CEPHALOSPORINS

Outline of lecture

Introduction
Chemistry
M.O.A
Classification
Individual drugs
Adverse effects
Therapeutic Uses
Introduction

 Important group of beta lactam antibiotics

 Isolated by Brotzu in 1948 from Cephalosporium acremonium
in a sewage
 Cephalothin was introduced to market in 1964 by Eli Lilly
 No. of semisynthetic cephalosporin have been derived
 Bactericidal
Chemistry
Dihydrothiazine and β lactam ring
Modification at position 7 – Antibacterial activity
Modification at position 3- Pharmacokinetic property
Mechanism of action
 Mechanism of Resistance
Alteration in target protein

Decrease in permeability

Production of β lactamase
Classification

Chronological
sequence of
development

Antibacterial
spectrum

Susceptibility or
resistance to b-
lactamase
 Oral
Oral
Oral Cefixime
Cefalexin
Cefaclor Ceftibuten
Cefadroxil Parenteral
Cef. Axetil Cefdinir Ceftaroline
Cefaclor Cefepime
Parenteral Parenteral Ceftobiprole
Parenteral Cefpirome
Cefoxitine Cefoperazone
Cephalothin
Cefuroxime Ceftriaxone
Cephaloridine
Cefotaxime

First Generation Second

Third
Fourth Fifth
 Classification
Gen Oral Parenteral
1st Cephaalexin Cephalothin,Cephaloridine
Cefadroxil Cefazolin

2nd Cefaclor Cefoxitin,Cefuroxime

Cefuroxime axetil

3rd Cefiixme,Ceftibuten Cefotaxime,Cefoperazone

Cefpodoxime proxetil Ceftriaxone,Ceftazidime
Cefdinir

4th Cefepime,Cefpirome

5th Ceftobiprole,Ceftaroline
Which of the following is not a first-generation cephalosporin?
A . Cefadroxil
B . Cephalothin
C . Cefaclor
D . Cephalexin
 General Pharmacokinetics

 Cephalosporin -Given parenterally and orally

 Cephalothin-Only IV others ( IM or IV)
 Plasma protein binding varies
 Cefazolin -80% ,Cephalexin-10-15%
 Absorption varies
 Cefaclor, Cefdinir-Anatcids ,Cefuroxime –Food
 Absorption of Cefpodoxime is reduced by antacid and food
 General Pharmacokinetics

 Cefuroxime,Ceftriaxone,Ceftizoxime,Cefepime-Cross BBB
 Cefoperazone-Can’t cross BBB
 Cefadroxil,Cephalexin,Ceftriaxone-Safe in pregnancy
 Some excreted by bile ( Cefoperazone,Cefpiramide)
 Some deacetylated (Cefotaxime,Cephalothin) and excreted by
kidney, others not metabolized and excreted
 Probenecid slows their elimination and prolong their half-live
First generation cephalosporins

 Gm +ve -Most effective, Gm-ve -Weakly effective

 Susceptible to β-lactamase
 Penetration of the cerebrospinal fluid (CSF) is inadequate
 Not used in serious systemic infections
Cefazolin
 Prototype of first generation
 Effective against most Penicillin G sensitive organisms
 Effective against E.coli,Klebsiella,M catarrhalis
 Susceptible to β lactamase
 Long duration of action
 Preferred for surgical prophylaxis
 Dose -250mg 8hrly IM/IV
Cephalexin

 Orally effective
 Similar spectrum to Cefazolin
 Less active against Penicillinase producing Staph, and
H.influenzae
 Excreted unchanged in urine
 Commonly used
 Dose 0.25-1gm 6hrly
Second Generation

 More active against Gm- ve organism

 Less active against Gm + ve organism
 Some( cefoxitin,cefotetan) are active against anaerobes
 Not active against P.aeruginosa
Cefuroxime
Resistant to β lactamase
 Highly effective for PPNG
 S.pneumoniae,H.influenzae, N.meningitidis
 Effective against some anaerobes but not B.fragilis
 Achieve high conc. in CSF
 Useful in meningitis Dose 0.75-1.5 gm 8hrly
 Gonorrhea—1.5mg with 1 gm probenecid

Cefurxome axetil
 Prodrug
 Dose 250-500mg BD
Cefaclor

 Orally effective
 More effective for H.Influenzae,E.Coli,Pr.mirabilis
 Use- Pneumonia,UTI
 Dose 0.25-1gm 8hrly
 Cefoxitin

 Resistant to beta lactamase

 Active against B.fragilis, Proteus
 Not available in India
 Third Generation

 Highly active against Gm-ve organism

 Active against anaerobic organism
 Some drug is active against P.aeruginosa
 Less active against Gm+ve,
 Resistant to B lactamase
Cefotaxime

 Prototype of 3rd generation

 Effective for aerobic Gm –ve, Gm +ve organisms
 Not effective for anaerobes, Ps. Aeruginosa,S.aureus
 Deacetylated in body
Uses
 Meningitis,Septicemia Hospital acquired infections
 Dose 1-2gm IM/IV 12hrly
Ceftriaxone
 Longer duration of action
 Widely distributed, Good CSF penetration
 Equal elimination in urine and bile
 Effective for pathogens of community acquired
pneumonia,meningitis,Salmonella,N.gonnorhea
Uses
 Meningitis,Typhoid,UTI,Septicemia,Gonorrhea
 Chancroid ( single dose)
A/E
 Diarhhea,Hypoprothrominemia,Pseudolithiasis
Dose
 Meningitis

4gm followed by 2gmIV OD for 7 days

 Typhoid

4gm IV OD for 2DAYS followed by 2gm/day till 2days after fever

subsides
 Skin/Soft tissue/UTI

1-2 gm IV/IM/day
Cefoperazone

 Effective against Pseudomonas, B. fragilis, S. typhi

 Susceptible to B lactamase
Uses
 UTI, Meningitis, Typhoid fever, Septicemia
Dose 1-3gm 8-12hrly
A/E
 Hypoprothrombinemia
 Disulfiram like reaction with alcohol
Ceftazidime

 Highly effective against Pseudomonas, Enterobacteriaceae

 Less effective for Gm +ve cocci,anaerobes
 Drug of choice for melidosis
 Dose-0.5-2gm IM/IV every 8hrs

A/E
 Neutropenia, Rise in plasma transaminase
 Cefixime

 Orally active
 Resistant to B lactamase
 Effective against Enterobacteriaceae, H.influenzae
 Not effective against Pseudomonas,S.aureus
 Excreted in bile
Uses
 URTI,UTI
 A/E Diarrhea
 Dose 200-400mg BD
Cefepime

 Fourth generation cephalosporin

 Anti-bacterial spectrum similar to 3rd generation
 Resistant to β lactamase
 Effective against Pseudomonas
 Not active against MRSA
 Useful in
 Pneumonia
 Febrile neutropenia,nosocomial infection, Septicemia
 Dose 1-2gm IV 8-12 hrly
Ceftobiprole

 Fifth generation cephalosporin

 Effective against Gm +ve cocci,MRSA,VRSA,Penicillin resistant

S.pneumoniae, Enterococcus
 Retain the activity against Gm-ve bacilli

 Limited activity against anaerobes,ESBL producing strains

Uses
 Community acquired pneumonia

 Skin infections including MRSA

 Dose -500 mg as 2-hour infusion every 8 hours

 Adverse effects

Hypersensitivity reactions

Pain,Thrombophlebitis(Cephalothin)

Diarrhea(Cephoperazone, Cefixime, Cephradine)

Bleeding ( Cefoperazone,Ceftriaxone)

Nephrotoxicity( Cephalothin,Cephaloridine)

Disulfiram like reaction(Cefoperazone)

Neutropenia(Ceftazidime)
Q. Which of the folllowing cephalospoin can be used in patient
with low GFR?
A.Cefuroxime
B.Cefixime
C.Ceftazidime
D.Cefoperazone
 Uses
Alternative to Penicillin G

Septicemia
Surgical prophylaxis
Respiratory tract infection
Urinary tract infection
Meningitis
Typhoid
Gonorrhea,Chancroid
Q.Which of the following antimicrobial has anti-pseudomonal
action?
A.Cefodoxime
B.Cephradine
C.Cefotetan
D.Cefoperazone
Q.Cephalosporin that does not require dose reduction in patient
with any degree of renal impairment is
A.Cefuroxime
B.Cefoperazone
C.Ceftazidime
D.Cefotaxime
 Preferred cephalosporin
S.aureus,S.pyogenes-Cefotaxime
Salmonella-Ceftriaxone,Cefoperazone
Pseudomonas-Ceftazidime,Cefoperazone
B.fragilis-Ceftizoxime,Cefoperazone
Community acquired pneumonia- Cefotaxime,Ceftriaxone
Meningitis- Cefotaxime,Ceftriaxone
 Beta lactamase inhibitors
 Clavulinic acid,Sulbactam,Tazobactam
 Do not possess any significant antibacterial activity
 Inhibits the breakdown of beta lactam antibiotics
 Co-amoxiclav
 Amoxycillin and Clavulinic acid( oral use)
 Ticarcillin and clavulanic acid( Parenteral use)
 Ampicillin +Sulbactam
 Pipercaillin+Tazobactam
 Summary

It is a beta lactam antibiotics

Cell wall synthesis inhibitors
Five generations
Third generation are most commonly used
Not effective against MRSA, E.faecalis,L.monocytogenes
Common uses are typhoid fever, UTI,Septicemia,Meningitis
Adverse effects -Hypersensitivity reactions, Diarrhea, Bleeding
,Nephrotoxicity,
Thank You