Derivatives of 7-amino-cephalosporanic acid

Cephamycins are fermented products of

streptomyces
Closely related in structure to penicillin (beta-
lactam ring).
They are highly resistant to penicillinase.
Somebacteria 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
S S

N N
O O
Penicillins Cephalosporins
share similar
• features of chemistry,
• mechanism of action,
• pharmacologic and
clinical effects.

N N
O O

Carbapenems Monobactams
4
 Cephalosporins inhibit the
peptido-glycan synthesis of
bacterial cell wall in a manner
similar to that of penicillin and are
considered bactericidal.
6
 Divided into 4 major groups called
“Generations”
 Are divided into Generations based on
 Parallel their chronological development
 Their antimicrobial spectrum
› First generation
› Second generation
› Third generation
› Fourth generation
 First Generation Cephalosporins
EXAMPLES: Cephalothin, Cefazolin,
Cephalexin , Cephadroxil

They havea 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
certain degree.
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
treat meningitis.
Treatment infection of the penicillinase-
productive S.aureus
Minor staphylococcal lesions
For surgical prophylaxis
Cephazolin drug of choice for k. pneumonie
infections
 Treatment of staphylococcal or streptococcal infection
whohave a h/o penicillin hypersensitivity.

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 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
generation.
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 crossesthe blood-
brain barrier : used for the treatment of
meningitis, especially H.influenzae
meningitis, and sepsis.
Sinusitis,
Otitis, LRTI, Community acquired
pneumonia
› caused by beta lactamase producing H.
influenza
Meningitis
Mixed infections :
› Peritonitis
› Diverticulitis
› pelvic infections

13
 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
against B.fragilis.
⑦ Some of them are effectiveagainst
P.aeruginosa and enteric bacilli.
(cefoperazone and ceftizidime)
 There are also some unique properties of
individual 3th generation.
 Ceftriaxone has the longesthalf-life(8h) of any
cephalosporin.
 Cefixime is an oral preparation.
 Ceftazidime is the best anti-pseudomonal
cephalosporin.
 Cefoperazone is eliminated(70%) in the bile,
and is thus very useful in patients with renal
failure.
 Used for serious infections caused by organisms
resistant to other drugs.
 Gonorrhea : cefixime / ceftriaxone
 Meningitis : Ceftriaxone, cefotaxime
 community acquired pneumonia: Ceftriaxone
 Septicemia Nosocomial
 infections UTI
 LRTI
 Soft tissue infections
 cellulitis
 Typhoid fever

 Mixed aerobic , anaerobic infections
 Urethral , biliary tract infections
Firstline drug for Gonorrhea caused by
Nisseria (ceftriaxone , Cefixime)
Meningitis caused by pneumococci,
meningococci, H. influenza.
Empirical theraphy for sepsis of unknown
cause
Urethral or biliary tract infections

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Cefepime
1. More resistant to hydrolysis by β-
lactamase
2. Active against P-aeruginosa &
Enterobacteriaceace.
3. Clinical use as third generations.
Generations First second Third

Cephalexin (O) Cefaclo r(o) Cefixim e (o)

Drugs Cefadroxi (O)
l Cefuroxime (o) Ceftriaxone (o)
Cefazoli n (im , iv) Cefoxati n (im , iv) Cefotaxim e (im ,
Cephalothin Cefoteta n (im ) iv)
(o,i m ) Cefoperazone

Antibacterial spectrum
G+Ve +++ ++ +

G -ve + ++ +++

Anaerobes Efectiv e against Very effective Effective

B.Fragalis ( cefoteta n & (Cefoperazon e)
cefoxiti n )
Pseudomonas -- -- effective

Salmonella -- - effective

Betalactamase Resistant to H, resistan tto G- Highly resistant

staphylococcal ve
BB --- Only cefuroxime Mos t 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
superinfections.
 Nephrotoxicity:
 The first-generation cephalosporins have
certain nephrotoxicity. (Renal damage,
including interstitial nephritis and even
tubular necrosis )
 The second-generation have slight
nephrotoxicity.
 The third-generation have no
nephrotoxicity.
 Monobactams - Aztreonam
① Aztreonam is highly resistant to beta-
lactamases
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
 Vancomycin
Mechanism of action Vancomycin is an
Pharmacologic effects antibiotic
produced by
Clinical Uses Streptococcus
Adverse Effects orientalis.
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
enterocolitis, septicemia
› Especially for those caused by penicilin-
resistant pneumococcus and staphylococci
① Phlebitis
› at the site of injection.
② Nephrotoxicity and Ototoxicity
› rare with monotherapy, more common when
administered with other nephro- or ototoxins
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
some cases
They are available only in fixed
combinations with specific penicillins:
Ampicillin + sulbactam
Amoxicillin + clavulanic acid
Ticarcillin + clavulanate potassium
Piperacillin + tazobactam sodium
 (Amp/Sulbactam)
 Spectrum: Amp + most anaerobes + many
enteric G (-) rods, OSSA

Sulbactam alone is very active against

Acinetobacter spp.

30
(Pip/Tazo)
THE most broad-spectrum penicillin
Tazobactam may improve the activity of
piperacillin vs. gram-negative rods,
including anaerobes
4.5g IV q8h = 3.375g IV q6h
4.5g IV q6h for Pseudomonas

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