Cephalosporins : Dr Rahul Kunkulol's Power point Presentations
Derivatives of 7-amino-cephalosporanic acid
Cephamycins are fermented products of
Closely related in structure to penicillin (beta-
They are highly resistant to penicillinase.
Some bacteria can produce a beta
lactamase called cephalosporinase
Many of them are resistant to the enzyme.
All of the drugs in this group contain
a β-lactam ring in their structure
• features of chemistry,
• mechanism of action,
• pharmacologic and
Cephalosporins inhibit the
peptido-glycan synthesis of
bacterial cell wall in a manner
similar to that of penicillin and are
Divided into 4 major groups called
Are divided into Generations based on
Parallel their chronological development
Their antimicrobial spectrum
› First generation
› Second generation
› Third generation
› Fourth generation
EXAMPLES: Cephalothin, Cefazolin,
Cephalexin , Cephadroxil
They have a stronger antimicrobial action on G+
bacteria than that of the other generations, but
they action on G- bacteria is relatively poor.
① These cephalosporins have nephrotoxicity to a
② They are NOT effective against pseudomonas.
First Generation Cephalosporins
④ Comparatively, they are less stable for
beta- lactamase (penicillinase ).
⑤ They are chiefly used in treating infection
of the penicillinase-producing S.aureus
and for surgical prophylaxis.
⑥ Cefazolin do not penetrate the central
nervous system and can not be used to
First Generation Cephalosporins
Treatment infection of the penicillinase-
Minor staphylococcal lesions
For surgical prophylaxis
Cephazolin drug of choice for k. pneumonie
Treatment of staphylococcal or streptococcal
infection who have a h/o penicillin
Cefamandole, Cefaclor, Cefuroxime,
Cefotetan, Cefoxitin (Cephamycins)
① Action of this generation on G+ bacteria is
the same or a little less than that of the first
② Their antimicrobial action on G- bacteria is
obviously increased. (H. influenza, Klebsiella)
③ Cephamycins are effective against
anaerobes such as B.fragilis, serratia
④ Ineffective against p.aeruginosa.
⑤ They are stable to many kind of beta-
lactamases and have less nephrotoxicity
than the first generation.
⑥ Cefuroxime is the only second-
generation drug that crosses the blood-
brain barrier : used for the treatment of
meningitis, especially H.influenzae
meningitis, and sepsis.
Sinusitis, Otitis, LRTI, Community acquired
› caused by beta lactamase producing H.
Mixed infections :
› pelvic infections
Cefotaxime, Ceftriaxone, Cefoperazone,
Cefixime, Ceftizidime, Cefodoxime.
① The broadest spectrums of all cephalo-
② The highest activities against G- bacteria.
③ The lowest activities against G+ bacteria.
④ The highest resistance to β-lactamase.
⑤ Can cross blood brain barrier
⑤ The best penetration into the CSF;
almost no nephrotoxicity.
⑥ Ceftizoxime have good activity
⑦ Some of them are effective against
P.aeruginosa and enteric bacilli.
(cefoperazone and ceftizidime)
There are also some unique properties of
individual 3th generation.
Ceftriaxone has the longest half-life(8h) of any
Cefixime is an oral preparation.
Ceftazidime is the best anti-pseudomonal
Cefoperazone is eliminated(70%) in the bile,
and is thus very useful in patients with renal
Used for serious infections caused by organisms
resistant to other drugs.
Gonorrhea : cefixime / ceftriaxone
Meningitis : Ceftriaxone, cefotaxime
community acquired pneumonia: Ceftriaxone
Soft tissue infections
Mixed aerobic , anaerobic infections
Urethral , biliary tract infections
First line drug for Gonorrhea caused by
Nisseria (ceftriaxone , Cefixime)
Meningitis caused by pneumococci,
meningococci, H. influenza.
Empirical theraphy for sepsis of unknown
Urethral or biliary tract infections
1. More resistant to hydrolysis by β-
2. Active against P-aeruginosa &
3. Clinical use as third generations.
Generations First second Third
Drugs Cephalexin (O)
Cefazolin (im, iv)
Cefoxatin (im, iv)
G+Ve +++ ++ +
G -ve + ++ +++
Anaerobes Efective against
Pseudomonas - - -- effective
Salmonella -- - effective
Betalactamase Resistant to
H, resistant to G-
BBB --- Only cefuroxime Most drugs
Relatively few and low
The most common ones are Allergy-
hypersensitivity reactions (5%-10%)
anaphylaxis, fever, skin rashes, nephritis,
granulocytopenia, and hemolytic anemia.
During treatment with third-generation
drugs, these resistant bacteria, as well as
fungi, often proliferate and may induce
The first-generation cephalosporins have
certain nephrotoxicity. (Renal damage,
including interstitial nephritis and even
tubular necrosis )
The second-generation have slight
The third-generation have no
Monobactams - Aztreonam
① Aztreonam is highly resistant to beta-
② It is highly active against aerobic G- bacteria,
including P.aeruginosa and penicillinase-
producing strains of H. influenzae and
gonococci. But it shows poor activity against
G+ cocci and anaerobic bacteria.
③ The antimicrobial spectrum of aztreonam is
similar to that of aminoglycosides
Mechanism of action
Vancomycin is an
① Vancomycin is very effective against
most staphylococci including those
producing beta-lactamases，and other
G+ cocci such as streptococcus viridans,
enterococci, and pneumococcus.
② It is also active against clostridium
species, Corynebacterium diphtheriae,
and Bacillus anthracis.
① Orally only for the treatment of antibiotic-
associated Pseudomembranous colitis
caused by C.difficile.
② Intravenous administration is mainly used
for serious G+ coccal infections, such as
› Especially for those caused by penicilin-
resistant pneumococcus and staphylococci
› at the site of injection.
② Nephrotoxicity and Ototoxicity
› rare with monotherapy, more common
when administered with other nephro- or
› risk factors include renal impairment,
prolonged therapy, high doses, high serum
concentrations, other toxic meds
③ “Red-Man”or “red neck” Syndrome
› flushing, pruritus, erythematous rash on face
and upper torso
› related to RATE of intravenous infusion;
should be infused over at least 60 minutes
› resolves spontaneously after discontinuation
› Prevent: may lengthen infusion (over 2 to 3
hours) or pretreat with antihistamines in
They are available only in fixed
combinations with specific penicillins:
Ampicillin + sulbactam
Amoxicillin + clavulanic acid
Ticarcillin + clavulanate potassium
Piperacillin + tazobactam sodium
Spectrum: Amp + most anaerobes + many
enteric G (-) rods, OSSA
Sulbactam alone is very active against
THE most broad-spectrum penicillin
Tazobactam may improve the activity of
piperacillin vs. gram-negative rods,
4.5g IV q8h = 3.375g IV q6h
4.5g IV q6h for Pseudomonas