Misc. Antibiotics

Question 1

Vancomycin

Answer 1

Tricyclic glycopeptide

Broad spec against gram + and MRSA
-most gram - are resistant

MOA- inhbition of cell wall synthesis
-the components of the cell wall have greater affinity for vanco than the cell

IV only - Renal elimination

Resistance - due to plasmids with the Van A trasposon

SE - hypersensitivity, Redman Syndrome, nephro/ototoxicity

Question 2

Clindamycin

Answer 2

Macrolide

Broad spec against gram + (strep, staph, MRSA, most anaerobic)

MOA - 50s close to erythromycin and chloramphenicol binding site – shouldn’t be used together
-macrolide plus clinda = bad

Resistance - due to induction of ribosomal methylation – confers cross-resistance to clinda

PK - oral or IV, food ok

• Poor CNS penetration
• Hepatic elimination

Use - alternative tx of skin and soft tissue staph or strep
-tx of anaerobic

SE - GI – POSSIBLY C DIFF

• pseudomembranous colitis - may be lethal
• can’t use with NM blocker

Question 3

Bacitracin

Answer 3

MOA - cell wall inhibitor

Use - gram +
-only used topically due to nephrotoxicity

Question 4

Polymyxin

Answer 4

MOA - cationic detergents that disrupt cell wall-cell membrane complex

• Resistance from shortage of lipid in outer wall
• Interaction with lipid A portion of endotoxin – inactivates

Use - gram -
-mixed with bacitracin becomes gram + and -

Question 5

Quinupristin/delfopristin (Synercid)

Answer 5

MOA - 50s synergistic

• Quinupristin binds at same site as macrolides - inhibits peptide elongation
• Dalfopristin causes conformational changes in 50s

Resistance

• Quinupristin - ribosomal methylation prevents drug binding – lactonase inactivates drug
• Dalfopristin - acetyltransferase inactivates drug – MDR efflux
• Ribosomal methylation render combo bacteriostatic instead of cidal

Active against gram +
-MRSA, pneumonia

Use - VRE, serious infections

PK - IV only, hepatic elimination

SE - phlebitis, pain, arthralgias
-3A4 inhibitor

Question 6

Linezolid

Answer 6

MOA - 50s – prevents fMet-tRNA and initiation of protein synthesis
-unique MOA makes it useful against resistant bacteria

Resistance - point mutations on two or more copies of 23s rRNA gene – no cross-resistance

Active against gram +

PK - widely distributed

• inactivated by oxidation yielding two metabolites that are excreted in the urine
• CYP metabolism

Use - VRE, nosocomial pneumonia, MRSA
-reserved for tx of resistant bacteria

SE - GI, HA

• BM – anemia, leukopenia, pancytopenia
• inhibitor of MAO

Question 7

Daptomycin

Answer 7

MOA - depolarizes bacterial membranes
-activity is concentration dependent

Active against aerobic, anaerobic and facultative gram +
-good fro VRSA, MDR bugs, MRS

PK - inactivated by pulmonary surfactant - can’t be used for PNU
-renal elimination

SE - muscle damage, increased CK, rhabdo

Question 8

Mupirocin

Answer 8

MOA - protein synth inhibitor via reversible binding to isoleucyl tRNA snythetase
-no cross-resistance with other drugs

Resistance - plasmid encodes bypass synthetase

Active against many gram + and some gram -

PK - topical; absorbed drug is inactivated to monic acid

Use - impetigo, traumatic skin legions secondary to staph, strep

SE - oint contains PEG which can be absorbed
-PEG caution in renal