Cephalosporins

Dr. Tejas K. Patel

Asst. Professor,
Department of Pharmacology,
GMERS Medical College, Gotri,
Vadodara
1/15/16

Cephalosporins
lactam antibiotic
Obtained from fungus
cephalosporinium
Structurally similar to penicillin

1/15/16

Mechanism of action
All cephalosporins are bactericidal
Similar to penicillin

1/15/16

Cephalosporins binds with CBPs and inhibits

transpeptidation process

This inhibits cell wall synthesis and leads to

information of imperfect cell wall

Osmotic drive of fluid from outside to inside of

bacteria

Bacteria swells and bursts to die

1/15/16

-lactam antibiotics

Mechanism of resistance
Elaboration of lactamase enzyme
(cephalosporinase) which destroy
cephalosporins
Alteration of target protein (PBP/CBP)
Impermeability of antibiotic
Efflux
1/15/16

Classification

First generation
Second generation
Third generation
Forth generation
Fifth generation

1/15/16

First generation
Parenteral
Cefazolin

Oral
Cephalexin
Cephradin
Cefadroxyl

1/15/16

Second
generation
Parenteral
Cefuroxime
Cefamandle
Cefoxitin

Oral
Cefaclor
Cefuroxime
axetil
7

Third generation
Oral
Parenteral
Cefotaxime
Ceftizoxime
Ceftriaxone
Ceftazidime
Cefoperazone
1/15/16

Cefixime
Cepodoxime
Cefdinir
Ceftibuten
Ceftamet

Forth
generation
Parenteral
Cefepime
Cefpirome

1/15/16

Fifth generation

Parenteral
Ceftaroline
Ceftabiprole

First generation
Parenteral
Cefazolin

Oral
Cephalexin
Cephradin
Cefadroxyl

1/15/16

Spectrum: similar to
Pn
High activity against
Gm+ve organisms
Weak activity against
Gm-ve organisms
10

Cefazoline
Prototype drug
Active against most Pn sensitive
organisms

1/15/16

11

Cefazoline
Spectrum
Gm+ve cocci
Sterp. Pyogenes
Strep. Viridans
Strep. Pneumoniae
Staph. aureus
( MRSA)
Gm-ve cocci
N. Gonorrhoea
N. Meningitidis
1/15/16

Gm+ve bacilli
C. diphtheriae
Clostridia
Gm-Bacilli
E.coli
Klebsiella
H. influenzae

Pharmacovigilance

 Not effective against

MRSA
Pseudomonas
Proteus vulgaris
Bacteroid fragilis

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13

Pharmacokinetics

Absorption : Not effective orally

Distribution: Better tissue distribution
Metabolism: not in liver
Excretion : through kidney (tubular
secretion)
Plasma half life: 1 to 2 hr

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14

 Dose: 1g 6 -8 hrly im/iv

Uses:
Surgical prophylaxis before
Cardiac surgery
Orthopedic prosthesis procedure

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15

Cephalexin/Cephradine/Cefa
droxyl
Orally effective first generation
cephalosporin
Antibacterial spectrum same as
cefazoline except
Pencillinase producing staph aureus
H. influenzae

Cefadroxyl has better tissue penetration

More sustained action at the site of infection
Can be given 12 hrly despite half life of 1 hr
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16

Therapeutic uses
Dose: 500 mg-1g BD (Cefadroxyl)
Uses
Pharyngitis, otitis media
Cellulitis, soft tissue abscess
Urinary tract infection

ADR
Diarrhoea
1/15/16

17

Second generation cephalopsporins

Parenteral
Cefuroxime
Cefamandle
Cefoxitin

Oral
Cefaclor
Cefuroxime axetil

1/15/16

As compare to 1st generation

More effective
against Gm-ve
organisms
Some are effective
This group
is largely
against
anaerobes
replaced by 3rd
generation
cephalosporins
18

Cefuroxime
Spectrum
Gm+ve cocci
Sterp. Pyogenes
Strep.
Pneumoniae
Gm-ve cocci
N. Gonorrhoea
(PPNG)
N. Meningitidis
1/15/16

Gm-ve bacilli
E.coli
Klebsiella
Proteus mirabillis
H.influenzae
Anaerobes
Bacteroiids

Pharmacovigilance

 Not effective against

Staphylococcus
Pseudomonas
Proteus vulgaris

1/15/16

20

Pharmacokinetics
Distribution: Good
cefuroxime penetrates the BBB
Metabolism: not in liver
Excretion :through kidney

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21

Therapeutic uses
Gonorrhea due to PPNG (250 mg
single IM inj)
Meningitis
Urinary tract infection

1/15/16

22

Cefuroxime axetil/ Cefaclor

Orally effective
Antibacterial activity - same as
cefuroxime

1/15/16

23

Third generation
Oral
Parenteral
Cefotaxime
Ceftizoxime
Ceftriaxone
Ceftazidime
Cefoperazone
1/15/16

Cefixime
Cepodoxime
Cefdinir
Ceftibuten
Ceftamet

24

Spectrum

Gm-ve bacilli
Gm+ve cocci
E.coli
Pneumococci
Klebsiella
Less effective than
Proteus
1st generation
Pseudomonas
Gm-ve cocci
(Cefoperazone,
ceftazidime)
N. Gonorrhoea
(PPNG)
Salmonella
(Ceftriaxone)
N. Meningitidis
Enterobacter
Anaerobes
Serratia (ceftazidime)
Bact. fragilis
H. influenzae
H. ducryei
(Ceftriaxone)
1/15/16

Pharmacovigilance

Pharmacokinetics
Distribution: Good, penetrates the
BBB
Metabolism: not metabolized except
cefotaxime (cefotaxime desacetylate)
Enterohepatic circulation: cefotaxime,
cefoperazone
Excretion :through kidney
Dose adjustment in renal insufficiency
1/15/16

26

Cefotaxime
Prototype 3rd generation
cephalosporin
Spectrum: GNC, GNB, few GPC
Not active against pseudomonas and
Bacteroids

Attains relatively high CSF levels

Active deacetylated metabolite
Dose: 1-2 g im/iv 8-12 hrly
1/15/16

27

 Indications
Gonorrhoea
Single dose (1g cefotaxime im + 1g
probenecid orally)

Meningitis caused by gram ve bacilli

Hospital acquired infection
Septicemia
Infection in immunocompromised
patient
1/15/16

28

Ceftizoxime
Same as cefotaxime except for
activity against bacteroids

1/15/16

29

Ceftriaxone
Same as cefotaxime
Active against GNC, GNB
Also active against Salmonella typhii,
H.ducreyii

Good CSF penetration

Equal elimination in urine and bile
Longer duration of action (OD/BD)
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30

 Indications
Bacterial meningitis (esp. in children)
4 g f/b 2g iv for 7-10 days (75-100 mg/kg/day)

Multi resistant typhoid fever

4 g iv OD for 2 days f/b 2 g OD

Complicated UTI
1-2 g iv OD

Abdominal sepsis
1-2 g iv OD

Septicemia
Gonorrhoea & chancroid
250 mg im single dose
1/15/16

31

 ADR
Hypoprothrombinemia
Related to its chemical structure
Mechanism same as warfarin

1/15/16

32

Ceftazidime
Spectrum:
Active against pseudomonas
Other spectrum same as cefotaxime

Used for pseudomonas infections

Dose: 1g iv 8 hrly

Ceftazidime + aminoglycoside synergistic

combination
ADR
Neutropenia, thrombocytopenia
Rise in liver enzymes
1/15/16

33

Cefoperazone
Active against
Pseudomonas
Salmonella
B. fragilis

Excreted in bile
Used for the pseudomonas infections
ADR
Diarrhoea
Hypoprothmobinemia
Disulfiram like reaction
1/15/16

34

Oral 3rd generation

cephalosporins

Cefixime
Cefopodoxime proxetil
Cefdinir
Ceftibuten
Ceftamet pivoxil

1/15/16

35

 Mainly effective against

Enterobacteriae
H. influenzae
Streptococci

Uses
Urinary tract infection
Biliary tract infection
Respiratory tract infection
Skin/soft tissue infection (cefopodoxime)

ADR
Diarrhoea
Rash
1/15/16

36

Fourth generation
Cefepime
Cefpirome

1/15/16

37

Antibacterial spectrum
Similar to 3rd generation, effective
against resistant Gm-ve organism
Highly effective againstEnterobacteriae
Their zwitterion
character permits
Pseudomonas
better penetration
Hemophyllius
through Gm ve
Neisseria
organisms
1/15/16

38

 Dose
1 g iv 8-12 hrly

Therapeutic uses
Hospital acquired pneumonia
Febrile neutropenia
Septicemia
Urinary tract infection

1/15/16

39

Adverse effects of
cephalosprins
Hypersensitivity reactions
Similar to penicillin, but incidence is lower
Rash is the most common manifestation
Urticaria, angioedema, asthma,
anaphylaxis are also reported
10% penicllin allergic pt shows cross
reactivity to cephalopsporin
Avoid cephalosporin, If h/o immidiate
hypersensitivity reaction to Pn
Skin testing is unreliable for cephalosporin
1/15/16

40

Adverse effects
Local irritant
Pain after im injection
Thrombophlebitis on iv injection

Diarrhoea
Due to irritation & alteration of gut flora
Mainly with oral cephalosporins and
cefoperazone

1/15/16

41

 Nephrotoxicity
Cephaloridin withdrawn
Nephrotoxicity enhanced by
Preexisting renal disease
Concurrent administration of nephrotoxic
drugs

Bleeding
Cefoperazone, ceftriaxone
Due to hypoprothrombinemia
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42

 Hematological toxicity
Neutropenia and thrombocytopenia due
to ceftazidime

Disulfiram like reaction

Ceforperazone

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43

Uses of cephalosporins
As an alternative to Pn G in allergic pt
But not with P/H of anaphylactic reaction
to penicillin
One of the 1st generation cephalosporin

Surgical Prophylaxis
Cefazoline (1st generation cephalosporin)

Respiratory tract infection

One of the orally acting 1st generation / 3rd
cephalosporin
1/15/16

44

 Penicllinase producing staphylococcal

infections
Cefopodoxime proxetil

Gonorrhoea (PPNG)
Ceftriaxone 250 mg single dose im

Chancroid
Ceftriaxone 250 mg single dose im

1/15/16

45

 Meningitis
3rd genrtation cephalosporins are preferred
due to
Bactericidal action
High CSF penetration (several times higher than
MIC)

For empirical therapy

Cefotaxime/ceftriaxone + Ampicillin/vancomycin

For pseudomonas meningitis

Ceftazidime + vancomycin
1/15/16

46

 Urinary tract infection

Cefotaxime/ceftriaxone (3rd generation
cephalosporin) or Cefuroxime (2nd
generation cephalosporin)
Orally acting 3rd generation
cephalosporins (cefixime)

Septicemia
By GNB
3rd generation cephalosporin +
aminoglycoside
1/15/16

47

 Typhoid fever
Ceftriaxone/cefoperazone iv
Fastest acting & most reliable antibiotic (all
strains are sensitive)
Alternative to fluroquinolones esp. in children
and pregnant lady

Mixed aerobic-anaerobic infection

in pts of cancer, colorectal surgery, obstetric
complications
One of the 3rd generation cephalosporin/
cefuroxime
1/15/16

48

 Hospital acquired infection

3rd / 4th generation cephalosporin

Prophylaxis & treatment of infections

in neutropenic pts
Ceftazidime with or without
aminoglycosides

1/15/16

49

Monobactams &
Carbapenems

Monbactams
Aztreonam
Monocyclic -lactam antibiotic

 Specific for GNB (enterobacteriae,

H.influenza, pseudomonas)
Not effective against GPC and
anaerobes

Lack of cross reactivity with other

lactum antibiotics