1. CELL WALL SYNTHESIS INHIBITORS

2. CELL WALL SYN. INHIBITORS
BETA LACTAM ANTI BIOTICS
PENCILLINS
CEPHALOSPORINS
CARBAPENEMS
MONOBACTAMS

4. Beta- Lactam Antibiotics

5. Beta- Lactam Antibiotics
Strep throat IM, syphilis
Skin infections fm staph/strep
Bacterial URI
SE: Hypersensitivity is primary problem. Pruritic rash. Anaphylaxis also occurs.

6. Penicillins Bactericidal Peptidoglycan cell wall organisms
Not effective against Mycobacterium, Protozoa , Fungi & viruses.

7. Interfere with last step of bacterial synthesis—trans peptidation
Results in exposure of less stable membrane.
Cell lysis occurs through osmotic pressure or activation of autolysins
Thus they are bactericidal.

8. Penicillin binding proteins
Penicillins inactivate many proteins on the bacterial cell membrane. These pbps are bacterial enzymes involved in the synthesis of the cell wall
Inhibition of trans peptidase
Production of autolysins

9. Antistaphylococcal penicillins
All are stable to penicillinase
Cloxacillin
Dicloxacillin
Methicillin
Nafcillin
Oxacillin

10. Antipseudomonal penicillins
Particularly active against P. aeruginosa
Azlocillin
Carbenicillin
Mezlocillin
Piperacillin
Ticarcillin

11. Clinical use of penicillin G.
Pneumococcal pneumonia
Syphilis single treatment with penicillin is curative. No resistance has been reported
gonorrhea

12. ROUTES :
PENCILLIN V , AMOXICILLIN + CLAVULANIC ACID ORAL
DEPOT : PROCAINE PENCILLIN G, BENZATHINE PENCILLIN G
DO NOT CROSS BBB UNLESS INFLAMED
EXCRETION : TUBULAR SECRETION

13. SE
HYPERSENSITIVITY—the metabolite penicilloic acid serves as a hapten to cause immune reaction.
Maculopapular rash—ampicillin
Angioedema
anaphylaxis

14. DIARRHEA– disruption of the normal balance of intestinal micro organisms. Pseudo membranous colitis may also occur.
NEPHRITIS ( Mostly Methicillin)
NEUROTOXICITY– care in epileptics
CATION TOXICITY
Platelet dysfunction ( Carbenicillin & Ticarcillin

15. Resistance
Beta lactamase enzyme hydrolyzes the cyclic bond of the beta lactam ring—results in loss of bactericidal activity.
Decreased penetration of the antibiotic through the outer cell membrane prevents the drug from reaching the target pbp.

16. Beta- Lactam Antibiotics
Commonly used, some resistance, lower cost
Also commonly used, less resistance, higher cost
$ $ $ $ Expensive $ $ $ $
Resistant/ Severe Infections
SE: all have some degree of cross reactivity w/pen allergic pt. 5-15%

17. 1st Generation Cefazolin Cephalexin Cefadroxil Cephradine
Broad spectrum, mostly oral, commonly used, some resistance, lower cost,
Active against - Proteus, E. coli,
K. pneumonia (PEcK)

18. 2nd Generation Cefamandole Cefoxitin Cefaclor Cefotetan Cefuroxime
Less resistance, higher cost, oral/IM/IV.
H. influenza, Enterobacter, Neisseria + 1st (HEN PEcK)

19. 3rd Generation Cefoperazone Ceftriaxone Cefixime Cefotaxime
Ceftazidime
Expensive, for resistant/severe infections, Septic shock, MENINGITIS.

20. 4th Generation
Cefepime
Newer agent
Very broad spectrum activity

21. Common usage Cephalexin - Pharyngitis Cefazolin - Bone penetration
Cefoxitin – Anaerobes ( Bacteroides fragilis)
abdominal sepsis and PID
Ceftazidime – most active against
P. aeruginosa
Ceftriaxone – good bone penetration, Neisseria

22. DISTRIBUTION BBB: ONLY 3rd GENERATION
MENINGITIS : CEFTRIAXONE, CEFOTAXIME
EXCRETION : RENAL SECRETION
(Ceftriaxone, Cefoperazone excreted mostly through bile)

23. Cephalosporins are mostly not effective against
MRSA,
Listeria monocytogenes
Clostridium difficile
Enterococci.
Newer agent classified as 4th generation (Cefepime) has shown some effectiveness

24. SE
HYPERSENSITIVITY
CEFOPERAZONE, CEFAMANDOLE – CI IN ALCOHOL
BLEEDING

25. Beta- Lactam Antibiotics
Nephrotoxic
Nephrotoxic & Ototoxic

26. CARBAPENEMS
Eg; Imipenem/Cilastatin
Cilastatin is not a antibiotic , it’s a peptidase inhibitor that protects imipenem from degradation.
Broad spectrum, Mostly IV route and excreted by glomerular filtration.
SE: Diarrhea, seizures if increased plasma levels.

27. Carbapenems
Empiric therapy – active against G positive and negative
Eosinophilia , neutropenia

28. MONOBACTAMS
Eg; Aztreonam
Only in this class.
Narrow spectrum – enterobacteria.
IV & IM routes , excreted through urine.
Relatively non toxic, but can cause skin rash, phlebitis.

29. Vancomycin
Inhibits synthesis of bacterial cell wall phospholipids and Peptidoglycan
Reserved for serious infections with gram +ve
Used mainly for Methicillin resistant Staphylococcus aureus (MRSA) and Methicillin resistant Staphylococcus epidermidis (MRSE)
And also for antibiotic associated Colitis due to Clostridium difficile or Staphylococci

30. Slow IV route preferred,
Excretion – glomerular filtration
SE: fever, chills , phlebitis at the site of the injection
Shock reported with fast rapid administration along with Flushing due to histamine release. ( RED MAN SYNDROME)

31. BETA LACTAMASE INHIBITORS
CLAVULANIC ACID
SULBACTAM
TAZOBACTAM
NO ANTI BACTERIAL ACTIVITY