Karin Thursky

A prospective comparison of severity scores for identifying patients with severe community acquired pneumonia: reconsidering what is meant by severe pneumonia

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.

Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab*.

There is an increasing use of monoclonal antibodies in the treatment of haematological malignancies. Alemtuzumab (Campath‐1H; Ilex Pharmaceuticals, San Antonio, TX, USA) is a monoclonal antibody reactive with the CD52 antigen used as first and second line therapy for two types of lymphoproliferative disorders: chronic lymphocytic leukaemia (CLL), and T‐cell lymphomas [both peripheral (PTCL) and cutaneous (CTCL)]. With alemtuzumab therapy, viral, bacterial and fungal infectious complications are frequent, and may be life threatening. An understanding of the patients at highest risk and duration of risk are important in developing recommendations for empirical management, antimicrobial prophylaxis and targeted surveillance. This review discusses the infection risks associated with these lymphoproliferative disorders and their treatment, and provide detailed recommendations for screening and prophylaxis.

Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death

BACKGROUND Candidaemia in cancer patients is associated with increasing fluconazole resistance. Models for predicting such isolates and their clinical impact are required. METHODS Clinical, treatment and outcome data from a population-based candidaemia survey (2001-2004) were collected at 5 and 30 days after diagnosis. Speciation and antifungal susceptibility testing was performed. RESULTS There were 138 candidaemia episodes (33% Candida albicans) in adults with haematological malignancies and 150 (51% C. albicans) in adults with solid organ malignancies. Thirty-nine isolates had fluconazole MICs of >or=64 mg/L and 40 had MICs of 16-32 mg/L (predominantly Candida glabrata and Candida krusei). By multivariate analysis, triazole therapy, gastrointestinal tract (GIT) surgery in the 30 days before candidaemia and age >65 years were predictive of fluconazole-resistant candidaemia. Thirty day crude mortality was 40% in haematology patients and 45% in oncology patients. Fluconazole-resistant isolates were associated with increased risk of mortality by univariate (P = 0.04) and Kaplan-Meier survival analyses. By Cox proportional hazards modelling, the strongest predictors of mortality at onset of candidaemia were invasive ventilation, elevated creatinine, intensive care unit (ICU) admission and receipt of systemic triazoles or corticosteroids in the previous 30 days. Removal of a central venous access device (CVAD) at or within 5 days of onset was associated with decreased mortality. CONCLUSIONS Risk factors for fluconazole-resistant candidaemia in adults with cancer include fluconazole/triazole exposure and GIT surgery. ICU admission, invasive ventilation, renal impairment, age >65 years and prior exposure to corticosteroids and triazoles are risk factors for death. CVAD removal reduced mortality. These findings should be integrated into surveillance and treatment algorithms.

Working towards a simple case definition for influenza surveillance

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.

Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia.

Resistance in virus-infected stem cell transplant recipients illustrates the need for surveillance.

Electronic antibiotic stewardship—reduced consumption of broad-spectrum antibiotics using a computerized antimicrobial approval system in a hospital setting

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.

Dosing of antibiotics in obesity.

Purpose of review Obesity is becoming a major burden on healthcare systems worldwide. The management of infections is problematic due to both an increased risk of morbidity and mortality, as well as a lack of information about dosing of antibiotics in the obese population. Recommendations in this patient group are severely lacking, so clinicians need to consider pharmacokinetic/pharmacodynamic parameters and the relative risks of overdosing and underdosing. Recent findings Since 2011, articles on a number of antibiotics have been published, including cefazolin/cephazolin, cefepime, cefoxitin, clindamycin, cotrimoxazole, daptomycin, ertapenem, levofloxacin, linezolid, meropenem, moxifloxacin, piperacillin/tazobactam and vancomycin. Summary Obesity causes a number of changes, including an increase in volume of distribution and changes in hepatic metabolism and renal excretion. Several antibiotics have sufficient data to be able to make recommendations, whereas other antibiotics may need to make use of doses at the upper end of the recommended range, or utilize other dose modifications based on pharmacokinetic/pharmacodynamic parameters, in an attempt to reach adequate levels and achieve similar efficacy.

Improved susceptibility of Gram-negative bacteria in an intensive care unit following implementation of a computerized antibiotic decision support system

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.

Vancomycin-resistant Enterococcus faecium infection in patients with hematologic malignancy: patients with acute myeloid leukemia are at high-risk.

Background:  Vancomycin‐resistant enterococci (VRE) are significant nosocomial pathogens in patients with hematologic malignancy. Identification of risk factors for infection is necessary for targeted prevention and surveillance.

Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period

Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs. 8%, P=0.011), premature discontinuations (46% vs. 22% P<0.001) and empiric antifungal treatment (31% vs. 8.5%, P<0.001). Microbiologically confirmed infections were molds. Posaconazole compared to other drugs was associated with fewer courses requiring computed-tomography (43% vs. 26%, P<0.001). Adoption of voriconazole/posaconazole has decreased invasive fungal disease incidence, empiric antifungal treatment and for posaconazole, computed-tomography demand, with effectiveness of posaconazole comparable to clinical trial experience.