Gram (+) Antibiotics

Question 1

Vancomycin Mechanism of Action

Answer 1

Inhibits synthesis and assemble of bacterial cell wall (@ D-alanyl-D-alanine portion of wall, diff than B-Lactam site) ; prevents cross-linking and further elongation of peptidoglycan

Question 2

Vancomycin- Bactericidal or Bacteriostatic?

Answer 2

Bactericida (time-dependent), except Enterococcus (bacteriostatic)

Question 3

Mechanism of Resistance for Vancomysin

Answer 3

Modification of the D-alanyl-D-alanine vancomycin-binding site in VRE and VRSA

Question 4

Vancomycin Spectrum of Activity

Answer 4

GRAM (+) AEROBIC AND ANAEROBIC BACTERIA
MSSA
MRSA
COAGULASE (-) STAPH
C-DIF
PRSP (Pen-Resistant Strep. pneumo)
others

NO ACTIVITY AGAINST GRAM (-) AEROBES OR ANAEROBES

Question 5

Vancomycin Absorption

Answer 5

Negligible oral absorption, thus INTERMITTENT IV INFUSION IS PREFERRED ROUTE OF ADMINISTRATION

Question 6

Vancomycin Distribution

Answer 6

• TAKES 1 HOUR TO DISTRIBUTE FROM PLASMA INTO TISSUE
• widely distributed, esp. to ADIPOSE
• TOTAL BODY WEIGHT should be used for dosing

Question 7

Vancomycin Elimination

Answer 7

Eliminated by kidney

Question 8

Vancomycin Half-Life

Answer 8

1/2 life progressively increases with decreases in renal function
- in end stage renal disease, 1/2 life= 7-14 days

Question 9

Vancomysin Serum Concentration Monitering

Answer 9

Peak should be drawn 60 MINUTES AFTER THE END OF INFUSION

Question 10

Vancomysin Clinical Uses

Answer 10

MRSA
B-LACTAM ALLERGIC PATIENTS
PRSP
MODERATE TO SEVERE C-DIF (oral)
endocarditis or surgical prophylaxis in select cases

Question 11

Vancomysin Adverse Effects

Answer 11

Red-Man Syndrome
Nephrotoxicity (Mississippi Mud!) & Ototoxicity
Dermatologic
Hematologic
Thrombophlebitis, interstitial nephritis

Question 12

Red-Man Syndrome

Answer 12

• Adverse effect of Vancomysin
• related to RATE of IV infusion
• flushing, pruruitus, erythematous rash on face, neck, and upper torso w/i 5-15 min.
• resolves spontaneously after discontinuation
• can lengthen infusion time

Question 13

Oxazolidinones

Answer 13

Developed in response to need for abx w/ activity against resistant Gram (+) organisms, namely MRSA, VISA (GISA), VRE
Linezolid is the only drug in this class.
AVAILABLE PO AND IV.

Question 14

Oxazolidinones/Linezolid Mech of Action

Answer 14

INHIBITS PROTEIN SYNTHESIS

binds to 50S RIBOSOMAL SUBUNIT, CAUSING INHIBITION OF 70S INITIATION COMPLEX

Question 15

Oxazolidinones/Linezolid- Bactericidal or Bacteriostatic?

Answer 15

Bacteriostatic (time-dependent bacteriocidal against some bacteria)

Question 16

Mechanism of Resistance against Oxazolidinones/Linezolid Abx

Answer 16

alteration of ribosomal subunit target site, has rarely emerged w/ Enterococcus and S. aureus

Question 17

Oxazolidinones/Linezolid Spectrum of Activity

Answer 17

Gram (+):
MSSA
MRSA
VANCOMYCIN-RESISTANT STAPH AUREUS
PRSP
E. FAECIUM AND FAECALIS, INCLUDING VRE
others

Relatively inactive against Gram (-) aerobes and not used with Atypical Bacteria

Question 18

Oxazolidinones/Linezolid Pharmacology

Answer 18

TIME-DEPENDENT BACTERICIDAL ACTIVITY is major predictor of efficacy
SIGNIFICANT PAE exists for Gram (+) organisms

Question 19

Oxazolidinones/Linezolid Absorption

Answer 19

RAPIDLY & COMPLETELY ABSORBED ORALLY W/ A BIOAVAILABILITY OF 100%

Question 20

Oxazolidinones/Linezolid Distribution

Answer 20

readily distributes into well-perfused tissues

CSF PENETRATION ~30%

Question 21

Oxazolidinones/Linezolid Elimination

Answer 21

eliminated by renal and non-renal routes

Question 22

Oxazolidinones/Linezolid Clinical uses

Answer 22

• VERY EXPENSIVE
• SERIOIUS/COMPLICATED INFECTIONS CAUSED BY RESISTANT GRAM POSITIVE INFECTIONS, esp. where vancomycin can’t be used
• VRE BACTEREMIA OR UTIs
• NOSOCOMIAL PNEUMONIA DUE TO MSSA OR MRSA

Question 23

Oxazolidinones/Linezolid Drug Interactions

Answer 23

Serotonin Syndrome w/ SSRIs (& MAOIs)

Question 24

Oxazolidinones/Linezolid Adverse Effects

Answer 24

LACTIC ACIDOSIS
PERIPHERAL NEUROPATHY
THROMBOCYTOPENIA OR ANEMIA 2-4%
headache

Question 25

Lipopeptides

Answer 25

Developed in response to need for abx w/ activity against Gram (+)s Daptomycin is only drug discussed in this class.

Question 26

Lipopeptides/Daptomycin Mech of Action

Answer 26

Binds to bacterial membranes and causes rapid depolarization, causing inhibition of protein, DNA, and RNA synthesis

Question 27

Mechanism of Resistance to Lipopeptides/Daptomycin Abx

Answer 27

rarely reported in VRE and MRSA due to altered cell membrane binding

Question 28

Lipopeptides/Daptomycin Spectrum of Activity

Answer 28

``` Excellent Gram (+) Activity MSSA MRSA VRSA PRSP E. FAECIUM AND FAECALIS, INCL. VRE ``` relatively inactive against Gram (-)

Question 29

Lipopeptides/Daptomycin- Bactericidal or Bacteriostatic?

Answer 29

RAPID, CONCENTRATION-DEPENDENT BACTERICIDAL ACTIVITY

Question 30

Lipopeptides/Daptomycin Pharmacology

Answer 30

only available parentally

Question 31

Lipopeptides/Daptomycin Distribution

Answer 31

readily distributes into well-perfused tissue, protein binding= 90%

Question 32

Lipopeptides/Daptomycin Elimination

Answer 32

excreted primarily by the kidneys, DOSAGE ADJUSTMENTS REQUIRED for renal insufficiency

Question 33

Lipopeptides/Daptomycin Clinical Uses and Dosing

Answer 33

COMPLICATED SKIN/SKIN STRUCTURE INFECTIONS CAUSED BY MSSA, MRSA, S. PYOGENES, ETC.) SHOULD NOT BE USED FOR PNEUMONIA

Question 34

Lipopeptides/Daptomycin Adverse Effects

Answer 34

``` MYOPATHY & CPK ELEVATION Gastrointestinal Headache Injection site reactions Rash ```

Question 35

Lipopeptides/Daptomycin Drug Interactions

Answer 35

HMG CoA-reductase inhibitors (i.e. Statins)- may lead to increased incidence of myopathy b/c statins also have this side effect