Select Committee on Health Written Evidence

Memorandum by ARHAI (PS 45)



  This response is on behalf of the Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infections (ARHAI). The advisory committee is tasked with providing practical and scientific advice to the Government on strategies to minimise the incidence of healthcare associated infections and to maintain the effectiveness of antimicrobial agents in the treatment and prevention of microbial infections in man and animals. ARHAI considers that health care acquired infections and antimicrobial resistance pose a significant threat to patient safety and therefore have responded to the committee's call for evidence.

  This paper concentrates on two different areas within the committee's remit

    —  the effects of the uncontrolled use of antibiotics and in particular their role in Clostridium difficile infection (CDI)

    —  reducing health care acquired infection (HCAI) by developing an organisational perspective on infection prevention delivery


  The use of antibiotics is a key factor for the development of healthcare associated CDI. CDI is a clear risk to patient safety and the treatment of CDI consumes significant healthcare resources primarily due to markedly increased hospital stay.

  The paper considers strategies for decreasing cases of CDI within the healthcare system. Restricting the use of certain classes of antibiotics has been shown to lower rates of CDI. Hospitals need to have a clear policy on the prescribing of antibiotics coupled with mandatory education and audit programmes. Audit and feedback to staff has been shown to facilitate implementation of evidence based guidelines on antibiotic prescribing and reduce incidence of CDI. However these studies are isolated studies and there are no overall figures for the level of antibiotic prescribing in the UK. Collecting data on the type and numbers of antibiotics prescribed would greatly enhance the value of the mandatory surveillance data already collected on CDI within hospitals. Collecting this additional data would allow a link to made between cause and effect and provide a powerful tool for investigating the correlations between antimicrobial prescribing and CDI. This data could aid the identification of antibiotics that are less likely to induce CDI and thus inform future prescribing.

Reducing health care acquired infection (HCAI) by developing an organisational perspective on infection prevention delivery

  Healthcare acquired infection (HCAI) occurs in 8.19% of all hospital inpatients in England. HCAI is also currently the most common concern of the population regarding the safety of an inpatient admission. As such, infection prevention should be regarded as a core aspect of patient safety. To deliver sustainable infection prevention within acute Trusts an organisational approach should be considered, embedding infection prevention in the organisation's culture, decision making, performance monitoring and all aspects of management and care.



  1.  Diarrhoea is one of the most common side effects of antibiotics, usually because of disturbance of the normal gut (friendly) bacteria or increased gut motility. However, some cases of antibiotic associated diarrhoea result from infection caused by Clostridium difficile (CDI). Antimicrobial agents that induce CDI are believed to perturb the normal gut bacteria, which facilitates the germination of C. difficile spores in patients who acquire, or are colonised by C. difficile. This leads to proliferation of C. difficile and subsequent toxin production. It is the toxins that C. difficile produces, once it has been stimulated by antibiotic exposure, that cause inflammation of the wall of the large bowel (colitis) with consequent diarrhoea. Cases that are complicated by severe inflammation of the gut wall (pseudomembranous colitis) may be more likely to lead to death. These are associated with recently recognised virulent C. difficile strains, notably, but not exclusively, in the frail elderly. Reports of CDI are generally increasing in many countries; this reflects the emergence of these virulent strains and greater detection as diagnostic testing increases. CDI consumes significant healthcare resources primarily due to markedly increased length of hospital stay. It is increasingly clear that CDI occurs in people in the community who have not had recent hospital stays.

Antibiotic prescribing and CDI risk

  2.  Use of antibiotics is the key risk factor for the development of healthcare associated CDI, especially third-generation cephalosporins given to the elderly, as well as clindamycin and prolonged use of aminopenicillins. In fact all antibiotics may predispose to CDI and this should influence prescribing practice ie all antibiotic prescriptions should be justifiable because there is a real risk of harm, especially if high risk agents are used in patients at high risk of CDI. The same is true concerning the number of antibiotic prescriptions and their duration. Thus, if a patient receives more antibiotic courses and or longer prescriptions (including administration of prophylactic peri-operative antibiotics for longer than the recommended 24 hours) then the risk of CDI increases.

Strength of evidence

  3.  The quality of the evidence concerning the level of CDI risk associated with specific antibiotics is modest. Crucially, studies have frequently failed to account for the risk of C. difficile acquisition, remembering that CDI cases are often caused by bacteria that have recently been acquired by the patient. Also, hospital patients often receive more than one antibiotic, and they may have had prior antibiotic exposure. Despite these issues, some antibiotics are less likely to induce CDI, including penicillin and vancomycin, and some broad spectrum agents such as gentamicin, and anti-pseudomonal penicillins, with or without a beta-lactamase inhibitor.

Effectiveness of altered antibiotic prescribing

  4.  If all the available evidence is examined to determine the effectiveness of changing antibiotic prescribing in order to reduce the risk of infection, the most robust finding is that restricting use of broad spectrum antibiotics, specifically cephalosporins or clindamycin, can reduce the incidence of CDI. Two crossover studies and a follow-on surveillance study on acute elderly wards, all performed in NHS hospitals, showed that effective restriction of third-generation cephalosporins was associated with a reduction in C. difficile. Such findings do not lessen the importance of good infection prevention and control practice that reduces to a minimum the chance that pathogens such as C. difficile can spread in healthcare settings. Clearly, even low risk antibiotic use could lead to CDI if it is undermined by patient acquisition of C. difficile.

Education and audit

  5.  No one sets out to induce CDI when they prescribe an antibiotic. Education of young and old doctors is important to reduce the risk of CDI occurring. Every prescriber should consider, "Is this patient at particular risk of CDI?" and should modify prescribing behaviour accordingly. Choosing the correct antibiotic(s) initially affects the success of treatment, including the chance of survival. Repeated changes to antibiotic therapy not only risk poor treatment response, but also increase the selection pressure for resistance bacteria and the risk of CDI. Hospitals should have policies to control antibiotic prescribing and mandatory education and audit programmes in place. Hospital pharmacy initiatives to improve antibiotic management, notably via the appointment of antimicrobial pharmacists, appear to facilitate greater local multidisciplinary working between pharmacy and microbiology/infectious diseases departments. Systematic reviews suggest that audit and feedback may improve the implementation of evidence-based guidelines by healthcare workers. This approach has been shown to reduce CDI rates following decreased cephalosporin prescribing.

Identifying high risk antibiotics

  6.  Identification of antibiotics that are less likely to induce CDI is important, particularly so that policies can be designed to promote their use, especially in at risk patients. Given the difficulties in the clinical setting of identifying which antibiotics are truly high risk agents for inducing CDI, greater attention should be paid to pre-clinical and pre-licensing assessment of this risk. It is commonplace not to recruit elderly and particularly frail patients to clinical trails of new antibiotics. Thus, at the time that licensing decisions and cautions for antibiotic use are agreed only very limited data on antibiotic risk of CDI are available. Post market surveillance to obtain real life data on CDI risk is important for new antibiotics and should be formally required, unless risk data are already available. Also, a model system has been described that can identify which antibiotics induce C. difficile to start producing toxins. This approach can provide data on CDI risk that appears to correlate well with clinical experience.

Monitoring antibiotic prescribing

  7.  An important gap currently exists in our ability to compare antibiotic prescribing practice between NHS hospitals. Systems are in place, and indeed targets have been set, to monitor rates of CDI (and MRSA). It is illogical, however, that a national systematic surveillance system to measure antibiotic prescribing is not available, as antimicrobial use is a key driver of healthcare associated pathogens. Information technology issues represent a significant barrier to achieving such a surveillance system, but a simplified mandatory scheme could be established for NHS hospitals. This could at least identify major outliers in terms of overall antibiotic use and/or prescribing of specific types of antimicrobials; this in turn could prompt further data collection and audit. Information technology can also be used to control real time antibiotic prescribing; for example, each prescription can automatically be compared against a standard, preventing deviations from agreed policies, minimising polypharmacy and/or broad spectrum therapy, and requiring the use of automatic stop or review dates.

  8.  Antibiotic prescribing data should of course be analysed alongside the considerable surveillance information that is available from the mandatory C. difficile scheme, which is managed by the Health Protection Agency. This approach would provide a powerful tool to investigate correlations between antimicrobial prescribing (overall and for specific antibiotics) and rates of CDI. Furthermore, detailed C. difficile fingerprinting data are also available from the Health Protection Agency's C. difficile Ribotyping Network for England. Thus, we would be able to identify which antibiotics were most responsible for CDI, including for established and emergent epidemic strains. Measuring both cause and effect would greatly increase the value of surveillance data.



  9.  The extreme public concern, media interest and political target setting around HCAIs as well as the incidence of occurrence, particularly in vulnerable patient groups makes infection prevention a patient safety priority for the NHS. Trusts need to recognise infection prevention as a key area of their patient safety and quality improvement agenda and should consider an organisational approach to address it.

  10.  External reinforcement provides a driving force for change and improvement and the targeting of some resources, but for effective and sustainable improvement, particularly in large complex organisations a comprehensive organisational perspective should be considered with strong internal reinforcement, systems based approaches and shared aspirations and values.

  11.  It is now increasingly recognised that an organisational development approach to embed infection prevention within the running of Trusts and the delivery of clinical care is the way forward rather than a historical model with reliance on a small separate expert team. Infection prevention relies on a complex interconnection of risk reduction, prioritisation, leadership, behaviours and practices across multiple management systems and clinical care as well as the intrinsic risk factors of the individual patient. A piecemeal approach will be limited in effectiveness.

The Organisational Development Approach

  12.  The organisational development approach can be understood at a trust (corporate) level, as well as at a unit (team/department) level, with a particular emphasis on high risk units such as intensive care units (ICUs) and high dependency units (HDUs). Organisational development approaches can be used to address the challenge of competing NHS priorities, developing a shared culture of safety and infection prevention and provide opportunities to also use infection prevention related measures (both processes and outcomes) as proxy quality indicators of systems management, governance and clinical service.

At Trust level

  13.  The emphasis is that achieving safety requires more than individual carefulness. It is a corporate responsibility that should have equal or higher status for hospital boards than finance. However, it is recognised that the corporate responsibility and action may require external pressure to achieve. From an organisational perspective, HCAIs can be considered a marker of organisational governance, management competence, reliability of systems, levels of training and levels of staffing. This is demonstrated in the Healthcare Commission's reports in which organisational issues are recurring themes; recent mergers, pre-occupation with the financial situation, service reconfigurations, conflicting priorities between finances and patient safety and poor antibiotic stewardship. These themes are reflective of systemic problems that are embedded in the culture of the organisation and can only be addressed through organisational-level interventions. The evidence-base for this perspective is weak in healthcare, but well-evidenced in high risk industries, such as the aviation, oil, gas and nuclear industries which have developed a high reliability approach to managing risk over the last two decades. Their risk strategies are informed by a human factors approach to error prevention that recognises the effect of behavioural issues on accidents.


    —  Further research is undertaken on the organisational development approach to patient safety and infection prevention in health

    —  The full integration of infection prevention into the patient safety agenda

    —  The development of toolkits to assist Trusts in the development of a sustainable strategy for infection prevention

    —  Infection prevention-focused impact assessments with senior sign-off for any changes to health infrastructure eg estates, policies, clinical systems, eg patient flows or service developments

    —  Table top exercises/decision making workshops with multidisciplinary teams of managers and senior clinicians to simulate the management of conflicting priorities and maintaining infection prevention goal.

At Unit Level with a focus on High Risk Areas

  14.  Recently, a growing recognition by clinicians of the nature and impact of organisational pressures on areas, such as ICUs has led to preliminary studies centred on high risk units within healthcare. Studies from the US have highlighted the patient safety and cost issues associated with infections. For example, infections in patients in intensive care are associated with an estimated attributable mortality of 35%, an additional cost of $40,000 per survivor and an additional 8 days length of stay in a surgical intensive care unit (SICU) admission. Further research has examined factors such as workload, staffing ratios, protocol adherence, hand hygiene promotion and training as having an impact on the effective management of infections. The economic, clinical and emotional impact of these results merits a re-examination of the use of conventional, organism-specific or device-related approaches to address infection occurrences in high risk units. The evidence-base for infection in UK healthcare high risk units is developing, as the contained nature of these units lend themselves to small, tightly focused research studies.


    —  Systems management indicators in ICUs particularly regarding staffing (ratios and levels of training) should be considered safety and infection prevention performance indicators

    —  Provision of feedback data on compliance with best practice (eg care bundles and antibiotic prescribing) and detailed infection surveillance with unit ownership to be considered a quality indicator of unit management and clinical care.

    —   Delivery and management of a regular planned programme of closure to allow maintenance and deep clean

    —  Learning from, and sharing experience of high risk units for vulnerable patient groups

Infection Outcomes as Indicators of Complex System Management

  15.  Infection related outcomes, such as rising infection rates and particular outbreaks may also be considered indicators of failures in organisational sustainability. To achieve the development of a safety culture in regards to infection prevention, attention has to be paid to managing staffing ratios, service configuration, bed management etc. Furthermore, infection prevention related outcomes can be considered markers of the extent to which organisations can work within competing priorities within the NHS without compromising patient safety and patient experience, an approach that more recently has been widely discussed in the light of the Darzi Report.

  16.  Infection related indicators in balanced scorecards are one mechanism to monitor outcomes in relation to other organisational indicators. Scorecards were originally developed as a framework to measure performance beyond finances in private industry. The drawback to scorecards is that they can skew activity as the organisation focuses only on the indicators measured and therefore needs regular refreshing and updating. To address this, checks and balances are needed within performance metrics to provide a level of sensitivity to patient safety factors. For example, to address high level of patient flow with high bed occupancy and admission targets, may lead to moving patients around the hospital from ward to ward several times. However, minimising bed moves for patients is a critical component of infection prevention, patient safety and the patient experience, therefore a bed move monitoring programme has been introduced locally as a quality indicator, and serves as a "check".

  17.  Whilst the evidence-base for the use of scorecards exists, less research has been undertaken on the use and effectiveness of infection-related indicators, or the extent to which they can be considered markers of effective organisational management.


    —  Research into the use of infection indicators as a barometer of patient safety

    —  Research into the use of checks and balances in Trust performance score cards to minimise the infection risk in the face of competing priorities and challenges.


  HCAIs present a risk to patient safety and are a considerable financial burden on NHS Trusts. Further research is needed to identify the best mechanisms to lower levels of HCAIs. However it is clear that an integrated approach to infection control within organisations, with support from staff at all levels, is essential to ensure good infection control. Robust hospital polices on antibiotic prescribing along with audits of compliance and feedback are important in reducing levels of antibiotics used and in reducing in CDI, an important HCAI. Surveillance of HCAIs and antibiotic prescribing is essential to identify areas where improvements can be made and also to provide new information about the most effective ways to control HCAIs.


  Annas GJ. The Patient's Right to Safety — Improving the Quality of Care through Litigation against Hospitals. N Engl J Med 2006; 354(19):2063-2066.

  Assadian O. Implications of staffing ratios and workload limitations on healthcare-associated infections and the quality of patient care. Crit Care Med 2007; 35(1):296-298.

  Attwood D, Khan F, Veitch B. Occupational accident models—Where have we been and where are we going? Journal of Loss Prevention in the Process Industries 2006; 19(6):664-682.

  BBC. Infections "the biggest NHS fear". Internet [ 2008 [cited 2008 Aug. 13]; Available from: URL:

  Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA et al. Why Don't Physicians Follow Clinical Practice Guidelines?: A Framework for Improvement. JAMA 1999; 282(15):1458-1465.

  Cooke FJ, Holmes AH. The missing care bundle: antibiotic prescribing in hospitals. Int J Antimicrob Agents 2007; 30(1):25-29.

  Darzi A. High Quality Care for all. NHS Next Stage Review Final Report. Department of Health [ 2008 [cited 2008 Aug. 4]; Available from: URL:

  Davey P, Brown E, Fenelon L et al. (2005). Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2005, Issue 4.

  Davey P, Brown E, Fenelon L et al. (2006). Systematic review of antimicrobial drug prescribing in hospitals. Emerg Infect Dis 12: 211-16.

  Department of Health. Board to Ward. How to embed a culture of HCAI prevention in acute Trusts. Internet [ 2008 [cited 2008 Sept. 19]; Available from: URL:

  George A, Tokars JI, Clutterbuck EJ, Bamford KB, Pusey C, Holmes AH. Reducing dialysis associated bacteraemia, and recommendations for surveillance in the United Kingdom: prospective study. BMJ 2006; 332(7555):1435.

  Grimshaw JM, Thomas RE, MacLennan G et al. (2004). Effectiveness and efficiency of guideline dissemination and implementation strategies. Health Technol Assess 8: iii-72.

  Harbarth S, Sudre P, Dharan S, Cadenas M, Pittet D. Outbreak of Enterobacter cloacae Related to Understaffing, Overcrowding, and Poor Hygiene Practices. Infect Control Hosp Epidemiol 1999; 20(9):598-603.

  Health Protection Agency. Surveillance of Healthcare Associated Infections Report: 2008. London: Health Protection Agency, July 2008. Available at: Last accessed 2 September 2008.

  Healthcare Commission. Investigation into outbreaks of Clostridium Difficile at Stoke Mandeville Hospital, Buckinghamshire Hospitals NHS Trust. Healthcare Commission [ 2006 [cited 2008 May 16]; Available from:

  Healthcare Commission. Investigation into outbreaks of Clostridium difficile at Maidstone and Tunbridge Wells NHS Trust. Healthcare Commission [ 2007 [cited 2008 July 11]; Available from:

  Holmes A, Dorq CJ, Saraswatula A, Bamford KB, Richards MS, Coello R et al. Risk factors and recommendations for rate stratification for surveillance of neonatal healthcare-associated bloodstream infection. J Hosp Infect 2008; 68(1):66-72.

  Holmes AH. Can organisational change reduce hospital acquired infections? J Hosp Infect 2007; 65(Supplement 2):191-192.

  Hugonnet S. The effect of workload on infection risk in critically ill patients. Crit Care Med 2007; 35(1):76-81.

  Jamtvedt G, Young JM, Kristoffersen DT et al. (2006). Audit and feedback: effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2006, Issue 1.

  Kadak AC, Matsuo T. The nuclear industry's transition to risk-informed regulation and operation in the United States. Reliability Engineering & System Safety 2007; 92(5):609-618.

  Kaplan RS, Norton DP. Using the Balanced Scorecard as a Strategic Management System. Harv Bus Rev 1996; 74(1):75-85.

  Khan FI, Amyotte PR, DiMattia DG. HEPI: A new tool for human error probability calculation for offshore operation. Safety Science 2006; 44(4):313-334.

  Lawson E, Price C. The psychology of change management. The McKinsey quarterly 2003;(2):30-41.

  Leape L, Epstein AM, Hamel MB. A Series on Patient Safety. N Engl J Med 2002; 347(16):1272-1274.

  Logan TJ. Error Prevention as Developed in Airlines. International Journal of Radiation Oncology*Biology*Physics 2008; 71(1, Supplement 1):S178-S181.

  Mah MW, Deshpande S, Rothschild ML. Social marketing: A behavior change technology for infection control. Am J Infect Control 2006; 34(7):452-457.

  National Clostridium difficile Standards Group (2004). Report to the Department of Health. J Hosp Infect 56(Suppl 1): S1-S38.

  Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1994; 271(20):1598-1601.

  Reason J. Human error: models and management. BMJ 2000; 320(7237):768-770.

  Saxton K, Baines SD, Freeman J, O'Connor R, Wilcox MH (2008). Effects of exposure of Clostridium difficile PCR ribotypes 027 and 001 to fluoroquinolones in a human gut model. Antimicrob Agents Chemother. Aug 18. [Epub ahead of print].

  Settle CD, Wilcox MH, Fawley WN et al. (1998). Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin-tazobactam. Aliment Pharmacol Ther 12: 1217-23.

  Smyth ETM, McIlvenny G, Enstone JE, Emmerson AM, Humphreys H, Fitzpatrick F et al. Four Country Healthcare Associated Infection Prevalence Survey 2006: overview of the results. J Hosp Infect 2008; 69(3):230-248.

  Stone S, Kibbler C, How A and Balstrini A (2000). Feedback is necessary in strategies to reduce hospital acquired infection. BMJ 321: 302-03. (Fowler et al., 2007)

  Thomas C, Stevenson M and Riley TV (2003). Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review. J Antimicrob Chemother 51: 1339-50.

  Wickens HJ and Jacklin A (2006). Impact of the Hospital Pharmacy Initiative for promoting prudent use of antibiotics in hospitals in England. J Antimicrob Chemother 58: 1230-7.

  Wilcox MH, Freeman J, Fawley W et al. (2004). Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea. J Antimicrob Chemother 54: 168-72.

  Wilcox MH, Mooney L, Bendall R et al. (2008). A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 62: 388-96.

  Xiao Y. Video-based training increases sterile-technique compliance during central venous catheter insertion. Crit Care Med 2007; 35(5):1302-1306.

September 2008

previous page contents next page

House of Commons home page Parliament home page House of Lords home page search page enquiries index

© Parliamentary copyright 2008
Prepared 30 October 2008