CME Infectious diseases Clinical Medicine 2013, Vol 13, No 5: 499–503 28 Department of Health Advisory Committee encompass initiatives that promote the on Antimicrobial Resistance and Healthcare Antibiotic responsible use of antibiotics, with the goal of Associated Infection. Antimicrobial steward- preserving their future effectiveness and safe- ship: ‘Start smart – then focus’. London: DH, stewardship 4–7 2011. www.gov.uk/government/uploads/ guarding public health. The physician may system/uploads/attachment_data/file/215308/ perceive the concept of stewardship as pat- dh_131181.pdf [Accessed 5 August 2013]. Kieran Hand, consultant pharmacist for ronising or insulting and a threat to clinical anti-infectives and post-doctoral clinical freedom; nonetheless, physicians in the USA academic fellow have recently called for mandatory imple- Address for correspondence: mentation of antibiotic stewardship backed Dr RA Seaton, Brownlee Centre for University Hospital Southampton NHS Foundation Trust by legislation.8 This article sets out the case Infectious Diseases, Gartnavel General for antibiotic stewardship and describes com- Hospital, 1053 Great Western Road, monly used stewardship strategies and the Glasgow G12 0YN. Introduction evidence supporting their effectiveness. Email: [email protected] Sir Frank MacFarlane Burnet, winner of the Nobel Prize for Medicine in 1960, wrote of the Misuse of antibiotics decline of infectious diseases in 1962: ‘One can Antibiotic misuse (Table 1) is common in the think of the middle of the twentieth century UK and throughout the world. In 2009, as the end of one of the most important social family doctors in Britain prescribed 50% and revolutions in history, the virtual elimination 25% more antibiotics per head of population of the infectious diseases’.1 Any clinician who than their contemporaries in the Netherlands has cared for a patient with severe sepsis due and Sweden, respectively.9 A cross-sectional to a multi-drug resistant (MDR) Klebsiella study of 8,057 general practices (GPs) in pneumoniae will recognise the significance of England revealed that antibiotic prescribing this misconception. Bacteraemias due to volumes varied fivefold between practices at MDR bacteria are estimated to have caused the extremes of the study sample and twofold more than 8,000 deaths and excess costs of between practices on the 10th and 90th per- €62 million in Europe in 2007, and prevailing centiles.10 Only one-sixth of this variability trends indicate that infections caused by MDR could be explained by patient characteristics. Gram-negative bacteria are rapidly increasing, A recent study of more than 1.5 million including in the UK.2 patient visits to GPs in the UK that resulted in Drug resistance is an inevitable conse- a diagnosis of acute respiratory infection quence of the evolution of microorganisms reported that the number needed to treat for under antibiotic selection pressure. This antibiotics to prevent one admission to hos- phenomenon mandates a perpetual quest to pital due to pneumonia was 12,255.11 Sixty- discover new agents that can circumvent five per cent of patient visits resulted in a emerging resistance mechanisms. Drug prescription, with prescribing rates varying discovery and development are expensive, and from 3% to 95% by practice. factors unique to antibiotics, such as relatively At any one time in hospitals in the UK, short treatment courses, have diverted invest- about one-third of inpatients are prescribed ment to more profitable areas, leaving an an antibiotic, with the main drivers being increasingly unmet clinical need.3 Although respiratory, urinary and skin and soft- resistance is inevitable, the pace and extent of tissue infections. Rates of antibiotic misuse propagation of resistant organisms is gov- in hospitals have remained unchanged at erned by human behaviour – most impor- about 50%.12,13 Overprescribing of broad- tantly antibiotic consumption by humans spectrum antibiotics is frequent, with such and animals, as well as hygiene, sanitation ‘defensive prescribing’ attributed to the and infection control. The profound conse- precedence of treatment success in current quences of antibiotic resistance for individual patients at the expense of loss of effective- patients and society create an ethical impera- ness due to resistance in the future.14 tive to protect public health by all available means, including antibiotic stewardship. Antibiotic prescribing and Stewardship is as an ethic that embodies resistance responsible planning and management of finite resources. The term antibiotic The relationship between antibiotic pre- stewardship has been adopted widely to scribing in the community and resistance is © Royal College of Physicians, 2013. All rights reserved. 499 CCMJ1305_CME_Seaton.inddMJ1305_CME_Seaton.indd 449999 99/17/13/17/13 77:44:46:44:46 AAMM CME Infectious diseases 15 Table 1. Examples of inappropriate use of antibiotics.4,7 well characterised. Exposure to antibiotics in primary care is consistently associated Type Example with a subsequent twofold risk of antibiotic Overuse • Prescribing antibiotics for viral infections resistance in respiratory and urinary bac- • Prescribing antibiotics for non-infectious processes (eg febrile patient with pancreatitis) teria for up to 12 months after treatment.16 • Treating minor bacterial infections that do not require antibiotics (eg small skin Antibiotic prescribing in hospitals also abscesses that resolve with incision and drainage) selects for resistance at both the patient and • Treating bacterial colonisation (eg positive catheter urine culture from an institutional levels.17 The risk of acquiring asymptomatic older patient) methicillin-resistant Staphylococcus aureus • Prescribing prolonged treatment courses (eg >24 hours for low-risk surgical prophylaxis) (MRSA) was increased 1.8-fold in patients Misuse • Use of broad-spectrum antibiotics effective against multidrug-resistant organisms exposed to antibiotics.18 Prescribing of inef- in a patient with a community-acquired infection fective antibiotics for patients harbouring • Failure to de-escalate broad-spectrum antibiotics according to culture results resistant organisms was associated with a • Failure to adjust antibiotic prescription according to culture results when the 1.6-fold increased risk of mortality from isolated organism is resistant to initial therapy infection.19 Table 2 lists MDR organisms Underuse • Inadequate dosing of antibiotics that are currently problematic according to • Premature discontinuation of antibiotics the Infectious Diseases Society of America. • Delay to prompt treatment of severe sepsis • Failure to prescribe an antibiotic regimen with an adequate spectrum of activity in Knowledge and confidence a patient with a life-threatening infection among doctors Abuse • Prescribing antibiotics for financial incentive • Prescribing particular antibiotics as a result of pressure from a pharmaceutical A survey of doctors in a teaching hospital industry representative in the USA in 2004 reported that 90% of doctors wanted more education about antibiotics, with only 21% of doctors feeling Table 2. ESKAPE pathogens: resistant micro-organisms identified as particularly very confident that they were using antibi- 3 problematic by the Infectious Diseases Society of America. otics optimally.20 A more recent survey of Gram positive Gram negative junior doctors in Scotland suggested that • Enterococcus faecium • Klebsiella species 75% were confident about choosing the cor- rect antibiotic, but only 36% felt confident – Vancomycin resistant (VRE) – ESBL producer 21 about planning the duration of treatment. • Staphylococcus aureus – Carbapenemase β-lactamase producer Of all antibiotic stewardship interventions, – Methicillin resistant (MRSA) • Acinetobacter baumannii junior doctors rated the availability of guide- – Vancomycin intermediate (VISA) – Carbapenem resistant lines most highly for promoting appropriate • Pseudomonas aeruginosa prescribing. A 2010 survey of more than – Carbapenem resistant 300 medical students in the USA reported • Enterobacter species and Escherichia coli that at least three-quarters of students – ESBL producers expressed a desire for more education about – Carbapenemase β-lactamase producers choice of antibiotic.22 ESBL = extended-spectrum β-lactamase. The impact of lack of knowledge of antibiotic pharmacology and pathogen epidemiology in practice is illustrated by a Key points recent study of guideline adherence for patients admitted to a Dutch university 1. Resistance to last-line antibiotics is emerging and spreading globally but few new hospital with sepsis.23 Off-guideline treat- antibiotic classes have been discovered or are close to market ment had a broader spectrum than on- 2. Antibiotic resistance increases morbidity and mortality for individual patients as guideline treatment in 87% of 108 off- well as posing a threat to public health guideline prescriptions, but the antibiotic 3. Doctors have a responsibility to prescribe antibiotics judiciously and participate susceptibility of isolated pathogens was actively in antibiotic stewardship similar for off- and on-guideline regimens 4. Antibiotic treatment must be prescribed only for patients with evidence of (or a (93% and 91% respectively). reasonable suspicion of) infection and administered promptly 5. Narrow-spectrum antibiotics should be selected where safe and effective, to Professional standards minimise collateral damage to normal flora and preserve