The Mortality Burden of Multidrug-resistant Pathogens in India: A Retrospective, Observational Study

Abstract Background The threat posed by antibiotic resistance is of increasing concern in low- and middle-income countries (LMICs) as their rates of antibiotic use increase. However, an understanding of the burden of resistance is lacking in LMICs, particularly for multidrug-resistant (MDR) pathogens. Methods We conducted a retrospective, 10-hospital study of the relationship between MDR pathogens and mortality in India. Patient-level antimicrobial susceptibility test (AST) results for Enterococcus spp., Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. were analyzed for their association with patient mortality outcomes. Results We analyzed data on 5103 AST results from 10 hospitals. The overall mortality rate of patients was 13.1% (n = 581), and there was a significant relationship between MDR and mortality. Infections with MDR and extensively drug resistant (XDR) E. coli, XDR K. pneumoniae, and MDR A. baumannii were associated with 2–3 times higher mortality. Mortality due to methicillin-resistant S. aureus (MRSA) was significantly higher than susceptible strains when the MRSA isolate was resistant to aminoglycosides. Conclusions This is one of the largest studies undertaken in an LMIC to measure the burden of antibiotic resistance. We found that MDR bacterial infections pose a significant risk to patients. While consistent with prior studies, the variations in drug resistance and associated mortality outcomes by pathogen are different from those observed in high-income countries and provide a baseline for studies in other LMICs. Future research should aim to elucidate the burden of resistance and the differential transmission mechanisms that drive this public health crisis.

Download Full-text

Perceptions of Antibiotic Use and Resistance: Are Antibiotics the Dentists’ Anxiolytics?

Antibiotics ◽

10.3390/antibiotics10060735 ◽

2021 ◽

Vol 10 (6) ◽

pp. 735

Author(s):

Julie Dormoy ◽

Marc-Olivier Vuillemin ◽

Silvia Rossi ◽

Jean-Marc Boivin ◽

Julie Guillet

Keyword(s):

Public Health ◽

Antibiotic Resistance ◽

Qualitative Method ◽

Oral Surgery ◽

Antibiotic Use ◽

Public Health Issue ◽

Clinical Factors ◽

Structured Interviews ◽

Health Crisis ◽

The Public

Background: Antibiotic resistance is a global health crisis. The aim of this study was to explore dentists’ perceptions of antibiotic resistance. Methods: A qualitative method was used. Seventeen dentists practising in the Nancy (Lorraine, France) region were surveyed. They were general practitioners or specialised in oral surgery, implantology, or periodontology. The practitioners took part in semi-structured interviews between September 2019 and July 2020. All of the interviews were transcribed in full and analysed thematically. Results: Four major themes have been selected: attitudes of the dentists in regard to the guidelines, clinical factors that influence prescriptions, non-clinical factors that influence prescriptions, and the perception of antibiotic resistance. The dentists stated that they were very concerned regarding the public health issue of antibiotic resistance. However, they often prescribe according to their own interests and habits rather than according to the relevant guidelines. Conclusions: Although dentists are generally well aware of antibiotic resistance, they often do not adequately appreciate the link between their prescribing habits and the phenomenon of antibiotic resistance. Regular updating of practitioners’ knowledge in this regard is necessary, but patients and the general public should also be made more aware of the issue.

Download Full-text

A UK-based survey of cat owners’ perceptions and experiences of antibiotic usage

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x19826353 ◽

2019 ◽

Vol 22 (2) ◽

pp. 69-76 ◽

Cited By ~ 1

Author(s):

Jennifer Stallwood ◽

Alex Shirlow ◽

Angie Hibbert

Keyword(s):

Antibiotic Resistance ◽

Antibiotic Stewardship ◽

Diagnostic Tests ◽

Bacterial Infections ◽

Viral Infections ◽

Diagnostic Testing ◽

Antibiotic Use ◽

Good Communication ◽

Long Acting ◽

Veterinary Antibiotic

Objectives The aim of this study was to explore owners’ knowledge of antibiotics, experience of antibiotic use in their cats and involvement in decision-making regarding antibiotic prescriptions. Methods Cat owners were recruited via social media and veterinary practices to complete a survey designed to evaluate general knowledge of antibiotics, attitudes to antibiotic stewardship and experiences of antibiotic use in their own cat between November 2017 and March 2018. Data were analysed descriptively. Results A total of 1436 surveys were completed; 247 respondents (17.2%) had a veterinary background. The majority of the remaining respondents correctly identified that antibiotics treat bacterial infections (84.0%; n = 999) but do not treat viral infections (72.8%; n = 865). A minority (n = 338; 28.4%) agreed that antibiotic resistance was a problem in cats in the UK; 92.3% (n = 1097) identified that resistance was a problem in human medicine. Seventy percent (n = 832) of the respondents’ cats had received antibiotics; 29.6% (n = 246) received a long-acting injectable antibiotic (14 days’ duration). Diagnostic tests were performed before antibiotic prescription in 38.7% (n = 322) of cats; 1.4% (n = 7) of respondents reported declining suggested tests and 65.8% (n = 778) indicated that they would be happy to pay for diagnostic tests to allow selection of the most appropriate antibiotic. Most respondents (95.8%; n = 792) indicated that they were happy to follow their veterinarian’s advice and recommendations; however, 49.2% (n = 405) had expected antibiotics to be prescribed. Conclusions and relevance Cat owners demonstrated good knowledge of antibiotic action; however, greater owner education regarding the potential for veterinary antibiotic resistance, requirement for diagnostic testing and training in the administration of oral medication with first-line antibiotics, as well as the use of veterinary antibiotic guidelines, will improve antibiotic stewardship. Good communication between veterinarians and owners is necessary for rational antibiotic use.

Download Full-text

Antibiotics in Food Chain: The Consequences for Antibiotic Resistance

Antibiotics ◽

10.3390/antibiotics9100688 ◽

2020 ◽

Vol 9 (10) ◽

pp. 688

Author(s):

Shashi B. Kumar ◽

Shanvanth R. Arnipalli ◽

Ouliana Ziouzenkova

Keyword(s):

Public Health ◽

Antibiotic Resistance ◽

Food Chain ◽

Bacterial Infections ◽

Antibiotic Resistance Genes ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Alternative Strategies ◽

Antibiotic Resistant ◽

Continuous Use

Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.

Download Full-text

Antibiotic Use and Resistance Pattern in Ethiopia: Systematic Review and Meta-Analysis

International Journal of Microbiology ◽

10.1155/2019/2489063 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Oumer Abdu Muhie

Keyword(s):

Multidrug Resistance ◽

Bacterial Infections ◽

Detection Rate ◽

Public Health Problem ◽

Antibiotic Use ◽

Multidrug Resistant ◽

Resistance Pattern ◽

Global Public Health ◽

Bacterial Strains ◽

Bacterial Detection

Background. In the last decades, medicines have had an unprecedented positive effect on health, leading to reduced mortality and disease burden and consequently to an improved quality of life. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. In the absence of the development of new generations of antibiotic drugs, appropriate use of existing antibiotics is needed to ensure the long-term availability of effective treatment for bacterial infections. Irrational use of antibiotics is an ongoing global public health problem that deserves more attention. This review is conducted to evaluate the prevalence of inappropriate antibiotic utilization and resistance to antibiotics in Ethiopia. Methods. Electronic search in PubMed/MEDLINE and Google was used to find published literature with reference lists of relevant articles searched manually. Titles and abstracts were initially screened for eligibility. The full texts of articles judged to be eligible were reviewed if they meet the inclusion criteria. Data were extracted on important variables like the sample size, region of the study, the inappropriate antibiotic use, bacterial detection rate, multidrug resistance pattern, and more other variables. Microsoft Excel was used for data extraction. Quantitative analysis was performed using STATA version 11. Results. The electronic searches identified 193 articles of which 33 were found eligible. The random-effects model was used to provide point estimates (with 95% confidence interval (CI)) of bacterial detection rate, inappropriate antibiotic use, and multidrug resistance rate to account for heterogeneity. The pooled bacteria detection rate was 29.1 with 95% CI (16.6–41.7). The pooled prevalence of multidrug resistant strains identified was 59.7% (95% CI: 43.5–75.9). The pooled estimate of inappropriate antibiotic use was 49.2% (95% CI: 32.2–66.2). The pooled proportion of self-antibiotic prescription was 43.3% (95% CI: 15.7–70.9). Other reasons for inappropriate antibiotic use included a wrong indication, wrong duration, improper route of administration, use of leftover antibiotics from a family member, and immature discontinuation of antibiotics. Conclusion and Recommendations. Inappropriate antibiotic use is a huge problem in Ethiopia, and many bacteria were resistant to commonly used antibiotics and similarly, multidrug-resistant bacterial strains are numerous. Appropriate antibiotic use should be ensured by prohibiting over-the-counter sale of antibiotics and strengthening antimicrobial stewardship.

Download Full-text

Bacterial infections in cirrhosis: a narrative review and key points for clinical practice

Italian Journal of Medicine ◽

10.4081/itjm.2020.1306 ◽

2020 ◽

Vol 14 (3) ◽

pp. 126-135

Author(s):

Mario Mitra ◽

Andrea Mancuso ◽

Flavia Politi ◽

Alberto Maringhini

Keyword(s):

Antibiotic Resistance ◽

Bacterial Infections ◽

Empirical Therapy ◽

Multidrug Resistant ◽

High Rate ◽

First Episode ◽

Bacterial Peritonitis ◽

Prophylactic Measures ◽

Tract Infections ◽

Healthcare Associated

Bacterial infections are frequent complications of liver cirrhosis, accounting for severe clinical courses, and increased mortality. The reduction of the negative clinical impact of infections may be achieved by a combination of prophylactic measures to reduce the occurrence, early identification, and management. Spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia, cellulitis, and spontaneous bacteremia are frequent in cirrhosis. The choice of initial empirical antimicrobial therapy should be based on both site, severity, and origin of infection (community-acquired, nosocomial, or healthcare-associated) and on antibiotic resistance patterns. 3rd generation cephalosporins are generally indicated as empirical therapy in most community-acquired cases. However, for nosocomial and healthcare-associated infections, due to a high rate of multidrug-resistant (MDR) pathogens, a broader spectrum treatment is appropriate. In order to prevent antibiotic resistance emergence, microbiological cultures should be collected, and a de-escalation applied when antimicrobial susceptibility tests are available. Standard measures to prevent infections and the identification of carriers of MDR bacteria are essential strategies to prevent infections in cirrhosis. Antibiotic prophylaxis should be applied only to gastrointestinal bleeding, SBP recurrence prevention, and cirrhotics at high risk of a first episode of SBP.

Download Full-text

Characteristics of a Nationwide Voluntary Antibiotic Resistance Awareness Campaign in India; Future Paths and Pointers for Resource Limited Settings/Low and Middle Income Countries

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16245141 ◽

2019 ◽

Vol 16 (24) ◽

pp. 5141

Author(s):

Ashok J. Tamhankar ◽

Ramesh Nachimuthu ◽

Ravikant Singh ◽

Jyoti Harindran ◽

Gautam Kumar Meghwanshi ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antibiotic Use ◽

World Health ◽

Awareness Campaign ◽

Resource Limited Settings ◽

Middle Income ◽

Middle Income Countries ◽

Awareness Campaigns ◽

Resource Limited ◽

Low And Middle Income

Antibiotic resistance has reached alarming proportions globally, prompting the World Health Organization to advise nations to take up antibiotic awareness campaigns. Several campaigns have been taken up worldwide, mostly by governments. The government of India asked manufacturers to append a ‘redline’ to packages of antibiotics as identification marks and conducted a campaign to inform the general public about it and appropriate antibiotic use. We investigated whether an antibiotic resistance awareness campaign could be organized voluntarily in India and determined the characteristics of the voluntarily organized campaign by administering a questionnaire to the coordinators, who participated in organizing the voluntary campaign India. The campaign characteristics were: multiple electro–physical pedagogical and participatory techniques were used, 49 physical events were organized in various parts of India that included lectures, posters, booklet/pamphlet distribution, audio and video messages, competitions, and mass contact rallies along with broadcast of messages in 11 local languages using community radio stations (CRS) spread all over India. The median values for campaign events were: expenditure—3000 Indian Rupees/day (US$~47), time for planning—1 day, program spread—4 days, program time—4 h, direct and indirect reach of the message—respectively 250 and 500 persons/event. A 2 min play entitled ‘Take antibiotics as prescribed by the doctor’ was broadcast 10 times/day for 5 days on CRS with listener reach of ~5 million persons. More than 85%ofcoordinators thought that the campaign created adequate awareness about appropriate antibiotic use and antibiotic resistance. The voluntary campaign has implications for resource limited settings/low and middle income countries.

Download Full-text

Strategic Approach for Prioritising Local and Regional Sanitation Interventions for Reducing Global Antibiotic Resistance

Water ◽

10.3390/w11010027 ◽

2018 ◽

Vol 11 (1) ◽

pp. 27 ◽

Cited By ~ 8

Author(s):

David Graham ◽

Myra Giesen ◽

Joshua Bunce

Keyword(s):

Antibiotic Resistance ◽

Antibiotic Use ◽

Middle Income ◽

Middle Income Countries ◽

National Priority ◽

Strategic Approach ◽

Starting Point ◽

Improved Sanitation ◽

Intervention Costs

Globally increasing antibiotic resistance (AR) will only be reversed through a suite of multidisciplinary actions (One Health), including more prudent antibiotic use and improved sanitation on international scales. Relative to sanitation, advanced technologies exist that reduce AR in waste releases, but such technologies are expensive, and a strategic approach is needed to prioritize more affordable mitigation options, especially for Low- and Middle-Income Countries (LMICs). Such an approach is proposed here, which overlays the incremental cost of different sanitation options and their relative benefit in reducing AR, ultimately suggesting the “next-most-economic” options for different locations. When considering AR gene fate versus intervention costs, reducing open defecation (OD) and increasing decentralized secondary wastewater treatment, with condominial sewers, will probably have the greatest impact on reducing AR, for the least expense. However, the best option for a given country depends on the existing sewerage infrastructure. Using Southeast Asia as a case study and World Bank/WHO/UNICEF data, the approach suggests that Cambodia and East Timor should target reducing OD as a national priority. In contrast, increasing decentralized secondary treatment is well suited to Thailand, Vietnam and rural Malaysia. Our approach provides a science-informed starting point for decision-makers, for prioritising AR mitigation interventions; an approach that will evolve and refine as more data become available.

Download Full-text

Risk factors and outcomes for multidrug-resistant Gram-negative bacilli bacteremia

Therapeutic Advances in Infectious Disease ◽

10.1177/2049936117727497 ◽

2017 ◽

Vol 5 (1) ◽

pp. 11-18 ◽

Cited By ~ 5

Author(s):

Swati Patolia ◽

Getahun Abate ◽

Nirav Patel ◽

Setu Patolia ◽

Sharon Frey

Keyword(s):

Risk Factors ◽

Urinary Catheter ◽

Medical Center ◽

Demographic Data ◽

Significant Risk ◽

Antibiotic Use ◽

Multidrug Resistant ◽

Solid Organ ◽

Gram Negative ◽

Source Of Infection

Background: The incidence of multidrug-resistant (MDR) organisms is increasing along with mortality. Identifying risk factors for the development of MDR Gram-negative bacilli (GNB) bacteremia could greatly impact patient care and management. Methods: Data from the electronic health record of patients with GNB over 13-month period were collected at a single university medical center. Baseline demographic data, risk factor, microbiological data, recurrence of bacteremia, and mortality were recorded. Results: A total of 177 patients were included in the analysis. MDR GNB occurred in 46 patients (26%). The mortality rate in the MDR group was 34.8% compared to 13.7% in non-MDR group ( p = 0.002). In multivariate analysis, diabetes mellitus [DM; odds ratio (OR): 2.8, 95% confidence interval (CI): 1–4.88], previous antibiotic use (OR: 2.93, 95% CI: 1.25–6.87), and urinary catheter as a source of infection (OR 5.96, 95% CI: 1.78–19.94) were significant risk factors for the development of MDR GNB. In addition, end-stage liver disease (OR: 3.64, 95% CI: 1.07–12.3), solid organ malignancy (OR: 3.64, 95% CI: 1.25–10.56), intra-abdominal source of infection (OR: 3.66, 95% CI: 1.14–11.73), inappropriate empiric antibiotics (OR 7.59, 95% CI: 1.68–34.34) and urinary catheter as a source of infection (OR 5.68, 95% CI: 1.37–23.5) were significant factors for mortality in patients with MDR GNB. Conclusion: Our study provides important information about the risk factors for the development of MDR GNB bacteremia and helps prognosticate patient with MDR GNB.

Download Full-text

Conjugative delivery of CRISPR-Cas9 for the selective depletion of antibiotic-resistant enterococci

10.1101/678573 ◽

2019 ◽

Cited By ~ 1

Author(s):

Marinelle Rodrigues ◽

Sara W. McBride ◽

Karthik Hullahalli ◽

Kelli L. Palmer ◽

Breck A. Duerkop

Keyword(s):

Antibiotic Resistance ◽

Enterococcus Faecalis ◽

Resistance Genes ◽

Bacterial Infections ◽

Antibiotic Resistance Genes ◽

Multidrug Resistant ◽

Conjugative Plasmid ◽

Antibiotic Resistant ◽

Resistance Determinants

AbstractThe innovation of new therapies to combat multidrug-resistant (MDR) bacteria is being outpaced by the continued rise of MDR bacterial infections. Of particular concern are hospital-acquired infections (HAIs) recalcitrant to antibiotic therapies. The Gram-positive intestinal pathobiontEnterococcus faecalisis associated with HAIs and some strains are MDR. Therefore, novel strategies to controlE. faecalispopulations are needed. We previously characterized anE. faecalisType II CRISPR-Cas system and demonstrated its utility in the sequence-specific removal of antibiotic resistance determinants. Here we present work describing the adaption of this CRISPR-Cas system into a constitutively expressed module encoded on a pheromone-responsive conjugative plasmid that efficiently transfers toE. faecalisfor the selective removal of antibiotic resistance genes. Usingin vitrocompetition assays, we show that these CRISPR-Cas-encoding delivery plasmids, or CRISPR-Cas antimicrobials, can reduce the occurrence of antibiotic resistance in enterococcal populations in a sequence-specific manner. Furthermore, we demonstrate that deployment of CRISPR-Cas antimicrobials in the murine intestine reduces the occurrence of antibiotic-resistantE. faecalisby several orders of magnitude. Finally, we show thatE. faecalisdonor strains harboring CRISPR-Cas antimicrobials are immune to uptake of antibiotic resistance determinantsin vivo. Our results demonstrate that conjugative delivery of CRISPR-Cas antimicrobials may be adaptable for future deployment from probiotic bacteria for exact targeting of defined MDR bacteria or for precision engineering of polymicrobial communities in the mammalian intestine.ImportanceCRISPR-Cas nucleic acid targeting systems hold promise for the amelioration of multidrug-resistant enterococci, yet the utility of such tools in the context of the intestinal environment where enterococci reside is understudied. We describe the development of a CRISPR-Cas antimicrobial, deployed on a conjugative plasmid, for the targeted removal of antibiotic resistance genes from intestinalEnterococcus faecalis. We demonstrate that CRISPR-Cas targeting reduces antibiotic resistance ofE. faecalisby several orders of magnitude in the intestine. Although barriers exist that influence the penetrance of the conjugative CRISPR-Cas antimicrobial among target recipientE. faecaliscells, the removal of antibiotic resistance genes inE. faecalisupon uptake of the CRISPR-Cas antimicrobial is absolute. In addition, cells that obtain the CRISPR-Cas antimicrobial are immunized against the acquisition of new antibiotic resistance genes. This study suggests a potential path toward plasmid based CRISPR-Cas therapies in the intestine.

Download Full-text

Metagenome-Wide Analysis of Rural and Urban Surface Waters and Sediments in Bangladesh Identifies Human Waste as a Driver of Antibiotic Resistance

mSystems ◽

10.1128/msystems.00137-21 ◽

2021 ◽

Author(s):

Ross Stuart McInnes ◽

Md Hassan uz-Zaman ◽

Imam Taskin Alam ◽

Siu Fung Stanley Ho ◽

Robert A. Moran ◽

...

Keyword(s):

Antibiotic Resistance ◽

Surface Waters ◽

Antibiotic Resistance Genes ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Middle Income ◽

Antibiotic Resistant ◽

Human Waste ◽

Middle Income Countries ◽

Rural And Urban

Low- and middle-income countries (LMICs) have higher burdens of multidrug-resistant infections than high-income countries, and there is thus an urgent need to elucidate the drivers of the spread of antibiotic-resistant bacteria in LMICs. Here, we study the diversity and abundance of antibiotic resistance genes in surface water and sediments from rural and urban settings in Bangladesh.

Download Full-text