Cephalosporins

Introduction
 Similar to penecillins

 Derived from Fungus “Acremonium”. Previously known

as “Cephalosporium”.

 More stable against β-Lactamases

 Have more activity Gram-positive bacteria, but latter

generations are active against Gram-Negative, often at
the expense of Gram-Positive activity.
Classification: Cephalosporins
 First Generations: Properties
 Gram-positive cocci, such as pneumococci, streptococci, and
staphylococci, E coli, K pneumoniae, and Proteus mirabilis.

 Cephalexin, cephradine, and cefadroxil are absorbed from

the gut to a variable extent.

 Urine concentration is usually very high

 Excretion is mainly by glomerular filtration and tubular

secretion into the urine
 First Generations: Properties
 Probenecid (tubular secretion blocler) may increase serum levels
substantially.

 In patients with impaired renal function, dosage must be

reduced.

 Cefazolin is the only first-generation parenteral cephalosporin

still in general use.

 Cefazolin can also be administered IM. Excretion is via the kidney,

and dose adjustments must be made for impaired renal function.
 First Generations: Properties
 Not to be used for serious systemic infections.

 Oral drugs may be used for the treatment of urinary

tract infections, for staphylococcal, or for
streptococcal infections including cellulitis or soft
tissue abscess.

 staphylococcal or streptococcal infections (In

patients with Penecillin allergy).
 Second Generations Properties
 First generations properties+ Extended Gram-positive
spectrum.

 As with first-generation agents, none is active against

enterococci or P aeruginosa.

 Intramuscular administration is painful and should be

avoided.

 There are marked differences in half-life, protein binding, and

interval between doses.
 Second Generations Properties
 All are renally cleared and require dosage adjustment in
renal failure.

 The oral second-generation cephalosporins are active

against β-lactamase-producing H influenzae or Moraxella
catarrhalis and have been primarily used to treat sinusitis,
otitis, or lower respiratory tract infections

 cefoxitin, cefotetan, or cefmetazole can be used to treat

mixed anaerobic infections such as peritonitis or
diverticulitis.
 Second Generations: Properties
 Cefuroxime is used to treat community-acquired
pneumonia
 Third Generations:Properties
 Compared with second-generation agents, these
drugs have expanded gram-negative coverage

 Poor activity against S aureus, and enterobacter

species.

 Penetrate body fluids and tissues well and, with the

exception of cefoperazone and all oral cephalosorins,
achieve levels in the CSF sufficient to inhibit most
pathogens, including gram-negative rods.
 Third Generations: Properties

 The half-lives and dose interval vary greatly:

Ceftriaxone (half-life 7–8 hours) can be injected once
every 24 hours at a dosage of 15–50 mg/kg/d.

 Cefoperazone (half-life 2 hours) can be injected

every 8–12 hours in a dosage of 25–100 mg/kg/d.
 Third Generations: Properties

 Cefixime can be given orally (200 mg twice daily or

400 mg once daily) for respiratory or urinary tract
infections.

 The excretion of cefoperazone and ceftriaxone is

mainly through the biliary tract, and no dosage
adjustment is required in renal insufficiency.
 Third Generations: Properties
 Strains expressing extended-spectrum β-lactamases,
however, are not susceptible

 Ceftriaxone and cefotaxime are approved for

treatment of meningitis.

 Other potential indications include empirical therapy

of sepsis of unknown cause in both the
immunocompetent and the immunocompromised
patient and treatment of infection.
 Third Generations: Properties
 Neutropenic, febrile immunocompromised patients,
third-generation cephalosporins are often used in
combination with an aminoglycoside
 Fourth Generation: Properties
 More resistant to hydrolysis by chromosomal β-
lactamases (eg, those produced by enterobacter).

 It has good activity against P aeruginosa,

Enterobacteriaceae, S aureus, and S pneumoniae.

 Cefepime is highly active against haemophilus and

neisseria.

 It penetrates well into cerebrospinal fluid

 Fourth Generation: Properties
 It is cleared by the kidneys and has a half-life of 2
hours, and its pharmacokinetic properties are very
similar to those of ceftazidime.
 Local irritation can produce severe pain after
intramuscular injection and thrombophlebitis after
intravenous injection
 Renal toxicity, including interstitial nephritis and
even tubular necrosis
 Fourth Generation: Properties
 Bleeding disorders
 Hypersensitivity reactions
 Anaphylaxis, fever, skin rashes, nephritis,
granulocytopenia, and hemolytic anemia.