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Fosfomycin (Monurol)
- Non-β-lactam drug
- structural analog of PEP, blocks step-1 PG synthesis
- pharmacokinetics: well absorbed and distributed, excreted unchanged in urine
- Broad spectrum
- resistance emerges from multiple doses
- toxicity: few, diarrhea and vaginitis
- use: single dose oral treatment of uncomplicated UTIs caused by susceptible E faecalis and E. coli
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D-cycloserine
- Non-β-lactam drug
- structural analog of D-alanine, blocks 2 steps of PG synthesis
- pharmacokinetics: oral, good CNS penetration, active form in urine
- Broad spectrum
- toxicity: serious CNS effects - dose related; reversible
- use: restricted second-line M tuberculosis drug
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Bacitracin
- Non-β-lactam drug
- mechanism: depletes lipid carrier for PG synthesis
- pharmacokinetics: topical application only, poorly absorbed
- narrow spectrum (gram+, Neisseria, T. pallidum)
- Toxicity: severe nephrotoxicity
- use: skin and ophthalmologic infections, good in combination with polymyxin B (membrane inhibitor)
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Vancomycin (Vancocin)
- Non-β-lactam drug
- Structure: glycopeptide; teicoplanin and dalbavancin
- mechanism: blocks cross-linking of PG synthesis by binding the substrate (binds D-ala - D-ala terminus of pentapeptide); rapidly bactericidal for dividing bacterial cultures (static in enterococci)
- pharmacokinetics: IV admin (SLOW), not IM; rarely oral - poor absorption; excellent distribution to bone and CNS
- narrow spectrum (gram + and most MRSA)
- resistance: 1. VRE - Enterococci vanA, vanB, or vanC genes; different cell wall subunits with reduced binding to vancomycin. 2. VRSA - overexpression of D-ala - D-ala acts as competitor, binds up drug
- Adverse effects: Red Man Syndrome, ototoxicity and nephrotoxicity
- use: reserved for serious gram+ infections resistant to other less toxic drugs, MRSA, penicillin-resistant S. pneumonia, synergistic combination with aminoglycosides
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Penicillin G
- β-lactam drug
- acid-labile - parenteral admin (usually IM, serious infections IV)
- 2 repository forms for IM injection
- - procaine and benzathine Pen G
- - water-insoluble, slow release into bloodstream
- spectrum: Gram+ and some Gram- cocci
- Adverse effects: allergies, dose-dependent neurotoxicity and seizures, Stevens-Johnson syndrome
- use (non-penicillinase producing microbes): S. pneumoniae, Staph. sp., N. meningitidis, Clostridium sp., Treponema pallidum
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Penicillin V
- β-lactam
- acid stable - oral administration, 60% absorption
- spectrum: Gram+ and some Gram- cocci
- Adverse effects: allergies, Stevens-Johnson syndrome
- use (non-penicillinase producing microbes): S. pneumoniae, Staph. sp., N. meningitidis, Clostridium sp., Treponema pallidum
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dicloxacillin and nafcillin
- β-lactam
- penicillinase-resistant penicillin
- pharmacokinetics: acid stable (nafcillin less), food interferes with absorption, can be given parenterally
- spectrum / use: penicillinase-producing staphylococci and streptococci
- resistance: MRSA (to methicillin), and PBP with lower affinity for drugs
- adverse effects: more than Pen G and Pen V; oxacillin: hepatitis at high doses
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amoxicillin
- extended-spectrum penicillin - aminopenicillin
- Destroyed by β-lactamases
- pharmacokinetics: acid stable, oral admin
- spectrum / use: non-lactamase Gram- bacilli (E. coli, H. influenza, Salmonella, Shigella)
- - not substitute for Pen G and V
- - for mixed infections
- - prophylaxis for bacterial endocarditis
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carbenicillin
- extended-spectrum penicillin - carboxypenicillin
- Destroyed by β-lactamases
- Retain Gram+ activity, enhanced Gram- activity
- - Pseudomonas, Klebsiella sp.
- Parenteral admin
- Often reserved for serious systemic infections caused by Pseudomonas or Klebsiella
- - HIV or burn pts
- - often combined with aminoglycoside
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piperacillin
- extended-spectrum penicillin - ureidopenicillin
- Destroyed by β-lactamases
- Retain Gram+ activity, enhanced Gram- activity
- - Pseudomonas, Klebsiella sp.
- Parenteral admin
- Often reserved for serious systemic infections caused by Pseudomonas or Klebsiella
- - HIV or burn pts
- - often combined with aminoglycoside
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Clavulanic acid
- β-lactamase inhibitor
- lacks antibiotic activity alone
- mechanism: structurally-related to penicillins, β-lactamase suicide inhibitors
- used in fixed [c] with extended spectrum penicillins (synergistic)
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tazobactam and sulbactam
- β-lactamase inhibitor
- lacks antibiotic activity alone
- mechanism: structurally-related to penicillins, β-lactamase suicide inhibitors
- used in fixed [c] with extended spectrum penicillins (synergistic)
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cephalexin (1st gen)
- cephalosporin
- pharmacokinetics: Acid stabile, mainly renal excretion, minimal metabolism, given orally, IV or IM, variable distribution
- resistance: can induce Amp C (cephalosporinase), low affinity PBPs
- adverse effects: very safe, hypersensitivity (5% pts), cross allergenic with Pens
- Broadest spectrum against Gram+ cocci (surgical prophylaxis); effective against Gram- bacilli
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cefoxitin (2nd gen)
- cephalosporin
- pharmacokinetics: Acid stabile, mainly renal excretion, minimal metabolism, given orally, IV or IM, variable distribution
- resistance: can induce Amp C (cephalosporinase), low affinity PBPs
- adverse effects: very safe, hypersensitivity (5% pts), cross allergenic with Pens, disulfiram-like rxn (antabuse effect)
- Only group with significant activity against anaerobes
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ceftriaxone (3rd gen)
- cephalosporin
- pharmacokinetics: Acid stabile, mainly renal excretion, minimal metabolism, given orally, IV or IM, variable distribution
- resistance: can induce Amp C (cephalosporinase), low affinity PBPs
- adverse effects: very safe, hypersensitivity (5% pts), cross allergenic with Pens, disulfiram-like rxn (antabuse effect)
- Anti-pseudomonal and pneumococcal; serious Gram- infections such as meningitis, pneumonia, gonorrhea
- Most widely used treatment in children and infants with moderate to severe infections
-
cefepime (4th gen)
- cephalosporin
- pharmacokinetics: Acid stabile, mainly renal excretion, minimal metabolism, given orally, IV or IM, variable distribution
- resistance: can induce Amp C (cephalosporinase), low affinity PBPs
- adverse effects: very safe, hypersensitivity (5% pts), cross allergenic with Pens
- Anti-pseudomonal
- High resistance to β-lactamases; useful for treating Enterobacter and penicillin-resistant strep
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Imipenem
- carbapenem - β-lactam ring, same mechanism as pens / cephs
- activity and spectrum: binds more efficiently to PBPs than pens/cephs; penetrates outer membrane of G- bacteria; broadest activity of all β-lactam drugs
- - NOT for MRSA or VRE
- - resistant to degradation by most β-lactamases, but induce those that inactivate pens and cephs (antagonize cidal effects of pens and cephs)
- resistance: alteration of PBPs
- pharmacokinetics: parenteral admin; renal metabolism and inactivation (administered with cilastatin, inhibits dehydropeptidases)
- Adverse effects: cross-allergic rxn to penicillin (~5%); rare - GI effects, superinfections, neurotoxicity
- use: 2nd line therapy for serious nosocomial infections
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aztreonam
- monobactam
- mechanism: binds PBPs, relatively resistant to β-lactamases
- pharmacokinetics: IM or IV, drug penetrates inflamed CNS
- NO significant cross-reactivity with pens
- spectrum: narrow - limited to G- aerobes (pseudomonas)
- use: G- UTI, lower RTIs, systemic infections
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