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A letter to the editor is presented regarding febrile neutropenia (FN) incidence reduction by fluoroquinolone (FQ) prophylaxis in the January 2011 issue.

Background Voriconazole (VOR) and posaconazole (POS) exhibit wide pharmacokinetic variability. Various factors including race and genetic polymorphisms are at play and this may affect treatment response. We aim to evaluate the utility of VOR/POS TDM among Southeast Asians that are predominantly intermediate/poor VOR metabolizers. Methods All adults with VOR/POS TDM performed at our institution from 2015 to 2018 were included. We determined proportion of patients and doses required to achieve TDM targets [(2 – 5.5 mg/L (VOR) or ≥ 0.7 and ≥ 1.0 mg/L (POS prophylaxis and treatment respectively)], and correlate levels with treatment efficacy and safety. Results VOR/POS TDM was performed mostly among patients with hematological malignancy or solid-organ transplant (146/174, 83.9%). Less than half (32/70, 45.7%) of patients on VOR achieved target—18 (25.7%) were < 2 mg/L while 20 (28.5%) had levels > 5.5 mg/L. Doses required to achieve TDM target ranged from 1.9–11.4 mg/kg/day. Drug interactions, critically ill state and change in drug formulation were major causes of intra-patient variability. One-fifth (n = 14) experienced transaminitis; corresponding VOR trough levels were 0.5–> 7.5 mg/L. Neurotoxicity was also seen in 3 (4.3%) patients—all 3 had VOR trough ≥ 6.7 mg/L and saw symptom resolution upon dose reduction. There appears to be no association between the achievement of TDM targets and response rates. Majority (81/104, 77.9%) of patients on POS achieved TDM targets. Patients prescribed POS tablet were significantly more likely to attain targets compared with suspension 600 mg/day [19/26 (73.0%) vs. 27/62 (43.5%), P < 0.05] and 800 mg/day [17/26 (65.3%) vs. 4/16 (25.0%), P < 0.05)]. Of 23 with sub-therapeutic levels, 19 (82.6%) responded to dose increase and/or change in acid-reducing agents. Breakthrough infection occurred despite troughs ≥ 0.7 mg/L [5/42 (11.9%) vs. 2/40 (5.0%) when < 0.7 mg/L (P = 0.3)]. Treatment failure was observed in 2 patients (troughs > 1.0 mg/L). Conclusion VOR/POS TDM should be implemented in Southeast Asians due to significant unpredictability in dose exposure and potential to avoid need for switch to alternative anti-fungals due to intolerability. Higher POS trough cutoff may be required for effective anti-fungal prophylaxis. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Rising rates of antimicrobial resistance worldwide has dire consequences on patient care, as infections with resistant organisms impair patients' recovery, resulting in protracted illness and hence prolonged hospital stay. Antimicrobial Stewardship Programs (ASPs) have shown to effectively reduce antibiotic resistance. Locally, we observed that patients with neurological conditions were often initiated on antibiotics for change in mental state or isolated fevers. Little is known whether these patients truly require antibiotics and hence, we aim to study the impact of ASP in these patients. Methods Retrospective review of ASP database between January 2014 and December 2017 was conducted, among all patients admitted to the neurology department in SGH and in whom the ASP team recommended discontinuation of empiric use of antibiotics. Demographics were collected. Clinical outcomes, duration of antibiotics therapy, length of hospital stay (LOS), infection-related readmissions and mortality, were compared between interventions accepted and rejected groups. Results The ASP team recommended 184 interventions [overall acceptance rate of 82.6% (152/184)]. There was no significant difference in underlying demographics, and Charlson Co-morbidity score between the 2 groups. However, the interventions-acceptance group had shorter duration of therapy by 1.67 days (4.99 ± 2.50 days vs. 6.66 ± 2.34 days; P < 0.01) and LOS by 2 days (22.5 ± 51.4 days vs. 24.5 ± 3.04 days; P = 0.83). There were no significant differences in 14-day mortality and readmission rates between the 2 groups. Conclusion In patients with neurological conditions, ASP interventions were safe, and associated with a significant reduction in the duration of therapy and LOS. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]