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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
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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