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Penicillins & Cephalosporins know the basics

Dr.T.V.Rao MD

Dr.T.V.Rao MD

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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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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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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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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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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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 & hosts defense mechanisms
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Effects of concentrated drug dosing

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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 its 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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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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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 Dr.T.V.Rao MD 11 PCN

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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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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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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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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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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Extended - Spectrum Penicillins

Carbenicillin (PO), Mezlocillin, Piperacillin, Ticarcillin, Ticarcillinclavulanate (Timentin) - IM & IV - Broad spectrum - good gram (-), fair gram (+) - Good against Pseudomonas aeruginosa - Not penicillinase resistant
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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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Most commonly used Antibiotics

Beta-lactam antibiotics are among the most commonly prescribed drugs, grouped together based upon a shared structural feature, the beta-lactam 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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From a fungus Cephalosperium acremonium - Gram (+) & gram (-) - Resistant to beta - lactamase - Bactericidal - action similar to PCNs - 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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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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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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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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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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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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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 soft-tissue 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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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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- 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 Dr.T.V.Rao MD 29 SE = GI disturbances, Allergic rxns = Hepatotoxicity

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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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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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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