Objective: To review the current literature describing pharmacology, pharmacokinetics/pharmacodynamics (PK/PD), efficacy, and safety of linezolid and daptomycin for the treatment of central nervous system (CNS) infections caused by vancomycin-resistant Enterococcus (VRE) faecium. Data Sources: A literature search of PubMed/MEDLINE databases was conducted (from 1950 to April 2020) utilizing the following key terms: vancomycin-resistant Enterococcus, VRE, meningitis, ventriculitis, CNS infection, daptomycin, and linezolid. Study Selection and Data Extraction: All relevant studies and case reports describing the treatment of VRE faecium from the CNS with linezolid or daptomycin were included. Data Synthesis: A total of 17 reports describing 22 cases were identified. There were 15 of 19 cases involving linezolid that reported clinical cure, of which 53.3% were monotherapy. Only 5 of 9 cases involving intravenous (IV) daptomycin resulted in cure; all 4 cases reporting daptomycin administration via the intrathecal or intraventricular route achieved clearance from the cerebrospinal fluid (CSF). Relevance to Patient Care and Clinical Practice: The preferred treatment option for VRE faecium infections involving the CNS remains unclear. Supporting evidence through observational case reports have described varying outcomes with linezolid and daptomycin. This review compares reported outcomes between the 2 agents and provides a thorough discussion on drug- and patient-specific variables to consider. Conclusions: Linezolid monotherapy appears to be safe and effective for the treatment of susceptible-VRE faecium CNS infections, with consideration of therapeutic drug monitoring in special populations and with prolonged treatment duration. Daptomycin is an effective treatment option via intrathecal or intraventricular administration when neurosurgical access is available. The role of IV daptomycin remains inconclusive.

A price increase of pyrimethamine tablets in the United States has made the life-saving drug difficult to acquire for hospitalized patients who need it most. We report the successful use of a pyrimethamine oral suspension compounded from an economical bulk powder in a patient with acute toxoplasmic encephalitis.

BackgroundThe impact of antimicrobial stewardship programs (ASPs) depends on physician perception of antimicrobial stewardship and institutional antibiotic prescribing culture. At Rush University Medical Center (RUMC), we conducted an antimicrobial stewardship study targeting inpatient levofloxacin (FQ) use and assessed rates of implementation of recommendations (IORs) by general medicine (GM), vs. surgical services (SS) (general surgery, urology, orthopedics and neurosurgery), vs. transplant surgery-immunocompromised host (T-ICH) teams when made by either infectious disease pharmacists (IDPharmD) or infectious disease fellows (IDMDF).MethodsBetween August 13, 2018 and January 15, 2019 at RUMC, IDPharmDs reviewed 251 inpatients on FQ, and made ASP recommendations on 36 (14%) that were communicated via telephone. No scripted discussion or note was utilized. From January 15, 2019 to April 19, 2019, an IDMDF reviewed 207 inpatients on FQ, and made ASP recommendations on 47 (22%). IDMDF’s recommendations were communicated via a scripted discussion describing the role of ASP, highlighting the importance of optimizing FQ use due to toxicity, low rates of RUMC’s FQ susceptibilities and to decrease rates of resistance. Telephone recommendations were made to the primary team house staff or attending followed by a templated electronic note left in the medical chart. Rates of IORs were assessed during each period and by each group.ResultsIn 20 out of 83 recommendations (24%), no antibiotic was indicated (Figure 1). GM teams had the highest overall (IDPharmD + IDMDF) IOR (76%), compared with 40% IOR for both SS and T-ICH groups. For all groups, the scripted IDMDF recommendations had higher IOR compared with the nonscripted IDPharmD recommendations (GM 89% vs. 61%; SS 50% vs. 29%; T-ICH 50% vs. 0%).ConclusionASP interventions using scripted discussions and notes by an IDMDF were more effective than nonscripted IDPharmD interventions across all service lines. Both interventions were less successful with SS or T-ICH compared with GM services. These findings demonstrate the need for further research to understand the importance of scripted vs. nonscripted communication methods by pharmacists and ID physicians, and to develop alternative communication models for nongeneral medicine service providers. Disclosures All authors: No reported disclosures.

BackgroundA previous pre–post quasi-experimental study performed at an academic medical center assessed benefits of daily stewardship review with and without rapid diagnostic technology (RDT). The study found no difference in time to effective antibiotic therapy when comparing daily stewardship review to RDT and historical control groups. However, vancomycin duration of therapy significantly decreased with daily stewardship review compared with control (31.8 vs. 66 hours, P < 0.001). Subsequent elimination of this RDT saved the institution $53,000 in annual costs. However, the effect of the decrease in vancomycin use on this institution’s annual costs is unknown.MethodsThe purpose of the present study is to determine the difference in institutional costs associated with vancomycin after implementation of a stewardship intervention. A retrospective cost analysis was performed which included hospitalized adults on vancomcyin for positive blood cultures from June to October 2014 (preintervention) and June to October 2015 (postintervention). The primary outcome was the amount of institutional cost saved, including drug, phlebotomy, laboratory, nursing, and pharmacy costs. Secondary outcomes included vancomycin DOT/1,000 patient-days, nephrotoxicity, in-hospital mortality, and length of stay.ResultsInstitutional cost savings associated with vancomycin over 5 months amounted to $2,900 for an extrapolated cost savings of $6,960 per year. Although this cost savings was minimal, there were decreases in each individual vancomycin cost component. Drug acquisition was associated with the largest cost reduction represented by a 26% decline. Next, phlebotomy and laboratory costs each decreased by 24%, while nursing and pharmacy costs decreased by 7% and 4%, respectively. There were no differences in vancomycin DOT/1,000 patient-days, nephrotoxicity, in-hospital mortality, or length of stay.ConclusionVancomycin is associated with many hidden ancillary costs, and pharmacy and nursing labor remain substantial despite a reduction in its use. The tracking of antimicrobial stewardship actions is highly recommended; however, more research is needed to determine the optimal process for a vancomycin cost analysis.Disclosures All authors: No reported disclosures.

Background Enterobacterales are a significant cause of bloodstream infections (BSI) in hospitalized patients. Prior evidence suggests that treatment with piperacillin/tazobactam may not be ideal for BSI. Piperacillin/tazobactam clinical breakpoints were recently updated by the Clinical and Laboratory Standards Institute (CLSI). Methods We retrospectively evaluated Enterobacterales blood isolates identified by MALDI-TOF (Vitek MS, bioMérieux) between January 1, 2017 through December 31, 2021 at Rush University Medical Center in Chicago, Illinois. Antimicrobial susceptibility testing was performed using NM43 or NM56 panels on the MicroScan WalkAway 96 (Beckman Coulter). The range of dilutions of piperacillin/tazobactam included on both panels was 8/4 to 64/4 μg/mL. Minimal inhibitory concentrations (MIC) were interpreted using current CLSI breakpoints. Results We evaluated 1597 Enterobacterales isolates. Most isolates identified were Escherichia coli [n=806 (50%)] and Klebsiella pneumoniae [n=358 (22%)]. The majority of isolates (90.4%) were susceptible; 28 (1.8%) isolates were susceptible-dose dependent and 125 (7.8%) were resistant to piperacillin/tazobactam using the new CLSI breakpoints (Table). 236 isolates had a multidrug-resistant phenotype, of which 216 (92%) were confirmed as an ESBL. Among ESBL-producing isolates, the majority (81%) were susceptible [MIC ≤ 8 µg/mL) to piperacillin/tazobactam. Isolates with confirmed carbapenemase production had off-scale MICs ( &gt; 64 µg/mL) (Figure). Piperacillin/Tazobactam Breakpoint Revision Table Overall changes in piperacillin/tazobactam interpretations using revised breakpoints. MDR-Enterobacterales piperacillin/tazobactam MIC distributions Piperacillin/tazobactam minimal inhibitory concentration distributions among multidrug-resistant Enterobacterales isolates. Conclusion While there was an increase in resistance, our results indicate that most Enterobacterales isolates tested susceptible to piperacillin/tazobactam using the revised CLSI breakpoints. Disclosures Nicholas M. Moore, PhD, D(ABMM), Abbott Molecular: Grant/Research Support|Cepheid: Grant/Research Support.