CELL WALL SYNTHESIS INHIBITORS

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

Beta- Lactam Antibiotics

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

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

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.

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

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

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

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

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

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

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

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.

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%

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

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

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

4th Generation Cefepime Newer agent Very broad spectrum activity

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

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

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

SE HYPERSENSITIVITY CEFOPERAZONE, CEFAMANDOLE – CI IN ALCOHOL BLEEDING

Beta- Lactam Antibiotics Nephrotoxic Nephrotoxic & Ototoxic

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.

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

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.

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

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)

BETA LACTAMASE INHIBITORS CLAVULANIC ACID SULBACTAM TAZOBACTAM NO ANTI BACTERIAL ACTIVITY