Dr. Cluck Clinical Application New Antimicrobials EXAM 3

Question 1

What are the Newer Antibiotics?

Answer 1

-Ceftolozane(5)-tazobactam
-Ceftazidim(3)-avibactam
-Delafloxacin (FQ)
-Vancins: Oritavancin, Dalbavancin
-Tedizolid

Question 2

What is Delafloxacin FDA-approved for?

Answer 2

Community-acquired bacterial pneumonia (CABP)

Question 3

What is Ceftolozane-tazobactam FDA-approved for?

Answer 3

-Hospital-acquired bacterial pneumonia (HABP)

-Ventilator-associated bacterial pneumonia (VABP)

Question 4

Newer Antimicrobial agents

Answer 4

-Plazomicin
-Eravacycline
-Omadacycline
-Imipenem-cilastatin/relebactam
-Lefamulin
-Cefiderocol

Question 5

How does Plazomicin (Zemdri) achieve stability to
most aminoglycoside modifying enzymes (AMEs)?

Answer 5

Structurally enhanced sisomicin pharmacophore

Question 6

What is Plazomicin (Zmedri) FDA-approved for?
!!!

Answer 6

Only for complicated urinary tract infections (cUTI)
!!!

Question 7

The antibacterial approach and way of Elimination for Aminoglycosides?

Answer 7

-Bacteriocidal
-Eliminated through the kidney

Question 8

MOA of Plazomicin

Answer 8

Inhibits bacterial protein synthesis at the 30S ribosome and is rapidly bactericidal

Question 9

How are Plazomicin concentrations monitored in patients?

Answer 9

-Through monitoring is acceptable
-in systemic infections: AUC-based dosing is preferred

Question 10

Which organism is susceptible to Plazomicin?
!!!

Answer 10

-MRSA (but not Strep and Enterococci)!!

-CRE !!!
-ESBL producing Enterobacterales !!!
-Variable activity against New Dehli metallo ß lactamases !!!

Question 11

What is the Mechanism of Resistance in Plazomicin?

Answer 11

16s ribosomal methyltransferases (16S RMTases) -> decreased affinity to the drug target

Question 12

Which antimicrobial agent is outdated and should be used?

Answer 12

-Colistin
-bc of its Nephro- and Ototoxicity

-used as Adjunctive in MDR, especially CRE

Question 13

What is Eravacycline (Xerava) approved for?

Answer 13

-for complicated intra-abdominal infection (cIAI)!!!
-only IV !!

-synthetic fluorocycline
-similar to Tigecycline, but more potent against gram (+) cocci and gram (-) rods

Question 14

Spectrum of activity for Eravacycline

Answer 14

-similar to Tigecycline
-wide spectrum to Gram(+) and Gram(-) including difficult-to-treat MRSA, VRE, ESBL, and carbapenemase-producers
-NO activity against Pseudomonas

-activity against non-tuberculous mycobacteria and C. diff (so less C. diff with Eravacycline)

Question 15

MOA for Eravacycline

Answer 15

-similar to other tetracyclines: binding to 30S subunit -> inhibits protein synthesis
-bacteriostatic against many organisms, but has also shown bacteriocidal activity

Question 16

At what point is Eravacycline different from Tigecycline?
!!!

Answer 16

PK/PD: higher plasma concentration !!!

-> so MIC can be achieved, whereas Tigecycline doesn’t reach MIC for many organisms

-BUT CYP mediated metabolism -> Drug-Drug Interaction !!!

Question 17

Why is the clinical use for Tigecycline low?

Answer 17

Because of its PK/PD profile
-low plasma concentration -> doesn’t reach MIC
-hence not used for in UTIs and bacteremia

Question 18

Other benefits of Eravacycline over Tigecycline

Answer 18

-better tolerated (less nausea)
-reduced risk of C. diff (but also with Tigecycline)

-BUT lack of oral formulation

Question 19

Omadacycline (Nuzyra) FDA-approved for?

Answer 19

-Community-acquired bacterial pneumonia (CABP)
-acute bacterial skin and skin structure infection (ABSSSI)
-IV and PO

Question 20

Spectrum of Activity for Omadacycline

Answer 20

-similar to Tigecycline and Eravacycline

-wide spectrum to Gram(+) and Gram(-) including difficult-to-treat MRSA, VRE, ESBL, and carbapenemase-producers
-NO Pseudomonas
-activity against non-tuberculous mycobacteria

Question 21

What makes Omadacycline inconvenient?

Answer 21

Direction of the drug
-fast for 4 hours -> take with water and fast for 2 hours
-inconsistent dosing regimen

Question 22

Where is Omadacycline used?

Answer 22

-almost only non-tuberculous mycobacteria infections

-could be used for CRE and Acinetobacter (but there are other drugs for that)

Question 23

RECARBRIO (Imipenem-cilastin/Relebactam)
Relebactam - Carbapenem - RIO

Answer 23

-FDA-approved for complicated intraabdominal infections (cIAIs), UTIs, and HABP/VABP
-Relebactam is similar to avibactam

Question 24

Why do providers still hesitate to use Recarbio?

Answer 24

Because of seizure (it is still a carbapenem)

Question 25

Spectrum for Ceftazidime/avibactam Meropenem/vaborbactam Imipenem-cilastatin/ relebactam

Answer 25

-they all cover KPC-producer -they do not cover NDM-producer -they do not cover Carbapenem-resistant Acinetobacter baumannii

Question 26

Relebactam shows activity against which clinically relevant organism?

Answer 26

Pseudomonas

Question 27

In a study where Imipenem-Relebactam was compared to Pip-Tazo, Linezolid was added. What was the purpose of Linezolid?

Answer 27

Coverage of MRSA

Question 28

What would be a scenario to use Imipenem/Relebactam?

Answer 28

-In patients with Pseudomonas resistant to Ceftolozane(5)-tazobactam -> use Ceftaroline/avibactam OR IMI-REP -> If resistant to those use Cefiderocol (Fetroja)

Question 29

What is Lemafulin (Xenleta) FDA-approved for?

Answer 29

-Community-acquired bacterial pneumonia (CABP) -potential future use in skin soft tissue infections (SSTIs) and STDIs -IV: 150mg q12 -PO: 600mg q12 (due to low oral bioavailability)

Question 30

What is Retapamulin used for?

Answer 30

-topical treatment for skin soft tissue infections (SSTIs) due to methicillin-susceptible Staphylococcus aureus

Question 31

Spectrum of Activity for Lemafulin

Answer 31

-Drug class: Pleuromutilin -NOT considered gram(-) drug, but covers Haemophilus influenzae; Moraxella catarrhalis -covers gram(+): Staphylococcus aureus (including MRSA), Streptococcus pneumoniae -does COVER E. faecium (VRE) -does NOT cover E. faecalis

Question 32

MOA for Lemafulin

Answer 32

-Protein synthesis inhibitor: binding to the A and P site of 50S -low resistance and low cross-resistance with other microbial (probably bc Pleuromutilin is not used routinely)

Question 33

Where could Lemafulin be used?

Answer 33

-First line for inpatient CABP -as a "step down" or alternative to FQ agents (due to FQ toxicity)

Question 34

What is Fetroja (cefiderocol) FDA-approved for?

Answer 34

-for complicated UTI -Drug class: siderophore cephalosporin -uses Iron to enter the periplasmic space of Gram(-) organisms

Question 35

Spectrum of activity !!!

Answer 35

-cUTIs -in the hospital: mainly Stenotrophomonas (Steno is resistant to Carbapenem) !!! -difficult Gram(-): MDR; Pseudomonas, Acinetobacter -weaker against Gram(+) and anaerobes

Question 36

Resistance mechanism in Fetroja

Answer 36

-involved in Fe-transport (the drug's way of getting in) -PiuA iron transporter deficiency1 -cirA and fiu iron transporter genes

Question 37

What does the warning for Cefiderocol imply?

Answer 37

-Overall higher overall mortality when used beyond UTI (so when treated with HABP, VABP, BSI/sepsis)

Question 38

When should Cefiderocol be used?

Answer 38

-Last-line treatment -Stenotrophomonas

Question 39

What is the main strategy of new pipeline drugs?

Answer 39

-Add a ß-lactamase inhibitor to a ß-lactam to restore the activity of the ß-lactam

Question 40

Cefepime(4)-taniborbactam is a new drug. The activity against which organism is intended to be restored?

Answer 40

ß-lactamase producing CRE AND CR-Pseudomonas

Question 41

Sulbactam-durlobactam restores activity against which organism?

Answer 41

Acinetobacter

Question 42

Which activity is restored by Cefepime-enmetazobactam?

Answer 42

against ESBL organism