Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral).

PURPOSE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.

Impact of an Asynchronous Training for the Early Intervention and Childcare Workforce Addressing the Developmental Impact of the Opioid Crisis on Young Children.

OBJECTIVES: The US opioid epidemic contributes to a growing population of children experiencing neonatal abstinence syndrome (NAS) and adverse childhood experiences (ACEs). A review of the developmental impacts of the opioid crisis highlights that both prenatal exposure to teratogens and ACEs can result in developmental delay and disabilities. Training for the early intervention/early childhood (EI) systems is needed to enable them to meet the needs of this growing population. METHODS: To address this, an IRB-approved online training on best practices for NAS, developmental monitoring and referral, and trauma-informed care was created for Ohio EI providers who provided informed consent to participate. The feasibility of utilizing an online training was assessed. Knowledge on opioid addiction, NAS, ACEs, and early intervention provider characteristics were collected for 2973 participants. RESULTS: Within 6 months, the training reached providers in all Ohio counties and seventeen other states. 57% of providers reported caring for one or more children with a caregiver who has confirmed opioid use. 31% reported these children had experienced four or more ACEs. Providers' ACEs awareness was moderately associated with their experiences with prenatally-exposed youth. There was a significant increase in knowledge following training. Differences in post-training knowledge differed only by county-level opioid death rates, where those providers with low-medium opioid death rates reported more awareness of children with prenatal opioid exposure compared to participants who lived in a county with medium and medium-high opioid death rates. CONCLUSIONS: Online-training is feasible for closing gaps in the early intervention system.

Tumor necrosis factor-blocker dose escalation in rheumatoid arthritis patients in a pharmacy benefit management setting.

INTRODUCTION: Dose escalation with tumor necrosis factor (TNF)-blockers is poorly characterized in pharmacy benefit management (PBM) settings. METHODS: This retrospective study used integrated pharmacy and medical claims from the PBM Medco to characterize dose escalation among rheumatoid arthritis (RA) patients treated with etanercept and adalimumab. Data from adults with RA with pharmacy claims for etanercept or adalimumab between 1/1/2007 and 12/31/2009 and continuous enrollment for ≥ 6 months before and ≥ 12 months after first (index) pharmacy claim were analyzed. "New" patients had no claim for TNF-blocker in the 6 months prior to receipt of their index TNF-blocker; otherwise, they were classified as "continuing" patients. Endpoints included 12-month persistence and duration on index medication and dose escalation. Dose escalation (allowed per adalimumab label but not for etanercept) in patients' persistent ≥ 12 months was estimated using five methods: (1) average weekly dose ≥ 110% of recommended label dose; (2) average subsequent dose ≥ 130% of starting dose; (3) last dose ≥ 110% of starting dose; (4) ≥ 2 consecutive instances of dose ≥ 130% of starting dose; and (5) any instance where dose increase connoted an additional syringe/vial use. RESULTS: Data from 1,260 patients on etanercept and 852 patients on adalimumab were analyzed; 45.3 and 45.9% of new patients on etanercept and adalimumab, respectively, and 60.5 and 60.8% of continuing patients had ≥ 12 months persistence on index medication. Across all five methods used to estimate dose escalation, patients receiving etanercept had significantly lower rates of dose escalation (P < 0.001) than patients receiving adalimumab. For new patients, rates of dose escalation were 0.4-1.2% for etanercept and 8.3-14.1% for adalimumab. For continuing patients, rates ranged from 1.1 to 2.9% for etanercept and 7.0-28.3% for adalimumab. CONCLUSIONS: New and continuing patients from this PBM database on etanercept had significantly lower rates of dose escalation than patients on adalimumab.