Penicillin's & cephalosporins basics

Dr.T.V.Rao MD 1

Penicillins & Cephalosporinsknow the basics

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.

Dr.T.V.Rao MD 2

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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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Antibacterials• Mechanism of Action:1. Inhibition of cell wall synthesis - Bactericidal2. Alteration in membrane permeability - ‘Cidal’

or ‘Static’3. Inhibition protein synthesis - ‘Cidal’ or ‘Static’4. Inhibition of bacterial RNA & DNA - Inhibits

synthesis of RNA & DNA5. 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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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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Effects of concentrated drug dosing

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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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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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AntibacterialsPenicillins (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 PCN

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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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AntibacterialsPenicillins

• 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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• 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, Ticarcillin-clavulanate (Timentin) - IM & IV

- Broad spectrum - good gram (-), fair gram (+)

- Good against Pseudomonas aeruginosa - Not penicillinase resistant

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• SE & adverse reactions of Penicillins1. Hypersensitivity - mild or severe Mild = rash, pruritus, & hives - Rx w/ antihistamines Severe = anaphylactic shock - occurs w/ in 20 min. - Rx

w/ epinephrine2. Super infection - secondary infection when normal

microbial flora of the body disturbed during antibiotic Rx

Mouth, resp. tract, GI, GU or skin - usually fungus3. Organ toxicity - esp. liver & kidneys where drugs

metabolized & excreted (aminoglycosides)

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CEPHALOSPORINS

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Most commonly used Antibiotics Cephalosporins

• 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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AntibacterialsCephalosporins

• 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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• 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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AntibacterialCephalosporins

• 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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• 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 beta-

lactamase bacteria• - greater gram (+) coverage than

3rd generation

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5th Generation Cephalosporins

• Ceftaroline is a novel fifth-generation cephalosporin, which exhibits broad-spectrum 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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- AntibacterialsMacrolides, 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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AntibacterialsLincosamide

• 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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AntibacterialsVancomycin

• 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

Dr.T.V.Rao MD 32

AntibacterialsVancomycin

• 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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Penicillin's & cephalosporins basics

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