Search

Background: Cefepime is a fourth-generation cephalosporin with a broad spectrum coverage and anti-pseudomonal activity. The safety profile of cefepime was relatively favourable until neurotoxicity was first reported in 1999. Despite cefepime-induced neurotoxicity (CIN), it continues to be a principal part of parenteral treatment for various infections. Objective: The study aimed to determine the incidence and risk factors for CIN compared to other antibiotics. Methods: A retrospective cohort study was conducted involving 738 patients over eight months in Kasturba Medical College and Hospital, Manipal, India. Patients with cefepime were selected as study cohort (SC; n= 496), and other antibiotics were included in the reference cohort (RC; n=242). Results: The results showed that 53 (10.7%) patients developed neurotoxicity in the SC, whereas 12 (5%) patients in the RC. A significant association was found between neurotoxicity and cefepime use (X2 =6.641; p=0.01). SC has a 2.29 times increased risk of neurotoxicity than RC (OR: 2.29; 95% CI: 1.2-4.38). Risk estimation showed that renal failure patients had a 5.5 times higher risk for CIN than non-renal failure patients (OR: 5.5; 95% CI: 2.98 - 10.17). CIN symptoms were disorientation (38.5%), loss of consciousness (23.1%), drowsiness (18.5%), etc. The calculated number needed to harm (NNH) for cefepime was 17.2. Conclusions: The study found a higher incidence of CIN compared to other antibiotics-induced neurotoxicity and a harmful association between cefepime use and CIN development. Besides, renal failure is a risk factor for CIN. Therefore, the study warrants the use of cefepime, where no other alternatives are available. more...

Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D - deficient individuals more susceptible to infection. Infections attributable to biofilm-producing microbes can be managed by adjuvant therapy with vitamin D because of its immunomodulatory role, particularly because of the ability of vitamin D-pathway to induce the antimicrobial peptides like cathelicidin and decrease proinflammatory cytokines.This narrative review covers biofilm formation, infections associated with biofilm due to vitamin D deficiency, putative role of vitamin D in host protection and the effect of vitamin D supplementation in biofilm-associated infections. A comprehensive literature search in PubMed and Google Scholar utilizing suitable keywords at multiple time points extracted relevant articles.Although vitamin D deficiency has been associated with infections by biofilm producing microbes, comprehensive clinical trials in various ethnicities are required to understand the likely relationships between vitamin D receptor gene expression, cathelicidin levels and infection outcome. Current evidence hypothesizes that maintaining normal vitamin D level can help prevent and treat these infections. more...

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and is rising in incidence with widespread prevalence. Multiple gene variants are associated with glucose homeostasis, complex T2DM pathogenesis, and its complications. Exploring more effective therapeutic strategies for patients with diabetes is crucial. Pharmacogenomics has made precision medicine possible by allowing for individualized drug therapy based on a patient’s genetic and genomic information. T2DM is treated with various classes of oral hypoglycemic agents, such as biguanides, sulfonylureas, thiazolidinediones, meglitinides, DPP4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, and GLP1 analogues, which exhibit various pharmacogenetic variants. Although genomic interventions in monogenic diabetes have been implemented in clinical practice, they are still in the early stages for complex polygenic disorders, such as T2DM. Precision DM medicine has the potential to be effective in personalized therapy for those suffering from various forms of DM, such as T2DM. With recent developments in genetic techniques, the application of candidate-gene studies, large-scale genotyping investigations, genome-wide association studies, and “multiomics” studies has begun to produce results that may lead to changes in clinical practice. Enhanced knowledge of the genetic architecture of T2DM presents a bigger translational potential. This review summarizes the genetics and pathophysiology of T2DM, candidate-gene approaches, genome-wide association studies, personalized medicine, clinical relevance of pharmacogenetic variants associated with oral hypoglycemic agents, and paths toward personalized diabetology. more...

Tuberculosis (TB) is a transnational public health concern, which requires more precise treatment strategies than the existing approaches. Vitamin D modulates the inflammatory and immune response to the disease. Robust evidence shows that vitamin D deficiency and its receptor gene polymorphism influence the susceptibility to TB and the outcome of the anti-tubercular treatment (ATT). However, in the different populations, these findings were inconsistent and even contradictory.The current review focuses on the association between vitamin D receptor (VDR) gene polymorphism with the risk of development of TB disease and response to the ATT. Additionally, it reviews various systematic reviews and meta-analyses on the impact of vitamin D supplements on both clinical and treatment outcomes in TB patients.Although the majority of the findings rule out the benefits of the supplementation, sufficient evidence is available to warrant larger epidemiological research that should be aimed to generate possible interaction among the VDR polymorphism, vitamin D status, and the outcome in TB. We conclude that establishing such an association in different ethnic populations will help design nutrigenomics- or pharmacogenomics-based vitamin D supplementation to develop a personalized medicine approach to flatten the curve of TB disease. more...

Despite the advancement in wound care, the effective therapy of chronic diabetic ulcers continues to be a challenge. Wound healing is a highly controlled process, which involves a sequence of complex overlapping steps. This healing pathway comprises of hemostasis, inflammation, proliferative, and remodeling phases. Recent evidence suggests that phytomedicines can prevent or repair different kinds of destructive cellular damage, including chronic wounds. Several phytochemicals such as polyphenols, alkaloids, flavonoids, terpenoids, and glycosides have pleiotropic effects, including stimulation of fibroblast proliferation, the main step in wound healing. Besides, the mechanism involves induction of collagen synthesis, migration, and reepithelization and their antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory actions. Similarly, the use of phytochemicals alone or as an adjuvant with standard therapy has demonstrated promising results in managing complications in the diabetic foot. For instance, the extract of Carica papaya has been shown antioxidant, antimicrobial, and anti-inflammatory, and immunomodulatory effects, which, together with proteolytic enzymatic activity, contributes to its wound healing property. It is generally believed that phytotherapy has no or minimal toxicity than synthetic therapeutic agents, favoring its use in diabetic foot ulcer management. The current review highlights the selected phytochemicals and their sources; and potential application in diabetic foot ulcer management. more...

Background/objectives Diabetic foot infections (DFI) are common complications among diabetics. These wounds can cause discomfort and often become infected. In India, currently there is a paucity of data on patient adherence towards antibiotic use in DFIs. Therefore, this study was aimed to evaluate antimicrobial susceptibility pattern, antimicrobial therapy and its adherence in DFI patients. Method A prospective observation study (N = 150, newly diagnosed DFI patients) was conducted in Kasturba hospital, Manipal over a period of 6 months. Culture and Sensitivity pattern of the microbes of the patients were obtained from hospital data management system to develop cumulative antimicrobial susceptibility pattern. Medication adherence was measured by using Culig adherence scale at the first follow-up visit. Results The most common microbes were Methicillin-sensitive Staphylococcus aureus (23.9%), Klebsiella pneumonia (13.3%) and Escherichia coli (13.3%). Inj. Amoxicillin-Clavulanic acid 1.2 gm (28.6%) was highest prescribed empirical therapy in DFI's followed by Inj. Cefuroxime-Sulbactam 2.25 gm (14.6%), Ceftriaxone (0.7%) and Trimethoprim- Sulfamethoxazole (2%) was the most sensitive antibiotic. Cumulative antimicrobial susceptibility pattern shows Chloramphenicol, Colistin, Levofloxacin, Rifampicin has developed resistance towards most of the common organisms in DFI. Statistically significant association was observed between empirical therapy with T.Cefuroxime 625 mg and improved clinical outcomes (p Conclusion Ceftriaxone and Trimethoprim-Sulfamethoxazole are most sensitive antibiotics towards most common organisms in DFIs. T. cefuroxime 625 mg showed statistically significant improvement in clinical outcomes while adherence is very low in most of the DFI patients. more...

Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19. more...

Background: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity. Objective: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients. Method: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review. Result: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant. Conclusion: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population. Prospero Registration Id: CRD42020211189 more...

Globally, mercury (Hg) poisoning cases have been accounted for consistently high mortality rate. Exposure with Hg is the second-highest common reason for toxicity with metal poisoning. Normally, Hg exists in three forms, which are essential as in thermometers, inorganic as batteries, and organic as methylmercury in fish. Heavy metal form of Hg has been used for medical as well as toxicological purposes for quite a long time. Recently, the metal has gained high focus due to the apprehension of environmental exposure. Long-term exposure to Hg compounds from various sources can adversely affect various biological systems. Pulmonary, cardiovascular, gastrointestinal, neurological, and dermatological systems are usually encountered in human beings after Hg poisoning. The level of Hg can be measured in blood, hair, and urine samples. Currently, along with supportive therapy, chelating agents such as dimercaprol (British anti-Lewisite; BAL), succimer (2,3-dimercaptosuccinic acid; DMSA), and unithiol (dimercaptopropanesulfoxid acid; DMPS) are used in Hg toxicity. The chapter discusses properties, uses, sources of Hg and its exposure, toxic dose, toxicokinetics, mechanism of toxicity, clinical presentations in humans and animals, diagnosis, and management of Hg. The authors discussed a pediatric case of Hg poisoning at the end of the chapter for the readers. more...

Vitamin D deficiency (VDD) partly explains geographical differences in COVID-19 susceptibility, severity, and mortality. VDD among African-Americans, diabetics, hypertensive, and aged populations possibly explain the higher death rate, aggravated by cocooning. Vitamin D is pleiotropic, mediating bone metabolism, calcium homeostasis, and immune functions, whereas VDD is associated with inflammatory reactions and immune dysfunction, predisposing individuals to severe infections. Vitamin D modulates innate and adaptive immunity via the expression of genes that code antimicrobial peptides (AMPs). And the expression of cluster of differentiation (CD)14, the co-receptor for epidermal toll-like receptor (TLR)4. AMPs stimulate TLR2 in macrophages, increasing the conversion of vitamin D into its active form by cytochrome P450 27B1. Antiviral properties of vitamin D-induced AMPs can shift the polarization of the adaptive immune response from helper T cells (Th)1 to the more regulatory Th2 responses that suppress immune over-reactivity by preventing cytokine storm, which is already demonstrated during the Spanish flu episode. Vitamin D induces antiviral effects by both direct and indirect mechanisms via AMPs, immunomodulation, the interplay between major cellular and viral elements, induction of autophagy and apoptosis, variation of genetic and epigenetic factors. The crosstalk between vitamin D and intracellular signaling pathways may operate as a primary regulatory action on viral gene transcription. VDD may increase the likelihood of infection with enveloped viruses, including retrovirus, hepatitis, and dengue. Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, suggesting benefits from supplementation.Key teaching pointsVitamin D induces antiviral effects by direct and indirect mechanisms via AMPs, immunomodulation, induction of autophagy, etc.Epidemiology of VDD partly explains geographical differences in COVID-19 susceptibility, severity, and mortality.Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, together suggesting benefits from supplementation.Many clinical trials are underway globally to delineate the role of vitamin D in both prevention and treatment of COVID-19. more...

Introduction:: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, as it can physically and emotionally impact the person. Its management can be challenging and expensive, depending on the severity of the wound and the presence of infection. Background:: The fat-soluble molecule, vitamin D, has gained great importance ever since its pleiotropism has been recognized. Its efficacy could be attributed to the presence of vitamin D receptors in most of the body tissues. Vitamin D plays a significant role in cell proliferation, differentiation, and immune modulation. It modulates the T and B cells resulting in the suppression of the immunoglobulins, autoimmunity, and inflammation. Methods:: We performed a literature search with the objective to highlight the role of vitamin D in peripheral vascular disease and peripheral neuropathy, which are the major risk factors for DFU, as well as evidences of its role in wound healing and management of DFU. Results:: Preclinical and clinical studies have shown that vitamin D influences multiple phases of wound healing and thereby accelerates the process. It modulates various cells involved in proliferation and remodelling phases. Vitamin D also enhances the expression of antimicrobial peptides that help to eliminate the microbes, as well as suppress the proinflammatory responses while enhancing the anti-inflammatory responses. Conclusion:: This review concludes vitamin D to have a protective role in the immune and vascular system, improve glycaemic outcomes, and wound healing. Therefore, vitamin D could be a preferred adjuvant in the management of DFU. more...

Rifampin (RF) is metabolized in the liver into an active metabolite 25-desacetylrifampin and excreted almost equally via biliary and renal routes. Various influx and efflux transporters influence RF disposition during hepatic uptake and biliary excretion. Evidence has also shown that Vitamin D deficiency (VDD) and Vitamin D receptor (VDR) polymorphisms are associated with tuberculosis (TB). Hence, genetic polymorphisms of metabolizing enzymes, drug transporters and/or their transcriptional regulators and VDR and its pathway regulators may affect the pharmacokinetics of RF. In this narrative review, we aim to identify literature that has explored the influence of single nucleotide polymorphisms (SNPs) of genes encoding drug transporters and their transcriptional regulators (SLCO1B1, ABCB1, PXR and CAR), metabolizing enzymes (CES1, CES2 and AADAC) and VDR and its pathway regulators (VDR, CYP27B1 and CYP24A1) on plasma RF concentrations in TB patients on antitubercular therapy. Available reports to date have shown that there is a lack of any association of ABCB1, PXR, CAR, CES1 and AADAC genetic variants with plasma concentrations of RF. Further evidence is required from a more comprehensive exploration of the association of SLCO1B1, CES2 and Vitamin D pathway gene variants with RF pharmacokinetics in distinct ethnic groups and a larger population to reach conclusive information. more...

Diabetes type II is a complex disease with unclear pathophysiology. Lack of adherence and high cost of medicines invariably make the management of diabetes type II highly challenging. Newer fixed drug combinations (FDC) are cost effective and can improve the medication adherence thereby prevent the complications of diabetes. Safety and efficacy of newer FDCs are not well established in all populations. Moreover, extrapolating the efficacy and safety data globally may not be pragmatic. Our review will discuss newer chemical combinations available for the treatment of diabetes type II. Areas covered: In the present review, the authors discussed the newer FDCs available as add on therapy to the existing pharmacological interventions of diabetes type II that have shown promising results in various randomised trials with regard to efficacy and safety. Expert opinion: Safety and efficacy data of newer FDCs available as an adjuvant therapy to conventional pharmacological interventions in diabetes type II revealed that fewer new FDCs are promising with their high efficacy and low adverse effect. However, there is a need to explore the place in therapy to establish the utility of FDC in diabetes type II management. more...

The purpose of the chapter is to view vitamin D in the context of sport nutrition and its vital role in enhancing athletic performance. The chapter focuses on the present understanding of the physiological functions of vitamin D in bone health, musculoskeletal system, and immunity, in addition to the potential impact on athletic performance. Based on the available evidence, retaining the serum 25-hydroxy vitamin D (25(OH)D) concentration above the optimal level (up to 100 nmol/L) increases musculoskeletal function, reduces fracture recovery period from exercise, improves both force as well as power production, and enhances production of testosterone, all of which influence the athletic performance. On the other hand, deficiency of vitamin D can cause numerous health problems, such as increased incidence of bone injuries, stress fracture, prolonged skeletal muscle pain, and respiratory tract illness. In spite of these, large populations of athletes are vitamin D deficient. Regular intake of dietary vitamin D sources alone is not enough to preserve sufficient level of vitamin D. Adequate level of sun exposure and regular supplements of vitamin D or a mixture of dietary intake and sun exposure along with vitamin D supplements are necessary to attain adequate levels vitamin D. Recommendation of vitamin D to each athletes should be individualized based on their serum 25(OH)D level, clinical symptoms, season, and diet. However, intoxication of vitamin D from over consumption of the supplements is unusual. Normally, athletes with insufficient vitamin D status need daily vitamin D supplementation with a minimum of 1500–2000 IU. more...

Etiology of childhood obesity and diabetes are multidimensional and environmental, comprising dietary, lifestyle, pathological, and genetic factors. This chapter focuses on the significance of diet as a consequent factor for childhood obesity and diabetes, especially through its action on gut microbiota maturation starting from infancy. The chapter also discusses existing approaches to exploit beneficial microbes to modulate the composition of the gut microbiota and thereby restrain energy harvest efficiency. Growing evidence shows that childhood obesity and diabetes are associated with alterations in the intestinal microbiome. Furthermore, experimental as well as clinical data demonstrate that modulation of the microbiota with prebiotics, probiotics, and synbiotics decreases fat accumulation and insulin resistance. Therefore the purpose of this chapter is to provide an overview on the role of gut microbiota in energy balance and obesity, as well as diabetes. The promising role of prebiotics and probiotics in optimizing body weight and composition recognizes them as novel nutraceuticals for the prevention and management of childhood obesity, as well as diabetes. more...