1.5 CONTACT HOURS 1.5 CONTACT HOURS David Mack / Science Source Newest lipoglycopeptides for the management of acute bacterial skin and skin structure infections By Allison M. Bell, PharmD; S. Travis King, PharmD; Katie E. Barber, PharmD; Kim G. Adcock, PharmD; Jamie L. Wagner, PharmD; and Kayla R. Stover, PharmD Abstract: Acute bacterial skin and skin kin and soft-tissue infections (SSTIs) repre- sent a broad spectrum of infections ranging structure infections (ABSSSIs) are some of S from superfi cial pyodermas to deep, necrotiz- the most commonly encountered infections ing infections.1,2 Most uncomplicated infections may worldwide. Hospitalizations as a result of be managed with topical therapies or simple surgical interventions; however, complicated SSTIs generally ABSSSIs are associated with high mortality. This require systemic antibiotic therapy and are likely to article discusses the role of oritavancin and require surgery.1,2 The common terminology through- dalbavancin, the two newest lipoglycopeptides, out the infectious disease literature has been SSTIs; however, in 2013, the FDA updated their industry in the context of the other available guidance for treatment of acute bacterial skin and I.V. infusion standard therapy options. skin structure infections and changed the terminology from complicated SSTIs to acute bacterial skin and Keywords: ABSSSIs, acute bacterial skin and skin structure infections, dalbavancin, daptomycin, lipoglycopeptides, oritavancin, telavancin, vancomycin www.tnpj.com The Nurse Practitioner • October 2018 31 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Newest lipoglycopeptides for the management of acute bacterial skin and skin structure infections skin structure infections (absssis) to better describe pathogens still account for a signifi cant proportion the type of infection suitable for treatment with newer of nonpurulent cellulitis, particularly in ambulatory antibiotics.3 patients.1,9,10 absssis are some of the most commonly encoun- Within the past decade, methicillin-resistant S. aureus tered infections and represent a major reason for (MRSA) infections have transitioned from a domi- seeking medical care worldwide. The combined emer- nant healthcare-associated pathogen to a major cause gence of antimicrobial resistance over the last few de- of both community-acquired (CA) and healthcare- cades and the lack of newly developed antimicrobial associated absssis.1,7,11 In an analysis of ambulatory agents complicate matters further. antibacterial therapy for uncomplicated skin infections Only within the last few years has the antimi- in otherwise healthy adults, MRSA accounted for ap- crobial armamentarium seen substantial growth. proximately 32% of all culture-confi rmed infections In particular, two recently approved lipoglycopep- and 77% of all S. aureus cultures.7 tides supplement the currently available options for The emergence of CA-MRSA and other resistant absssis: dalbavancin and oritavancin. phenotypes has altered the approach that clinicians must take when considering empiric antibiotic ther- ■ Epidemiology apy. The CDC continues to list MRSA as a “serious” absssis are prominent in both the inpatient and threat and strongly advocates for the development and ambulatory populations. Rates of infections have approval of novel therapeutic agents.12 increased signifi cantly over the past decades. When considering hospital admission rates for absssis from ■ Overview of current therapy 2000 to 2004, Edelsberg and colleagues found a 29% Vancomycin. A slowly bactericidal glycopeptide, van- increase in the number of admissions, whereas admis- comycin has activity against many Gram-positive or- sions for other infection types remained constant.4 ganisms, including pathogens frequently implicated in Of note, increases in absssis-related admissions were absssis. It is now a mainstay of therapy for the treat- largest in adults under age 65 and in patients from ment of serious absssis.13 Vancomycin disrupts the urban areas.4 cell wall synthesis pathways by binding to the terminal A more recent analysis of the Health-Core Inte- D-alanyl–D-alanine amino acids on cell wall precur- grated Research Database from 2005 to 2010 found sors, preventing transpeptidation reactions.13 It is dosed over 2.2 million absssis episodes, with more than based on actual body weight and administered by I.V. 90% diagnosed in the ambulatory setting.5 Hospital- infusion every 8 to 12 hours for patients with normal izations for absssis are now more common than for kidney function.14,15 community-acquired pneumonia. These hospitaliza- Current practice guidelines from the Infectious tions, particularly those associated with staphylococ- Diseases Society of America (IDSA) recommend I.V. cal absssis, are associated with a longer length of stay, infusion vancomycin as a fi rst-line empiric treatment higher hospital costs, and increased mortality.6 for management of severe purulent (abscess, furuncle, carbuncle) and nonpurulent (cellulitis, erysipelas, ■ Causative pathogens necrotizing infection) absssis.1 Gram-positive organisms, specifi cally Staphylococcus Although vancomycin has been the treatment of aureus and Streptococcus species, are the most common choice, its slow bactericidal activity, associated tox- causes of absssis. The distribution of these pathogens icities (including nephrotoxicity and ototoxicity), varies among infection types; however, among culture- hematologic abnormalities (thrombocytopenia and positive absssis, S. aureus predominates.7 Data from the neutropenia), infusion-related reactions, need for SENTRY surveillance program found S. aureus to be therapeutic monitoring, and frequent dosing schedule the causative pathogen in 48.1% of all absssis, followed have led to concerns about its continued utility.13 by Pseudomonas aeruginosa (9.4%) and Enterococcus Vancomycin should be monitored using serum species (8.8%).8 Beta-hemolytic Streptococcus species concentrations.1 In addition to necessary routine mon- accounted for only 4.2% of culture-positive infections. itoring, the frequency of dosing required can make Despite the lack of culture positivity for Streptococcus vancomycin a suboptimal choice for patients using species in numerous epidemiologic assessments, these outpatient I.V. infusion antibiotics for absssis. 32 The Nurse Practitioner • Vol. 43, No. 10 www.tnpj.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Newest lipoglycopeptides for the management of acute bacterial skin and skin structure infections Resistance to vancomycin is also an increasing con- and vancomycin-susceptible E. faecalis. Telavancin was cern due to an emergence of vancomycin-resistant S. fi rst FDA approved for treatment of absssis in 2009.21 aureus, vancomycin-intermediate S. aureus (VISA), and Similar to the mechanism of action of vancomycin, heteroresistant VISA (a possible precursor to VISA).13 telavancin inhibits bacterial cell wall synthesis and dis- Additionally, S. aureus has most recently been display- rupts the bacterial membrane.21,22 It is administered via ing an “MIC creep” (a gradual increase in minimum I.V. infusion.21 inhibitory concentration [MIC] of a drug required to Clinical success rates range between 80% and inhibit bacterial growth) toward vancomycin, with the 96%.23-26 Like daptomycin, telavancin is recommended majority of isolates demonstrating an MIC of 1 mcg/ in the current IDSA guidelines for absssis as an option mL rather than 0.25 mcg/mL as in previous decades.16 for empiric treatment of severe purulent absssis in As a result, an increased number of treatment fail- adults. Telavancin is only available as an I.V. infusion.1,27 ures and/or toxicities due to the use of elevated dos- Toxicities associated with telavancin include ages needed to overcome the higher MICs are being nephrotoxicity (with a black box warning for tela- observed.16 Vancomycin utility in enterococci is also di- vancin regarding increased mortality in patients with minishing, as vancomycin-resistant enterococci (VRE) moderate-to-severe kidney impairment). Warnings rates are approximately 83% in Enterococcus faecium include the risk of prolonged QT interval, hypersen- and 10% in Enterococcus faecalis (up from 8%).17 sitivity reactions, and prolongation of prothrombin Daptomycin. This cyclic lipopeptide antibiotic has time (PT) and activated partial thromboplastin time rapid bactericidal activity against various Gram-positive (aPTT).21 Despite a narrow spectrum susceptibility organisms, such as S. aureus (including MRSA) and profi le and comparable effi cacy, the nephrotoxicity, enterococci (including VRE). It was fi rst approved by black box warning, and increased cost compared with the FDA in 2003 for treatment of absssis.18 Daptomy- vancomycin have largely limited its clinical usage. cin binds in the septum of dividing bacteria, inducing rapid depolarization of cell membrane potentials and ■ Overview of newer agents disrupting synthesis of DNA, RNA, and proteins, ulti- Oritavancin. This semisynthetic lipoglycopeptide mately leading to cell death.18 It is administered via I.V. antibacterial is approved by the FDA for absssis infusion. Daptomycin is recommended as an option for caused by susceptible isolates of S. aureus, Strepto- empiric treatment of severe purulent absssis in adults coccus pyogenes, Streptococcus agalactiae, Streptococcus in the current IDSA guidelines for treatment of severe dysgalactiae, Streptococcus anginosus, Streptococcus in- complicated absssis.1 termedius, Streptococcus