Beta Lactam Antibiotic Cephalosporin Ref Book :Dr SK Srivastava,Dr H L Sharma and Dr KK sharma,Dr K D Tripathi, Dr Sparsh Gupta

1. Beta Lactam Antibiotic
Cephalosporin
Dr Lokendra Sharma
Professor

2. Beta Lactam Antibiotic ?
Major
Penicillins
Cephalosporins
Minor
Monobactum
Carbapenum

3. An ideal antibiotics ?
• Broad-spectrum ? Narrow ?
• Did not induce resistance
• Selective toxicity, low side effects
• Preserve normal microbial flora
For lecture only

4. CEPHALOSPORINS ?
• Cephalosporium fungus
• Dihydrothiazine ring + B lactum
• Semisynthetic B-lactams derived from
chemical side chains added to 7-
aminocephalosporanic acid.
• 4 generations CS add 5th
• Generally more resistant to B-lactamases.

5. .

6. SPECTRUM
1ST GENERATION gram(+). cefazolin (used
as prophylactic following surgery)
2ND GENERATION: gram (+) & gram (-)
3RD GENERATION: good against gram (-)
aerobes
some cross into CNS readily e.g. cefotaxime !
used to
treat meningitis
4TH GENERATION: like 3rd gen but more
resistant to betalactamases
5th
GENERATION

7. Fifth Generation
Ceftobiprole and ceftaroline both parental
Inhibit Bind to Penicillin binding protein -2a
produce by MRSA resistance S
Pneumonia
Ceftaroline 2010 for MRSA
Ceftobiprole – post antibiotic effect on
MRSA

8. Ceftolozane 5 GN

9. ??
• All CEF = 1 GN (Except cefaclor 2GN)
• Pi = 4 GN (CefPime, CefPirome)
• ME end =3 rd generation (Exept
CefuroxiME)
• ROL (CeftibipRole,CeftaRoline) 5 GN
• ME,ONE,TEN (3 GN)
• OR oral (CefacLOr,)
• T Injectable (CefoTetan)

10. .
 Bactericidal
 Less susceptible to β-lactamases.
 Disrupt the synthesis of the peptidoglycan .
 The peptidoglycan layer =important structural integrity.
 The final transpeptidation step in the synthesis of the
peptidoglycan
 Facilitated by transpeptidases known as
penicillin-binding proteins (PBPs).
 PBPs bind to the D-Ala-D-Ala at the end of muropeptides
(peptidoglycan precursors) to crosslink the peptidoglycan.
 Beta-lactam antibiotics mimic the D-Ala-D-Ala site
 Irreversibly inhibiting PBP crosslinking of peptidoglycan.

12. 1. drugs that affect the bacterial cell wall
Inhibit Transpeptidase &Carboxipeptidase

13. .Pharmacokinetics
• 7 aminocephalosporinic acid = active
nucleous
• New modification at position 3 & 7
• Modification position 3 PK & toxicity
• Modification position 7 Antibacterial
Spectrum

14. .
• Conc dependent killing(CDK)= FQ,Aminog
• Time dependent killing(TDK)= beta lactum
• postantibiotic effects(PAE)
• MIC

15. Cephalosporins
Antibacterial Spectrum
First Generation Second Generation Third Generation Fourth Generation
+Cocci Ө Cocci Ө Cocci Ө Cocci
Ө Bacclli Ө Bacclli Ө Bacclli Ө Bacclli
Anaerobes Anaerobes
Resistance
3GN
LESS LESS LESS LESS
+ Bacclli +Cocci +Cocci
Ө Cocci
+ Bacclli + Bacclli
+Cocci

17. Cephalosporins
First Generation Second Generation Third Generation Fourth Generation
* Oral Agent
CEFADROXIL *
(tissue)
CEFACLOR * CEFDINIR
CEFEPIME
(100% renal)
CEFAZOLIN
(surgical
prophylaxis)
CEFAMANDOLE CEFOPERAXONE
CEFPIROME
Cefalidin
CEFELIXIN *
(bile)
CEFONICID
CEFOTAXIME
(prototype)
CEPHALOTHIN
(prototype)
(IM pain)
CEFORANIDE
CEFTAZIDIME
(Thrombocytopeni)
CEPHAPRIN
CEFOTETAN
(anaerobics)
CEFTIBUTEN
CEPHRADINE *
(diarrhoea)
CEFOXITIN
(prototype )
CEFTIZOXIME
CEFUROXIME
CEFTRIAXONE

18. First generation cephalosporins:
 CEPHALOTHIN, CEFAZOLIN,
CEFALEXIN. (Streptococcus,
pneumococcus but not or methicillin-
resistant Staphylococcus).
 + Cocci > - Bacilli > + Bacilli > - Cocci >
Anaerobics
 Do not cross blood-brain barrier.
 Primarily excreted = kidney
 Ineffective Pseudomonas aeruginosa,
Enterobacter, and indole-positive Proteus
species

20. Second generation
cephalosporins:
 CEFUROXIME, CEFAMANDOLE, CEFOXITIN, CEFACLOR.
 - Cocci
>+ Cocci > +Bacilli
- Bacilli
 Cefuroxime cross BBB ,Resistant to beta-
lactamase
 Do not achieve adequate levels in the CSF.

22. Cephalosporins
 Third generation
cefotaxime
cefixime
cefpodoxime
ceftazidime
cefdinir
Fourth generation (cefilidin,cefoselin,cefluprenam)
cefe Pime
cef Pirome
Fifth GN
- CeftobipRole
- ceftaRoline

23. Third generation
cephalosporins:
 MOXALACTAM, CEFAPERAZONE, CEFTAZIDIRNE,
CEFTRIAXONE.
 Extended Gram negative coverage,
 resistant to non-Staphylococcus b-lactamase,
 Cross the blood-brain barrier.
 Enterobacter, Pseudomonas (ceftazidime and
cefaperazone only), Serratia, b-lactamase producing
Haemophillus influenza and Neisseria species.
 Ceftizoxime and moxalactam retain good activity against
Bacteroides fragilis.
 - cocci & Bacilli & Anaerobes > + Cocci & Bacilli

24. Fourth generation
 CEFEPIME ,CEFPIROME .
 Comparable to third-generation but more
resistant to some beta-lactamases.
 - Cocci & Bacilli (Resistant to 3rd
Gn) & > +
Cocci &
 + Bacilli & Anaerobes ----NO

25. Fifth Generation
CeftobipRole and ceftaRoline both
parental
Inhibit Bind to Penicillin binding protein -2a
produce by MRSA resistance S
Pneumonia
CeftaRoline 2010 for MRSA
CeftobipRole – post antibiotic effect on
MRSA

26. Pharmacokinetics
 Some orally most parenterally (IM or IV).
 widely distributed .
 CEFOPERAZONE, CEFOTAXIME,
CEFUROXIME, CEFTRIAXONE, AND
CEFTAZIDIME (third generation) also cross the blood-
brain barrier
 Drugs of choice for meningitis due to Gram-
negative intestinal bacteria.

27. .
Almost all eliminated via the kidneys and
actively secreted by renal tubules.
CEFAPERAZONE AND CEFTRIAXONE
eliminated through biliary tract----Q.
Nephrotoxicity increase with loop diurtics
…..Q

28. ADVERSE EFFECTS
 Hypersensitivity reactions =similar
penicillins.
 Nephrotoxicity =CEPHALORIDINE----Q
 Intolerance to alcohol (disulfiram like
reaction)(Q----cefamandole, cefotetan,
moxalactam, cefoperazone=MTT group)
 Diarrhea= oral forms. cephaloridine ,third
cefoperazone,cefixime
 Superinfection. resistant organisms , fungi,
often proliferate

29. ADVERSE EFFECTS
BLEEDING
 Hyperprothrombinemia= (Q-----MTT group=
cefamandole, cefotetan, moxalactam,
cefoperazone)
 Thrombocytopenia, Platelet dysfunction.
Administration of vitamin K (10mg) twice a week can
prevent this.
 Neutropenia=Rare
 Serum sickness=cefaclor ----- Q

30. Coinfection and
Superinfection ?

31. CEPHALOSPORINS
• Adverse reactions.
– 5-10% cross-sensitivity
with pcn allergic pts.
– 1-2% hypersensitivity
reactions in non-pcn
allergic pts.
– Broader spectrum leads to
opportunistic infections
(candidiasis, C. difficile
colitis).

32. CEPHALOSPORINS
1. Identify this manifestation ?
2. What is Opportunistic
infection ?
3. What is the treatment and
Preventive Majors ?
4. Spectrum of Bacteria ?

33. Identify ?
Cause ?
Biliary
sludging
syndrome
?

39. USES:
 A cephalosporin with or without aminoglycoside
1st
Trt Klebsiella pneumococci.
 First GN surgical prophylaxis (Cefazolin) of wound
infection.
 Third GN meningitis due to, meningococci, and
Haemophillus influenza.
 CEFTRIAXONE = TOC beta-lactamase producing
Neisseria gonorrhea.
 E coli (G1),
 Salmonella Typhoid,Parathyphoid = CEFTRIAXONE
 H .Ducreyi = CEFTRIAXONE
 Pseudo Pseudomalli = CEFTRIAXONE

41. 1.Antimicrobial agent acting by inhibition of cell wall synthesis is
a.Erythromycin
b.Tetracycline
c.Lomefloxacin
d.Cefepime
(d)
2.Which one of the following drugs is an antipseu-domonal
penicillin?
a.Cephalexin
b.Cloxacillin
c.Piperacillin
d.Dicloxacillin
(c)

42. 3.All of the following drugs can cause renal failure EXCEPT
a.Cephaloridine
b.Amphotericin B
c.Cefoperazone
d.Gentamicin
(c)
4.Which of the following drug is NOT used for the treatment of
methicillin resistant staphylococcus aureus (MRSA)?
a.Cefaclor
b. Cotrimoxazole
c.Ciprofloxacin
d.Vancomycin
(a)

43. 5. Which of the following is a fourth generation cephalosporin?
a.Ceftriaxone
b.Cefaclor
c.Cefepime
d.Cefuroxime
(c)
6. All of the following cephalosporins have good activity against pseudomonas
aeruginosa EXCEPT
a.Cephadroxil
b.Cefepime
c.Cefoperazone
d.Ceftazidime
(a)
7. Treatment of penicillin producing Neisseria gonorrhoeae is /are
a.Amoxicillin
b.Ciprofloxacin
c.Cefotaxime
d.Doxycycline
e.Azithromycin
(b) (c)

44. 8.Which of these antibiotics are safe in renal
failure?
a.Cephalexin
b.Tetracycline
c.Nitrofurantion
d.Gentamicin
e.Doxycycline
(a)

45. 9. Which of the following statement are true regarding cefepime
a.It is a fourth generation cephalosporin
b.Once a day dose is sufficient
c.It possess antipseudomonal action
d.Its dose should not be reduced in renal pathology
e.It is a prodrug
(a)
10.The mechanism of antibacterial action of cephalosporins involves
a.Inhibition of the synthesis of precursors of peptidoglycan
b.Interference with the synthesis of ergosterol
c.Inhibition of transpeptidation reaction
d.Inhibition of beta lactamase
(c)

46. 11.Second generation cephalosporin that can be used orally is
a.Cefepime
b.Cefalothin
c.Cefaclor
d.Cefadroxil
(b)
12.Third generation cephalosporin that can be given orally is
a.Cefixime
b.Cefpirome
c.Cefaclor
D.Cefadroxil
(a)

47. 13. The antibiotic which can be given safely in
a pregnant women is
a.Ciprofloxacin
b.Cefuroxime
c.Metronidazole
d.Chloramphenicol
(b)
14. Linezolid is best used for
a.MRSA
b.VRSA
c,.K.pneumoniae
d.E.coli
(b)

48. 15.Which one of the following is a fourth generation cephalosporin?
a.Cefuroxime
b.Ceftazidime
c.Cefepime
d.Cefamandole
(c)
16.Neutropenia is associated with
a.Nafcillin
b.Methicillin
c.Carbencillin
d.Ampicillin
(a)

49. 17.Which of the following antimicrobials has
antipseudomonal action?
(a)Cefopodoxime
(b)Cephradine
(c)Cefotetan
(d)Cefoperazone
(d)

50. 18.Treatment of penicillinase producing
neisseria gonarrhoeae is/are
(a)Amoxycillin
(b)Ciprofloxacin
(c)Cefotaxime
(d)Doxycycline
(e)Azithromycin
(b)*(c)

51. 19.Which of the following antimicrobials has
antipseudomonal action?
(a)Cefopodoxime
(b)Cephradine
(c)Cefotetan
(d)Cefoperazone
(d)

52. 20.All are first generation cephalosporins
except
a.Cefadroxil
b.Cefazolin
c.Cephalexin
d.Cefaclor
D

53. 21.A patient develops an infection of
methicillin resistant Staphylococcus
aureus.All of the following can be used to
treat this infection except.
a.Cotrimoxazole
b.Cefaclor
c.Ciprofloxacin
d.Vancomycin
(b)

54. 22.All are true about cephalosporins,EXCEPT
a.Ceftazidime is a 3rd
generation cephalosporin.
b.Cefoperazone has got antipseudomonal
effect.
c.Cefoxitin has got no activity against
anaerobes.
d.Cephalosporins act by inhibiting cell wall
synthesis.
(c)

55. 23.Which of the following cephalosporins can be used in patients
with low GFR?
a.Cefuroxime
b.Cefixime
c.Ceftazidime
d.Cefoperazone
(d)

56. 24.Cephalosporin that does not require
dose reduction in patient with any degree
of renal impairment is
a.Cefuoxime
b.Cefoperazone
c.Ceftazidime
d.Cefotaxime
(b)

57. 25.Which of the following drugs is not
used for MRSA?
a.Cefaclor
b.Cotrimoxazole
c.Ciprofloxacin
d.Vancomycin
(a)

58. Cephalosporin vs Penicillin
• Cephalosporin advantages
– cover staphylococci
– better vs. Klebsiella, enteric gram-neg.
bacilli, gonococci
• Cephalsporin disadvantages
– cost
– poor distribution to CSF (1st & 2nd
gen)
– not cover enterococcus

60. Learning objective achieved ?
• Classification
• ABS
• Mechanism of Action
• AE
• Use

61. Thank You
Dr Lokendra Sharma