Disclosure Statement Resistance is Futile Gerard L. Woolyhand, PharmD PGY 1 Resident St. Vincent s Medical Center Riverside NEFSHP Presentation January 23, 2016 I have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have direct or indirect interest in the subject matter of this presentation. Objectives History of Antimicrobial Development Describe the Generating Antibiotic Incentives Now (GAIN) Act Identify new antimicrobial therapies approved by the Food and Drug Administration (FDA) Discuss the mechanism of action, side effects, and place in therapy of antimicrobials approved by the FDA Decrease in antimicrobial development 1 2014 2015: 6 antimicrobials Factors in development 1,2,3 Production cost Drug discovery shift Novel mechanism Controlling resistance 1. Spellberg B, et al. Clin Infect Dis. (2004) 38 (9): 1279 1286. 2. IDSA. Clin Infect Dis. (2011) 52 (suppl 5): S397 S428. 3. ʺChallenges for the Development of New Antimicrobials Rethinking the Approaches: Report of a Workshop.ʺ 2006. Bad Bugs, No Drugs Bad bugs, no drugs report 2004 1 2010 report 2 Target ESKAPE 10 x 20 Initiative 2 Initiated IDSA in 2010 Promotes research and development Revision to Food and Drug Administration Safety and Innovation Act of 2012 2 Generating Antibiotic Incentives Now (GAIN) Act Bill introduced in June 2011; passed in July 2012 1 Purpose to promote development of antibacterial and antifungal drugs 1,2,3 Response to increasing organism resistance Serious or life threatening infection 1. IDSA. Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews. July 2014. 2. Boucher HW, et al. Clin Infect Dis 2009;48:1 12. 3. IDSA. Clin Infect Dis. (2010) 50 (8): 1081 1083. 1. ʺH.R.2182 Generating Antibiotic Incentives Now Act of 2011. 2. FDA. The Federal Register. 79 FR 32464 32481. 3. Brown ED. Can J Microbiol. 2013 Mar;59(3):153 6. 4. http://www.fda.gov/aboutfda/aboutthiswebsite/websitepolicies/ucm218116.htm 1
Defining Qualifying Pathogens Certain qualified pathogens FDA lists 4 criteria to be a qualified pathogen 1,2 Impact on public health Growth of drug resistant organisms Increase in resistance rates Morbidity and mortality Qualified pathogens Qualified Infectious Disease Product (QIDP) Generating Antibiotic Incentives Now (GAIN) Act Requires FDA to review clinical trial guidelines Recommendations by IDSA Consult with infectious disease and resistance experts Financial incentives Expedited review by FDA Market exclusivity for 5 additional years Additional 6 months for a companion diagnostic test 1. ʺH.R.2182 Generating Antibiotic Incentives Now Act of 2011. 2. FDA. The Federal Register. 79 FR 32464 32481. 1. ʺH.R.2182 Generating Antibiotic Incentives Now Act of 2011. 2. FDA. The Federal Register. 79 FR 32464 32481. Antibiotic Timeline 2014 Dalbavancin (Dalvance ) Oritavancin (Orbactiv ) Ceftolozane Tazobactam Brand name: Zerbaxa Cephalosporin/ beta lactamase inhibitor combination Complex side chains overcome resistant mechanisms of P. aeruginosa Beta lactamase inhibitor prevents hydrolysis of ceftolozane Tedizolid (Sivextro ) Ceftolozane tazobactam (Zerbaxa ) 2015 Ceftazidime avibactam (Avycaz ) Isavuconazonium (Cresemba ) 1. Ceftolozane tazobactam (Zerbaxa) [package insert]. 2. Zhanel GG, et al. Drugs. 2014 Jan;74(1):31 51. Ceftolozane Tazobactam MoA: Inhibits cell wall synthesis and binds to penicillin binding proteins (PBPs) 1 Bactericidal activity; time/mic parameter Indications 1,2 Complicated urinary tract infections (cuti) including pyelonephritis Complicated intra abdominal infections (ciai) with metronidazole Pending use for nosocomial pneumonia (phase III) Ceftolozane Tazobactam: Spectrum of Activity Gram negative Anaerobes Gram positive E. coli K. pneumoniae K. oxytoca P. aeruginosa P. mirabilis E. cloacae Prevotella Fusobacteriums Limited Clostridium species B. fragilis Streptococcus species Limited Staphylococcus species 1. Ceftolozane tazobactam (Zerbaxa) [package insert]. 2. Zhanel GG, et al. Drugs. 2014 Jan;74(1):31 51. 1. Ceftolozane Tazobactam (Zerbaxa) [package insert]. 2. Zhanel GG, et al. Drugs. 2014 Jan;74(1):31 51. 3. Snydman DR, et al. Antimicrob Agent Chemother. 2014;58(2):1218 122. 2
Ceftolozane Tazobactam: Recommended Dosing 1 g ceftolozane/ 0.5 g tazobactam IV q8hr 1 Infusion time 1 hr 1 Pneumonia dose: 2 g ceftolozane/ 1 g tazobactam IV q8hr 1 Label confusion 2 Renal adjustment when creatinine clearance (CrCl) < 50 ml/min 3,4 Creatinine clearance* Recommendeddose 30 to 50 ml/min 500 mg/ 250 mg IV q8hr 15 to 29 ml/min 250 mg/ 125 mg IV q8hr < 15 ml/min No recommendation ESRD Single loading dose of 500 mg/ 250 mg IV; 100 mg/ 50 mg q8hr IV Ceftolozane Tazobactam Adverse effects 1,2 Nausea (5.2%) Diarrhea (3.9%) Headache (4.2%) Pyrexia (3.3%) Monitoring 2 Renal function Cost 3 Wholesale acquisition cost (WAC) $83 per vial WAC per day $25 $240 *Using Cockcroft Gault formula 1. Liscio JL, et al. Int J Antimicrob Agents. 2015 Sep;46(3):266 71. 2. ʺFDA Drug Safety Communication: Ceftolozane and Tazobactam). 3. ʺCeftolozane Tazobactam (Zerbaxa) [package insert]. 4. Zhanel GG, et al. Drugs. 2014 Jan;74(1):31 51. 1. Liscio JL, et al. Int J Antimicrob Agents. 2015 Sep;46(3):266 71. 2. Ceftolozane Tazobactam (Zerbaxa) [package insert]. 3. ʺProduct Guide for Pharmacy: Zerbaxa Ceftolozane Tazobactam.ʺ Ceftazidime Avibactam Brand name: Avycaz 3 rd generation cephalosporin/ beta lactamase inhibitor 1,2 MoA: Inhibits cell wall synthesis and binds to PBPs 1,3 Bactericidal activity; time/mic parameter Indications 1,2 cuti including pyelonephritis ciai Pending use nosocomial pneumonia (phase III) Avibactam: The New Kid on the Block Novel non beta lactam, beta lactamase inhibtor 1 Acyl enzyme stabilizes beta lactamase and promotes recyclization 2,3 Combined with beta lactam to extend spectrum of activity 1,4 Avibactam Clavulanic acid Tazobactam Sulbactam 1. Zhanel GG, et al. Drugs. 2013 Feb;73(2):159 77. 2. Lagacé Wiens P, et al. Core Evid. 2014 Jan 24;9:13 25. 3. Ceftazidime avibactam (Avycaz). [package insert] 1. Zhanel GG, et al. Drugs. 2013 Feb;73(2):159 77. 2. Winkler ML, et al. Antimicrob. Agents Chemother. 2015 59(7): 3700 3709. 3. Ehmann DE, et al. J Biol Chem 2013 288(39): 27960 27971. 4. Lagacé Wiens P, et al. Core Evid. 2014 Jan 24;9:13 25. Ceftazidime Avibactam: Spectrum of Activity Gram negative coverage 1 Avibactam enhances coverage to AmpC, CRE, and ESBL Ambler classification system 2 Classes A, C, and D 3 Klebsiella species E. coli MDR P. aeruginosa Citrobacter species Enterobacter species Ceftazidime Avibactam: Spectrum of Activity Gram positive Streptococcus species Limited Staphylococcus Ceftazidime avibactam not fully assessed Anaerobes B. fragilis C. perfringens Prevotella species 1. Lagacé Wiens P, et al. Core Evid. 2014 Jan 24;9:13 25.. 2. Liscio JL, et al. Int J Antimicrob Agents. 2015 Sep;46(3):266 71. 3. Zhanel GG, et al. Drugs. 2013 Feb;73(2):159 77. 1. Lagacé Wiens P, et al. Core Evid. 2014 Jan 24;9:13 25.. 2. Stachyra, et al. J Antimicrob Chemother. 2009;64:326 329. 3. Zhanel GG, et al. Drugs. 2013 Feb;73(2):159 77. 3
Ceftazidime Avibactam: Recommended Dosing 2 g ceftazidime/ 0.5 g IV avibactam Infusion time 2 hr Renal dose adjustment required Creatinine clearance* Recommended dose 31 to 50 ml/min 1 g/ 0.25 g IV q8hr 16 to 30 ml/min 0.75 g/ 0.19 g IV q12hr 6 to 15 ml/min 0.75 g/ 0.19 g IV q24hr Ceftazidime Avibactam Adverse effects( 10%) 1 Vomiting Nausea Constipation Anxiety Monitoring 1 Renal function Cost 2 WAC $285 per vial 5 ml/min 0.75 g/ 0.19 g IV q48hr *Using Cockcroft Gault formula Ceftazidime avibactam (Avycaz). [package insert]. 1. Ceftazidime avibactam (Avycaz). [package insert]. 2. ʺAvycaz Approval and Labeling Restrictions.ʺ Ceftolozane tazobactam Ceftazidime avibactam Novel structure Ceftolozane Avibactam Indications ciai and cuti ciai and cuti Pending pneumonia Pending pneumonia Microbiology Potent against P. aeruginosa Streptococcus species B. fragilis (CRE) Ambler classes A,C, D Streptococcus species B. fragilis C. perfringens Dosing q8hr, renal adjustment q8hr, renal adjustment Adverse events GI related GI related Clinical trials Phase III approval Phase II approval Limited evaluation of Cost $83 per vial $285 per vial Ceftazidime avibactam preferred therapy Liscio JL, et al. Int J Antimicrob Agents. 2015 Sep;46(3):266 71. Tedizolid: The New Ox on the Block Brand name: Sivextro Oxazolidinone drug class 1 Prodrug tedizolid phosphate to tedizolid 1,2 MoA: Inhibits bacterial protein synthesis 1,2 Bacteriostatic activity; AUC/MIC parameter Overcomes chloramphenicol florfenicol resistance (cfr) resistance mechanism Indications 3 Acute bacterial skin and skin structure infections (ABSSSI) Pending approval for nosocomial pneumonia Dosing 1 200 mg PO or IV q24hr for 6 days 1:1 conversion for IV to PO 1. Tedizolid (Sivextro) [package insert] 2. Wong E, et al. Pharmacy and Therapeutics. 2014;39(8):555 579. 3. Zhanel GG, et al. Drugs. 2015 Feb;75(3):253 70. Tedizolid: Spectrum of Activity Overcomes chloramphenicol florfenicol resistance (cfr) resistance mechanism Gram Positive 1,2 S. Aureus (MSSA and MRSA) Streptococcus species E.faecalis E. faecium Gram Negative 2 Anaerobes 3 Haemophilus influenzae Moraxella cattarhalis Bacteroides species Clostridum species Peptostreptococcus species Tedizolid Medication Safety Adverse effects 1,2 Nausea (8%) Headache (6%) Diarrhea (4%) Thrombocytopenia (2%) Incidence less in tedizolid 2.1% vs linezolid 4.5% (p=0.0175) Monitoring 1,3 CBC 1. Tedizolid (Sivextro) [package insert] 2. Kisgen JJ, et al. Am J Health Syst Pharm. 2014 Apr 15;71(8):621 33 3. Zhanel GG, et al. Drugs. 2015 Feb;75(3):253 70. 1. Tedizolid (Sivextro) [package insert] 2. Zhanel GG, et al. Drugs. 2015 Feb;75(3):253 70. 3. Wong E, et al. Pharmacy and Therapeutics. 2014;39(8):555 579 4
Tedizolid 1 Linezolid 2,3 Indications ABSSSI ABSSSI CAP and HCAP Microbiology Resistance MSSA MRSA Enterococcus species (VRE) Potent concentrations Overcome cfr resistance MSSA MRSA Enterococcus species (VRE) MRSA resistance Dosing 200 mg IV/PO for 6 days 600 mg IV/PO for 10 days Adverse events GI upset GI upset Thrombocytopenia (less) Thrombocytopenia Drug Interactions Cost Minimal MAO inhibitor No adrenergic agents No serotonergic agents $368.67 per tablet $282 per vial MAO inhibitor Adrenergic agents Serotonergic agents $183.67 per tablet $75 per IV solution 1. Tedizolid (Sivextro) [package insert] 2. Linezolid (Zyvox) [package insert]. Linezolid preferred therapy in clinical practice 3. Linezolid (Zyvox). Lexicomp Online. Isavuconazonium Sulfate Brand name: Cresemba Azole antifungal Prodrug that converts to active form isavuconazole 1 MoA: Inhibits the enzyme lanosterol 14 alphademethylase reducing production of ergosterol 1 Indications 1,2,3 Invasive aspergillosis Invasive mucormycosis 1. Isavuconazonium sulfate (Cresemba )[package insert]. 2. NCT00413218. 3. Viljoen J, et al. Antimicrob Agents Chemother. 2015 Mar;59(3):1671 9. Isavuconazonium: Spectrum of Activity Mold and yeast 1 Aspergillus flavus Aspergillus fumigatus Aspergillus niger Mucorales (Rhizopus oryzae and mucormycetes species) Isavuconazonium: Dosage Forms and Dosing Capsule 186 mg 2 caps PO q8hr for 6 doses 186 mg 2 caps PO q24hr 186 mg of isavuconazonium sulfate is equivalent to 100 mg of isavuconazole Injection LD: 372 mg IV q8hr for 6 doses MD: 372 mg IV q24hr 372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole 1. Isavuconazonium sulfate (Cresemba )[package insert]. 2. http://www.rxlist.com/cresemba drug.htm Isavuconazonium sulfate (Cresemba )[package insert]. Isavuconazonium: Medication Safety Isavuconazonium Sulfate No renal impairment adjustments No mild or moderate hepatic adjustments; unknown with severe hepatic impairment Contraindications Strong CYP3A4 inhibitors/ inducers Short QT syndrome Warnings/ Precautions Hepatic adverse reactions Infusion related reactions Adverse effects ( 5%) 1 Nausea/ vomiting/ diarrhea Hypokalemia Cough Peripheral edema Back pain Monitoring 1 Liver function Infusion reactions Cost 2 AWP $84 per capsule AWP $286.20 per vial Isavuconazonium sulfate (Cresemba )[package insert]. Isavuconazonium sulfate (Cresemba )[package insert]. Isavuconazonium (Cresemba). Lexicomp Online. 5
Isavuconazonium Sulfate Pros IV and PO options Daily dosing for maintenance Therapy for resistance or refractory patients Cons Limited clinical trials (small sample size) Drug interactions Place in therapy Second to third line option Summary GAIN Act promotes the creation of new antimicrobials that overcome MDRO Antimicrobials approved by the FDA provide clinical use in MDRO Recently approved antimicrobials have new mechanisms of actions, limited side effects, and distinct places in therapy Assessment Question #1 Which of the following drug class(es) does the GAIN Act provide incentives and promote as a QIDP? A. Antibacterials B. Antifungals C. Antivirals D. Anti parasitics E. A and B only Assessment Question #2 What feature describes ceftolozane tazobactam mechanism of action allowing it to overcome resistant mechanisms of P. aeruginosa? A. The beta lactamase inhibitor, tazobactam, is potent towards resistant mechanisms B. The complex side chains of ceftolozane are able to neutralize resistant mechanisms C. The large molecule size of ceftolozane diverts resistant mechanisms to tazobactam D. The potent killing activity of ceftolozane tazobactam overcomes resistant mechanisms Assessment Question #3 What feature(s) is/are TRUE about avibactam? A. Non beta lactam, beta lactamase inhibitor B. Recycling of the beta lactamase inhibitor allows repeated use to overcome resistance C. Avibactam enhances coverage to AmpC, CRE, and ESBL infections D. A and B only E. All statements above are true Resistance is Futile Gerard L. Woolyhand, PharmD PGY 1 Resident St. Vincent s Medical Center Riverside NEFSHP Presentation January 23, 2016 6
Meet the Vancins Dalbavancin (Dalvance ) Indication: ABSSSI Dose: 1000 mg IV once; 500 mg IV 1 week later (over 30 min) Microbiology: S. aureus (including MRSA), Streptococcus species, and Enterococcus species Adverse effects: Nausea, headache, and diarrhea Oritavancin (Orbactiv ) Indication: ABSSSI Dose: 1200 mg IV single dose (infused 3 hr) Microbiology: S. aureus (including MRSA), Streptococcus species, and Enterococcus species Adverse effects: Nausea, vomiting, headache, and diarrhea Ceftazidime Avibactam: Spectrum of Activity Ambler Classification Enzyme Most Common Bacteria Class A Class B (metallo βlactamase) Class C KPC, SME, IMI, NMC, GES IMP, VIM, GIM, SPM AmpC, FOX, CMY, LAT, ACC, DHA (ESBL and carbapenemases) P. Aeruginosa Acinetobacter spp. Class D OXA Acinetobacter spp. Zhanel GG, et al. Drugs. 2010 May 7;70(7):859 86. 1. Lagacé Wiens P, et al. Core Evid. 2014 Jan 24;9:13 25. 2. Sader HS, et al. Antimicrob Agents Chemother. 2014;58(3):1684 92. 3. Zhanel GG, et al. Drugs. 2013 Feb;73(2):159 77. Ceftolozane Tazobactam MIC Values Ceftazidime Avibactam MIC Values Ceftolozane tazobactam (Zerbaxa) [package insert]. Ceftazidime avibactam (Avycaz). [package insert] Tedizolid Phosphate MIC Values References 1. Spellberg B, Powers JH, Brass EP, et al. Trends in antimicrobial drug development: implications for the future. Clin Infect Dis. (2004) 38 (9): 1279 1286. 2. Infectious Diseases Society of America (IDSA). Combating antimicrobial resistance: policy recommendations to save lives. Clin Infect Dis. (2011) 52 (suppl 5): S397 S428. 3. ʺChallenges for the Development of New Antimicrobials Rethinking the Approaches: Report of a Workshop.ʺ Treating Infectious Diseases in a Microbial World: Report of Two Workshops on Novel Antimicrobial Therapeutics. Washington, DC: The National Academies Press, 2006. 4. IDSA. Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews. July 2014. http://www.idsociety.org/uploadedfiles/idsa/policy_and_advocacy/current_topics_and_issue s/advancing_product_research_and_development/bad_bugs_no_drugs/statements/as%20an tibiotic%20discovery%20stagnates%20a%20public%20health%20crisis%20brews.pdf. Web. 10 Oct 2015. 5. Boucher HW, Talbot GH, Bradley JS. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. (2010) 50 (8): 1081 1083. 6. Infectious Diseases Society of America. The 10 ʹ20 Initiative: Pursuing a Global Commitment to Develop 10 New Antibacterial Drugs by 2020. Clin Infect Dis. (2010) 50 (8): 1081 1083. 7. Food and Drug Administration. Establishing a List of Qualifying Pathogens That Have the Potential to Pose a Serious Threat to Public Health Under the Food and Drug Administration Safety and Innovation Act. The Federal Register. 79 FR 32464 32481. 8. ʺH.R.2182 Generating Antibiotic Incentives Now Act of 2011 112th Congress (2011 2012).ʺ Library of Congress, 11 June 2011. Web. 29 Aug. 2015. <https://www.congress.gov/bill/112thcongress/house bill/2182/text>. Tedizolid (Sivextro) [package insert] 7
References Continued 11. Brown ED, Is the GAIN Act a turning point in new antibiotic discovery? Can J Microbiol. 2013 Mar;59(3):153 6. 12. Liscio JL, Mahoney MV, Hirsch EB. Ceftolozane/tazobactam and ceftazidime/avibactam: two novel β lactam/β lactamase inhibitor combination agents for the treatment of resistant Gramnegative bacterial infections. Int J Antimicrob Agents. 2015 Sep;46(3):266 71. 13. ʺFDA Drug Safety Communication: FDA Cautions about Dose Confusion and Medication Errors for Antibacterial Drug Zerbaxa (ceftolozane and Tazobactam).ʺ U.S. Food and Drug Administration, 1 June 2015. Web. 26 Sept. 2015. <http://www.fda.gov/drugs/drugsafety/ucm445919.htm>. 14. Ceftolozane Tazobactam (Zerbaxa) [package insert]. Lexington, MA: Cubist Pharmaceuticals; May 2015. 15. Zhanel GG, Chung P, Adam H et al. Ceftolozane/tazobactam: a novel cephalosporin/βlactamase inhibitor combination with activity against multidrug resistant gram negative bacilli. Drugs. 2014 Jan;74(1):31 51. 16. Snydman DR, McDermott LA, Jacobus NV. Activity of ceftolozane tazobactam against a broad spectrum of recent clinical anaerobic isolates. Antimicrob Agents Chemother. 2014;58(2):1218 23. 17. ʺProduct Guide for Phamracy: Zerbaxa Ceftolozane Tazobactam.ʺ Merck Sharp & Dohme Corp, 1 June 2015. Web. 11 Oct. 2015. <http://zerbaxa.com/pdf/zerbaxa ordering dosing.pdf>. 18. Ceftazidime Avibactam (Avycaz). [package insert]. Verona, Italy: GlaxoSmithKline Manufacturing; February 2015. References Continued 19. Winkler ML, Papp Wallace KM, Taracila MA, et al. Avibactam and Inhibitor Resistant SHV {beta} Lactamases. Antimicrob. Agents Chemother. 2015 59(7): 3700 3709. 20. Ehmann DE, Jahic H, Ross PL, et al. Kinetics of Avibactam Inhibition against Class A, C, and D {beta} Lactamases. J Biol Chem 2013 288(39): 27960 27971. 21. Sader HS, Castanheira M, Flamm RK et al. Antimicrobial activity of ceftazidime avibactam against Gram negative organisms collected from U.S. medical centers in 2012. Antimicrob Agents Chemother. 2014;58(3):1684 92. 22. Stachyra T, Premvathy L, Pechereau MC, et al. J Antimicrob Chemother. 2009;64:326 329. 23. Zhanel GG, Lawson CD, Adam H, et al. Ceftazidime avibactam: a novel cephalosporin/βlactamase inhibitor combination. Drugs. 2013 Feb;73(2):159 77. 24. Lagacé Wiens P, Walkty A, and Karlowsky JA. eftazidime avibactam: an evidence based review of its pharmacology and potential use in the treatment of Gram negative bacterial infections. Core Evid. 2014 Jan 24;9:13 25. 25. ʺAvycaz Approval and Labeling Restrictions.ʺ Allphase Pharma Consulting LLC, 26 Aug. 2015. Web. 12 Oct. 2015. <http://allphasepharma.com/dir/2015/08/26/1887/avicaz approval and labelingrestrictions/>. 26. Tedizolid (Sivextro) [package insert]. Cubist Pharmaceuticals Inc.; Lexington (MA): July 2015. 27. Wong E, Rab S. Tedizolid Phosphate (Sivextro): A Second Generation Oxazolidinone to Treat Acute Bacterial Skin and Skin Structure Infections.Pharmacy and Therapeutics. 2014;39(8):555 579. 28. Zhanel GG, Love R, Adam H, et al. Tedizolid: a novel oxazolidinone with potent activity against multidrug. resistant gram positive pathogens. Drugs. 2015 Feb;75(3):253 70. 29. Kisgen JJ, Mansour H, Unger NR, et al. Tedizolid: a new oxazolidinone antimicrobial. Am J Health Syst Pharm. 2014 Apr 15;71(8):621 33. References Continued 30. Linezolid (Zyvox) [package insert]. Pfizer US Pharmaceuticals; New York (NY): August 2015. 31. Linezolid (Zyvox). Lexicomp Online, Pediatric and Neonatal Lexi Drugs Online, Hudson, Ohio: Lexi Comp, Inc.; 2015. Web. 15 Oct 2015. 32. Isavuconazonium Sulfate (Cresemba )[package insert]. Northbrook, IL: Astellas Pharma US, Inc; April 2015. 33. Isavuconazonium (Cresemba). Lexicomp Online, Pediatric and Neonatal Lexi Drugs Online, Hudson, Ohio: Lexi Comp, Inc.; 2015. Web. 14 Oct 2015. 34. Zhanel GG, Calic D, Schweizer F, et al. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs. 2010 May 7;70(7):859 86. 8