Volume 171 Issue 3

Research Vancomycin and teicoplanin use in Victorian hospitals Marion B Robertson, Jonathan G A Dartnell and Tony M Korman, on behalf of the Victorian Drug Usage Evaluation Group MJA 1999; 171: 127-131 See also Ferguson, Grayson et al & Collignon Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Pharmacology Abstract Objective: To determine patterns of prescribing of glycopeptide antibiotics (vancomycin and teicoplanin) in Victorian hospitals and identify areas for targeted intervention. Design: A concurrent, observational, multisite evaluation of drug use. Setting: Thirty-five Victorian hospitals, 1-14 September 1997. Study population: Patients commencing a glycopeptide antibiotic course. Main outcome measures: Rate of glycopeptide antibiotic use; indications; duration of use; main hospitals using glycopeptide antibiotics. Results: 293 patients (269 adults and 24 neonates) commenced on 302 glycopeptide antibiotic courses: 296 intravenous (IV) vancomycin courses and three each of oral vancomycin and parenteral teicoplanin. The overall rate of use was 10.3 courses per 1000 inpatient separations. Of 271 IV vancomycin courses for adults, 176 (65%) were for treatment -- 120 empirically. The median duration of treatment courses was 4.7 days (interquartile range, 2.0-8.2 days). A flucloxacillin-resistant organism was confirmed for 44% of treatment courses. Ninety-five IV vancomycin courses were for prophylaxis, including for cardiac (54%) and vascular surgery (21%); 82% of prophylactic courses were administered for less than 24 hours. Of all the glycopeptide antibiotic courses, 69% were administered at five major metropolitan hospitals. Conclusions: Glycopeptide antibiotic use in Victoria is concentrated in the major metropolitan hospitals. Prolonged durations of vancomycin therapy, including for surgical prophylaxis and empirical therapy not subsequently confirmed by microbiology findings, would be suitable targets for interventional strategies. Introduction The emergence of resistant strains of Staphylococcus aureus and coagulase-negative staphylococci has resulted in increased use of the glycopeptide antibiotics vancomycin and teicoplanin.1 These antibiotics are the only effective treatments for infections with these pathogens, but the emergence of vancomycin-resistant enterococci (VRE) threatens their utility.1,2 VRE can cause serious life-threatening infections, and can transfer their resistance in vitro to other pathogens, such as Staphylococcus, rendering the bacteria resistant to currently available antimicrobials.3,4The emergence of VRE has been linked to both overuse and inappropriate use of antibiotics such as vancomycin, teicoplanin and extended-spectrum cephalosporins.2,4 There is also a strong relationship with the use of glycopeptide antibiotics in animals.5 Australian studies have reported inappropriate use of vancomycin ranging from 42% to 65% in individual hospitals.6,7 Responding to these concerns, consensus guidelines have been disseminated to all Victorian hospitals.8 The aim of this study was to examine patterns of prescribing vancomycin and teicoplanin in Victorian hospitals in order to identify potential areas for targeted intervention to improve use of these antibiotics. Methods This study was conducted by the Victorian Drug Usage Evaluation Group, a multidisciplinary group that aims to promote and improve coordination of drug use evaluation activities as a means to improve drug use. All Victorian public and private hospital pharmacy departments listed in the Society of Hospital Pharmacists of Australia directory9 were invited to participate. All patients at participating hospitals who commenced a course (Box 1) of oral or intravenous (IV) vancomycin or teicoplanin between 1-14 September 1997 inclusive were enrolled. Pharmacists at each hospital collected data concerning: demographic details, the indication for antibiotic therapy as determined from the medical record or by consultation with the prescriber, site and source of infection, beta-lactam hypersensitivity, and past history of methicillin-resistant S. aureus (MRSA) or methicillin-resistant S. epidermidis (MRSE), microbiology results of specimens taken up to seven days before or concurrent with vancomycin or teicoplanin therapy, administration of antibiotics before, during and immediately after vancomycin or teicoplanin therapy, and specialist consultation and advice. Prescription data were collected until the end of the course, until the day of discharge or death, or until 28 September 1997. Each hospital provided details of the number of inpatient separations between 1-14 September 1997. This was used to estimate the number of glycopeptide antibiotic courses commenced per 1000 inpatient separations. Data were evaluated by the Mann-Whitney rank sum test of the equivalence of medians of samples not drawn from a normally distributed population. Proportions were compared using the χ2 test. Data are presented as proportions, medians and interquartile ranges. Results Hospitals: Thirty-five hospitals participated in the study: 33 of 58 public and two of 14 private hospitals invited to participate. Twenty hospitals were in the Melbourne metropolitan area and 15 in regional areas. Patients: In the study period, 293 patients (mean age, 54 years; range, 0-90 years; 112 females) commenced a course of vancomycin or teicoplanin. The 293 patients received 302 courses of glycopeptide antibiotics -- three teicoplanin, three oral vancomycin, and 296 intravenous vancomycin (Box 2). Five of Melbourne's six major metropolitan hospitals participated and administered 209 (69%) of the 302 courses. Twenty hospitals enrolled between one and 11 patients and contributed the remaining 93 courses. Glycopeptide antibiotic use in neonates: Four hospitals enrolled 24 neonates who were prescribed 25 courses of IV vancomycin, with a median duration of 2.3 days (interquartile range, 2.0-4.6 days). One course was for prophylaxis for abdominal surgery; the other 24 courses were for empirical treatment. One treatment course was for respiratory infection and the others were for an unknown site of infection. Flucloxacillin-resistant organisms were isolated for six courses (two MRSA, four coagulase-negative staphylococci). Glycopeptide antibiotic use in adults: Twenty-five hospitals enrolled 269 adults who commenced 277 glycopeptide antibiotic courses; 143 (53%) patients were treated by a medical unit and 126 (47%) by a surgical unit; 73 (27%) of the patients were in an intensive care unit at some stage during the glycopeptide antibiotic course. Of the 269 patients, 235 (87%) were discharged, 30 (11%) died, and 4 (1%) were still in hospital three months after the study. For 94 courses (34%), specialist consultation for the use of vancomycin and teicoplanin was noted in the records. More than 80% of these consultations were with infectious disease/microbiology specialists. There were 263 patients who received 271 courses of IV vancomycin -- 176 (65%) for treatment and 95 for prophylaxis (Box 3). Of the 176 IV vancomycin treatment courses, 120 (68%) were for empirical treatment and 56 (32%) as specific treatment. Empirical courses were shorter than specific courses (P < 0.02). Patients being treated empirically had been in hospital for fewer days before the course commenced than patients receiving specific treatment (P < 0.001). The duration of empirical courses for which a flucloxacillin-resistant organism was subsequently identified was significantly greater than that of the unconfirmed courses (P < 0.05). Of the other six patients, three received a course of oral vancomycin for the treatment of confirmed (two cases) or suspected (one case) Clostridium difficile diarrhoea, and three received IV teicoplanin for treatment of wound infections (2 patients) or cellulitis (1 patient), commenced on the advice of infectious diseases clinicians. Other antibiotic use in adults: In the seven days before IV vancomycin treatment courses, the most frequently prescribed antibiotics were ceftriaxone and cefotaxime (28% of courses), metronidazole (16%), flucloxacillin (15%), and gentamicin (15%). The most frequently prescribed concurrent antibiotics were ceftriaxone and cefotaxime (11% of vancomycin courses), gentamicin (11%), ceftazidime (9%), imipenem (7%), ciprofloxacin (6%) and metronidazole (6%). For 14 treatment courses, vancomycin was continued beyond the close of the study. Immediately following the 162 completed courses (in 162 patients), other antibiotic therapy was commenced for 57 patients (35%), concurrent antibiotic therapy continued for 35 patients (22%), and there was no antibiotic therapy for 50 patients (31%). On-going therapy was not recorded for nine patients (6%), and the remaining 11 patients (7%) died. The antibiotics most frequently commenced immediately after vancomycin were oral flucloxacillin (12 courses), oral fusidic acid and oral rifampicin (12 courses), and oral ciprofloxacin (eight courses). For the 95 IV vancomycin prophylaxis courses, other antibiotics were given concurrently for 46 (48%) courses, most frequently gentamicin (14% of vancomycin courses), ceftriaxone (14%), cephazolin (6%) and ticarcillin/clavulanate (5%). Comparison of five main vancomycin users: The five hospitals that used most vancomycin were major metropolitan university teaching hospitals where use was restricted by protocols and consultations. Use by number of courses was greatest in Hospital 1 but the total quantity used was less than half that used at Hospital 2 (Box 4). Rate of use was significantly lower in Hospital 4 than in the other four hospitals. Surgical use of vancomycin predominated in Hospital 1, while medical use predominated in Hospital 4. Hospitals 2, 3 and 5 had a significantly smaller proportion of single doses for prophylaxis than Hospitals 1 and 4. Discussion We have examined the pattern of use of vancomycin in a large sample of Victorian hospitals. We found that use of teicoplanin and oral vancomycin was low, and that intravenous vancomycin was used predominantly for empirical treatment or prophylaxis. Our study is the first to capture a statewide picture of hospital drug use linked to indication, and we are not aware of any published comparable multihospital pharmacoepidemiological data. Based on the number of inpatient separations for Victorian public hospitals in 1996-97 (about 890 000),10 we reviewed an estimated 82% of public hospital inpatient separations in the two-week study period. We estimated the overall rate of glycopeptide antibiotic use to be 10.3 courses per 1000 inpatient separations, which suggests about 9160 courses are used annually in Victorian public hospitals. The main limitation of our study was that vancomycin courses were not individually compared against explicit criteria to determine the proportion of appropriate use on the basis of indication, dosage and duration. We chose not to compare against criteria because of the variety of prescribing restrictions in participating hospitals. The most frequent indications for empirical IV vancomycin were febrile neutropenia, pneumonia and wound infections. The indications for and duration of empirical therapy could be targets for intervention. For pneumonia, IV vancomycin use may be reasonable for hospital-acquired infections in institutions with a high prevalence of MRSA. For febrile neutropenia, IV vancomycin may be best restricted to patients with suspected associated IV line sepsis. For wound infections, unless there is a high prevalence of MRSA, IV vancomycin treatment should wait until after microbiological confirmation. Oral vancomycin should be restricted to the treatment of antibiotic-associated colitis due to toxigenic C. difficile unresponsive to or relapsing after an adequate course of metronidazole (or bacitracin), or for patients with severe colitis.11 Clinicians should be encouraged to regularly review the need for ongoing drug therapy; however, to improve the current situation, we need effective decision support tools to facilitate timely attention to important test findings.12 Almost half the treatment courses were sanctioned or recommended by infectious diseases/microbiology specialists, who should be familiar with relevant guidelines for vancomycin use. Surgical prophylaxis consumed 35% of IV vancomycin courses, with cardiac and vascular surgery accounting for 75% of prophylactic courses. The duration of vancomycin prophylaxis was generally according to recommendations, with 72% of courses given as single doses and 82% of courses given for less than 24 hours. However, there was considerable interhospital variation in the duration of surgical prophylaxis. The implementation of hospital policies on duration of surgical prophylaxis would be an important target for intervention. Glycopeptide antibiotic use was concentrated in five major metropolitan teaching hospitals. Although these five hospitals all had policies in place, vancomycin use varied substantially. It is of critical importance for patient care and resource management that there is a conscious effort to preserve the utility of vancomycin and teicoplanin. This should be founded on good infection control practice, but there is also a need for all hospitals to implement effective interventional strategies to improve the use of the glycopeptide antibiotics. Acknowledgements Financial support for the employment of the Project Coordinator was provided by the Victorian Drug Usage Advisory Committee and the Victorian Standing Committee on Infection Control. The project was also reliant on the voluntary work of pharmacists at the participating hospitals who undertook all the data collection. We acknowledge the assistance of the other members of the Victorian Drug Usage Evaluation Group in the planning and execution of the study and the preparation of this manuscript: Stephanie J Alvarez, Drug Utilisation Evaluation Pharmacist, Monash Medical Centre; Dr Jo-anne Brien, Senior Lecturer, Department of Pharmacy Practice, Monash University (Parkville Campus); Dr Lisa L Ioannides-Demos, Senior Research Fellow, Department of Epidemiology and Preventative Medicine, Monash University, and Senior Research Officer, Victorian Centre for Ambulatory Care Innovation, Alfred Hospital; Sam Koroneos, Senior Drug Utilisation Pharmacist, Pharmacy Department, Austin and Repatriation Medical Centre; Anne Leversha, Senior Lecturer, Monash University, Faculty of Medicine, and Victorian College of Pharmacy, and Deputy Manager Pharmacy Services, Latrobe Regional Hospital, Traralgon West; Julie A V Lord, Senior Drug Information and Clinical Research Pharmacist, St Vincent's Hospital, Melbourne; Heather J Lyall, Deputy Director of Pharmacy, Geelong Hospital; Roslyn I McKinnon, Executive Officer, Victorian Drug Usage Advisory Committee; Associate Professor R Moulds, Director, Department of Clinical Pharmacology and Therapeutics, Royal Melbourne Hospital; Susan G Poole, Deputy Director, Peter MacCallum Cancer Institute; Dr Gail J Ware, Drug Usage Evaluation Pharmacist, Alfred Hospital. References Ena J, Dick RW, Jones RN, Wenzel RP. The epidemiology of intravenous vancomycin usage in a university hospital: a 10 year study. JAMA 1993; 269: 598-602. Heath CH, Blackmore TK, Gordon DL. Emerging resistance in Enterococcus spp. Med J Aust 1996; 164: 116-120. Reduced susceptibility of Staphylococcus aureus to vancomycin -- Japan, 1996. MMWR Morb Mortal Wkly Rep 1997; 46: 624-626. Quale J, Landman D, Atwood E, et al. Experience with a hospital-wide outbreak of vancomycin-resistant enterococci. Am J Infect Control 1996; 24: 372-379. Witte W. Medical consequences of antibiotic use in agriculture. Science 1998; 279: 996-997. Misan GMH, Martin ED, Smith ER, et al. Drug utilisation review in a teaching hospital: experience with vancomycin. Eur J Clin Pharmacol 1990; 39: 457-461. Radford JM, Whitby RM, Looke DFM, Coombes JA. Vancomycin usage review in the era of vancomycin-resistant enterococci (VRE). Aust J Hosp Pharm 1997; 27: 1410-1413. Guidelines for preventing emergence of vancomycin-resistant enterococci. Melbourne: Victorian Drug Usage Advisory Committee and the Standing Committee on Infection Control in collaboration with the Writing Group for the Therapeutic Guidelines: Antibiotic, 1997. Vernon G, Thomson W, editors. Directory of hospital pharmacy and pharmaceutical organisations. Melbourne: Society of Hospital Pharmacists of Australia, 1996. Department of Human Services Annual Report 1996-97. Melbourne: Department of Human Services, Victoria, 1997. Therapeutic Guidelines: Antibiotic, 10th ed. Melbourne: Therapeutic Guidelines Limited, 1998. Schiff GD, Rucker D. Computerized prescribing. Building the electronic infrastructure for better medication usage. JAMA 1998; 279: 1024-1029. (Received 21 Dec 1998, accepted 17 May 1999) Authors' details Victorian Drug Usage Evaluation Group, Melbourne, VIC. Marion B Robertson, BPharm, MSc, Project Coordinator. Royal Melbourne Hospital, Melbourne, VIC. Jonathan G A Dartnell, BPharm, MPS, Senior Pharmacist, Department of Clinical Pharmacology and Therapeutics. Monash Medical Centre, Melbourne, VIC. Tony M Korman, FRACP, Infectious Diseases Physician. Reprints will not be available from the authors. Correspondence: Mr J G A Dartnell, Department of Clinical Pharmacology and Therapeutics, c/- Post Office, Royal Melbourne Hospital, VIC 3050. Email: Jonathan. DartnellATnwhcn.org.au 1: Definitions Course: The administration to a patient of at least one dose of vancomycin or teicoplanin. If a dose was administered more than 24 hours after a previous dose (and the drug was re-prescribed), this was considered a new course. Patients with renal impairment on regimens with dosing intervals longer than 24 hours were considered to have received a continuous course. Prophylaxis: Antibiotic administration commenced perioperatively to prevent postoperative infection. Empirical treatment: Antibiotic administration commenced before or without identification of flucloxacillin-resistant bacterial pathogens. Specific treatment: Antibiotic administration commenced after identification of flucloxacillin-resistant bacterial pathogens. Duration: Durations of courses were calculated by subtracting the date and time of the first dose from the date and time of the last dose. The duration of a single dose was considered to be 0 hours. Back to text 2: Glycopeptide antibiotic courses commenced in participating hospitals during study period*Hospital locationNumber of courses † (patients)Number of inpatient separationsCourses per 1000 separationsMelbourne52 (51)‡235622.0Melbourne49 (48)245520.0Melbourne38 (37)194319.6Melbourne37 (37)299712.3Melbourne33 (30)§141623.3Regional11 (11)14777.4Melbourne10 (9)53818.6Melbourne10 (10)14776.7Melbourne9 (9)10718.4Melbourne8 (8)10897.3Melbourne8 (7)13575.9Melbourne7 (7)42316.5Regional5 (5)8086.2Melbourne5 (5)10554.7Melbourne3 (3)15002.0Melbourne3 (2)27111.1Regional3 (3)3748.0Regional2 (2)§14613.7Melbourne2 (2)8772.3Melbourne2 (2)4694.3Melbourne1 (1)6681.5Regional1 (1)7251.4Regional1 (1)§2663.8Melbourne1 (1)6361.6Melbourne1 (1)5102.0Overall*302 (293)2944510.3*Another 9 regional and 1 Melbourne hospital accounted for 2785 inpatient separations but did not use glycopeptide antibiotics during the study period. †Intravenous vancomycin except where indicated. ‡Includes 3 courses of teicoplanin. §Includes 1 course of oral vancomycin. Private hospital. Back to text 3: Intravenous vancomycin courses commenced in adultsAll treatment courses 176 treatment courses median duration, 4.7 days (interquartile range, 2.0-8.2 days) indications: wound infections33 (18.8%)pneumonia29 (16.5%)febrile neutropenia21 (11.9%)septicaemia12 (6.8%)intravenous catheter-associated sepsis11 (6.3%)cellulitis9 (5.1%)infected prosthesis9 (5.1%)peritonitis/CAPD8 (4.5%)meningitis3 (1.7%)other16 (9.1%)not recorded25 (14.2%)Gram-positive bacteria, including Staphylococcus, Streptococcus, Enterococcus and Bacillus species isolated for 113 (64%) courses Isolated organism confirmed flucloxacillin-resistant in 78 courses; organism was MRSA in 67 coursesEmpirical treatment courses 120 empirical treatment courses (68% of all treatment courses) median duration, 4.4 days (interquartile range, 1.5-8.0 days) patients in hospital for median 4.0 days (interquartile range, 1-12 days) before course commenced most frequent indications: febrile neutropenia (18%), pneumonia (16%) and wound infections (12%) 32 (26%) of patients had history of beta-lactam antibiotic hypersensitivity or a previous infection with MRSA or MRSE. Two patients had a history of severe hypersensitivity that may have necessitated use of vancomycin rather than beta-lactam antibiotics. flucloxacillin-resistant organism subsequently identified in 24 (20%) empirical courses duration of courses with confirmed resistant organism was 6.9 days (interquartile range, 2.0-13.8 days) compared with 3.9 days (interquartile range, 1.3-6.7 days) for unconfirmed courses (P<0.05) Specific treatment courses 56 specific treatment courses (32% of all treatment courses) median duration, 6.1 days (interquartile range, 3.0-11.6 days) patients in hospital for median 12 days (interquartile range, 4-22 days) before course commenced Surgical prophylaxis courses95 surgical prophylaxis courses 68 (72%) single-dose courses, 78 (82%) less than one day, 12 (12%) one to three days, 5 (5%) more than three days 12 (13%) were for patients with history of beta-lactam hypersensitivity, including four severe cases, and 5 (5%) were for patients with history of MRSA or MRSE infection 51 (54%) used in cardiac surgery; 31 single doses, 12 (24%) lasted more than 36 hours 20 (21%) used in vascular surgery; all were single dosesCAPD=chronic ambulatory peritoneal dialysis. MRSA=methicillin-resistant Staphylococcus aureus. MRSE=methicillin-resistant S. epidermidis. Back to text 4: Comparison of intravenous vancomycin in adults in the major teaching hospitalsHospital 1Hospital 2Hospital 3Number of courses494938Number of patients484837Courses per 1000 separations*20.820.019.6Vancomycin used (g)177371280Median length of stay (days)121816Courses given in intensive care9 (18%)9 (18%) 17 (45%)Courses prescribed by medical unit12 (24%)28 (57%)20 (53%)Indication: prophylaxisNumber of courses (%)28 (57%)15 (31%)15 (39%)Number (%) as single doses †28 (100%)7 (47%)9 (60%)Surgery type (number of courses) cardiac2476 vascular241 other248Indication: treatmentNumber (%) empirical13 (62%)30 (88%) 19 (83%)Median duration of courses (days) empirical3.73.64.8 specific3.04.511.0Indications (number of courses) pneumonia724 wound infection436 febrile neutropenia181 other92112 Hospital 4Hospital 5Number of courses3332Number of patients3229Courses per 1000 separations*12.322.6Vancomycin used (g)299118Median length of stay (days)209Courses given in intensive care6 (18%)9 (28%)Courses prescribed bymedical unit30 (91%)17 (53%)Indication: prophylaxisNumber of courses (%)8 (24%) 16 (50%)Number (%) as single doses †8 (100%)11 (69%)Surgery type (number of courses) cardiac18 vascular63 other15Indication: treatmentNumber (%) empirical18 (72%)10 (62%)Median duration of courses (days) empirical5.51.5 specific3.02.0Indications (number of courses) pneumonia60 wound infection33 febrile neutropenia24 other149* Hospital 4 significantly less than Hospitals 1, 2, 3 and 5 (P<0.02). †Hospitals 2, 3, and 5 significantly less than Hospital 1 (P<0.01) and Hospital 4 (P<0.1). Back to text

Marion B Robertson

Research Outcome of a screening program for vancomycin-resistant enterococci in a hospital in Victoria M Lindsay Grayson, Elizabeth A Grabsch, Paul D R Johnson, Dianne Olden, Melissa Aberline, H Y Li, Geoffrey Hogg, Marguerite Abbott and Peter G Kerr MJA 1999; 171: 133-136 See also Ferguson, Robertson et al & Collignon Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Infectious diseases and parasitology Abstract Objective: To screen for faecal colonisation with vancomycin-resistant enterococci (VRE) among potentially at-risk patients. Design: Infection control screening program. Setting: Monash Medical Centre (a tertiary care hospital), Melbourne, Victoria, in the seven months from June 1997. Patients: Patients in the Renal, Oncology and Intensive Care (ICU) Units. Main outcome measures: Presence of VRE in a rectal swab or faecal specimen taken at admission and at regular intervals during inpatient stay; presence of vancomycin-resistance genes (vanA, vanB and vanC) assessed by polymerase chain reaction (PCR); genetic clonality of isolates assessed by pulsed-field gel electrophoresis (PFGE). Results: 574 patients (356 renal, 134 ICU and 84 oncology) were screened; 12 were colonised with VRE -- nine renal inpatients, two having peritoneal dialysis or in-centre haemodialysis, and one ICU patient. Nine isolates were Enterococcus faecalis (seven positive for vanB and two negative for all three resistance genes) and three were Enterococcus faecium (all positive for vanB). Eight were high-level gentamicin resistant. PFGE suggested genetic clonality between the index isolate and five other isolates from renal patients. No specific clinical practice was associated with VRE colonisation. Attempts to clear rectal carriage with oral ampicillin/amoxycillin or bacitracin were of limited success. Although antibiotic prescribing in the Renal Unit was generally consistent with defined protocols, use of vancomycin and third-generation cephalosporins has been further restricted. Conclusions: Renal inpatients in our institution appear most at risk of VRE colonisation (4.6% overall) and therefore of VRE infection. Routine screening, especially of potentially high-risk patients, should be considered in major Australian hospitals. Introduction Vancomycin-resistant enterococci (VRE) were first reported in the United Kingdom, Europe and the United States in 1988,1-6 and in Australia in 1994.7 In the United States, VRE have become common and potentially fatal nosocomial pathogens; they account for 14% of enterococcal bacteraemias in intensive care patients, while VRE bacteraemia has an attributable mortality of 30%-46%.4,8 In Australia, cases of VRE infection have now been reported from hospitals in all States and Territories except the Australian Capital Territory and Tasmania.9,10In May 1997, a patient receiving renal haemodialysis at Monash Medical Centre, Melbourne, developed a VRE urinary tract infection (see Box 1). This was the first identified case of VRE infection at this institution. As the patient had had close contact with other patients and had suffered diarrhoea, we were concerned about a significant nosocomial outbreak of VRE infection. Clinical infection is almost always associated with faecal colonisation with this organism. We therefore assessed the extent of faecal VRE colonisation among renal and other high-risk patients by active screening, and isolated infected or colonised patients. We describe the results of this screening program and our infection control measures, and highlight some of the clinical issues. Methods An infection control screening program for faecal colonisation with VRE was implemented in the Renal, Oncology and Intensive Care Units at Monash Medical Centre, Melbourne, Victoria, for the seven months from June 1997. These patients were chosen as experience (local, US and European) suggested they were at greatest risk of VRE infection.4-6,8,10 Patients In the Renal Unit, screening was planned for all patients receiving care in the renal ward and in-centre haemodialysis or continuous ambulatory peritoneal dialysis and, when possible, for dialysis patients managed at home. In the Oncology and Intensive Care Units (ICU), screening was planned for an arbitrary number of 100 consecutive patients admitted to each unit. All inpatients were screened on admission and discharge. In the renal ward this was later modified to on admission and a regular day of the week (Tuesday). Patients managed by the in-centre haemodialysis unit were screened every three months, and other outpatients were screened at least once. Screening Rectal swabs were obtained using standard cotton-alginate-tipped sterile swabs from all patients except neutropenic oncology patients. In these, a perianal swab or faecal specimen was substituted for a rectal swab because of their increased risk of septicaemia after rectal trauma.13 Specimens were plated on media specifically selective for vancomycin-resistant enterococci (bile esculin azide agar with 6 µg/mL vancomycin) and cultured for up to 72 hours. Esculin-positive isolates with possible resistance to vancomycin were identified, and single colonies of each morphology type were assessed to identify Enterococcus faecalis and Enterococcus faecium (the pathogenic enterococcal species most commonly associated with vancomycin resistance). Assessment included Gram stain, tests of motility and pigment production, the pyrrolidonyl arylamidase test (Murex Diagnostics Ltd, Dartford, UK) and streptococcal latex grouping.14 VRE assessment VRE isolates were tested further for antibiotic susceptibility. Minimum inhibitory concentrations (MICs) were determined for vancomycin, teicoplanin and ampicillin and high-level gentamicin (MIC > 500 µg/mL) using the E test (AB Biodisk, Dalvagen, Sweden). Production of β-lactamase was assesssed by nitrocephin disc (Becton Dickinson Microbiology Systems, Cockeysville, MD, USA). Enterococcal species was confirmed and presence of vancomycin-resistance genes vanA, vanB or vanC was assessed by polymerase chain reaction (PCR) genetic probe using a modification of techniques described previously.10,15 Genetic similarity (ie, potential clonality) of VRE isolates was assessed by pulsed-field gel electrophoresis (PFGE) using a method modified after Miranda et al.16 Factors that were potentially associated with VRE colonisation were assessed retrospectively.6,8 Statistical analyses were by χ2 or t test. Results Patients Screening was undertaken on 574 patients -- 356 renal, 134 ICU and 84 oncology patients. Renal patients comprised: 194 of 238 inpatients in the renal ward (82%); 66 of 82 peritoneal dialysis and in-centre haemodialysis patients (80%); 94 outpatients (mostly satellite and home haemodialysis patients); and 2 of 180 renal transplantation patients. In general, consecutive oncology and ICU patients were screened; none refused screening. In the Oncology Unit, the target number (100 patients) was not attained because of a protocol lapse. VRE colonisation Faecal colonisation with VRE was found in 12 patients, including the index patient -- 11 renal patients (3% of renal patients tested) and one ICU patient (0.7% of ICU patients tested). Their characteristics are shown in Box 2. No VRE colonisation was found in oncology patients. The 11 renal patients with VRE colonisation comprised nine inpatients (9/194 [5%]) and two having peritoneal dialysis or in-centre haemodialysis (2/66 [3%]). No non-dialysis renal outpatients were colonised. VRE colonisation was found on the initial rectal swab for seven patients and after a series of negative cultures for the remaining five patients. Characteristics of VRE isolates Characteristics of the 12 VRE isolates are shown in Box 2. Nine of the 12 were E. faecalis -- seven testing positive for vanB, including the index isolate (vancomycin MICs, 12-32 µg/mL), and two testing negative for vanA, vanB and vanC (vancomycin MICs, 6 and 8 µg/mL, respectively). The other three isolates were E. faecium -- all testing positive for vanB (vancomycin MICs, 16, 64 and > 256 µg/mL, respectively). All isolates were susceptible to teicoplanin. While all E. faecalis isolates were susceptible to ampicillin, all E. faecium isolates were resistant (MICs > 256 µg/mL). Six of the nine E. faecalis isolates and two of the three E. faecium isolates had high-level resistance to gentamicin. None of the 12 produced detectable β-lactamase. Eleven isolates were assessed by PFGE. Results are shown in the Figure. Six of the seven vanB E. faecalis isolates, including the index isolate, appeared genetically similar (lanes 4-8 and index isolate in lane 9). Three of these similar isolates, plus one dissimilar vanB E. faecalis isolate (not shown), were isolated from patients who had been nursed together in a four-bed area. One of these patients (with vanB E. faecalis) had been nursed with the index patient six months before screening positive. The three E. faecium isolates and the non-ABC E. faecalis isolate (lanes 1-3 and 10, respectively) showed a variety of electrophoretic patterns on PFGE, suggesting they were genetically dissimilar from each other. Factors potentially associated with VRE Among the 12 patients with VRE colonisation, nine had received vancomycin in the previous month, four of whom had also received a third-generation cephalosporin (ceftriaxone). Information on previous antibiotics was not available for patients without VRE colonisation. Among the six renal patients found to have VRE colonisation on their initial swab (including the index case), five had been inpatients during the previous three months, compared with 127 of the 350 non-colonised patients (36%). Mean duration of preswab inpatient stay for these six colonised patients was 17.5 days (range, 0-62), compared with 2.6 days (range, 0-43) for non-colonised patients (P < 0.001). VRE control measures All patients identified with faecal VRE colonisation were nursed in a single room according to infection control guidelines.11 In January 1998, an eight-bed VRE isolation facility was established. Continued, less rigorous screening of renal inpatients identified four new cases of VRE colonisation in the following three months (not described here), but these VRE strains were dissimilar on PFGE to the previous 12 strains. Antibiotic usage patterns were also reviewed. Most antibiotic use in the Renal Unit was found to be consistent with the unit's protocols. These were amended to further restrict use of third-generation cephalosporins and glycopeptides to specific situations, such as nosocomial pneumonia and serious staphylococcal infections. In seven patients, an attempt was made to "clear" faecal VRE colonisation with either ampicillin or amoxycillin (variable doses, depending on renal function) or oral bacitracin (25 000 units four times a day for 7-14 days).17,18 In four of these patients, follow-up rectal swabs were taken, and in two (one taking ampicillin and one bacitracin) VRE was no longer detected 18 and 13 days, respectively, after therapy. At completion of the study, nine of the 12 patients with VRE colonisation had died, although, other than the index patient, none had developed VRE infection. Discussion A screening program introduced at Monash Medical Centre after identification of VRE infection in a renal patient found faecal VRE colonisation in another 10 renal patients (3% of renal patients overall) and one ICU patient (0.7%). Isolates from six of the renal patients, including the index patient, were genetically similar and probably clonal. No patients except the index patient developed VRE infection. VRE is now a major nosocomial pathogen in many US and European centres, but until recently relatively few clinical VRE infections had been reported in Australia.6,8-10 To our knowledge, this is the first Australian report of a systematic screening program for VRE among potentially at-risk patients. Our results were consistent with those of previous studies, which suggested that 10-20 patients are likely to have faecal colonisation for every case of clinical VRE infection.6,8,19,20 Although risk factors for VRE infection have been identified by US and European investigators,6,8the factors associated with VRE colonisation are less clear and may vary depending on the epidemiology of VRE in different countries. Antibiotic prescribing patterns, nosocomial transmission and use of antibiotics (eg, avoparcin) in the veterinary industry appear of varying importance in different regions.8,10 Our study did not allow valid assessment of all factors potentially associated with VRE colonisation in our patients. Nevertheless, the fact that renal patients with VRE colonisation spent significantly more days in hospital in the previous three months than patients without colonisation raises the possibility that the hospital environment or illness-related factors influenced the likelihood of VRE colonisation. Resistance to vancomycin among enterococci is generally due to presence of one of four resistance genes -- vanA, vanB, vanC and vanD. These genes result in synthesis of abnormal precursors in the peptidoglycan layer of the bacterial cell wall, thereby reducing the affinity with which vancomycin binds to this target site.8VanA is associated phenotypically with resistance to vancomycin (MIC > 64 µg/mL) and teicoplanin (MIC > 16 µg/mL), and is the most common genotype found in Europe and some centres in the US.8VanB is associated with medium-level resistance to vancomycin (MIC > 4 µg/mL) but susceptibility to teicoplanin. Consistent with our findings, it is the predominant genotype noted in Australia.9,10VanC is associated with naturally occurring low-level resistance to vancomycin and susceptibility to teicoplanin among less pathogenic enterococcal species, while vanD, which is phenotypically similar, has been occasionally noted in some E. faecium isolates.8,21,22 It is possible that our two non-ABC E. faecalis isolates contain vanD, but we are currently unable to test for this gene. Presence of faecal VRE colonisation among 5% of renal inpatients at our institution (3% of renal patients overall) was higher than expected, but suggested that nosocomial transmission of VRE was not yet a widespread problem. Nevertheless, our PFGE data suggested that six of the seven vanB E. faecalis strains were clonal, raising infection control issues for the Renal Unit. As reported previously,17,18 we found attempts to clear faecal VRE carriage with antibiotic therapy were unsuccessful and not worthwhile. The screening program and establishment of VRE isolation facilities to readily cohort and barrier-nurse patients with VRE colonisation appeared to assist in limiting nosocomial VRE transmission, while continuing to provide medical care for patients in a compassionate manner. The incidence of faecal VRE colonisation that we found among high-risk patients at our institution suggests that routine screening for faecal VRE colonisation should now be considered by other similar Australian hospitals. Acknowledgements We wish to acknowledge the contribution of the nursing staff of the Renal, Oncology and Intensive Care Units and the Outpatient Department in obtaining rectal cultures. References Leclercq R, Derlot E, Duval J, Courvalin P. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med 1988; 319: 157-161. Uttley AHC, Collins CH, Naidoo J, George RC. Vancomycin-resistant enterococci. Lancet 1988; 1: 57-58. Clark NC, Cooksey RC, Hill BC, et al. Characterization of glycopeptide-resistant enterococci from U. S. hospitals. Antimicrob Agents Chemother 1993; 37: 2311-2317. Centers for Disease Control. Nosocomial enterococci resistant to vancomycin -- United States, 1989-1993. MMWR Morb Mortal Wkly Rep 1993; 42: 597-599. Frieden TR, Munsiff SS, Low DE, et al. Emergence of vancomycin-resistant enterococci in New York City. Lancet 1993; 342: 76-79. Boyce JM. Vancomycin-resistant enterococcus. Detection, epidemiology, and control measures. Infect Dis Clin North Am 1997; 11: 367-384. Kamarulzaman A, Tosolini FA, Boquest AL, et al. Vancomycin resistant Enterococcus faecium infection in a liver transplant recipient [abstract]. Aust N Z J Med 1995; 25: 560. Eliopoulos GM. Vancomycin-resistant enterococci. Mechanism and clinical relevance. Infect Dis Clin North Am 1997; 11: 851-865. Bell J, Turnidge J, Coombs G, O'Brien F. Emergence and epidemiology of vancomycin-resistant enterococci in Australia. Commun Dis Intell 1998; 22: 249-252. Bell JM, Paton JC, Turnidge J. Emergence of vancomycin-resistant enterococci in Australia: phenotypic and genotypic characteristics of isolates. J Clin Microbiol 1998; 36: 2187-2190. Standing Committee on Infection Control (SCIC), Department of Human Services, Victoria. Guidelines for the management of patients with confirmed vancomycin-resistant enterococci (VRE) infection/colonisation. Melbourne: Department of Human Services, 1996. Moellering RC Jr. The Garrod lecture. The enterococcus: a classic example of the impact of antimicrobial resistance on therapeutic options. J Antimicrob Chemother 1991; 28: 1-12. Weinstein JW, Tallapragada S, Farrel P, Dembry L-M. Comparison of rectal and perirectal swabs for detection of colonisation with vancomycin-resistant enterococci. J Clin Microbiol 1996; 34: 210-212. Facklam RR, Sahm DF. Enterococcus. In: Murray PR, Baron EJ, Pfaller MA, et al, editors. Manual of clinical microbiology. 6th ed. Washington: ASM Press, 1995: 308-314. Dutka-Malen A, Evers S, Courvalin P. Detection of glycopeptide resistance genotypes and identification to the species level of clinically relevant enterococci by PCR. J Clin Microbiol 1995; 33: 24-27. Miranda AG, Singh KV, Murray BE. A fingerprinting of Enterococcus faecium by pulsed-field gel electrophoresis may be a useful epidemiologic tool. J Clin Microbiol 1991; 29: 2752-2757. O'Donovan CA, Fan-Havard P, Tecson-Tumang FT, et al. Enteric eradication of vancomycin-resistant Enterococcus faecium with oral bacitracin. Diagn Microbiol Infect Dis 1994; 18: 105-109. Chia JKS, Nakata MM, Park SS, et al. Use of bacitracin therapy for infection due to vancomycin-resistant Enterococcus faecium. Clin Infect Dis 1995; 21: 1520. Jordens JZ, Bates J, Griffith DT. Faecal carriage and nosocomial spread of vancomycin-resistant Enterococcus faecium. J Antmicrob Chemother 1994; 34: 515-528. Montecalvo MA, deLaencastre H, Carraher M, et al. Natural history of colonization with vancomycin-resistant Enterococcus faecium. Infect Control Hosp Epidemiol 1995; 16: 680-685. Leclercq R, Courvalin P. Resistance to glycopeptides in enterococci. Clin Infect Dis 1997; 24: 545-556. Perichon B, Reynolds P, Courvalin P. VanD-type glycopeptide-resistant Enterococcus faecium BM4339. Antimicrob Agents Chemother 1997; 41: 2016-2018. (Received 15 Dec 1998, accepted 23 Apr 1999) Authors' details Infectious Disease and Clinical Epidemiology Department, Monash Medical Centre, Melbourne, VIC. M Lindsay Grayson, MD, FRACP, Director, and Professor of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC; Elizabeth A Grabsch, BSc, GradDipClinEpid, Infection Control Scientist; Paul D R Johnson, PhD, FRACP, Infectious Disease Physician, and Senior Lecturer, Microbiology Department, Monash University, Melbourne, VIC; Dianne Olden, PhD, Research Scientist. Infection Control Unit, Monash Medical Centre, Melbourne, VIC. Melissa Aberline, RN, BSc, Infection Control Nurse. Microbiological Diagnostic Unit, Melbourne University, Melbourne, VIC. H Y Li, MMed, Scientist; Geoffrey Hogg, FRACP, FRCPA, Director. Nephrology Department, Monash Medical Centre, Melbourne, VIC. Marguerite Abbott, RN, BAppSci, Nurse Director; Peter G Kerr, PhD, FRACP, Deputy Director. Reprints will not be available from the authors. Correspondence: Professor M L Grayson, Infectious Diseases and Clinical Epidemiology Department, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168. Email: Lindsay. GraysonATmed.monash.edu.au Pulsed-field gel electrophoresis of vancomycin-resistant enterococcal isolates. Lanes 1-3: E. faecium (vanB) isolates from renal patients. Lanes 4-9: E. faecalis (vanB) isolates from renal patients, including index isolate (lane 9). Lane M: Molecular weight markers. Lane 10: E. faecalis (non-ABC) isolate from renal patient. Back to text 1: Case history of the index patient In May 1997, a 26-year-old woman presented to Monash Medical Centre with a fever and urinary tract infection caused by vancomycin-resistant enterococci (VRE). She had faecal colonisation with the same VRE strain. She had endstage renal failure requiring in-centre haemodialysis three times a week. Ten days later, the patient presented in status epilepticus with faecal incontinence that led to substantial faecal contamination of the Emergency Department and the in-centre Haemodialysis Unit. Appropriate cleaning protocols11 were implemented in each area, and limited environmental cultures suggested no contamination. Five months later, the patient developed symptomatic VRE bacteraemia after surgical insertion of a femoral Goretex arteriovenous fistula. The VRE isolate was phenotypically identical to the initial urinary isolate. As it had high-level gentamicin resistance, she was treated with continuous-infusion ampicillin, continuing for 10 weeks because of the possibility of graft sepsis.12 The patient continued to show faecal VRE colonisation until her death (not related to VRE) in September 1998. Back to text

Elizabeth A Grabsch · Dianne Olden · Melissa Aberline · H Y Li · Geoffrey Hogg · Marguerite Abbott · Peter G Kerr

Research Australian suicide trends 1964-1997: youth and beyond? Christopher H Cantor, Kerryn Neulinger and Diego De Leo MJA 1999; 171: 137-141 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Psychiatry Abstract Objective: To examine Australian suicide rates across all ages, and compare Australian rates with those of other Western nations. Design: Australian Bureau of Statistics data were used to examine Australian suicide trends, 1964-1997, by age and sex. For comparison, suicide rates of 22 other Western nations, 1990-1994, were obtained from the World Health Organization. Results: Australian suicide rates for males 15-24 years and 25-34 years rose from 1964-1997. Comparable rates for females showed no significant change. Suicide rates for several of the older age and sex groups declined over this period. Comparison with suicide rates of other Western nations showed that, while Australian youth suicide rates are relatively high, this is not the case for older age groups. Australian suicide rates are higher than those in the European nations of origin of our major migrant groups, but similar to those of other Western nations also recently colonised by Europeans (Canada, the United States and New Zealand). Conclusions: Priorities for suicide prevention in Australia are correctly concentrated on youth, but the targeted age range should be extended to include men aged 25-34 years. A comprehensive policy should also not neglect the needs of other age groups. Further epidemiological study of national and international data may suggest new approaches to suicide prevention. Introduction It is well known that there is a high suicide rate in Australian males aged 15-24 years, and previous and present governments have instituted committees to address youth suicide rates.1 There have been only sporadic reports of suicide rates in other age groups,2 including suggestions of high rates in elderly people.2,3We present suicide rates and trends across all ages, placing them in context by comparing them with rates from other Western nations. The national focus on youth suicide to the relative exclusion of older age groups is examined in the light of these data. Methods Australian suicide and population data for 1964-1997 were obtained from the Australian Bureau of Statistics (ABS) and annual suicide rates (per 100 000 estimated mean resident population) were calculated (see Appendix). These were plotted by 10-year age groups and sex over time. Change over time was examined by comparing the suicide rate in 1964-1966 (rates were averaged to smooth out random fluctuations within one-year periods) with the suicide rate in 1995-1997; 95% confidence intervals were calculated for these two time periods to assess the significance of change. Variations in suicide rate trends over this 34-year period were assessed by calculating the series autocorrelation suicide rates and the values of Pearson's correlation coefficient. Years of potential life lost (YPLL) were calculated for 10-year age and sex groups for the most recent year (1997). The formula used was adapted from that used by the Australian Bureau of Statistics4 in order to incorporate age groups (Box 1). The Australian population at 30 June 1991 was chosen as the standard population, as suggested by the Australian Bureau of Statistics. International data were obtained from the World Health Organization (WHO)5-8 and Lester and Yang.9 Mean suicide rates were calculated for 23 Western countries (including Australia), averaged over 1990-1994, for 10-year age and sex groups. These 10-year age and sex rates were then ranked to compare Australia with other nations. Results Figures 1-8 show suicide rates over time for sex and 10-year age groups, as well as all ages combined. Males Suicide rates overall and for those aged 15-24 and 25-34 years increased significantly over time (1964-1966 to 1995-1997). The rise in suicide rates from 1973-1997 for men aged 25-34 years was of similar magnitude to the rise for those aged 15-24 years (Figures 2 and 3). Suicide rates in the older age groups (35 to 75 years and over) declined (for men aged 35-44 years and 75 years and over these declines were not statistically significant). Significant autocorrelations (P < 0.01) were found in each age group and for all ages combined. Females Suicide rates overall and for each age group from 25 to 75 years and over declined significantly (1964-1966 to 1995-1997). There was no change in suicide rates for females aged 15-24 years. Significant autocorrelations (P < 0.01) were found for all ages combined and for most age groups (the exceptions were those aged 15-24 years and 75 and over). Years of potential life lost by suicide in 1997 are shown in Box 2. Boxes 3a and 3b list the mean suicide rates (per 100 000 population) by age group and sex for 23 Western nations, including Australia. Discussion The priority accorded to youth suicide prevention by successive Australian governments is supported by our data. In the last three decades, when overall suicide rates were falling, the suicide rate of males 15-24 years more than doubled. Suggestions of a plateauing of this rate since 1989 are not supported by the latest figures for 1997, although it is premature to draw conclusions either way. (It should also be noted that at the time of submission of this article there were significant concerns about the validity of the 1997 suicide rate figures. For example, major rises in rates in New South Wales and Victoria were absent from Queensland -- the next most populous State -- suggesting the possibility of interstate data collection influences.) From a policy perspective, the most important finding is that suicide rate increases since 1973 for men aged 25-34 years have paralleled those of 15-24 year olds, with even less evidence of a recent plateau. Despite having shorter life expectancies, the toll in potential years of life lost (in 1997) was greatest for 25-34 year olds. These years are also the peak years for early parenthood, making the likelihood of there being bereaved offspring greater than in the younger group. These findings suggest that priority initiatives for youth suicide prevention should be extended to those aged 15-34 years, if not further (the high level of potential years of life lost continues to 44 years). The Federal Government's recently announced National Suicide Prevention Policy provides for ages beyond youth, by recognising that rising rates are not confined to the age group 15-24 years and that high suicide rates in the elderly should not be overlooked. It is unclear whether or to what extent the suicide phenomenon in boys and young men might be a cohort effect -- a "damaged" generation. The later commencement of the rise in suicide rate in men aged 25-34 years and the, as yet, absence in this age group of the possible 1990s plateau could be seen as consistent with this. Rates in females aged 15-24 years showed no convincing rise. It has previously been noted that suicide rates in females aged 15-19 years rose modestly between 1960 and 1989, while rates for those aged 20-24 years showed no overall change over this period.10 However, much of the rise in females aged 15-19 years was in the early 1960s, predating the rise in rates of 15-19-year-old males, but coinciding with a general, transient rise in suicide rates in females of all ages. Perhaps the most important observation regarding young females in the present study is that their suicide rates remained relatively static at a time when rates for most other female age groups declined. Suicide rates in children under 15 years of age have not significantly altered over time, although the small numbers involved do not lend confidence to rate estimates. The recording of suicide in children under the age of 10 years is affected by the different criteria used by the Australian Bureau of Statistics for determining suicide: it is considered that children have a limited ability to form an intent to suicide. Hence, more explicit evidence of suicidal intent is required,11 usually a coroner having stated explicitly that suicide was the cause of death. As most State and Territory Coroners' Acts discourage if not prohibit such findings (for all ages), such explicit statements are unlikely.11 Beyond 35 years in women, and 45 years in men, and up to 75 years and over for both sexes, Australian suicide trends are striking. In both sexes there have been major declines, and for much of the period these declining male and female rates have been parallel, quite unlike the trends for 15-24 year olds. It is unclear whether these declining rates have as yet plateaued. Even if this were not the case, it is inevitable that these declining rates will shortly level out and increase again (from the trends over the complete period a number of these age rates would reach zero in the early decades of the next century). In the early 1960s, suicide rates, particularly in women and in older age groups, rose in association with an epidemic of barbiturate poisoning, subsequently to fall in the late 1960s, reaching rates in the early 1970s similar to those before this epidemic.12,13 The causal factors determining the subsequent decline in rates of those between 35 and 74 years are yet to be determined. It is possible that such determination might yield valuable clues as to the causes and possible methods of preventing suicide in young people. International comparisons should be interpreted conservatively, as variations in data collection systems will account for some of the variations. With these reservations in mind, among 23 Western nations, Australian suicide rates for 15-24 year olds ranked fourth for males and eighth for females (Boxes 3a and 3b). Australian rates for both sexes between the ages of 35 and 74 years, as well as declining, compared favourably internationally (ranking in the middle of or below those of other Western nations). Although Australian suicide rates for those over 75 years were not declining, they nevertheless again compared favourably from an international perspective. Whereas the Australian suicide rate for 15-24-year-old males was over half that of the highest-placed nation (Finland), the corresponding ratio for males 75 years and over was about one-sixth. For females, these comparisons were even more marked. Nevertheless, a comprehensive policy should not overlook the needs of men over 75 years, especially as, in Australia, suicide rates in this age group surpass those of all other age groups. The Western nations with lower suicide rates include those that provided most of the early immigrants to Australia: Greece, Italy (except in the elderly), the United Kingdom and Ireland. The highest suicide rates were in mainland Western Europe (especially Hungary) and Scandinavia (especially Finland). Some of these nations, for example Denmark, have profiles radically different from that of Australia, with lower youth suicide rates but much higher rates in those over 35 years of age. Canada and, to a lesser extent, the United States and New Zealand are the nations with suicide rate profiles most similar to Australia's. All four of these nations have common characteristics of European migration, a comparatively short history (apart from their indigenous populations), geographical isolation, climatic extremes and more.10 They serve as potentially valuable nations to study shared characteristics that may affect suicide rates. Studies have yet to provide explanations for these similarities and differences which have often been overlooked, largely as a consequence of the worldwide lack of epidemiological mental health data. While differences in prevalence of psychiatric disorders are potentially relevant, the magnitude of the different international rates suggests other factors may operate. Hungary and Finland share common cultural origins and high suicide rates. It has been suggested that Finland's high suicide rates in young men may relate to cultural expectations that men should be tough and resilient14 -- a suggestion that might be equally relevant in Australia, New Zealand, the United States and Canada. It is possible that a better understanding of cultural influences and how to positively modify them might be relevant to suicide prevention. Acknowledgements The study was funded by Griffith University and Queensland Health through their co-funding of the Australian Institute for Suicide Research and Prevention. We thank the Australian Bureau of Statistics for providing information on suicide and population numbers. References Commonwealth Department of Health and Family Services. Youth suicide in Australia: a background monograph. 2nd edition. Canberra: AGPS, 1997. Snowdon J. Suicide rates and methods in different age groups: Australian data and perceptions. Int J Geriat Psychiatry 1997; 12: 253-258. Hassan R, Carr J. Changing patterns of suicide in Australia. Aust N Z J Psychiatry 1989; 23: 226-234. Australian Bureau of Statistics. Causes of death, Australia, 1996: 73. (Catalogue No. 3303.0.) World Health Organization. World Health Statistics Annual 1992. Geneva: WHO, 1993. World Health Organization. World Health Statistics Annual 1993. Geneva: WHO, 1994. World Health Organization. World Health Statistics Annual 1994. Geneva: WHO, 1995. World Health Organization. World Health Statistics Annual 1995. Geneva: WHO, 1996. Lester D, Yang B. Suicide and homicide in the twentieth century: Changes over time. Commack, NY: Nova Science, 1998: 165-204. Cantor CH, Leenaars AA, Lester D, et al. Suicide trends in eight predominantly English-speaking countries 1960-1989. Soc Psychiatry Psychiatr Epidemiol 1996; 31: 364-373. Cantor CH, Neulinger K, Roth J, Spinks D. The epidemiology of suicide and attempted suicide among young Australians: a report to the National Health and Medical Research Council: Australian Institute for Suicide Research and Prevention. In press. Oliver G, Hetzel BS. An analysis of recent trends in suicide rates in Australia. Int J Epidemiol 1973; 2: 91-101. Whitlock FA. Suicide in Brisbane, 1956-1973: The drug-death epidemic. Med J Aust 1975; 1: 737-743. Retterstol N. Suicide in the Nordic countries. Psychopathology 1992; 25: 254-265. (Received 14 Jan, accepted 7 Jun, 1999) Authors' details Australian Institute for Suicide Research and Prevention, Griffith University, Nathan, QLD. Christopher H Cantor, FRANZCP, MRCPsych, Senior Research Psychiatrist; Kerryn Neulinger, BBehSc, GradDipPsych, Research Assistant; Diego De Leo, MD, PhD, Director. Reprints will not be available from the authors. Correspondence: Dr C H Cantor, Australian Institute for Suicide Research and Prevention, Griffith University, Nathan, QLD 4111. Email: C. CantorATmailbox.gu.edu.au Back to textBack to text Back to text 3a: Mean male suicide rates (per 100000 population) for 23 Western countries by 10-year age groups, 1990-199415-24 yearsFinland 41.4 New Zealand 39.0 Switzerland 25.8 Australia 25.7 Canada 25.2 Norway 24.9 Austria 24.3 USA 21.9 Hungary 20.1 Scotland 19.0 Ireland 18.3 N Ireland 17.6Belgium 15.7 France 15.3 Germany 14.0 Sweden 13.4 Denmark 13.0 Engl/Wales 11.1 Netherlands 9.3 Spain 7.0 Italy 6.1 Portugal 5.8 Greece 4.0 25-34 yearsFinland 60.7 Hungary 54.4 Switzerland 32.7 New Zealand 32.0 France 32.0 Belgium 30.5 Austria 30.3 Australia 29.0 Canada 29.0 Ireland 27.1 Denmark 26.4 Norway 26.1Scotland 26.1 USA 24.6 Sweden 23.9 N Ireland 22.4 Germany 21.3 Engl/Wales 16.3 Netherlands 15.9 Portugal 13.2 Spain 10.6 Italy 10.3 Greece 5.635-44 yearsHungary 82.0 Finland 67.8 France 40.1 Denmark 38.1 Austria 37.2 Belgium 35.6 Switzerland 33.0 Sweden 29.3 Canada 27.3 Norway 26.9 Scotland 26.2 Germany 26.0Australia 25.2 New Zealand 23.9 USA 23.5 Ireland 22.9 Netherlands 17.7 Engl/Wales 17.4 N Ireland 15.5 Portugal 11.8 Italy 10.6 Spain 9.4 Greece 5.945-54 yearsHungary 95.1 Finland 64.1 Denmark 47.5 Austria 41.5 France 40.1 Switzerland 39.8 Belgium 36.2 Sweden 31.9 Germany 31.1 Norway 28.8 Canada 25.6 Scotland 24.2Australia 24.2 New Zealand 24.2 USA 23.1 Ireland 19.6 Netherlands 16.7 Engl/Wales 16.2 N Ireland 15.1 Portugal 14.6 Italy 12.6 Spain 11.9 Greece 6.755-64 yearsHungary 84.6 Finland 57.3 Austria 46.7 Denmark 42.6 Switzerland 41.9 belgium 38.9 France 38.1 Germany 32.2 Sweden 30.7 Norway 28.8 Ireland 25.9 USA 25.0 Canada 24.2 New Zealand 23.2 Australia 22.9 Portugal 21.5 Netherlands 18.6 Scotland 18.1 N Ireland 17.4 Spain 17.4 Italy 17.1 Engl/Wales 12.8 Greece 7.865-74 yearsHungary 92.5 Austria 61.1 Belgium 50.4 Switzerland 47.4 France 47.1 Denmark 46.4 Finland 45.9 Germany 35.9 Sweden 33.7 USA 30.9 Norway 30.7 Portugal 30.1 Australia 24.4 Spain 23.2 Italy 22.9 Canada 22.1 New Zealand 21.2 Netherlands 19.7 Ireland 18.3 Scotland 14.3 N Ireland 12.8 Engl/Wales 11.9 Greece 10.175+ yearsHungary 183.0 Austria 118.0 France 103.0 Belgium 98.6 Switzerland 89.8Germany 86.1 Denmark 74.9 Finland 71.9 Portugal 59.1 USA 55.4Sweden 51.9 Spain 47.8 Italy 44.3 Netherlands 35.4 Australia 32.8 Norway 31.8 New Zealand 29.8 Canada 28.9 Engl/Wales 17.1 Scotland 16.0Greece 15.8 Ireland 13.8 N Ireland 13.3Back to text Appendix: Identifying suicide deaths in Australia11 Coding deaths as suicide relies on an interaction between the Australian Bureau of Statistics (ABS) and State and Territory coroners and government medical officers. The six States and two Territories of Australia each have different Coroners' Acts. Most States and Territories discourage coroners from making formal pronouncements about suicide. Western Australia and New South Wales are the only States that routinely use suicide verdicts. ABS receives information from coroners that is generally sufficient for coding in most cases. Deaths that were in reality suicides, but were not deemed as such by coroners or the ABS, will most likely be coded as undetermined deaths or accidents, and involve similar causes as suicide deaths (eg, poisoning). There has been a rise in both undetermined and accidental deaths in recent years. However, the impact of these uncertainties is unlikely to be sufficient to greatly alter our overall study findings. Back to text 3b: Mean female suicide rates (per 100000 population) for 23 Western countries by 10-year age groups, 1990-199415-24 yearsFinland 7.5 Austria 6.2 Hungary 6.2 New Zealand 6.2 Sweden 5.9 Switzerland 5.8 Norway 5.5 Australia 5.1 Belgium 5.1 Canada 4.9 France 4.5 USA 3.8Netherlands 3.7 Scotland 3.7 Germany 3.5 Denmark 3.3 Ireland 2.5 N Ireland 2.4 Portugal 2.2 Engl/Wales 2.1 Italy 1.8 Spain 1.7 Greece 0.725-34 yearsFinland 12.0 Belgium 11.8 Hungary 11.6 Sweden 10.1 Switzerland 9.0 France 9.0 Scotland 8.3 Austria 8.0 Denmark 7.7 New Zealand 7.3 Netherlands 7.2 Norway 7.1Ireland 6.7 Australia 6.6 Canada 6.4 Germany 5.7 Germany 5.7 N Ireland 3.9 Portugal 3.5 Engl/Wales 3.5 Italy 2.9 Spain 2.6 Greece 1.435-44 yearsHungary 20.3 Finland 17.4 Denmark 15.7 Belgium 14.5 Switzerland 13.5 France 13.0 Austria 12.1 Sweden 11.8 Norway 9.8 Netherlands 9.6 Canada 8.1 Germany 7.7New Zealand 6.9 Scotland 6.8 N Ireland 6.8 Australia 6.6 USA 6.6 Ireland 4.8 Engl/Wales 3.9 Italy 3.9 Portugal 3.8 Spain 3.0 Greece 1.3 45-54 yearsHungary 26.5 Denmark 25.5 Finland 20.4 Belgium 18.2 Austria 17.1 Switzerland 16.7 France 16.5 Sweden 15.0 Germany 12.1 Norway 11.5 Netherlands 9.5 N Ireland 9.4New Zealand 8.9 Canada 8.1 USA 7.3 Scotland 7.2 Australia 7.0 Ireland 6.8 Portugal 5.0 Italy 4.9 Engl/Wales 4.7 Spain 3.9 Greece 2.355-64 yearsDenmark 28.5 Hungary 28.0 Belgium 17.9 France 17.6 Finland 17.5 Austria 17.4 Switzerland 17.0 Sweden 15.4 Germany 12.9 Norway 12.0 Netherlands 10.9 New Zealand 7.7Ireland 7.7 Australia 6.9 USA 6.8 Italy 6.8 Scotland 6.7 Canada 6.4 Portugal 6.2 Spain 6.0 N Ireland 4.8 Engl/Wales 4.7 Greece 2.4 65-74 yearsHungary 37.6 Denmark 31.5 Belgium 23.5 Switzerland 19.8 Austria 18.5 France 17.9 Germany 16.7 Sweden 13.5 Finland 13.3 Norway 12.4 Netherlands 10.4 Spain 8.8Portugal 8.1 Italy 8.0 New Zealand 6.6 Australia 6.6 Ireland 6.4 Scotland 6.4 USA 6.2 Canada 6.1 Engl/Wales 5.2 N Ireland 3.9 Greece 2.875+ yearsHungary 67.3 Denmark 30.2 Austria 28.5 Germany 26.4 France 25.3Belgium 24.2 Switzerland 23.0 Sweden 14.2 Portugal 12.2 Netherlands 12.1Spain 11.9 Finland 9.6 Italy 9.3 Norway 9.2 Australia 8.0Scotland 6.0 USA 6.0 Engl/Wales 5.9 Canada 4.7 New Zealand 4.3 Greece 3.4 Ireland 3.0 N Ireland 2.5Back to text

Christopher H Cantor · Kerryn Neulinger

Viewpoint Vancomycin-resistant enterococci and use of avoparcin in animal feed: is there a link? Australia is unique among Western countries in allowing animal use of this vancomycin-like antibiotic Peter J Collignon MJA 1999; 171: 144-146 See also Ferguson, Robertson et al & Grayson et al. Introduction - What is the evidence that avoparcin use in animals contributes to VRE in humans? - What other factors have a role in amplification and spread of VRE? - How much vancomycin resistance is there in Australia? - Recommendations - Acknowledgments - References - Authors' details - - More articles on Infectious diseases and parasitology Introduction Antibiotics are used in animals to treat and to prevent infections.1,2 They are also used extensively in subtherapeutic doses to promote growth by increasing weight gain and improving feed utilisation. In Australia (as in many other countries), more antibiotics are used on a tonnage basis in animals than in humans.2One such antibiotic is the glycopeptide avoparcin. In Australia, it is registered for use as a growth promoter in chickens, pigs, calves, beef and dairy cattle.3 It is also approved for prophylaxis of necrotic enteritis (caused by Clostridium perfringens) in broiler chickens.3 Glycopeptide antibiotics are also used in human medicine, the two most important being vancomycin and teicoplanin.1 Indeed, these glycopeptides are the only effective therapy currently available for some infections (eg, bacteraemia caused by multiresistant Staphylococcus aureus). They are also important in therapy of serious infections caused by enterococci, antibiotic-resistant pneumococci and coagulase-negative staphylococci.1,4-6 The potential problem with use of avoparcin in animals is that it may lead to selection and amplification of vancomycin-resistant pathogens, such as enterococci. These resistant bacteria may be potentially transferred to humans via the food chain4,6-8 and may cause human disease in appropriate circumstances (eg, abdominal sepsis). More often, the genes encoding vancomycin resistance (especially the transposon Tn1546 which encodes the resistance gene cluster known as "VanA") may be transferred to other strains of enterococci4,9,10 or to other, far more virulent, organisms, such as S. aureus. However, to date, this latter transfer has been observed only in the laboratory.11 Vancomycin-resistant enterococci (VRE) have been frequently reported in Europe and the United States.4,9 Recently, strains of S. aureus with intermediate resistance to vancomycin have been isolated from patients in countries including Japan, France and the US,12,13 although none have been described to date in Australia.12Vancomycin resistance is of major concern to medical practice, as there are no antibiotics currently approved to treat infections caused by most vancomycin-resistant bacteria, which may be life-threatening; a US study found that bacteraemia with VRE was associated with markedly higher death rates than bacteraemia with antibiotic-sensitive strains of enterococci.14 What is the evidence that avoparcin use in animals contributes to VRE in humans? A likely direct link has been shown between avoparcin use in animals and VRE infection in a farm worker with a compound fracture.15 However, it is much more difficult to show that VRE strains are transmitted through the food chain and cause infection in the general population. The evidence comes from observational studies, as it is neither practicable nor ethical to carry out direct experiments in humans, as was the case in trying to demonstrate the link between lung cancer and smoking.16A strong case that avoparcin use in animals is associated with development and amplification of VRE, and that these resistant bacteria may cause infection in humans, needs to show that: VRE are present in animals receiving avoparcin; VRE are more common in animals, farm areas and countries where avoparcin has been used (and rare or absent in areas where it has not been used); VRE are detectable in food products from animals fed avoparcin; and VRE are found in the general community in people who have, or are likely to have, consumed these products. In Europe, unlike Australia, studies have addressed these issues, and all these conditions have been satisfied for VanA VRE, the most common European form. This has led the European Union to ban the use of avoparcin in animals. Requirements 1 and 2: VRE have commonly been found in a wide range of animals on farms that have used avoparcin in Germany and Denmark. For example, VRE made up 0-59% of enterococcal isolates from animals on farms that had used avoparcin,6-8 but were not found in animals on nearby farms not using avoparcin.7 In studies from the US (where avoparcin has never been approved for use) and from Sweden (where its use was discontinued 10 years ago), no VRE were isolated from farm animals.6,8 Requirement 3: VRE have been isolated from many different food products from animals fed avoparcin. For example, in Germany, VRE have been found in 8% of minced beef and pork samples, and in the Netherlands in 79% of poultry products at the retail level.10,17 Requirement 4: In Europe, VRE are widespread among people in the community who have had no association with hospitals. VRE were found in the bowel of 2% to 17% of the general community in countries including the United Kingdom, the Netherlands, Germany and Belgium.7,9 However, when volunteers in Belgium were given oral glycopeptides, VRE were found in more than 60% of those tested.18 As mutation to vancomycin resistance is believed extremely rare -- it is encoded by a very complex cluster of genes6,18 -- it is most likely that these volunteers were already harbouring VRE in very small numbers, which were amplified by the glycopeptides. The most likely explanation for the widespread nature of VRE among people in the community with no association with hospitals is that the organism has been acquired from food.4,7,9 The molecular evidence also strongly suggests that VRE are transmitted from animals to humans, not the reverse.19Although VRE strains display many different phenotypes and genotypes, even in a single patient,6,20 the transposon that encodes the VanA type of vancomycin resistance (Tn1546) is highly conserved. This transposon carries many genes,19 but only a few (vanA, vanH and vanX) are essential for resistance. Characterisation of the transposon from isolates from Europe, the US and the Middle East found only minor variations, and none in the essential genes, except a single base-pair variation (G or T) at one position in the vanX gene.19 All strains of VRE isolated from poultry had a G at this position and nearly all from pigs had a T, but strains from humans included both variants,19 implying that animals were the primary source of the human strains. These findings amount to strong, albeit observational, evidence that animal use of avoparcin in Europe has resulted not only in selection of VRE but, more importantly, its major amplification in animals (particularly VanA strains of VRE).4,6,7,9 These VRE strains may be present on food products distributed throughout Europe and overseas (possibly to the US and Australia). They may then colonise and persist in the human intestine, usually in small numbers, and possibly transfer their resistance to other, more human-adapted, enterococci. What other factors have a role in amplification and spread of VRE? Human medicine has undoubtedly contributed to spread of VRE. If VRE are present in the bowel of any patient, then their numbers will be potentially amplified by use of any glycopeptide or other antibiotics, especially broad-spectrum antibiotics, such as cephalosporins and fluoroquinolones.4,21,22Hospital use of vancomycin appears the major factor in development and spread of VRE in the US, where avoparcin has not been approved for use in animals, but where human use of vancomycin is far greater than in Europe or Australia (11 200 kg in the US, compared with 2200 kg in France, Germany and the UK combined in 199623). In contrast, in Europe, amounts of glycopeptides used in animals before the recent ban far exceeded amounts used in humans. For example, in Denmark, 24 000 kg of avoparcin were used annually in animals in 1994, compared with 24 kg of glycopeptides in humans; in Austria, corresponding figures were 20 000 kg versus 66 kg.24,25 Given this difference and the evidence outlined above, it appears probable that, in Europe, animal use of avoparcin has been a major contributing factor to both development and widespread dissemination of VanA VRE in the community and hospitals. In Australia, as until recently in Europe, animal use of avoparcin greatly exceeds human use of glycopeptides. Between 1991 and 1993, 125 000 kg of avoparcin were used annually, compared with 193 kg of vancomycin in humans.2 Also, Australia has had no obvious centre of VRE development, in contrast to the US, where the first VRE isolates were found in New York and then spread.4 VRE isolates in Australia are sporadic, polyclonal and widely distributed throughout the country; they have been found even in smaller non-metropolitan hospitals, where extensive use of vancomycin is unlikely.26 This suggests that spread of VRE in Australia is likely to be similar to spread in Europe -- through the food chain. Once VRE strains are introduced into a hospital, in a patient's bowel, they and the resistance genes they carry are amplified by antibiotic use, and their dissemination is facilitated by poor infection control. How much vancomycin resistance is there in Australia? Reports of infection caused by VRE are still relatively few in Australia compared with the US and Europe, but numbers appear to be rising.26 VRE strains have appeared independently in diverse locations and are highly polyclonal.26 To August 1998, at least 69 strains or clusters of strains had been detected in patients with VRE infection. However, nearly three times as many strains or clusters were detected by screening contacts or high risk groups.26 The strains causing infection were found in 26 institutions in 10 widely separated cities or regions without any obvious temporal association. They comprised at least 20 distinct types of enterococci (based on species, antibiotic sensitivity and gel electrophoresis patterns). Most of the 69 strains were Enterococcus faecium, with the rest Enterococcus faecalis. In contrast to European VRE strains, most of the Australian strains were positive for the vanB gene rather than the vanA gene (51 vanB versus 15 vanA). Virtually no data are available on how widespread VRE are in animals or the food chain in Australia. It is to be hoped that VRE numbers in animals are still low, as suggested by the only study available, involving 29 farms in New South Wales. Only two isolates of VRE with acquired resistance were found in 197 animals (one vanA and one vanB, both E. faecium).27 Recommendations Approval for use of an antibiotic as a growth promoter or in-feed antibiotic for animals in Australia is supposedly based on the criteria espoused in the 1969 Swann Report from the UK28 (Box). These criteria were recommended after an outbreak of severe human infection caused by antibiotic-resistant salmonella strains derived from animals. Avoparcin does not appear to satisfy at least two of the three criteria, and the evidence that it satisfies the third -- providing economic benefit to Australian agriculture -- is unconvincing: Avoparcin is similar to an important therapeutic antibiotic used in humans -- vancomycin. Use of avoparcin is associated with development of antibiotic resistance that is of importance to humans -- development and spread of VRE. While data indicate that avoparcin confers some benefits, through improved feed conversion and weight gain, these benefits appear greatest in animals that are stressed or subject to poor animal husbandry practices.6 It is hoped that, in Australia, higher standards are generally observed. To my knowledge no double-blind, placebo-controlled trials of the claimed economic and disease-prevention benefits have been published in peer-reviewed journals. Furthermore, many less critical antibiotics than avoparcin (eg, penicillin) would be equally efficacious in treating clostridial infections, for which avoparcin is promoted as prophylaxis. Moreover, these infections can be prevented by changes in animal husbandry practices and feed, without antibiotics.6The European Union has now banned the use of avoparcin because of concerns about development and spread of VRE. In the US, avoparcin was never approved for use, as it was classified as a carcinogen.9 Australia appears unique in the Western world in still allowing use of avoparcin in animals.4,9 At present, it is available without even a prescription from a veterinarian, but "over the counter"! I believe that avoparcin and other glycopeptides should not be available for use in food-producing animals as either growth promoters or for therapy or prophylaxis. I also believe that avoparcin did not fulfil the necessary criteria for approval when first introduced in Australia more than two decades ago. Glycopeptides, which represent the "last line" of defence in treatment of many infections, should not be used at all in food-producing animals. It is time to ban the use of avoparcin in animals in Australia. Acknowledgments I would like to thank the many infectious diseases physicians, microbiologists and scientists who helped in preparation of this paper with their helpful advice and information, particularly Associate Professor Christopher Fairley, Alfred Hospital, Monash University, Melbourne, VIC. References Collignon P. Antibiotic resistance: is it leading to the re-emergence of many infections from the past? In: Asche V, editor. Recent advances in microbiology. Vol 5. Melbourne: Australian Society for Microbiology, 1997: 203-256. Turnidge J, Howard R. Australia's antibiotic burden. Microbiol Aust 1996; 17: 11. Roche Products. Product information for Avotan 100, feed supplement (active constituent: avoparcin 100g/kg). National Registration Authority for Agricultural and Veterinary Chemicals approval no. 45710/01. Sydney: Roche Products. French GL. Enteroccoci and vancomycin resistance. Clin Infect Dis 1998; 27 Suppl 1: S75-S83. Collignon PJ, Bell JM, on behalf of the Australian Group on Antimicrobial Resistance. Drug-resistant Streptococcus pneumoniae: the beginning of the end for many antibiotics? Med J Aust 1996; 164: 64-67. Swedish Commission on Antimicrobial Feed Additives. Antimicrobial feed additives. Stockholm: Ministry of Agriculture, 1997. Witte W. Impact of antibiotic use in animal feeding on resistance of bacterial pathogens in humans. Ciba Found Symp 1997; 207: 61-75. Wegener HC, Aarestrup FM, Bogo Jensen L, et al. Use of antimicrobial growth promoters in food animals and Enterococcus faecium resistance to therapeutic antimicrobial drugs in Europe. Emerg Infect Dis 1999; 5: 329-335. McDonald LC, Kuehnert MJ, Tenover FC, Jarvis WR. Vancomycin-resistant enterococci outside the health-care setting: prevalence, sources, and public health implications. Emerg Infect Dis 1997; 3: 311-317. Van den Braak N, van Belkum A, van Keulen M, et al. Molecular characterization of vancomycin-resistant enterococci from hospitalized patients and poultry products in the Netherlands. J Clin Microbiol 1998; 36: 1927-1932. Noble W, Virani Z, Cree R. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 1992; 72: 195-198. 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. Paterson D. Reduced susceptibility of Staphylococcus aureus to vancomycin -- a review of current knowledge. Commun Dis Intell 1999; 24: 69-73. Edmond MB, Ober JF, Dawson JD, et al. Vancomycin-resistant enterococcal bacteremia: natural history and attributable mortality. Clin Infect Dis 1996; 23: 1234-1239. Das I, Fraise A, Wise R. Are glycopeptide-resistant enterococci in animals a threat to human beings? Lancet 1997; 349: 997-998. Doll R, Peto R. Mortality in relation to smoking: 20 years' observation on male British doctors. BMJ 1976; 2: 1525-1536. Klein G, Pack A, Reuter G. Antibiotic resistance patterns of enterococci and occurrence of vancomycin-resistant enterococci in raw minced beef and pork in Germany. Appl Environ Microbiol 1998; 64: 1825-1830. Van der Auwera P, Pensart N, Korten V, et al. Influence of oral glycopeptides on the fecal flora of human volunteers: selection of highly glycopeptide-resistant enterococci. J Infect Dis 1996; 173: 1129-1136. Jensen LB. Differences in the occurrence of two base pair variants of Tn1546 from vancomycin-resistant enterococci from humans, pigs, and poultry. Antimicrob Agents Chemother 1998; 42: 2463-2464. Schoonmaker D, Bopp L, Baltch A, et al. Genetic analysis of multiple vancomycin-resistant Enterococcus isolates obtained serially from two long-term-care patients. J Clin Microbiol 1998; 36: 2105-2108. Zervos M, Bacon A, Patterson J, et al. Enterococcal superinfection in patients treated with ciprofloxacin. J Antimicrob Chemother 1988; 21: 113-115. Moellering R. Enterococcal infections in patients treated with moxalactam. Rev Infect Dis 1982; 4 Suppl: S708-S711. Kirst H, Thompson D, Nicas T. Historical yearly usage of vancomycin. Antimicrob Agents Chemother 1998; 42: 1303-1304. Witte W. Medical consequences of antibiotic use in agriculture. Science 1998; 279: 996-997. Allerberger F, Lass-Florl C, Dierich MP, et al. Vancomycin resistant enterococci in Austria. [Original title: Vancomycin resistente Enterokokken in Osterreich.] Wien Klin Wochenschr 1997; 109: 312-320. Bell J, Turnidge J, Coombs G, O'Brien F. Emergence and epidemiology of vancomycin-resistant enterococci in Australia. Commun Dis Intell 1998; 22: 249-252. Butt H, Bell J, Ferguson J. Are vancomycin-resistant enterococci prevalent in Hunter region farm animals? Abstracts of the Australian Society for Microbiology Annual Conference; 1997 29 Sep - 3 Oct; Adelaide, SA. Microbiol Aust 1997; 18(4): abstract PO4.8. Joint Committee of Houses of Parliament. Report on the use of antibiotics in animal husbandry and veterinary medicine ("Swann Report"). London: HMSO, 1969, reprinted 1971. Authors' details Departments of Infectious Diseases and Microbiology, Canberra Hospital, University of Sydney, Canberra, ACT. Peter J Collignon, FRACP, FRCPA, Clinical Associate Professor, Canberra Clinical School. Reprints will not be available from the author. Correspondence: Professor P J Collignon, Departments of Infectious Diseases and Microbiology, Canberra Hospital, PO Box 11, Woden, ACT 2606. Email: peter_collignonATdpa.act.gov.au Recommendations on use of antibiotics in animal husbandry and veterinary medicine in the United Kingdom (from the Swann Report28) Permission to supply and use an antibiotic without prescription for adding to animal feed should be restricted to antibiotics which: Have little or no application as therapeutic agents in man or animals; Will not impair the efficiency of prescribed therapeutic antibiotic(s) through development of resistant strains of organisms; and Are of economic value in livestock production under UK farming conditions. Back to text

Peter J Collignon

Letter Rethinking the early childcare agenda MJA 1999; 171: 166-167 To the Editor: We are concerned that Cook's article1 lacks a balanced review of the literature on childcare, being biased in its portrayal of the possible negative effects without consideration of the likely positive ones. This could have detrimental consequences for the many children in formal childcare in Australia, their parents, and the staff and others involved in what is now an integral and vital component of Australian society. Cook's article also draws strongly on overseas studies, although childcare systems in Australia are likely to be different from those in other countries. Positive health outcomes for children attending childcare include the detection of vision and hearing problems, higher vaccination rates, appropriate nutrition, the detection of child abuse and neglect, primary health and dental care, psychosocial benefits, and opportunities for health promotion.2 The issue of socioemotional development, including attachment theory, has been debated in the literature. Cook cites Belsky, but Belsky has been noted as often citing research that did not take into account the specific characteristics and quality of care.3 It is probable that social and cognitive development are related to quality of care, and Caldwell's study suggests that childcare may provide better quality of care, at least for cognitive development, than home care.4 Thus, childcare does not appear to be consistently detrimental to cognitive and language development and may have a positive influence.4 The investigation of the influence of childcare on children's development is complex and should be considered in interpreting such research. Harvey,5 in an extensive longitudinal study, found that parental employment had "minimal effects on children's later functioning", and that increased early parental income could positively affect childhood development. We do agree with Cook that increased flexibility for working parents should be encouraged. Flexible options, such as parental leave and part-time work for parents of young children, are often advantageous. In addition to increasing work options for parents, it is important that we strive for high quality childcare, subsidised if necessary, so that all families have the choice of providing such care for their children. Linda M Slack-Smith Senior Lecturer, School of Oral Health Sciences 179 Wellington Street, Perth, WA 6000 lindasATcyllene.uwa.edu.au Anne W Read Senior Research Officer, Division of Psychosocial Research TVW Telethon Institute for Child Health Research, Perth Stephen R Zubrick Associate Professor, and Head, Division of Psychosocial Research TVW Telethon Institute for Child Health Research, Perth Cook P. Rethinking the early childcare agenda. Med J Aust 1999; 170: 29-31. Andersson B. Children's development related to day-care, type of family and other home factors. Eur Child Adolesc Psychiatry 1996; 5: 73-75. Melhuish E, Moss P. Current and future issues in policy and research. In: Melhuish E, Moss P, editors. Day care for young children. London: Tavistock/Routledge, 1991: 225. Caldwell B. Impact of day care on the child. Pediatrics 1993; 91(1 Pt 2): 225-228. Harvey E. Short-term and long-term effects of early parental employment on children of the National Longitudinal Survey of Youth. Dev Psychol 1999; 35: 445-459. In reply: A literature review was beyond my purpose, but I summarised findings of a major meta-analysis, and explained why psychological outcomes are of most concern. Benefits of childcare are often publicised, but risks, proven or probable, should not be concealed from parents and policy-makers.1 Notwithstanding the 1971 New South Wales child psychiatrists' memorandum,2 it became politically incorrect to express concerns about childcare. In social sciences, the now-discredited ideology of cultural determinism prevailed, denying the relevance of evolutionary biology to human behaviour, even mothering. A pro-childcare "spin" has pervaded research reports. Slack-Smith and colleagues' statement that "childcare does not appear to be consistently detrimental to cognitive and language development . . ." is a typical childcare-advocacy "straw man". The reply is: nobody said it was! Ochiltree's review3 seemed to me to have eight such statements within five paragraphs, and was so "unbalanced" that I wrote a book,1 to which I refer readers. It covers the points made by Slack-Smith et al, which cannot be answered in a few words. Childcare advocates seldom acknowledge that "high quality childcare" is not reliably achievable. They quote overseas studies when favourable, but, when not, they claim Australian childcare is of higher quality.3 But one carer to five infants is "nobody's definition of quality".4 I argue that the early childcare agenda is misconceived and needs rethinking. Qualitatively better outcomes should be achievable without the associated risks.1,5,6 Peter S Cook Child Psychiatrist (retired) PO Box 84, Repton, NSW 2454 Cook PS. Early child care -- infants and nations at risk. Melbourne: News Weekly Books, 1997. New South Wales Branch of the Child Psychiatry Section of the Australian and New Zealand College of Psychiatrists. Memorandum on some aspects of the welfare of children aged under three years whose mothers are in full-time employment. Med J Aust 1971; 1: 446-448. Ochiltree G. Effects of child care on young children: forty years of research. Melbourne: Australian Institute of Family Studies, 1994: 65-66. (Early Childhood Study Paper No. 5.) Hope D. Spare the non-maternal care and nurture the child. The Australian 1998; June 4. Cook PS. Home truths absent in early childcare debate: we need parent-friendly options [opinion]. The Australian 1999; March 24. Cook PS. The role of myth in childcare policy [letter]. The Australian 1999; April 14. ª 1999 Medical Journal of Australia.