Issues
Volume 175 Issue 9
Editorials Are the new Lipid Management Guidelines good for Australia's health? Rodney T Jackson (MJA 2001; 175: 452-453)Chronic pain in children John J Collins, Lynette J Lane, Susan Thompson (MJA 2001; 175: 453-454)Acute myocardial infarction: improving quality of care Richmond W Jeremy (MJA 2001; 175: 454-455)Breaking the back of back pain Rachelle Buchbinder, Damien Jolley, Mary Wyatt (MJA 2001; 175: 456-457) Research Cost-effectiveness of prescribing statins according to Pharmaceutical Benefits Scheme criteria Stephen S Lim, Theo Vos, Anna Peeters, Danny Liew, John J McNeil (MJA 2001; 175: 459-464)The effects of quality improvement interventions on inhospital mortality after acute myocardial infarction Ian A Scott, Michael D Coory, Catherine M Harper (MJA 2001; 175: 465-470)Lipid lowering and coronary heart disease risk: how appropriate are the national guidelines? Brett H Forge, Esther M Briganti (MJA 2001; 175: 471-475) Healthcare Management of chronic pain in children George A Chalkiadis (MJA 2001; 175: 476-479) Notable Cases Treatment failure due to methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin Peter B Ward, Paul D R Johnson, Elizabeth A Grabsch, Barrie C Mayall, M Lindsay Grayson (MJA 2001; 175: 480-483)Meningitis and septicaemia in a child caused by non-typable Haemophilus influenzae biotype III Stephen E Kay, Zoltan Nack, Bernard M Jenner (MJA 2001; 175: 484-485) Clinical Update Statin-associated myopathy Ian Hamilton-Craig (MJA 2001; 175: 486-489) EBM: Trials on Trial Selecting participants for clinical trials Anthony C Keech, Val J Gebski (MJA 2001; 175: 490-491)Is aggressive lipid-lowering therapy preferable to angioplasty in stable coronary artery disease? Peter M Ellis (MJA 2001; 175: 492-493) Diagnostic Dilemmas Role of breast magnetic resonance imaging in difficult diagnostic situations Kerry E McMahon, Dennis R Osborne, Anne L Davidson (MJA 2001; 175: 494-497)
Editorials
Are the new Lipid Management Guidelines good for Australia's health?
Editorial Are the new Lipid Management Guidelines good for Australia's health? Recommendations, possibly resulting in the long-term treatment of one million Australians, require a serious cost-benefit analysis MJA 2001; 175: 452-453 The new Australian Lipid Management Guidelines 2001, published as a supplement with this issue of the Journal, provide an excellent overview of the current evidence on the cardiovascular disease (CVD) benefits of cholesterol lowering. They also signal the acceptance by Australian experts that treatment decisions should be driven primarily by a patient's estimated "absolute CVD risk" — the probability of developing CVD over a specified time period — rather than primarily by his or her blood lipid level. The Guidelines comprehensively summarise the extensive evidence showing the benefits of cholesterol-lowering interventions in people with low-density lipoprotein (LDL) levels above about 2.5-3.0 mmol/L (equivalent to a total cholesterol level above about 4.5-5.0 mmol/L). But they don't tell us that over 90% of Australians aged 45-75 years have a total cholesterol level above 4.5 mmol/L (Dr Danny Liew, Department of Epidemiology and Preventive Medicine, Monash University, VIC, unpublished analysis). The Guidelines correctly emphasise the need to base treatment decisions primarily on absolute CVD risk rather than on lipid levels, as the benefits of cholesterol lowering are determined far more by individual absolute risk than by pre-treatment level of LDL cholesterol. But the advice provided on how to identify patients at high absolute risk, particularly those without previous symptomatic disease, is rather loose, as discussed below. Moreover, the potential size of the target group for drug-based primary prevention is not mentioned. ...it is estimated that this year statins will account for almost a fifth of the total Australian Pharmaceutical Benefits Scheme budget. Lipid-lowering drugs are appropriately recommended for secondary prevention when the total cholesterol level is above 4 mmol/L, given the high absolute risk and large potential benefit of treatment. This patient group includes about 5% of Australians aged 30-79 years (Professor Andrew Tonkin, National Heart Foundation Australia, personal communication). Aboriginal people and Torres Strait Islanders are appropriately identified as high-risk groups, as are people with diabetes (types 1 and 2), although the recommended treatment threshold for Indigenous people and people with diabetes is unclear. If the cholesterol threshold for treatment is also 4 mmol/L in these groups, I estimate this will add at least another 5% of the middle-aged and older Australian population to the numbers eligible for treatment. The authors of the Guidelines endorse the CVD risk charts used in New Zealand for estimating absolute CVD risk.1 This brings Australian lipid management recommendations more in line with those of the international community. Similar charts or risk calculators, all based on data from the Framingham Heart Study, are now included in most major national and international CVD management guidelines.2-6 The Guidelines state that people with an estimated five-year absolute CVD risk of 10%-15% or above (identified using risk charts) are the "at-risk" group who should be targeted for treatment. Alternatively, for doctors who don't use risk charts, the at-risk group includes everyone over 45 years of age with at least one of seven listed risk factors, some of which are ill-defined in the Guidelines (ie, "hypertension" and "overweight"), yet are very prevalent using some common definitions. For people less than 45 years of age, having two listed risk factors also places them in the at-risk group. This "count the risk factors" definition of at-risk is an unnecessarily crude approach and will identify some people with only a 5% five-year CVD risk and exclude others with a five-year risk above 15%. It is also difficult to find a clear statement in the Guidelines about when to initiate drug treatment in this "at-risk" group, and no mention is made of the potential size of the group. I estimate it will include at least another 20% of Australians aged 45-75 years if the cut-off for drug treatment is an LDL cholesterol level of 4 mmol/L or a total cholesterol level of 6 mmol/L (Professor Michael Hobbs, Department of Public Health, University of Western Australia, personal communication). The authors of the Australian guidelines are to be congratulated for their high quality review of the evidence of effectiveness of both population- and individual-level interventions, and for explicitly linking the level of evidence with their recommendations. However, they are remiss in not considering the implications of implementing the recommendations. For example, it is estimated that this year statins will account for almost a fifth of the total Australian Pharmaceutical Benefits Scheme budget.7 While this may or may not be good value for money, it is increasingly accepted that clinical leaders, as well as taking responsibility for individual patients, must also consider the wider resource implications of their recommendations. The practical implications and potential alternative uses of the substantial dollar and people resources required to implement these recommendations should have been considered. For example, it may (or may not) be better value to fund more coronary angioplasties, or to develop more comprehensive rehabilitation programs for patients who have had a myocardial infarction, than to give statins to hundreds of thousands of Australians with a modestly raised risk of CVD. It would also be illuminating to estimate the implications of these recommendations for health professionals, particularly general practitioners and dietitians. It may be that the implementation costs of the new Lipid Management Guidelines 2001 are justified by the magnitude of the benefits. But recommendations that could result in the long-term treatment of perhaps one million Australians, require a substantial amount of general practitioner and dietitian time and consume a significant proportion of the national pharmaceutical budget will require a serious cost-benefit analysis if they are to be endorsed by healthcare funders. Healthcare costs will be cut by insiders with a scalpel or by outsiders with a meat axe.7 In their current form, these Guidelines unfortunately present an exposed neck to a large axe. Rodney T Jackson Professor; and Head, Division of Community Health and Effective Practice Institute, Faculty of Medical and Health Sciences, University of Auckland, NZ Jackson R. Updated New Zealand cardiovascular disease risk-benefit prediction guide. BMJ 2000; 320: 709-710. Dyslipidaemia Advisory Group. 1996 National Heart Foundation clinical guidelines for the assessment and management of dyslipidaemia. N Z Med J 1996; 109: 224-232. Wood D, Durrington P, Poulter N, et al. Joint British recommendations on prevention of coronary heart disease in clinical practice. Heart 1998; 80 (Suppl 2):S1-S29. Wood D, De Backer G, Faergeman O, et al. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Atherosclerosis 1998; 140: 199-270. Guidelines Subcommittee. 1999 World Health Organization - International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens 1999; 17: 151-183. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. JAMA 2001; 285: 2486-2497. Health Insurance Commission. Annual Report 1999-2000. <www.hic.gov.au/statistics/dyn_pbs/forms/pbs_tab1.shtml> Eddy D. What do we do about costs? JAMA 1990; 264: 1161-1170. Make a comment
Rodney T Jackson
Chronic pain in children
Editorial Chronic pain in children Despite the effects on children and their families, children's pain is often under-recognised MJA 2001; 175: 453-454 The International Association for the Study of Pain (IASP) defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage".1 Implicit in this definition is that pain is a subjective experience and is modulated not only by biological factors, but also by previously painful experiences, the meaning and context of the pain, fear, anxiety, depression, and a range of other factors. Chronic pain is defined as continuous or recurrent pain that persists past the normal time of healing, most commonly about three months' duration.1 If chronic pain refers simply to any pain with this predetermined duration, then all persistent pain of childhood, such as that related to chronic disease (eg, cancer, arthritis, sickle-cell disease), neuropathic pain (eg, complex regional pain syndrome, phantom limb pain) and recurrent pain syndromes (eg, migraine, recurrent abdominal pain), could be classified as causes of chronic pain in children. Little is known about the epidemiology of chronic pain in children. A recent random survey of more than 6000 children in the Netherlands aged 0-18 years indicated an overall prevalence of 25%.2 The prevalence of chronic pain increased with age, and was significantly higher for girls, particularly girls 12-14 years old. The most common types of pain were limb, abdominal pain or headache. Half of the respondents who had experienced chronic pain reported multiple sites of pain, and a third experienced pain as frequent and severe.2 Multiple sites of pain and severe pain were reported more often by girls. The combination of headache and abdominal pain was reported most frequently. These findings indicate that chronic pain is common in children and adolescents. In this issue of the Journal, Chalkiadis presents the first report on chronic pain in children in Australia.3 It is a prospective, descriptive study of the demographic and clinical characteristics of 207 children presenting to the Chronic Pain Clinic at the Royal Children's Hospital, Melbourne, over a two-year period. The study reveals that chronic pain had disturbing consequences for many children. The incidence of school absenteeism, sleep disruption and inability to play sport was high. Implied in these data is a significant psychological burden for the children and the families caring for them. Despite a relatively high prevalence of chronic pain in paediatrics and its significant physical, psychological, social and economic impact on children and their families, it is often under-recognised by clinicians. The reasons for this are multiple and include children's dependency on caregivers to be their advocate. Children with chronic pain can often be met with a dismissive attitude from their caregivers, especially if no organic cause of their pain is found. Furthermore, the advancement in our understanding of the pharmacology of analgesics in children is a relatively recent development.4 The extent to which children may suffer from inadequately managed chronic pain is not known. Recently, in the United States, a major study of children in the terminal phase of cancer painted a chilling picture of suffering, including a high incidence of problems associated with the treatment of pain.5 According to the parents surveyed, 89% of the children suffered "a lot" or "a great deal" from at least one symptom in their last month of life, most commonly pain, fatigue, or dyspnoea. Of the children who were treated for specific symptoms, treatment was successful in 27% of those with pain and 16% of those with dyspnoea.5 Given the many physical and psychological variables in children experiencing chronic pain and the different modalities of treatment now available, the assessment of a child with chronic pain needs to be comprehensive. The team approach involves: an assessment of the physical, psychological and environmental parameters; developing pain management strategies, including pharmacological and non-pharmacological approaches; and individual and family therapy as required. The long term outcomes of these strategies are not known, although Chalkiadis's report reveals at least short term benefit. There has been a long-standing recognition of the need for a comprehensive assessment of chronic pain in adults. In Australia, this has led to multidisciplinary pain centres in many of the major teaching hospitals. In addition, five medical specialist bodies recently came together to form a single physician training program and examination process for the Faculty of Pain Medicine of the Australian and New Zealand College of Anaesthetists. In contrast, it is only in recent years that a team approach to chronic pain in children has evolved in Australia and other countries. It is disturbing to read in Chalkiadis's report that only three paediatric centres in Australia and New Zealand have chronic pain management services which meet the minimum requirements for multidisciplinary staffing. Given the prevalence of chronic pain in children and the potentially serious physical and psychological consequences, a review of these services for children is required. On the basis of US data,5 strategies for the incorporation of pain management and palliative care principles into the care of children with life-threatening and life-limiting illness are a high priority. John J Collins Head, Pain and Palliative Care Service Lynette J Lane Coordinator, Chronic Pain Clinic, Pain and Palliative Care Service Susan Thompson Child and Adolescent Psychiatrist, Chronic Pain Clinic The Children's Hospital at Westmead, Sydney, NSW Merskey H, Bogduk N, editors. Classification of chronic pain: description of chronic pain syndromes and definitions of pain terms. Seattle: IASP Press, 1994. Perquin CW, Hazebroek-Kampschreur AAJM, Hunfeld JAM, et al. Pain in children and adolescents: a common experience. Pain 2000; 87: 51-58. Chalkiadis GA. Management of chronic pain in children. Med J Aust 2001; 175: 476-479. McGrath PJ, Unruh AM, Branson SM. Chronic nonmalignant pain with disability. In: Tyler DC, Krane EJ, editors. Advances in Pain Research and Therapy. Volume 15. New York: Raven Press, 1988. Wolfe J, Grier HE, Klar N, et al. Symptoms and suffering at the end of life in children with cancer. N Engl J Med 2000; 342: 326-333. Make a comment
John J Collins · Lynette J Lane · Susan Thompson
Messages
Editorial Breaking the back of back pain Public policy initiatives directed towards managing the disability of back pain can be highly successful MJA 2001; 175: 456-457 Disability from low back pain is a growing public health problem in Australia and developed countries worldwide, and one of the major issues targeted in the Bone and Joint Decade (2000-2010).1 Most population-based surveys of back pain report a point prevalence of 15%-30%, a one-year prevalence of 50%, and a lifetime prevalence of 60%-80%.2 Although episodes of acute low back pain are mostly short-lived, back complaints still constitute the second most common symptom (after upper respiratory complaints) prompting general practice encounters.3 Furthermore, disability from back pain places a significant socioeconomic burden on the individual and the community. In Australia, back problems are the leading specific musculoskeletal cause of health system expenditure, with an estimated total cost of $700 million in 1993-1994.4 Moreover, these costs are rising: in Victoria alone, claims lodged for back injury with the workers' compensation scheme cost the community $510 million in the 1999-2000 financial year.5 Attempts to reduce the burden of disability associated with back pain have often been directed towards prevention of pain per se, particularly in an occupational setting. Although direct involvement of workplace management in primary prevention strategies has had positive effects, interventions such as education, training and exercise programs for the back, ergonomic interventions and screening potential employees for risk factors for the development of back pain or injury have had limited success.6 Paradoxically, interventions aimed at preventing chronicity, such as early exercise, physiotherapy, rehabilitation and education programs, when implemented early (ie, within the first few weeks of back pain), are largely ineffective for improving longer-term outcomes.7 Attitudes and beliefs, particularly fear-avoidance beliefs, pain-coping strategies and illness behaviours, are important issues to consider when treating patients with back pain.8 While psychosocial approaches that seek to remedy unfounded fears and poor coping methods have met with limited success in treating patients with established chronic back disability, these approaches may be effective when implemented early in the course of back pain and could even be of value when directed towards those who have yet to develop back complaints. Provision of positive messages, such as those designed to improve attitudes to back pain and diminish fear, reduce self-reported disability in patients presenting with low back pain in general practice.9 These interventions also reduce extended work absence in industrial settings.10,11 The Victorian WorkCover Authority's statewide media campaign "Back pain — don't take it lying down", which commenced in 1997 (Box 1), aimed to provide a new approach through prime-time television advertisements featuring health professionals, and sports and local television celebrities. The messages, all endorsed by the relevant professional healthcare organisations, were simple: back pain is not a serious medical problem; disability can be reduced and even prevented by positive attitudes; and treatment should consist of continuing to perform usual activities, not resting for prolonged periods, exercising and remaining at work. The campaign counselled individuals with low back pain, their doctors and employers to avoid excessive medicalisation of the problem, and unnecessary diagnostic testing and treatment. A three-part evaluation of this campaign (evaluating general population attitudes, general practitioners, and the WorkCover Authority claims database) suggests that there has been widespread adoption of these messages (Box 2).13,14 The campaign successfully managed to: "de-medicalise" a public health problem; ease the burden on general practitioners and specialists; empower workers to solve their own health challenges; and save workers' compensation payments. The success of the campaign has been attributed to many factors, including the simple, direct language used to convey the messages, and the evidence-based content, both pioneered by the authors of The back book.12 In addition, virtually every professional body with a stake in back pain in Australia supported the campaign. Before this campaign, there was limited empirical evidence that primary preventive interventions reduce the overall burden of illness associated with low back pain. Now, evaluation of the campaign has shown that a public policy initiative directed towards managing the disability of back pain can be highly successful. There are compelling arguments for this approach. These include, firstly, the impression that informative interventions may be of more value when initiated early, even before the onset of symptoms; and, secondly, predictive models of low back pain are not presently able to identify those at risk of disability. By targeting the entire population, this public health approach reaches those hard-to-identify high-risk groups. There is evidence that a population strategy of universal change has greater overall effect than targeted high-risk strategies. Finally, the population approach may be an effective way of modifying doctors' behaviour, both through direct influences as well as through a change in the attitudes of their patients. Media campaigns are an established strategy for delivering preventive health messages. They have been particularly successful in Australia in altering health-related behaviours, such as sunlight exposure through the Slip! Slop! Slap program and smoking through the Quit program. With good evidence that negative attitudes and beliefs are important predictors of disability related to back pain, altering societal views of back pain would seem a highly appropriate policy to adopt. The long-term impact of this campaign is not clear. Recent publicity by the Victorian WorkCover Authority has focused on ergonomic interventions in the workplace — strategies that the United States has controversially rejected. Clinical effectiveness is not the only influence on policy:15 policymakers' own interests and ideologies are often significant. We may have to look to other interested industrialised societies, such as Sweden, the Netherlands or Canada, for evidence of this novel campaign's long-term effectiveness. Competing interests We received funding from the Victorian WorkCover Authority to conduct an independent evaluation of the media campaign. Rachelle Buchbinder Director, Department of Clinical Epidemiology, Cabrini Hospital; and Associate Professor, Monash University Department of Epidemiology and Preventive Medicine, Melbourne, VIC Damien Jolley Associate Professor, School of Health Sciences Deakin University, Melbourne, VIC Mary Wyatt Occupational Physician, Melbourne, VIC Brooks PM, Hart JAL. The Bone and Joint Decade: 2000-2010. Med J Aust 2000; 172: 307-308. Nachemson A, Waddell G, Norlund A. Epidemiology of neck and back pain. In: Nachemson A, Jonsson E, editors. Neck and back pain: The scientific evidence of causes, diagnosis, and treatment. Philadelphia: Lippincott Williams & Wilkins, 2000: 165-188. Bridges-Webb C, Britt H, Miles DA, et al. Morbidity and treatment in general practice in Australia 1990-1991. Med J Aust 1992; 157(Suppl Oct 19): S1-S56. Mathers C, Penn R. Health system costs of injury, poisoning and musculo-skeletal disorders in Australia 1993-94. Canberra: Australian Institute of Health and Welfare, 1999. AIHW Catalogue No. HWE 12 (Health and Welfare Expenditure Series No. 6). Annual Report Victorian WorkCover Authority 1999/2000. Melbourne (VIC): Victorian WorkCover Authority, 2001. Frank JW, Kerr MS, Brooker A-S, et al. Disability resulting from occupational low back pain. Part I: What do we know about primary prevention? A review of the scientific evidence on prevention before disability begins. Spine 1996; 21: 2908-2917. Frank JW, Brooker A-S, DeMaio SE, et al. Disability resulting from occupational low back pain. Part II: What do we know about secondary prevention? A review of the scientific evidence on prevention after disability begins. Spine 1996; 21: 2918-2929. Waddell G, Newton M, Henderson I, Somerville D, Main CJ. A Fear-Avoidance Beliefs Questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability. Pain 1993; 52: 157-168. Burton A, Waddell G, Tillotson KM, Summerton N. Information and advice to patients with back pain can have a positive effect. A randomised controlled trial of a novel educational booklet in primary care. Spine 1999; 24: 1-8. Symonds TL, Burton AK, Tillotson KM, Main CJ. Absence resulting from low back trouble can be reduced by psychosocial intervention at the work place. Spine 1995; 20: 2738-2745. Indahl A, Velund L, Reikeraas O. Good prognosis for low back pain when left untampered. A randomized clinical trial. Spine 1995; 20: 473-477. Roland M, Waddell G, Moffat J, et al. The back book. London: The Stationery Office; 1996. Buchbinder R, Jolley D, Wyatt M. Population based intervention to change back pain beliefs and disability: three part evaluation. BMJ 2001; 322: 1516-1520. Buchbinder R, Jolley D, Wyatt M. Effects of a media campaign on back pain beliefs and its potential influence on management of low back pain in general practice. Spine 2001. In press. Black N. Evidence based policy: proceed with care. BMJ 2001; 323: 275-278. Make a comment 1: Victorian WorkCover Authority back pain campaign (1997-2000): "Back pain — don't take it lying down" The campaign was based on the messages outlined in The back book, an evidence-based patient educational booklet.12 Messages Positive advice to stay active and exercise, not to rest for prolonged periods, and to remain at work; Encouragement for patients to take responsibility for getting better and coping; Advice that physical activity and work won't cause harm, that investigations may not be helpful, and surgery may not be the answer. Campaign Concentrated campaign for 3 months initially, followed by a low-key maintenance campaign, with a top-up 3-month concentrated campaign 2 years later; Television commercials, aired in prime-time slots; radio and printed advertisements; outdoor billboards, posters, seminars; workplace visits and publicity articles; Promotion by recognised international and national medical experts, Australian sporting and television personalities, and endorsement by the relevant national professional bodies; The back book, translated into 16 languages, made widely available; and Management guidelines for compensable back pain provided to all Victorian doctors. Target audience The general community, health professionals, and employers. Back to text 2: Evaluation of the Victorian WorkCover Authority back pain campaign Study design Quasi-experimental, non-randomised, non-equivalent, before-after telephone surveys of the general population in Victoria, with New South Wales as the control group; Similar before-after postal surveys of general practitioners in both States; and Descriptive analysis of Victorian WorkCover Authority claims database Results Attitudes of the general population to back pain and its treatment in Victoria changed by more than 10%, while in NSW they remained essentially static. Doctors in Victoria, in contrast to those in NSW, reported much lower probabilities of instigating medical interventions for patients presenting with low back pain. There was an immediate and significant impact of the campaign on the patterns of workers' compensation back claims in Victoria. The rate of medical payments for back claims fell by more than 25% during the period October 1997 - October 2000, and the rate of compensated days for back claims dropped from 75 days per 1000 claim-days to 55 days per 1000 claim-days during the same period. Back to text
Rachelle Buchbinder · Damien Jolly · Mary Wyatt
Healthcare
Management of chronic pain in children
Healthcare Management of chronic pain in children George A Chalkiadis MJA 2001; 175: 476-479 For editorial comment, see Collins et al. Abstract - Methods - Results - Discussion - Reference - Authors' details - - - More articles on Paediatrics Abstract Objectives: To describe the demography, clinical characteristics, treatment, functional limitations and outcomes of patients referred to a paediatric multidisciplinary pain clinic. Design: Prospective data collection, descriptive study. Patients and setting: Tertiary referral centre pain clinic (Royal Children's Hospital, Melbourne) over two years (March 1998 - March 2000). Main outcome measures: Pain profile; functional disability (school absenteeism, sleep disturbance and inability to perform sport); treatments received; outcome. Results: 207 patients (mean age, 13.1 years; 73% females; 29% rural residents) were referred in the two years. Concomitant medical conditions were present in 106/207 (51%) patients, the commonest being cerebral palsy or spasticity (22 patients) and malignancy (18). Complex regional pain syndrome was diagnosed in 44 patients. Functional disability due to pain included school absenteeism (95% of school attenders), sleep disruption (71% of all patients) and inability to perform sport (90% of those able to participate in sport previously). Of the 105 patients who missed five or more days of school because of pain, 93 attended school regularly after treatment. Sleep disturbance improved in 129/146 (88%) patients, and 129/147 (88%) resumed sporting activity after multidisciplinary intervention. Outcome was classified as good in 134 patients (65%), moderate in 32 (15%) and poor in 16 (8%). Conclusions: Chronic pain in children and adolescents often results in considerable functional disability. Functional improvement can be achieved using a multidisciplinary approach to pain management in children. No data are available on the prevalence or incidence of paediatric chronic pain in Australia, and only limited data exist on the functional limitation that chronic and recurrent pain has on affected children, their parents and siblings.1 Specialised integrated pain management clinics that offer cognitive behavioural therapy programs are successful in the management of adults with chronic pain,2 but few programs exist for children and adolescents in Australia. As no Australian epidemiological or demographic data exist for children and adolescents with chronic pain, I performed a prospective, descriptive study to investigate the demography, clinical characteristics, treatment, functional limitations and outcomes of patients referred to a paediatric multidisciplinary pain clinic. Methods Patient population The Royal Children's Hospital is a tertiary paediatric referral centre servicing Victoria. A multidisciplinary clinic for children and adolescents with chronic pain, the Children's Pain Management Clinic, was established in March 1998. From March 1998 to March 2000, patients aged 0-18 years of age were prospectively and consecutively included in the analysis. The Statistical Local Areas defined by the Australian Bureau of Statistics3 were used to classify residential location as rural or metropolitan Victoria. Interviewers All patients were assessed by one of three paediatric anaesthetists. The initial interview involved taking a full medical and social history and physical examination of the patient in the presence of one or both parents. One or more allied health professionals (physiotherapist, occupational therapist or clinical psychologist) also assessed the children. Interview The interview followed a structured format. Responses to questions were obtained from both child and parent(s), unless the child was cognitively impaired, in which case the parent(s) or carer provided information. The questions related to diagnostic information (nature, site and intensity of the pain), functional disability (time off school, inability to partake in sporting activities) and sleep dysfunction. Definitions Chronic pain was defined as "pain persisting beyond the time of healing or pain which is persistent or near constant for three months or longer".4 Complex regional pain syndrome (CRPS) Types I and II were diagnosed according to previously published criteria.5 CRPS is a condition in which pain and disability are sustained, out of proportion to an initiating noxious event, by mechanisms that are still incompletely understood. Diagnosis is based on clinical findings, including allodynia (non-painful stimulus eliciting pain) or hyperalgesia (exaggerated sensitivity to pain) beyond the territory of a single peripheral nerve, oedema, skin blood flow abnormality (colour and/or temperature change) or abnormal sudomotor (sweating) activity. CRPS Type I is distinguished from Type II in that Type II follows nerve injury. Pain intensity was assessed by a pain assessment tool appropriate for the patient's age and cognition: Eland pain diagram; visual analogue scale; verbal numerical rating (1-10) scale; Wong-Baker faces; and parental or carer report in the case of non-verbal patients, toddlers and those with cognitive impairment. Outcomes were recorded as: Good: Marked reduction in the intensity of pain (no or minimal pain) and marked functional improvement (return to school and sport where applicable, and resumption of normal sleep pattern); Moderate: Partial reduction in pain intensity and/or some functional improvement (return to school or sport where applicable or resumption of normal sleep pattern); or Poor: No improvement in pain intensity or functional activity. Outcome was classified as unknown if there was no follow-up. The frequency and duration of follow-up were as clinically indicated. Results Over the two-year study period, 207 patients aged 1-18 years were referred to the Children's Pain Management Clinic (Box 1). Most patients (57%) were referred by orthopaedic surgeons. Medical conditions and associated disability Concomitant medical conditions (Box 2) were present in 106 (51%) patients. The disease process, its treatment, complications of the disease or side effects of the treatment accounted for the pain experienced by 93 of these 106 patients. A clear organic precipitant to the pain was identified in 39 of the 101 patients with no pre-existing medical condition. The cause of pain in these patients was neuropathic (nerve injury, nerve entrapment or neuroma) in 20 patients, soft tissue injury in 14, bone- or joint-related in four, and renal colic in one. In 62 of these 101 patients, no clear aetiology was found. The abdomen (10 patients) was the most common single site of presenting pain in this group, followed by headache or facial pain (9), multiple sites of pain (9), and pain in the foot (9), hand or forearm (8), knee (7), leg (5), back (2), shoulder (1), chest (1) and neck (1). CRPS was diagnosed in 44 of the 207 patients (Type I, 40 patients; Type II, 4 patients). Females (33 patients) and the lower limb (33 patients) were predominantly affected. Mean age was 13.7 (range, 9-17) years. CRPS was precipitated by minor trauma in 18 patients, and lower-limb surgery in six patients. No precipitant was identified in nine patients. Overall, 105 patients (95% of school attenders) missed at least five days of school because of pain (independent of medical appointments) (Box 3). There were 147 (71%) patients with impaired ability to participate in sport because of their pain. Of the remaining 60 patients, 43 were unable to participate in sport because of their concomitant condition, and 17 had no such inability on presentation. Overall, 146 patients (71%) suffered daily or almost daily sleep disruption attributable to pain. Of this group, 140 (96%) patients woke up three times or less. Parents of children with cerebral palsy, cognitive impairment or intellectual disability reported sleep disruption in 16 of 22 patients. Waking each night in these patients was more frequent and difficult to manage. Interventions Medications prescribed are listed in Box 4, and interventions are listed in Box 5. Individuals may have received one or more of these simultaneously or consecutively. No medication was prescribed in 75 of 207 (36%) patients; however, this group may have received any one or more of the interventions listed. The median duration of follow-up was four months (range, 2 weeks to 16 months). Patients diagnosed with CRPS were treated as inpatients (26 patients) or outpatients (18 patients) depending on the severity of their condition. Inpatients underwent a more intense and structured rehabilitation program tailored to their individual requirements. This involved cognitive behavioural therapy, physiotherapy (with graded return to physical activity) and re-integration into school and social activities. The median length of hospital stay was five days. Outcomes Outcome was good in 134 (65%) patients, moderate in 32 (15%), poor in 16 (8%) and unknown in 25 (12%). Box 6 shows the outcomes for patients diagnosed with CRPS. Of the 29 patients who had missed more than 40 days of school because of pain, 23 began attending school regularly once treatment for their pain syndrome commenced. Ten successfully underwent a graded return-to-school program coordinated in conjunction with the school, the Royal Children's Hospital Education Institute and the Children's Pain Management Clinic. Of the 76 patients who had missed between five and 40 days of school and who completed follow-up, 70 attended school regularly after intervention. Of the 147 patients who had impaired ability to participate in sport because of pain, 129 (88%) regained the ability after treatment. Sleep disturbance was successfully managed in 129 of 146 patients (88%). Most (122 patients or their parents) reported uninterrupted sleep as a result of either analgesic intervention or successful use of relaxation techniques. The remaining seven patients (or their parents) reported marked improvement in the frequency of waking and less troublesome return to sleep when they woke during the night. Twelve (6%) of the 207 patients died of their underlying terminal condition or its complications. There were three complications related to therapy for pain. Two were epidural-related in patients with cerebral palsy and CRPS: both developed back pain and fever. One had an epidural infection and the other paraspinous myositis with possible osteomyelitis. One patient developed paraesthesiae after lumbar sympathetic nerve block. All three patients recovered with no long-term sequelae. Discussion In my study, chronic pain in children and adolescents was associated with considerable functional limitation, most commonly school absenteeism, sleep disturbance and inability to perform sporting activities. The duration of school absenteeism was significant and could be expected to affect school performance, although this was not specifically recorded. Previous studies from other countries have reported on the incidence of functional disability in relation to specific painful sites or conditions.1 In our patients, chronic pain, irrespective of aetiology or site, commonly resulted in significant functional disability. More females than males were referred in all age brackets. CRPS, headache, fibromyalgia, recurrent abdominal pain and somatoform pain all occur more frequently in females than in males aged less than 18 years.6 More than a third of all patients referred were aged 12 years or less. Recurrent abdominal pain is commonly reported in this age group.7 However, only 11% of children in this age group referred to our clinic complained of abdominal pain, whereas half presented with limb pain. This may indicate that recurrent abdominal pain is successfully dealt with and understood by paediatricians, whereas limb pain is more likely to be referred. Patients from rural Victoria accounted for 29% of all referrals, in keeping with the population distribution in Victoria.3 This has implications regarding the provision of education of general practitioners and services to rural areas. CRPS was diagnosed in 21% of patients referred. The lower limb was more commonly involved than the upper, and females were more often affected than males. Previous studies from the United States8 and Sweden9 have shown a similar ratio of limb involvement. In these studies, females were more commonly affected than in this study (5 and 13 times more often than males, respectively). Unlike in those studies, in which a large percentage of girls with CRPS were active in sports, gymnastics, skating and dance, this was true for only 10% of our patients. Children and adolescents with cerebral palsy made up the largest single group of patients with a concomitant condition. Locating the source of pain can be difficult in this group,10 especially in those with cognitive impairment. Hip and/or back pain was the source in 55%. Spasticity itself can cause pain11 and contributes to deformity, subluxation, dislocation, capsulitis and osteoarthritis in these regions. Sleep disruption was more frequent and problematic in these children, both overall and on a nightly basis. Addressing pain resulted in most patients sleeping uninterrupted through the night. Eliminating or minimising sleep disruption is of obvious benefit to the child and carers.12 The nature and management of chronic pain in children and adolescents differs from that in adults. Bullying, sexual or physical abuse, marital disharmony and difficulties at school may all contribute to abnormal pain behaviour in children. Family therapy may be indicated, as family situations can contribute to exacerbating and maintaining pain behaviour in children. Parents as well as afflicted children often need to be taught behavioural modification and pain-coping strategies. Abolition of pain, particularly in patients with chronic conditions, is not always achievable. The diverse aetiologies which manifest as pain behaviour necessitate a coordinated, multidisciplinary approach. My results support this multidisciplinary approach and focus on regaining function and minimising pain behaviour. The lack of a psychologist (a psychologist was initially a team member, but only for three months) and psychiatrist as integral team members may have contributed to the poor outcomes observed in some patients. Poor outcome was commonest in patients from chaotic family environments or in those with moderate intellectual disability. The latter are least likely to respond to cognitive behavioural techniques. Behavioural modification is better suited to this group, but may be difficult and time consuming to implement. A recent unpublished survey of tertiary paediatric hospitals in Australia and New Zealand, conducted by the Paediatric Pain Working Party of the Faculty of Pain Medicine, Australian and New Zealand College of Anaesthetists, revealed that only three centres in Australia and New Zealand have chronic pain management services which meet their minimum requirements for multidisciplinary staffing.13 Given the magnitude of functional disability demonstrated in our population, the provision of funding for paediatric chronic pain services requires urgent attention. The socioeconomic cost of chronic pain in children and adolescents is considerable. Although not specifically addressed in this study, it was apparent that there were implications for the child (education, self-esteem, friendships), the parents (time off work caring for the child and attending appointments, cost of medication, hospitalisation and complementary therapies) and the healthcare system (medical care, including serial referrals to multiple specialists, medication and hospitalisation and allied healthcare costs). Future studies should address the prevalence and epidemiology of pain in Australian children and adolescents, the early identification of those in whom significant functional disability exists and the cost-benefits of establishing multidisciplinary paediatric pain centres. Future directions should include education programs for GPs, paediatricians, schoolteachers and counsellors and allied health professionals to recognise early warning signals such as school absenteeism, frequent sick bay attendances, failure to respond to treatment, and poor school sports participation. References Palermo TM. Impact of recurrent and chronic pain on child and family daily functioning: a critical review of the literature. J Dev Behav Pediatr 2000; 21: 58-69. Becker N, SjØgren P, Bech P, et al. Treatment outcome of chronic non-malignant pain patients managed in a Danish multidisciplinary pain centre compared with general practice: a randomised controlled trial. Pain 2000; 84: 203-211. Australian Bureau of Statistics. Melbourne. A Social Atlas. 1996. Census of Population and Housing. Canberra: Commonwealth of Australia, 1998. (Catalogue no. 2030.2.) McGrath PJ, Finley GA. Chronic and recurrent pain in children and adolescents. Progress in Pain Research and Management, Vol. 13. Seattle: IASP Press, 1999. Boas RA. Complex regional pain syndromes: symptoms, signs, and differential diagnosis. In: Janig W, Stanton-Hicks M, editors. Reflex Sympathetic Dystrophy: A Reappraisal. Progress in Pain Research and Management, Vol. 6. Seattle: IASP Press, 1999; 82. Perquin CW, Hazebroek-Kampschreur AAJM, Hunfield JAM, et al. Pain in children and adolescents: a common experience. Pain 2000; 87: 51-58. Faull C, Nicol AR. Abdominal pain in six-year-olds: an epidemiological study in a new town. J Child Psychol Psychiatr 1986; 27: 251-260. Wilder RT, Wolohan M, Masek BJ, et al. Reflex sympathetic dystrophy in children and adolescents: a follow-up of a cohort of 70 patients and development of a treatment algorithm. J Bone Joint Surg Am 1992; 6: 910-919. Olsson GL, Arnér S, Hirsch G. Reflex sympathetic dystrophy in children. In: Tyler DC and Krane EJ, editors. Advances in pain research and therapy, Vol 15. New York: Raven Press, 1990; 323-331. Nolan J, Chalkiadis GA, Low J, et al. Anaesthesia and pain management in cerebral palsy. Anaesthesia 2000; 55: 32-41. Barwood S, Ballieu C, Boyd R, et al. The analgesic effects of botulinum toxin A: a randomised, double blind, placebo controlled clinical trial. Dev Med Child Neurol 2000; 42: 116-121. Lewin DS, Dahl RE. Importance of sleep in the management of pediatric pain. J Dev Behav Pediatr 1999; 20: 244-252. Requirements for multidisciplinary pain centres offering training in pain medicine. Faculty of Pain Medicine, Australian and New Zealand College of Anaesthetists College Policy Document PM2, 2000. (Received 28 Nov 2000, accepted 18 Jun 2001) Authors' details The Royal Children's Hospital, Melbourne, VIC. George A Chalkiadis, DA, FANZCA, Anaesthetist, and Co-ordinator Pain Management. Reprints will not be available from the author. Correspondence: Dr GA Chalkiadis, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052. chalkiagATcryptic.rch.unimelb.edu.au Make a comment 1: Demographic data Residential location Age* (years) Number (%) Female City Rural Other 0-9 27 (13%) 70% 17 8 2 10-12 47 (23%) 64% 33 11 3 13-15 75 (36%) 73% 53 20 2 16-18 58 (28%) 83% 36 21 1 All 207 (100%) 73% 139 60 8 *Mean age, 13.1 years (range, 1-18 years); median age, 13 years. These patients resided in the Australian Capital Territory, New South Wales or South Australia. Back to text 2: Concomitant medical conditions Condition Number Cerebral palsy/spasticity 22* Malignant tumours 18 Scoliosis 11* Benign tumours 7 Cystic fibrosis 6 Fibromyalgia 5 Intellectual delay 4 Talipes equinovarus or flat feet 4 Vertebral or spinal cord abnormalities 4 Others 33 *Four patients had both scoliosis and cerebral palsy, one had Duchenne muscular dystrophy and scoliosis and one had spinal muscular atrophy and scoliosis. Back to text 3: School days missed because of pain Number of school days missed * Nine children did not miss any days. †Seven children no longer attended school because of their pain. na= Not applicable; patients were unable to attend school because of a concomitant condition or because they were not of school age. Back to text 4: Medications prescribed Number of patients Tricyclic antidepressant (amitriptyline or nortriptyline) 78 Paracetamol 21 Non-steroidal anti-inflammatory drug (oral or topical, including COX-2 inhibitors) 31 Opioid: oxycodone (oral) or morphine (oral, subcutaneous or intravenous) 21 Anticonvulsants (carbamazepine, sodium valproate or gabapentin) 10 Clonidine (oral, intravenous or transdermal) 14 Benzodiazepines (diazepam, clonazepam) 7 Mexiletine 10 Capsaicin 7 Ketamine (intravenous) 5 Buscopan 2 Others (gaviscon, omeprazole, quinine, vitamin C) 1 for each medication Back to text 5: Interventions Number of patients Acupuncture 15 Relaxation techniques 98 Trigger point injection 7 Tendon, neuroma or joint injection 12 Nerve block 29* Epidural 28 Psychology/psychiatry 84 Physiotherapy 126 Iontophoresis (dexamethasone) 11 Self-administered medication 132 *62 blocks performed on 29 patients. 3 patients received 2 epidurals each. Back to text 6: Outcome in patients with complex regional pain syndrome Outcome* Upper limb Lower limb Good 8 26 Moderate 1 6 Poor 2 1 *Good: marked reduction in pain and marked functional improvement. Moderate: some reduction in pain and some functional improvement. Poor: no improvement in pain or functional ability. Back to text
George A Chalkiadis
Notable cases
Treatment failure due to methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin
We report the first instance in Australia of treatment failure due to a strain of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin — heteroresistant vancomycin-intermediate S. aureus (hVISA). The infection occurred in a 41-year-old man with multiple risk factors. No transmission of the organism to other patients or the environment was detected. This case may herald the beginning of a new phase of staphylococcal resistance in Australia. Peter B Ward, Paul D R Johnson, Elizabeth A Grabsch, Barrie C Mayall and M Lindsay Grayson MJA 2001; 175: 480-483 Clinical record - Assessment of patient isolates - Results - Discussion - Competing interests - Acknowledgements - References - Author's details - - - More articles on Infectious diseases and parasitology The glycopeptides, vancomycin and, to a lesser extent, teicoplanin, are the mainstay of therapy for infections caused by methicillin-resistant Staphylococcus aureus (MRSA),1,2 and currently up to half of all S. aureus strains isolated in hospitals in Australia are MRSA.3,4 Despite substantial glycopeptide use over many years, the emergence of MRSA strains with reduced susceptibility to vancomycin and teicoplanin has been reported only recently.5-7 Subsequently, MRSA strains have been reported that contain limited subpopulations with intermediate resistance to glycopeptides, while most of the population remains glycopeptide-susceptible.8-14 These are termed heteroresistant vancomycin-intermediate S. aureus (hVISA) (see glossary in Box 1). We report here the first Australian case of infection due to hVISA. Clinical record A 41-year-old male smoker with long-standing type 1 diabetes, haemodialysis-dependent end-stage renal failure, hepatitis C and peripheral vascular disease was admitted to hospital in late August 2000 with bilateral lower-limb ischaemia refractory to prostacyclin therapy. Despite hyperbaric oxygen and multiple courses of antibiotics (including cephalexin, flucloxacillin, gentamicin and clindamycin), the patient developed increasing lower-limb gangrene, necessitating a right below-knee amputation on Day 41 of hospital admission. On Day 47, ulcers on his left foot were found to be infected with MRSA and Enterobacter spp. Therapy with vancomycin (1 g) and meropenem (500 mg) postdialysis (ie, three times a week) was commenced. Intravenous teicoplanin (400 mg every third day) was later substituted for vancomycin, as the patient developed a rash after the initial dose of vancomycin. However, his condition worsened, necessitating a left below-knee amputation on Day 50. Therapy was continued with teicoplanin, intravenous gentamicin (160 mg daily) and metronidazole (500 mg twice daily), but both amputation wounds broke down and repeated cultures grew MRSA and E. coli, finally necessitating a left above-knee amputation on Day 105. Despite therapeutic serum levels of teicoplanin (troughs of 6.5-15.9 mg/L, measured on 10 occasions over eight weeks), both amputation sites remained actively infected with MRSA and E. coli. On Day 120 (after 73 days' glycopeptide therapy), teicoplanin was ceased, and a new oxazolidinone, linezolid (600 mg intravenously, twice daily), was commenced in combination with oral ciprofloxacin and metronidazole. Over the next five days, dramatic improvement was noted in all infected wounds. After 11 days, intravenous linezolid was changed to oral linezolid (600 mg twice daily). MRSA was isolated from the amputation sites nine days after linezolid was begun, but was not detected again in any subsequent cultures. The patient continued to receive oral linezolid for 81 days. His condition improved steadily, and he was transferred to a rehabilitation unit on Day 179. Over the subsequent six months, he remained reasonably well, with no evidence of MRSA infection. Assessment of patient isolates After attending a presentation during which new laboratory methods for the accurate identification of VISA and hVISA were presented (Annual Conference of the Australian Society for Antimicrobials, Melbourne, April, 2001), we decided to further investigate stored MRSA isolates from the patient. Two MRSA strains obtained from the right below-knee amputation stump were retrieved from storage at -70ºC. These strains (AR1 and AR2) were isolated on hospital Day 104 (after 57 days of teicoplanin therapy) and Day 129 (nine days after changing from teicoplanin to linezolid therapy), respectively. The two strains were assessed for in-vitro antibiotic susceptibility using routine methods (agar dilution and broth microdilution).15 They were also assessed for glycopeptide-resistant subpopulations using methods described previously.5-7 These comprised: Colony morphology: Each isolate was examined macroscopically for the heterogeneous colony morphology typical of hVISA; pure cultures have been reported to produce a mix of both large and small colonies when cultured on Columbia agar with 5% horse blood (Oxoid, Basingstoke, UK) and other media.6,7 Colonies suspected of glycopeptide resistance were further assessed for vancomycin and teicoplanin resistance. Vancomycin gradient plates: Vancomycin resistance was assessed using vancomycin gradient plates prepared as described previously.6 Thirty mL of brain-heart infusion (BHI) agar (Oxoid, Basingstoke, UK) containing vancomycin (4 mg/L) was poured into a 10 cm square petri dish raised on one edge by 6 mm. After setting, the resultant wedge was overlaid with a 30 mL layer of BHI agar without antibiotic and allowed to set horizontally. Plates were stored for 24 hours at 4ºC to allow diffusion of vancomycin into the upper agar layer. Twenty-four-hour cultures of organisms in brain-heart infusion (BHI) broth were adjusted to a 0.5 McFarland standard, and 20 µL aliquots were spread on the gradient plates in an even line along the increasing antibiotic gradient. Plates were assessed after 48 hours' aerobic incubation at 37ºC.6 E test minimum inhibitory concentration: Both vancomycin and teicoplanin resistance was assessed by E test (AB Biodisk, Solna, Sweden), using methods and interpretations recommended in the United States7 and Europe.11 US methods use Mueller-Hinton agar (Oxoid, Basingstoke, UK) and an inoculum equivalent to the 0.5 McFarland standard, and define intermediate vancomycin resistance as MIC, 8-16 mg/L. European methods use BHI agar and a heavier inoculum (2 McFarland standard) and define intermediate vancomycin resistance as MIC ≥8 mg/L. Teicoplanin intermediate resistance is defined as MIC > 8 mg/L (US) or > 6 mg/L (Europe). Inoculated media were incubated aerobically for 24 hours at 37ºC.7,11 Population analysis profile: The proportion of cells in the population of each isolate that was resistant to a range of vancomycin and teicoplanin concentrations was assessed, using methods described previously.6,9 Assessment of nosocomial transmission As the presence of hVISA was first recognised five months after the patient's infection was cured empirically, screening was undertaken to ascertain whether hVISA had been transmitted nosocomially: Nose, groin, hand and wound specimens from the index patient were cultured to assess current MRSA and hVISA infection or colonisation. Nose and groin specimens were collected from all patients attending the in-centre haemodialysis units also attended by the index patient. These were assessed, along with multiple environmental samples from the units, for the presence of MRSA and hVISA. All patients in the Nephrology Department who had been diagnosed with MRSA infection or colonisation between October 2000 and May 2001 were identified from the hospital's microbiology database. Their clinical course was reviewed to identify those whose condition did not respond to vancomycin. Stored MRSA isolates from these patients were assessed for glycopeptide resistance, as described above. All MRSA isolates obtained at our institution since May 2001 were assessed prospectively for hVISA using a screening plate of BHI agar with vancomycin (4 mg/L).12 Results Antibiotic susceptibility of index isolate Routine antibiotic sensitivity testing: The two patient isolates, AR1 and AR2, were confirmed to be MRSA and to have identical susceptibility profiles. Both tested resistant to penicillin, methicillin, erythromycin, trimethoprim, cotrimoxazole, clindamycin and ciprofloxacin, but susceptible to tetracycline, chloramphenicol, mupirocin, fusidic acid, vancomycin (MIC, 2 mg/L) and teicoplanin (MIC, ≤ 8 mg/L) using agar dilution methods,15 and to linezolid (MIC, 1.5 mg/L) using the E test.15 Glycopeptide-resistant subpopulations: Both AR1 and AR2 displayed small and large colony variants, consistent with previous reports of hVISA, VISA and VRSA.6,7 By E test, both isolates had a vancomycin MIC of 6-8 mg/L (US method) and 8 mg/L (European method), and a teicoplanin MIC of 24 mg/L (US method) and 16-24 mg/L (European method). Repeated analysis of AR2 using vancomycin gradient plates demonstrated growth across the entire 4 mg/L vancomycin gradient, confirming the MIC to be > 4 mg/L, and the isolate to be hVISA. Population analysis profiles were also consistent with both isolates' being hVISA. In particular, detailed analyses of AR2 demonstrated that colony subpopulations were able to grow on 3 mg/L and 4-6 mg/L vancomycin plates at frequencies of 1 in 10 and 1 in 105-106, respectively (Box 2). In comparison, control organisms generated resistant colonies at a rate of < 1 in 108 at these concentrations. Similarly, population analysis of AR2 using 8 mg/L and 16 mg/L teicoplanin demonstrated presence of resistant subpopulations at frequencies of 1 in 103 and 1 in 105-106, respectively (Box 2). These findings are consistent with those for hVISA reported by Hiramatsu.5,6,9 Nosocomial transmission of hVISA MRSA, hVISA and VISA were not detected in cultures obtained from the index patient after completion of linezolid therapy. Similarly, hVISA was not detected from nose or groin cultures of 85 patients who were either current renal ward inpatients or undergoing in-centre haemodialysis. Also, hVISA was not detected in cultures of 28 environmental sites in the ward and haemodialysis units, suggesting that routine cleaning was effective in limiting significant hVISA colonisation and contamination. Twenty-six renal patients were identified from the microbiology database with MRSA infection during the eight months between October 2000 and May 2001. Six of these patients were considered by the Nephrology Department to have had a slow clinical response to anti-MRSA treatment. MRSA isolates were retrieved from frozen storage for all six patients, and the most recently obtained MRSA isolate was assessed for all (except one patient in whom the second most recent isolate was assessed). None of these MRSA strains were hVISA. Prospective screening of all MRSA isolates at our institution for hVISA began in July 2001. Of 315 isolates obtained from 128 patients, none were hVISA. Discussion This is the first report of clinical treatment failure caused by MRSA with reduced susceptibility to glycopeptides in Australia. Similar cases have been described in Europe, North America and South-East Asia,7,16 and a single strain of vancomycin-resistant S. aureus has been reported in Japan.17Slow clinical response, and even treatment failures, associated with glycopeptide therapy for MRSA infections have been described previously.1,18-20 This has generally been attributed to the characteristics of glycopeptides: their penetration into sites of established sepsis, which is generally inferior to that of other agents, such as β-lactams, and their slow bactericidal activity.20-22 Empirically, we attributed the clinical failure of teicoplanin in our patient to multiple factors, including his advanced vascular disease, and poor drug delivery (despite adequate serum teicoplanin levels), as well as the inherent characteristics of the drug.2 However, the patient's very rapid clinical improvement and the ultimate clearance of MRSA soon after commencement of linezolid is consistent with our later identification of the infecting strain as hVISA. Our detailed search did not detect hVISA contamination of the haemodialyis environment, or colonisation or infection of other haemodialysis patients, or any subsequent patients with MRSA at our hospital. Thus, we believe that hVISA is not widespread in our hospital, and that our case is unusual. Now that the microbiological methods to identify hVISA have been clearly described,6,7,14 it is likely that strains will be identified in Australia. However, it is a challenge to establish a laboratory screening protocol for hVISA and to determine what resources should be allocated to screening for hVISA. The Centers for Disease Control and Prevention in Atlanta recommend that routine screening of all MRSA isolates for vancomycin resistance is currently unnecessary and probably wasteful. Instead, attention should be focused on patients in whom glycopeptide therapy is failing, or those at increased risk of MRSA carriage and infection, such as patients undergoing haemodialysis or chronic ambulatory peritoneal dialysis.7,12 Our identification of hVISA may be the beginning of a new phase in the emergence of antibiotic resistance in Australia, when the glycopeptides vancomycin and teicoplanin will no longer be effective in some cases of MRSA infection.18-20,23 This raises challenges for clinical management, laboratory detection and infection control. Furthermore, while two recently available agents, linezolid and quinupristin-dalfopristin, appear active against hVISA, VISA, MRSA and vancomycin-resistant enterococci, resistance to linezolid has already been reported among strains of both MRSA and Enterococcus faecium.21,22,24 Thus, we may be approaching an era when there are no effective therapies for some strains of MRSA. Competing interests None declared. Acknowledgements We wish to acknowledge the invaluable assistance of the infection control practitioners and staff of the Microbiology and Nephrology departments. References Kucers A. Vancomycin. In: Kucers A, Crowe S, Grayson ML, Hoy J. The use of antibiotics. 5th ed. Oxford: Butterworth Heinemann, 1997: 763-790. Fekety R. Vancomycin, teicoplanin, and the streptogramins: quinupristin and dalfopristin. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone, 2000: 382-392. Turnidge JD, Bell JM. Methicillin-resistant Staphylococcus aureus evolution in Australia over 35 years. Microb Drug Resist 2000; 6: 223-229. Gottlieb T, Mitchell D. The independent evolution of resistance to ciprofloxacin, rifampicin and fusidic acid in methicillin-resistant Staphylococcus aureus in Australian teaching hospitals (1990-1995). Australian Group for Antimicrobial Resistance (AGAR). J Antimicrob Chemother 1998; 42: 67-73. Hiramatsu K, Hanaki H, Ino T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997; 40: 135-136. Hiramatsu K. The emergence of Staphylococcus aureus with reduced susceptibility to vancomycin in Japan. Am J Med 1998; 104 Suppl 5A: 7S-10S. Tenover FC, Biddle JW, Lancaster MV. Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Emerg Infect Dis 2001; 7: 327-332. Howe RA, Wootton M, Walsh TR, et al. Heterogeneous resistance to vancomycin in Staphylococcus aureus. J Antimicrob Chemother 2000; l45: 130-132. Trakulsomboon S, Danchaivijitr S, Rongrungruang Y, et al. First report of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Thailand. J Clin Microbiol 2001; 39: 591-595. Wong SS, Ho PL, Woo PC, Yuen KY. Bacteremia caused by staphylococci with inducible vancomycin heteroresistance. Clin Infect Dis 1999; 29: 760-767. Walsh TR, Bolmstrom A, Qwarnstrom A, et al. Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides. J Clin Microbiol 2001; 39: 2439-2444. Fridkin SK. Vancomycin-intermediate and -resistant Staphylococcus aureus: what the infectious disease specialist needs to know. Clin Infect Dis 2001; 32: 108-115. Wootton M, Howe RA, Hillman R, et al. A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital. J Antimicrob Chemother 2001; 47: 399-403. Centers for Disease Control and Prevention. Staphylococcus aureus with reduced susceptibility to vancomycin-Illinois, 1999. MMWR Morb Mortal Wkly Rep 2000; 48: 1165-1167. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. Supplement M100 S11. Wayne, Pa: The Committee, 2001. Geisel R, Schmitz FJ, Thomas L, et al. Emergence of heterogeneous intermediate vancomycin resistance in Staphylococcus aureus isolates in the Dusseldorf area. J Antimicrob Chemother 1999; 43: 846-848. Hiramatsu K, Aritaka N, Hanaki H, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 1997; 350: 1670-1673. Levine DP, Fromm BS, Reddy BR. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 1991; 115: 674-680. Wood CA, Wisniewski RM. Beta-lactams versus glycopeptides in treatment of subcutaneous abscesses infected with Staphylococcus aureus. Antimicrob Agents Chemother 1994; 38: 1023-1026. Small PM, Chambers HF. Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother 1990; 34: 1227-1231. Drew RH, Perfect JR, Srinath L, et al. Treatment of methicillin-resistant Staphylococcus aureus infections with quinupristin-dalfopristin in patients intolerant of or failing prior therapy. J Antimicrob Chemother 2000; 46: 775-784. Prystowsky J, Siddiqui F, Chosay J, et al. Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycin-resistant enterococci. Antimicrob Agents Chemother 2001; 45: 2154-2156. Hanaki H, Kuwahara-Arai K, Boyle-Vavra S, et al. Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50. J Antimicrob Chemother 1998; 42: 199-209. Tsiodras S, Gold HS, Sakoulas G, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 2001; 358: 207-208. (Received 10 Sep, accepted 26 Sep, 2001) Authors' details Austin and Repatriation Medical Centre, Melbourne, VIC. Peter B Ward, BAppSc, PhD, Senior Scientist, Microbiology Department; Paul D R Johnson, FRACP, PhD, Deputy Director, Infectious Diseases Department, and Associate Professor, Department of Medicine, University of Melbourne, VIC; Elizabeth A Grabsch, BSc, MPH, Infection Control Scientist, Microbiology Department; Barrie C Mayall, FRACP, FRCPA, Medical Microbiologist, Microbiology Department; M Lindsay Grayson, FRACP, FAFPHM, MD, Director, and Professor, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, and Department of Medicine, University of Melbourne, Melbourne, VIC. Reprints: Dr P B Ward, Microbiology Department, Austin and Repatriation Medical Centre, Studley Road, Heidelberg, VIC 3084. Peter. WardATarmc.org.au Make a comment 1: Glossary (adapted from references 7 and 12) MRSA: Methicillin-resistant Staphylococcus aureus. An isolate of S. aureus, resistant to methicillin, with minimum inhibitory concentration (MIC) to vancomcyin ≤2mg/L. MRSA does not produce vancomycin-resistant subpopulations during routine laboratory susceptibility tests. hVISA: Heteroresistant vancomycin-intermediate S. aureus. An isolate of MRSA which produces subpopulations with vancomycin MICs ≥4mg/L, typically at a rate of 1:105 to 1:106 resistant:sensitive colonies. Antibiotic-resistance detection methods that use large inocula, such as E test, are needed to screen for hVISA. VISA: Vancomycin-intermediate S. aureus. An isolate of MRSA which produces colonies with vancomycin MICs of 8-16mg/L at high frequency, and is detectable as "intermediate resistant" using standard low-inocula susceptibility tests. VRSA: Vancomycin-resistant S. aureus. An isolate of MRSA which produces populations of colonies with vancomycin MICs >32mg/L at high frequency. Back to text 2: Number of colonies resistant to defined concentrations of vancomycin and teicoplanin among subpopulations of a Staphylococcus aureus strain, AR2, isolated from the index patient. A range of inocula (103-109) were used to measure viable subpopulations at each antibiotic concentration. Back to text
Peter B Ward · Elizabeth A Grabsch · Barrie C Mayall
The changing face of dying in Australia
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The intention to hasten death: a survey of attitudes and practices of surgeons in Australia
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On causing death
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Glucosamine therapy: does it work?
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Gonorrhoea screening in general practice: perceived barriers and strategies to improve screening rates
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Anaphylactoid reactions associated with menstruation affecting two sisters
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