Modified Pitt bacteremia score for predicting mortality in patients with candidaemia: A multicentre seven-year retrospective study conducted in Japan.

BACKGROUND: Several severity indexes have been reported for critically ill patients. The Pitt bacteremia score (PBS) is commonly used to predict the risk of mortality in patients with bacteraemia. OBJECTIVES: To develop a scoring system for predicting mortality in candidaemia patients. METHODS: Medical records at five Japanese tertiary hospitals were reviewed. Factors associated with mortality were analysed using logistic regression modelling. The discriminatory power of scoring models was evaluated by assessing the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: In total, 422 candidaemia patients were included. Higher PBS, dialysis and retainment of central venous catheter were independent risk factors for all-cause 30-day mortality. However, among the five PBS components, fever was not associated with mortality; therefore, we developed a modified version of the PBS (mPBS) by replacing fever with dialysis. AUC for PBS and mPBS were 0.74 (95% confidence interval [CI]: 0.68-0.80) and 0.76 (95% CI: 0.71-0.82), respectively. The increase in predictive ability of mPBS for 30-day mortality was statistically significant as assessed by NRI (0.24, 95% CI: 0.01-0.46, p = .04) and IRI (0.04, 95% CI: 0.02-0.06, p = .0008). When patients were stratified by mPBS into low (scores 0-3), moderate (4-7) and high risk (≥8), there were significant differences among the survival curves (p < .0001, log-rank test), and 30-day mortality rates were 13.8% (40/290), 36.8% (28/76) and 69.4% (34/49), respectively. CONCLUSIONS: mPBS can be a useful tool for predicting mortality in candidaemia patients.

Effects of antifungal stewardship using therapeutic drug monitoring in voriconazole therapy on the prevention and control of hepatotoxicity and visual symptoms: A multicentre study conducted in Japan.

BACKGROUND: Hepatotoxicity and visual symptoms are common adverse effects (AEs) of voriconazole therapy. OBJECTIVE: To retrospectively evaluate the effects of treatment modification based on therapeutic drug monitoring on AEs in patients undergoing voriconazole therapy. METHODS: The target voriconazole trough concentration (Cmin ) was 1-5 µg/mL. Receiver operating characteristic curves were used to determine Cmin cut-offs for AEs. RESULTS: A total of 401 patients were included. Among 108 patients with high initial Cmin , voriconazole was discontinued in 32 and the dose was reduced in 71. Among 44 patients with low initial Cmin , voriconazole was discontinued in 4 and the dose was increased in 19. Hepatotoxicity occurred in 6.0% of patients, after a median of 10 days. Visual symptoms were evident in 9.5% of patients after a median of 4 days. Initial Cmin was significantly associated with visual symptoms but not hepatotoxicity, which suggested the effect of treatment modification on hepatotoxicity. However, both hepatotoxicity and visual symptoms were significantly correlated with Cmin at the onset of AEs, and the Cmin cut-offs were 3.5 µg/mL for hepatotoxicity and 4.2 µg/mL for visual symptoms. Voriconazole was discontinued after the occurrence of AEs in 62.5% of patients with hepatotoxicity but only 26.3% of patients with visual symptoms. With dose adjustment, treatment was completed in 8/9 patients with hepatotoxicity and 27/28 patients with visual symptoms. CONCLUSIONS: A significant preventive effect was demonstrated on hepatotoxicity, but not on visual symptoms because of earlier occurrence. With treatment modification after the occurrence of AEs, most patients completed therapy.

The incidence of endophthalmitis or macular involvement and the necessity of a routine ophthalmic examination in patients with candidemia.

BACKGROUND: The incidence of ocular candidiasis (OC) in patients with candidemia varies across different reports, and the issue of whether routine ophthalmoscopy improves outcomes has been raised. This study investigated the incidence of OC and evaluate whether the extent of OC impacts the clinical outcomes. METHODS: This retrospective study included non-neutropenic patients with candidemia who underwent treatment at one of 15 medical centers between 2010 and 2016. Chorioretinitis without other possible causes for the ocular lesions and endophthalmitis was classified as a probable OC. If signs of chorioretinitis were observed in patients with a systemic disease that causes similar ocular lesions, they were classified as a possible OC. RESULTS: In total, 781 of 1089 patients with candidemia underwent an ophthalmic examination. The prevalence of OC was 19.5%. The time from the collection of a positive blood culture to the initial ophthalmic examination was 5.0 ± 3.9 days in patients with OC. The leading isolate was Candida albicans (77.9%). Possible OC was associated with unsuccessful treatments (resolution of ocular findings) (odds ratio: 0.354, 95% confidence interval: 0.141-0.887), indicating an overdiagnosis in patients with a possible OC. If these patients were excluded, the incidence fell to 12.8%. Endophthalmitis and/or macular involvement, both of which require aggressive therapy, were detected in 43.1% of patients; a significantly higher incidence of visual symptoms was observed in these patients. CONCLUSION: Even when early routine ophthalmic examinations were performed, a high incidence of advanced ocular lesions was observed. These results suggest that routine ophthalmic examinations are still warranted in patients with candidemia.