Lecture 4 - Linezolid, Tedizolid, Clindamycin & Lefamulin Flashcards
Oxazolidinones
Linezolid
Tedizolid
Miscellaneous Gram + antibiotics
Clindamycin
Lefamulin
Gram + antibiotics
Glycopeptides & Lipoglycopeptides
Oxazolidinones
Miscellaneous
Linezolid MOA
- Protein synthesis inhibitor (Binds to V-domain of 23S RNA component of the 50S ribosomal subunit)
- Its bacteriostatic
- Manipulation of A/B are necessary for antibacterial activity
Linezolid Spectrum of Activity Gram +
Broad Gram + activity
Active against Enterococcus species, inc E.faecalis + VRE (considered Txm of choice depending on source)
Active against MSSA/MRSA (good if no DI + can tolerate)
Active against all Streptococcal species
** Used in Polymicrobial inf (intra-abdominal or SSTI) when also need to cover Enterococci or MRSA
Linezolid Spectrum of Activity Gram + Bacillus
Active against Listeria Monocytogenes (Txm of choice is Ampicilin+Gentamicin tho)
Active against Nocardia species (Txm of choice is Bactrim tho)
Linezolid Spectrum of Activity Anaerobes
Broad active against Gram + anaerobes
Active against: Actinomyces, Propionbacterium, peptostreptococci
Some activity: Prevotella, Fusobacterium
Limited activity: B. fragilis (Gram - anaerobes in GI)
Linezolid has no activity in….
Gram - and Atypical
Linezolid Activity in Other organisms
Has activity against Mycobacteria, including M.tuberculosis….txm option for drug resistant TB**
Also active against non-TB Mycobacteria (inc Mycobacterium abscenssus - MDR and MAC, Mycobacterium avid complex)
Linezoid M & E
Bioavailability is ~ 100%, so PO and IV dose is same
High conc into epithelial lining fluid (>100%), bone and joint tissues
Doesn’t req renal adjustment due to majority elim non-renal
** Linezolid Drug Interactions **
- Reversible, non-selective monoamine oxidase inhibitor
- Associated w/ development of Serotonin Syndrome in pts receiving concurrent serotonergic agents
Small inc in BP in pt using Tyramine
** don’t use with Serotonin drugs **
Tedizolid MOA
Protein Synthesis inhibitor
And to V-domain of 23S RNA component of 50S ribosomal unit
Tedizlod Gram + Spectrum of activity
shown to be 2-8 X more potent than Linezoid
active against Enterococcus species, inc E.faecalis + VRE
Active against MSSA + MRSA
Active against all Streptococcal species
Tedizolid Gram + bacillus activity
Has shown to have MIC90 values several-old lower than those of linezolid for a number of species
exception: Nocardia nova complex & Nocardia brasiliensis
Tedizolid Spectrum of activity Anaerobes
broad activity against Gram + anaerobes
Where does Tedizolid not have activity?
Gram - and Atypical
Tedizolid Spectrum of activity in Mycobacteria
appears to be more potent for strains tested, but clinical significance of in vitro findings is unclear
Tedizolid M & E
12hrs 1/2life = QD dosing
Pro drug, given Oral or IV
No renal dose adjustment required
Tedizolid DI
- weak, reversible monoamine oxidase inhbition
- wasn’t tested for use with serotonergic agents but no negatives shown in animal investigation and other preliminary tests
OK to use in pts on Serotonin drugs
Oxazolidinones ADR
GI - Diarrhea
Hepatic - inc LFT
Hematologic toxicity = inc w/ linezolid
Neuropathy = inc w/ linezolid
Clindamycin MOA
Lincosamide antibiotic
Protein synthesis inhib, reversibel binde to 50S ribo subunit
Suppression of exotoxins (a toxins, TSST-1, PVL, enterotoxins)
Clindamycin Spectrum of Activity
No enterococcal coverage
Active against MSSA/MRSA but not good choice, but ager doing D-test can possibly use
Limited in Streptococcal species due to resistant
** used in combo with Penicillin for Group A Streptococcal toxic shock syndrome **
Combo of Penicillin and Clindamycin is used in….
Group A streptococcal toxic shock syndrome
What does Clindamycin not cover
Gram - and Atypical
Clindamycin Spectrum of Activity anaerobes
Clindamycin considered treatment of choice for Gram + anaerobes
** use limited due to resistance and high risk of C.difficile infections
Gram - anaerobic (B. fragilis = GI) limited due to resistance
Clindamycin other uses
Activity against Toxoplasmosis
activity against Pneumocystis used as combo with Primaquine
Activity against malaria (Plasmodium falciparum) and is alternative for malaria in pregnancy
Clindamycin M & E
Absorption ~90%, delayed by ingestion of food.
most drug metabolized to products with variable antibacterial activity
normal 1/2life is 2.4hrs, dosing q6/8hrs
Clindamycin DI
CYP3A4 Inducers decrease serum conc
CYP3A4 Inhibitors inc serum conc
Clindamycin ADR
GI = 20% diarrhea, C.dif infection**
Dermatologic
Hepatic
Lefamulin MOA
Pleuromutilin antibiotic
protein synthesis inhibitor, tight-fit binding to A/P sites of 50S ribosomal subunit
Lefamulin Gram + Spectrum of activity
Active against MSSA, MRSA, Staphylococci
Strep, including susceptible and resistant S.pneumoniae
active against B/A hemolytic strep
Some against E.faecium, not against E.faecalis tho
Lefamulin Gram - Spectrum of Activity
No activity against Enterobacterales
No activity against non-fermenting Gram -
** good activity against Gram - organisms associated with community acquired pneumonia (H. influenzae, M.catarrhalis)
Lefamulin Anaerobes Spectrum of activity
Activity against common anaerobes
acts coverage against C.difficile and B.fragilis
Lefamulin Activity against Atypical?
C.pneumoniae
M.pneumoniae
L.pneumophilia
Lefamulin M & E
Absorption dec by food, take 1hr before or 2hr after meal
dose reduced in pics with Child-Pugh Class C
Lefamulin DI
can cause inc in QT interval
** CI in Pimozide ***
Lefamulin ADR
GI = diarrhea, n,v Prolonged QTc CNS Hermatologic & oncologic Local injection site
