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Objectives Blood culture rapid diagnostic testing (RDT) aids in early organism identification and resistance gene detection. This information allows quicker transition to tailored antimicrobial therapy, improved patient outcomes and prevention of antimicrobial resistance. An antimicrobial treatment algorithm based on RDT results and local antibiograms can serve as a valuable clinical decision-support tool. This study assessed the proportion of appropriate antibiotic therapy recommendations using a novel paediatric RDT-guided treatment algorithm compared with standard care (SC) in paediatric bacteraemia. Methods This was a retrospective, observational study of admitted paediatric patients who received antibiotics for RDT-confirmed bacteraemia. Appropriateness of SC was compared with algorithm-recommended treatment. Antimicrobial appropriateness was defined as in vitro susceptibility to the organism identified through traditional microbiology. Clinical appropriateness took into consideration the ability to tailor therapy within 12 h of RDT results. Appropriateness was evaluated by two blinded, independent reviewers. Key findings Eighty-six blood cultures were included with 15 unique Gram-positive and Gram-negative species or genus identified. Comparative antimicrobial appropriateness of SC and algorithm-recommended treatment was 94.2% (81/86) and 100% (86/86), respectively (P = 0.06). Clinical assessment determined 39.5% (34/86) of SC patients were on appropriate therapy within 12 h of RDT result. Algorithm-recommended therapy was clinically appropriate in 97.7% (84/86) of patients (P < 0.001). There was a median time savings of 42.7 h (IQR 40.6, 49.4) for the patients able to be de-escalated as compared with waiting on final sensitivities. Conclusions Algorithm-guided treatment may allow most patients to be de-escalated to organism-tailored therapy earlier in their therapeutic course.

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Dementia-related psychosis (DRP) is common among patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD) and is associated with poor outcomes. HARMONY (NCT03325556) was a Phase 3, placebo-controlled, randomized, relapse-prevention study evaluating the efficacy and safety of pimavanserin for treating hallucinations and delusions associated with DRP. Patients with dementia and moderate-severe psychosis received open-label (OL) pimavanserin for 12 weeks. Patients with sustained response (≥30% reduction in Scale for the Assessment of Positive Symptoms hallucinations+delusions Total Score AND Clinical Global Impression-Improvement score of much/very much improved) at Weeks 8 and 12 were randomized 1:1 to continue pimavanserin or receive placebo for up to 26 weeks in the double-blind (DB) period. The primary endpoint was time from randomization to relapse of DRP. 392 patients enrolled. 217 (61.8%) eligible patients experienced sustained response and were randomized. OL response was similar regardless of dementia subtype (randomization rates: 59.8% AD, 71.2% PDD, 71.4% VaD, 45.5% DLB, 50.0% FTD), baseline disease characteristics, age, dementia severity, or previous drug therapy. The study stopped early for superior efficacy when a prespecified interim analysis revealed >2.8-fold reduction in risk of relapse with pimavanserin (hazard ratio: 0.353; 95% CI: 0.172, 0.727; 1-sided p=0.0023). Adverse event rates were low and balanced (OL: 36.2%; DB: 41.0% pimavanserin, 36.6% placebo). No negative impact on cognition or motor function was observed. The Harmony study demonstrated a robust decrease in hallucinations and delusions and significant maintenance of efficacy with pimavanserin treatment in DRP.