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24 Cards in this Set
- Front
- Back
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Classification
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Beta-lactam antibiotics:
Penicillins (derived from Penicillium spp.) Cephalosporins (from Cephalosporium spp.) Carbapenems (synthetic) Monobactams (synthetic) |
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Classification: penicillins
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Narrow spectrum: flucloxacillin, penicillin G, penicillin V
Extended spectrum: amoxicillin, ampicillin, bacampicillin Penicillinase resistant / Antistaphylococcal Penicillins: cloxacillin, dicloxacillin, methicillin Antipseudomonal penicillins: ticarcillin, carbenicillin, piperacillin, mezlocillin |
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Mechanism of action of penicillins
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Peptidoglycan - a component of cell wall that provides rigidity, made of 2 alternating amino sugars (N-acetylmuramic acid and N-acetylglucosamine) crosslinked by peptide chains
Transpeptidation is last step in synthesis of peptidoglycan, which is blocked by penicillins Bind to penicillin binding proteins (PBP) in the bacteria, inhibit transpeptidase enzyme and block transpeptidation step in cell wall synthesis Disruption of cell wall morphology and autolysins contribute to cell death Bactericidal for growing / dividing cells |
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Mechanisms of resistance
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Altered penicillin binding proteins
Production of beta-lactamases by bacteria which degrade the penicillins |
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Penicillin G and V
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Unstable in acid, not absorbed orally
Half-life of 30 minutes. Probenicid was used to prolong its action by inhibition of tubular secretion CSF concentration only 1-3% of plasma concentration Very high doses can cause seizures Active against streptococci, meningococci, enterococci, pneumococci, staphylococci, Treponema pallidum (syphilis), Clostridium spp, actinomyces, other G- rods and G- anaerobes Penicillin V is potassium salt, acid stable, can be given orally, but poor bioavailability and short half-life (qid) Only in minor infections, narrow spectrum 1 mg of pure penicillin G contains 1667 units Preference given to amoxicillin |
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Depot preparations of penicillin G
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Procaine penicillin G
Benzathine penicillin G Yield low but prolonged blood levels Clinical uses of penicillin G Streptococcal infections, gonococcal infections, syphilis, actinomyces infections, diphtheria (Corynebacterium diphtheriae, aerobic G+), anthrax (Bacillus anthracis), listeriosis (Listeria monocytogenes) Prophylactic Uses : Recurrence of Rh. Fever, surgical procedures in pt with Valvular HD, SYPHILIS |
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Adverse reactions
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Hypersensitivity: 1-10% patients treated
Penicilloic acid- hapten for immune reaction Rashes, urticaria to angioedema to anaphylaxis Beta-lactam cross-hypersensitivity Ampicillin in mononucleosis: rash in more than 90% Diarrhea due to disruption of commensal intestinal flora Nephritis- methicillin Neurotoxicity- intrathecal or seizure disorders Platelet dysfunction- carbenicillin, ticarcillin Cation toxicity- watch sodium (congenstive heart failure) and potassium (cardiac toxicity esp in renal failure) |
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Cephalosporins
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First Generation
Gram+ cocci, Gram- bacilli, anaerobic cocci Staphylococcus aureus, Proteus mirabilis, E. coli, Klebsiella pneumonia cefazolin, cephalothin (parenteral) cephalexin, cefadroxil, cephradine (oral) Cefazolin DOC for surgical prophylaxis |
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Second generation
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Less active against G+, more G-
Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp Cefaclor, cefuroxime axetil (p.o.) Cefamandole, cefonicid, cefuroxime, cefotetan, ceforanide (parenteral) Cefoxitin- Bacteroides fragilis Used in combination with aminoglycosides for G- bacilli |
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Third generation
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More G- coverage, less effective against G+ than 1st and 2nd generation, more resistant to beta-lactamase enzyme
Cefixime (p.o.), cefotaxime, ceftaxidime, ceftriaxone, cefpodoxime Effective against Pseudomonas (more than anti-pseudomonal penicillins) ceftazidime, cefoperazone, ceftizoxime Only third generation penetrates well into CSF Cefoperazone and ceftriaxone excreted through bile and feces |
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Third Generation: Uses
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Third Generation: Uses
Ceftriaxone therapy of choice for gonorrhea and severe forms of Lyme disease (Borrelia burgdorferi) Drug of choice for meningitis caused by H. influenzae, N. meninigidis and enteric bacteria. Used for empirical treatment of meningitis in children older than 3 months (combined with vancomycin and ampicillin). Ceftazidime + aminoglycoside : DOC for pseudomonas meningitis. Cefepime: DOC for nosocomial infections caused by Enterobacter, Citrobacter, Serratia. |
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Fourth generation
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Similar spectrum to third generation
More resistance to beta-lactamases Cefepime hydrochloride |
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Adverse effects of cephalosporins
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Allergy: 15% cross-hypersensitivity with penicillin allergy
1-2% without penicillin allergy Disulfiram-like effect Cefamandole, cefoperazone when ingested with alcohol block second step in oxidation and acetaldehyde accumulation Bleeding cefamandole, cefoperazone- anti-vitamin K effects Renal, hepatic dysfunction |
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Carbapenems
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Imipenem/cilastatin (Tienam ®), meropenem
Spectrum and clinical use: Gram-, Gram+ Resistant to beta-lactamase Restricted use for serious nosocomial infections, esp. Pseudomonas spp PK: I.V. Administration, renally cleared, dose adjustments Penetrate well into CSF and other body tissues Imipenem is combined with cilastatin: Cilastatin inhibits renal dehydropeptidase-I enzyme which breaks down imipenem. |
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Monobactams
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Narrow spectrum- enterobacteriaceae, pseudomonas; no G+ or anaerobic activity
Resistant to beta-lactamase Aztreonam IV or IM Phlebitis, skin rash, abnormal liver function tests Little cross reactivity with penicillin |
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Beta-lactamase inhibitors
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Inhibit beta-lactamase enzyme produced by bacteria and protect beta-lactam antibiotics from degradation. They do not widen the spectrum of the antibiotic but only protect against beta-lactamase producing strains.
Clavulanic acid + amoxicillin (Augmentin ®) Sulbactam+ ampicillin (Unasyn ®) Tazobactam + piperacillin (Tazocin ®) |
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Other cell wall- or membrane active agents
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Vancomycin
Bacitracin Teicoplanin Daptomycin Fosfomycin Cycloserine |
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Vancomycin
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Produced by Amycolatopsis orientalis
Glycopeptide of MW 1500, soluble in water, quite stable Narrow-spectrum: against methicillin-resistant staphylococci , S. pneumoniae, pseudomembranous colitis caused by Clostridium difficile Binds with high affinity to d-alanyl-d-alanine terminus of cell wall precursor units and is bactericidal Prophylaxis for subacute bacterial endocarditis caused by viridans streptococci: in penicillin allergic patients for high risk surgery Oral route only for pseudomembranous colitis Intravenous for systemic infections |
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Vancomycin
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Minimal resistant bacteria, but not vancomycin resistant enterococci (VRE)
Renal elimination Fever, chills, phlebitis at infusion site, rash with chronic administration, ototoxicity, nephrotoxicity Slow IV administration - fast causes histamine release (“red -man syndrome”/ red-neck syndrome) due to direct toxic effect of vancomycin on mast cells, hypotension |
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Bacitracin
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Gram positive cocci, Neisseria, Haemophilus, treponemas.
Topical application due to nephrotoxicity Often used for traumatic abrasions.eardrops |
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Teicoplanin
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Glycopeptide antibiotic
Very similar in mechanism of action and spectrum to vancomycin Both i.m. and i.v., half-life 45-70 hours: once daily Available in Europe, not (yet?) in the U.S.A. “Spare” antibiotic, reserverd for methicillin resistant staphylococci |
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Daptomycin
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Cyclic lipopeptide fermentation product of Streptomyces roseosporus
Spectrum similar to vancomycin, also active against vancomycin resistant enterococci and S. aureus Skin and soft tissue infections, bacteremia and and endocarditis Renally cleared, dose adjustments Effective alternative to vancomycin |
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Fosfomycin
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Analog of phospho-enolpyruvate, structurally unrelated to any other antibiotic
Blocks formation of N-acetylmuramic acid Active against G+ and G- Synergy with beta-lactams, aminoglycosides, fluoroquinolones Oral preparation for for uncomplicated UTI in women, single dose of 3g |
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Cycloserin
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Antibiotic produced by Streptomyces orchidaceus
Water-soluble, very unstable in acid Active against many G+ and G- Used almost exclusively for resistant M. tuberculosis Structural analog of D-alanine, inhibits its incorporation in peptidoglycan pentapeptide by inhibition of alanine racemase Adverse effects: CNS toxicity: headaches, tremors, acute psychosis, convulsions |
