Samantha Trumm, Pharm.D. PGY-1 Resident
Avera McKennan Hospital and University Center
I have had no financial relationship over
the past 12 months with any commercial
sponsor with a vested interest in this
presentation
Describe common factors causing the development of multidrug-resistant bacteria.
Compare and contrast bacterial
susceptibility of the following 3 new antibiotics used to treat multidrug-resistant gram-negative infections: AVYCAZ™ (ceftazidime and avibactam), VABOMERE™ (meropenem and vaborbactam), and ZERBAXA™ (ceftolozane and tazobactam).
Identify the antibiotic class of each of the
components of the three medications
presented for treating multidrug-resistant
gram-negative infections.
Compare and contrast the three
medications in regards to administration,
storage, and/or stability characteristics.
Multidrug-resistant (MDR)-
nonsusceptible to at least 1 antimicrobial
from ≥ 3 medication classes
Extensively drug resistant (XDR)-
nonsusceptible to at least 1 antimicrobial
from ≥ 5 medication classes
Walkty A, Adam H, Baxter M et al. In vitro activity of ceftolozane/tazobactam versus antimicrobial non-
susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across
Canada as part of the CANWARD study, 2008–16. Journal of Antimicrobial Chemotherapy. 2017.
IDSA ‘’10 x ‘20 Initiative launched in 2010
CDC issued Class 1a recommendation to
monitor trends in the incidence of MDR • Class 1b recommendation to make MDR
prevention and control a patient safety priority
-Boucher H, Talbot G, Benjamin Jr D et al. 10 × ’20 Progress—Development of New Drugs Active Against Gram-
Negative Bacilli: An Update From the Infectious Disease Society of America. Clinical Infectious Diseases.
2013;56(12):1685-1694.
-MDRO Management | Guidelines Library | Infection Control | CDC. Cdcgov. 2017.
Khan Academy. Khan Academy. 2017.
Gram-negative bacteria
Cocci
Neisseria
Coccobacilli
Haemophilus influenzae
Rods
Lactose fermenting
Escherichia coli Klebsiella
Proteus Salmonella
Non-lactose fermenting
Pseudomonas
Efflux pump activation
Enzyme production
Porin reduction
Target site protection + modification
Environmental cell adaptation
Munita J, Arias C. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016;4(2).
Munita J, Arias C. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016;4(2).
Indications: Complicated urinary tract
infections and intra-abdominal infections
Dose: 2.5 grams IV q8h *Renal*
Adverse effects: Constipation, anxiety
(≥10%)
AVYCAZ® [package insert]. Italy: GlaxoSmithKline, 2016.
International Network for Optimal
Resistance Monitoring (INFORM)
program
Compared susceptibility of
ceftazidime/avibactam for Gram-
negative UTIs
Total = 7,272 isolates
Sader H, Castanheira M, Flamm R, Jones R. Antimicrobial Activities of Ceftazidime-Avibactam and Comparator
Agents against Gram-Negative Organisms Isolated from Patients with Urinary Tract Infections in U.S. Medical
Centers, 2012 to 2014. Antimicrobial Agents and Chemotherapy. 2016;60(7):4355-4360.
Sader H, Castanheira M, Flamm R, Jones R. Antimicrobial Activities of Ceftazidime-Avibactam and Comparator
Agents against Gram-Negative Organisms Isolated from Patients with Urinary Tract Infections in U.S. Medical
Centers, 2012 to 2014. Antimicrobial Agents and Chemotherapy. 2016;60(7):4355-4360.
Indication: Complicated urinary tract
infections
Dose: 4 grams IV q8h *Renal*
Adverse effects: Headache, phlebitis,
diarrhea (≥ 3%)
Vabomere [package insert]. Italy: Facta Farmaceutici, 2017
Compared susceptibility of meropenem-
vaborbactam for Gram-negative bacilli • Total = 14,304 isolates
• MDR = 1,210 isolates
• XDR = 161 isolates
• CRE = 264 isolates
Castanheira M, Huband M, Mendes R, Flamm R. Meropenem-Vaborbactam Tested against
Contemporary Gram-Negative Isolates Collected Worldwide during 2014, Including Carbapenem-
Resistant, KPC-Producing, Multidrug-Resistant, and Extensively Drug-Resistant Enterobacteriaceae.
Antimicrobial Agents and Chemotherapy. 2017;61(9):e00567-17.
Castanheira M, Huband M, Mendes R, Flamm R. Meropenem-Vaborbactam Tested against
Contemporary Gram-Negative Isolates Collected Worldwide during 2014, Including
Carbapenem-Resistant, KPC-Producing, Multidrug-Resistant, and Extensively Drug-Resistant
Enterobacteriaceae. Antimicrobial Agents and Chemotherapy. 2017;61(9):e00567-17.
Castanheira M, Huband M, Mendes R, Flamm R. Meropenem-Vaborbactam Tested against
Contemporary Gram-Negative Isolates Collected Worldwide during 2014, Including
Carbapenem-Resistant, KPC-Producing, Multidrug-Resistant, and Extensively Drug-Resistant
Enterobacteriaceae. Antimicrobial Agents and Chemotherapy. 2017;61(9):e00567-17.
Castanheira M, Huband M, Mendes R, Flamm R. Meropenem-Vaborbactam Tested against
Contemporary Gram-Negative Isolates Collected Worldwide during 2014, Including
Carbapenem-Resistant, KPC-Producing, Multidrug-Resistant, and Extensively Drug-Resistant
Enterobacteriaceae. Antimicrobial Agents and Chemotherapy. 2017;61(9):e00567-17.
Ceftolozane/tazobactam Indications: Complicated urinary tract
infections and intra-abdominal infections Dose: 1.5 grams IV q8h *Renal*
Adverse effects: Nausea, diarrhea,
headache, fever (≥5 %)
Zerbaxa [package insert]. Massachusetts: Cubist Pharmaceuticals, 2015.
Pseudomonas aeruginosa isolates
collected from 10-15 hospitals in Canada
from 2008-2016 • Total = 3,229 isolates
• MDR = 462 isolates (14.3%)
• XDR = 84 isolates (2.6%)
Tested ceftolozane/tazobactam
susceptibility Walkty A, Adam H, Baxter M et al. In vitro activity of ceftolozane/tazobactam versus antimicrobial non-
susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from
across Canada as part of the CANWARD study, 2008–16. Journal of Antimicrobial Chemotherapy. 2017.
Results:
MDR: 90.5% susceptibility to
ceftolozane/tazobactam
XDR: 78.6% susceptibility to
ceftolozane/tazobactam
Walkty A, Adam H, Baxter M et al. In vitro activity of ceftolozane/tazobactam versus antimicrobial non-
susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from
across Canada as part of the CANWARD study, 2008–16. Journal of Antimicrobial Chemotherapy. 2017.
Avycaz™ Vabomere™ Zerbaxa™
Preparation Reconstituted and
further diluted
Reconstituted
and further
diluted
Reconstituted
and further
diluted
IV
Compatibility
D5W, NS NS only D5W, NS
Storage Room temp: 12 h
Refrigerated: 24 h
Room temp: 4h
Refrigerated: 22 h
Room temp: 24 h
Refrigerated: 7 d
Cost per day $850-1100 $900-1200 $300-350
AVYCAZ® [package insert]. Italy: GlaxoSmithKline, 2016.
Vabomere [package insert]. Italy: Facta Farmaceutici, 2017
Zerbaxa [package insert]. Massachusetts: Cubist Pharmaceuticals, 2015.
Avycaz™
CRE
ESBL
Vabomere™
CRE
Zerbaxa™
MDR Pseudomonas
CRE: carbapenem-resistant
Enterobacteriaceae
1. Which of the following are mechanisms
in which bacteria develop resistance to
antibiotics?
A. Production of β-lactamase
B. Activation of efflux pumps
C. Decreased number of porins
D. All of the above
Efflux pump activation
Enzyme production
Porin reduction
Target site protection + modification
Environmental cell adaptation
Munita J, Arias C. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016;4(2).
2. Which of the following antibiotics would
be the BEST option for treating a MDR
Pseudomonas aeruginosa infection?
A. Avycaz™ (ceftazidime/avibactam)
B. Vabomere™ (meropenem/vaborbactam)
C. Zerbaxa™ (ceftolozane/tazobactam)
1. Which of the following trade names are
correctly matched up with its
corresponding generic name?
A. Vabomere (ceftazidime/vaboractam)
B. Avycaz (ceftaroline/avibactam)
C. Zerbaxa(ceftolozane/tazobactam)
D. Vabomere (meropenem/avibactam)
2. Which of the following antibiotics has the
longest stability in room temperature AND
refrigeration?
A. Avycaz™ (ceftazidime/avibactam)
B. Vabomere™ (meropenem/vaborbactam)
C. Zerbaxa™ (ceftolozane/tazobactam)
D. All have the same BUD
AVYCAZ® [package insert]. Italy: GlaxoSmithKline, 2016.
Vabomere [package insert]. Italy: Facta Farmaceutici, 2017
Zerbaxa [package insert]. Massachusetts: Cubist Pharmaceuticals, 2015.
Avycaz™ Vabomere™ Zerbaxa™
Preparation Reconstituted and
further diluted
Reconstituted
and further
diluted
Reconstituted
and further
diluted
IV
Compatibility
D5W, NS NS only D5W, NS
Storage Room temp: 12 h
Refrigerated: 24 h
Room temp: 4h
Refrigerated: 22 h
Room temp: 24 h
Refrigerated: 7 d
Cost per day $850-1100 $900-1200 $300-350
Walkty A, Adam H, Baxter M et al. In vitro activity of ceftolozane/tazobactam versus antimicrobial non-
susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across
Canada as part of the CANWARD study, 2008–16. Journal of Antimicrobial Chemotherapy. 2017.
Boucher H, Talbot G, Benjamin Jr D et al. 10 × ’20 Progress—Development of New Drugs Active Against Gram-
Negative Bacilli: An Update From the Infectious Disease Society of America. Clinical Infectious Diseases.
2013;56(12):1685-1694.
MDRO Management | Guidelines Library | Infection Control | CDC. Cdcgov. 2017.
Munita J, Arias C. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016;4(2).
AVYCAZ® [package insert]. Italy: GlaxoSmithKline, 2016.
Sader H, Castanheira M, Flamm R, Jones R. Antimicrobial Activities of Ceftazidime-Avibactam and Comparator
Agents against Gram-Negative Organisms Isolated from Patients with Urinary Tract Infections in U.S. Medical
Centers, 2012 to 2014. Antimicrobial Agents and Chemotherapy. 2016;60(7):4355-4360. doi:10.1128/aac.00405-
16.
Vabomere [package insert]. Italy: Facta Farmaceutici, 2017
Castanheira M, Huband M, Mendes R, Flamm R. Meropenem-Vaborbactam Tested against Contemporary
Gram-Negative Isolates Collected Worldwide during 2014, Including Carbapenem-Resistant, KPC-Producing,
Multidrug-Resistant, and Extensively Drug-Resistant Enterobacteriaceae. Antimicrobial Agents and
Chemotherapy. 2017;61(9):e00567-17.
Zerbaxa [package insert]. Massachusetts: Cubist Pharmaceuticals, 2015.
Walkty A, Adam H, Baxter M et al. In vitro activity of ceftolozane/tazobactam versus antimicrobial non-
susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across
Canada as part of the CANWARD study, 2008–16. Journal of Antimicrobial Chemotherapy. 2017.