Antimicrobials part 1

Question 1

Penicillin V indication

Answer 1

Less active against gram -ve than PCN G

Gram +ve (except staph b/c beta lactamase)
Most anaerobes

DOC for strep throat

Question 2

Penicillin V PK/PD

Answer 2

Acid stable

Oral version of PCN G

Question 3

Ticarcillin, Carbenicillin, Piperacillin indication

Answer 3

TCP-takes care of pseudomonas
DOC for P. aeruginosa infections**

Effective agianst many gram -ve bacilli (better than other PCN’s)

Combine with a beta-Lactamase inhibitor**

Question 4

Ticarcillin, Carbenicillin, Piperacillin PK/PD

Answer 4

useful in moderate to severe infections

Question 5

Penicillin G (Benzathine, procaine) indication

Answer 5

Gram +ve
Except staph -> beta lactamase **
Gram -ve cocci (Neisseria)
Most anaerobes

DOC for syphilis (benzathine)
Strep (preventing rheumatic fever)
Pneumococci

Question 6

Penicillin G (benzathine, procaine) PK/PD

Answer 6

Susceptible to beta lactamases

Procaine -> IM increasing resistances so decreased use; not IV due to toxicity

Benzathine -> IM, half life 3-4 weeks; prolongs life of penicillin G

Question 7

Amoxicillin, Ampicillin indication

Answer 7

Extended spectrum -> some gram -ve activity
Susceptible to beta lactamase -> adminitser with beta lactamase inhibitor

***URT’s (H. flu & S. pneumo); UTI’s (E. coli), P. mirabilis, Salmonella, Shigella
“HELPSS kill enterococci”

Amoxicillin -> endocarditis prophylaxis during dental or respiratory tract procedures **

Ampicillin -> used in combination with aminoglycoside to treat Listeria and enterococci

Question 8

Amoxicillin, Ampicillin PK/PD

Answer 8

Amoxicillin -> highest oral bioavailability

**Safe for children and pregnancy**

Ampicillin rash

Question 9

Nafcillin adverse

Answer 9

Neutropenia

Question 10

Oxacillin adverse

Answer 10

Hepatitis

Question 11

Ticarcillin adverse

Answer 11

inhibits platelet function therefore increased bleeding time

Question 12

Methicillin, Nafcillin, Oxacillin, Dicloxacillin indication

Answer 12

Anti staphylococcal
Beta lactamase resistance
Methicillin never used clinically (Causes AIN)
Inactive against MRSA/ORSA

DOC for staph endocarditis without a prosthetic valve

Question 13

Nafcillin PK/PD

Answer 13

Has erratic oral absorption and is excreted in the bile

Question 14

Beta lactamase inhibitors

Answer 14

Clavulanic acid
Sulbactam
Tazobactam

Question 15

Calvulanic acid, Sulbactam, Tazobactam description

Answer 15

aka: penicillinase or cephalosporinase

Contain a beta lactam ring, but do not have significant antibacterial activity
Available only in fixed combinations with specific PCN’s

Bind and inhibit most beta lactamases

Question 16

Penicillin mechanism

Answer 16

Bactericidal -> bind to PBP’s inhibiting the last step in peptidoglycan synthesis

PCN activates autolysin - bacterial enzymes which mediates cell lysis

Autolysin + lack of cell wall synthesis= death

Oral absorption impaired by food
Distribution: do not achieve sufficient levels in prostate and eye
CSF penetration is poor except in meningitis
Nafcillin, ampicillin, and piperacillin -> high levels in bile

Question 17

Penicillin excretion

Answer 17

Primarily excreted in kidney except for

• Nafcillin -> bile (useful when patients have renal insufficiency**)
• Oxacillin/dicloxacillin - renal and biliary excretion*

Question 18

Penicillin description

Answer 18

Widely effective with little toxicity
Overuse -> increase levels of resistance (due to PBP mutations)

All have beta lactam ring

PCN + aminoglycoside (gram +ve and -ve)

Question 19

Penicillin synergistic effect

Answer 19

PCN facilitates movement of AG through the cell wall
Formas an inactive complex if placed in the same IV solution

DOC for Empiric treatment of infective endocarditis … PCN G + gentamicin (nowadays a lot of MD’s use vancomycin instead of PCN)

Question 20

Penicillin Hypersensitivity

Answer 20

Major Ag determinant -> penicilloic acid
Anything from a rash to anaphylaxis
Cross allergic reactivity between beta lactam ABx can occur (ex. cephalosporins)

Question 21

Penicillin AE

Answer 21

Hypersensitivity
Interstitial nephritis -> esp. methicillin -> oliguria, fever, rash, + EOS in urine

GI disturbance
*Pseudomembranous colitis (esp ampicillin) or vaginal candida

Maculopapular rash when ampicillin or amoxicillin is given for a viral infection (not a hypersensitivity reaction)

Neurotoxicity in epileptics
Ticarcillin: inhibits platelet function, increase bleeding time
Nafcillin -> neutropenia
Oxacillin -> hepatitis

Question 22

Penicillin mechanisms of resistance

Answer 22

Inactivation by betalactamase
Modified PBP’s
Impaired penetration
Increased efflux

Question 23

Penicillin time dependent killing

Answer 23

increasing concentration only adds to risk for AE; length of time spent over MIC is the most important

Question 24

Penicillin spectrum

Answer 24

Spectrum is based on the ability to ‘reach” the PBP’s -> based on size, charge and hydrophobicity

Gram +ve -> cell wall is easily accessed
Gram -ve -> porins permit entry

Question 25

Penicillin desensitization

Answer 25

used in pregnant women with penicillin allergy (because nothing else can be used to treat them*

Question 26

PBPs

Answer 26

PBPs are penicillin binding proteins (bacterial enzymes) involved in peptidoglycan synthesis Penicillins require the microbe to be actively proliferating (cell wall synthesis must be occurring)

Question 27

Beta lactam antibiotics

Answer 27

Penicillins Cephalosporins Carbapenems Monobactams All target PBPs

Question 28

Monobactam drug

Answer 28

Aztreonam

Question 29

Aztreonam indication

Answer 29

**Only for aerobic gram -ve rods** | Including pseudomonas, UTI's, sepsis

Question 30

Aztreonam PK/PD

Answer 30

IV or IM - parenteral only *Inhalation (Cystic fibrosis patients)* Penetrates CSF when inflamed

Question 31

Aztreonam mechanism

Answer 31

Binds PBP's -> inhibits cell wall synthesis Eliminated in urine (monitor renal function)

Question 32

Aztreonam AE

Answer 32

Little cross-reactivity -> can be used in patients with PCN anaphylaxis Relatively non toxic Rarely causes increase aminotransferase, skin rash, GI upset, vertigo, HA

Question 33

Aztreonam Funcat

Answer 33

Resists hydrolysis by most beta lactamases

Question 34

Carbapenem drugs

Answer 34

Imipenem | Meropenem

Question 35

Carbapenem indication

Answer 35

Synthetic beta lactam antibiotics **DOC for Enterobacter infection and extended spectrum beta lactamase producing gram -ve's**

Question 36

Carbapenem PK/PD

Answer 36

*Very broad spectrum* but not effective against MRSA IV

Question 37

Carbapenem Mechanism

Answer 37

*Resist hydrolysis by most beta lactamases* Resistance is becoming a huge problem -> restrict use

Question 38

Carbapenem AE

Answer 38

GI distress *Imipenem ->seizures* *Partial cross reactivity with PCN*

Question 39

Carbapenem fun facts

Answer 39

Imipenem forms a *nephrotoxic* metabolite -> combine with *Cilastatin* to *reduce toxicity and increase availability*