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.

Cost-utility analysis of antiviral use under pandemic influenza using a novel approach - linking pharmacology, epidemiology and heath economics.

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

Pharmacoeconomic evaluation of micafungin versus caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in Turkey.

Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (€2693) incurred a lower total cost than micafungin (€4422), with a net cost saving of €1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of ±100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.

Cost effectiveness of caspofungin vs. voriconazole for empiric therapy in Turkey.

Invasive fungal infections from febrile neutropenia are associated with significant cost and mortality. The mainstay of treatment has been liposomal amphotericin B, however, echinocandins and azoles have shown promise as alternative treatments. Data on clinical efficacy exist, however, data incorporating pharmacoeconomic considerations are required in Turkey. The aim of this study was to investigate the cost effectiveness of caspofungin vs. voriconazole in empiric treatment of febrile neutropenia in Turkey. A decision analytic model was utilised, built upon two randomised-controlled trials and supplemented with expert panel input from clinicians in Turkey. A five-point composite outcome measure was utilised and sensitivity analyses were performed to demonstrate the robustness of the model. The base case scenario resulted in caspofungin being preferred by TL2,533, TL29,256 and TL2,536 per patient treated, successfully treated patient and patient survival, respectively (approx. USD1414, 16 328 and 1415); sensitivity analyses did not change the outcome. Monte Carlo simulation highlighted a 78.8% chance of favouring caspofungin. The result was moderately sensitive to treatment duration and acquisition cost of the antifungal agents compared. This is the first pharmacoeconomic study comparing caspofungin to voriconazole within Turkey, resulting in an advantage towards caspofungin. The study will aid in formulary decision-making based on the clinical and economic consequences of each agent in the Turkish health care setting.

Factors influencing the cost of prosthetic joint infection treatment.

BACKGROUND: Prosthetic joint infection (PJI) is associated with significant costs to the healthcare system. Current literature examines the cost of specific treatment modalities without assessing other cost drivers for PJI. AIMS: To examine the overall cost of the treatment of PJI and to identify factors associated with management costs. METHODS: The costs of treatment of prosthetic joint infections were examined in 139 patients across 10 hospitals over a 3-year period (January 2006 to December 2008). Cost calculations included hospitalization costs, surgical costs, hospital-in-the-home costs and antibiotic therapy costs. Negative binomial regression analysis was performed to model factors associated with total cost. FINDINGS: The median cost of treating prosthetic joint infection per patient was Australian $34,800 (interquartile range: 20,305, 56,929). The following factors were associated with increased treatment costs: septic revision arthroplasty (67% increase in treatment cost; P = 0.02), hypotension at presentation (70% increase; P = 0.03), polymicrobial infections (41% increase; P = 0.009), surgical treatment with one-stage exchange (100% increase; P = 0.002) or resection arthroplasty (48% increase; P = 0.001) were independently associated with increased treatment costs. Culture-negative prosthetic joint infections were associated with decreased costs (29% decrease in treatment cost; P = 0.047). Treatment failure was associated with 156% increase in treatment costs. CONCLUSIONS: This study identifies clinically important factors influencing treatment costs that may be of relevance to policy-makers, particularly in the setting of hospital reimbursement and guiding future research into cost-effective preventive strategies.

Pharmacoeconomic evaluation of caspofungin versus liposomal amphotericin B in empirical treatment of invasive fungal infections in Turkey.

Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB.

Economic evaluation of micafungin versus caspofungin for the treatment of candidaemia and invasive candidiasis.

BACKGROUND: Micafungin demonstrated non-inferiority to caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in a major randomised clinical trial. AIM: The aim of this study was to investigate if micafungin is a cost-saving option compared with caspofungin for treating candidaemia and IC. METHODS: A decision analytical model was constructed to capture downstream consequences of using either agent as initial therapy for candidaemia and IC. The main outcomes were treatment success and treatment failure (i.e. death, mycological persistence, emergent infection, clinical failure but microbiological success). Outcome probabilities and treatment pathways were derived from the literature. Cost inputs were from the latest Australian resources, and resource use was estimated by expert panel. The analysis was from the Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted. RESULTS: Micafungin (AU$52 816) was associated with a lower total cost than caspofungin (AU$52 976), with a net cost-saving of $160 per patient. This was primarily due to the lower cost associated with alternative antifungal treatment in the micafungin arm. Hospitalisation was the main cost-driver for both arms. The model outcome was most sensitive to the proportion of treatment success in the micafungin arm. Uncertainty analysis demonstrated that micafungin had a 58% chance of being cost-saving compared with caspofungin. CONCLUSIONS: Micafungin was cost-equivalent to caspofungin in treating candidaemia and IC, with variation in drug acquisition cost the critical factor.

Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization.

Enterococci are a major cause of nosocomial bacteraemia. The impacts of vanB vancomycin resistance and antibiotic therapy on outcomes in enterococcal bacteraemia are unclear. Factors that affect length of stay (LOS) and costs of managing patients with enterococcal bacteraemia are also unknown. This study aimed to identify factors associated with mortality, LOS and hospitalization costs in patients with enterococcal bacteraemia and the impact of vancomycin resistance and antibiotic therapy on these outcomes. Data from 116 patients with vancomycin-resistant Enterococci (VRE), matched 1:1 with patients with vancomycin-susceptible Enterococcus (VSE), from two Australian hospitals were reviewed for clinical and economic outcomes. Univariable and multivariable logistic and quantile regression analyses identified factors associated with mortality, LOS and costs. Intensive care unit admission (OR, 8.57; 95% CI, 3.99-18.38), a higher burden of co-morbidities (OR, 4.55; 95% CI, 1.83-11.33) and longer time to appropriate antibiotics (OR, 1.02; 95% CI, 1.01-1.03) were significantly associated with mortality in enterococcal bacteraemia. VanB vancomycin resistance increased LOS (4.89 days; 95% CI, 0.56-11.52) and hospitalization costs (AU$ 28 872; 95% CI, 734-70 667), after adjustment for confounders. Notably, linezolid definitive therapy was associated with lower mortality (OR, 0.13; 95% CI, 0.03-0.58) in vanB VRE bacteraemia patients. In patients with VSE bacteraemia, time to appropriate antibiotics independently influenced mortality, LOS and hospitalization costs, and underlying co-morbidities were associated with mortality. The study findings highlight the importance of preventing VRE bacteraemia and the significance of time to appropriate antibiotics in the management of enterococcal bacteraemia.