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Flashcards in Antibacterial: Cell Wall Synthesis Inhibitors Deck (23)
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1

list the cell wall synthesis inhibitors

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

2

CWSI are inactive against? and require? 

  • Inactive against organisms without peptidoglycan cell wall eg. mycoplasma, protozoa, fungi, viruses

  • Require actively proliferating bacteria (cell wall synthesis must be occurring)

3

describe B-lactamase

  • 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

4

what is the target site for B-lactam antibiotics

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

5

B-lactam MOA

  • 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

6

Penicillin G clinical application

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

7

Penicillin V 

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

8

Anti-Staph Penicillins

  • 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

9

Ampicillin, Amoxicillin

  • 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

10

Good penicillin for children? 

Amoxicillin

11

Anti-Pseudomonal Penicillins

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

12

Penicillin AEs

  • 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)

13

Positive Coombs Test?

Penicillin G, V

14

Carbapenems

  • 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)

15

Aztreonam

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

16

Vancomycin MOA/resistance

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

17

Vancomycin Clinical use 

  • 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 

18

Vancomycin AEs

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

19

Daptomycin MOA

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

20

Daptomycin

  • 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

21

Daptomycin AE

Elevated creatinine phosphokinases - myopathy 
(don't take with statins)

22

Bacitracin

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

23

Fosfomycin

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