David Wareham

David Wareham
Barts Health NHS Trust · Department of Infection

MB BS, MSc, PhD, MRCP, FRCPath

About

200
Publications
44,081
Reads
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5,802
Citations
Additional affiliations
September 2005 - August 2013
Homerton University Hospital NHS Foundation Trust
Position
  • Honorary Consultant Microbiologist
June 2005 - present
Barts Health NHS Trust
Position
  • Honorary Consultant Microbiologist
June 2005 - October 2015
Queen Mary University of London
Position
  • Senior Clinical Lecturer

Publications

Publications (200)
Article
Full-text available
Objectives Metallo-β-lactamase (MBL)-based resistance is a threat to the use of most β-lactam antibiotics. Multiple variants of the New Delhi MBL (NDM) have recently been reported. Previous reports indicate that the substitutions affect NDM activity despite being located outside the active site. This study compares the biochemical properties of sev...
Article
Full-text available
Objectives Effective treatment of Gram-negative bacterial infections is increasingly challenging due to the spread of multidrug-resistant strains and a lack of new antimicrobials in development. Bacterial type I signal peptidases (SPases) represent a highly conserved and essential target for inhibition by novel compounds. SPases are required for th...
Article
Full-text available
Accepted manuscript - Small, carboxymethyl-starch-stabilised zinc oxide nanoparticles with a defined shape, size and morphology were prepared in situ in water at relatively low reaction temperatures using soluble carboxymethyl starch (CMS) as a combined crystallising, stabilising and solubilising agent and triethanolamine as the reducing agent. Aqu...
Article
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A new variant of the New Delhi metallo-enzyme (NDM) carbapenemase was identified in a multidrug-resistant Escherichia coli ST648 isolate recovered from the perineum and throat of a patient in the United Kingdom with a recent history of hospitalization in India. NDM-5 differed from existing enzymes due to substitutions at positions 88 (Val→Leu) and...
Article
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Multidrug-resistant Acinetobacter baumannii (MRAB) is an increasing problem in UK hospitals, with many strains now resistant to all available antibiotics except polymyxins. Tigecycline has been used for the treatment of MRAB as it demonstrates activity in vitro, but there are limited data on its clinical efficacy in Gram-negative infections, especi...
Article
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Polymyxin antibiotics B and colistin are considered drugs of last resort for the treatment of multi-drug and carbapenem-resistant Gram-negative bacteria. With the emergence and dissemination of multi-drug resistance, monitoring the use and resistance to polymyxins imparted by mobilised colistin resistance genes (mcr) is becoming increasingly import...
Article
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Objectives: The aim of this study was to characterize an unusual case of spontaneous, community-acquired Escherichia coli meningitis in an adult presenting to a general hospital in Kenya, where initial clinical recovery was followed by reinfection with an MDR, hospital-acquired strain. Patient and methods: An adult presented to a hospital in Ken...
Article
Objectives : We report the draft genome sequence of a multi-drug resistant Pseudomonas aeruginosa isolate (PA3) producing SIM carbapenemase from a patient in the United Kingdom. Methods : Isolation, identification and antimicrobial susceptibility testing were performed according to local routine microbiology protocols. Whole genomic DNA was sequen...
Article
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A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous bla OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399...
Article
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Objectives Cefiderocol (CFDC) is a novel siderophore cephalosporin approved in Europe for the treatment of infections caused by aerobic Gram-negative (GN) bacteria in adults with limited treatment options. The aim of the ARTEMIS study was to evaluate the in vitro activity of CFDC and comparators against recent clinical isolates collected across fiv...
Article
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Background Carbapenem resistance due to MBL production is relatively uncommon in Pseudomonas aeruginosa infections in the UK. We report a case of post-operative meningitis caused by a New-Delhi MBL-producing (NDM-1) strain, outlining the microbiological and management challenges. Patient case The patient was admitted to intensive care after cranio...
Chapter
The discovery of penicillin over 90 years ago and its subsequent uptake by healthcare systems around the world revolutionised global health. It marked the beginning of a golden age in antibiotic discovery with new antibiotics readily discovered from natural sources and refined into therapies that saved millions of lives. Towards the end of the last...
Article
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Repurposing old antibiotics into more effective and safer formulations is an emergent approach to tackle the growing threat of antimicrobial resistance. Herein, a peptide hydrogel is reported for the localized and sustained release of polymyxin B (PMB), a decade‐old antibiotic with increasing clinical utility for treating multidrug‐resistant Gram‐n...
Article
Full-text available
Background Cefiderocol is a recently licensed novel siderophore-conjugated cephalosporin stable to hydrolysis by serine and MBLs. It has been successfully used to treat Enterobacterales infections and is approved for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options. Objectives To describe...
Article
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Preventing infantile anaemia and ensuring optimal growth and development during early childhood, particularly in resource-constrained settings, represent an ongoing public health challenge. Current responses are aligned to treatment-based solutions, instead of determining the roles of its inter-related causes. This project aims to assess and unders...
Chapter
Research and new tools in biomaterials development by using peptides are currently growing, as more functional and versatile building blocks are used to design a host of functional biomaterials via chemical modifications for health care applications. It is a field that is attracting researchers from across soft matter science, molecular engineering...
Chapter
Sepsis is a serious complication of infection in which a dysregulated immune response leads to organ dysfunction and sometimes death. It is the final common pathophysiological pathway in patients who die from infection. It is estimated that, worldwide, 49 million people develop sepsis every year and 11million die. Sepsis is a medical emergency; ant...
Article
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Resistance to last-resort antibiotics is significant public health issue. Antibiotic use in animal husbandry may be a driver of resistance that can subsequently be disseminated via the food chain. This study sought to determine the level of polymyxin resistance in Gram-negative pathogens present in Australian poultry, particularly the presence of m...
Preprint
Full-text available
A hospital outbreak of carbapenem-resistant Enterobacteriales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacteriales were involved in the outbreak. Escherichia coli ST399 ac...
Article
Full-text available
The primary reason for skin graft failure and the mortality of burn wound patients, particularly those in burn intensive care centers, is bacterial infection. Several animal models exist to study burn wound pathogens. The most commonly used model is the mouse, which can be used to study virulence determinants and pathogenicity of a wide range of cl...
Presentation
The British Society for Antimicrobial Chemotherapy (BSAC) meeting – Into Clinical Practice: Meeting the challenges of Gram-negative infection management. Held at the Royal College of Physicians, London on 19th November 2019
Article
Background: β-Lactam (BL)/β-lactamase inhibitor (BLI) combinations are widely used for the treatment of Gram-negative infections. Cefepime has not been widely studied in combination with BLIs. Sulbactam, with dual BL/BLI activity, has been partnered with very few BLs. We investigated the potential of cefepime/sulbactam as an unorthodox BL/BLI comb...
Article
Full-text available
Background: Extended-spectrum β-lactamase-producing Escherichia coli isolates (ESBL-E coli) cause more than 5000 cases of bacteraemias annually in the UK. The contribution of the food chain to these infections is debated. We aimed to identify the most important reservoirs of ESBL-E coli that colonise and infect humans to identify strategic interve...
Chapter
Although antibiotic resistance has come to the fore in the media and clinical practice relatively recently, it is by no means a new issue; Alexander Fleming discussed the risks of penicillin resistance more than sixty years ago, but even he was behind the times. Bacteria have been competing with each other for millions of years, producing compounds...
Chapter
To optimize antimicrobial therapy for the management of individual patient’s infection. ● For surveillance purposes, which in turn inform local/national/international clinical guidelines. ● For the management of infection control and prevention. Broadly speaking, resistance is detected by observing its phenotypic expression (activity of the candida...
Article
Microbiology and virology laboratories provide a diagnostic service that supports the management of patients under the care of front-line clinicians. Despite the significant overlap, laboratory expertise and clinical patient management are traditionally viewed as independent entities. Trainees in the infection disciplines of microbiology, virology,...
Poster
Background: Infections caused by carbapenemase-producing Klebsiella pneumoniae (CRKP) are a global concern owing to limited theraputic options. Published evidence suggests that carbapenem combination therapies may be clinically useful. A double-carbapenem regime has been proposed as an alternative to mono-therapy with a single carbapenem. Previous...
Conference Paper
Full-text available
Background: Established β-lactam / β-lactamase inhibitor (BL / BLI) therapies are increasingly compromised due to extended-spectrum β-lactamase (ESBL) and carbapenemase production. Cefepime remains stable to many β-lactamases but has not been widely studied in combination with BLIs. Likewise, sulbactam, a compound with dual activity has been partne...
Article
Full-text available
Objectives The potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time–kill experiments in order to estimate clinical effic...
Article
Objectives: Here we report the draft genome sequence of a colistin-resistant hypermucoviscous Klebsiella pneumoniae isolated from a hospitalised patient with acute kidney injury in Kolkata, India. Methods: Whole genomic DNA was sequenced using an Illumina HiSeq platform. The generated reads were de novo assembled using SPAdes v.3.7.1. Genome ann...
Article
In recent years, several plasmids harbouring genes encoding phosphoethanolamine transferases conferring colistin resistance have been described in multiple Enterobacteriaceae species. Avian Pathogenic E. coli (APEC) causes colibacillosis and is responsible for a considerable proportion of the disease burden in commercial poultry flocks, and may be...
Article
Background: ESBL-producing Escherichia coli have expanded globally since the turn of the century and present a major public health issue. Their in vitro susceptibility to penicillin/inhibitor combinations is variable, and clinical use of these combinations against ESBL producers remains controversial. We hypothesized that this variability related...
Article
Full-text available
Multidrug-resistant lineages of Acinetobacter baumannii (MDRAB) are important nosocomial pathogens. As tigecycline remains active against most MDRAB we sought to investigate whether tigecycline resistance impacts biological fitness. The effects of treatment-emergent tigecycline resistance were investigated in vitro and in vivo using two pre- (AB210...
Article
Purpose: Glycopeptides are widely used for the treatment of meticillin-resistant Staphylococcus aureus (MRSA) infections. Although difficult to detect, isolates with reduced (GISA), hetero (hGISA) or complete (GRSA) resistance to glycopeptides are increasingly reported. Optimal therapy for such strains is unknown. We compared the in vitro and in v...
Article
Objectives: Although carbapenem susceptibility testing has been recommended for all Enterobacteriaceae from clinical specimens, for practical reasons a carbapenem is not included in many primary antibiotic panels for urine specimens. The 'iCREST' study sought carbapenemase-producing Enterobacteriaceae (CPE) in routine urine specimens yielding Gram...
Article
Purpose: A selective chromogenic culture medium for the laboratory isolation and differentiation of colistin resistant Acinetobacter, Pseudomonas, Stenotrophomonas and Enterobacteriaceae spp. (CHROMagar COL-APSE) was developed, evaluated and compared to an existing selective bacterial culture medium (SuperPolymyxin). Methodology: The medium was...
Article
Background: Successful laboratory detection of carbapenemase-producing Enterobacteriaceae (CPE) in patient surveillance samples is a diagnostic challenge. In the absence of a gold standard for screening rectal swabs for CPE many phenotypic, genotypic, culture and non-culture based assays have been proposed for identifying these bacteria. Aim: To...
Article
Full-text available
Carbapenem-resistant Klebsiella pneumoniae infection is a rising public health threat due to limited therapeutic options. Here, we report the genome sequence of a multidrug-resistant K. pneumoniae sequence type 231 (ST231) strain associated with an outbreak of infections in an intensive care unit that carries a unique complement of resistance deter...
Data
Utili R and Durante Mangoni E: F1000Prime Recommendation of [Hornsey M and Wareham DW, Antimicrob Agents Chemother 2011 55(7):3534-7]. In F1000Prime, 12 Jul 2011; 10.3410/f.11804957.12901055
Article
Full-text available
Introduction: Acinetobacter baumannii is an important human nosocomial pathogen; most clinical isolates are multidrug-resistant (MDR). Infections caused by A. baumannii often lead to high morbidity and mortality, with limited treatment options. Owing to the small number of anti-Gram-negative antibiotics in the development pipeline, researchers are...
Conference Paper
Full-text available
Acinetobacter baumannii is an important human nosocomial pathogen; most clinical isolates are multidrug-resistant (MDR). Infections caused by A. baumannii often lead to high morbidity and mortality, with limited treatment options. Owing to the small number of anti-Gram-negative antibiotics in the development pipeline, researchers are looking to oth...
Article
Full-text available
Staphylococcus haemolyticus strain SW007 was isolated from a nasal swab taken from a healthy dog. The isolate is resistant to methicillin, mupirocin, macrolides, and sulfonamides. The SW007 draft genome is 2,325,410 bp and contains 2,277 coding sequences, including 60 tRNAs and nine complete rRNA-coding regions.
Article
Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) are identified as a major global health concern. The success of CRE is facilitated by the emergence, acquisition and spread of successful clones carrying plasmid-encoded resistance genes. In this study, an outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients...
Article
Full-text available
β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, tazobactam, and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistan...
Article
Full-text available
The identification, treatment and control of carbapenem resistant Enterobacteriaceae (CRE) infections are a major challenge for healthcare institutions and diagnostic laboratories worldwide.…
Article
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Providencia stuartii is frequently associated with nosocomial outbreaks and displays intrinsic resistance to many commonly used antimicrobials. We report here the draft genome sequence of a P. stuartii strain carrying acquired resistance genes conferring panresistance to cephalosporins ( blaSHV-5 and blaVEB-1 ), carbapenems ( blaVIM-1 ), and aminog...
Article
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and chromogenic media are widely used in clinical microbiology laboratories to facilitate the rapid selection and identification of pathogens. The aim of this study was to evaluate whether usage of chromogenic media limits the diagnostic performance of MALDI...
Article
Full-text available
Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate ant...
Article
Full-text available
Staphylococcus cohnii subsp. urealyticus strain SW120 was isolated from the ear swab of a healthy dog. The isolate is resistant to methicillin and fusidic acid. The SW120 draft genome is 2,805,064 bp and contains 2,667 coding sequences, including 58 tRNAs and nine complete rRNA coding regions.
Cover Page
Full-text available
NMR-filtered virtual screening leads to non-metal chelating metallo-β-lactamase inhibitors A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of the clinically relevant Verona Integron-encoded MBL (VIM)-2. Crystallographic analyses reveal a new mode of MBL inhibition involving binding ad...
Article
Full-text available
There are no clinically useful inhibitors of metallo-β-lactamases (MBLs), which are a growing problem because they hydrolyse almost all β-lactam antibacterials. Inhibition by most reported MBL inhibitors involves zinc ion chelation. A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of t...
Article
Full-text available
Extra-intestinal pathogenic Escherichia coli are a significant cause of urinary tract infection and bacteraemia within the UK. We sought to identify the serogroups of 658 E. coli isolates collected in the UK between January 2011 and March 2012, to better understand the ExPEC population and understand the relevance of serogroups in this pathotype. I...
Article
Full-text available
Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of Acinetobacter baumannii. Checkerboard assays and growth curves showed synergy both against colistin-susceptible (FICindex= 0.13-0.24) and colistin-resistant strains with mutations in pmrB and phosphoethanolamine modification of...
Conference Paper
Carbapenem resistant Enterobacteriaceae (CRE) are recognised as a major threat to human health. Strains producing serine (KPC) or metallo-β-lactamases (NDM, IMP, VIM) are often extensively drug resistant (XDR) and carry multiple resistance determinants on large conjugative plasmids. Fosfomycin (FOS), an old drug with proven efficacy in the treatmen...
Article
Full-text available
Bacterial infections resulting from nonsurgical traumatic wounds can be life threatening, especially those caused by multidrug-resistant (MDR) bacteria with limited therapeutic options. The antimicrobial activity of polymyxin B (1) and curcumin (2) alone and in combination was determined versus MDR bacterial isolates associated with traumatic wound...
Article
Selective decontamination of the digestive tract (SDD) using combinations of oral non-absorbable antibiotics has been proposed as a means of preventing multidrug-resistant (MDR) infections. The minimum inhibitory concentrations (MICs) of rifaximin (RIFAX) were determined against 262 Gram-negative and Gram-positive bacterial isolates by broth microt...
Article
Full-text available
We evaluated an immunochromatographic lateral flow assay to detect OXA-48-like carbapenemases (OXA-48 K-SeT) in Enterobacteriaceae (n = 82). One hundred percent sensitivity and specificity were observed using bacteria recovered from both solid medium and spiked blood culture bottles, and the results were obtained in <10 min.
Article
Providencia stuartii has emerged as an important nosocomial pathogen. We describe an outbreak due to a multidrug-resistant strain over a 4-month period in a critical care unit in Athens. Molecular typing revealed each of the isolates to be clonally related with coresistance to cephalosporins, carbapenems, aminoglycosides, and quinolones. Each isola...
Article
Objectives: The objectives of this study were to characterize ESBL-producing Enterobacteriaceae present in 24 neonatal units (NNUs) in eight networks participating in a multicentre probiotic study and to test the hypothesis that specific strains would cluster within individual units and networks. Methods: We performed analysis of stool samples f...
Article
Full-text available
The thioenol ML302F was recently identified as an inhibitor of class B metallo-β-lactamases (MBLs). We assessed the activity of ML302F when combined with meropenem (MEM) against 31 carbapenem resistant Gram-negative clinical isolates. Minimum inhibitory concentrations of MEM:ML302F were determined at fixed ratios of 1:4 and 1:8 using strains produc...
Article
The multidrug-resistant ST131-O25b clone of Escherichia coli is well established as a significant cause of extra-intestinal infections worldwide. However, there have been only two small regional studies comparing ST131 isolates from the UK. Therefore, we characterised 143 ST131 E. coli (38 urinary, 105 bloodstream) collected between January 2011 an...
Conference Paper
Full-text available
ML302 is a recently described Class B rhodanine inhibitor with activity against metallo-β-lactamases (IMP, VIM, NDM). Crystallographic and kinetic studies show that ML302F, a thioenalote, chelates zinc ions and can act as a broad spectrum MBL inhibitor. We assessed the in-vitro and in-vivo activity of ML302F combined with meropenem (MEM) against ca...
Article
Full-text available
Enterococcus faecium is an emerging nosocomial pathogen associated with antibiotic therapy in the hospital environment. Whole-genome sequences were determined for three pairs of related, consecutively collected E. faecium clinical isolates to determine putative mechanisms of resistance to tigecycline. The first isolates (1S, 2S and 3S) in each of t...
Article
Full-text available
The spread of multi-drug resistant Acinetobacter baumannii (MDRAB) has led to the renaissance of colistin (COL), often the only agent to which MDRAB remains susceptible. Effective therapy with COL is beset with problems due to unpredictable pharmacokinetics, toxicity and the rapid selection of resistance. Here, we describe a potent synergistic inte...
Conference Paper
Full-text available
Objectives: There is growing interest in the emergence of glycopeptide resistance in Staphylococcus aureus (GRSA), especially in patients with chronic meticillin-resistant S. aureus (MRSA) infections receiving prolonged glycopeptide therapy. Resistance most commonly arises through the accumulation of multiple mutations as part of an adaptive respon...
Article
Extra-intestinal pathogenic Escherichia coli (ExPEC) are a significant cause of urinary tract infections and bacteraemia worldwide. Currently no single virulence factor or ExPEC lineage has been identified as the sole contributor to severe extra-intestinal infection and/or urosepsis. Galleria mellonella has recently been established as a simple mod...