Cephalosporins

CEPHALOSPORINS
Dr. Lokendra Sharma
Sr Professor Pharmacology
S.M.S.Medical College,
Jaipur

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

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

What is the mechanism of action of
Cephalosporin ?

Write Generation Classification of Cephalosporin.

Write spectrum of different generations cephalosporin.

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

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.

Pharmacokinetic properties of cephalosporin

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

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.

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

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

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

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

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

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).

ADRs of Cephalosporin
Hypersensitivity

Adverse effects of cephalosporin

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

Write indications of cephalosporin's.

Cephalosporin's
First Generation Second Generation Third Generation Fourth Generation
* Oral Agent
CEFADROXIL *
(tissue)
CEFACLOR * CEFDINIR
CEFEPIME
(100% renal)
CEFAZOLIN
(surgical prophylaxis)
CEFAMANDOLE CEFOPERAXONE
CEFPIROME
CEFELIXIN *
(bile)
CEFONICID
CEFOTAXIME
(prototype)
CEFIPIME
CEPHALOTHIN
(prototype)
(IM pain)
CEFORANIDE
CEFTAZIDIME
(Thrombocytopeni)
CEPHAPRIN
CEFOTETAN
(anaerobics)
CEFTIBUTEN
CEPHRADINE *
(diarrhoea)
CEFOXITIN
(prototype )
CEFTIZOXIME
CEFUROXIME
(BBB)
MOXALACTAM
CEFTRIAXONE
(MDR Typhoid)

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.

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.

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

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

Q. 1 Which cephalosporins are secreted in the bile?
Ceftriaxone and Cefoperazone

Q. 2 Which Cephalosporin is used as a DOC in surgical prophylaxis?
Cefazoline

Q. 3 ADRs of ceftriaxone, when used chronically.
Biliary sludging syndrome, cholelithiasis

Q. 4 Which Cephalosporins are active against pseudomonas?
Ceftazidime (Max.), ceftolozane and cefoperazone

Q. 5 Treatment of choice for pseudomonas infection.
Ceftazidime and aminoglycosides

Q. 6 DOC for melioidiosis.
Ceftazidime

Q.7 ADRs of cephalosporins.
Hypersensitivity reactions, Neutropenia with ceftazidime

Q. 8 Ceftriaxone is first choice drug for-
Gonorrhoea, Salmonellosis, E. coli sepsis, Proteus, Haemophilus, Bacterial Meningitis

Cephalosporins

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Editor's Notes