Antibiotics for Cardiovascular Infections

Question 1

Acute rheumatic fever is a _______ reaction to infection with ___________, due to molecular mimicry; ARF is primarily found in children age 5-14

Answer 1

Autoimmune; Group A streptococcus

Question 2

Who is at increased risk of exposure to streptococcal infections?

Answer 2

Children and adolescents, parents of young children, teachers, physicians, nurses, day-care workers, military recruits, individuals living in crowded situations (i.e., college dorms)

Question 3

Empiric tx for ARF

Answer 3

Penicillin G + gentamycin

[Also give NSAIDs like ASA or ibuprofen for joint pain and fever]

Question 4

Tx of ARF in pt with penicillin allergy or hypersensitivity to beta lactams

Answer 4

Macrolides: erythromycin, azithromycin, clarithromycin, or clindamycin

Question 5

When it comes to concern for prophylaxis of recurrent ARF in a pt hypersensitive to beta lactams, what macrolide is avoided?

Answer 5

Clindamycin due to the chance of eliciting opportunistic infection of the GI tract by C.diff

Drugs that can still be used = erythromycin, azithromycin, clarithromycin

Question 6

MOA of aminoglycosides

Answer 6

Protein synthesis inhibitors

Question 7

AEs of aminoglycosides

Answer 7

Nephrotoxicity (reduced by not combining with vancomycin)

With high risk use (>75 days, high doses, elderly pt, pre-existing renal insufficiency, etc.), can lead to ototoxicity and auditory damage

Question 8

Macrolides MOA

Answer 8

Protein synthesis inhibitor [stops tRNA at A site, conformational change in 50S, disruption of 50S formation]

Question 9

4 resistance mechanisms associated with macrolides

Answer 9

Active drug efflux pumps

Methylase enzymes modify binding site

Degradation by esterases from enterobacter sp (cannot be used to tx infection with this etiology!)

Mutation of binding site itself

Question 10

AEs associated with macrolides

Answer 10

GI distress (n/v/anorexia) — most frequent with erythromycin

Prolonged erythromycin use —> hepatotoxicity

Hypersensitivity —> eosinophilia, fever

Question 11

T/F: macrolides should never be given with other abx

Answer 11

False — they are often combined with other abx for wide spectrum coverage

Question 12

Prototypic lesion associated with IE

Answer 12

Vegetation

Question 13

Oral cavity, skin, and upper respiratory tract organisms associated with IE

Answer 13

Oral cavity = streptococcus viridans

Skin = staph

Upper respiratory = HACEK

Question 14

Empiric tx for IE

Answer 14

Vancomycin (must be given IV) + ceftriaxone

Question 15

What drug options are utilized in IE d/t streptococcus viridans if highly penicillin susceptible organism?

Answer 15

Penicillin G or ceftriaxone

Question 16

What drug options are utilized in IE d/t streptococcus viridans for shorter drug course, and if pt has no renal dz?

Answer 16

Gentamycin + Pencillin G

Gentamycin + ceftriaxone

Question 17

What drug options are utilized in IE d/t streptococcus viridans if pt has mild penicillin allergy?

Answer 17

Ceftriaxone

Gentamycin + ceftriaxone

Question 18

What drug options are utilized in IE d/t streptococcus viridans if pt has severe penicillin allergy?

Answer 18

Vancomycin, or perform penicillin desensitization (preferred)

Question 19

How does penicillin desensitization work?

Answer 19

Small dose of drug that is gradually increased until the therapeutic dose is achieved [1 unit of drug is given IV and pt observed for 15-30min]

If no reaction —> dose gradually increased every 15-30 min (tenfold or doubling, depending)

Once 2 million units is reached, the remainder of the dose can be given

The sensitivity is d/t IgE-mediated allergic reaction, but slow exposure allows IgG to compete. Note that drug must be physically present to maintain desensitization (meaning this process must be repeated each time the pt gets PCN)

Question 20

Drug(s) utilized for IE d/t S.aureus that is methicillin-susceptible

Answer 20

Nafcillin or oxacillin

Question 21

Drug(s) utilized for IE d/t S.aureus in pt with mild beta lactam sensitivity

Answer 21

Cefazolin

Question 22

Drug(s) utilized for IE d/t S.aureus in pt with severe beta-lactam hypersensitivity

Answer 22

Vancomycin or daptomycin

Question 23

Drug(s) utilized for IE d/t S.aureus in pts with complication of a brain abscess

Answer 23

Nafcillin

Question 24

Drug(s) utilized for IE d/t MRSA

Answer 24

Vancomycin or daptomycin (alternative)

Question 25

Daptomycin is a new abx with similar spectrum of activity as vancomycin. It works on ________ organisms including MRSA

Answer 25

Gram positive

Question 26

MOA of daptomycin

Answer 26

Not completely understood Binds to cell membrane via Ca-dependent insertion of its lipid tail leading to depolarization, K+ efflux, and rapid cell death

Question 27

Drug(s) utilized for IE d/t S.epidermidis and other coagulase negative staphylococci

Answer 27

Vancomycin

Question 28

Drug(s) utilized for IE d/t HACEK infection

Answer 28

Ceftriaxone

Question 29

Drug(s) utilized for IE d/t enterococci (mostly e.faecalis)

Answer 29

[penicillin G or ampicillin or vancomycin] + gentamycin [note that vanco is chosen in pts with PCN allergy]

Question 30

Pericarditis tx in immunocompetent pts

Answer 30

NSAID (i.e., ASA or naproxen) + colchicine

Question 31

What lab test is important to order to track treatment of pericarditis?

Answer 31

CRP

Question 32

_______ may be used to treat pericarditis in severe or refractory cases, but carry the risk of prolonging illness or increasing the chance of relapse

Answer 32

Corticosteroids (i.e., prednisone)

Question 33

Colchicine has anti-inflammatory action mediated by binding to ______, preventing its polymerization and leading to inhibition of _____ migration and phagocytosis

Answer 33

Tubulin; leukocyte

Question 34

AEs with colchicine

Answer 34

Diarrhea and occasional nausea, vomiting, and abd pain No longer approved for IV use, but when it was used IV it carried risk of hair loss, bone marrow depression, peripheral neuritis, and myopathy

Question 35

A 42-year-old patient presents to clinic complaining of a fever and unintentional weight loss. A diagnosis of infective endocarditis is made and blood cultures point towards infection with S. epidermidis. Which pharmacologic agent would specifically target S.epidermidis in the setting of acute IE? ``` A. Penicillin G B. Moxifloxacin C. Aztreonam D. Methicillin E. Vancomycin ```

Answer 35

E. Vancomycin

Question 36

What is the MOA of vancomycin?

Answer 36

Cell wall synthesis inhibitor; indirectly damages cell wall

Question 37

A 54-year-old male patient was admitted to the hospital with fever (100.6 ºF, 38.1 ºC), joint pain, night sweats, and 15 lb (6.8 kg) of unintentional weight loss. Past history was significant for rheumatic fever at the age of 9 and for dental surgery 1 month ago. The symptoms started about 2 weeks after the dental procedure. Physical examination was significant for mitral regurgitation. Three blood cultures were ordered, and an empiric therapy was started. Which of the following would be appropriate for the pt at this time? ``` A. Ampicillin and erythromycin B. Piperacillin C. Aztreonam D. Penicillin G and gentamicin E. Ciprofloxacin ```

Answer 37

D. Penicillin G and gentamicin

Question 38

Why are penicillin G and gentamycin considered synergistic?

Answer 38

Cell wall active agents like penicillin G and ceftriaxone increase uptake of aminoglycosides like gentamicin

Question 39

A 32-year-old female heroin addict was admitted to the hospital with a 2-day history of fever, shaking chills, rigors, and night sweats. Her vital sign were: blood pressure 100/60 mm Hg, pulse 120 bpm, respirations 24/min, temperature 102.2 ºF (39 ºC). Two-dimensional echocardiography revealed three small vegetations on the tricuspid valve. Three blood cultures were drawn and empiric therapy was initiated. What drugs were initiated as empiric therapy? A. Ceftriaxone and vancomycin B. Gentamicin C. Ciprofloxacin D. Piperacillin and ceftriaxone

Answer 39

A. Ceftriaxone and vancomycin

Question 40

A 32-year-old female heroin addict was admitted to the hospital with a 2-day history of fever, shaking chills, rigors, and night sweats. Her vital sign were: blood pressure 100/60 mm Hg, pulse 120 bpm, respirations 24/min, temperature 102.2 ºF (39 ºC). Two-dimensional echocardiography revealed three small vegetations on the tricuspid valve. Three blood cultures were drawn and empiric therapy was initiated. The patient does not respond to vancomycin and the blood cultures later reveal MRSA. What alternative drug could be used in this case? ``` A. Piperacillin B. Daptamycin C. Clindamycin D. Gentamicin E. Aztreonam ```

Answer 40

B. Daptamycin