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Infectous Disease > Dr. Cluck Clinical Application New Antimicrobials EXAM 3 > Flashcards

Dr. Cluck Clinical Application New Antimicrobials EXAM 3 Flashcards

1
Q

What are the Newer Antibiotics?

A

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

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2
Q

What is Delafloxacin FDA-approved for?

A

Community-acquired bacterial pneumonia (CABP)

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3
Q

What is Ceftolozane-tazobactam FDA-approved for?

A

-Hospital-acquired bacterial pneumonia (HABP)

-Ventilator-associated bacterial pneumonia (VABP)

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4
Q

Newer Antimicrobial agents

A

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

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5
Q

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

A

Structurally enhanced sisomicin pharmacophore

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6
Q

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

A

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

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7
Q

The antibacterial approach and way of Elimination for Aminoglycosides?

A

-Bacteriocidal
-Eliminated through the kidney

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8
Q

MOA of Plazomicin

A

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

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9
Q

How are Plazomicin concentrations monitored in patients?

A

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

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10
Q

Which organism is susceptible to Plazomicin?
!!!

A

-MRSA (but not Strep and Enterococci)!!

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

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11
Q

What is the Mechanism of Resistance in Plazomicin?

A

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

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12
Q

Which antimicrobial agent is outdated and should be used?

A

-Colistin
-bc of its Nephro- and Ototoxicity

-used as Adjunctive in MDR, especially CRE

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13
Q

What is Eravacycline (Xerava) approved for?

A

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

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

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14
Q

Spectrum of activity for Eravacycline

A

-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)

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15
Q

MOA for Eravacycline

A

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

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16
Q

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

A

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 !!!

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17
Q

Why is the clinical use for Tigecycline low?

A

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

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18
Q

Other benefits of Eravacycline over Tigecycline

A

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

-BUT lack of oral formulation

19
Q

Omadacycline (Nuzyra) FDA-approved for?

A

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

20
Q

Spectrum of Activity for Omadacycline

A

-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

21
Q

What makes Omadacycline inconvenient?

A

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

22
Q

Where is Omadacycline used?

A

-almost only non-tuberculous mycobacteria infections

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

23
Q

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

A

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

24
Q

Why do providers still hesitate to use Recarbio?

A

Because of seizure (it is still a carbapenem)

25
Q

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

A

-they all cover KPC-producer

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

26
Q

Relebactam shows activity against which clinically relevant organism?

A

Pseudomonas

27
Q

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

A

Coverage of MRSA

28
Q

What would be a scenario to use Imipenem/Relebactam?

A

-In patients with Pseudomonas resistant to Ceftolozane(5)-tazobactam

-> use Ceftaroline/avibactam OR IMI-REP
-> If resistant to those use Cefiderocol (Fetroja)

29
Q

What is Lemafulin (Xenleta) FDA-approved for?

A

-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)

30
Q

What is Retapamulin used for?

A

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

31
Q

Spectrum of Activity for Lemafulin

A

-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

32
Q

MOA for Lemafulin

A

-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)

33
Q

Where could Lemafulin be used?

A

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

34
Q

What is Fetroja (cefiderocol) FDA-approved for?

A

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

35
Q

Spectrum of activity

!!!

A

-cUTIs

-in the hospital: mainly Stenotrophomonas (Steno is resistant to Carbapenem) !!!

-difficult Gram(-): MDR; Pseudomonas, Acinetobacter

-weaker against Gram(+) and anaerobes

36
Q

Resistance mechanism in Fetroja

A

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

37
Q

What does the warning for Cefiderocol imply?

A

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

38
Q

When should Cefiderocol be used?

A

-Last-line treatment
-Stenotrophomonas

39
Q

What is the main strategy of new pipeline drugs?

A

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

40
Q

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

A

ß-lactamase producing CRE AND CR-Pseudomonas

41
Q

Sulbactam-durlobactam restores activity against which organism?

A

Acinetobacter

42
Q

Which activity is restored by Cefepime-enmetazobactam?

A

against ESBL organism

43
Q
A

Infectous Disease (29 decks)

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