Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014.

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.

Impact of source of infection and vancomycin AUC0-24/MICBMD targets on treatment failure in patients with methicillin-resistant Staphylococcus aureus bacteraemia.

Despite recent controversies about toxicity and reduced efficacy, vancomycin remains the current treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. The parameter associated with treatment success is the vancomycin 24-h area under concentration-time curve to MIC ratio (AUC0-24/MIC). We aimed to determine the utility of calculated AUCs and explore the optimal AUC0-24/MIC targets associated with treatment success. In this single-centre retrospective observational cohort study of 127 patients with MRSA bacteraemia, forty-five (35.4%) did not respond to vancomycin treatment. Patient characteristics were essentially the same between those who did not respond to vancomycin treatment and those with treatment success, with independent predictors of treatment failure being source of bacteraemia (odds ratio (OR), 4.29; 95% confidence interval (CI), 1.50-12.26; p 0.007) and not achieving an AUC0-24/MICBMD (using broth microdilution) target of ≥398 (OR, 11.4; 95% CI, 4.57-28.46; p< 0.001). Bacteraemic source-specific thresholds were observed with a higher AUC0-24/MICBMD target of 440 required for high-risk sources (e.g. infective endocarditis) compared with 330 for low-risk sources (line related bacteraemia). Overall treatment success in patients with MRSA bacteraemia was associated with a vancomycin AUC0-24/MICBMD target of ≥398, with source-specific targets observed. Future vancomycin practice guidelines will need to take into account MIC methodology, source of bacteraemia and patient populations prior to setting targets and monitoring recommendations.

Support for the EUCAST and revised CLSI fluconazole clinical breakpoints by Sensititre® YeastOne® for Candida albicans: a prospective observational cohort study.

OBJECTIVES: Species-specific clinical breakpoints (CBPs) for Candida spp. were established following consideration of clinical outcomes in patients with oesophageal candidiasis. We sought to further determine the validity of the current CBPs based on data from a prospective candidaemia study. PATIENTS AND METHODS: All Candida albicans candidaemia episodes in patients enrolled in the Australian Candidaemia Study and who were treated with fluconazole monotherapy were included. Fluconazole MICs were established using Sensititre(®) YeastOne(®). RESULTS: Two hundred and seventeen evaluable episodes were identified, 93.5% of which occurred in adult patients. Fluconazole was commenced within 72 h of blood culture positivity in 96.3% (209/217) of episodes. Fluconazole doses were appropriate in 89.9% (195/217) of episodes and the median duration of therapy was 14 days (IQR 8-21 days) for the whole cohort. The all-cause 30 day mortality was 19.8% (43/217), with 37.2% (16/43) of deaths attributed to candidaemia. Classification and regression tree (CART) analysis identified a fluconazole MIC target of ≥2 mg/L for infection-related mortality and ≥4 mg/L for overall 30 day mortality. Overall mortality was no different in episodes with isolates above or below the identified MIC target, although there was a trend towards significance (P = 0.051). On univariate analysis, infection-related mortality was significantly increased in C. albicans episodes with an MIC ≥2 mg/L compared with those below this MIC target (20.6% versus 4.9%; P = 0.001). This target remained an independent predictor of infection-related mortality (OR 8.2; 95% CI 2.3-29.7; P = 0.001). CONCLUSIONS: We observed a direct relationship between infection-related mortality and rising fluconazole MIC for C. albicans candidaemia; overall, the data support the EUCAST and revised CLSI fluconazole clinical breakpoints.

The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis.

BACKGROUND: Emerging data suggest that vancomycin may be less effective against serious methicillin-resistant Staphylococcus aureus (MRSA) infections with minimum inhibitory concentration (MIC) values at the higher end of the susceptibility range. The purpose of this review is to examine the strength of these associations. METHODS: All relevant studies pertaining to treatment outcomes or mortality associated with vancomycin MIC were retrieved from the medical literature from January 1996 through August 2011 and analyzed according to Cochrane guidelines. RESULTS: Of the 270 studies identified, 48 studies were reviewed, with 22 studies included in the final meta-analysis. Vancomycin MIC was significantly associated with mortality for MRSA infection irrespective of the source of infection or MIC methodology (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.14-2.37; P < .01). This mortality association was predominantly driven by bloodstream infections (BSIs; OR, 1.58; 95% CI, 1.06-2.37; P = .03) and isolates with a vancomycin MIC of 2 µg/mL by Etest (OR, 1.72; 95% CI, 1.34-2.21; P < .01). Vancomycin MIC was significantly associated with treatment failure irrespective of source of infection or MIC methodology (OR, 2.69; 95% CI, 1.60-4.51; P < .01). CONCLUSION: High vancomycin MIC was associated with a higher mortality rate in MRSA BSI. Thus, institutions should consider conducting Etest MICs on all MRSA BSI isolates. Although these data highlight concerns about vancomycin, currently, there are no data to support better survival rates with alternative antibiotics. Data are sorely needed to determine whether other agents can remedy these outcomes observed with vancomycin for MRSA infections with elevated vancomycin MIC values.