Cephalosporins drugs

1. CEPHALOSPORINS, MONOBACTAMS
&CARBAPENEMS
Dr . Dinesh Babu ,MBBS,MD
Asst Prof
Dept of Pharmacology
Annapoorana medical college & Hospital , Salem

2. Chemistry of Cephalosporins
• Semi-Synthetic
antibiotics derived
from
“Cephalosporium-C”
Obtained from fungus
Cephalosporium

3. • It belongs to β-lactam antibiotics
• It is similar in structure to penicillin
• β-lactam is common for both penicillin as well
as Cephalsporins
• Depending on the various substitution of
chemical group
i. Pk
ii. Anti bacterial spectrum
iii. Stability

5. • Inhibit wide variety of gram(+) and gram(-)
bacteria.
• Acquired resistance is due to
a) Alteration in target protein (PBPs) reducing
affinity for the antibiotic
b) Impermeability to the antibiotic or its efflux
pump
c) Elaboration of β-lactamases which destroy
specific cephalosporins (Cephalosporinases) the
MOST COMMON MECHANISM

6. Cephalosporins
• Individual cephalosporins have differ in their
I. Anti-bacterial spectrum
II. Relative potency
III. Susceptabilty to β-lactamases
IV. Pk Properity

7. 1 •First Generation
2 •Second Generation
3 •Third Generation
4 •Fourth Generation
5 •Fifth Generation

8. First Generation
Cephalosporins
• 1st Generation were developed in 1960s
• Highly active against gram(+) but weak against
gram(-) bacteria.
• Parenteral – Cefazolin
• Oral – Cephalexin
- Cefadroxil

9. Cefazolin
• It is the Prototype first generation that is active
against most PnG sensitive Organisms
• Streptococci
• Gonococci
• Meningiococci
• C.diptheriae
• H.Infuenzae
• Clostridia
• Actinomyces
It is the preferred parenteral
1st Generation
Cephalosporin, esp for
SURGICAL PROPHYLAXIS

10. Spectrum
First Generation
Gram +ve Cocci
• Streptococci
• Staphylococci
• Remarks : Not active against penicillin
resistant strains

11. Second Generation
Cephalosporins
• More active against gram(-) organisms with
wider coverage , inc some strains resistant to
first generation cephalosporins
• Parenteral – Cefuroxime
• Oral- Cefaclor , Cefuroxime axetil, Cefprozil

12. 2nd Gen .Parenteral – Cefuroxime
• This group of drugs is less active against gram
positive organisms than first generation
agents
• But has extended gram negative coverage.
• Cefuroxime attains higher CSF levels as
compared to other second generation
cephalosporins.

13. Spectrum
Second Gram –ve bacilli
• E. coli
• Klebsiella
• Proteus
• H. influenza
• M. catarrhalis
• Bacteroides

14. Third generation Cephalosporins
• It is active against gram(+) cocci , gram(-)
cocci, gram(-) bacilli , anaerobs
• Parentral – Cefotaxime , Ceftizoxime,
Ceftriaxone , Ceftazidime, Cefoperazone
• Oral – Cefixime , Cefpodoxime
proxetil,Cefdinir,Ceftibuten,Ceftamet pivoxil

15. 3rd generation spectrum
Gram +ve cocci
• Streptococci
• Staphylococci
Gram –ve cocci
• Gonococci
Gram –ve bacilli
• Enterobacteriaceae
• Serratia
• Pseudomonas
Anaerobes
• Bacteroides
Only ceftazidime and cefoperazone
are effective against Pseudomonas

16. • Active against gram (-) organisms resistant to
other beta lactam antibiotics.
• penetrate the blood brain barrier (except
cefoperazone and cefixime).
• Ceftazidime (maximum), ceftolozane and
cefoperazone are active against
pseudomonas.
• Ceftazidime is drug of choice for melioidiosis
(caused by Burkholderia pseudomallei).

17. • Ceftizoxime has maximum activity against
Bacteroides.
• Ceftriaxone is the first choice drug for
gonorrhoea, salmonellosis (including
typhoid), E. coli sepsis, Proteus, and empirical
therapy for bacterial meningitis.

18. Fourth Generation Cephalosporins
• These drugs possess activity against gram (-)
organisms (including pseudomonas) resistant
to 3rd generation cephalosporins.
• Their efficacy against gram positive cocci is
similar to 3rd generation compounds.
• However, these are not active against
anaerobes.

19. Fourth Generation Cephalosporins
• Parenteral – Cefepime & Cefpirome

20. Newer Drugs
• Fifth generation cephalosporins
• Only Parenteral – Ceftaroline fosamil &
Ceftobiprole medocaril
• It is active against MRSA & penicillin resistance
(PBP altered)
• Ceftaroline fosamil – Prodrug
• Rapidly converted by Phosphatases to the
active Ceftaroline

21. Ceftaroline fosamil
• Inhibit wide variety of gram(+) and gram(-)
bacteria.
• MRSA
• Penicillin resistant Strep. Pneumoniae &
Enterococcus fecalis
• Ceftaroline – ability to bind to altered PBPs
expressed in theses bacteria

22. • It has high affinity for
• PBP2a (in MRSA)
• PBP2b and PBP2x (in penicillin resistant
Strep.Pneumonia)
• M.O.A- interferes with transpeptidation step
of bacterial cell wall synthesis- lethal effect

23. • Ceftaroline fosamil approved by CDSCO india in
2016 ,
• For the treatment of complicated skin and soft
tissue infection as well as community acquired
pneumonia(CAP) particularly MRSA & penicillin
resistant Strep.Pneumonia

24. Pharmacokinetics
• Most cephalosporins are excreted via kidney
through tubular secretion.
• Ceftriaxone and cefoperazone are secreted in
the bile.
• Nephrotoxicity of these drugs is increased with
loop diuretics.

25. Adverse effects
• PAIN – at the site of injection (IM) ,
Thrombophlebitis (IV)
• DIARRHOEA- due to altered Gut flora
• HYPERSENSITIVEITY REACTION – most
important adverse effect similar to penicillin
• Rashes(MC),anaphylaxis,angioedema,asthma
and urticaria

26. • NEPHROTOXICITY
• BLEEDING – Hypoprothrombinaemia
• NEUTROPENIA & THROMBOCYTOPENIA – rare
event
• DISULFIRAM LIKE REACTION

27. USES
• As alternative to penicillin for ENT,upper
respiratory and cutaneous infections
• Urinary tract infection & Soft tissue infection
• CAP,HAP
• Complicated skin and soft tissue infection due
to MRSA ( Ceftaroline fosamil)
• Septicaemias

28. • Surgical Prophylaxis
• Meningitis
• Gonorrhoea caused by penicillinase producing
organisms
• Typhoid
• Mixed aerobic-anaerobic infection

29. Monobactams
• Monocyclic β-lactam ring
• Unique – β-lactam ring is not fused to another
ring
• Drug included in this class- Aztreonam
• Structure similarity to 3rd generation
• Spectrum of activity is similar to 3rd generation
Cephalosporins

30. Spectrum of activity
• Limited to aerobic gram negative rods
• Excellent activity against Enterobacteriaceae.
• Pseudomonas aeruginosa
• No activity against gram positive bacteria or
anaerobes

31. Pharmacokinetics
• Route – IM or IV
• Absorption – poor oral absorbtion
• Rapid and complete absorption after IM inj
• Distribution – Penetrate well into CSF
• Metabolism – Hydrolytic opening of β-lactam
ring
• Elimination – mostly unaltered

32. Pharmacodynamics
• Bactericidal activity
• M.O.A – it binds to Penicillin binding protein-3
(PPB3)
• Uses:
• Safe in patient who have allergy to penicillin
or cephalosporin
• Pneumonia

33. • Hospital acquired Pneumonia
• Meningitis
• Gram(-) Sepsis
• Urinary tract infection
• Osteomylitis
ADVERSE EFFECTS:
• Skin rashes
• Elevated serum Aminotrnsferases

34. CARBAPENEMS
• Carbapenems are β-Lactams that contains
fused β-Lactam ring system- different from
penicillins
• Group consist of – Imipenem ,
Meropenem,Etrapenem,Faropenem,
Doripenem

35. Imipenem
• Mechanism of Action
• β – lactam antibiotics inhibit the key enzyme
in bacterial wall synthesis ( transpeptidase)
• They also appear to activate one or more cell-
wall autolytic enzymes, causing lysis of the
bacterium

36. Spectrum
Aerobic & anaerobic micro-organisms
• Streptococci
• Staphylococci
• Enterococci
• Listeria
• Pseudomonas
• Acinetobacter
• Bacteroids

37. Pharmacokinetics
• Not absorbed orally
• So, IV route is used for admistration
• The drug is hydrolyzed rapidly by
Dhydrodipeptidase I found in the brush border
of Proximal renal tuble
• Cilastatin ( reversible inhibitor of
dehydropeptidase I )
• Dose adjustment is needed in renal
insufficiency

38. Adverse effects
• Nause and Vomiting are most common
• Hypersensitivity
• Seizure – 1.5% ( if high dose is given for
patient with CNS lesion)

39. Therapeutic uses
• Urinary tract infection
• Lower respiratory infection
• Intar-abdominal infection
• Gynecological infection
• Skin and soft tissue , bone and joint infections

40. Meropenem
• Newer Carbapenem is not hydrolyzed by Renal
Peptidase
• Like Imipenem it is active against both gram(+)
& garm(-) , aerobes as well as anaerobes
• MEROPENEM is “reserve drug” for the
treatment of serious nosocomial infections like

41. • Septicaemia
• Febrile neutropenia
• Intra-abdominal infection
• Pelvic infection
• Diabetic foot
• ADVERSE EFFECTS are similar to imepenem ,
but it is less likely to cause seizure, therefore
preferred over imipenem-cilastatin.

42. Tutorial Questions
1. Cephaloxin Vs Cefadroxil.
2. Name the Cephalosporins used in PPNG (Penicilinase
producing Neisseria Gonorrhoea).
3. Ceftriaxone Vs Cefotaxime.
4. Name the Cephalosporins used in Pseudo monas infection.
5. Name the Cephalosporins used in MDR (Multi Drug Resistant)
typhoid fever ?
6. Which is highly nephrotoxic Cephalosporins.
7. Name the Cephalosporins used in menigitis caused by gram –
ve bacilli.
8. Orally active Cephalosporins.
9. 4th Generation Cephalosporins – Advantages.
10. What are the common adverse effects ?
11. What are the common uses of cephato sporins ? what are the
specific reasons for their prescription.