2. Introduction
Antibacterial agents which inhibit bacterial cell
wall synthesis
Discovered from a fungal colony in Sardinian
sewer water (1948)
Cephalosporin C identified in 1961
Generally more resistant to B-lactamases
3. What are the advantages and disadvantages
of cephalosporin?
Disadvantages
• Polar due to the side chain - difficult to isolate and purify
• Low potency - limited to the treatment of urinary tract infections where it
is concentrated in the urine
• Not absorbed orally
Advantages
• Non toxic
• Lower risk of allergic reactions compared to penicillins
• More stable to acid conditions
• More stable to b-lactamases
• Ratio of activity vs Gram -ve and Gram +ve bacteria is better
4. What is the mechanism of action of
Cephalosporin ?
7. Cephalosporin Spectrum
ABS
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 3
LESS LESS LESS LESS
+ Bacclli +Cocci +Cocci
Ө Cocci
+ Bacclli + Bacclli
+Cocci
8. Write Pharmacokinetic properties of cephalosporin.
Some cephalosporins may be given orally but most are given parenterally
(IM or IV).
They are widely distributed in the body like penicillins.
Some such as 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.
Almost all are eliminated via the kidneys and are actively secreted by
the renal tubules.
CEFAPERAZONE AND CEFTRIAXONE are eliminated through the biliary
tract----Q.
10. Mention properties of first generation
cephalosporin's.
CEPHALOTHIN, CEFAZOLIN, CEFALEXIN. (Streptococcus,
pneumococcus but not or methicillin-resistant
Staphylococcus).
+ Cocci > - Bacilli > + Bacilli > - Cocci > Anaerobics
Do not cross the blood-brain barrier.
Primarily excreted by kidney
Ineffective Pseudomonas aeruginosa, Enterobacter,
and indole-positive Proteus species
11. Write some important properties of Second generation
cephalosporin's.
CEFUROXIME, CEFAMANDOLE, CEFOXITIN, CEFACLOR.
- Cocci
>+ Cocci > +Bacilli
- Bacilli
Cefuroxime cross BBB ,Resistant to beta-lactamase
Do not achieve adequate levels in the CSF.
12. Mention properties of Third generation cephalosporin's.
MOXALACTAM, CEFAPERAZONE, CEFTAZIDIRNE, CEFTRIAXONE.
Extended Gram negative coverage,
resistant to non-Staphylococcus b-lactamase,
Cross the blood-brain barrier.
The spectrum is extended to include: 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
13. What are the important properties of Fourth
generation cephalosporin?
CEFEPIME ,CEFPIROME .
Comparable to third-generation but more resistant to some beta-
lactamases.
- cocci & Bacilli (Resistant to 3rd Gn) & > + Cocci &
+ Bacilli & Anaerobes ----NO
14. Mention some properties of Fifth Generation
cephalosporin .
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
15. What are the adverse effects of cephalosporin ?
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
16. What are the adverse effects of cephalosporin ?
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
17. ADRs of Cephalosporin
• 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).
21. What are the clinical uses of cephaloporin
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
25. Key points for clinical uses of Cephalosporins
First Generation:
Cefazolin: Drug of choice for surgical prophylaxis
Second Generation:
Cefotetan, Cefmetazole & Cefoxitin: Active against anaerobes like Bacteroides
fragilis
Third Generation:
Cefazidime( maximum), Ceftolozane & Cefoperazone: Active against Pseudomonas
Fifth Generation:
Ceftaroline & Ceftobiprole: Approved for community acquired pneumonia & MRSA
infection
Reference: Garg GR, Gupta S. Review of Pharmacology, 13th edition.
26. Key points for clinical uses of Cephalosporins
• No Cephalosporin is active against E. fecalis, MRSA and L.
monocytogenes
• Cefazidime+ Aminoglycoside : Treatment of choice for pseudomonas
infections
• Cefazolin: Drug of choice for surgical prophylaxis
• Ceftriaxone & Cefoperazone: Secreted in the bile.
27. GUIDANCE OF ANTIMICROBIAL THERAPY
• Minimum inhibitory concentration: lowest concentration of
antibiotic that inhibits visible growth
• Minimum bactericidal concentration: lowest concentration of
antibiotic that kills 99.9% of the inoculum
• Serum bactericidal title: dilution of serum that kills 99.9% of the
inoculum
• Synergy test: synergistic activity of multiple antibiotics
For lecture only
28.
29. An ideal antibiotics
• Broad-spectrum
• Did not induce resistance
• Selective toxicity, low side effects
• Preserve normal microbial flora
For lecture only
30. Q. 1 Which cephalosporins are secreted in the bile?
Ceftriaxone and Cefoperazone
31. Q. 2 Which Cephalosporin is used as a DOC in surgical prophylaxis?
Cefazoline
32. Q. 3 ADRs of ceftriaxone, when used chronically.
Biliary sludging syndrome, cholelithiasis
33. Q. 4 Which Cephalosporins are active against pseudomonas?
Ceftazidime (Max.), ceftolozane and cefoperazone
34. Q. 5 Treatment of choice for pseudomonas infection.
Ceftazidime and aminoglycosides
Active against Gram negative organisms (Escherichia co1i Kiebsiella pneumoniae, and the indole negative Proteus mirabilis).
Effective against some anaerobic cocci (Peptococcus and Peptosteptococcus, but NOT Bacteroides fragilis).
The spectrum is extended to more Gram negative bacteria Enterobacter species, Klebsiella species, and indole-positive Proteus species.
Also, Haemophilus influenza is covered by cefuroxime, cefamandole, cefaclor; Bacteroides fragilis by cefoxitin