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Background: Accurate and timely diagnosis is critical in providing prognostic information and guiding treatment in acutely unwell patients with suspected monogenic disorders. Aim(s): We describe the development and implementation of a rapid genomic diagnosis program in a routine clinical setting. Method(s): Rapid singleton wholeexome sequencing was performed in acutely unwell patients with suspected monogenic disorders from two pediatric tertiary centers. Technical, organizational, and clinician barriers to implementation were addressed through a cycle of continuous audit and improvement. Service performance parameters and the diagnostic and clinical utility of providing rapid WES were assessed. Result(s): During the study period, time to result reduced from 109 days to 13 days (median 18 days), and this was accompanied by changes in referral and test initiation patterns. Of 26 enrolled patients, 14 (54%) received a molecular genetic diagnosis. Clinical management changed in nine diagnosed patients (64%), including the provision of lifesaving treatment, avoidance of invasive biopsies, and palliative care guidance. A result was provided prior to death or discharge from hospital in 16 of 26 cases (62%). The rapid diagnosis of a riboflavin transporter defect in one patient is estimated to have saved 113 days in intensive care (AUD$508,500) compared to providing the result with a standard turnaround time. Discussion(s): The provision of rapid genomic results in acutely unwell patients with suspected monogenic disorders is feasible in the routine clinical setting and has high diagnostic and clinical utility. It challenges traditional clinical and laboratory genetics service models, and requires a whole-of-system approach for successful implementation.

Introduction: ICU patients are at higher risk of becoming colonised or infected with antibiotic resistant micro-organisms such as Methicillin Resistant Staphylococcus (MRSA) and Vancomycin Resistant Enterococcus (VRE). Transmission-based contact precautions and correct hand hygiene practices are designed to minimise the transmission of such micro-organisms.Through direct observation and routine auditing in a metropolitan Level II ICU it was observed that compliance to both Transmission-based contact precautions and correct hand hygiene associated with glove use, was poor. This has led to a Quality project aimed at improving this compliance and minimising the transmission of antibiotic resistant micro-organisms. Method(s): For a period of 6 months the routine use of long sleeve impervious gowns and gloves on entering the room or bedspace of a patient isolated in Transmission based Contact Precautions for MRSA and VRE was replaced with disposable plastic aprons and gloves for direct patient contact only. Changes were also made to when staff could enter a room or bedspace without PPE. All patients admitted to the ICU colonised or infected with MRSA or VRE during the trial period were cared for with these modified contact precautions. Result(s): Results included an overall trend downward in transmissions when adjusted for bed days, increased compliance with both hand hygiene associated with glove use and contact precautions. Increased staff satisfaction and patient outcomes, a decrease in the production of waste and cost savings. This has led to a sustained practice change which has been supported by both the Infection Control and Infectious Diseases Departments.

Introduction: ICU patients are at higher risk of becoming colonised or infected with antibiotic resistant micro-organisms such as Methicillin Resistant Staphylococcus (MRSA) and Vancomycin Resistant Enterococcus (VRE). Transmission-based contact precautions and correct hand hygiene practices are designed to minimise the transmission of such micro-organisms.Through direct observation and routine auditing in a metropolitan Level II ICU it was observed that compliance to both Transmission-based contact precautions and correct hand hygiene associated with glove use, was poor. This has led to a Quality project aimed at improving this compliance and minimising the transmission of antibiotic resistant micro-organisms. Method(s): For a period of 6 months the routine use of long sleeve impervious gowns and gloves on entering the room or bedspace of a patient isolated in Transmission based Contact Precautions for MRSA and VRE was replaced with disposable plastic aprons and gloves for direct patient contact only. Changes were also made to when staff could enter a room or bedspace without PPE. All patients admitted to the ICU colonised or infected with MRSA or VRE during the trial period were cared for with these modified contact precautions. Result(s): Results included an overall trend downward in transmissions when adjusted for bed days, increased compliance with both hand hygiene associated with glove use and contact precautions. Increased staff satisfaction and patient outcomes, a decrease in the production of waste and cost savings. This has led to a sustained practice change which has been supported by both the Infection Control and Infectious Diseases Departments.

Nursing homes represent a unique and important methicillin-resistant Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from hospitals and the community, strains can be transported back into these settings from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet relatively poorly studied in this setting, a multicenter, regional assessment of the frequency and diversity of MRSA in the nursing home reservoir was carried out and compared to that of the MRSA from hospitals in the same region. The prospective study collected MRSA from nasal swabbing of residents of 26 nursing homes in Orange County, California, and characterized each isolate by spa typing. A total of 837 MRSA isolates were collected from the nursing homes. Estimates of admission prevalence and point prevalence of MRSA were 16% and 26%, respectively. The spa type genetic diversity was heterogeneous between nursing homes and significantly higher overall (77%) than the diversity in Orange County hospitals (72%). MRSA burden in nursing homes appears largely due to importation from hospitals. As seen in Orange County hospitals, USA300 (sequence type 8 [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant MRSA clones in Orange County nursing homes, representing 83% of all isolates, although the USA100 variant was predominant in nursing homes, whereas USA300 was predominant in hospitals. Control strategies tailored to the complex problem of MRSA transmission and infection in nursing homes are needed in order to minimize the impact of this unique reservoir on the overall regional MRSA burden.

Nursing homes represent a unique and important methicillin-resistant Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from hospitals and the community, strains can be transported back into these settings from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet relatively poorly studied in this setting, a multicenter, regional assessment of the frequency and diversity of MRSA in the nursing home reservoir was carried out and compared to that of the MRSA from hospitals in the same region. The prospective study collected MRSA from nasal swabbing of residents of 26 nursing homes in Orange County, California, and characterized each isolate by spa typing. A total of 837 MRSA isolates were collected from the nursing homes. Estimates of admission prevalence and point prevalence of MRSA were 16% and 26%, respectively. The spa type genetic diversity was heterogeneous between nursing homes and significantly higher overall (77%) than the diversity in Orange County hospitals (72%). MRSA burden in nursing homes appears largely due to importation from hospitals. As seen in Orange County hospitals, USA300 (sequence type 8 [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant MRSA clones in Orange County nursing homes, representing 83% of all isolates, although the USA100 variant was predominant in nursing homes, whereas USA300 was predominant in hospitals. Control strategies tailored to the complex problem of MRSA transmission and infection in nursing homes are needed in order to minimize the impact of this unique reservoir on the overall regional MRSA burden.

A clonal strain of Pseudomonas aeruginosa (PA) was isolated in 1999 at the Royal Children's Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged <5 yrs. Subsequently, more than half of the patients in the clinic with PA were found to harbour this strain, and segregation measures were instituted at the hospital to prevent further spread. The aim of this study was to assess CF parent and patient responses to the segregation measures to determine overall support. A questionnaire was sent out to the families of 291 CF children treated at the centre. A 65% response rate was obtained. The majority of parents (85%) and patients >=12 yrs old (63%) were positive about the segregation measures instituted. A total of 11% of parents and 25% of patients were unsure, and 4% of parents and 12% of children gave negative responses. Those who were not happy listed reasons such as concerns about the emotional impact of not socialising with other CF children, inconclusive evidence about person-person spread of infection and feelings of alienation created in the clinic by the separation. In conclusion, the majority of responding cystic fibrosis patients and their families understand and are supportive of infection control measures instituted at the Royal Children's Hospital, Melbourne, Australia. © ERS Journals Ltd 2004.

The efficacy and safety of continuous infusion flucloxacillin as home-based treatment was assessed in 62 consecutive patients with proven serious methicillin-susceptible Staphylococcus aureus (MSSA) infections (n = 36) and cellulitis (n = 26). The treatment was well tolerated and resulted in cure or adequate suppression of infection in 27 of 28 (96%) patients in the serious MSSA infection group, and in 24 of 26 (92%) patients in the cellulitis group.

Introduction: There is a wide range of bacterial causes for childhood empyema worldwide; however the bacterial causes in Australia are unknown. The 7-valent conjugate pneumococcal vaccine (7vPCV) was added to the national immunisation program in Australia in 2005. Aim(s): To determine the causative bacterial pathogens and pneumococcal serotypes of childhood empyema in Australia, and the efficacy of the 7vPCV. Method(s): A research network comprising all 13 major paediatric hospitals in Australia recruited empyema patients over a 2 year period. Blood and pleural fluid underwent standard culture. Additionally all pleural fluid underwent polymerase chain reaction (PCR) to identify Streptococcus pneumoniae (SP) - targeting autolysin (lytA), Haemophilus influenzae (HI), Mycoplasma pneumoniae, Chlamydia pneumoniae, Staphylococcus aureus (SA) and methicillin-resistant SA (MRSA). All SP PCR-positive specimens were tested using multiplex PCR reverse line blot assays to identify individual, or groups of related serotypes. Result(s): 143 children, 81 male, median age 4.9 (range 0.4-15.5) years were recruited. of 124 blood cultures; 27 (21.8%) were positive as follows: SP, n=16 (59.3%); Streptococcus pyogenes, n=2 (7.4%); coagulase-negative staphylococcus n=3 (11.1%); Neisseria meningitidis, n=1 (3.7%); HI, n=1 (3.7%); MRSA, n=1 (3.7%); Streptococcus sanguinis, n=1 (3.7%); Actinomyces naeslundii, n=1 (3.7%). Two bacteria were isolated from one patient: Staphylococcus hominis (3.7%) and SA (3.7%). Forty seven (33.6%) of 140 pleural fluid samples were culture positive: S. pyogenes, n=14 (29.8%); SP, n=10 (21.3%); SA, n=9 (19.1%); MRSA, n=5 (10.6%); Streptococcus milleri, n=3 (6.4%); coagulase-negative staphylococcus, n=2 (4.3%); Pseudomonas aeruginosa, n=1 (2.1%); Mycobacterium tuberculosis, n=1 (2.1%); Staphylococcus cohnii, n=1 (2.1%); Bacillus cereus, n=1 (2.1%).Two or more organisms were isolated from two subjects; one with MRSA and SA and one with Eikenella corrodens (2.1%)

Objective: To document the types of, and mortality from, Staphylococcus aureus bacteraemia in Australia and New Zealand, and determine factors associated with mortality. Design and setting: Prospective observational study in 27 independent or hospital pathology laboratories in Australia (24) and New Zealand (3), employing a web-based database to prospectively record demographic features, selected risk factors, principal antibiotic treatment and mortality data on all patients with positive blood cultures for S. aureus from June 2007 to May 2008. Main Outcome Measure(s): 30-day all-cause mortality. Result(s): 1994 episodes of S. aureus bacteraemia were identified, and complete 30-day follow-up data were available for 1865. Most episodes had their onset in the community (60.8%; 95% CI, 58.7%-63.0%). Methicillin-resistant S. aureus (MRSA) caused 450 episodes (24.1%; 95% CI, 22.2%-25.9%), and 123 of these (27.3%) had a susceptibility profile consistent with community-associated MRSA. All-cause mortality at 30 days was 20.6% (95% CI, 18.8%-22.5%). On univariate analysis, increased mortality was significantly associated with older age, European ethnicity, MRSA infection, infections not originating from a medical device, sepsis syndrome, pneumonia/empyema, and treatment with a glycopeptide or other non-beta-lactam antibiotic. On multivariable analysis, independent predictors of mortality were age, sepsis syndrome, pneumonia/empyema, device-associated infection with a secondary focus, left-sided endocarditis, and treatment with a glycopeptide such as vancomycin, but not MRSA infection. Conclusion(s): S. aureus bacteraemia is a common infection in both the community and hospitals in Australia and New Zealand, and is associated with appreciable mortality. Invasive MRSA infection may be more life-threatening, partly because of the inferior efficacy of the standard treatment, vancomycin. National web-based surveillance of S. aureus bacteraemia and its outcomes is not only import

Background. There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range. Methods. We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB. Results. We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 mug/mL, compared with thosewith lower MIC isolates (26.8% vs 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, butmethicillin resistance and antibiotic choice were not. Conclusions. We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Since the discovery of penicillin, bacteria have counteracted the action of antibiotics leading to a worrisome situation about antibiotic efficiency. During our research on non-traditional 1,3-bridged β-lactams embedded into macrocycles as potential inhibitors of Penicillin Binding Proteins (PBPs), we unexpectedly synthesized bis-2-oxoazetidinyl macrocycles arising from a dimerization reaction under ring closing metathesis (RCM) conditions. These molecules were revealed to be good inhibitors of the d,d-peptidase from Actinomadura R39, which is commonly used as a model of PBPs. To pursue the research on this type of novel compounds, a complete family of cyclodimers 4 and 5 was synthesized and evaluated against R39, and high molecular weight d,d-peptidases: PBP2a of methicillin-resistant Staphylococcus aureus and PBP5 of resistant Enterococcus faecium. Some bis-2-oxoazetidinyl macrocycles exhibited very promising activities against PBP2a. In order to explain the biological results, docking experiments of one cyclodimer (5e) into the R39 and PBP2a crystallographic structures were performed. The 3D structures of all the dimers were studied by quantum chemistry calculations and the reactivity of one cyclodimer (5e) was evaluated using an elaborate model of the R39 active site. Our results highlighted that the activity of the compounds is most probably related to their conformational adaptability, depending on the size of the macrocycles and the geometrical constraints induced by intramolecular H bonds. © 2012 The Royal Society of Chemistry.

Since the discovery of penicillin, bacteria have counteracted the action of antibiotics leading to a worrisome situation about antibiotic efficiency. During our research on non-traditional 1,3-bridged β-lactams embedded into macrocycles as potential inhibitors of Penicillin Binding Proteins (PBPs), we unexpectedly synthesized bis-2-oxoazetidinyl macrocycles arising from a dimerization reaction under ring closing metathesis (RCM) conditions. These molecules were revealed to be good inhibitors of the d,d-peptidase from Actinomadura R39, which is commonly used as a model of PBPs. To pursue the research on this type of novel compounds, a complete family of cyclodimers 4 and 5 was synthesized and evaluated against R39, and high molecular weight d,d-peptidases: PBP2a of methicillin-resistant Staphylococcus aureus and PBP5 of resistant Enterococcus faecium. Some bis-2-oxoazetidinyl macrocycles exhibited very promising activities against PBP2a. In order to explain the biological results, docking experiments of one cyclodimer (5e) into the R39 and PBP2a crystallographic structures were performed. The 3D structures of all the dimers were studied by quantum chemistry calculations and the reactivity of one cyclodimer (5e) was evaluated using an elaborate model of the R39 active site. Our results highlighted that the activity of the compounds is most probably related to their conformational adaptability, depending on the size of the macrocycles and the geometrical constraints induced by intramolecular H bonds. © 2012 The Royal Society of Chemistry.

A clonal strain of Pseudomonas aeruginosa (PA) was isolated in 1999 at the Royal Children's Hospital, Melbourne, Australia, after five unrelated children with cystic fibrosis (CF) died from severe lung disease aged <5 yrs. Subsequently, more than half of the patients in the clinic with PA were found to harbour this strain, and segregation measures were instituted at the hospital to prevent further spread. The aim of this study was to assess CF parent and patient responses to the segregation measures to determine overall support. A questionnaire was sent out to the families of 291 CF children treated at the centre. A 65% response rate was obtained. The majority of parents (85%) and patients >=12 yrs old (63%) were positive about the segregation measures instituted. A total of 11% of parents and 25% of patients were unsure, and 4% of parents and 12% of children gave negative responses. Those who were not happy listed reasons such as concerns about the emotional impact of not socialising with other CF children, inconclusive evidence about person-person spread of infection and feelings of alienation created in the clinic by the separation. In conclusion, the majority of responding cystic fibrosis patients and their families understand and are supportive of infection control measures instituted at the Royal Children's Hospital, Melbourne, Australia. © ERS Journals Ltd 2004.

The efficacy and safety of continuous infusion flucloxacillin as home-based treatment was assessed in 62 consecutive patients with proven serious methicillin-susceptible Staphylococcus aureus (MSSA) infections (n = 36) and cellulitis (n = 26). The treatment was well tolerated and resulted in cure or adequate suppression of infection in 27 of 28 (96%) patients in the serious MSSA infection group, and in 24 of 26 (92%) patients in the cellulitis group.

There is minimal published longitudinal data about pathogenic microorganisms in adults with bronchiectasis. Therefore a study was undertaken to assess the microbiologic profile over time in bronchiectasis. A prospective study of clinical and microbiologic outcomes was performed. Subjects were assessed by a respiratory physician and sputum sample were collected for analysis. Subjects were followed up and had repeat assessment performed. Eighty-nine subjects were followed up for a period of 5.7+/-3.6 years. On initial assessment the two most common pathogens isolated were Haemophilus influenzae (47%) and Pseudomonas aeruginosa (12%) whilst 21% had no pathogens isolated. On follow-up review results were similar (40% H. influenzae, 18% P. aeruginosa and 26% no pathogens). The prevalence of antibiotic resistance of isolates increased from 13% to 30%. Analysis of a series of H. influenzae isolates showed they were nearly all nontypeable and all were different subtypes. Subjects with no pathogens isolated from their sputum had the mildest disease, while subjects with P. aeruginosa had the most severe bronchiectasis. Many subjects with bronchiectasis are colonized with the same bacterium over an average follow-up of 5 years. Different pathogens are associated with different patterns of clinical disease. © 2007 Elsevier Ltd. All rights reserved.

Introduction: There is a wide range of bacterial causes for childhood empyema worldwide; however the bacterial causes in Australia are unknown. The 7-valent conjugate pneumococcal vaccine (7vPCV) was added to the national immunisation program in Australia in 2005. Aim(s): To determine the causative bacterial pathogens and pneumococcal serotypes of childhood empyema in Australia, and the efficacy of the 7vPCV. Method(s): A research network comprising all 13 major paediatric hospitals in Australia recruited empyema patients over a 2 year period. Blood and pleural fluid underwent standard culture. Additionally all pleural fluid underwent polymerase chain reaction (PCR) to identify Streptococcus pneumoniae (SP) - targeting autolysin (lytA), Haemophilus influenzae (HI), Mycoplasma pneumoniae, Chlamydia pneumoniae, Staphylococcus aureus (SA) and methicillin-resistant SA (MRSA). All SP PCR-positive specimens were tested using multiplex PCR reverse line blot assays to identify individual, or groups of related serotypes. Result(s): 143 children, 81 male, median age 4.9 (range 0.4-15.5) years were recruited. of 124 blood cultures; 27 (21.8%) were positive as follows: SP, n=16 (59.3%); Streptococcus pyogenes, n=2 (7.4%); coagulase-negative staphylococcus n=3 (11.1%); Neisseria meningitidis, n=1 (3.7%); HI, n=1 (3.7%); MRSA, n=1 (3.7%); Streptococcus sanguinis, n=1 (3.7%); Actinomyces naeslundii, n=1 (3.7%). Two bacteria were isolated from one patient: Staphylococcus hominis (3.7%) and SA (3.7%). Forty seven (33.6%) of 140 pleural fluid samples were culture positive: S. pyogenes, n=14 (29.8%); SP, n=10 (21.3%); SA, n=9 (19.1%); MRSA, n=5 (10.6%); Streptococcus milleri, n=3 (6.4%); coagulase-negative staphylococcus, n=2 (4.3%); Pseudomonas aeruginosa, n=1 (2.1%); Mycobacterium tuberculosis, n=1 (2.1%); Staphylococcus cohnii, n=1 (2.1%); Bacillus cereus, n=1 (2.1%).Two or more organisms were isolated from two subjects; one with MRSA and SA and one with Eikenella corrodens (2.1%)

Objective: To document the types of, and mortality from, Staphylococcus aureus bacteraemia in Australia and New Zealand, and determine factors associated with mortality. Design and setting: Prospective observational study in 27 independent or hospital pathology laboratories in Australia (24) and New Zealand (3), employing a web-based database to prospectively record demographic features, selected risk factors, principal antibiotic treatment and mortality data on all patients with positive blood cultures for S. aureus from June 2007 to May 2008. Main Outcome Measure(s): 30-day all-cause mortality. Result(s): 1994 episodes of S. aureus bacteraemia were identified, and complete 30-day follow-up data were available for 1865. Most episodes had their onset in the community (60.8%; 95% CI, 58.7%-63.0%). Methicillin-resistant S. aureus (MRSA) caused 450 episodes (24.1%; 95% CI, 22.2%-25.9%), and 123 of these (27.3%) had a susceptibility profile consistent with community-associated MRSA. All-cause mortality at 30 days was 20.6% (95% CI, 18.8%-22.5%). On univariate analysis, increased mortality was significantly associated with older age, European ethnicity, MRSA infection, infections not originating from a medical device, sepsis syndrome, pneumonia/empyema, and treatment with a glycopeptide or other non-beta-lactam antibiotic. On multivariable analysis, independent predictors of mortality were age, sepsis syndrome, pneumonia/empyema, device-associated infection with a secondary focus, left-sided endocarditis, and treatment with a glycopeptide such as vancomycin, but not MRSA infection. Conclusion(s): S. aureus bacteraemia is a common infection in both the community and hospitals in Australia and New Zealand, and is associated with appreciable mortality. Invasive MRSA infection may be more life-threatening, partly because of the inferior efficacy of the standard treatment, vancomycin. National web-based surveillance of S. aureus bacteraemia and its outcomes is not only import

Background. There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range. Methods. We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB. Results. We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 mug/mL, compared with thosewith lower MIC isolates (26.8% vs 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, butmethicillin resistance and antibiotic choice were not. Conclusions. We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

New insights concerning methicillin-resistant Staphylococcus aureus disease

Recent efforts to combat infections have focused on pharmaceutical interventions. However, the global spread of antimicrobial resistance calls for the reappraisal of personal and institutional hygiene. Hygiene embodies behavioural and procedural rules that prevent bacterial transmission. Consequently, the chance of spreading bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is significantly reduced. Hygiene is part of the primacy and totality of patient care, ensuring that no harm is done. Any prevention and control strategy must be underpinned by changes in attitude, embraced by all. The major components of preventing and controlling MRSA include hand and environmental hygiene (as part of standard precautions), patient isolation, and patient/staff decolonization. Improving hand hygiene practice is especially important where the risk of infection is highest, e.g. in intensive care. Physical isolation has two advantages: the physical barrier interrupts transmission, and this barrier emphasizes that precautions are required. With limited isolation facilities, risk assessment should be conducted to indicate which patients should be isolated. Environmental hygiene, although important, has a lower priority than standard precautions. When a patient is ready for discharge (home) or transfer (to another healthcare facility), the overall interests of the patient should take priority. All patients should be informed of their MRSA-positive status as soon as possible. Because of increased mupirocin resistance, a selective approach to decolonization should be taken. When MRSA-positive staff are identified, restricting their professional activity will depend on the nature of their work. Finally, politicians and others need to commit to providing the necessary resources to maximize MRSA prevention and control.

The assessment of MDRO infection and colonization should include the identification of known carriers, the detection of hospital-specific and healthcare-associated acquisition, an estimation of the burden of serious infection, an understanding of the reservoir affecting the transmission of MDROs, and an evaluation of the effect of intervention. Several strategies can be used to obtain data that aid in this assessment. We have defined and categorized the recommended metrics for each of these aspects of measuring MDRO infection and colonization, for use by healthcare facilities. © 2008 by The Society for Healthcare Epidemiology of America. All rights reserved.

BackgroundPatients with newly acquired methicillin-resistant Staphylococcus aureus (MRSA) have significant risks of short-term morbidity and mortality due to this pathogen. We were interested in assessing whether long-term carriers have persistent risks of disease and whether all carriers, regardless of the duration of carriage, should be considered to be reasonable candidates for interventions to reduce the risk of infection.MethodsWe conducted a single-center retrospective cohort study to evaluate the risk of subsequent MRSA infection and death among patients known to have harbored MRSA for at least 1 year (i.e., prevalent carriers).ResultsAmong 281 prevalent carriers, 65 (23%) developed a total of 96 discrete and unrelated MRSA infections in the year after their identification as prevalent carriers. The most common infections were pneumonia (accounting for 39% of MRSA infections), soft-tissue infection (14%), and central venous catheter infection (14%). Twenty-four percent of all infections involved bacteremia. Thirty-eight MRSA infections occurred during a new hospitalization, and 32 (84%) of these infections were the reason for admission to the hospital. MRSA contributed to 14 deaths, with 6 of these deaths deemed to be attributable to MRSA. Harboring MRSA for <2 years and MRSA colonization at the time of detection as a prevalent carrier were predictive of subsequent infection with MRSA.ConclusionsIndividuals who are known to have harbored MRSA for >1 year are at high risk for subsequent MRSA morbidity and mortality and should be considered to be targets for intervention, in addition to individuals who have newly acquired this pathogen.

BackgroundPatients with newly acquired methicillin-resistant Staphylococcus aureus (MRSA) have significant risks of short-term morbidity and mortality due to this pathogen. We were interested in assessing whether long-term carriers have persistent risks of disease and whether all carriers, regardless of the duration of carriage, should be considered to be reasonable candidates for interventions to reduce the risk of infection.MethodsWe conducted a single-center retrospective cohort study to evaluate the risk of subsequent MRSA infection and death among patients known to have harbored MRSA for at least 1 year (i.e., prevalent carriers).ResultsAmong 281 prevalent carriers, 65 (23%) developed a total of 96 discrete and unrelated MRSA infections in the year after their identification as prevalent carriers. The most common infections were pneumonia (accounting for 39% of MRSA infections), soft-tissue infection (14%), and central venous catheter infection (14%). Twenty-four percent of all infections involved bacteremia. Thirty-eight MRSA infections occurred during a new hospitalization, and 32 (84%) of these infections were the reason for admission to the hospital. MRSA contributed to 14 deaths, with 6 of these deaths deemed to be attributable to MRSA. Harboring MRSA for <2 years and MRSA colonization at the time of detection as a prevalent carrier were predictive of subsequent infection with MRSA.ConclusionsIndividuals who are known to have harbored MRSA for >1 year are at high risk for subsequent MRSA morbidity and mortality and should be considered to be targets for intervention, in addition to individuals who have newly acquired this pathogen.

BackgroundPatients with newly acquired methicillin-resistant Staphylococcus aureus (MRSA) have significant risks of short-term morbidity and mortality due to this pathogen. We were interested in assessing whether long-term carriers have persistent risks of disease and whether all carriers, regardless of the duration of carriage, should be considered to be reasonable candidates for interventions to reduce the risk of infection.MethodsWe conducted a single-center retrospective cohort study to evaluate the risk of subsequent MRSA infection and death among patients known to have harbored MRSA for at least 1 year (i.e., prevalent carriers).ResultsAmong 281 prevalent carriers, 65 (23%) developed a total of 96 discrete and unrelated MRSA infections in the year after their identification as prevalent carriers. The most common infections were pneumonia (accounting for 39% of MRSA infections), soft-tissue infection (14%), and central venous catheter infection (14%). Twenty-four percent of all infections involved bacteremia. Thirty-eight MRSA infections occurred during a new hospitalization, and 32 (84%) of these infections were the reason for admission to the hospital. MRSA contributed to 14 deaths, with 6 of these deaths deemed to be attributable to MRSA. Harboring MRSA for <2 years and MRSA colonization at the time of detection as a prevalent carrier were predictive of subsequent infection with MRSA.ConclusionsIndividuals who are known to have harbored MRSA for >1 year are at high risk for subsequent MRSA morbidity and mortality and should be considered to be targets for intervention, in addition to individuals who have newly acquired this pathogen.

The assessment of MDRO infection and colonization should include the identification of known carriers, the detection of hospital-specific and healthcare-associated acquisition, an estimation of the burden of serious infection, an understanding of the reservoir affecting the transmission of MDROs, and an evaluation of the effect of intervention. Several strategies can be used to obtain data that aid in this assessment. We have defined and categorized the recommended metrics for each of these aspects of measuring MDRO infection and colonization, for use by healthcare facilities. © 2008 by The Society for Healthcare Epidemiology of America. All rights reserved.

Legislation aimed at controlling antimicrobial-resistant pathogens through the use of active surveillance cultures to screen hospitalized patients has been introduced in at least 2 US states. In response to the proposed legislation, the Society for Healthcare Epidemiology of America (SHEA) and the Association for Professionals in Infection Control and Epidemiology, Inc., (APIC) have developed this joint position statement. Both organizations are dedicated to combating health care-associated infections with a wide array of methods, including the use of active surveillance cultures in appropriate circumstances. This position statement reviews the proposed legislation and the rationale for use of active surveillance cultures, examines the scientific evidence supporting the use of this strategy, and discusses a number of unresolved issues surrounding legislation mandating use of active surveillance cultures. The following 5 consensus points are offered. (1) Although reducing the burden of antimicrobial-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is of preeminent importance, the APIC and the SHEA do not support legislation to mandate use of active surveillance cultures to screen for MRSA, VRE, or other antimicrobial-resistant pathogens. (2) The SHEA and the APIC support the continued development, validation, and application of efficacious and cost-effective strategies for the prevention of infections caused by MRSA, VRE, and other antimicrobial-resistant and antimicrobial-susceptible pathogens. (3) The APIC and the SHEA welcome efforts by health care consumers, together with private, local, state, and federal policy makers, to focus attention on and formulate solutions for the growing problem of antimicrobial resistance and health care-associated infections. (4) The SHEA and the APIC support ongoing additional research to determine and optimize the appropriateness, utility, feasibility, and

Legislation aimed at controlling antimicrobial-resistant pathogens through the use of active surveillance cultures to screen hospitalized patients has been introduced in at least 2 US states. In response to the proposed legislation, the Society for Healthcare Epidemiology of America (SHEA) and the Association for Professionals in Infection Control and Epidemiology, Inc., (APIC) have developed this joint position statement. Both organizations are dedicated to combating health care-associated infections with a wide array of methods, including the use of active surveillance cultures in appropriate circumstances. This position statement reviews the proposed legislation and the rationale for use of active surveillance cultures, examines the scientific evidence supporting the use of this strategy, and discusses a number of unresolved issues surrounding legislation mandating use of active surveillance cultures. The following 5 consensus points are offered. (1) Although reducing the burden of antimicrobial-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is of preeminent importance, the APIC and the SHEA do not support legislation to mandate use of active surveillance cultures to screen for MRSA, VRE, or other antimicrobial-resistant pathogens. (2) The SHEA and the APIC support the continued development, validation, and application of efficacious and cost-effective strategies for the prevention of infections caused by MRSA, VRE, and other antimicrobial-resistant and antimicrobial-susceptible pathogens. (3) The APIC and the SHEA welcome efforts by health care consumers, together with private, local, state, and federal policy makers, to focus attention on and formulate solutions for the growing problem of antimicrobial resistance and health care-associated infections. (4) The SHEA and the APIC support ongoing additional research to determine and optimize the appropriateness, utility, feasibility, and

Objective: To assess the changes in antibiotic resistances in Staphylococcus aureus, both methicillin-susceptible and methicillin-resistant strains, in Australia. Design(s): Retrospective review of data collected annually. Setting(s): Twenty metropolitan teaching hospitals in the six States of Australia and the Australian Capital Territory from 1988 to 1994. Outcome measures: Changes in prevalence and resistance rates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible strains, based on antibiotic susceptibility testing of clinical isolates of S. aureus. Result(s): Prevalence of MRSA has remained constant on the eastern seaboard of Australia. A distinctive strain of MRSA emerged in Western Australia which had different antimicrobial susceptibilities. Resistances emerged in MRSA strains from eastern Australia, principally to ciprofloxacin and rifampicin, while resistance to fusidic acid remained stable and resistance to chloramphenicol significantly declined. Resistances in methicillin-susceptible strains remained fairly stable, except for a decline in resistance levels for tetracycline. High levels of resistance were seen to penicillin, moderate levels to erythromycin and low levels to trimethoprim and fusidic acid in methicillin-susceptible strains. Conclusion(s): The continued high prevalence of and increasing resistance in MRSA in some Australian hospitals have meant that some strains are now untreatable with oral antibiotics.

Objective: To assess the changes in antibiotic resistances in Staphylococcus aureus, both methicillin-susceptible and methicillin-resistant strains, in Australia. Design(s): Retrospective review of data collected annually. Setting(s): Twenty metropolitan teaching hospitals in the six States of Australia and the Australian Capital Territory from 1988 to 1994. Outcome measures: Changes in prevalence and resistance rates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible strains, based on antibiotic susceptibility testing of clinical isolates of S. aureus. Result(s): Prevalence of MRSA has remained constant on the eastern seaboard of Australia. A distinctive strain of MRSA emerged in Western Australia which had different antimicrobial susceptibilities. Resistances emerged in MRSA strains from eastern Australia, principally to ciprofloxacin and rifampicin, while resistance to fusidic acid remained stable and resistance to chloramphenicol significantly declined. Resistances in methicillin-susceptible strains remained fairly stable, except for a decline in resistance levels for tetracycline. High levels of resistance were seen to penicillin, moderate levels to erythromycin and low levels to trimethoprim and fusidic acid in methicillin-susceptible strains. Conclusion(s): The continued high prevalence of and increasing resistance in MRSA in some Australian hospitals have meant that some strains are now untreatable with oral antibiotics.