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).


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.



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.


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


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™

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


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™ 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




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.





Centers, 2012 to 2014. Antimicrobial Agents and Chemotherapy. 2016;60(7):4355-4360. doi:10.1128/aac.00405-

16.


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.





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.

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