The prevalence of vancomycin-resistant enterococci has increased substantially over the last several years, and treatment options are limited [2 ]. Vancomycin has been a mainstay of therapy for Gram-positive infections, especially MRSA, but long-term outpatient parenteral antimicrobial therapy (OPAT) with vancomycin is complicated due to frequent dosing and the need for therapeutic drug monitoring to prevent potential toxicities [6 ]. Some patients are not candidates for prolonged intravenous antibiotics, including those likely to abuse a vascular access system and those unable to adhere to an OPAT regimen [7 ]. Furthermore, approximately 10% of OPAT regimens must be stopped prematurely due to adverse reactions, which may complicate the course of treatment and require a longer treatment duration with other antibiotics [7 ]. Treatment of Gram-positive infections, especially with S. aureus, presents a clinical challenge in need of creative therapeutic approaches. The single dose is sufficient for ABSSSIs due to the initial peak serum concentration of 140 mg/L and prolonged terminal half-life, which ranges from 245 to 393 h (~10–17 days) [10 , 11 ]. Pharmacokinetic data demonstrate that, on average, oritavancin maintains concentrations in several body compartments above the MIC90 threshold for at least a month from initial dosing [10 ]. Oritavancin is active against a variety of Gram-positive species, and surveillance data from 2008 to 2012 of over 9000 S. aureus isolates demonstrate a minimum inhibitory concentration (MIC)90 of only 0.06 mg/L [12 ]. Among the 205 isolates with vancomycin MICs of 2 mg/L and the 100 isolates with daptomycin MICs of ≥1 mg/L within this study, the oritavancin MIC90 was 0.12 mg/L, and only 13 of these 305 (4%) isolates possessed oritavancin MICs >0.12 mg/L, the current FDA breakpoint for susceptibility [12 ]. From 2013 to 2014, when oritavancin was tested against 780 invasive community-acquired and 218 invasive healthcare-associated S. aureus isolates from blood culture specimens, all S. aureus were susceptible to oritavancin and the MIC50/90 values were 0.03/0.06 mg/L, respectively [13 ]. These MICs were consistent regardless of oxacillin susceptibility or multi-drug resistance phenotypes.

Data Sources: PubMed (January 1980-June 2016) was searched using combinations of the search terms methicillin-resistant Staphylococcus aureus, MRSA, bacteremia, ceftaroline, refractory , and persistent . Supplemental references were generated through review of identified literature citations. Ceftaroline fosamil (CPT) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI). Abstract presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-21, 2015; San Diego, CA. 51.

Address for correspondence: Martin Krsak, Medicine, Treatment Services for Patients with Concurrent Substance Use Disorders and Infections, Department of Infectious Diseases, University of Colorado School of Medicine, Anschutz Medical Campus, Mail Stop B163, Anschutz Outpatient Pavilion, 1635 Aurora Court, Aurora, CO 80045; e-mail: martin.krsak@cuanschutz.edu . Search for more papers by this author Taylor Morrisette , Taylor Morrisette Department of Pharmacy-Infectious Diseases, University of Colorado Hospital, Aurora, Colorado Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado Co first authors contributed equally to this work.Search for more papers by this author Matthew Miller , Matthew Miller Department of Pharmacy-Infectious Diseases, University of Colorado Hospital, Aurora, Colorado Search for more papers by this author Kyle Molina , Kyle Molina Department of Pharmacy-Infectious Diseases, University of Colorado Hospital, Aurora, Colorado Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado Search for more papers by this author Misha Huang , Misha Huang Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado Search for more papers by this author Laura Damioli , Laura Damioli Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado Search for more papers by this author Larissa Pisney , Larissa Pisney Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado Search for more papers by this author Megan Wong , Megan Wong Department of Pharmacy-Orthopedics, University of Colorado Hospital, Aurora, Colorado Search for more papers by this author Eric Poeschla , Eric Poeschla Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado Search for more papers by this author First published: 02 April 2020 Citations: 16 Funding: This research received no specific grant from any institution. Barriers to broader use of laLGPs include, among others, a relative lack of prospective data regarding efficacy in serious infections, a narrow United States Food and Drug Administration–approved indication restricted to only acute bacterial skin and skin structure infections, and lack of reimbursement infrastructure for inpatient settings.

Objective: To evaluate the efficacy and safety of long-acting lipoglycopeptides (laLGPs) in patients with osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections . Methods: A systematic literature search was performed using ‘dalbavancin’ and ‘oritavancin’ as search terms. One study found that more than one-quarter of patients experienced a complication while on therapy, most commonly complications of IV access [9], which result in rehospitalization in as many as 40% of patients [14]. Another limitation of OPAT is the high failure rate among persons who inject drugs (PWID), which is unfortunate as these patients are at risk for complicated infections that require prolonged hospitalization for IV antibiotics [15]. For these reasons, there is interest in using oritavancin and dalbavancin for complicated Gram-positive infections, beyond ABSSSIs, as an alternative to OPAT or in-hospital IV antibiotic administration because of their infrequent dosing which precludes the need for long-term IV placement.

Methods A rigorous literature search was conducted for studies involving vancomycin and suitable alternatives such as teicoplanin, linezolid, tedizolid, dalbavancin, telavancin, daptomycin, tigecycline, quinupristin/dalfopristin (streptogramins) and ceftobiprole/ceftaroline (cephalosporins). Key findings This review explored the limitations associated with the clinical utility of vancomycin in day-to-day clinical practice. It has been approved for the treatment of adult patients with hospital-acquired pneumonia (excluding ventilator-acquired pneumonia) and community-acquired pneumonia (CAP) in 12 European countries by the European Medicines Agency (EMA). The drug is highly safe and provides a suitable alternative to vancomycin for VISA treatment.[ 3 ] Ceftaroline fosamil is another fifth-generation cephalosporin that is FDA labelled for CAP (not caused by MRSA) and ABSSSI in adults and children above 2 months of age.

The most common use of oritavancin was in patients with acute bacterial skin and skin structure infections (ABSSSI), defined as cellulitis, abscess or non-surgical wounds (n = 25, 33%), followed by surgical wound infections (n = 12, 16%) and osteomyelitis or septic arthritis (n = 10, 13%). Clinical cure or improvement was achieved in 68 patients (93.2%), while five patients (6.8%) failed treatment; adverse reactions were reported in nine patients (12%). Thirty-five patients received oritavancin as inpatients; 20 patients (57%) had at least one hospital day avoided due to inpatient oritavancin administration resulting in a total cost avoidance of US$343,654. Conclusion In this series of 75 patients with Gram-positive infections, oritavancin treatment resulted in clinical cure or improvement in most patients, and was generally well tolerated. Oritavancin is FDA approved for ABSSSI treatment, although off-label use has been previously described [7 ,8 ,9 ]. The primary indication for oritavancin in our patient population was ABSSSI; these patients demonstrated clinical outcomes consistent with previous literature confirming usefulness of oritavancin for treatment of ABSSSI in a real-world setting [4 , 5 ]. Oritavancin was used for non-ABSSSI infection types in 49 patients (67%); our data suggest oritavancin is a safe and effective treatment option for complex Gram-positive infections, as 93.2% of patients had an outcome consistent with previous case series [7 ,8 ,9 , 15 ]. Reported oritavancin adverse reactions include infusion reactions, anemia, and chest pain [4 , 5 , 9 ]. The SOLO clinical trial report identified six patients with osteomyelitis, coded as an adverse event, leading to a warning in the prescribing information about use of oritavancin in osteomyelitis [5 ]. All osteomyelitis cases were discovered within 9 days of oritavancin administration, suggesting the osteomyelitis may have been subacute at the time of oritavancin administration.

Adequate home care, family support, and community resources must be considered [ 8 , 9 ]. Decisions about antibiotic choice and dosing and route of therapy should ideally be made by physicians with expertise in infectious diseases [ 10 ]. OPAT is usually provided by a team consisting of a physician, pharmacist, intravenous therapy nurse, and other support personnel who see patients frequently for clinical evaluations, are continually available to address problems, and regularly monitor laboratory parameters. These include infusion centers, extended care facilities, and self-administration by the patient or family [ 19 ]. For the series that have been collected for OPAT studies, the infections most commonly treated are osteomyelitis and skin and skin structure infections [ 6 ]. It is clear, however, that virtually any infection, including pneumonia, meningitis, and endocarditis, can be and has been treated with outpatient parenteral therapy after the patient is stabilized and responding in the hospital [ 20–23 ]. Another problem with outpatient care is that of reimbursement, which is often not sufficient for the resources and staff needed to provide optimal care and safety in some communities.