Dr. Cluck Clinical Application New Antimicrobials EXAM 3 Flashcards
What are the Newer Antibiotics?
-Ceftolozane(5)-tazobactam
-Ceftazidim(3)-avibactam
-Delafloxacin (FQ)
-Vancins: Oritavancin, Dalbavancin
-Tedizolid
What is Delafloxacin FDA-approved for?
Community-acquired bacterial pneumonia (CABP)
What is Ceftolozane-tazobactam FDA-approved for?
-Hospital-acquired bacterial pneumonia (HABP)
-Ventilator-associated bacterial pneumonia (VABP)
Newer Antimicrobial agents
-Plazomicin
-Eravacycline
-Omadacycline
-Imipenem-cilastatin/relebactam
-Lefamulin
-Cefiderocol
How does Plazomicin (Zemdri) achieve stability to
most aminoglycoside modifying enzymes (AMEs)?
Structurally enhanced sisomicin pharmacophore
What is Plazomicin (Zmedri) FDA-approved for?
!!!
Only for complicated urinary tract infections (cUTI)
!!!
The antibacterial approach and way of Elimination for Aminoglycosides?
-Bacteriocidal
-Eliminated through the kidney
MOA of Plazomicin
Inhibits bacterial protein synthesis at the 30S ribosome and is rapidly bactericidal
How are Plazomicin concentrations monitored in patients?
-Through monitoring is acceptable
-in systemic infections: AUC-based dosing is preferred
Which organism is susceptible to Plazomicin?
!!!
-MRSA (but not Strep and Enterococci)!!
-CRE !!!
-ESBL producing Enterobacterales !!!
-Variable activity against New Dehli metallo ß lactamases !!!
What is the Mechanism of Resistance in Plazomicin?
16s ribosomal methyltransferases (16S RMTases) -> decreased affinity to the drug target
Which antimicrobial agent is outdated and should be used?
-Colistin
-bc of its Nephro- and Ototoxicity
-used as Adjunctive in MDR, especially CRE
What is Eravacycline (Xerava) approved for?
-for complicated intra-abdominal infection (cIAI)!!!
-only IV !!
-synthetic fluorocycline
-similar to Tigecycline, but more potent against gram (+) cocci and gram (-) rods
Spectrum of activity for Eravacycline
-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)
MOA for Eravacycline
-similar to other tetracyclines: binding to 30S subunit -> inhibits protein synthesis
-bacteriostatic against many organisms, but has also shown bacteriocidal activity
At what point is Eravacycline different from Tigecycline?
!!!
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 !!!
Why is the clinical use for Tigecycline low?
Because of its PK/PD profile
-low plasma concentration -> doesn’t reach MIC
-hence not used for in UTIs and bacteremia
Other benefits of Eravacycline over Tigecycline
-better tolerated (less nausea)
-reduced risk of C. diff (but also with Tigecycline)
-BUT lack of oral formulation
Omadacycline (Nuzyra) FDA-approved for?
-Community-acquired bacterial pneumonia (CABP)
-acute bacterial skin and skin structure infection (ABSSSI)
-IV and PO
Spectrum of Activity for Omadacycline
-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
What makes Omadacycline inconvenient?
Direction of the drug
-fast for 4 hours -> take with water and fast for 2 hours
-inconsistent dosing regimen
Where is Omadacycline used?
-almost only non-tuberculous mycobacteria infections
-could be used for CRE and Acinetobacter (but there are other drugs for that)
RECARBRIO (Imipenem-cilastin/Relebactam)
Relebactam - Carbapenem - RIO
-FDA-approved for complicated intraabdominal infections (cIAIs), UTIs, and HABP/VABP
-Relebactam is similar to avibactam
Why do providers still hesitate to use Recarbio?
Because of seizure (it is still a carbapenem)
Spectrum for
Ceftazidime/avibactam
Meropenem/vaborbactam
Imipenem-cilastatin/
relebactam
-they all cover KPC-producer
-they do not cover NDM-producer
-they do not cover Carbapenem-resistant Acinetobacter baumannii
Relebactam shows activity against which clinically relevant organism?
Pseudomonas
In a study where Imipenem-Relebactam was compared to Pip-Tazo, Linezolid was added.
What was the purpose of Linezolid?
Coverage of MRSA
What would be a scenario to use Imipenem/Relebactam?
-In patients with Pseudomonas resistant to Ceftolozane(5)-tazobactam
-> use Ceftaroline/avibactam OR IMI-REP
-> If resistant to those use Cefiderocol (Fetroja)
What is Lemafulin (Xenleta) FDA-approved for?
-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)
What is Retapamulin used for?
-topical treatment for skin soft tissue infections (SSTIs) due to methicillin-susceptible Staphylococcus aureus
Spectrum of Activity for Lemafulin
-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
MOA for Lemafulin
-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)
Where could Lemafulin be used?
-First line for inpatient CABP
-as a “step down” or alternative to FQ agents (due to FQ toxicity)
What is Fetroja (cefiderocol) FDA-approved for?
-for complicated UTI
-Drug class: siderophore cephalosporin
-uses Iron to enter the periplasmic space of Gram(-) organisms
Spectrum of activity
!!!
-cUTIs
-in the hospital: mainly Stenotrophomonas (Steno is resistant to Carbapenem) !!!
-difficult Gram(-): MDR; Pseudomonas, Acinetobacter
-weaker against Gram(+) and anaerobes
Resistance mechanism in Fetroja
-involved in Fe-transport (the drug’s way of getting in)
-PiuA iron transporter deficiency1
-cirA and fiu iron transporter genes
What does the warning for Cefiderocol imply?
-Overall higher overall mortality when used beyond UTI (so when treated with HABP, VABP, BSI/sepsis)
When should Cefiderocol be used?
-Last-line treatment
-Stenotrophomonas
What is the main strategy of new pipeline drugs?
-Add a ß-lactamase inhibitor to a ß-lactam to restore the activity of the ß-lactam
Cefepime(4)-taniborbactam is a new drug. The activity against which organism is intended to be restored?
ß-lactamase producing CRE AND CR-Pseudomonas
Sulbactam-durlobactam restores activity against which organism?
Acinetobacter
Which activity is restored by Cefepime-enmetazobactam?
against ESBL organism
