Cephalosporins are a class of β-lactam antibiotics similar to penicillin. They were first isolated from fungus in 1945 and work by inhibiting bacterial cell wall synthesis. There are several generations that have increased gram-negative spectrum. Common uses include skin/respiratory infections, sepsis, UTIs, and surgical prophylaxis. Adverse effects include hypersensitivity reactions, nephrotoxicity, and diarrhea. Resistance can develop through bacterial production of β-lactamases or changes to penicillin-binding proteins.

1. Cephalosporins
Dr.Ramachandrudu
M.D(Pharma)

2. β-Lactam antibiotics (beta-lactam
antibiotics)
• β-Lactam antibiotics (beta-lactam antibiotics)
are a broad class of antibiotics, consisting of
all antibiotic agents that contains a β-lactam
ring in their molecular structures. This
includes penicillin derivatives (penams),
cephalosporins (cephems), monobactams, and
carbapenems.

3. Cephalosporin & Penicillin
penicillin
cephalospo
rin

4. HISTORY OF CEPHALOSPORINS
• ISOLATED FROM CULTURES OF
CEPHALOSPORIUM ACREMONIUM
• IN 1945 –Italian scientist Brotzu
• Later cephalosporin-c is isolated in
University of Oxford
• 7amino cephalosporinic acid(7ACA)which
was derived from cephalosporin-c is
analogous to penicillin nucleus(6APA)

5. Cephalosporins
B-Lactam antibiotics ( similar to penicillins)
Broad spectrum
Act by inhibition of cell wall synthesis
Bactericidal
Inactive against : enterococci, MRSA, legionella ,
mycoplasma, chlamydia spp.
Widely used in surgical procedures to reduce the risk of
post operative infections
Cephalosporins are less succeptable to penicillinases
Disrupt synthesis of peptidoglycon layer
Final step of synthesis of peptidoglycon layer is inhibited

6. Pharmacological actions
• Earlier generation cephalosporins are G-positive
Successive generations have increased G-negativity
activity
• Cephalosporins reach poor conc. In c.s.f

7. Classification
• First generation (Moderate spectrum)
• Cefazolin · Cephalexin · Cephalosporin C ·
Cephalothin
• Second generation (Moderate spectrum)
• With anti-Haemophilus activity
• Cefaclor · Cefamandole · Cefuroxime
• With anti-anaerobic activity
• Cefotetan · Cefoxitin
• Third generation (Broad spectrum)
• Cefixime · Cefotaxime · Cefpodoxime ·
Ceftazidime · Ceftriaxone
• Fourth generation (Broad spectrum)

8. • (With β-lactamase stability and enhanced
activity against Gram-positive bacteria and
Pseudomonas aeruginosa)
• Cefepime · Cefpirome
• Fifth generation* (Broad spectrum)
• (Antipseudomonal in addition to activity
against MRSA and VRE. *Not universally
accepted nomenclature. )
• Ceftobiprol & Ceftaroline

9. FIRST GENERATION
Active against G+ cocci ( except.enterococci &
MRSA ):
S.pneumoniae, S.pyogenes,S. aureus,
S.epidermidis
Indicated for streptococcal pharyngitis ( e.g.
cephalexin)
Commonly used ( eg. Cefazolin) as prophylacic for
surgical procedures.
Modest activity against G- bacteria

10. SECOND GENERATION
Mainly effective against G- bacteria
Modest activity against G+ bacteria
Cefoxitin active against bowel anaerobes (B.
fragilis )
Cefuroxim active against H. influenzae, M.
catarrhalis, S. pneumoniae
Cef. Axetil- oral form of cefuroxim

11. Cefaclor active against H. influenzae, M.
catarrhalis &E.coli
Cefprozil- similar to cefaclor, c. axetil and
augmentin- Liked by children
Second Generations are used primarily for URTIs (
acute otitis media, sinusitis ) and Lower RTIs (
acute exacerbation of chronic bronchitis)

12. THIRD GENERATION
Ceftriaxone ( rocephin )
Cefotaxime ( claforan )
Cetazidime ( fortum )
Cefoperazone ( cefobid )
Cefixime ( suprax )
Cefpodoxime(Mahacef-O)
They have enhanced G- activity, H. influenzae, N.
meningitidis, N.gonorrhea, P. aeruginosae,
M. catarrhalis, E.coli, most Klebsiella

13. Ceftriaxone has long half-life . Not advised in
neonates (interferes with bilirubin
metabolism)
Cefotaxime preferred in neonate ( does not
interfere with bilirubin metabolism ), as may
ceftriaxone.
Ceftazidime & cefoperazone have excellent
activity against p. aeruginosae.
Cefixime has similar activity to amoxicillin &
cefaclor for actute otitis media

14. Fourth Generation
Cefipime
Active against G+ bacteria than cefazolin
against S. pyogenes, S.pneumoniae but lower
against S. aureus Similar to cefotaxime against
E.coli & K. pneumoniae but forp.aeruginosa.

15. Fifth generation
• Ceftaroline & ceftobiprole
• Fifth-generation cephalosporins are effective
against MRSA
• Ceftobiprole has powerful antipseudomonal
characteristics and appears to be less
susceptible to development of resistance.
Ceftaroline has also been described as "fifth-generation"
cephalosporin, but does not have
the anti-pseudomonal effect.

16. Pharmacokinetics
Cephalosporins are given parenterally and orally.
Extent of binding to plasma protein vary from one
to another.
e.g. Cefazolin is 80% protein bound ( hence, long
t1/2 )
Cephalexin is 10-15% protein bound
Relatively lipid insoluble ( like penicillins )
Hence,do not penetrate cells or the CNS, except for
third generations

17. Mostly excreted unchanged by the kidney
(glomerular & tubular secretion ), except,
ceftazidime & cefoperazone( glomerular)
Probenecid slows their elimination and prolong
their half-live ( except Ceftazidime &
cefoperazone)
Half-life 30-90 min; ceftriaxone 4-7 hr

18. Mechanism of action
• Cephalosporins are bactericidal and have the
same mode of action as other beta-lactam
antibiotics (such as penicillins) but are less
susceptible to penicillinases. Cephalosporins
disrupt the synthesis of the peptidoglycan layer
of bacterial cell walls. The peptidoglycan layer is
important for cell wall structural integrity. The
final transpeptidation step in the synthesis of the
peptidoglycan is facilitated by transpeptidases
known as penicillin-binding proteins (PBPs)

19. • EagleGet Downloads

20. Therapeutic uses
1. Alternative to penicillin in allergic patients
2. Upper respiratory tract infections and otitis media
cefaclor cefuroxime axetil
cefixime cefprozil
3. Septicaemia caused by G- bacteria( P.aeruginosae)
A cephalosporin(eg.ceftazidime )
4. Urinary tract infections
Cefuroxime, Cefixime

21. Therapeutic uses contd---
. 5. Prophlaxis in surgery
Appendectomy ( bowel anaerobes ) eg. Cefoxitin
Obstetrical &gynecological,urological, orthopedic
procedures, etc
( S. aureus & S. epidermidis ) eg. Cefazoline
6. Meningitis- N. Meningitidis
Ceftriaxone
Cefotaxime( pref. in neonate)
7. Gonococcal infections
Ceftriaxone

22. Preperations & Dosages
• Oral-1stgen-cephelexin250-500mg TID
• Cefadroxil-500mg-1gm BD
• Parenteral -1stgen-cefazolin500-1gm i.vTID
• Oral -2ndgen-cefaclor250-500mgTID
• Cefuroxime 250-500mgTID
• Parenteral-2ndgen-cefoxitin1-2gm i.vTID
• Oral -3rdgen-cefpodoxime200-400mgBD
• Parenteral-3rdgen-ceftrioxone & cefotoxime1-
2gms i.v OD & BD

23. Adverse effects
1. Hypersensitivity reactions- most common
Anaphylaxis, bronchspasm, urticaria
Maculopapular rash- more common
10% of people who are sensitive to penicillins
sensitive to cephalosporins also.
2. Nephrotoxicity ; esp. cephradine
3. Thrombophlebitis ( i.v admin. )
4. Superinfections
5. Diarrhea-oral cephalosporins, cefoperazone,
ceftriaxone & moxalactam.

24. Adverse effects contd---
6. cefamandole, moxalactam & cefoperazone may cause:
a) bleeding disorders
b) Flushing, tachycardia, vomiting with alcohol
intake
7) Disulfiram like reactions when combined with
alcohol(newer)
8) Drug fever.
9)Blood Toxicity
includesHypoprothobenemia,abnormalities in
platelet aggregation,false positive coomb’s test with
certain cephalosporins likeCephalothin.
10) CNS irritation following intra thecal administration.

25. Bacterial Resistance
• Destruction of B-lactum ring by B-lactamases
• Altered affinity of cephalosporins
• Decreased penetration of antibiotic to
penicillin binding protein
• (Applicable to G-negative bacteria)

27. Clinical applications
• Cephalosporins are used in the treatment of
infections caused by bacteria
• Cephalosporins are used to treat infections in
many different parts of the body. They are
sometimes given with other
antibiotics(Cefixime+Ofloxcillin )Some
cephalosporins given by injection are also used to
prevent infections before, during, and after
surgery. However, cephalosporins will not work
for colds, flu, or other virus infections

28. • cephalosporins are used in certain patients
with the following medical conditions
• Amoxicillin-resistant sinusitis (treatment)—
Cefaclor
• Bacterial endocarditis (prophylaxis)—
Cefadroxil, cefazolin, and cephalexin
• Melioidosis (treatment)—Ceftazidime
• Melioidosis is an infectious disease caused by
a Gram-negative bacterium, Burkholderia
pseudomalle.