I M Gould

NHS Health Scotland, Edinburgh, Scotland, United Kingdom

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Publications (186)945.71 Total impact

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    ABSTRACT: Objectives: To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Design: Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. Setting: Regional hospital and primary care in a Scottish Health Board. Participants: General adult (N=1 051 993) or intensive care (18 235) admissions and primary care registrations (460 000 inhabitants) between January 1997 and December 2012. Interventions: Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and ‘4Cs’ (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). Outcome measures: Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10 000 inhabitant-days). Results: 67% of all clinical MRSA isolates (10 707/15 947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of ‘4Cs’ and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R2=0.63–0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4 days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135–141, and 48–81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes. Conclusions: Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts
    BMJ Open 03/2015; 5(3). DOI:10.1136/bmjopen-2014-006596 · 2.06 Impact Factor
  • New England Journal of Medicine 01/2015; 372(3):293. DOI:10.1056/NEJMc1414306#SA3 · 54.42 Impact Factor
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    ABSTRACT: Meticillin-resistant Staphylococcus aureus (MRSA) infection continues to be a substantial global problem with significant associated morbidity and mortality. This review summarises the discussions that took place at the 4th MRSA Consensus Conference in relation to the current treatment options for serious MRSA infections and how to optimise whichever therapy is embarked upon. It highlights the many challenges faced by both the laboratory and clinicians in the diagnosis and treatment of MRSA infections.
    09/2014; DOI:10.1016/j.jgar.2014.03.009
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    ABSTRACT: Background: The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK. Methods: A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews. Results: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation. Conclusions: This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs. © 2014 S. Karger AG, Basel.
    Chemotherapy 07/2014; 59(6):427-434. DOI:10.1159/000363280 · 1.55 Impact Factor
  • Deirdre J O'Brien, Ian M Gould
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    ABSTRACT: Despite concerns regarding efficacy and tolerability, vancomycin continues to be the standard treatment for skin and soft tissue infections (SSTIs) when β-lactam antimicrobials cannot be used. This review sought to establish the role of both old and new alternatives to vancomycin. Methods for achieving optimization of vancomycin therapy are also explored. Several meta-analyses have demonstrated poorer clinical outcomes when the vancomycin minimum inhibitory concentration approaches the breakpoint of 2 μg/ml. Higher doses should be utilized to optimize pharmacokinetics and pharmacodynamics when higher volumes of distribution occur (e.g. sepsis).Newer agents with established noninferiority to vancomycin include the oxazolidinones linezolid and tedizolid, the lipopeptide daptomycin, the anti-meticillin-resistant Staphylococcus aureus cephalosporin ceftaroline and the glycylcycline tigecycline. Linezolid is thus far the only agent that has been shown to be associated with better clinical and microbiological cure rates. Ceftaroline and tigecycline are broad-spectrum agents best reserved for polymicrobial infections (e.g. diabetic foot infections). When vancomycin is used for the treatment of SSTIs, maximizing the dose should be performed to improve efficacy. Cost is often the main limiting factor with regard to the newer agents, but their suitability for outpatient antimicrobial therapy may counteract this.
    Current Opinion in Infectious Diseases 02/2014; 27(2). DOI:10.1097/QCO.0000000000000048 · 5.03 Impact Factor
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    ABSTRACT: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.
    The Lancet Infectious Diseases 11/2013; 13(12). DOI:10.1016/S1473-3099(13)70318-9 · 19.45 Impact Factor
  • Deirdre J O'Brien, Ian M Gould
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    ABSTRACT: The decline in the development and approval of new antimicrobial agents, especially those with activity against multidrug-resistant Gram-negative bacteria, has arisen as one of the major public health threats of the 21st century. Antimicrobial stewardship has emerged as a key available means to attenuate this threat. Because of the immediacy of the crisis imposed by the dearth of new antimicrobial agents, this review aims to seek out innovative mechanisms that could complement existing programmes to maximize their effectiveness. Provision of expedited microbiological identification and susceptibility profiles utilizing molecular diagnostic techniques are means that are showing promise in complementing existing stewardship interventions. Biomarkers such as procalcitonin that facilitate clinical decision-making processes in discriminating between noninfectious causes masquerading as sepsis can assist in withholding or earlier discontinuation of antimicrobial agents. Seasonal influenza and polyvalent pneumococcal vaccine have a role to play by preventing secondary bacterial infections. Electronic learning tools are a means of disseminating information rapidly and universally. Coordinated national and international stewardship efforts play an essential role in promotion, engaging the public, and ensuring provision of sufficient resources. The safeguarding of antimicrobial agents for future generations is necessary, if we as a public do not wish to face a world without antibiotics. All potentially available resources must be recruited to order to protect antimicrobials. Robust methods of evaluating each of these interventions needs to be included from inception to evaluate which strategies are the most effective.
    Current Opinion in Infectious Diseases 08/2013; 26(4):352-358. DOI:10.1097/QCO.0b013e3283631046 · 5.03 Impact Factor
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    ABSTRACT: Daptomycin, a cyclic lipopeptide with rapid bactericidal activity, is approved at doses of 4mg/kg and 6mg/kg for the treatment of its respective indications [i.e. complicated skin and soft-tissue infections (cSSTIs) caused by Gram-positive bacteria; and Staphylococcus aureus bacteraemia associated with right-sided infective endocarditis (RIE) or cSSTIs, or RIE due to S. aureus]. Higher doses and combination therapy strategies have been investigated in some difficult-to-treat infections in order to: enhance clinical success rates; treat pathogens that may be non-susceptible to standard doses; and minimise the risk of resistance development in patients, particularly those who may need an extended treatment duration, who may have had suboptimal surgical management and/or who may have not responded to prior antibiotic therapy. Although clinical trial data of daptomycin doses >6mg/kg and of daptomycin in combination with other antibiotics are limited, clinical experience reported to date suggests that daptomycin is effective and well tolerated at higher doses and in combination. In this review, the rationale both for high-dose and combination therapy strategies with daptomycin is explored and the available evidence is presented by indication and evaluated from a clinical perspective. Safety and efficacy are discussed from prospective and retrospective clinical studies, together with case reports for a variety of infections, including bacteraemia, endocarditis, cSSTIs and osteomyelitis, and expert recommendations are provided in summary of the evidence. The use of high-dose daptomycin, alone or in combination, may be useful for difficult-to-treat Gram-positive infections and further evaluation of these strategies is warranted.
    International journal of antimicrobial agents 07/2013; 42(3). DOI:10.1016/j.ijantimicag.2013.05.005 · 4.26 Impact Factor
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    ABSTRACT: The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has increased during the past 10 years. Its detection is frequently difficult, because they do not always show a minimum inhibitory concentration (MIC) value for carbapenems in the resistance range. Both broth microdilution and agar dilution methods are more sensitive than disk diffusion method, Etest and automated systems. Studies on antimicrobial treatment are based on a limited number of patients; therefore, the optimal treatment is not well established. Combination therapy with two active drugs appears to be more effective than monotherapy. Combination of a carbapenem with another active agent - preferentially an aminoglycoside or colistin - could lower mortality provided that the MIC is ≤4 mg/l and probably ≤8 mg/l, and is administered in a higher-dose/prolonged-infusion regimen. An aggressive infection control and prevention strategy is recommended, including reinforcement of hand hygiene, using contact precautions and early detection of CPE through use of targeted surveillance.
    Journal of chemotherapy (Florence, Italy) 06/2013; 25(3):129-40. DOI:10.1179/1973947812Y.0000000062 · 1.07 Impact Factor
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    I.M. Gould
    International Journal of Antimicrobial Agents 06/2013; 41:S6. DOI:10.1016/S0924-8579(13)70021-9 · 4.26 Impact Factor
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    I.M. Gould
    International Journal of Antimicrobial Agents 06/2013; 42:S12. DOI:10.1016/S0924-8579(13)70152-3 · 4.26 Impact Factor
  • I M Gould
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    ABSTRACT: Around the world, Staphylococcus aureus remains a dominant cause of bacteraemia. Whilst meticillin resistance remains the major phenotype of concern, various levels of reduced glycopeptide susceptibility are emerging with increasing frequency. The most common MRSA phenotypes now have raised vancomycin MICs within the susceptible range (MICs of 1-2mg/L). This phenomenon, known as MIC creep, is hotly contested and often denied. Key to detecting MIC creep may be to examine isolates fresh, as freezing can allow reversion to wild-type MIC, presumably by loss of mutations. Treatment failure is common with vancomycin and it is uncertain whether higher doses are beneficial. At the other extreme, when enough mutations have accumulated, full VISA status is achieved, although this can also be unstable on storage. Heteroresistant and VISA strains can be considered the inevitable end result of continued MIC creep and are even more likely to fail glycopeptide treatment. Currently full vancomycin resistance is uncommon, with only approximately 20 strains described and confirmed worldwide. Empirical treatment for patients with undefined Gram-positive sepsis can undoubtedly be improved by knowledge of MRSA status, so this is a potential advantage of hospital admission screening. If a patient is risk-assessed or screen-positive for MRSA, and infection is not serious, then vancomycin or teicoplanin is appropriate empirical therapy, providing loading doses are given to achieve therapeutic concentrations immediately (trough 15mg/L). For life-threatening infections, the glycopeptides are inadequate unless the isolate is likely to be fully susceptible (Etest<1.5mg/L). If not, daptomycin (8-10mg/L) can be used as monotherapy but the MIC should be measured as soon as possible.
    International journal of antimicrobial agents 05/2013; DOI:10.1016/j.ijantimicag.2013.04.006 · 4.26 Impact Factor
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    ABSTRACT: The first publication of this review in Issue 3, 2005 included studies up to November 2003. This update adds studies to December 2006 and focuses on application of a new method for meta-analysis of interrupted time series studies and application of new Cochrane Effective Practice and Organisation of Care (EPOC) Risk of Bias criteria to all studies in the review, including those studies in the previously published version. The aim of the review is to evaluate the impact of interventions from the perspective of antibiotic stewardship. The two objectives of antibiotic stewardship are first to ensure effective treatment for patients with bacterial infection and second support professionals and patients to reduce unnecessary use and minimize collateral damage.
    Cochrane database of systematic reviews (Online) 04/2013; DOI:10.1002/14651858.CD003543.pub3 · 5.94 Impact Factor
  • Journal of Antimicrobial Chemotherapy 03/2013; 68(7). DOI:10.1093/jac/dkt070 · 5.44 Impact Factor
  • Ian M. Gould
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    ABSTRACT: Recent evidence from publications describing the success of interventions to control hospital meticillin-resistant Staphylococcus aureus (MRSA), often in the endemic setting, is reviewed. Overall, there is cautious ground for optimism that MRSA can be controlled in a cost-effective manner by employing a bundle approach, the mainstay of which is widespread admission screening to inform patient-specific control measures.
    03/2013; 1(1):43–45. DOI:10.1016/j.jgar.2013.01.006
  • I.M. Gould
    03/2013; 1(1):3. DOI:10.1016/j.jgar.2013.02.002
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    ABSTRACT: Infection with meticillin-resistant Staphylococcus aureus (MRSA) continues to have significant morbidity and mortality. Vancomycin, which has been the mainstay of treatment of invasive MRSA infections, has several drawbacks related to its pharmacological properties as well as varying degrees of emerging resistance. These resistant subpopulations are difficult to detect, making therapy with vancomycin less reliable. The newer agents such as linezolid, daptomycin, ceftaroline, and the newer glycopeptides telavancin and oritavancin are useful alternatives that could potentially replace vancomycin in the treatment of certain conditions. By summarising the discussions that took place at the III MRSA Consensus Conference in relation to the current place of vancomycin in therapy and the potential of the newer agents to replace vancomycin, this review focuses on the challenges faced by the laboratory and by clinicians in the diagnosis and treatment of MRSA infections.
    03/2013; 1(1):23–30. DOI:10.1016/j.jgar.2013.01.002
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    Ian M Gould, Abhijit M Bal
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    ABSTRACT: Bacterial resistance is a growing threat and yet few new antibiotics active against multi-resistant bacteria are being explored. A combination of falling profits, regulatory mechanisms and irrational and injudicious use of antibiotics has led to an alarming situation where some infections have no cure. In this article, we summarize the new developments that have been suggested to incentivize the pharmaceutical industries toward the field of infections. We also briefly mention the new compounds on the horizon and some newly approved compounds that might help us tide over this crisis.
    Virulence 01/2013; 4(2). DOI:10.4161/viru.22507 · 3.32 Impact Factor
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    ABSTRACT: The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalised patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with healthcare. The most rapidly spreading and tenacious healthcare-associated clone in Europe currently is EMRSA-15, a lineage that was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. To understand the genetic events that have accompanied the emergence of the EMRSA-15 pandemic, we obtained genome sequences for 193 isolates that were chosen for their geographical and temporal diversity, and belong to the same multilocus sequence type as EMRSA-15. Using phylogenomic methods, we were able to show that the current pandemic population of EMRSA-15 descends from a healthcare-associated MRSA epidemic that spread through England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 sub-clone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this sub-clone over the last twenty years has grown four times faster than its progenitor. Using comparative genomic analysis we were able to identify the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.
    Genome Research 01/2013; DOI:10.1101/gr.147710.112 · 13.85 Impact Factor
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    ABSTRACT: The International Society of Chemotherapy's Working Groups on Antibiotic Resistance and Antibiotic Stewardship convened a half-day workshop on the burden of multidrug-resistant organisms in the Asia-Pacific. This short review is a summary of their discussion and conclusions.
    01/2013; DOI:10.1016/j.jgar.2013.10.005

Publication Stats

3k Citations
945.71 Total Impact Points

Institutions

  • 2012
    • NHS Health Scotland
      Edinburgh, Scotland, United Kingdom
  • 2011–2012
    • NHS Grampian
      Aberdeen, Scotland, United Kingdom
    • NHS Ayrshire and Arran
      Ayr, Scotland, United Kingdom
  • 1994–2009
    • University of Aberdeen
      • Health Services Research Unit
      Aberdeen, Scotland, United Kingdom
  • 2004
    • Statens Serum Institut
      København, Capital Region, Denmark
  • 2000–2001
    • University of Trnava
      • Department of Public Health
      Nagyszombat, Trnavský, Slovakia
  • 1997
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 1988–1995
    • Aberdeen City Council
      Aberdeen, Scotland, United Kingdom