Cephalosporins : Dr Rahul Kunkulol's Power point Presentations
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Transcript of Cephalosporins : Dr Rahul Kunkulol's Power point Presentations
CephalosporinsDR RAHUL
Inhibitors of Cell Wall Synthesis
Cephalosporins and cephamycins
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. Some bacteria can produce a beta
lactamase called cephalosporinase Many of them are resistant to the enzyme.
b-lactam Antibiotics
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Monobactams
All of the drugs in this group contain
a β-lactam ring in their structure
Penicillins
NO
S
Carbapenems
NO
NO
NO
S
Cephalosporins
share similar• features of chemistry,• mechanism of action, • pharmacologic and clinical effects.
Mechanism of action
Cephalosporins inhibit the peptido-glycan synthesis of bacterial cell wall in a manner similar to that of penicillin and are considered bactericidal.
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Cephalosporin
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
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 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.
First Generation Cephalosporins
USES 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 who have a h/o penicillin hypersensitivity.
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Second Generation Cephalosporin
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
Second Generation Cephalosporin
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.
USES :
Sinusitis, Otitis, LRTI, Community acquired pneumonia › caused by beta lactamase producing H.
influenza Meningitis Mixed infections :
› Peritonitis › Diverticulitis› pelvic infections
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Third Generation Cephalosporins
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
Third Generation Cephalosporins
⑤ The best penetration into the CSF; almost no nephrotoxicity.
⑥ Ceftizoxime have good activity against B.fragilis.
⑦ Some of them are effective against P.aeruginosa and enteric bacilli. (cefoperazone and ceftizidime)
Third Generation Cephalosporins
There are also some unique properties of individual 3th generation.
Ceftriaxone has the longest half-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.
Uses 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
uses
First line 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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Fourth -Generations
Cefepime1. More resistant to hydrolysis by β-
lactamase2. Active against P-aeruginosa &
Enterobacteriaceace.3. Clinical use as third generations.
Generations First second Third
Drugs Cephalexin (O)Cefadroxil (O)Cefazolin (im, iv)Cephalothin (o,im)
Cefaclor (o)Cefuroxime (o)Cefoxatin (im, iv)Cefotetan (im)
Cefixime (o)Ceftriaxone (o)Cefotaxime (im, iv)Cefoperazone
Antibacterial spectrumG+Ve +++ ++ +
G -ve + ++ +++
Anaerobes Efective against B.Fragalis
Very effective (cefotetan &
cefoxitin)
Effective(Cefoperazone)
Pseudomonas - - -- effective
Salmonella -- - effective
Betalactamase Resistant to staphylococcal
H, resistant to G-ve
Highly resistant
BBB --- Only cefuroxime Most drugs
Adverse effects 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.
Adverse effects 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.
The Other Beta-lactam antibiotics
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
Other inhibitions of cell wall
synthesis
Mechanism of action Pharmacologic effects Clinical Uses Adverse Effects
VancomycinVancomycin
Vancomycin is an antibiotic
produced by Streptococcus
orientalis.
Pharmacologic effects
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.
Vancomycin: Clinical Uses
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
Vancomycin: Adverse Effects
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
Vancomycin: Adverse Effects
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
Beta lactamase inhibitors
They are available only in fixed combinations with specific penicillins:
Ampicillin + sulbactam Amoxicillin + clavulanic acid Ticarcillin + clavulanate potassium Piperacillin + tazobactam sodium
Sulbactam
(Amp/Sulbactam) Spectrum: Amp + most anaerobes + many
enteric G (-) rods, OSSA
Sulbactam alone is very active against Acinetobacter spp.
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Tazobactam
(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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