosed with TB using a composite reference standard (CRS). The overall sensitivity of Xpert was 64.29% [95% confidence interval (CI) 51.93-75.93%] and that of Xpert Ultra was 80% (95% CI 68.73-88.61%) with 100% overall specificity for both. The sensitivity of Xpert and Xpert Ultra in pulmonary specimens (n = 112) was 66.67% and 79.37% and in extrapulmonary specimens (n = 18) was 42.86% and 85.71%, respectively. CONCLUSION: Our study found Ultra to be more sensitive than Xpert for the detection of Mycobacterium tuberculosis in children. Our findings support the use of Xpert Ultra as initial rapid molecular diagnostic test in children under evaluation for TB.

Heavy metal contamination in river water, sediment, groundwater and human blood, from Kanpur, Uttar Pradesh, India.

Exponential industrialization and anthropogenic activities have resulted in water contamination by various heavy metals in Kanpur city, India. Heavy metal pollution, an issue of great concern, is not only affecting river water, but contamination of groundwater is creating health issues and worries. In the present investigation, blood samples were collected from selected volunteers, water and sediment samples from four sites of river Ganga and drinking groundwater samples from 23 locations of Kanpur city. Heavy metals analysis in river water, sediment, and human blood, was done by inductively coupled plasma optical emission spectroscopy (ICP-OES) and atomic absorption spectroscopy (AAS) was used for groundwater samples. Human blood showed a high concentration of arsenic (As) (66.6 ± 0.00 and 76.9 ± 0.01 µg L-1 in males and female subjects, respectively) and thallium (Tl) (13.4 ± 0.004 and 16.6 ± 0.005 µg L-1 in males and female subjects, respectively) with higher concentrations in females than males. Other heavy metals (Nickle, Beryllium, Cadmium, Cobalt, Chromium, Lithium, Molybdenum, Lead) were not observed in any of the tested human blood samples. However, in groundwater sampling, iron (Fe), copper (Cu), and arsenic (As) were detected, one sample had the presence of chromium (Cr), and two samples showed lead (Pb) contamination. River water [Cu (32-125 µg L-1), Cr (19-725 µg L-1), Cd (1-59 µg L-1), Pb (37-163 µg L-1), As (32-153 µg L-1), Th (26.75 µg L-1)] showed a high level of the heavy metals, as compared to reference values of BIS, CPCB (2016a), WHO, EPA and USEPA. River sediment [Cu (4168-34,470 µg Kg-1), Cr (4040-145,650 µg Kg-1), Cd (326-5340 µg Kg-1), Pb (1840-19,350 µg Kg-1), As (103-188 µg Kg-1)] also showed high concentration when compared to reference values of USEPA and PASS. River site 4, with high Cr (725 µg L-1), also showed Cr levels (19.8 µg L-1) in the groundwater samples, indicating Cr contamination in groundwater while Pb was observed at groundwater samples close to two industrial sites. Drinking water might be the primary exposure pathway for As and Tl to enter the human body. The study recommends periodic monitoring of river water, sediment, groundwater, and human blood samples for contamination of heavy metals.

Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities.

INTRODUCTION: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models. METHODS: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively. RESULTS: From the synthesized molecules, pregnane-oximino-amino-alkyl-ether (compound 14b) improved glucose clearance in sucrose-loaded rats and exerted antihyperglycemic activity on STZ-induced diabetic rats. Further evaluation in genetically diabetic db/db mice showed temporal decrease in blood glucose, and improvement in glucose tolerance and lipid parameters, associated with mild improvement in the serum insulin level. Moreover, compound 14b treatment displayed an anti-dyslipidemic effect characterized by significant improvement in altered lipid parameters of the high-fructose, HFD-fed dyslipidemic hamster model. In vitro analysis in the cellular system suggested that compound 14b decreased glucose production in liver cells and stimulated glucose utilization in skeletal muscle cells. These beneficial effects of compound 14b were associated with the activation of the G-protein-coupled bile acid receptor TGR5. CONCLUSION: Compound 14b exhibits antidiabetic and anti-dyslipidemic activities through activating the TGR5 receptor system and can be developed as a lead for the management of type II diabetes and related metabolic complications.

Acute disseminated encephalomyelitis due to a zoonotic co-infection.

Acute disseminated encephalomyelitis (ADEM) is a post-infectious, autoimmune, demyelinating neurological illness, usually attributed to infection with viruses. We describe a case of ADEM occurring in a child with Leptospira-Brucella co-infection. The 12-year-old girl developed a biphasic febrile illness with encephalopathy. On evaluation, she was found to have serological evidence of Brucella and Leptospira infections. Persistence of neurological symptoms after initiating treatment for the co-infection led us to do a magnetic resonance imaging scan of the brain which showed typical findings suggestive of ADEM. Patient responded appropriately to treatment of ADEM with glucocorticoids. The high prevalence of these zoonotic infections in developing countries, and the risk that these may lead to ADEM highlights the importance of detailed evaluation of such cases for proper treatment and better outcomes.

ADEM is a serious neurological disease which occurs as an uncommon complication of certain infections that lead to formation of antibodies which attack the cells of the nervous system. It usually occurs after viral infections, but we came across a 12-year-old girl with ADEM who tested positive for simultaneous infection with two different micro-organisms, both not viruses. These microbes, called Leptospira and Brucella, are common in developing countries and usually lead to infection in individuals in close contact with animals, or with consumption of infected, unpasteurized animal products. Neurological symptoms are uncommon in both infections. However, our case highlights that both infections can occur together and lead to serious neurological illness which needs proper evaluation and a different kind of treatment so that patient has better recovery.

Comparative Evaluation of Three Phenotypic Tests-Carba NP, Modified Carba NP and Rapidec Carba NP Test for Rapid Detection of Carbapenem Resistance in Blood Culture Isolates of Escherichia coli in an ICU Setting.

Background: To determine the antibiotic resistance pattern, the prevalence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance in blood culture isolates of E. coli. Further, we evaluated and compared Carba NP, Modified Carba NP and a kit-based Rapidec Carba NP test to detect carbapenem resistance rapidly. Methods: Twenty-six carbapenem-resistant strains and four susceptible strains were selected. The three methods mentioned above were evaluated as per Clinical Laboratory Standards Institute (CLSI). These tests are based on biochemical detection of the hydrolysis of the beta-lactam ring of a carbapenem-imipenem, followed by the colour change of a pH indicator. Results: Carba NP test was positive in 24 out of 26 isolates; the Modified Carba NP and Rapidec Carba NP tests were positive for all the isolates (26/26). All the carbapenemase non-producers (100%, 04/04) were negative. Conclusion: Modified Carba NP is a more effortless and inexpensive alternative to the Carba NP test, allowing the detection of carbapenemase activity directly from bacterial cultures of Enterobacteriaceae. The test could be used in low-income countries with large reservoirs for carbapenemase producers and can be implemented in any laboratory worldwide.

In vitro evaluation of antibiotic synergy for carbapenem-resistant Klebsiella pneumoniae clinical isolates.

Background & objectives: The prevalence of severe infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) strains has increased worldwide. With rising resistance to polymyxins, the treatment has become challenging. Given the paucity of novel agents and limited data on combination therapy for CRKP, the present study was performed to test antibiotic combinations, for synergy against clinical isolates of CRKP. Methods: A total of 50 clinical isolates of CRKP were included. Modified carbapenem inactivation method was performed for the detection of carbapenemases. In vitro synergy testing was done for the following combinations: meropenem+colistin, imipenem+tigecycline and polymyxin B+levofloxacin. It was performed with epsilometric test and microdilution checkerboard method. The time kill assay (TKA) was used to confirm the results. The fractional inhibitory concentration was also calculated. Results: All CRKP isolates (100%) were ESBL producers and were completely resistant to amoxicillin-clavulanic acid, cefepime, cefotaxime, ceftazidime and piperacillin-tazobactam. Resistance to ciprofloxacin, amikacin and tetracycline was 96, 88 and 54 per cent, respectively. Overall, 78 (39/50) and 88 per cent (44/50) of the 50 CRKP isolates exhibited synergy by TKA for meropenem-colistin and imipenem-tigecycline, respectively. No synergy was detected for levofloxacin-polymyxin B combination. The best combination among the three was that of imipenem and tigecycline followed by meropenem-colistin. Interpretation & conclusions: Of the three combinations tested, imipenem and tigecycline followed by meropenem-colistin were found to be best. No synergy was detected for levofloxacin-polymyxin B combination.

Dual RNA-Seq analysis of Medicago truncatula and the pea powdery mildew Erysiphe pisi uncovers distinct host transcriptional signatures during incompatible and compatible interactions and pathogen effector candidates.

Powdery mildew (PM) is a serious fungal disease of legumes. To gain novel insights into PM pathogenesis and host resistance/susceptibility, we used dual RNA-Seq to simultaneously capture host and pathogen transcriptomes at 1 d post-inoculation of resistant and susceptible Medicago truncatula genotypes with the PM Erysiphe pisi (Ep). Differential expression analysis indicates that R-gene mediated resistance against Ep involves extensive transcriptional reprogramming. Functional enrichment of differentially expressed host genes and in silico analysis of co-regulated promoters suggests that amplification of PTI, activation of the JA/ET signaling network, and regulation of growth-defense balance correlate with resistance. In contrast, processes that favor biotrophy, including suppression of defense signaling and programmed cell death, and weaker cell wall defenses are important susceptibility factors. Lastly, Ep effector candidates and genes with known/putative virulence functions were identified, representing a valuable resource that can be leveraged to improve our understanding of legume-PM interactions.

Increasing Resistance to Reserve Antibiotics: The Experience of a Tertiary Level Neonatal Intensive Care Unit.

BACKGROUND: Blood stream infections are considered as a major cause of morbidity and mortality in neonates. Recent trend shows increasing resistance to commonly used antibiotics. AIMS AND OBJECTIVES: The aim of this study is to find the antibiotic susceptibility pattern of various bacteria from blood samples in neonates and associated risk factors. METHODS: All consecutive cases of intramural neonatal sepsis were enrolled for >12 months. Before starting or changing antibiotic, blood sample under all aseptic precautions was taken for culture. Clinical and demographic details were recorded to analyze risk factors for sepsis. Antibiotic sensitivity tests were done as per CLSI 2019 guidelines. RESULTS: Of the 898 participants, 107 showed culture positivity. Klebsiella pneumoniae (25.2%) and Coagulase-negative Staphylococcus (23.3%). The blood culture positivity rate was 11.9%. Approximately 79% of isolates were multidrug-resistant: extended-spectrum beta-lactamase 90%, carbapenemase-resistant Enterobacteriaceae 27.7% and MRSA 43%. The risk factors found to be associated with sepsis were period of gestation ≤37 weeks, meconium-stained liquor, birth weight <1500 g, mechanical ventilation, partial exchange transfusion, duration of antibiotics for >10 days and duration of both NICU stay and hospital stay for >10 days. The case fatality rate (CFR) was more due to K. pneumoniae (19.2%) and the relative risk of death was 2.53 in culture-positive cases with an attributable risk of 60% and the population attributable risk of 15.4%. CONCLUSION: Increase in antibiotic resistance organisms can lead to an increase in the neonatal CFR, so regular surveillance is needed.

Post-traumatic thrombotic microangiopathy: What trauma surgeons need to know?

Thrombotic microangiopathy (TMA) is characterized by systemic microvascular thrombosis, target organ injury, anemia and thrombocytopenia. Thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome and Shiga toxin E-coli-related hemolytic uremic syndrome are the three common forms of TMAs. Traditionally, TMA is encountered during pregnancy/postpartum period, malignant hypertension, systemic infections, malignancies, autoimmune disorders, etc. Recently, the patients presenting with trauma have been reported to suffer from TMA. TMA carries a high morbidity and mortality, and demands a prompt recognition and early intervention to limit the target organ injury. Because trauma surgeons are the first line of defense for patients presenting with trauma, the prompt recognition of TMA for these experts is critically important. Early treatment of post-traumatic TMA can help improve the patient outcomes, if the diagnosis is made early. The treatment of TMA is also different from acute blood loss anemia namely in that plasmapheresis is recommended rather than platelet transfusion. This article familiarizes trauma surgeons with TMA encountered in the context of trauma. Besides, it provides a simplified approach to establishing the diagnosis of TMA. Because trauma patients can require multiple transfusions, the development of disseminated intravascular coagulation must be considered. Therefore, the article also provides different features of disseminated intravascular coagulation and TMA. Finally, the article suggests practical points that can be readily applied to the management of these patients.

Antibacterial properties and in vivo efficacy of a novel nitrofuran, IITR06144, against MDR pathogens.

OBJECTIVES: The emergence of MDR Gram-negative pathogens and increasing prevalence of chronic infections presents an unmet need for the discovery of novel antibacterial agents. The aim of this study was to evaluate the biological properties of a small molecule, IITR06144, identified in a phenotypic screen against the Gram-negative model organism Escherichia coli. METHODS: A small-molecule library of 10956 compounds was screened for growth inhibition against E. coli ATCC 25922 at concentration 50 µM. MICs of lead compounds were determined by the broth microdilution method. Time-kill kinetics, anti-persister activity, spontaneous frequency of resistance, biofilm inhibition and disruption were assessed by standard protocols. Resistant mutants were generated by serial passaging followed by WGS. In vitro toxicity studies were carried out via the MTT assay. In vivo toxicity and efficacy in a mouse model were also evaluated. RESULTS: IITR06144 was identified as the most promising candidate amongst 29 other potential antibacterial leads, exhibiting the lowest MIC, 0.5 mg/L. IITR06144 belongs to the nitrofuran class and exhibited broad-spectrum bactericidal activity against most MDR bacteria, including the 'priority pathogen', carbapenem-resistant Acinetobacter baumannii. IITR06144 retained its potency against nitrofurantoin-resistant clinical isolates. It displayed anti-persister, anti-biofilm activity and lack of spontaneous resistance development. IITR06144 demonstrated a large therapeutic index with no associated in vitro and in vivo toxicity. CONCLUSIONS: In the light of excellent in vitro properties displayed by IITR06144 coupled with its considerable in vivo efficacy, further evaluation of IITR06144 as a therapeutic lead against antibiotic-resistant infections is warranted.

Determinants of intramyocellular lipid accumulation in early childhood.

BACKGROUND/OBJECTIVES: Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood. SUBJECTS/METHODS: This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6. RESULTS: The mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6. CONCLUSION: This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.

Azetidine-based selective glycine transporter-1 (GlyT1) inhibitors with memory enhancing properties.

A strategy to conformationally restrain a series of GlyT1 inhibitors identified potent analogs that exhibited slowly interconverting rotational isomers. Further studies to address this concern led to a series of azetidine-based inhibitors. Compound 26 was able to elevate CSF glycine levels in vivo and demonstrated potency comparable to Bitopertin in an in vivo rat receptor occupancy study. Compound 26 was subsequently shown to enhance memory in a Novel Object Recognition (NOR) behavioral study after a single dose of 0.03 mg/kg, and in a contextual fear conditioning (cFC) study after four QD doses of 0.01-0.03 mg/kg.

Spatial changes in water and heavy metal contamination in water and sediment of river Ganga in the river belt Haridwar to Kanpur.

Despite heavy investments and a number of government schemes, deterioration in water quality of river Ganga and its tributaries is an issue of serious concern. Among all the cities, thriving on Ganga, Kanpur is considered to add maximum pollution in the river. In the present study, water samples were collected seasonally from nine selected sites within the middle stretch of river Ganga from Haridwar to Kanpur. The velocity, temperature, pH, alkalinity, hardness, dissolved oxygen (DO), biological oxygen demand (BOD) and chemical oxygen demand (COD) were analyzed during winter (November-January), summer (March-June) and monsoon (July-September) season from November 2016 to September 2017 along with heavy metal analysis of water and sediment samples of the winter season. The levels of Cr, Cu, Cd and Pb were analyzed by atomic absorption spectrophotometer. Water quality was evaluated by water quality index (WQI) using BIS and WHO standards. The WQI values showed good water quality at Haridwar site (< 100) while it was very poor at other sites and Kanpur (> 100) which renders it highly unfit for human consumption and survival of some fish species because of low DO value (4.65 ± 1.08 mg L-1) and high values of pH (8.82 ± 0.10), alkalinity (187.88 ± 8.88 mg L-1), BOD (66.64 ± 2.19 mg L-1) and COD (240.00 ± 17.33 mg L-1). WQI showed highly unsuitable water quality at all sites except control site, of which S9 (Siddhanath Ghat) was highly polluted. Lead concentration was higher at Kannauj sites while high Cr was observed at Siddhanath Ghat (S9), Kanpur. The examined metals, such as Cr, Cu, and Pb, were far above the prescribed limits of various standards.

Methicillin-resistant Staphylococcus aureus in Intensive Care Unit Setting of India: A Review of Clinical Burden, Patterns of Prevalence, Preventive Measures, and Future Strategies.

AIM: The aim of this review article is not only to analyze the clinical burden of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care unit (ICU) setting of India, along with the patterns of prevalence and its prevention measures, but also to focus on the new anti-MRSA research molecules which are in late stage of clinical development. BACKGROUND: Methicillin resistance is reported to be present in 13-47% of Staphylococcus aureus infections in India. Therapeutic options to combat MRSA are becoming less, because of emerging resistance to multiple classes of antibiotics. Intensive care units are the harbinger of multidrug-resistant organisms including MRSA and are responsible for its spread within the hospital. The emergence of MRSA in ICUs is associated with poor clinical outcomes, high morbidity, mortality, and escalating treatment costs. There is an urgency to bolster the antibiotic pipeline targeting MRSA. The research efforts for antibiotic development need to match with the pace of emergence of resistance, and new antibiotics are needed to control the impending threat of untreatable MRSA infections. REVIEW RESULTS: Fortunately, several potential antibiotic agents are in the pipeline and the future of MRSA management appears reassuring. CLINICAL SIGNIFICANCE: The authors believe that this knowledge may help form the basis for strategic allocation of current healthcare resources and the future needs. HOW TO CITE THIS ARTICLE: Mehta Y, Hegde A, Pande R, Zirpe KG, Gupta V, Ahdal J, et al. Methicillin-resistant Staphylococcus aureus in Intensive Care Unit Setting of India: A Review of Clinical Burden, Patterns of Prevalence, Preventive Measures, and Future Strategies. Indian J Crit Care Med 2020;24(1):55-62.

Dual-Arm Nanocapsule Targets Neuropilin-1 Receptor and Microtubule: A Potential Nanomedicine Platform.

A multiarm nanomedicine template has been designed following bottom-up approach, which target neuropilin-1 (Nrp-1) receptor of cancer cells. Through this venture, we discovered that cucurbit [6] uril (CB [6]) binds with tubulin close to binding pocket of vinblastine site and perturbs tubulin polymerization. To increase the specificity of gold nanoparticle (GNP) toward Nrp-1-rich cancer cells, we further modified this GNP with Nrp-1 receptor-specific short peptide (CGNKRTR). Remarkably, we found an interesting self-assembly process upon addition of curcumin into the CB [6] and peptide-functionalized GNP, leading to the formation of a spherical nanocapsule (CGNP·Cur). It can deliver and release significantly higher amounts of anticancer drug curcumin in Nrp-1-rich cancer cells. It causes microtubule depolymerization and significant tumor regression in Nrp-1 overexpressed mice melanoma model. These interesting findings show that nanocapsule has high potential to develop a powerful anticancer nanomedicine and help in its preclinical validation.

Biocompatible Lipopeptide-Based Antibacterial Hydrogel.

A biocompatible hydrogel containing a hexapeptide as a key unit has been designed and fabricated. Our design construct comprises a ß-sheet-rich short hexapeptide in the center with a hydrophobic long chain and hydrophilic triple lysine unit attached at the N- and C-terminals, respectively. Thus, it is this amphiphilic nature of the molecule that facilitates gelation. It can capture solvent molecules in the three-dimensional cross-linked fibrillar networks. The amphiphilic character of the construct has been modulated to produce an excellent biocompatible soft material for the inhibition of bacterial growth by rupturing the bacterial cell membrane. This hydrogel is also stable against enzymatic degradation (proteinase K) and, most importantly, offers a biocompatible environment for the growth of normal mammalian cells due to its noncytotoxic nature as observed through the cell viability assay. From the hemolytic assay, the morphology of the human red blood cells is found to be almost intact, which suggests that the hydrogel can be used in biomedical applications. Thus, this newly designed antibacterial hydrogel can be used as both an antibacterial biomaterial and a biocompatible scaffold for mammalian cell culture.

Next-generation strategy for treating drug resistant bacteria: Antibiotic hybrids.

Resistance against nearly all antibiotics used clinically have been documented in bacteria. There is an ever-increasing danger caused by multidrug-resistant Gram-negative bacteria in both hospital and community settings. In Gram-negative bacteria, intrinsic resistance to currently available antibiotics is mainly due to overexpressed efflux pumps which are constitutively present and also presence of protective outer membrane. Combination therapy, i.e., use of two or more antibiotics, was thought to be an effective strategy because it took advantage of the additive effects of multiple antimicrobial mechanisms, lower risk of resistance development and lower mortality and improved clinical outcome. However, none of the benefits were seen in in vivo studies. Antibiotic hybrids are being used to challenge the growing drug resistance threat and increase the usefulness of current antibiotic arsenal. Antibiotic hybrids are synthetic constructs of two molecules which are covalently linked. These could be two antibiotics or antibiotic with an adjuvant (efflux pump inhibitor, siderophore, etc.) which increases the access of the antibiotics to the target. The concepts, developments and challenges in the future use of antibiotic hybrids are discussed here. Majority of the studies have been conducted on fluoroquinolones and aminoglycosides molecules. The antibiotic tobramycin has the property to enhance the action of antimicrobial agents against which the multidrug-resistant Gram-negative bacteria were earlier resistant, and thus potentiating the action of legacy antibiotics. Antibiotic hybrids may have a role as the silver bullet in Gram-negative bacteria to overcome drug resistance as well as extend the spectrum of existing antibiotics.