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Article ; Online: Multidrug-resistant Gram-negative bacteria: a product of globalization.

Hawkey, P M

2015 Volume 89, Issue 4, Page(s) 241–247

Abstract: ... of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group ...

Abstract	Global trade and mobility of people has increased rapidly over the last 20 years. This has had profound consequences for the evolution and the movement of antibiotic resistance genes. There is increasing exposure of populations all around the world to resistant bacteria arising in the emerging economies. Arguably the most important development of the last two decades in the field of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group. A consequence of the very high rates of ESBL production among Enterobacteriaceae in Asian countries is that there is a substantial use of carbapenem antibiotics, resulting in the emergence of plasmid-mediated resistance to carbapenems. This article reviews the emergence and spread of multidrug-resistant Gram-negative bacteria, focuses on three particular carbapenemases--imipenem carbapenemases, Klebsiella pneumoniae carbapenemase, and New Delhi metallo-β-lactamase--and highlights the importance of control of antibiotic use.
MeSH term(s)	Bacterial Proteins/genetics ; Bacterial Proteins/secretion ; Disease Transmission, Infectious ; Drug Resistance, Multiple, Bacterial ; Global Health ; Gram-Negative Bacteria/drug effects ; Gram-Negative Bacteria/enzymology ; Gram-Negative Bacteria/isolation & purification ; Gram-Negative Bacterial Infections/epidemiology ; Gram-Negative Bacterial Infections/transmission ; Humans ; Internationality ; beta-Lactamases/genetics ; beta-Lactamases/secretion
Chemical Substances	Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6)
Language	English
Publishing date	2015-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	779366-2
ISSN	1532-2939 ; 0195-6701
ISSN (online)	1532-2939
ISSN	0195-6701
DOI	10.1016/j.jhin.2015.01.008
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Article ; Online: Revisiting the donor screening protocol of faecal microbiota transplantation (FMT): a systematic review.

Ng, Rita Wy / Dharmaratne, Priyanga / Wong, Sunny / Hawkey, Peter / Chan, Paul / Ip, Margaret

Gut

2023

Language	English
Publishing date	2023-05-04
Publishing country	England
Document type	Letter
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2023-329515
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Article ; Online: Economic evaluation of Faecal microbiota transplantation compared to antibiotics for the treatment of recurrent

Abdali, Zainab I / Roberts, Tracy E / Barton, Pelham / Hawkey, Peter M

EClinicalMedicine

2020 Volume 24, Page(s) 100420

Abstract: Background: Clostridioides difficile: Method: A cost utility analysis was conducted using a decision model representing the cost per additional Quality Adjusted Life Year (QALY) from a National Health Service (NHS) perspective. A Markov model was ... ...

Abstract	Background: Clostridioides difficile Method: A cost utility analysis was conducted using a decision model representing the cost per additional Quality Adjusted Life Year (QALY) from a National Health Service (NHS) perspective. A Markov model was constructed to compare FMT NGT and colonoscopy to antibiotic treatment (fidaxomicin or vancomycin). The model was informed by a literature review of clinical evidence, specifically focussing on hospitalised patients with rCDI over 65 years. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainties around the model inputs and assumptions. Findings: The base case analysis showed that FMT is a less costly and more effective treatment than either fidaxomicin or vancomycin. FMT colonoscopy was slightly more effective than FMT NGT leading to an additional 0.012 QALYs but more expensive and the incremental cost effectiveness ratio (ICER) was £242,514/QALY. The Probabilistic sensitivity analysis based on 10,000 simulations suggested the probability of FMT NGT being cost effective was almost 78% at £20,000/QALY Willingness-To-Pay (WTP) threshold. Interpretation: FMT is both more effective and less costly option than antimicrobial therapy. FMT NGT was the preferred route of administration and is likely to be considered the most cost-effective strategy by decision makers given current acceptable thresholds.
Language	English
Publishing date	2020-06-27
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2020.100420
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Article ; Online: Low-level glycopeptide resistance in methicillin-resistant Staphylococcus aureus and how to test it.

Hawkey, P M

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2009 Volume 15 Suppl 7, Page(s) 2–9

Abstract: Vancomycin resistance in Staphylococcus aureus has emerged over the last ten years due to varying mechanisms and giving variable levels of resistance to vancomycin. The most resistant strains (fortunately rare) bear the vanA gene cluster and these are ... ...

Abstract	Vancomycin resistance in Staphylococcus aureus has emerged over the last ten years due to varying mechanisms and giving variable levels of resistance to vancomycin. The most resistant strains (fortunately rare) bear the vanA gene cluster and these are generally recognisable as MICs of vancomycin are usually found to be in the range 32-64mg/L. It should be noted that some automated systems have failed to detect these isolates. The much more commonly encountered GISA and hGISA vancomycin resistant strains of MRSA and methicillin sensitive Staph. aureus (MSSA) exhibit lower levels of resistance and difficulty is encountered in reliably defining and identifying these strains in clinical laboratories. No single completely reliable, convenient test either phonotypical genetic currently exists which can be readily applied in the clinical laboratory for the detection of hGISA/GISA. The population analysis profile (PAP) method is currently regarded as the reference method but is slow and tedious to perform on a large number of isolates. This enables the differentiation of hGISA and GISA from fully vancomycin sensitive strains. In the clinical laboratory the use of Meuller-Hinton agar with 5mg/L teicoplanin and a 10microL innoculum of MacFarland 0.5 incubated for 48h represents the most reliable and economical screening test. Further confirmation would be required using either macrodilution Etest methodology using an MIC >or= 8mg/L of vancomycin and/or teicoplanin as the cut off for hGISA or the newer GRD (glycopeptide resistance detection) strip.
MeSH term(s)	Culture Media/chemistry ; Culture Media/economics ; Glycopeptides/pharmacology ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Methicillin-Resistant Staphylococcus aureus/isolation & purification ; Microbial Sensitivity Tests/economics ; Microbial Sensitivity Tests/methods ; Staphylococcal Infections/microbiology ; Time Factors ; Vancomycin Resistance
Chemical Substances	Culture Media ; Glycopeptides
Language	English
Publishing date	2009-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1111/j.1469-0691.2009.03094.x
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Zs.A 4541: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Molecular characterization of plasmids encoding bla

Bevan, E R / Powell, M J / Toleman, M A / Thomas, C M / Piddock, L J V / Hawkey, P M

The Journal of hospital infection

2021 Volume 114, Page(s) 134–143

Abstract: ... is rising and is dominated by bla: Aims: To determine the conjugative ability of CTX-M-EC acquired ... by healthy volunteers after travel to South Asia, the proportion of travel-acquired CTX-M-EC where bla ... and CTX-M-EC were cultured. After short- and long-read sequencing, 10 plasmid sequences were ...

Abstract	Background: The global prevalence of extended-spectrum beta-lactamase-producing Escherichia coli is rising and is dominated by bla Aims: To determine the conjugative ability of CTX-M-EC acquired by healthy volunteers after travel to South Asia, the proportion of travel-acquired CTX-M-EC where bla Methods: Faecal samples were collected pre- and post-travel from 23 volunteers who visited South Asia, and CTX-M-EC were cultured. After short- and long-read sequencing, 10 plasmid sequences were identified and compared with previously sequenced plasmids in GenBank. Conjugation to E. coli K-12 was undertaken using filter mating. Findings: Thirty-five percent of CTX-M-EC isolates tested transferred the bla Conclusion: Globally successful epidemic plasmids are involved in the spread of CTX-M-EC. Targeted strategies may be used to displace such plasmids from the host strain as part of efforts in infection prevention and control in healthcare settings. Bacteria with bla
MeSH term(s)	Animals ; Anti-Bacterial Agents ; Asia/epidemiology ; Escherichia coli/genetics ; Escherichia coli Infections/epidemiology ; Humans ; Plasmids/genetics ; United Kingdom ; beta-Lactamases/genetics
Chemical Substances	Anti-Bacterial Agents ; beta-Lactamases (EC 3.5.2.6)
Language	English
Publishing date	2021-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	779366-2
ISSN	1532-2939 ; 0195-6701
ISSN (online)	1532-2939
ISSN	0195-6701
DOI	10.1016/j.jhin.2021.03.030
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Article: Prevalence and clonality of extended-spectrum beta-lactamases in Asia.

Hawkey, P M

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2008 Volume 14 Suppl 1, Page(s) 159–165

Abstract: ... differences have since been seen in the pattern of ESBL genes, particularly in relation to the CTX-M family ... The early emergence of TOHO CTX-M-2 in Japan contrasted with CTX-M-3 and -14 in China and many other parts ... with Europe. In most countries, there are mixtures of CTX-M types, with VEB appearing significantly in Vietnam ...

Abstract	Asia is almost certainly a part of the world in which extended-spectrum beta-lactamases (ESBLs) have emerged de novo, with some early antimicrobial resistance studies showing high levels of the ESBL phenotype, particularly among Klebsiella, and most notably in China, Korea, Japan and India. There is a lack of genotyping studies but work from the late 1990s suggests that SHV-5 and SHV-12 were most common then, with only very rare reports of TEM-related ESBL genes. As in other parts of the world, quite marked differences have since been seen in the pattern of ESBL genes, particularly in relation to the CTX-M family. The early emergence of TOHO CTX-M-2 in Japan contrasted with CTX-M-3 and -14 in China and many other parts of the Far East, suggesting the separate transfer of genes from the genome of Kluyvera spp. to mobile genetic elements in human-associated Enterobacteriaceae. ESBL production rates are now very high compared with Europe. In most countries, there are mixtures of CTX-M types, with VEB appearing significantly in Vietnam and Thailand, and ESBL isolates from India being completely dominated by the presence of bla(CTX-M-15) alone, with no other CTX-M types reported. With the total population of India and China being c. 2.4 billion and with faecal carriage rates of, probably, c. 10%, these countries represent major reservoirs of bla(CTX-M) genes. Increasing international travel and trade will lead to the movement of many of these ESBL genes. The high prevalence of ESBL genes in Asia means that the empirical treatment of serious infections with beta-lactam antibiotics, except carbapenems, is seriously compromised.
MeSH term(s)	Asia/epidemiology ; China/epidemiology ; Enterobacteriaceae/drug effects ; Enterobacteriaceae/enzymology ; Enterobacteriaceae/genetics ; Enterobacteriaceae Infections/drug therapy ; Enterobacteriaceae Infections/epidemiology ; Enterobacteriaceae Infections/microbiology ; Humans ; India/epidemiology ; Integrons/genetics ; beta-Lactam Resistance/genetics ; beta-Lactamases/biosynthesis ; beta-Lactamases/classification ; beta-Lactamases/genetics ; beta-Lactams/pharmacology ; beta-Lactams/therapeutic use
Chemical Substances	beta-Lactams ; beta-Lactamases (EC 3.5.2.6)
Language	English
Publishing date	2008-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1198-743X ; 1470-9465
ISSN (online)	1469-0691
ISSN	1198-743X ; 1470-9465
DOI	10.1111/j.1469-0691.2007.01855.x
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Zs.A 4541: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The growing burden of antimicrobial resistance.

Hawkey, P M

The Journal of antimicrobial chemotherapy

2008 Volume 62 Suppl 1, Page(s) i1–9

Abstract: ... genotypes of CTX-M extended-spectrum beta-lactamases (particularly CTX-M-14 and -15) and the emergence ...

Abstract	Since the first usage of antimicrobials, the burden of resistance among bacteria has progressively increased and has accelerated within the last 10 years. Antibiotic resistance genes were present at very low levels prior to the introduction of antibiotics and it is largely the selective pressure of antibiotic use and the resulting exposure of bacteria, not only in humans but also in companion and food animals and the environment, which has caused the rise. The increasing mobility across the globe of people, food and animals is another factor. Examples of this are the international pandemic of different genotypes of CTX-M extended-spectrum beta-lactamases (particularly CTX-M-14 and -15) and the emergence of the carbapenemase KPC-1 in both the USA and Israel. This review details examples of both the emergence and dissemination through different genetic routes, both direct and indirect selective pressure, of significance resistance in Staphylococcus aureus, Enterococcus species, Enterobacteriaceae and Pseudomonas/Acinetobacter. The response made by society to reduce resistance involves surveillance, reduced usage, improved infection control and the introduction of new antimicrobial agents. Although efforts are being made in all these areas, there is an urgent need to increase the effectiveness of these interventions or some bacterial infections will become difficult if not impossible to treat reliably.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections/drug therapy ; Bacterial Infections/microbiology ; Drug Resistance, Bacterial ; Gram-Negative Bacteria/drug effects ; Gram-Positive Bacteria/drug effects ; Humans ; Selection, Genetic
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2008-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkn241
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Molecular epidemiology of clinically significant antibiotic resistance genes.

Hawkey, P M

British journal of pharmacology

2008 Volume 153 Suppl 1, Page(s) S406–13

Abstract: ... particularly of CTX-M extended-spectrum beta-lactamases (ESBLs) is described together with the molecular ...

Abstract	Antimicrobials were first introduced into medical practice a little over 60 years ago and since that time resistant strains of bacteria have arisen in response to the selective pressure of their use. This review uses the paradigm of the evolution and spread of beta-lactamases and in particular beta-lactamases active against antimicrobials used to treat Gram-negative infections. The emergence and evolution particularly of CTX-M extended-spectrum beta-lactamases (ESBLs) is described together with the molecular mechanisms responsible for both primary mutation and horizontal gene transfer. Reference is also made to other significant antibiotic resistance genes, resistance mechanisms in Gram-negative bacteria, such as carbepenamases, and plasmid-mediated fluoroquinolone resistance. The pathogen Staphylococcus aureus is reviewed in detail as an example of a highly successful Gram-positive bacterial pathogen that has acquired and developed resistance to a wide range of antimicrobials. The role of selective pressures in the environment as well as the medical use of antimicrobials together with the interplay of various genetic mechanisms for horizontal gene transfer are considered in the concluding part of this review.
MeSH term(s)	Animals ; Bacteria/genetics ; Bacterial Infections/drug therapy ; Bacterial Infections/genetics ; Bacterial Infections/microbiology ; Drug Resistance, Microbial/genetics ; Genes, Bacterial/physiology ; Humans ; Molecular Epidemiology
Language	English
Publishing date	2008-02-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1038/sj.bjp.0707632
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Article ; Online: The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

Mullish, B H / Merrick, B / Quraishi, M N / Bak, A / Green, C A / Moore, D J / Porter, R J / Elumogo, N T / Segal, J P / Sharma, N / Marsh, B / Kontkowski, G / Manzoor, S E / Hart, A L / Settle, C / Keller, J J / Hawkey, P / Iqbal, T H / Goldenberg, S D /

Williams, H R T

The Journal of hospital infection

2024

Abstract: The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base ( ... ...

Abstract	The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.
Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	779366-2
ISSN	1532-2939 ; 0195-6701
ISSN (online)	1532-2939
ISSN	0195-6701
DOI	10.1016/j.jhin.2024.03.001
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Article ; Online: Pre-clinical experience with daptomycin.

Hawkey, P M

The Journal of antimicrobial chemotherapy

2008 Volume 62 Suppl 3, Page(s) iii7–14

Abstract: Daptomycin is a broad-spectrum, bactericidal agent active against Gram-positive bacteria, acting largely and unusually through membrane depolarization. Activity is markedly affected in vitro by the availability of calcium ions, and its high molecular ... ...

Abstract	Daptomycin is a broad-spectrum, bactericidal agent active against Gram-positive bacteria, acting largely and unusually through membrane depolarization. Activity is markedly affected in vitro by the availability of calcium ions, and its high molecular weight with associated poor diffusion means that conventional disc diffusion testing is not reliable (and as a consequence not available). In order to allow susceptibility categorization, it is recommended that the MIC be determined in the presence of a defined calcium concentration. The activity of daptomycin is concentration-dependent with a prolonged post-antibiotic effect. It has linear pharmacokinetics, with a half-life of 8-9 h, the primary route of excretion is renal, it exhibits serum protein binding of approximately 92% and there is no interaction with the P450 cytochrome. Daptomycin is inactivated by surfactant in the lung and, in consequence, is not recommended for the treatment of respiratory infections. Daptomycin is currently licensed for the treatment of complicated skin and soft tissue infections and for bacteraemia and right-sided endocarditis due to methicillin-susceptible and -resistant Staphylococcus aureus. To date, daptomycin-resistant bacteria have rarely been isolated from patients, although increases in vancomycin MIC may be linked to reduced susceptibility to daptomycin. Close monitoring of resistance is essential to maintain the clinical utility of the drug. Using once-daily dosing, daptomycin has been generally well tolerated; however, weekly monitoring of creatinine phosphokinase is recommended, as myopathy in skeletal muscles has been seen, albeit rarely. The rapid bactericidal action of daptomycin makes it a useful addition to the therapeutic armamentarium for the treatment of Gram-positive infections, providing a valuable alternative to vancomycin when it is inappropriate or resistance is a problem.
MeSH term(s)	Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Daptomycin/adverse effects ; Daptomycin/pharmacokinetics ; Daptomycin/pharmacology ; Daptomycin/therapeutic use ; Drug Resistance, Bacterial ; Gram-Positive Bacteria/drug effects ; Humans ; Microbial Sensitivity Tests/methods ; Microbial Viability/drug effects ; Soft Tissue Infections/drug therapy ; Staphylococcal Skin Infections/drug therapy
Chemical Substances	Anti-Bacterial Agents ; Daptomycin (NWQ5N31VKK)
Language	English
Publishing date	2008-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkn367
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