Initial micafungin treatment does not improve outcomes compared to fluconazole treatment in immunocompromised and critically ill patients with candidaemia.

BACKGROUND: Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. OBJECTIVES: To understand optimal initial treatment of candidaemia. METHODS: We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. RESULTS: A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome. CONCLUSIONS: These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.

Evaluation of the efficacy of ursodiol for prevention of hepatotoxicity in patients receiving gemtuzumab ozogamicin and inotuzumab ozogamicin.

Gemtuzumab ozogamicin (GO) and inotuzumab ozogamicin (InO) are indicated for newly diagnosed or relapsed/refractory CD33-positive acute myeloid leukemia and relapsed/refractory B-cell precursor acute lymphoblastic leukemia respectively. Patients undergoing therapy with these agents are at increased risk for hepatotoxicity. Forty-nine patients received either GO or InO with concomitant ursodiol (n=14) or no ursodiol (n=35) for hepatotoxicity prophylaxis. Hepatotoxicity occurred in 2 (14%) patients in the ursodiol group compared to 15 (43%) patients in the no ursodiol group (p=0.10). Median days (17 versus 11; p=0.66) and doses (4 versus 2; p=0.28) to development of hepatotoxicity were higher in the ursodiol versus no ursodiol group. After adjusting for concomitant hepatotoxic medications and prior chemotherapy, ursodiol did not significantly reduce the incidence of hepatotoxicity. Ursodiol prophylaxis was associated with a similar incidence of hepatotoxicity compared to no ursodiol, but may delay the time to occurrence.

Evaluation of the efficacy and safety of arsenic trioxide dosing in obese patients with acute promyelocytic leukemia.

Arsenic trioxide (ATO) is the backbone of acute promyelocytic leukemia (APL) treatment and is dosed based on weight with no upper limit, therefore obese patients receive large doses and may be vulnerable to adverse effects and dose holdings. Twenty-seven patients receiving ATO during induction were categorized as obese (N = 16) or non-obese (N = 11) based on body mass index (BMI) ≥30 kg/m2 in this retrospective study. Doses were held or modified due to composite adverse effects in 9 (56%) obese patients and 7 (64%) non-obese patients (p = 1.00). There were higher rates of dose holdings (13% versus 0%; p = .5) and dose modifications (13% versus 0%; p = .5) due to hepatotoxicity in obese versus non-obese patients. There were no differences in efficacy parameters. These data suggest that obese patients have similar overall incidence of adverse effects to ATO as non-obese patients; any difference in risk of hepatotoxicity will require clarification in a larger study.