11

CELL WALL SYNTHESIS CELL WALL SYNTHESIS INHIBITORSINHIBITORS

22

CELL WALL SYN. INHIBITORSCELL WALL SYN. INHIBITORS

BETA LACTAM ANTI BIOTICSBETA LACTAM ANTI BIOTICS

PENCILLINSPENCILLINS

CEPHALOSPORINSCEPHALOSPORINS

CARBAPENEMSCARBAPENEMS

MONOBACTAMSMONOBACTAMS

33

44

Beta- Lactam Antibiotics

55

Strep throat IM, syphilis

Skin infections fm staph/strepBacterial

URI

SE: Hypersensitivity is primary problem. Pruritic rash. Anaphylaxis also occurs.

Beta- Lactam Antibiotics

66

PenicillinsPenicillins

BactericidalBactericidal

Peptidoglycan cell wall organismsPeptidoglycan cell wall organisms

Not effective against Mycobacterium, Not effective against Mycobacterium, Protozoa , Fungi & viruses.Protozoa , Fungi & viruses.

77

Interfere with last step of bacterial Interfere with last step of bacterial synthesis—trans peptidationsynthesis—trans peptidation

Results in exposure of less stable Results in exposure of less stable membrane.membrane.

Cell lysis occurs through osmotic pressure Cell lysis occurs through osmotic pressure or activation of autolysinsor activation of autolysins

Thus they are bactericidal.Thus they are bactericidal.

88

Penicillin binding proteinsPenicillin binding proteins

Penicillins inactivate many proteins on the Penicillins inactivate many proteins on the bacterial cell membrane. These pbps are bacterial cell membrane. These pbps are bacterial enzymes involved in the bacterial enzymes involved in the synthesis of the cell wallsynthesis of the cell wall

Inhibition of trans peptidaseInhibition of trans peptidase

Production of autolysinsProduction of autolysins

99

Antistaphylococcal penicillinsAntistaphylococcal penicillins

All are stable to penicillinaseAll are stable to penicillinase

CloxacillinCloxacillin

DicloxacillinDicloxacillin

MethicillinMethicillin

NafcillinNafcillin

Oxacillin Oxacillin

1010

Antipseudomonal penicillinsAntipseudomonal penicillins

Particularly active against P. aeruginosaParticularly active against P. aeruginosa

AzlocillinAzlocillin

CarbenicillinCarbenicillin

MezlocillinMezlocillin

PiperacillinPiperacillin

TicarcillinTicarcillin

1111

Clinical use of penicillin G.Clinical use of penicillin G.

Pneumococcal pneumoniaPneumococcal pneumonia

Syphilis single treatment with penicillin is Syphilis single treatment with penicillin is curative. No resistance has been reportedcurative. No resistance has been reported

gonorrheagonorrhea

1212

ROUTES : ROUTES : PENCILLIN V , AMOXICILLIN + PENCILLIN V , AMOXICILLIN + CLAVULANIC ACID ORALCLAVULANIC ACID ORALDEPOT : PROCAINE PENCILLIN G, DEPOT : PROCAINE PENCILLIN G, BENZATHINE PENCILLIN GBENZATHINE PENCILLIN G

DO NOT CROSS BBB UNLESS DO NOT CROSS BBB UNLESS INFLAMEDINFLAMED

EXCRETION : TUBULAR SECRETIONEXCRETION : TUBULAR SECRETION

1313

SESE

HYPERSENSITIVITY—the metabolite HYPERSENSITIVITY—the metabolite penicilloic acid serves as a hapten to penicilloic acid serves as a hapten to cause immune reaction.cause immune reaction.

Maculopapular rash—ampicillinMaculopapular rash—ampicillin

AngioedemaAngioedema

anaphylaxisanaphylaxis

1414

DIARRHEA– disruption of the normal DIARRHEA– disruption of the normal balance of intestinal micro organisms. balance of intestinal micro organisms. Pseudo membranous colitis may also Pseudo membranous colitis may also occur.occur.NEPHRITIS ( Mostly Methicillin)NEPHRITIS ( Mostly Methicillin)NEUROTOXICITY– care in epilepticsNEUROTOXICITY– care in epilepticsCATION TOXICITYCATION TOXICITYPlatelet dysfunction ( Carbenicillin & Platelet dysfunction ( Carbenicillin & TicarcillinTicarcillin

1515

ResistanceResistance

Beta lactamase enzyme hydrolyzes the Beta lactamase enzyme hydrolyzes the cyclic bond of the beta lactam ring—cyclic bond of the beta lactam ring—results in loss of bactericidal activity.results in loss of bactericidal activity.

Decreased penetration of the antibiotic Decreased penetration of the antibiotic through the outer cell membrane prevents through the outer cell membrane prevents the drug from reaching the target pbp.the drug from reaching the target pbp.

1616

Commonly used, some resistance, lower cost

$ $ $ $ Expensive $ $ $ $

Resistant/ Severe Infections

Also commonly used, less resistance, higher cost

SE: all have some degree of cross reactivity w/pen allergic pt. 5-15%

Beta- Lactam Antibiotics

1717

1st Generation1st Generation

CefazolinCefazolinCephalexinCephalexinCefadroxilCefadroxilCephradineCephradineBroad spectrum, mostly oral, commonly Broad spectrum, mostly oral, commonly used, some resistance, lower cost,used, some resistance, lower cost,Active against - Proteus, E. coli,Active against - Proteus, E. coli,

K. pneumonia (PEcK)K. pneumonia (PEcK)

1818

2nd Generation2nd Generation

CefamandoleCefamandoleCefoxitinCefoxitinCefaclorCefaclorCefotetanCefotetanCefuroximeCefuroximeLess resistance, higher cost, oral/IM/IV.Less resistance, higher cost, oral/IM/IV.H. influenza, Enterobacter, Neisseria + 1st H. influenza, Enterobacter, Neisseria + 1st (HEN PEcK)(HEN PEcK)

1919

3rd Generation3rd Generation

CefoperazoneCefoperazone

CeftriaxoneCeftriaxone

CefiximeCefixime

CefotaximeCefotaxime

CeftazidimeCeftazidime

Expensive, for resistant/severe infections, Expensive, for resistant/severe infections, Septic shock, MENINGITIS. Septic shock, MENINGITIS.

2020

44thth Generation Generation

CefepimeCefepime

Newer agentNewer agent

Very broad spectrum activityVery broad spectrum activity

2121

Common usageCommon usage

Cephalexin - Pharyngitis Cephalexin - Pharyngitis Cefazolin - Bone penetration Cefazolin - Bone penetration Cefoxitin – Anaerobes ( Bacteroides Cefoxitin – Anaerobes ( Bacteroides fragilis)fragilis)

abdominal sepsis and PIDabdominal sepsis and PIDCeftazidime – most active against Ceftazidime – most active against

P. aeruginosaP. aeruginosaCeftriaxone – good bone penetration, Ceftriaxone – good bone penetration, NeisseriaNeisseria

2222

DISTRIBUTIONDISTRIBUTION

BBB: ONLY 3BBB: ONLY 3rdrd GENERATION GENERATION

MENINGITIS : CEFTRIAXONE, MENINGITIS : CEFTRIAXONE, CEFOTAXIMECEFOTAXIME

EXCRETION : RENAL SECRETIONEXCRETION : RENAL SECRETION

(Ceftriaxone, Cefoperazone excreted (Ceftriaxone, Cefoperazone excreted mostly through bile)mostly through bile)

2323

Cephalosporins are mostly Cephalosporins are mostly not effectivenot effective against against

MRSA, MRSA,

Listeria monocytogenesListeria monocytogenes

Clostridium difficile Clostridium difficile

Enterococci.Enterococci.

Newer agent classified as 4Newer agent classified as 4thth generation generation (Cefepime(Cefepime) has shown some effectiveness) has shown some effectiveness

2424

SESE

HYPERSENSITIVITYHYPERSENSITIVITY

CEFOPERAZONE, CEFAMANDOLE – CI CEFOPERAZONE, CEFAMANDOLE – CI IN ALCOHOLIN ALCOHOL

BLEEDINGBLEEDING

2525

Beta- Lactam Antibiotics

Nephrotoxic & Ototoxic

Nephrotoxic

2626

CARBAPENEMSCARBAPENEMSEg; Imipenem/CilastatinEg; Imipenem/CilastatinCilastatin is not a antibiotic , it’s a peptidase Cilastatin is not a antibiotic , it’s a peptidase

inhibitor that protects imipenem from inhibitor that protects imipenem from degradation.degradation.

Broad spectrum, Mostly IV route and Broad spectrum, Mostly IV route and excreted by glomerular filtration.excreted by glomerular filtration.

SE: Diarrhea, seizures if increased plasma SE: Diarrhea, seizures if increased plasma levels.levels.

2727

Carbapenems Carbapenems

Empiric therapy – active against G positive Empiric therapy – active against G positive and negative and negative

Eosinophilia , neutropeniaEosinophilia , neutropenia

2828

MONOBACTAMSMONOBACTAMS

Eg; AztreonamEg; Aztreonam

Only in this class.Only in this class.

Narrow spectrum – enterobacteria.Narrow spectrum – enterobacteria.

IV & IM routes , excreted through urine.IV & IM routes , excreted through urine.

Relatively non toxic, but can cause skin Relatively non toxic, but can cause skin rash, phlebitis.rash, phlebitis.

2929

VancomycinVancomycin

Inhibits synthesis of bacterial cell wall Inhibits synthesis of bacterial cell wall phospholipids and Peptidoglycanphospholipids and Peptidoglycan

Reserved for serious infections with gram +veReserved for serious infections with gram +ve

Used mainly for Methicillin resistant Used mainly for Methicillin resistant Staphylococcus aureus (MRSA) and Methicillin Staphylococcus aureus (MRSA) and Methicillin resistant Staphylococcus epidermidis (MRSE)resistant Staphylococcus epidermidis (MRSE)

And also for antibiotic associated Colitis due to And also for antibiotic associated Colitis due to Clostridium difficile or StaphylococciClostridium difficile or Staphylococci

3030

Slow IV route preferred,Slow IV route preferred,

Excretion – glomerular filtrationExcretion – glomerular filtration

SE: fever, chills , phlebitis at the site of the SE: fever, chills , phlebitis at the site of the injectioninjection

Shock reported with fast rapid Shock reported with fast rapid administration along with Flushing due to administration along with Flushing due to histamine release. ( RED MAN histamine release. ( RED MAN SYNDROME)SYNDROME)

3131

BETA LACTAMASE BETA LACTAMASE INHIBITORSINHIBITORS

CLAVULANIC ACIDCLAVULANIC ACID

SULBACTAMSULBACTAM

TAZOBACTAMTAZOBACTAM

NO ANTI BACTERIAL ACTIVITYNO ANTI BACTERIAL ACTIVITY