Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study
Karthikeyan Kumarasamy,Mark Toleman,Timothy R. Walsh,Jay Bagaria,Fafhana Butt,Ravikumar Balakrishnan,Uma Chaudhary,Michel Doumith,Christian G. Giske,Seema Irfan,Padma Krishnan,Anil Kumar,Sunil Maharjan,Shazad Mushtaq,Tabassum Noorie,David L. Paterson,A. Pearson,Claire Perry,Rachel Pike,Bhargavi Rao,Ujjwayini Ray,Jayanta B. Sarma,Madhu Sharma,Elizabeth Sheridan,M A Thirunarayan,Jane F. Turton,Supriya Upadhyay,Marina Warner,William Welfare,David M. Livermore,Neil Woodford +30 more
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The prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK is investigated, and co-ordinated international surveillance is needed.Abstract:
Summary Background Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK. Methods Enterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla NDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan. Findings We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries. Interpretation The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed. Funding European Union, Wellcome Trust, and Wyeth.read more
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Review: Lessons Learned From Clinical Trials Using Antimicrobial Peptides (AMPs)
TL;DR: In this paper, the potential of AMPs as alternatives to antibiotics, challenges toward clinical implementation and strategies to improve the success rate of AMP in clinical trials, emphasizing the lessons we could learn from these trials.
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Human Neutrophil Clearance of Bacterial Pathogens Triggers Anti-Microbial γδ T Cell Responses in Early Infection
Martin S. Davey,Chan Yu Lin,Chan Yu Lin,Gareth Roberts,Sinead Heuston,Amanda C. Brown,James Chess,Mark Toleman,Cormac G. M. Gahan,Colin Hill,Tanya Parish,John D. Williams,Simon J. Davies,David W. Johnson,David W. Johnson,Nicholas Topley,Bernhard Moser,Matthias Eberl +17 more
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Plasmid-mediated resistance in Enterobacteriaceae: changing landscape and implications for therapy.
TL;DR: Clinical studies of antimicrobial therapy and outcome of patients infected with ESBL- or carbapenemase-producing strains of Enterobacteriaceae compared with patientsinfected with susceptible strains are limited in their design but suggest a worse outcome after infection with resistant strains.
Journal ArticleDOI
Extremely Drug-Resistant Citrobacter freundii Isolate Producing NDM-1 and Other Carbapenemases Identified in a Patient Returning from India
Laurent Poirel,A. Ros,Anne Carricajo,Philippe Berthelot,Bruno Pozzetto,Sandrine Bernabeu,Patrice Nordmann +6 more
TL;DR: The case of an 18-year-old French female, with a history of cerebral vascular malformation, who developed an intracerebral hemorrhage during her vacation in southeast India in July 2010, and the first PCR screening as described previously and identified the blaNDM-1 gene in C. freundii STE is reported here.
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Antibacterial activity of quinoxalines, quinazolines, and 1,5-naphthyridines
Ajit K. Parhi,Yongzheng Zhang,Kurt W. Saionz,Padmanava Pradhan,Malvika Kaul,Kalkal A. Trivedi,Daniel S. Pilch,Edmond J. LaVoie +7 more
TL;DR: The notable differences observed between nonquaternized and quaternized quinoxaline derivatives suggest that differing mechanisms of action are associated with their antibacterial properties.
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