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CEPHALOSPORINS
CEPHALOSPORINS
- Cephalosporins are b-lactam
antibiotics that differ from the
penicillins in that the B ring is a 6-
membered dihydrothiazine ring.
Variations among the
cephalosporins are made on either
the acyl side chain at the 7-
position to change antibacterial
activity or at the 3-position to alter
the pharmacokinetic profile.
Cephalosporin C was first isolated
in 1948 by Dr. Abraham from a
fungus, Cephalosporium
acremonium, collected in
seawater near a sewage outlet in
Sardinia by Professor Guiseppe
Brotzu in 1945.
-
- They have a beta-lactam ring which
interferes with bacterial cell wall synthesis
by binding to penicillin binding proteins,
eventually leading to cell lysis and death.
Like amoxicillin clavulanate, cephalosporins
should be avoided when a narrower
spectrum antibiotic would be effective
because they increase the risk of
Clostridium difficile, MRSA and other
resistant infections.
General structure of
the Cephalosporins
FIRST-GENARATION CEPHALOSPORINS
This include:
Adverse reaction
Nausea, vomiting, diarrhoea, allergic rashes may occur
Parenteral
P-Cefazolin
-Is the only first generation parenteral cephalosporin still in general
use.
-usually preferred among the first generation ceph,
-administered less frequently owing to its longer t1/2.
-maybe also a choice in infections for w/c it is the least toxic drug and
in individuals with Stap. or strep. infections who have a history of
penicillin allergy other than immediate hypertensive.
-usual IV dosage: 0.5-2g every 8 hrs.
-excretion: glomerular filtration; plasma proteins (85%).
MOA: inhibits the 3rd and final stage of bacterial cell wall synthesis by
preferentially binding to specific PBPs.
-ability to interfere with PBP-mediated cell wall synthesis
cell lysis.
bacterial cell wall autolytic enzymes (i.e., autolysins).
ADVERSE REACTIONS:
interstitial nephritis, serum sickness ,hemolytic anemia
seizures, anaphylactic shock ,anaphylactoid reactions,
azotemia , renal failure (unspecified), toxic epidermal
necrolysis , angioedema , erythema multiforme
CONTRAINDICATIONS :
-HPLC techniques
-theophylline
A. Oral
adults: 10-15mg/kg/d (2 - 4 divided doses)
children: 20-40mg/kg/d up to a maximum of 1g/d.
-Cefaclor is more susceptible to B-lactamase hydrolysis
compared with other agents
B.Parenteral
-after a 1g iv infusion, serum levels (75-125 mcg/ml)
-IM (painful)
SECOND-GENERATION CEPHALOSPORINS
Clinical Uses:
-Cefoxitin, cefotetan
peritinosis, diverticulitis, and pelvic inflammatory disease.
-Cefuroxime
treat community-acquired pneumonia because of its
active against B-lactamase producing H-influenza and some
penicillin-non-susceptible pneumococci.
-Cefuroxime widely used for empiric therapy
-Has activity vs. many ampicillin-resistant H. influenzae
strains.
-Community-acquired pneumonia
CLINICAL USE
-Skin and soft tissue infection
-Urinary tract infections
- Upper respiratory tract infections (otitis media,
sinusitis). Some resistance to H. influenzae to cefaclor
(20-30%).
- Surgical prophylaxis - Cefoxitin or cefotetan are widely
used in cases where mixed aerobic & anaerobic
infections may occur, esp. intra-abdominal, colorectal,
and gynecologic operations.
- Cefuroxime; cefazolin
For cardiovascular and orthopedic procedures
cheaper and appears to work well.
Mode of action:
-As with other cephalosporins, the bactericidal action
of this drugs result from inhibition of cell-wall synthesis.
Adverse Reactions:
-serum-sickness-like- reactions; hypersensitivity
-2nd (subsequent) course of therapy with Cefaclor.
Contraindications
2nd generation cephalosporins is contraindicated in patients with known allergy to the
cephalosporin group of antibiotics.
Drug Interactions:
Patients receiving Cefaclor may show a false-positive reaction for glucose in the urine with tests
that use Benedict's and Fehling's solutions and also with Clinitest tablets.
Adverse Reactions:
CNS
Rarely, reversible hyperactivity, agitation, nervousness, insomnia, confusion, hypertonia, dizziness,
hallucinations, and somnolence have been reported.
Contraindications
2nd generation cephalosporins is contraindicated in patients with known allergy to the
cephalosporin group of antibiotics.
Drug Interactions:
Patients receiving Cefaclor may show a false-positive reaction for glucose in the urine with tests
that use Benedict's and Fehling's solutions and also with Clinitest tablets.
THIRD-GENERATION-CEPHALOSPORINS
-Cefepime
-stable to hydrolysis by many of the previously
identified plasmid-encoded B-lactamases
-(TEM-1, TEM2 and SHV-1)
-It is a poor inducer/resistant type I
chromosomally encoded, extended-spectrum B-
lactamases.
-Thus, it is active against many Enterobacteriaceae
that are resistant to other cephalosporins via
induction of type I B-lactamases but remains
susceptible to many bacteria expressing extended-
spectrum plasmid-mediated B-lactames (such as
KPC , TEM3, and TEM10).
ADVERSE REACTION:
-The reaction (same with penicillins)