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Objectives: Emergence of multiresistant Gram-negative organisms in intensive care units (ICUs) throughout the world is a concerning problem. Therefore we undertook a study to follow the resistance patterns of the most common clinically isolated Gram-negative organisms within our ICU following an antibiotic stewardship intervention to evaluate whether a reduction in broad-spectrum antibiotics improves local antibiotic resistance patterns., Methods: This prospective study was conducted over a 7 year period within an ICU at a tertiary teaching hospital in Melbourne, Australia. All clinically isolated Gram-negative organisms were identified and extracted from the hospital pathology system. Three monthly antibiograms were created. The pre-interventional period occurred between January 2000 and June 2002 (10 quarters) and the post-interventional period was defined from July 2002 to December 2006 (18 quarters). Segmented linear regression was used to analyse for a difference in the rates of change in susceptibility., Results: A total of 2838 Gram-negative organisms were isolated from clinical sites from ICU patients during the study period. There was significant improvement in susceptibility of Pseudomonas to imipenem 18.3%/year [95% confidence interval (CI): 4.9-31.6; P = 0.009] and gentamicin 11.6%/year (95% CI: 1.8-21.5; P = 0.02) compared with the pre-intervention trend. Significant changes in the rates of gentamicin and ciprofloxacin susceptibility were also observed in the inducible Enterobacteriaceae group although these were less clinically significant., Conclusions: This study demonstrates improved antibiotic susceptibility of ICU Gram-negative isolates including Pseudomonas following an intervention aimed at reducing broad-spectrum antibiotics.

Objectives: Infectious gastrointestinal disease (IGD) is a significant cause of morbidity in returned international travellers. This study aims to elucidate host and travel characteristics associated with IGD presentation, and describe the broad spectrum of aetiological pathogens responsible by geographic region of acquisition and reason for travel., Methods: We analyzed demographic, clinical and microbiological data recorded for ill, returned international travellers presenting to GeoSentinel Surveillance Network sites globally during the period September 1996-December 2005., Results: A total of 25,867 returned travellers were analyzed, of whom 7442 (29%) patients had a total of 8273 IGD diagnoses. Multivariate analysis demonstrated that IGD presentation was associated significantly with female sex (OR: 1.11; p=0.001); younger age group; attending a pre-travel medical appointment (OR: 1.28; p<0.0001); and travelling for the reason of tourism. Travelling for longer periods (>28 days) was associated with lower risk (OR: 0.93; p=0.04). Of the 2902 clinically significant pathogens isolated, 65% were parasitic, 31% bacterial and 3% viral. Presentation of IGD by specific pathogen varied markedly dependent on geographic region of recent travel, and reason for travel., Conclusions: Host characteristics, region of travel and category of traveller, significantly impact on the relative likelihood of presenting with a broad range of pathogen-specific IGD.

In immunocompromised patients, endovascular infection due to Candida albicans is associated with significant morbidity and mortality. Recommended management includes removal of any existing central venous catheter. Rarely, complications of endocarditis or infected mural thrombi may arise, with poorer clinical outcomes. For large endoluminal lesions, particularly of the great vessels or those that are intra-atrial, thrombolysis has been used in paediatric populations or before surgery for dissolution of infected thrombus. We describe the case of an adult patient with lung carcinoma who developed persisting candidaemia with a large endovascular fungal lesion adherent to the tip of a peripherally inserted central venous catheter. Local urokinase infusion enabled safe removal of the catheter without embolization. As an adjunct to antifungal therapy, local thrombolysis may play a contributory role in the management of central venous catheter-related candidal septic thrombosis.

Objectives: Antibiotic stewardship is important, but the ideal strategy for providing stewardship in a hospital setting is unknown. A practical, sustainable and transferable strategy is needed. This study evaluates the impact of a novel computerized antimicrobial approval system on antibiotic-prescribing behaviour in a hospital. Effects on drug consumption, antibiotic resistance patterns of local bacteria and patient outcomes were monitored., Methods: The study was conducted at a tertiary referral teaching hospital in Melbourne, Australia. The system was deployed in January 2005 and guided the use of 28 restricted antimicrobials. Data were collected over 7 years: 5 years before and 2 years after deployment. Uptake of the system was evaluated using an in-built audit trail. Drug utilization was prospectively monitored using pharmacy data (as defined daily doses per 1000 bed-days) and analysed via time-series analysis with segmental linear regression. Antibiograms of local bacteria were prospectively evaluated. In-hospital mortality and length of stay for patients with Gram-negative bacteraemia were also reported., Results: Between 250 and 300 approvals were registered per month during 2006. The gradients in the use of third- and fourth-generation cephalosporins (+0.52, -0.05, -0.39; P < 0.01), glycopeptides (+0.27, -0.53; P = 0.09), carbapenems (+0.12, -0.24; P = 0.21), aminoglycosides (+0.15, -0.27; P < 0.01) and quinolones (+0.76, +0.11; P = 0.08) all fell after deployment, while extended-spectrum penicillin use increased. Trends in increased susceptibility of Staphylococcus aureus to methicillin and improved susceptibility of Pseudomonas spp. to many antibiotics were observed. No increase in adverse outcomes for patients with Gram-negative bacteraemia was observed., Conclusions: The system was successfully adopted and significant changes in antimicrobial usage were demonstrated.

Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment.

Evidence-based guidelines for the treatment of established fungal infections in the adult haematology/oncology setting were developed by a national consensus working group representing clinicians, pharmacists and microbiologists. These updated guidelines replace the previous guidelines published in the Internal Medicine Journal by Slavin et al. in 2004. The guidelines are pathogen-specific and cover the treatment of the most common fungal infections including candidiasis, aspergillosis, cryptococcosis, zygomycosis, fusariosis, scedosporiosis, and dermatophytosis. Recommendations are provided for management of refractory disease or salvage therapies, and special sites of infections such as the cerebral nervous system and the eye. Because of the widespread use newer broad-spectrum triazoles in prophylaxis and empiric therapy, these guidelines should be implemented in concert with the updated prophylaxis and empiric therapy guidelines published by this group.

Background: Community acquired pneumonia is one of the most common infections for which antibiotics are prescribed in Australia., Methods: We audited empiric antibiotic prescribing for 392 adults with community-acquired pneumonia., Results: Only 61.9% of patients received empiric antibiotic coverage for both typical and atypical pathogens. Of those who required intensive care unit management, 34.6% did not receive antibiotic cover for atypical pneumonia pathogens within the first 24 h. Approximately 21.9% of patients reporting antibiotic allergies were given antibiotics to which they had a documented allergy., Conclusion: Efforts to improve prescribing practices could be focused towards identifying patients with severe illness early and improving recognition of documented allergies.

European studies have suggested that the esp gene and other virulence factors have roles in vancomycin-resistant Enterococcus faecium (VREfm) infections. The aim of this study was to examine the relationship between the spectrum of clinical disease and putative virulence factors in vanB VREfm isolates. A multiplex polymerase chain reaction was used to amplify potential virulence genes (asa1, gel E, cylA, esp and hyl) in VREfm isolates obtained from an Australian population of haematology patients. Clonality was assessed by pulsed-field gel electrophoresis (PFGE) and automated ribotyping. Infection, requirement for intensive care unit (ICU) admission and all-cause 30-day mortality were used as clinical indicators of organism virulence. Forty-one VREfm vanB isolates (41 patients; 14 infected and 27 colonised only) were analysed. Thirty-five of these isolates were typed by PFGE, 31 of which were represented by three clusters. The esp gene was identified in 22 of 27 (81.5%) screening and 11 of 14 (78.6%) infection-associated isolates. One isolate was hyl gene positive, and no isolate contained asa1, gel E or cylA genes. VREfm infection was independently associated with host factors (underlying diagnosis of acute myeloid leukaemia, age

Scedosporium apiospermum and S. prolificans are fungi of increasing clinical importance, particularly in persons with underlying diseases. We reviewed the records of 59 patients in Australia from whom Scedosporium spp. were isolated from June 30, 1997, through December 31, 2003. S. apiospermum was isolated predominantly from the respiratory tracts of 28 of 31 patients with underlying lung diseases and resulted in 2 infections and 1 death. The annual number of S. apiospermum isolates remained constant. S. prolificans was isolated from 28 patients only after November 1999. Eight patients with acute myeloid leukemia or hematopoietic stem cell transplants had invasive infection; 4 had fungemia and 6 died from infection. S. prolificans caused locally invasive infection in 2 immunocompetent patients and was found in the respiratory tract of 18 patients with underlying respiratory disease but did not cause fungemia or deaths in these patients. Scedosporium spp. showed distinct clinical and epidemiologic features.

We performed a randomized comparison of pre-emptive and empiric antibiotic therapy for adult patients undergoing allogeneic or autologous stem cell transplantation. One hundred and fifty-three patients were randomized to receive cefepime either pre-emptively on the day that neutropenia (ANC<1.0 x 10(9) cells/l) developed irrespective of the presence of fever, or at onset of fever and neutropenia (empiric). Although there was no difference between the two arms in the proportion of patients developing fever or in the median number of days of fever, the time to onset of fever was a mean of 1 day longer in each patient on the pre-emptive arm (log rank P<0.001). The number of patients with bloodstream infections was significantly reduced in those receiving pre-emptive therapy (16/75) compared to the empiric arm (31/76) (P<0.01) but this did not translate into an appreciable clinical benefit as measured by days of hospitalization, time to engraftment, use of additional antimicrobial agents or mortality at 30 days. This study does not support the use of pre-emptive intravenous antibiotic therapy in adult stem cell transplant recipients.

This decade will see the emergence of the electronic medical record, electronic prescribing and computerized decision support in the hospital setting. Current opinion from key infectious diseases bodies supports the use of computerized decision support systems as potentially useful tools in antibiotic stewardship programs. However, although antibiotic decision support systems appear beneficial for improving the quality of prescribing and reducing the costs of antibiotic prescribing, their overall cost-effectiveness, impact on patient outcome and antimicrobial resistance is much less certain. This review describes computerized decision support systems used to assist with antibiotic prescribing, the evidence for their effectiveness and the current and future roles.

Background: Several severity scores have been proposed to predict patient outcome and to guide initial management of patients with community acquired pneumonia (CAP). Most have been derived as predictors of mortality. A study was undertaken to compare the predictive value of these tools using different clinically meaningful outcomes as constructs for "severe pneumonia"., Methods: A prospective cohort study was performed of all patients presenting to the emergency department with an admission diagnosis of CAP from March 2003 to March 2004. Clinical and laboratory features at presentation were used to calculate severity scores using the pneumonia severity index (PSI), the revised American Thoracic Society score (rATS), and the British Thoracic Society (BTS) severity scores CURB, modified BTS severity score, and CURB-65. The sensitivity, specificity, positive and negative predictive values were compared for four different outcomes (death, need for ICU admission, and combined outcomes of death and/or need for ventilatory or inotropic support)., Results: 392 patients were included in the analysis; 37 (9.4%) died and 26 (6.6%) required ventilatory and/or inotropic support. The modified BTS severity score performed best for all four outcomes. The PSI (classes IV+V) and CURB had a very similar performance as predictive tools for each outcome. The rATS identified the need for ICU admission well but not mortality. The CURB-65 score predicted mortality well but performed less well when requirement for ICU was included in the outcome of interest. When the combined outcome was evaluated (excluding patients aged >90 years and those from nursing homes), the best predictors were the modified BTS severity score (sensitivity 94.3%) and the PSI and CURB score (sensitivity 83.3% for both)., Conclusions: Different severity scores have different strengths and weaknesses as prediction tools. Validation should be done in the most relevant clinical setting, using more appropriate constructs of "severe pneumonia" to ensure that these potentially useful tools truly deliver what clinicians expect of them.

Background and Objectives: Despite increasing intensity and profound immunosuppression associated with newer therapies for hematologic malignancies, little information exists regarding cytomegalovirus (CMV) reactivation in settings other than allogeneic stem cell transplantation (SCT)., Design and Methods: We reviewed the epidemiology of CMV disease in patients who were CMV polymerase chain reaction (PCR) positive during treatment for hematologic malignancies without allogeneic SCT from June 1999 to June 2004., Results: Thirty-six patients with CMV reactivation were identified. Of these, 92% were undergoing investigation for fever. Fifteen patients with CMV DNAemia were treated with ganciclovir without CMV disease developing. Notably, 20 patients with untreated CMV DNAemia did not develop CMV disease during a median follow-up of 3.5 (1-19) months. The highest rates of reactivation were observed with HyperCVAD (7.8%) and alemtuzumab (50%)., Interpretation and Conclusions: We recommend that screening for CMV DNAemia be instituted and pre-emptive therapy contemplated for asymptomatic CMV reactivation only in patients receiving alemtuzumab therapy, but not routinely for other patients outside the allogeneic SCT setting. Indeed for such patients, detection of isolated CMV DNAemia does not imply the need for immediate therapy and future studies are needed to validate PCR detection of CMV DNA and CMV DNA titers as predictors for CMV disease.

The majority of invasive aspergillosis (IA) in allogeneic stem cell transplantation (SCT) occurs during the post-engraftment period. We used Cox proportional hazards regression to evaluate post-engraftment IA risk in a cohort of 217 allogeneic SCT recipients from 1991 to 1998. The aim was to quantify the effects of dose-intensity and duration of corticosteroids and other risk factors. Median duration of follow-up was 330 days. There were 19 cases of IA (overall 8.8%) with 14 post-engraftment infections. In the final model, the risk of IA was greatest within 2 weeks of high-dose corticosteroids (HR 8.5, P=0.003), with risk extending to 4 weeks with doses of 0.25-1 mg/kg/day (HR 3.1, P=0.08). Ganciclovir was associated with greatest risk (HR 13.6). Grade 3 or 4 acute GVHD (HR 5.7) and secondary neutropenia (HR=1.3) were also additive risks. In the univariate analysis, corticosteroid doses of 0.25-1.0 mg/kg/day for any duration between 2 and 10 weeks demonstrated prolonged risk for IA. Moderate doses of corticosteroids can confer an increased risk for IA for extended periods which is almost as marked as that conferred by higher doses. Knowledge of these risks may facilitate the development of targeted surveillance and prophylaxis strategies for prevention of IA.

ABSTRACT Treatment of invasive fungal infections is increasingly complex. Amphotericin B deoxycholate has long been the mainstay of treatment. However, there has been increasing recognition of both the propensity for nephro-toxicity in haematology, transplant and intensive care patients as well as its adverse impact on morbidity and mortality. This has coincided with the availabilty of newer, and in certain settings, more effective antifungal agents. Although the newer agents clearly cause less nephrotoxicity than amphotericin B, drug interactions, hepatic effects and unique side-effects need to be considered. The spectrum of the newer triazoles and echinocandins varies, highlighting the importance of accurate identification of the causative organism where possible. Consensus Australian guidelines have been developed to assist clinicians with treatment choices by reviewing the current evidence for the efficacy, the toxicity and the cost of these agents.

Background: A single definition of influenza-like illness (ILI) has been recommended by the Australian Influenza Pandemic planning committee for influenza surveillance systems throughout Australia., Objectives: To examine combinations of clinical symptoms and determine which combination was most likely to predict laboratory-confirmed influenza in adult patients with ILI., Study Design: Sentinel general-practices in Western Australia and Victoria, 1998 and 1999. Univariate analysis and stepwise logistic regression were used to determine significant independent clinical predictors of influenza in adults. Sensitivity, specificity and positive predictive value (PPV) were calculated for various symptom complexes., Results: The combination of cough, fever and fatigue was both sensitive (43.5-75.1%) and specific (46.6-80.3%) with PPVs ranging from 23.3 to 59.7% in the surveillance data sets from both states. The symptom complex of cough, fever and fatigue was more likely to predict laboratory-confirmed influenza than the three different surveillance case definitions actually used in those years., Conclusions: We recommend the symptom complex of cough, fever and fatigue as a simple case definition for ILI in influenza surveillance. Accurate identification of influenza activity still requires laboratory confirmation in at least a proportion of cases.

Patients in intensive care units (ICUs) have a higher risk of acquiring hospital-associated infections than those in non-critical care areas. ICUs are sites of considerable broad-spectrum antibiotic use, and antibiotic-resistant pathogens are frequent. Bloodstream infections (BSIs), pneumonias, and urinary tract infections (UTIs) are the most common hospital-acquired infections and are most often associated with the use of invasive devices. They differ in importance in different types of ICUs. Coagulase-negative staphylococcus BSIs have recently increased in frequency, and enterococci have been as frequently reported as Staphylococcus aureus as causing BSIs in increasing numbers of U.S. ICUs. Fungal urinary tract sepsis has also increased. Device-associated infection rates represent the most useful surveillance rates for comparison between units and over time, but they differ considerably between ICU types. Outbreaks are common in ICUs. Recently, gram-negative bacilli have been reported more frequently than gram-positives in this setting, especially in NICUs. Considerable crude mortality and major costs are associated with these infections, but controversy persists over the degree of mortality attributable to them.