Antibacterial: Cell Wall Synthesis Inhibitors

Question 1

list the cell wall synthesis inhibitors

Answer 1

• B-lactam antibiotics
  
  • penicillins
  • cephalosporins
  • carbapenems
  • monobactams
• Vancomycin
• Daptomycin
• Bacitracin
• Fosfomycin

Question 2

CWSI are inactive against? and require?

Answer 2

• Inactive against organisms without peptidoglycan cell wall eg. mycoplasma, protozoa, fungi, viruses
• Require actively proliferating bacteria (cell wall synthesis must be occurring)

Question 3

describe B-lactamase

Answer 3

• Bacterial enzymes that hydrolyze B-lactam ring
  
  • resist effects of penicillins eg. Staph aureus
• B-lactamase inhibitors
  
  • protect penicillins from inactivation via binding and inactivating B-lactamase
  • Clavulanic Acid, Sulbactam, Tazobactam

Question 4

what is the target site for B-lactam antibiotics

Answer 4

• Penicillin-binding proteins (PBPs)
• bacterial enzymes (transpeptidases) involved in cell
• wall synthesis = target site for B-lactam antibiotics
• resistance = PBP mutations

Question 5

B-lactam MOA

Answer 5

• Bactericidal
• Inhibit last step in peptidoglycan synthesis through binding to PBPs
• Activate autolytic enzymes to initiate cell death
• Bacteria eventually lyse due to activity of autolysins and inhibition of cell-wall assembly

Question 6

Penicillin G clinical application

Answer 6

• Mostly used for Gram + organisms
• Given IV
• Commonly used for:
  
  • Syphilis (benzathine penicillin G)
  • Strep infections
  • Susceptible pneumococci

Question 7

Penicillin V

Answer 7

• more acid stable than G (can give orally)
• used for mild-moderate infections eg. pharyngitis, tonsilitis, skin infections (caused by Strep)

Question 8

Anti-Staph Penicillins

Answer 8

• Nafcillin
• Methicillin (inactive against MRSA)
• Oxacillin
• Dicloxacillin
• ONLY Penicillin resistant to B-lactamase
  
  • NO NEED FOR B-lactamase inhibitor
• TXT for B-lactamase-producing staphylococci

Question 9

Ampicillin, Amoxicillin

Answer 9

• Similar to Penicillin G but with Gram negative activity
• Given w/ B-lactamase inhibitor
• Clinical use:
  
  • acute otitis media
  • streptococcal pharyngitis
  • pneumonia
  • skin infections
  • UTIs
• AE: maculopapular rash
• AE for Ampicillin only: Pseudomembranous colitis

Question 10

Good penicillin for children?

Answer 10

Amoxicillin

Question 11

Anti-Pseudomonal Penicillins

Answer 11

• Carbenicillin, Ticarcillin, Piperacillin
• Against Gram negative and positive bacilli
• Active against Pseudomonas Aeruginosa
• Treats moderate-severe conditions of susceptible organisms

Question 12

Penicillin AEs

Answer 12

• GI disturbances (eg, diarrhea)
• Pseudomembranous colitis (ampicillin)
• Maculopapular rash (ampicillin, amoxicillin)
• Interstitial nephritis (particularly methicillin)
• Neurotoxicity (epileptic patients at risk)
• Hematologic toxicities (ticarcillin)
• Neutropenia (nafcillin)
• Hepatitis (oxacillin)
• Secondary infections (eg, vaginal candidiasis)

Question 13

Positive Coombs Test?

Answer 13

Penicillin G, V

Question 14

Carbapenems

Answer 14

• Doripenam, Ertapenam, Meropenam, Imipenam
• “DIME antibiotics for 10/10 infections”
• Very broad → Gram (-), (+), anaerobe, aerobe
• Not active against MRSA or carbapenamse producing bacteria (klebsiella)
• Ertapenam = not active against P. Aureginosa
• Imipenam given with Cilastatin to prevent nephrotoxicity - inhibits dehyropeptidase I (high levels of imipenam = seizures)

Question 15

Aztreonam

Answer 15

• Monobactam
• Gram negative only
• given to penicillin allergic patients
• Little AE’s, no cross resistance with penillin

Question 16

Vancomycin MOA/resistance

Answer 16

• binds to D-Ala-D-Ala terminus
• Resistance: D-Ala-D-LAC, plasmid-mediated changes

Question 17

Vancomycin Clinical use

Answer 17

• Gram positive only
• Effective against MRSA
• Given to severely penicillin allergy patients
• Vancomycin + Amingoglycoside = txt infective endocarditis + PRSP
• Oral for pseudomembranous colitis, or staph enterocolitis

Question 18

Vancomycin AEs

Answer 18

• slow IV infusion 60-90 min otherwise RED-MAN syndrome
• Nephrotoxicity
• Ototoxicity
• Thrombophlebitis

Question 19

Daptomycin MOA

Answer 19

• Ca2+ dependent insertion of lipid tail → depolarization → k+ efflux → cell death

Question 20

Daptomycin

Answer 20

• Cidal, IV only
• Resistant Gram +ve (MRSA, VRE, VRSA - b/c of novel MOA)
• Surfactant inhibits drug → NOT given for pneumonia
• Clinical use: complicated skin/structure infections by s. aureus

Question 21

Daptomycin AE

Answer 21

Elevated creatinine phosphokinases - myopathy

(don’t take with statins)

Question 22

Bacitracin

Answer 22

• Gram positive
• Unique MOA → no cross resistance
• HUGE molecule → mainly topical for burns/skin wounds
• AE: Nephrotoxicity

Question 23

Fosfomycin

Answer 23

• Gram negative and positive
• MOA: Inhibits enolpyruvate transferase in early cell wall synthesis (all others = late)
• Oral
• Treats: uncomplicated lower UTI’s