Penicillin's & cephalosporins basics

1. Penicillins & Cephalosporins
know the basics
Dr.T.V.Rao MD
Dr.T.V.Rao MD
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2. Beginning of Antibiotics with
Discovery of Penicillin
• The discovery of
penicillin has been
attributed to Scottish
scientist Alexander
Fleming in 1928 and the
development of
penicillin for use as a
medicine is attributed
to the Australian Nobel
Laureate Howard
Walter Florey.
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3. Antibacterial agents
• Antibacterials/antimicrobial drugs - Substances that
inhibit the growth of or kill bacteria or other
microorganisms (microscopic organisms =
bacteria, viruses, fungi, protozoa)
• Bacteriostatic = Inhibits growth of bacteria
• Bactericidal = Kills bacteria
• Peaks & Troughs = Serum antibacterial levels for drugs w/
a narrow therapeutic index
- Too high = drug toxicity (Peak - 1 hr. after drug infused)
- Too low = therapeutic range (Trough - before dose)
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4. Uses of Antimicrobial Agents
• Antimicrobial agents are widely
employed to cure bacterial diseases
• Definition of Antibiotic – Antibiotics are
substances that are derived from a
various species of microorganisms and
are capable of inhibiting the growth of
other microorganism even in small
concentrations.
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5. Antibacterials
• Mechanism of Action:
1. Inhibition of cell wall synthesis - Bactericidal
2. Alteration in membrane permeability - ‘Cidal’
or ‘Static’
3. Inhibition protein synthesis - ‘Cidal’ or ‘Static’
4. Inhibition of bacterial RNA & DNA - Inhibits
synthesis of RNA & DNA
5. Interferes with metabolism in the cell - ‘Static’
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6. Antibacterial Drugs
• Drugs 1. Penetrate bacterial cell wall in sufficient
concentrations
2. Affinity to the binding sites on the bacterial
cell:
- Time drug remains at binding sites =
effect
- Time controlled by pharmacokinetics
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7. Antibacterials
• Pharmacodynamics - Concentration at site or exposure time for drug plays an
important role in bacteria eradication
- Duration of time for use of antibacterial varies according
to type of pathogen, site of infection & condition of host
- With some severe infections - continuous infusion more
effective than intermittent
- Body defense & drugs work together to stop infectious
process
- Effect = drug & host’s defense mechanisms
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8. Effects of concentrated drug dosing
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9. Antibacterials
• Bacterial Resistance - result naturally or may be
acquired
* Natural (inherent) = w/o previous exposure to antibiotic
ie. pseudomonas resistant to Penicillin G
* Acquired = prior exposure to antibacterial
ie. staph aureus was sensitive to PCN G, now it’s not
• Nosocomial infections - infections acquired while
clients are in the hosp. Many are mutant strains resistant
to many Antibacterials
Prolonged hospital stay
• Antibacterial resistance occurs when antibiotics are used
frequently
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10. Antibacterials
• Culture & Sensitivity - Blood test done to determine
effect drugs have on a specific organism
Culture = organisms responsible
Sensitivity = what antibiotic will work best
• Narrow & Broad Spectrum
Narrow - primarily effective against 1 type of organism
Broad - effective against both gram + & gram - organisms
* Used before isolating organism through C & S
* Not as effective as narrow spectrum against those
single organisms
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11. Antibacterials
Penicillins (PCN)
• From mold genus Penicillium - ‘miracle drug’ from
WWII
• A beta-lactum structure (beta-lactum ring) interferes
w/ bacterial cell wall synthesis by inhibiting the
bacterial enzyme necessary for cell division &
synthesis
• Bacteria die of cell lysis (breakdown)
• Both ‘static’ & ‘cidal’ in nature
• Mainly referred to as beta-lactum antibiotics
(enzymes produced by bacteria that can inactivate
PCN - Penicillinase = beta-lactamases which attack
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PCN

12. Penicillins and Cephalosporins
• Penicillin and cephalosporins act inhibiting Trans
peptidases, the enzyme catalyzes the final linking
step in synthesis of peptidoglycan.
• Due to this reason Penicillin in bactericidal for
growing bacteria since new peptidoglycan is
synthesized at that stage only.
• In nongrwoing cells penicillin is inactive
• An intact beta – lactum is essential for antibacterial
activity of penicillins
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13. Antibacterials
Penicillins
• Natural Penicillins
Penicillin G, Penicillin V, Procaine, Bicillin
- Good gram +, fair gram - , good
anaerobic
- PCN G = more effective IV or IM, but
painful d/t aqueous solution
- PCN V = PO; peak 2 - 4 hrs
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14. Classification of Penicillins
• Natural
Benzyl penicillin
Phenoxymethyl penicillin v
Semi synthetic and pencillase resistant
1 Methicillin
2 Nefcillin
3 Cloxacillin
4 Oxacillin
5 Floxacillin
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15. Antibacterials
Penicillins
• Aminopenicillins (Broad Spectrum)
Amoxicillin (Amoxil), Ampicillin
(Omnipen), Bacampicillin HCL (Spectrobid)
- Gram + & Gram - Costlier
- Inactivated by beta-lactamases = ineffective
against Staphylococcus aureus (staph. A)
- Amoxicillin = most prescribed PCN derivative
for adults & children
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16. Antibacterials
Penicillins
• Penicillinase - Resistant Penicillins
Methicillin (Staphcillin), Nafcillin
(Unipen), Oxacillin (Bactocil)
- Used to treat penicillinase-producing
Staph A.
- Gram + , not effective against Gram - IV & PO
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17. Antibacterials
Penicillins
• Extended - Spectrum Penicillins
Carbenicillin
(PO), Mezlocillin, Piperacillin, Ticarcillin, T
icarcillin-clavulanate (Timentin) - IM & IV
- Broad spectrum - good gram (-), fair
gram (+)
- Good against Pseudomonas aeruginosa
- Not penicillinase resistant
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18. Antibacterials
Penicillins
• SE & adverse reactions of Penicillins
1. Hypersensitivity - mild or severe
Mild = rash, pruritus, & hives - Rx w/ antihistamines
Severe = anaphylactic shock - occurs w/ in 20 min. - Rx w/
epinephrine
2. Super infection - secondary infection when normal
microbial flora of the body disturbed during antibiotic Rx
Mouth, resp. tract, GI, GU or skin - usually fungus
3. Organ toxicity - esp. liver & kidneys where drugs
metabolized & excreted (aminoglycosides)
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19. CEPHALOSPORINS
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20. Most commonly used Antibiotics
Cephalosporins
• Beta-lactam antibiotics are among the
most commonly prescribed
drugs, grouped together based upon a
shared structural feature, the betalactam ring. Cephalosporins cover a
broad range of organisms, are generally
well-tolerated, and are easy to
administer; thus, these agents are
frequently used beta-lactam drugs
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21. Antibacterials
Cephalosporins
• From a fungus Cephalosperium acremonium
- Gram (+) & gram (-)
- Resistant to beta - lactamase
- Bactericidal - action similar to PCN’s
- 4 groups (generations) - each effective against
a broader spectrum of bacteria
- about 10% of people allergic to PCN also to
allergic to cephalosporins
- Action - inhibits bacterial cell wall synthesis
- IM & IV - onset = almost immediate
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22. Antibacterials
Cephalosporins
• 1st Generation Cephalosporins - cefadroxil
(Duricef) & cephalexin (Keflex) - PO; Cefazolin
(Ancef) & cephalothin (Keflin) - IM
- Gram (+), & gram (-)
- Esp. used for skin/skin structure
infections
- Keflin used for resp, GI, GU, bone, &
joint infections
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23. Antibacterial
Cephalosporins
• 2nd Generation Cephalosporins cefaclor (ceclor) - PO, cefoxitin
(Mefoxin), cefuroxime
(Zinacef), cefotetan (Cefotan) - IM & IV
- Gram (+), slightly boarder gram (-)
effect than 1st generation
- for harder to treat infections
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24. Antibacterials
Cephalosporins
• 3rd Generation Cephalosporins cefotaxime (Claforan), ceftazidime
(Fortaz), ceftriaxone (Rocephin), cefixime
(Suprax) - IM or IV
- More effective against gram (-), less
effective against gram (+)
- for harder yet to treat infections
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25. 4th Generation Cephalosporins
• 4th Generation Cephalosporins cefepime (Maxipime) - IV or IM
• - Resistant to most betalactamase bacteria
• - greater gram (+) coverage than
3rd generation
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26. 5th Generation Cephalosporins
• Ceftaroline is a novel fifth-generation
cephalosporin, which exhibits broadspectrum activity against Gram-positive
bacteria, including MRSA and
extensively-resistant strains, such as
Vancomycin-intermediate S. aureus
(VISA), heteroresistant VISA (hVISA), and
Vancomycin-resistant S. aureus (VRSA)
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27. Why 5th Generation Cephalosporins
• Microbial resistance has reached alarming
levels, threatening to outpace the ability to counter
with more potent antimicrobial agents. In
particular, methicillin-resistant Staphylococcus aureus
(MRSA) has become a leading cause of skin and softtissue infections and PVL-positive strains have been
associated with necrotizing pneumonia. Increasing
reports of growing resistance to glycopeptide have
been noted, further limiting the efficacy of standard
antibiotics, such as Vancomycin.
• A need for newer Antibiotics is growing need
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28. ceftaroline is effective in
•
In addition to being an exciting new
agent in the anti-MRSA
armamentarium, ceftaroline provides
efficacy against many respiratory
pathogens including Streptococcus
pneumoniae, Haemophilus
influenza, and Moraxella catarrhalis.
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29. - Antibacterials
Macrolides, Lincosamide, Vancomycin
• All differ in structure, but similar spectrums of antibiotic
effectiveness to PCN
• Used as PCN substitutes, esp. w/ people allergic to PCN
• Erythromycin frequently prescribed if hypersensitive to
PCN
• Macrolides - Erythromycin, Azithromycin
(Zithromaz), Clarithromycin (Biaxin) - PO/IV, Dirithromycin
(Dynabac) - PO - Broad spectrum of activity
- Low to mod dose = bacteriostatic
- high doses = bactericidal
SE = GI disturbances, Allergic rxns = Hepatotoxicity
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30. Antibacterials
Lincosamide
• Clindamycin (Cleosin), Lincomycin
(Lincorex) - PO, IM, IV
- Inhibit bacterial protein synthesis
- ‘Static’ & ‘cidal’ actions depending on drug
dosage
- effective against most gram (+), no gram (-)
- Clindamycin more effective than lincomycin
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31. Antibacterials
Vancomycin
• Glycopeptide bactericidal antibiotic - IV
- Use: Drug resistant Staph A., cardiac surgery prophylaxis for clients w/ PCN allergies
- SE = Ototoxicity - damage to auditory branch
of 8th cranial nerve permanent hearing loss
or loss of balance & Nephrotoxicity
- Serum Vancomycin levels drawn to minimize
toxic effects
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32. Antibacterials
Vancomycin
• Glycopeptide bactericidal antibiotic - IV
- Use: Drug resistant Staph A., cardiac surgery prophylaxis for clients w/ PCN allergies
- SE = Ototoxicity - damage to auditory branch
of 8th cranial nerve permanent hearing loss
or loss of balance & Nephrotoxicity
- Serum Vancomycin levels drawn to minimize
toxic effects
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Medical and Paramedical Students in the
Developing World
• Email
• doctortvrao@gmail.com
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