miscellaneous abx

Question 1

Vancomycin (Vancocin) administration/metabolism

Answer 1

IV (poor oral absorption)

• widely distributed and does penetrate the CSF when the meninges are inflamed
• 90% of vancomycin is eliminated by renal excretion, adjust dose with renal failure

Question 2

Vancomycin (Vancocin) MOA

Answer 2

inhibits bacterial cell wall synthesis by binding to the D- alanyl-D-alanine portion of the peptidoglycan pentapeptide, bactericidal

Question 3

how does resistance to Vancomycin develop?

Answer 3

bacterial enzymes that can induce alterations in the cell wall precursors so that vancomycin can’t bind as well
i.e. Vancomycin resistant enterococci replace D-alanyl-D- alanine with D-alanyl-D lactate or D-alanyl-D-serine

Question 4

vanco spectrum

Answer 4

MRSA, MSSA, S. epidermidis, Streptococci, Corynebacterium diptheria, Clostridium spp. (the only anaerobe effective against)

NOT against G-s

Question 5

vanco uses

Answer 5

serious staph infections
G+ infections in pts allergic to PCNs/cephs (tx w. aminoglycoside for synergism)
C. diff colitis (oral vanco)
staph meningitis in a PCN-allergic pt, if caused by S. pneumo include with a 3rd gen ceph

Question 6

vanco SEs

Answer 6

-Ototoxicity and Nephrotoxicity: (rare)m ore common when given in combo with another ototoxic abx (i.e. amino glycoside)
-“Red man” or “Red Neck” syndrome – If vancomycin is infused too rapidly
is can cause flushing of the face, neck and torso due to histamine release.
minor: Injection site irritation, and chills and fever

Question 7

Clindamycin (Cleocin)

Answer 7

• oral and parental, distributed widely EXCEPT does not penetrate well into the CNS even with inflammation of the meninges
• does have good abscess penetration

Question 8

clindamycin MOA: similar to ??

Answer 8

imilar to erythromycin and chloramphenicol – binds to 50 S ribosomal subunit and inhibits bacterial protein synthesis; bacteriostatic

Question 9

resistance to clindamycin develops how?

Answer 9

• Mutations in the 50 S bacterial ribosomal subunit which prevents Clindamycin binding
• Modification of the binding site by the enzyme methylase that prevent clindamycin binding
• Enzymatic inactivation of clindamycin
• Bac resistant to clindamycin are usually resistant to
  erythromycin. (similar mech)

Question 10

clindamycin spectrum

Answer 10

most Staph aureus strains (has activity against some community acquired MRSA), Strept. Pneumoniae, but enterococci are resistant.

• NOT useful against G- AEROBES
• is active against G- and G+ anaerobes (B. fragilis and C. perfringens)

Question 11

clindamycin uses

Answer 11

• anaerobic infections (abscesses)- NOT brain abscesses
• used in combo w. amino glycoside/ceph to tx deep wounds
• *ppx against endocarditis in valvular heart dis. pts who are having dental procedures
• alternative to PCN/ceph in allergic pts
• PCP and toxoplasma gondii (+pyrimethamine) in AIDS pt

Question 12

clindamycin SEs

Answer 12

C. diff-induced Pseudomembranous colitis (tx w. oral Vancomycin, Metronidazole, and Cholestyramine (not orally w. vanco: antagonistic effect)

Question 13

Nitrofurantoin (Furadantin, Macrobid, Macrodantin)

Answer 13

• Rapidly absorbed after oral admin, metabolized/excreted by glomerular filtration and tubular secretion (40% of free drug is found in the urine), often so quickly drug effects not seen!
• don’t use in renal failure
• reduced forms can damage DNA, both bactericidal and static
• admin w. acidifying agent (more active @ pH

Question 14

nitrofurantoin spectrum?

resistance development??

Answer 14

• G+ and G- bac
• NOT effective against Pseudomonas and many Proteus strains (resistant)
• Bac resistance takes a long time to develop and there is no cross resistance with other abx

Question 15

nitrofurantoin uses

Answer 15

-tx UTIS and for ppx for recurrent UTIs (used of UTIs caused by E. coli resistant to TMP-SMX and FQs)

Question 16

nitrofurantoin SEs

Answer 16

• GI: anorexia, N/V
• hemolytic anemia (rare, seen in pts w. G6PD deficiency)
• neurological, pulmonary fibrosis, chronic active hepatitis, allergic reactions
• contraindicated in renal failure, caution w. preggos

Question 17

Polymyxin B sulfate (generic) MOA

what does resistance involve?

Answer 17

interacts with cell membrane phospholipids, and disrupts cell membrane perm., and causing leakage of intracellular components, bactericidal
-Resistance may involve inability of the polymyxins to pass through the cell wall.

Question 18

polymyxin B spectrum

Answer 18

only susceptible G- bac (e.g. Enterobacter aerogenes, E. coli, Klebsiella pneumonia, H. influenzae, Acinetobacter baumannii, Pseudomonas aeuriginosa)

Question 19

polymyxin B uses

Answer 19

topical treatment of Infections of the eye, skin, mucous membranes, ear, wounds, burns (G-s)

• used IV as alternative for drug-resistant resp. tract infections (HAP, HCAP, VAP) caused by DR-G-
• septicemia, UTIs (IV, IM)
• meningitis (typ. in combo)
• irrigate the bladder to prevent bacteriuria/bacteremia assoc. w. indwelling catheters (used w. neomycin)

Question 20

polymyxin B SEs (both dose-dependent) (why polymyxins are reserved as alternate tx)

Answer 20

• Neurotoxicity*: (facial flushing; dizziness that may progress to ataxia; mental confusion; nystagmus; muscle weakness; drowsiness; giddiness; peripheral paresthesia, visual disturbances, slurred speech, coma and seizures)
• Nephrotoxicity*: (albuminuria, proteinuria, cylindruria, azotemia, inc. in serum creatinine (dec. in creatinine clearance), acute tubular necrosis, oliguria, hematuria, leukocyturia, and excessive excretion of e-lytes)

Question 21

Metronidazole (Flagyl)

Answer 21

• oral, IV, rectal, topical (vag)
• widely distributed, including the CNS and brain abscesses
• crosses the placenta and appears in breast milk
• metabolized in the liver and exreted by the kidneys

Question 22

metronidazole MOA

Answer 22

reduction of the drug to compounds that bind to intracellular macromolecules, bactericidal

Question 23

metronidazole spectrum

Answer 23

• active against clindamycin-resistant B. fragilis (drug of choice in adults*)
• bactericidal activity against Anaerobes (including bacteriodes fragilis)
• NOT v. effective against Not very effective against G+ and G- AEROBES

Question 24

metronidazole uses

Answer 24

• Anaerobic infections (soft tissue infection, intra-abdominal infections, pelvic infections, brain abscesses).
• C. diff Pseudomembranous colitis
• PUD caused by H. pylori (Triple therapy)

Question 25

metronidazole SEs

Answer 25

- Carcinogenic potential, don’t use in pregnancy or in women during breast - Disulfiram-like interaction with alcohol.

Question 26

Bacitracin

Answer 26

- opthalmic and dermatologic ointments | - not used much parenterally because of nephrotoxicity

Question 27

Bacitracin MOA

Answer 27

- inhibits cell wall formation, interferes with the lipid that carries peptidoglycan subunits to the site of cell wall formation. - No cross resistance with other antimicrobials.

Question 28

Bacitracin spectrum

Answer 28

-similar spec. to PCN: G+ cocci and bacilli -G-s such as Neisseria, H. influenzae; and the spirochete Treponema palladium -

Question 29

Bacitracin uses

Answer 29

-topically for open wounds to eradicate mixed microorgs -eye infections (e.g. conjunctivitis) (may be used in combo, i.e.: bacitracin + polymyxin + neomycin)

Question 30

bacitracin SEs

Answer 30

Serious nephrotoxicity from parenteral use; renal failure due to tubular and glomerular necrosis. -Hypersensitivity reactions from topical use are rare.

Question 31

Quinupristin/Dalfopristin (Synercid) used for ?? | spectrum:

Answer 31

IV tx of bacteremia and other life threatening infections caused by vancomycin-resistant Enterococcus faecium, and complicated skin infections caused by S. aureus and Strep pyogenes (when resistant to other abx, or contraindicated due to allergy) -Enterococcus faecium, MRSA/MSSA, S. epidermidis, PCN-susc. and resistant S. pneumo

Question 32

Quinupristin/Dalfopristin (Synercid) MOA

Answer 32

(similar to the macrolide) - inhibits bac protein synthesis by binding to the *50 S* ribosomal subunit. - The two drugs bind to different sites on the 50 S ribosome and prevent the extrusion of new proteins which results in bacterial cell death.

Question 33

Quinupristin/Dalfopristin (Synercid) resistance occurs via ??

Answer 33

Modification of the quinupristin binding site on the 50S ribosomal subunit, enzymatic destruction of dalfopristin or efflux

Question 34

Quinupristin/Dalfopristin SEs

Answer 34

- Erythema, pain, itching and burning at the site of infusion - Arthralgias/myalgias - inhibit CYP3A4

Question 35

Linezolid (Zyvox) | MOA?

Answer 35

Oral admin, Parenteral Bacterial protein synthesis inhibitor by binding to the 50S bacterial ribosomal subunit and prevents formation of the 70S translational initiation complex; Bactericidal for Streptococci with bacteriostatic activity against many other bac

Question 36

Linezolid Resistance in ?? and ?? is caused by ??

Answer 36

enterococci and staphylococci point mutations in the 23S rRNA of the 50S subunit.

Question 37

Linezolid spectrum/uses

Answer 37

-Vanco-resistant Enterococcus facacium -Nosocomial pneumonia or CAP due to S. aureus or PCN-susc. Strep pneumo -Skin/skin structure infections: MRSA and Strep Pyogenes

Question 38

Linezolid SEs

Answer 38

*reversible inhibitor of monoamine oxidase* (co- admin with tyramine rich foods can result in HTN) -N/V/D -Thrombocytopenia -oral formulation contains phenylalanine, avoid in PKUs -C. diff-assoc. colitis

Question 39

Daptomycin (Cubicin)

Answer 39

- poor oral absorption, admin IV - avoid IM due to musc. tox - 80% excreted in the urine, adjust dose if creatinine clearance is below 30 mL/min

Question 40

Daptomycin (Cubicin) MOA

Answer 40

concentration-dependent killing effect by binding to and depolarizing bacterial cell membranes which leads to loss of membrane potential, postassium efflux, and cell death. -no known resistance mechs

Question 41

Daptomycin spectrum/uses

Answer 41

- Bactericidal for aerobic, facultative and anaerobic G+ bac | - Complicated skin/skin structure infections caused by MRSA/MSSA, hemolytic streptococci, and vanco-susc. E. faecalis

Question 42

Daptomycin SEs

Answer 42

Skeletal muscle damage/Myopathy | Peripheral neuoropathy