Cell wall inhibitor C ephalosporins - PowerPoint Presentation

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Cell wall inhibitorCephalosporins Dr. Naza M. Ali Lec 513-12-2016 D

CephalosporinsThe cephalosporins are beta-lactam antibiotics that are closely related both structurally & functionally to penicillins.Are produced semisynthetically by the chemical attachment of side chains to 7-aminocephalosporanic acid.

Mechanism of action and resistanceBind to PBPs on bacterial cell membrane to inhibit bacterial cell wall synthesis.Structural differences from penicillins render cephalosporin less susceptible to penicillinase produced by staphlococci, but many bacteria are resistance through the production of other beta-lactamase that can inactivate cephalosporins.Resistance also from decreased in membrane permeability to cephalosporins and from changes in PBPs.Methicillin-resistant staphylococci are also resistant to cephalosporin.

Antibacterial spectrum1.First-generation drug Cefazolin ( parenteral) , Cephalexin and Cefadroxil (oral) active against +gm cocci (staphylococci, streptococci)Proteus, E.coli , K pneumoniae (PEck)Used in surgical prophylaxis in selected condition.

2.Second generation: have greater activity against three additional gram-negative H. influenzae, Enterobacter aerogenes, Neisseria whereas activity against gram-positive is weaker HENPEcK Cefoxitin, Cefotetan active against Bacteroides Fragilis / IV Cefuroxime in community acquire pneumonia / oralCefaclor in otitis, lower RTI , sinusitis / oral Cefamandole

active against H. influenza

3.Third generation: have enhanced activity against gram-negative bacilli and some are able to cross BBBCeftriaxone or Cefotaxime drug of choice in meningitis and for empiric therapyCeftriaxone , Cefixime drug of choice in gonorrheaCeftazidime, Cefoperazone activity against P.aeruginosa Cefpodoxime, Cefdinir are orally

4.Fourth generation: Cefepime parenterally has a wide antibacterial spectrum.Combine gram positive activity of 1st generation with wider gram negative spectrum of 3rd generation. ( Enterobacter, E. coli, K. pneumoniae, Proteus mirabilis, P. aeruginosa).

5. Fifth generation: Ceftobiprole Ceftaroline A new cephalosporin with activity against Methicillin-Resistant Staphylococcus (MRSA)

GenerationSpectrumName of drugstreatment1stGm+ cocci, PEckCefazolin / InjCephalexin /oralCefdroxil / oral

surgical

prophylaxis,

penetration to bone

pharyngitis

2nd

HENPEcK

Bacteroides

fragilis

Cefoxitin

/

inj

Cefotetan

/

inj

Cefuroxime

oral

Cefaclor

/oral

community acquire

Pneumonia

Otitis

, lower RTI, sinusitis

3rd

gram-negative

bacilli

some are able to cross BBB

Ceftriaxone /

inj

Cefotaxime

/

inj

Ceftriaxone/

inj

Cefixime

/oral

Meningitis

Gonorrhea

P

.

aeruginosa

Ceftazidime

/

inj

Cefoperazone

/

inj

Cefpodoxime

/

oral

Cefdinir

/ oral

GenerationSpectrumName of drugDisease 4 thwide antibacterial .Combine gram positive 1st with wider gram negative 3rd Enterobacter, E. coli, K.

pneumoniae

,

Proteus

mirabilis

,

P

.

aerugin

,

Cefepime

p

arenteral

5

th

MRSA

Enterobacter

,

Gm-

ve

rods

Ceftobiprole

,

Ceftaroline

:

PharmacokineticsAdministration: IV , IM or oralDistribution: cross the placentaFate: tubular secretion and GF (Ceftriaxone is excreted through the bile into the feces)

Adverse effects: Allergic manifestationsPatients who have had an anaphylactic response, Stevens-Johnson syndrome to penicillins should not receive cephalosporins. Should be avoided or used with caution in individuals who are allergic to penicillins ( 8-10% show cross- sensitivity). Cephalosporin that contain methylthiotetrazole group: Cefamandole, cefotetan, cefoperazone cause hypoprothrombinemia and bleeding disorders.

Other Beta-Lactam Antibiotics Dr. Naza M Ali Lec 6 13-12-2016

Other beta-Lactam AntibioticsA. CarbapenemsB. MonobactamC. Beta-Lactamase inhibitors

A. CarbapenemsChemically different from penicillins but retaining the beta-lactam ring structure. Imipenem, meropenem, ertapenem , doripenemHave wide activity against gram positive cocci, gram negative rods, anaerobes.Plays a role in empiric therapy because it is active against penicillinase-producing gram-positive and gram- negative organism, anaerobes, P. aeruginosa Used in combination with aminoglycoside for pseudomonal infection

They are used parenterally & are useful for infections caused by organism resistant to other antibiotics.They are drugs of choice for infections caused by Enterobacter.Imipenem is compounded with cilastatin to protect it from metabolism by renal dehydropeptidase.Imipenem & meropenem are administered IV and penetrate well into body tissues & fluids, including CSF when meninges are inflamed.

B. MonobactamDrugs with monocyclic beta-lactam ring.Aztreonam is resistant to action of beta -lactamases.has antimicrobial activity against gram-negative rods (Enterobacteriaceae) including pseudomonas It lacks activity against gram-positive organisms and anaerobes.It is administered (IV or IM), is excreted in urine, it can accumulate in patients with renal failure.Aztreonam is relatively nontoxic, can use as alternative for treating patients who are allergic to penicillins or cephalosporins.

C. Beta-Lactamase Inhibitors Hydrolysis of the beta-lactam ring by enzymatic cleavage or by acid, destroys the antimicrobial activity.Clavulanic acid, Sulbactum, Tazobactam contain a beta-lactam ring but, by themselves, do not have significant antibacterial activity.They bind to and inactivate beta-lactamases protecting the antibiotics that are substrates for these enzymes.clavulanic acid and amoxicillin combination.

Carbapenem:Imipenem,MeropenemErtapenem

differ in

str

contain

bete

lactam

ring

Gm+

cocci

gm- rods (

enterobacteriaceae

)

anaerobes

pseudomonas +

aminoglycosid

Parenterally

Monobactam

:

Aztreonam

Monocyclic beta lactam ring

narrow spec.

-

ve

rode

P.

aeruginosa

No activity for +

ve

No toxic,safe

IM,IV

Beta-lactam inhibitors:

Clavulanic acid,

Sulbactam,

tazobactam

Contain beta lactum ring,

do not have significant antibacterial activity

Oral,

parenteral