Cephalosporins

Beta Lactam
Antibiotics- Cephalosporins

Contents

Cephalosporins

•       Mechanism
of action

•       Classification

•       Pharmacokinetics

•       Adverse
effects

•       Clinical
uses

Objective

At the
end of this lecture, the student will be able to:

•       Describe
the antimicrobial spectrum of cephalosporins

•       Explain
the mechanism of action of caphalosporins

•       Discuss
the pharmacokinetics and adverse effects of cephalosporins

Cephalosporins

•       Cephalosporins
chemical analogues – cefamycins

•       Dihydrothiazine
ring fused to β-Lactam ring
with an appropriate side chain on position-7

•       Isolated
from Cephalosporinium acremonium and Streptomyces lactamdurans

Structure of Cephalosporins

Structure of Penicillin vs Cephalosporins

Mechanism of Action of Cephalosporins

•       Identical
to penicillin

•       Inhibition
of transpeptidation

•       Formation
of imperfect cell wall

•       Osmotic
changes

•       Activation
of autolysin enzyme

•       Lysis
of bacteria – Bactericidal

Classification and Antimicrobial Spectrum

•       According
to their ‘generation’ and antibacterial spectrum, stability to β-Lactamase and year of production

•       First
generation – 1960s

•       Second
generation – 1970s

•       Third
generation – 1980s

•       Fourth
generation – 1997-1998

•       Fifth
Generation- 2000-

First Generation Cephalosporins

•       Cephalexin,
Cephapirin, Cefadroxil – Oral

•       Cephradine
– oral & parenteral

•       Cephalothin
& cefazolin – parenteral

•       β-Lactamase sensitive

•       Oral
drugs- well absorbed from GIT

•       High
serum level than tissues

•       Metabolism
not significant

•       Excreted
through urine

Antimicrobial
spectrum

•       Sensitivity
against gram positive cocci

•       Gram
negative bacteria like E. coli, K. pneumoniea, Proteus mirabilis

•       Anaerobic
cocci sensitive are – peptococcus and peptostreptococcus

Clinical uses

•       UTI,
minor staphylococcus infections

•       Cefazolin
– surgical prophylaxis before cardiac surgery, orthopaedic prosthesis
procedures

•       Ineffective
in meningitis

•       As
an alternative to penicillins

Second Generation Cephalosporins

•       Cefaclor,
Cefmetazole, Cefprozil – Oral

•       Cefoxitin
Cefamandol, cefotetan – parenteral

•       Cefuroxime
– oral or parenteral

Antimicrobial spectrum

•       Extended
spectrum against gram negative organisms

K. Pneumonia

H. influenza

Bacteriodis fragilis

Pharmacokinetics

•       Well
absorbed from GIT

•       Resistance
to β– lactamase – except
cefaclor

•       Protein
binding is significant

•       Cefuroxime
– cross BBB

•       Excreted
unchanged in urine

Clinical uses

•       Sinusitis

•       Otitis

•       Lower
respiratory tract infection

•       Effective
against anerobes – peritonitis & diverticulitis

•       Cefuroxime
– community acquired pneumonia

Third Generation Cephalosporins

Advantages

•       Extended
spectrum gram negative

•       Effective
against β-lactamase producing
haemophillus and nesseria

•       All
can cross BBB

Disadvantage

•       Sensitive
to constitutively produced β-lactamase
in organisms like enterobacter

Pharmcokinetics

•       Oral
– good bioavailability

•       Given
i.v with anesthetic

•       Distribution
is good – except cefoperazone

•       Reaches
good level in CNS

Uses – Gonorrhae, meningitis and sepsis

Fourth Generation Cephalosporins

•       Cefipime

•       Cefpirome

•       Cefozoram

•       Extended
gram negative coverage

•       Resistance
to β-lactamase

•       Used
in gonorrhae, meningitis and sepsis

Adverse effects

•       Super
infection

•       Pain
when injected IM

•       Thrombophlebitis
may occur after i.v

•       Allergic
reaction

•       Renal
toxicity

•       Interstitial
nephritis

•       Bleeding
disorders and fall in prothrombin time

•       Ceftobiprole
and Ceftaroline

•       Inhibit
cell wall synthesis

•       Inhibit
penicillin binding protein 2a produced by MRSA and penicillin resistant S.
pneumoniae

•       Super
infection, coagulation abnormalities and pseudolithiasis

Summary

•       Cephalosporins
and their chemical analogues – cefamycins consists of dihydrithiazine ring
fused to β-Lactam ring with
an appropriate side chain on position-7

•       Isolated
from Cephalosporinium acremonium and Streptomyces lactamdurans

•       Mechanism
of action is similar to that of penicillins

•       Anti-Microbial
spectrum-First generation cephalosporins: Sensitivity against gram positive
cocci; Gram negative bacteria like E. coli, K. pneumoniea, Proteus mirabilis;
Anaerobic cocci sensitive are – peptococcus and peptostreptococcus

•       Second
generation cephalosporins: Extended spectrum against gram negative organisms-
K. Pneumonia, H. influenza, Bacteriodis fragilis

•       Third
and fourth generation cephalosporins: Gonorrhae, meningitis and sepsis

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