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Purpose: Healthcare-associated infections (HCAIs/ HAIs) are the most common adverse occurrences during health care delivery. Across the globe, millions of patients are affected by HAIs annually, with a higher burden and impact in developing nations. a major lacuna in planning preventing protocols is the absence of National Surveillance Systems in most low-middle income countries, which also prevents allocation of resources to the high-priority areas. Among all the HAIs, there is a huge global burden of SSIs, in terms of morbidity, prolonged hospital stays, increased antimicrobial treatment as well as attributable mortality. Method: This manuscript details the process of establishment of an SSI surveillance protocol at a level-1 trauma centre in North India. Result and Conclusion: Surveillance is an essential tool to reduce this burden. It is also an important primary step in recognizing problems and priorities, and it plays a crucial role in identifying risk factors for SSI and to be able to target modifiable risk factors. Therefore, it is imperative to establish reliable systems for surveillance of HAIs, to regularly estimate the actual burden of HAIs, and to use these data for developing indigenous preventive measures, tailored to the country's priorities.
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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.
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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.
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Growing resistance to antimicrobials has become one of the most important problems of the 21st century. The development of new antibiotics is a time-consuming process involving huge financial resources. An alternate approach is proper utilization of the existing antibiotics through the surveillance of resistance. An important component of surveillance is the informatics tool for collection, management and analysis of antimicrobial resistance susceptibility testing data. Based on the scope, antimicrobial resistance surveillance resistance tools can be broadly classified as collectors and integrators. Individually, both the integrators and collectors have limitations which restrict their use in India. There is a strong requirement to develop a hybrid AMR surveillance tool that captures standardized data from small laboratories and integrates data from multiple sources to present a complete picture of the country. Here we describe a tooli-AMRSS developed by the Indian Council of Medical Research for collection, storage and management of AMR data from collaborating institutes/laboratories and to generate real-time analytics and reports.
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Background & objectives: Antimicrobial resistance is a major challenge in the treatment of typhoid fever with limited choices left to empirically treat these patients. The present study was undertaken to determine the current practices of antibiotic use in children attending a tertiary care hospital in north India. Methods: This was a descriptive observational study in children suffering from enteric fever as per the case definition including clinical and laboratory parameters. The antibiotic audit in hospitalized children was measured as days of therapy per 1000 patient days and in outpatient department (OPD) as antibiotic prescription on the treatment card. Results: A total of 128 children with enteric fever were included in the study, of whom, 30 were hospitalized and 98 were treated from OPD. The mean duration of fever was 9.5 days at the time of presentation. Of these, 45 per cent were culture positive with Salmonella Typhi being aetiological agent in 68 per cent followed by S. Paratyphi A in 32 per cent. During hospitalization, the average length of stay was 10 days with mean duration of defervescence 6.4 days. Based on antimicrobial susceptibility ceftriaxone was given to 28 patients with mean duration of treatment being six days. An additional antibiotic was needed in six patients due to clinical non-response. In OPD, 79 patients were prescribed cefixime and additional antibiotic was needed in five during follow up visit. Interpretation & conclusions: Based on our findings, ceftriaxone and cefixime seemed to be the first line of antibiotic treatment for typhoid fever. Despite susceptibility, clinical non-response was seen in around 10 per cent of the patients who needed combinations of antibiotics.
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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.
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Background & objectives: Bacillary dysentery caused by Shigella spp. remains an important cause of the crisis in low-income countries. It has been observed that Shigella species have become increasingly resistant to most widely used antimicrobials. In this study, the antimicrobial resistance, virulence and plasmid profile of clinical isolates of Shigella species were determined. Methods: Sixty clinical Shigella isolates were subjected to whole-genome sequencing using Ion Torrent platform and the genome sequences were analyzed for the presence of acquired resistance genes, virulence genes and plasmids using web-based software tools. Results: Genome analysis revealed more resistance genes in Shigella flexneri than in other serogroups. Among ?-lactamases, blaOXA-1was predominantly seen followed by the blaTEM-1B and blaEC genes. For quinolone resistance, the qnr S gene was widely seen. Novel mutations in gyr B, par C and par E genes were observed. Cephalosporins resistance gene, blaCTX-M-15 was identified and plasmid-mediated AmpC ?-lactamases genes were found among the isolates. Further, a co-trimoxazole resistance gene was identified in most of the isolates studied. Virulence genes such as ipaD, ipaH, virF, senB, iha, capU, lpfA, sigA, pic, sepA, celb and gad were identified. Plasmid analysis revealed that the IncFII was the most commonly seen plasmid type in the isolates. Interpretation & conclusions: The presence of quinolone and cephalosporin resistance genes in Shigella serogroups has serious implications for the further spread of this resistance to other enteric pathogens or commensal organisms. This suggests the need for continuous surveillance to understand the epidemiology of the resistance.
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Background & objectives: Acinetobacter baumannii is an opportunistic pathogen responsible for causing nosocomial infections. A. baumannii develops resistance to various antimicrobial agents including carbapenems, thereby complicating the treatment. This study was performed to characterize the isolates for the presence of various ?-lactamases encoding genes and to type the isolates to compare our clones with the existing international clones across five centres in India. Methods: A total 75 non-repetitive clinical isolates of A. baumannii from five different centres were included in this study. All the isolates were confirmed as A. baumannii by bl aOXA-51-likePCR. Multiplex PCR was performed to identify the presence of extended spectrum ?-lactamases (ESBL) and carbapenemases. Multilocus sequence typing was performed to find the sequence type (ST) of the isolates. e-BURST analysis was done to assign each ST into respective clonal complex. Results: blaOXA-51-likewas present in all the 75 isolates. The predominant Class D carbapenemase was blaOXA-23-likefollowed by Class B carbapenemase, blaNDM-like. Class A carbapenemase was not observed. blaPER-likewas the predominant extended spectrum ?-lactamase. ST-848, ST-451 and ST-195 were the most common STs. Eight-novel STs were identified. e-BURST analysis showed that the 75 A. baumannii isolates were clustered into seven clonal complexes and four singletons, of which, clonal complex 208 was the largest. Interpretation & conclusions: Most of the isolates were grouped under clonal complex 208 which belongs to the international clonal lineage 2. High occurrence of ST-848 carrying blaOXA-23-likegene suggested that ST-848 could be an emerging lineage spreading carbapenem resistance in India.
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Background & objectives: Plasmid has led to increase in resistant bacterial pathogens through the exchange of antimicrobial resistance (AMR) genetic determinants through horizontal gene transfer. Baseline data on the occurrence of plasmids carrying AMR genes are lacking in India. This study was aimed to identify the plasmids associated with AMR genetic determinants in ESKAPE pathogens. Methods: A total of 112 ESKAPE isolates including Escherichia coli (n=37), Klebsiella pneumoniae (n=48, including 7 pan-drug susceptible isolates), Acinetobacter baumannii (n=8), Pseudomonas aeruginosa (n=1) and Staphylococcus aureus (n=18) were analyzed in the study. Isolates were screened for antimicrobial susceptibility and whole genome sequencing of isolates was performed using Ion Torrent (PGM) sequencer. Downstream data analysis was done using PATRIC, ResFinder, PlasmidFinder and MLSTFinder databases. All 88 whole genome sequences (WGS) were deposited at GenBank. Results: Most of the study isolates showed resistant phenotypes. As analyzed from WGS, the isolates included both known and unknown sequence types. The plasmid analysis revealed the presence of single or multiple plasmids in the isolates. Plasmid types such as IncHI1B(pNDM-MAR), IncFII(pRSB107), IncFIB(Mar), IncFIB(pQil), IncFIA, IncFII(K), IncR, ColKP3 and ColpVC were present in K. pneumoniae. In E. coli, IncFIA, IncFII, IncFIB, Col(BS512), IncL1, IncX3 and IncH were present along with other types. S. aureus harboured seven different plasmid groups pMW2 (rep 5), pSAS1 (rep 7), pDLK1 (rep 10), pUB110 (rep US12), Saa6159 (rep 16), pKH12 (rep 21) and pSA1308 (rep 21). The overall incidence of IncF type plasmids was 56.5 per cent followed by Col type plasmids 18.3 per cent and IncX 5.3 per cent. Other plasmid types identified were <5 per cent. Interpretation & conclusions: Results from the study may serve as a baseline data for the occurrence of AMR genes and plasmids in India. Information on the association between phenotypic and genotypic expression of AMR was deciphered from the data. Further studies on the mechanism of antibiotic resistance dissemination are essential for enhancing clinical lifetime of antibiotics.
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Background & objectives: The increasing prevalence of extended-spectrum ?-lactamases (ESBLs) has abated therapeutic options worldwide. This study was undertaken to investigate the molecular profile and resistance patterns of ESBLs among clinical isolates of Escherichia coli and Klebsiella pneumoniae at four tertiary care centres in India. Methods: Clinical isolates of E. coli and K. pneumoniae were collected from the All India Institute of Medical Sciences (AIIMS), New Delhi; the Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry; Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh and Christian Medical College (CMC), Vellore, over one and a half year period. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion method. ESBLs were confirmed phenotypically, and multiplex PCR was performed to identify genes for ?-lactamases (blaTEM, blaSHV, blaOXA-1, blaCTXM-1, blaCTXM-2, blaCTXM-9 and blaCTXM-15). Results: Among 341 E. coli isolates collected during the study period, 171 (50%) harboured blaTEM, 145 (43%) blaOXA-1,70 (21%) blaCTXM-1, 19 (6%) blaSHV and four (1%) harboured blaCTXM-2. Phenotypically, combined disc test detected ESBL production in 98/298 (33%) E. coli. Among 304 K. pneumoniae isolates, 115 (38%), 89 (29%), 83 (27%), 64 (21%) and two (0.6%) harboured blaTEM, blaOXA-1, blaCTXM-1, blaSHV and blaCTXM-2, respectively. Combined disc test (CDT) detected ESBL production in 42 per cent K. pneumoniae. Most of the blaCTXM-1positive isolates were also blaCTXM-15 positive. The carbapenem susceptibility ranged from 56 to 88 per cent for E. coli and from 20 to 61 per cent for K. pneumoniae. Antibiotic sensitivity patterns showed that colistin (CST) was the most sensitive drug for both E. coli (271/274, 99%) and K. pneumoniae (229/234, 98%). Interpretation & conclusions: The prevalence of ESBL among four study centres varied, and blaTEM, blaOXA-1 and blaCTXM-15 were the most common genotypes in E. coli and K. pneumoniae isolates in India. The growing carbapenem resistance and emerging colistin resistance warrant the judicious use of these antimicrobials.
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Background & objectives: Klebsiella pneumoniae (KP), a common cause of invasive infections, is often extensively drug resistant in India. At present, studies on resistance mechanism and clonal relationship of KP from India are limited. The present study was undertaken to determine the resistance mechanism and clonal relationship of colistin-resistant isolates obtained from various specimens. Carbapenemases were also determined since the isolates were carbapenem resistant. Methods: Sixty five isolates from blood, exudates and respiratory specimens collected between 2016 and 2017 were studied. Colistin minimum inhibitory concentration (MIC) was performed by broth-micro dilution method. Multiplex PCR was carried out to determine carbapenemases. Targeted sequencing was performed to determine mutations in mgrB, phoP, phoQ and multilocus sequence typing was performed to determine the prevalent clones. Results: Colistin MIC ranged from 4 to 256 ?g/ml. SHV, TEM and CTX-M were co-produced in 60 per cent and OXA48-like in 71 per cent. Thirteen isolates had mutations in mgrB. Mutations included a premature stop codon at 21st amino acid, the presence of insertion sequences such as IS903, IS Kpn 14 and ISK pn 26; and elongation of mgrB. Novel mutations were also observed among phoP and phoQ genes. Colistin resistance due to mcr genes was absent. Fifteen clonal types were seen with ST231, ST14 and ST2096 being predominant. Interpretation & conclusions: This study revealed the changing trend of carbapenem resistance mechanism predominantly to OXA48-like from NDM. Known mgrB mutations and novel mutations in phoP and phoQ were detected. There was no plasmid-mediated colistin resistance. ST14 and ST231 were international clones associated with carbapenem resistance. Colistin-resistant KP was of diverse clones with predominantly ST231, ST14 and ST2096.
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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.
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Background: Pseudomonas aeruginosa is one of the most common opportunistic pathogens that cause severe infections in humans. The burden of carbapenem resistance is particularly high and is on the rise. Very little information is available on the molecular mechanisms and its clonal types of carbapenem-resistant P. aeruginosa seen in Indian hospitals. This study was undertaken to monitor the ?-lactamase profile and to investigate the genetic relatedness of the carbapenemase-producing (CP) P. aeruginosa collected across different hospitals from India. Materials and Methods: A total of 507 non-duplicate, carbapenem-resistant P. aeruginosa isolated from various clinical specimens collected during 2014–2017 across seven Indian hospitals were included. Conventional multiplex polymerase chain reaction for the genes encoding beta-lactamases such as extended-spectrum beta-lactamase (ESBL) and carbapenemase were screened. A subset of isolates (n = 133) of CP P. aeruginosa were genotyped by multilocus sequence typing (MLST) scheme. Results: Of the total 507 isolates, 15%, 40% and 20% were positive for genes encoding ESBLs, carbapenemases and ESBLs + carbapenemases, respectively, whilst 25% were negative for the ?-lactamases screened. Amongst the ESBL genes, blaVEB is the most predominant, followed by blaPER and blaTEM, whilst blaVIM and blaNDM were the most predominant carbapenemases seen. However, regional differences were noted in the ?-lactamases profile across the study sites. Genotyping by MLST revealed 54 different sequence types (STs). The most common are ST357, ST235, ST233 and ST244. Six clonal complexes were found (CC357, CC235, CC244, CC1047, CC664 and CC308). About 24% of total STs are of novel types and these were found to emerge from the high-risk clones. Conclusion: This is the first large study from India to report the baseline data on the molecular resistance mechanisms and its association with genetic relatedness of CP P. aeruginosa circulating in Indian hospitals. blaVIM- and blaNDM-producing P. aeruginosa is the most prevalent carbapenemase seen in India. Majority of the isolates belongs to the high-risk international clones ST235, ST357 and ST664 which is a concern.
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Antimicrobial resistance (AMR) is a major public health concern across the globe, and it is increasing at an alarming rate. Multiple classes of antimicrobials have been used for the treatment of infectious diseases. Rise in the AMR limits its use and hence the prerequisite for the newer agents to combat drug resistance. Among the infections caused by Gram-negative organisms, beta-lactams are one of the most commonly used agents. However, the presence of diverse beta-lactamases hinders its use for therapy. To overcome these enzymes, beta-lactamase inhibitors are being discovered. The aim of this document is to address the burden of AMR in India and interventions to fight against this battle. This document addresses and summarises the following: The current scenario of AMR in India (antimicrobial susceptibility, resistance mechanisms and molecular epidemiology of common pathogens); contentious issues in the use of beta-lactam/beta-lactamase inhibitor as an carbapenem sparing agent; role of newer beta-lactam/beta-lactamase inhibitor agents with its appropriateness to Indian scenario and; the Indian Council of Medical Research interventions to combat drug resistance in terms of surveillance and infection control as a national response to AMR. This document evidences the need for improved national surveillance system and country-specific newer agents to fight against the AMR.
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Background: Surveillance of antimicrobial resistance (AMR) is of great importance. Pseudomonas aeruginosa and Acinetobacter baumannii are important pathogens and emergence of resistance in these have increased the morbidity and mortality rates. This surveillance study was initiated by the Government of India ‑ Indian Council of Medical Research. The aim of this study is to determine the antimicrobial susceptibility profile and to characterise the enzyme mediated antimicrobial resistance such as extended spectrum beta‑lactamases (ESBLs) and carbapenemases among multidrug‑resistant (MDR) P. aeruginosa and A. baumannii. Materials and Methods: A multi‑centric study was conducted from January 2014 to December 2015 with a total number of 240 MDR P. aeruginosa and 312 MDR A. baumannii isolated from blood, cerebrospinal fluid, respiratory, pus, urine and intra‑abdominal infections. Kirby–Bauer disc diffusion was done to determine the antimicrobial susceptibility profile. Further, MDR isolates were characterised by multiplex polymerase chain reaction to determine the resistance genes for ESBLs and carbapenemases. Results: Among the ESBLs, blaVEB (23%), blaTEM (5%) and blaSHV (0.4%) in P. aeruginosa and blaPER (54%), blaTEM (16%) and blaSHV (1%) in A. baumannii were the most prevalent. Likewise, blaVIM (37%), blaNDM (14%), blaGES (8%) and blaIMP (2%) in P. aeruginosa and blaOXA‑23like (98%), blaOXA‑58like (2%), blaNDM (22%) and blaVIM (3%) in A. baumannii were found to be the most prevalent carbapenemases. blaOXA‑51like gene, intrinsic to A. baumannii was present in all the isolates tested. Conclusion: The data shown highlight the wide difference in the molecular mechanisms of AMR profile between P. aeruginosa and A. baumannii. In P. aeruginosa, plasmid‑mediated mechanisms are much lesser than the chromosomal mediated mechanisms. In A. baumannii, class D oxacillinases are more common than other mechanisms. Continuous surveillance to monitor the trends in AMR among MDR pathogens is important for implementation of infection control and to guide appropriate empirical antimicrobial therapy.
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PURPOSE: To determine the effect of acute and chronic primary angle closure glaucoma (PACG) on the trabecular meshwork. METHODS: Trabecular specimens of 16 consecutive patients with primary angle closure glaucoma (PACG)--6 acute PACG eyes, and 10 chronic PACG eyes without an acute attack--were studied by light and electron microscopy. RESULTS: Acute PACG: The trabecular meshwork revealed a generalised oedema and an accumulation of pigment in the widened trabecular spaces and Schlemm's canal. Attenuated trabecular endothelial cells appeared to be devoid of subcellular components. Chronic PACG: In chronic PACG eyes the trabecular architecture had lost its regular arrangement, with fewer and narrower trabecular spaces and fusion of the trabecular beams in areas. There were numerous electron-dense bodies in the trabecular tissues, both within the trabecular beams and in the extracellular spaces, which had a banded fibrillar structure. An overall loss of endothelial cells was noted; the remaining cells were crowded together and were polymorphic. Melanin pigment was present both within the stroma and in the endothelial cells. CONCLUSIONS: Pigment accumulation in the trabecular spaces and within the cells and a noninflammatory degeneration appeared to be the primary changes in the trabecular meshwork after acute angle closure glaucoma. In chronic PACG eyes, there was evidence of loss of endothelial cells and reactive repair processes. These changes were present in areas away from visible peripheral anterior synechiae. A gonioscopic evaluation of the extent of peripheral anterior synechiae alone may not reflect the extent of trabecular meshwork damage in acute and chronic PACG. Patients experiencing an acute attack of PACG require a long-term follow up, because the intraocular pressure (IOP) may rise later, due to ongoing changes compromising the outflow facility, or due to the effects of aging in the trabecular meshwork.