A novel plasmid-mediated polymyxin resistance determinant (mcr-1.8) in escherichia coli recovered from broiler chickens in Brunei Darussalam
- Authors: Momin, Abdul , Liakopoulos, Apostolos , Bean, David , Phee, Lynette , Wareham, David
- Date: 2019
- Type: Text , Journal article , Letter
- Relation: Journal of Antimicrobial Chemotherapy Vol. 74, no. 11 (2019), p. 3392-3394
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- Description: Sir, MDR Gram-negative bacteria are identified as critical pathogens and their effective treatment increasingly relies on the polymyxins (polymyxin B, colistin), either alone or as part of unorthodox combination therapies.1 The rapid emergence of polymyxin resistance due to mutations/insertions in genes involved in LPS modifications (lpxCAD, pmrA/B, mgrB, phoP/Q, ccrAB) has been reported among individuals exposed to or treated with polymyxins.1Of greater concern are increasing reports of resistance due to the acquisition of phosphoethanolamine (PEtN) transferases, enzymes that catalyse the addition of phosphoethanolamine to lipid A, resulting in lower binding affinity of polymyxins.1 Since the first identification in China,1 multiple gene variants have been reported in diverse bacterial genera recovered from a range of human, retail food, foodproducing animal and environmental sources.2 Here, we report a novel variant of PEtN transferase, designated MCR-1.8, and its genetic context in an MDR Escherichia coli isolate recovered from poultry in Brunei Darussalam.
Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility
- Authors: Farrukee, Rubaiyea , Leang, Sookkwan , Butler, Jeff , Lee, Raphael , Maurer-Stroh, Sebastian , Tilmanis, Danielle , Sullivan, Sheena , Mosse, Jennifer , Barr, Ian , Hurt, Aeron
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Antimicrobial Chemotherapy Vol. 70, no. 7 (2015), p. 2004-2012
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- Description: Objectives: The burden of disease due to influenza B is often underestimated. Clinical studies have shown that oseltamivir, a widely used neuraminidase inhibitor (NAI) antiviral drug, may have reduced effectiveness against influenza B viruses. Therefore, it is important to study the effect of neuraminidase mutations in influenza B viruses that may further reduce NAI susceptibility, and to determine whether these mutations have the same effect in the two lineages of influenza B viruses that are currently circulating (B/Yamagata-like and B/Victoria-like). Methods: We characterized the effect of 16 amino acid substitutions across five framework residues and four monomeric interface residues on the susceptibility to four different NAIs (oseltamivir, zanamivir, peramivir and laninamivir). Results: Framework residue mutations E117A and E117G conferred highly reduced inhibition to three of the four NAIs, but substantially reduced neuraminidase activity, whereas other framework mutations retained a greater level of NA activity. Mutations E105K, P139S and G140R of the monomeric interface were also found to cause highly reduced inhibition, but, interestingly, their effect was substantially greater in a B/Victoria-like neuraminidase than in a B/Yamagata-like neuraminidase, with some susceptibility values being up to 1000-fold different between lineages. Conclusions: The frequency and the effect of key neuraminidase mutations on neuraminidase activity and NAI susceptibility can differ substantially between the two influenza B lineages. Therefore, future surveillance, analysis and interpretation of influenza B virus NAI susceptibility should consider the B lineage of the neuraminidase in the same manner as already occurs for different influenza A neuraminidase subtypes.
Increasing chloramphenicol resistance in Streptococcus pneumoniae isolates from Papua New Guinean Children with acute bacterial meningitis
- Authors: Manning, Laurens , Laman, Moses , Greenhill, Andrew , Michael, Audrey , Siba, Peter , Mueller, Ivo , Davis, Timothy
- Date: 2011
- Type: Text , Journal article
- Relation: Antimicrobial Agents and Chemotherapy Vol. 55, no. 9 (2011), p. 4454-4456
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- Description: In Papua New Guinean (PNG) children with acute bacterial meningitis (ABM), all Haemophilus influenzae isolates were resistant to chloramphenicol. Although Streptococcus pneumoniae isolates had a median chloramphenicol MIC of 3 μg/ml, it was ≥4 μg/ml in 42.8%, and the likelihood of an area under the 24-hour concentration-time curve/MIC ratio of >100 h at a MIC of ≥4 μg/ml was approximately 50%. All isolates were ceftriaxone sensitive. These data support ceftriaxone rather than conventional chloramphenicol for all PNG children with suspected ABM.
Paradoxical effect of 1-(1-naphthylmethyl)-piperazine on resistance to tetracyclines in multidrug-resistant Acinetobacter baumannii
- Authors: Bean, David , Wareham, David
- Date: 2009
- Type: Text , Journal article
- Relation: Journal of Antimicrobial Chemotherapy Vol. 63, no. 2 (2009), p. 349-352
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- Description: Objectives The efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) has been demonstrated to reverse multidrug resistance in Acinetobacter baumannii. We investigated the interaction of NMP with tigecycline and three other tetracyclines on clinical isolates of A. baumannii. Methods One hundred and four clinical isolates of Acinetobacter were tested for susceptibility to tigecycline, minocycline, doxycycline and tetracycline by disc diffusion, and tigecycline MICs were determined by Etest, both in the presence and absence of NMP. Tigecycline MICs and zones of inhibition were interpreted using the BSAC guidelines. An OXA carbapenemase multiplex PCR was also performed on each isolate. Results Mean zones of inhibition for tetracycline, doxycycline and minocycline increased by 11.3%, 22.9% and 11.2%, respectively, in the presence of NMP. In contrast, tigecycline susceptibility was decreased in the presence of NMP, with mean zones of inhibition decreasing by 8.4%. Based on PCR results, all but six isolates belonged to the OXA-23 clone 1. Conclusions Susceptibility to tigecycline of the A. baumannii OXA-23 clone 1 prevalent in the UK is reduced (∼2-fold) by the presence of the efflux inhibitor NMP. NMP does not have the same effect on susceptibility to other tetracyclines.
- Description: C1
Plasmids imparting sulfonamide resistance in Escherichia coli: Implications for persistence
- Authors: Bean, David , Livermore, David , Hall, Lucinda
- Date: 2009
- Type: Text , Journal article
- Relation: Antimicrobial Agents and Chemotherapy Vol. 53, no. 3 (2009), p. 1088-1093
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- Description: Sulfonamide resistance remains prevalent among clinical isolates of Escherichia coli in the United Kingdom, despite a dramatic (>97%) national decline in the rate of prescription of sulfonamides in the 1990s. To investigate potential mechanisms accounting for this persistence, we characterized plasmids carrying sul2, the most prevalent determinant of sulfonamide resistance. Among 33 conjugative and 5 nonconjugative plasmids carrying sul2, resistance to other antimicrobial agents was common, but the spectrum of resistance profiles was diverse: 82%, 74%, and 45% carried resistance to ampicillin, streptomycin, and trimethoprim, respectively. Resistance to mercury was carried by 33% of the plasmids, but none conferred significant resistance to silver or to any of three disinfectants tested. The potential virulence genes iutA (aerobactin system) and traT (serum survival) were carried by 21% and 36% of the plasmids, respectively. The 33 conjugative plasmids belonged to five different incompatibility groups, FIB, B/O, I1, K/B, and P (42%, 33%, 9%, 3% and 3%, respectively), with 3 plasmids being unassigned, and to 19 similarity groups on the basis of their restriction profiles. The sequences flanking sul2 were diverse and suggested more than one mechanism of genetic mobility. The five nonconjugative plasmids were all related to p9123 (pBP1), which was previously found to confer a fitness advantage on its host. We propose that the persistence of sul2, despite the reduced rate of prescription of sulfonamides, is due to a combination of coselection by antibiotics still in common use, a lack of a selective disadvantage in sul2 carriage, and the genetic mobility of sul2. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
- Description: C1