Superbugs and Superdrugs: A history of MRSA

Annotated and edited transcript of a Witness Seminar held on 11 July 2006. Introduction by Professor David Greenwood, University of Nottingham.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2008.©The Trustee of the Wellcome Trust, London, 2008.All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 11 July 2006. Introduction by Professor David Greenwood, University of Nottingham.Annotated and edited transcript of a Witness Seminar held on 11 July 2006. Introduction by Professor David Greenwood, University of Nottingham.Annotated and edited transcript of a Witness Seminar held on 11 July 2006. Introduction by Professor David Greenwood, University of Nottingham.Annotated and edited transcript of a Witness Seminar held on 11 July 2006. Introduction by Professor David Greenwood, University of Nottingham.Annotated and edited transcript of a Witness Seminar held on 11 July 2006. Introduction by Professor David Greenwood, University of Nottingham.Annotated and edited transcript of a Witness Seminar held on 11 July 2006. Introduction by Professor David Greenwood, University of Nottingham.Because of its unique adaptability and resistance to many antibacterial drugs and antiseptics, methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial menace of the present day. It has invaded medical and surgical wards in hospitals, infecting patients already ill or recovering, and endangering clean surgical operations, encouraged by overcrowding and limited air circulation. It has now spread from hospitals to families and communities. Infection control microbiologists and the Public Health Laboratory Service developed assays, ‘phage typing and other tests to identify strains, with better understanding of their behaviour aided by the discovery of the mecA gene. This Seminar addressed the biological reasons for this behaviour; the difference between resistant and non-resistant strains; the development, evolution and elucidation of drug resistance in hospital infection and its geographical distribution. Suggested by Professor Gordon Stewart and chaired by Dr Robert Bud, surgeons, microbiologists, infection control experts and representatives of the pharmaceutical industry and of the public included: Professor Graham Ayliffe, Professor Mark Casewell, Dr Bilwanath Chattopadhyay, Dr Stephanie Dancer, Dr Bernard Dixon, Dr Georgia Duckworth, Professor Brian Duerden, Professor Michael Emmerson, Professor Gary French, Professor Curtis Gemmell, Professor Alan Glynn, Dr Ian Gould, Professor David Greenwood, Professor Jeremy Hamilton-Miller, Dr Angela Kearns, Dr Bill Newsom, Professor Ian Phillips, Dr Tyrone Pitt, Dr Elizabeth Price, Professor Sir Mark Richmond, Dr Geoffrey Scott, Dr Joe Selkon, Dr David Shanson, Dr Norman Simmons, Professor Dale Smith, Professor Brian Spratt, Dr Robert Sutherland, Professor John West. Reynolds L A, Tansey E M. (eds) (2008) Superbugs and superdrugs: A history of MRSA, Wellcome Witnesses to Twentieth Century Medicine, vol. 32. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

Revisiting antimicrobial therapy in critically ill patients through pharmacometri

Contains fulltext : 251476.pdf (Publisher’s version ) (Open Access)Radboud University, 29 augustus 2022Promotor : Burger, D.M. Co-promotores : Bruggemann, R.J.M., Heine, R. ter, Schouten, J.A

Cost effectiveness of treatment with percutaneous Kirschner wires versus volar locking plate for adult patients with a dorsally displaced fracture of the distal radius: Analysis from the DRAFFT trial

We present an economic evaluation using data from the Distal Radius Acute Fracture Fixation Trial (DRAFFT) to compare the relative cost effectiveness of percutaneous Kirschner wire (K-wire) fixation and volar locking-plate fixation for patients with dorsally-displaced fractures of the distal radius. The cost effectiveness analysis (cost per quality-adjusted life year; QALY) was derived from a multi-centre, two-arm, parallel group, assessor-blind, randomised controlled trial which took place in 18 trauma centres in the United Kingdom. Data from 460 patients were available for analysis, which includes both a National Health Service cost perspective including costs of surgery, implants and healthcare resource use over a 12-month period after surgery, and a societal perspective, which includes the cost of time off work and the need for additional private care. There was only a small difference in QALYs gained for patients treated with locking-plate fixation over those treated with K-wires. At a mean additional cost of £714 (95% confidence interval 588 to 865) per patient, locking-plate fixation presented an incremental cost effectiveness ratio (ICER) of £89 322 per QALY within the first 12 months of treatment. Sensitivity analyses were undertaken to assess the ICER of locking-plate fixation compared with K-wires. These were greater than £30 000. Compared with locking-plate fixation, K-wire fixation is a 'cost saving' intervention, with similar health benefits

Therapeutic drug monitoring of antimicrobial drugs in neonates. An opinion paper

Neonatal infections are associated with high morbidity and mortality rates. Optimal treatment of these infections requires knowledge of neonatal pharmacology and integration of neonatal developmental pharmacokinetics (PKs) of antimicrobial drugs in the design of dosing regimens for use with different gestational and postnatal ages. Population PK and pharmacodynamic models are used to personalize the use of these drugs in these fragile patients. The final step to further minimize variability in an individual patient is therapeutic drug monitoring (TDM), where the same population PK/pharmacodynamic models are used in concert with optimally drawn blood samples to further fine-tune therapy. The purpose of this article is to describe the present status and future role of model-based precision dosing and TDM of antimicrobial drugs in neonates. METHODS: PubMed was searched for clinical trials or clinical studies of TDM in neonates. RESULTS: A total of 447 articles were retrieved, of which 19 were concerned with antimicrobial drugs. Two articles (one aminoglycoside and one vancomycin) addressed the effects of TDM in neonates. We found that, in addition to aminoglycosides and vancomycin, TDM also plays a role in beta-lactam antibiotics and antifungal drugs. CONCLUSIONS: There is a growing awareness that, in addition to aminoglycosides and vancomycin, the use of beta-lactam antibiotics, such as amoxicillin and meropenem, and other classes of antimicrobial drugs, such as antifungal drugs, may benefit from TDM. However, the added value must be shown. New analytical techniques and software development may greatly support these novel developments

Statistical correlation based methods for enhanced interpretation of and information recovery from NMR metabolic data sets

Owing to its ability to capture a systemic and temporal metabolic description of an organism’s response to a treatment, metabonomics is a well-established and valuable approach in elucidating the effects and mechanisms of a given perturbation. However, to optimise information recovery from the complex datasets generated, chemometric methods are essential. The work presented in this thesis focuses on the development of novel methods, and the use of existing methods in new applications to ease data interpretation and enhance information recovery from 1H Nuclear Magnetic Resonance (NMR) metabonomic datasets using correlation based methods. Although the methods here are largely applied to toxicological data, they could be equally valuable in the analysis of any metabonomic dataset, and indeed potentially to other ‘omics’ data presenting similar analytical challenges. The first two methodological approaches relate to novel extensions of Statistical Total Correlation Spectroscopy (STOCSY), a valuable tool in elucidation of both inter- and intra-metabolite spectral intensity correlations in NMR metabonomic datasets. In the first, STOCSY is utilised in STOCSY-editing, a method for the selective identification and downscaling of the peaks from unwanted metabolites such as those arising from xenobiotics. Structurally correlated peaks from drug metabolites are first identified using STOCSY, and the returned correlation information utilised to scale the spectra across these regions, producing a modified set of spectra in which drug metabolite contributions are reduced, endogenous peaks reconstructed and thus, analysis by pattern recognition methods without drug metabolite interferences facilitated. In the second, the STOCSY approach is extended in Iterative-STOCSY, where metabolic associations are followed over several rounds of STOCSY through calculation of correlation coefficients initially from a driver spectral peak of interest, and subsequently from all peaks identified as correlating above a set threshold to peaks picked in the previous round. The condensation of putatively structurally related peaks into single nodes, and representation of the otherwise complex network in a fully interactive plot of node-to-node connections and corresponding spectral data, allows the ready exploration of both inter- and intrametabolite relationships and a more directed approach to the identification of biomarkers of the studied perturbation. Finally various clustering methods are investigated with the aim of providing improved structural (intra-metabolite) versus non-structural (inter-metabolite) assignment. Thus, this thesis presents a framework for the enhanced identification, recovery and characterisation of inter- and intrametabolite relationships and how these are affected by metabonomic perturbation

Hip arthroplasty

A 68- year old gentleman presented to outpatients clinic complaining of pain in his right hip, 10 years after undergoing a total hip replacement. Following a thorough history, physical, lab and radiographic investigations, aseptic loosening of the hip prosthesis was diagnosed. One-stage revision surgery was carried out and the patient is currently undergoing rehabilitation and being followed up. Aim: This report will review the history, examination, investigations and management of a case of aseptic loosening of a total hip arthroplasty (both acetabular and femoral components). It will also serve as an excellent illustration of the various examination techniques and other investigations which are made use of for the diagnosis of hip (and other orthopaedic) conditions. Apart from describing the main surgical therapy required in this case i.e. revision arthroplasty, the case report will also deal with the complex yet equally essential perioperative drug management which complements the surgical treatment. Moreover, this case highlights the holistic approach to patient care, requiring a multidisciplinary team (including proper nursing, physiotherapy etc.).peer-reviewe

Surgical site infection following major lower limb amputation : analysing the clinical effectiveness of antibiotic prophylaxis duration and skin preparation

Background: Major LLA remains a common operation in the United Kingdom with ⁓5000 procedures performed yearly. Amputations are described as ‘clean surgery’ and SSIs in this patient cohort have been previously under-reported. The true incidence lies between 13-35% and is associated with patient mortality, morbidity and implications on health economics. Previous work done in this thesis has demonstrated lack of consensus in clinical practice regarding perioperative antibiotic prophylaxis, and lack of high quality studies to formulate and sustain a common practice across the UK.Methods: A single centre RCT was designed to which a total of 161 patients were recruited and randomised to receive either a 5-day or a 24-hour prophylactic antibiotic course. Within the groups further allocation to skin preparation (alcoholic chlorhexidine Vs. alcoholic povidone iodine) was performed by stratification.Results: A total of 153 patients were included in the final analysis. Groups were well matched for comorbidities and demographics. The use of a 5-day course was associated with a statistically significant lower incidence of SSI(n=9, 11.5%) when compared to the 24-hour group (n=27, 36%) (P<0.001) and lower incidence of IWH(n=20, 25.6% Vs. n=40, 53.3% respectively) (P<0.001). History of diabetes, smoking, and transmetatarsal amputations performed, were statistically significant independent factors associated with an increase in SSI incidence (P=0.018, P=0.005, and P<0.001 respectively). Choice of skin preparation between alcoholic chlorhexidine and povidone iodine had no effect on the incidence of SSI / IWH (P=0.851 and P=0.326 respectively). The presence of SSI statistically significantly increased the post-operative length of hospital stay (from median 14 to 28 days, P=0.015)Conclusions: This is a Level 1 study which demonstrated that the use of a 5-day over a 24-hour antibiotic course can significantly reduce incidence and risk of SSI/IWH development. It has also highlighted 3 independent factors, 2 of which could be addressed during the preoperative optimisation stage to reduce the risk of developing an SSI post-operatively. The presence of SSI is associated with prolonged hospital stay, something which has significant implications on patient morbidity as well as incurring significant costs on healthcare resources.[Includes two articles published in Annals of vascular surgery (pages 254-267 of thesis, removed):https://doi.org/10.1016/j.avsg.2014.06.055 - A survey of perioperative management of major lower limb amputations : current UK practicehttps://doi.org/10.1016/j.avsg.2013.10.017 - The impact of previous surgery and revisions on outcome after major lower limb amputation

Evaluation of pharmacist interventions on drug and dosage prescribing in pediatric settings

Objectives: To evaluate the influence of pharmacist interventions on drug and dosage prescribing in pediatric settings. Method: Demographic, clinical, and prescribing data and parents’ measurement data were evaluated by pre- and post studies including time series studies and control groups. The data was evaluated against Australian Therapeutic Guidelines. Educational intervention strategies were designed and administered and a post-intervention evaluation was conducted. Group comparisons were made using x2 and Student’s t-test statistics. Time series analysis involved multiple linear regression analysis. Results: The major study involved antibiotics and analgesic drugs and dosages in appendectomy in children. Significant improvements occurred in the selection and dosages of prophylactic antibiotics @<0.001) and in subsequent ward antibiotic treatments @<0.001) also showed marked conformity with the guidelines Other pediatric studies involved liquid medication dosing and prescribing accuracy for paracetamol in a developing country where a simple intervention produced very marked improvements @<0.001). An intervention in severe community-acquired pneumonia showed an improvement in the prescription of appropriate drugs @<0.001) and appropriate dosages of paracetamol (p<O.OOl) according to the guidelines. In drug utilisation evaluation of cefiriaxone, flucloxacillin and Liquigesic COB, there was a significant improvement in the dosage prescribing of ceftriaxone and flucloxacillin and no change in Liquigesic COB following the intervention. O f the total, 38/218 (17%) o f the patients received appropriate post-operative antibiotic dosages. 286/368 (78%) of the analgesic prescriptions and 31/218 (14%) of the patients on postoperative antibiotic choice and dosage that were identified as appropriate in tonsillectomy.Conclusion: This study has identified deficiencies related to the prescribing of antibiotics and analgesics in children. There was a varied level of improvement in the drug dosage prescribing of pediatricians following the pharmacist educational intervention. Locally developed guidelines are more likely to be accepted and followed than those developed nationally without local input