Validation of the Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) quality assessment tool.

BACKGROUND: The Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) was developed to undertake streamlined quality audits of antifungal prescribing. The validity and reliability of such tools is not characterized. OBJECTIVES: To assess the validity and reliability of the AF-NAPS quality assessment tool. METHODS: Case vignettes describing antifungal prescribing were prepared. A steering group was assembled to determine gold-standard classifications for appropriateness and guideline compliance. Infectious diseases physicians, antimicrobial stewardship (AMS) and specialist pharmacists undertook a survey to classify appropriateness and guideline compliance of prescriptions utilizing the AF-NAPS tool. Validity was measured as accuracy, sensitivity and specificity compared with gold standard. Inter-rater reliability was measured using Fleiss' kappa statistics. Assessors' responses and comments were thematically analysed to determine reasons for incorrect classification. RESULTS: Twenty-eight clinicians assessed 59 antifungal prescriptions. Overall accuracy of appropriateness assessment was 77.0% (sensitivity 85.3%, specificity 68.0%). Highest accuracy was seen amongst specialist (81%) and AMS pharmacists (79%). Prescriptions with lowest accuracy were in the haematology setting (69%), use of echinocandins (73%), mould-active azoles (75%) and for prophylaxis (71%). Inter-rater reliability was fair overall (0.3906), with moderate reliability amongst specialist pharmacists (0.5304). Barriers to accurate classification were incorrect use of the appropriateness matrix, knowledge gaps and lack of guidelines for some indications. CONCLUSIONS: The AF-NAPS is a valid tool, assisting assessors to correctly classify appropriate prescriptions more accurately than inappropriate prescriptions. Specialist and AMS pharmacists had similar performance, providing confidence that both can undertake AF-NAPS audits to a high standard. Identified reasons for incorrect classification will be targeted in the online tool and educational materials.

Interventions for rapid recognition and treatment of sepsis in the emergency department: a narrative review.

BACKGROUND: Sepsis is a major cause of morbidity and mortality worldwide. Early recognition and treatment of sepsis is associated with improved outcome. The emergency department (ED) is the department where patients with sepsis seek care. However, recognition of sepsis in the ED remains difficult. Different alert and triage systems, screening scores and intervention strategies have been developed to assist clinicians in early recognition of sepsis and to optimize management. OBJECTIVES: This narrative review describes currently applied interventions or interventions we can start using today, such as screening scores, (automated) triage systems, sepsis teams and clinical pathways in sepsis care; and it summarizes evidence for the effect of implementation of these interventions in the ED on patient management and outcomes. SOURCES: A systematic literature search was conducted in PubMed, resulting in 39 eligible studies. CONTENT: The main sepsis interventions in the ED are (automated) triage systems, sepsis teams and clinical pathways, the most integrative being a clinical pathway. Implementation of any of these interventions in sepsis care will generally lead to increased protocol adherence. Presumably increased adherence to sepsis guidelines and bundles will lead to better patient outcomes, but the level of evidence to support this improvement is low, whereas implementation of interventions is often complex and costly. No studies comparing different interventions were identified. Two essential factors for success of interventions in the ED are obtaining the support from all professionals and providing ongoing education. The vulnerability of these interventions lies in the lack of accurate tools to identify sepsis; diagnosing sepsis ultimately still relies on clinical assessments. A lack of specificity or sepsis alerts may lead to alert fatigue and/or overtreatment. IMPLICATIONS: The severity and poor outcome of sepsis as well as the frequency of its presentation in EDs make a structured, protocol-based approach towards these patients essential, preferably as part of a clinical pathway.

Establishing essential metrics for antifungal stewardship in hospitals: the results of an international Delphi survey.

BACKGROUND: Guidance on assessment of the quantity and appropriateness of antifungal prescribing is required to assist hospitals to interpret data effectively and structure quality improvement programmes. OBJECTIVES: To achieve expert consensus on a core set of antifungal stewardship (AFS) metrics and to determine their feasibility for implementation. METHODS: A literature review was undertaken to develop a list of candidate metrics. International experts were invited to participate in sequential web-based surveys to evaluate the importance and feasibility of metrics in the area of AFS using Delphi methodology. Three surveys were completed. Consensus was predefined as ≥80% agreement on the importance of each metric. RESULTS: Eighty-two experts consented to participate from 17 different countries. Response rate for each survey was >80%. The panel included adult and paediatric physicians, microbiologists and pharmacists with diverse content expertise. Consensus was achieved for 38 metrics considered important to routinely include in AFS programmes, and related to antifungal consumption (n = 5), quality of antifungal prescribing and management of invasive fungal infection (IFI) (n = 24), and clinical outcomes (n = 9). Twenty-one consensus metrics were considered to have moderate to high feasibility for routine collection. CONCLUSIONS: The identified core AFS metrics will provide a framework to comprehensively assess the quantity and quality of antifungal prescribing within hospitals to develop quality improvement programmes aimed at improving IFI prevention, management and patient-centred outcomes. A standardized approach will support collaboration and benchmarking to monitor the efficacy of current prophylaxis and treatment guidelines, and will provide important feedback to guideline developers.

How to start an antimicrobial stewardship programme in a hospital.

BACKGROUND: Antimicrobial stewardship (AMS) describes a coherent set of actions that ensure optimal use of antimicrobials to improve patient outcomes, while limiting the risk of adverse events (including antimicrobial resistance (AMR)). Introduction of AMS programmes in hospitals is part of most national action plans to mitigate AMR, yet the optimal components and actions of such a programme remain undetermined. OBJECTIVES: To describe how health-care professionals can start an AMS programme in their hospital, the components of such a programme and the evidence base for its implementation. SOURCES: National and society-led guidelines on AMS, peer-reviewed publications and experience of AMS experts conducting AMS programmes. CONTENT: We provide a step-by-step pragmatic guide to setting up and implementing a hospital AMS programme in high-income or low-and-middle-income countries. IMPLICATIONS: Antimicrobial stewardship programmes in hospitals are a vital component of national action plans for AMR, and have been shown to significantly reduce AMR, particularly when coupled with infection prevention and control interventions. This step-by-step guide of 'how to' set up an AMS programme will help health-care professionals involved in AMS to optimally design and implement their actions.

Epidemiology and risks for infection following cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.

BACKGROUND: CRS-HIPEC is associated with improved cancer survival but an increased risk of infection. METHODS: Consecutive patients undergoing CRS-HIPEC between January 2016 and May 2018 were retrospectively reviewed. Malignancy type, comorbidities, perioperative risk factors and infectious complications were captured, using standardised definitions. Association between risk factors and infection outcomes was evaluated by logistic regression modelling. RESULTS: One-hundred patients underwent CRS-HIPEC, predominantly for colorectal cancer and pseudomyxoma peritonei. Overall, 43 (43.0%) experienced an infectious complication, including infections at surgical site (27), respiratory tract (9), urinary tract (11), Clostridium difficile (2) and post-operative sepsis (15). In most, infection onset was within 7 days post-operatively. Median length of hospitalisation was 19 days for patients with infection, compared to 8 days for those without (p = 0.000). There were no deaths at 60 days. Of variables potentially associated with surgical site infection, small bowel resection (OR 4.01, 95% confidence interval [CI] 1.53-10.83; p = 0.005) and number of resected viscera (OR 1.41, 95% CI 1.00-1.98; p = 0.048) were significantly associated with infection. CONCLUSIONS: We demonstrate a significant burden of early infective complications in patients undergoing CRS-HIPEC. Higher-risk subgroups, including those with small bowel resection and increased number of resected viscera, may benefit from enhanced monitoring.

Skin and soft tissue infections and current antimicrobial prescribing practices in Australian aged care residents.

To determine the burden of skin and soft tissue infections (SSTI), the nature of antimicrobial prescribing and factors contributing to inappropriate prescribing for SSTIs in Australian aged care facilities, SSTI and antimicrobial prescribing data were collected via a standardised national survey. The proportion of residents prescribed ⩾1 antimicrobial for presumed SSTI and the proportion whose infections met McGeer et al. surveillance definitions were determined. Antimicrobial choice was compared to national prescribing guidelines and prescription duration analysed using a negative binomial mixed-effects regression model. Of 12 319 surveyed residents, 452 (3.7%) were prescribed an antimicrobial for a SSTI and 29% of these residents had confirmed infection. Topical clotrimazole was most frequently prescribed, often for unspecified indications. Where an indication was documented, antimicrobial choice was generally aligned with recommendations. Duration of prescribing (in days) was associated with use of an agent for prophylaxis (rate ratio (RR) 1.63, 95% confidence interval (CI) 1.08-2.52), PRN orders (RR 2.10, 95% CI 1.42-3.11) and prescription of a topical agent (RR 1.47, 95% CI 1.08-2.02), while documentation of a review or stop date was associated with reduced duration of prescribing (RR 0.33, 95% CI 0.25-0.43). Antimicrobial prescribing for SSTI is frequent in aged care facilities in Australia. Methods to enhance appropriate prescribing, including clinician documentation, are required.

Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach.

OBJECTIVES: With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. METHODS: A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. RESULTS: The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased. CONCLUSIONS: This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide.

FDG PET/CT imaging in detecting and guiding management of invasive fungal infections: a retrospective comparison to conventional CT imaging.

PURPOSE: Invasive fungal infections (IFIs) are common in immunocompromised patients. While early diagnosis can reduce otherwise high morbidity and mortality, conventional CT has suboptimal sensitivity and specificity. Small studies have suggested that the use of FDG PET/CT may improve the ability to detect IFI. The objective of this study was to describe the proven and probable IFIs detected on FDG PET/CT at our centre and compare the performance with that of CT for localization of infection, dissemination and response to therapy. METHODS: FDG PET/CT reports for adults investigated at Peter MacCallum Cancer Centre were searched using keywords suggestive of fungal infection. Chart review was performed to describe the risk factors, type and location of IFIs, indication for FDG PET/CT, and comparison with CT for the detection of infection, and its dissemination and response to treatment. RESULTS: Between 2007 and 2017, 45 patients had 48 proven/probable IFIs diagnosed prior to or following FDG PET/CT. Overall 96% had a known malignancy with 78% being haematological. FDG PET/CT located clinically occult infection or dissemination to another organ in 40% and 38% of IFI patients, respectively. Of 40 patients who had both FDG PET/CT and CT, sites of IFI dissemination were detected in 35% and 5%, respectively (p < 0.001). Of 18 patents who had both FDG PET/CT and CT follow-up imaging, there were discordant findings between the two imaging modalities in 11 (61%), in whom normalization of FDG avidity of a lesion suggested resolution of active infection despite a residual lesion on CT. CONCLUSION: FDG PET/CT was able to localize clinically occult infection and dissemination and was particularly helpful in demonstrating response to antifungal therapy.

Measurement of Humoral Immune Competence and the Risk of Sinopulmonary Infection in a Cohort of Kidney Transplant Recipients.

PURPOSE: The aim of this study was to determine if measurement of B cell protective immunity was associated with susceptibility to sinopulmonary infection in kidney transplant recipients. METHODS AND MATERIALS: A prospective cohort of 168 patients with stable graft function (median 4.1 years) underwent assessment of B-lymphocyte antigen CD19 (CD19+) cell number, immunoglobulin G concentration, and seroresponses to influenza vaccination upon study entry. Patients received a single dose of a trivalent, seasonal influenza vaccine. RESULTS: After 2 years follow-up, 31 patients (18%) developed sinopulmonary infection. CD19+ cell number was strongly associated with future sinopulmonary infection. A higher proportion of patients with CD19+ cell counts below the fifth percentile for controls developed sinopulmonary infections than those above the fifth percentile, 30% (23 of 77 patients) compared with 9% (7 of 79 patients; P = .001). There was a trend toward a higher proportion of patients with reduced immunoglobulin G concentrations developing infections than in the normal range for controls, 29% (14 of 48 patients) compared with 15% (16 of 108 patients; P = .060). Influenza vaccination seroresponses were poor in patients and controls such that they could not be used to identify a subgroup of patients at high risk for the development of severe pulmonary infection. CONCLUSIONS: Monitoring B-cell numbers represents a simple, inexpensive means of stratifying transplant recipients' risk of sinopulmonary infection.

Antimicrobial labelling in Australia: a threat to antimicrobial stewardship?

Antimicrobial resistance is a public health emergency, placing veterinary antimicrobial use under growing scrutiny. Antimicrobial stewardship, through appropriate use of antimicrobials, is a response to this threat. The need for antimicrobial stewardship in Australian veterinary practices has had limited investigation. A 2016 survey undertaken to investigate antimicrobial usage patterns by Australian veterinarians found that antimicrobial dose rates were varied and often inappropriate. Doses of procaine penicillin in horses and cattle were often low, with 68% and 90% of respondents, respectively, reporting doses that were unlikely to result in plasma concentrations above minimum inhibitory concentrations for common equine and bovine pathogens. Frequency of penicillin administration was also often inappropriate. Gentamicin doses in horses were largely appropriate (89% of dose rates appropriate), but 9% of respondents reported twice daily dosing. Amoxycillin and amoxycillin-clavulanate were administered at the appropriate doses, or above, to dogs and cats by 54% and 70% of respondents, respectively. Here, we explore the potential reasons for inappropriate antimicrobial dose regimens and report that antimicrobial labels often recommend incorrect dose rates and thus may be contributing to poor prescribing practices. Changes to legislation are needed to ensure that antimicrobial drug labels are regularly updated to reflect the dose needed to effectively and safely treat common veterinary pathogens. This will be especially true if changes in legislation restrict antimicrobial use by veterinarians to the uses and doses specified on the label, thus hampering the current momentum towards improved antimicrobial stewardship.

Barriers to and enablers of implementing antimicrobial stewardship programs in veterinary practices.

BACKGROUND: Antimicrobial stewardship (AMS) programs are yet to be widely implemented in veterinary practice and medical programs are unlikely to be directly applicable to veterinary settings. OBJECTIVE: To gain an in-depth understanding of the factors that influence effective AMS in veterinary practices in Australia. METHODS: A concurrent explanatory mixed methods design was used. The quantitative phase of the study consisted of an online questionnaire to assess veterinarians' attitudes to antimicrobial resistance (AMR) and antimicrobial use in animals, and the extent to which AMS currently is implemented (knowingly or unknowingly). The qualitative phase used semi-structured interviews to gain an understanding of the barriers to and enablers of AMS in veterinary practices. Data were collected and entered into NVivo v.11, openly coded and analyzed according to mixed methods data analysis principles. RESULTS: Companion animal, equine, and bovine veterinarians participated in the study. Veterinary practices rarely had antimicrobial prescribing policies. The key barriers were a lack of AMS governance structures, client expectations and competition between practices, cost of microbiological testing, and lack of access to education, training and AMS resources. The enablers were concern for the role of veterinary antimicrobial use in development of AMR in humans, a sense of pride in the service provided, and preparedness to change prescribing practices. CONCLUSION AND CLINICAL IMPORTANCE: Our study can guide development and establishment of AMS programs in veterinary practices by defining the major issues that influence the prescribing behavior of veterinarians.

Antimicrobials used for surgical prophylaxis by equine veterinary practitioners in Australia.

BACKGROUND: Antimicrobials are widely used in Australian veterinary practices, but no investigation into the classes of antimicrobials used, or the appropriateness of use in horses, has been conducted. OBJECTIVES: The aim of the study was to describe antimicrobial use for surgical prophylaxis in equine practice in Australia. STUDY DESIGN: Cross-sectional questionnaire survey. METHODS: An online questionnaire was used to document antimicrobial usage patterns. Information solicited in the questionnaire included demographic details of the respondents, the frequency with which antimicrobials were used for specific surgical conditions (including the dose, timing and duration of therapy) and practice antimicrobial use policies and sources of information about antimicrobials and their uses. RESULTS: A total of 337 members of the Australian veterinary profession completed the survey. Generally, the choice of antimicrobial was appropriate for the specified equine surgical condition, but the dose and duration of therapy varied greatly. While there was poor optimal compliance with British Equine Veterinary Association guidelines in all scenarios (range 1-15%), except removal of a nonulcerated dermal mass (42%), suboptimal compliance (compliant antimicrobial drug selection but inappropriate timing, dose or duration of therapy) was moderate for all scenarios (range 48-68%), except for an uninfected contaminated wound over the thorax, where both optimal and suboptimal compliance was very poor (1%). Veterinarians practicing at a university hospital had higher odds of compliance than general practice veterinarians (Odds ratio 3.2, 95% CI, 1.1-8.9, P = 0.03). MAIN LIMITATIONS: Many survey responses were collected at conferences which may introduce selection bias, as veterinarians attending conferences may be more likely to have been exposed to contemporary antimicrobial prescribing recommendations. CONCLUSIONS: Antimicrobial use guidelines need to be developed and promoted to improve the responsible use of antimicrobials in equine practice in Australia. An emphasis should be placed on antimicrobial therapy for wounds and appropriate dosing for procaine penicillin.

What are the similarities and differences in antimicrobial prescribing between Australian public and private hospitals?

BACKGROUND: Identifying themes associated with inappropriate prescribing in Australian public and private hospitals will help target future antimicrobial stewardship initiatives. AIMS: To describe current antimicrobial prescribing practices, identify similarities and differences between hospital sectors and provide target areas for improvement specific to each hospital sector. METHODS: All hospitals included in the study were part of the 2014 national antimicrobial prescribing survey and conducted one of the following: a whole hospital point prevalence survey, serial point prevalence surveys or a sample of randomly selected patients. Data on the types of antibiotics used, their indications for use and the quality of prescription based on compliance with national and local prescribing guidelines were collected. RESULTS: Two hundred and two hospitals (166 public and 36 private) comprising 10 882 patients and 15 967 antimicrobial prescriptions were included. Public hospitals had higher proportions of prescriptions for treatment (81.5% vs 48.4%) and medical prophylaxis (8.8% and 4.6%), whilst private hospitals had significantly higher surgical prophylaxis use (9.6% vs 46.9%) (P < 0.001). In public hospitals, the main reasons for non-compliance of treatment prescriptions were spectrum being too broad (30.5%) while in private it was incorrect dosing. Prolonged duration was the main reason for non-compliance among surgical prophylaxis prescriptions in both types of hospitals. CONCLUSIONS: Australian hospitals need to target specific areas to improve antimicrobial use. Specifically, unnecessary broad-spectrum therapy should be a priority area in public hospitals, whilst emphasis on curtailing antimicrobial overuse in surgical prophylaxis needs to be urgently addressed across in the private hospital sector.

Oral pristinamycin for the treatment of resistant Gram-positive infections in patients with cancer: Evaluation of clinical outcomes.

Pristinamycin has been used to treat a range of Gram-positive infections, but reported experience in patients with malignancy is limited. This study aimed to evaluate the use of pristinamycin in patients with cancer at an Australian centre. All patients commenced on oral pristinamycin therapy at the Peter MacCallum Cancer Centre between January 2005 and December 2014 were identified using the hospital pharmacy dispensing system. Information on demographics, co-morbidities, cancer diagnosis, infection characteristics, pristinamycin regimen, pristinamycin tolerability and outcomes was collected. The median duration of follow-up was 398 days. In total, 26 patients received pristinamycin, with median age of 61 years and a male predominance (65%). Underlying diagnoses were haematological malignancies (50%) and solid tumours (50%). Pathogens included 13 meticillin-resistant Staphylococcus aureus, 6 vancomycin-resistant Enterococcus faecium, 4 meticillin-resistant Staphylococcus epidermidis, 2 meticillin-susceptible S. aureus and 1 vancomycin-susceptible E. faecium. Infection sites were osteomyelitis (6), skin and soft-tissue (4), intra-abdominal/pelvic abscess (4), bloodstream (3), empyema (3), endocarditis/endovascular (3), prosthesis-related infection (2) and epididymo-orchitis (1). One patient ceased pristinamycin due to nausea. Regarding outcome, 13 patients (50%) were cured of infection, 8 (31%) had suppression and 5 (19%) had relapse. Relapses included 1 endovascular infection, 2 episodes of osteomyelitis, 1 pelvic abscess and 1 skin and soft-tissue infection. Overall, 81% of patients achieved cure or suppression of antibiotic-resistant or complex Gram-positive infections, consistent with published experience in non-cancer populations. A favourable tolerability profile makes oral pristinamycin a viable treatment option, particularly in settings where outpatient management of cancer is the objective.

Antimicrobial allergy 'labels' drive inappropriate antimicrobial prescribing: lessons for stewardship.

BACKGROUND: The presence of antimicrobial allergy designations ('labels') often substantially reduces prescribing options for affected patients, but the frequency, accuracy and impacts of such labels are unknown. METHODS: The National Antimicrobial Prescribing Survey (NAPS) is an annual de-identified point prevalence audit of Australian inpatient antimicrobial prescribing using standardized definitions of guideline compliance, appropriateness and indications. Data were extracted for 2 years (2013-14) and compared for patients with an antimicrobial allergy label (AAL) and with no AAL (NAAL). RESULTS: Among 21 031 patients receiving antimicrobials (33 421 prescriptions), an AAL was recorded in 18%, with inappropriate antimicrobial use significantly higher in the AAL group versus the NAAL group (OR 1.12, 95% CI 1.05-1.22, P < 0.002). Patterns of antimicrobial use were significantly influenced by AAL, with lower ß-lactam use (AAL versus NAAL; OR 0.47, 95% CI 0.43-0.50, P < 0.001) and higher quinolone (OR 2.07, 95% CI 1.83-2.34, P < 0.0001), glycopeptide (OR 1.59, 95% CI 1.38-1.83, P < 0.0001) and carbapenem (OR 1.74, 95% CI 1.43-2.13, P < 0.0001) use. In particular, among immunocompromised patients, AAL was associated with increased rates of inappropriate antimicrobial use (OR 1.68, 95% CI 1.21-2.30, P = 0.003), as well as increased use of quinolones (OR 1.88, 95% CI 1.16-3.03, P = 0.02) and glycopeptides (OR 1.82, 95% CI 1.17-2.84, P = 0.01). CONCLUSIONS: AALs are common and appear to be associated with higher rates of inappropriate prescribing and increased use of broad-spectrum antimicrobials. Improved accuracy in defining AALs is likely to be important for effective antimicrobial stewardship (AMS), with efforts to 'de-label' inappropriate AAL patients a worthwhile feature of future AMS initiatives.

Sepsis following cancer surgery: the need for early recognition and standardised clinical care.

Despite the implementation of multimodal bundles of care in hospitalised patients, post-operative sepsis in patients with cancer still accounts for a significant burden of illness and substantial healthcare costs. Patients undergoing surgery for cancer are at particular risk of sepsis due to underlying malignancy, being immunocompromised associated with cancer management and the complexity of surgical procedures performed. In this review, we evaluate the burden of illness and risks for sepsis following surgery for cancer. Current evidence supporting standardised strategies for sepsis management (including early recognition and resuscitation) is examined together with challenges in implementing quality improvement programs.