Samantha Trumm, Pharm.D. › images › downloads › Preparing_for...ceftazidime/avibactam for Gram-negative UTIs Total = 7,272 isolates Sader H, Castanheira M, Flamm R, Jones R.

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.