Medical Research

Creating political commitment for antimicrobial resistance in developing countries Rajesh Bhatia, Vishwa Mohan Katoch, Hajime Inoue Indian Journal of Medical Research 2019 149(2):83-86

Antimicrobial susceptibility profile & resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India Balaji Veeraraghavan, Kamini Walia Indian Journal of Medical Research 2019 149(2):87-96 Antimicrobial resistance is a major concern globally. Infections due to drug-resistant pathogens are becoming difficult and a challenge to treat. As treatment choices are limited due to the high-drug resistance rates, there is an increase in the health care cost, duration of hospital stay, morbidity and mortality rates. Understanding the true burden of antimicrobial resistance for a geographical location is important to guide effective empirical therapy. To have a national data, it is imperative to have a systemic data capturing across the country through surveillance studies. Very few surveillance studies have been conducted in India to generate national data on antimicrobial resistance. This review aims to report the cumulative antibiogram and the resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India.

Next-generation strategy for treating drug resistant bacteria: Antibiotic hybrids Varsha Gupta, Priya Datta Indian Journal of Medical Research 2019 149(2):97-106 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

Understanding policy dilemmas around antibiotic use in food animals & offering potential solutions Kamini Walia, Monica Sharma, Sonam Vijay, Bibek R Shome Indian Journal of Medical Research 2019 149(2):107-118 The looming concern of antimicrobial resistance (AMR) has prompted the government of many countries of the world to act upon and come up with the guidelines, comprehensive recommendations and policies concerning prudent use of antibiotics and containment of AMR. However, such initiatives from countries with high incidence of antibiotic-resistant bacteria in food animals are still in infancy. This review highlights the existing global policies on antibiotics use in food animals along with details of the various Indian policies and guidelines. In India, in spite of availability of integrated policies for livestock, poultry and aquaculture sector, uniform regulations with coordinated initiative are needed to formulate strict policies regarding antimicrobial use both in humans and animals. In an attempt to create effective framework to tackle the AMR, the Indian Council of Medical Research initiated a series of dialogues with various stakeholders and suggested various action points for urgent implementation. This review summarizes the recommendations made during the various consultations. The overarching aim of this review is to clearly delineate the action points which need to be carried out urgently to regulate the antibiotic use in animals.

Antimicrobial resistance in the environment: The Indian scenario Neelam Taneja, Megha Sharma Indian Journal of Medical Research 2019 149(2):119-128 Antimicrobial resistance (AMR) continues to pose a significant public health problem in terms of mortality and economic loss. Health authorities of several countries including India have formulated action plans for its containment. In this fight against AMR, it is important to realize the contribution by all the following four spheres: humans, animals, food and environment. This review incorporates all the spheres of One Health concept from the Indian perspective. India has one of the highest rates of resistance to antimicrobial agents used both in humans and food animals. The environment, especially the water bodies, have also reported the presence of resistant organisms or their genes. Specific socio-economic and cultural factors prevalent in India make the containment of resistance more challenging. Injudicious use of antimicrobials and inadequate treatment of waste waters are important drivers of AMR in India. Use of sludge in agriculture, improper discard of livestock animals and aquaculture industry are considered AMR contributors in other countries but Indian data regarding these are lacking. Efforts to combat AMR have been initiated by the Indian health authorities but are still at preliminary stages. Keeping in view the challenges unique to India, future directions are proposed.

Efflux pump inhibitors for bacterial pathogens: From bench to bedside Atin Sharma, Vivek Kumar Gupta, Ranjana Pathania Indian Journal of Medical Research 2019 149(2):129-145 With the advent of antibiotics, bacterial infections were supposed to be a thing of past. However, this instead led to the selection and evolution of bacteria with mechanisms to counter the action of antibiotics. Antibiotic efflux is one of the major mechanisms, whereby bacteria pump out the antibiotics from their cellular interior to the external environment using special transporter proteins called efflux pumps. Inhibiting these pumps seems to be an attractive strategy at a time when novel antibiotic supplies are dwindling. Molecules capable of inhibiting these pumps, known as efflux pump inhibitors (EPIs), have been viewed as potential therapeutic agents that can rejuvenate the activity of antibiotics that are no longer effective against bacterial pathogens. EPIs follow some general mechanisms of efflux inhibition and are derived from various natural as well as synthetic sources. This review focuses on EPIs and identifies the challenges that have kept these futuristic therapeutics away from the commercial realm so far.

Mismatch amplification mutation assay-polymerase chain reaction: A method of detecting fluoroquinolone resistance mechanism in bacterial pathogens Vijaya Kumar Deekshit, Kadeeja Jazeela, Gunimala Chakraborty, Anusha Rohit, Anirban Chakraborty, Indrani Karunasagar Indian Journal of Medical Research 2019 149(2):146-150 The mismatch amplification assay is a modified version of polymerase chain reaction (PCR) that permits specific amplification of gene sequences with single base pair change. The basis of the technique relies on primer designing. The single nucleotide mismatch at the 3' proximity of the reverse oligonucleotide primer makes Taq DNA polymerase unable to carry out extension process. Thus, the primers produce a PCR fragment in the wild type, whereas it is not possible to yield a product with a mutation at the site covered by the mismatch positions on the mismatch amplification mutation assay (MAMA) primer from any gene. The technique offers several advantages over other molecular methods, such as PCR-restriction fragment length polymorphism (RFLP) and oligonucleotide hybridization, which is routinely used in the detection of known point mutations. Since multiple point mutations in the quinolone resistance determining region play a major role in high-level fluoroquinolone resistance in Gram-negative bacteria, the MAMA-PCR technique is preferred for detecting these mutations over PCR-RFLP and sequencing technology.

A systematic review of antimicrobial resistance of typhoidal Salmonella in India Carl D Britto, Jacob John, Valsan P Verghese, Andrew J Pollard Indian Journal of Medical Research 2019 149(2):151-163 Background & objectives: The temporal trends in the development of antimicrobial resistance (AMR) among Salmonella Typhi and Salmonella Paratyphi in India have not been systematically reported. We aimed to systematically review the temporal AMR trends (phenotypic and molecular mechanisms) in bacterial isolates from patients with enteric fever over two decades in India. Methods: To identify trends in AMR in India, resistance patterns among 4611 individual S. Typhi isolates and 800 S. Paratyphi A isolates, reported from 1992 to 2017 in 40 publications, were analysed. Molecular resistance determinants were extracted from 22 publications and also reviewed in accordance with the PRISMA guidelines. Articles were sourced using a predefined search strategy from different databases. Results: The analyses suggested that multidrug-resistant (MDR) enteric fever was declining in India and being replaced by fluoroquinolone (FQ) resistance. Mutations in gyrA and parC were key mechanisms responsible for FQ resistance, whereas MDR was largely driven by resistance determinants encoded on mobile genetic elements (plasmids, transposons). Interpretation & conclusions: The results reflect the effect of antimicrobial pressure which has been driving AMR in typhoidal Salmonella in India. Understanding these trends is important in planning future approaches to therapy, which serve as a baseline for assessment of the impact of new typhoid conjugate vaccines against these resistant organisms.

Establishing Antimicrobial Resistance Surveillance & Research Network in India: Journey so far Kamini Walia, Jayaprakasam Madhumathi, Balaji Veeraraghavan, Arunaloke Chakrabarti, Arti Kapil, Pallab Ray, Harpreet Singh, Sujatha Sistla, VC Ohri Indian Journal of Medical Research 2019 149(2):164-179 The Indian Council of Medical Research, in 2013, initiated the Antimicrobial Resistance Surveillance & Research Network (AMRSN) to enable compilation of data on six pathogenic groups on antimicrobial resistance from the country. The overarching aim of this network was to understand the extent and pattern of antimicrobial resistance (AMR) and use this evidence to guide strategies to control the spread of AMR. This article describes the conception and implementation of this AMR surveillance network for India. Also described are the challenges, limitations and benefits of this approach. Data from the Network have shown increasing resistance in Gram-negative bacteria in the hospitals that are part of this network. Combined resistance to third-generation cephalosporins and fluoroquinolones and increasing carbapenem resistance are worrisome, as it has an important bearing on the patients' outcome and thus needs to be addressed urgently. Data generated through this Network have been used to develop treatment guidelines, which will be supportive in harmonizing treatment practices across the tertiary level healthcare institutions in the country. While, the major benefit of having a surveillance system is the collection of real-time accurate data on AMR including the mechanisms of resistance, representativeness to community, sustaining the current effort and expanding the current activities to next levels of healthcare settings are the major challenges. The data emanating from the network besides providing evidence, expose several gaps and lacunae in the ecosystem and highlight opportunities for action by multiple stakeholders.

Policy document on antimicrobial stewardship practices in India Kamini Walia, VC Ohri, Jayaprakasam Madhumathi, V Ramasubramanian Indian Journal of Medical Research 2019 149(2):180-184 Antimicrobial resistance (AMR) in India has become a great threat because of high rate of infectious diseases. One of the key contributing factors is high antibiotic use due to poor prescription practices, self-medication, over-the-counter sale of drugs and lack of awareness. Antimicrobial stewardship programme (AMSP) have been proved to be successful in restraining sale and use of antibiotics to a large extent in many countries. An AMSP programme for a hospital is imperative for rational and evidence-based antimicrobial therapy. The ultimate aim is to improve patient outcomes, reduce emergence of bacterial resistance and ensure longevity of the existing antimicrobials. The primary goal of AMSP is to encourage cautious use of available antibiotics by training the healthcare workers and creating awareness. This article describes the strategies and recommendations for formulation of AMSP policy for India.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com