Bacte Book

• Beta-lactam ring


  All penicillin-family antibiotics have this
• Penicillin-family antibiotics


  Also called beta-lactam antibiotics
• Mechanism of action of penicillin

  1. Penicillin doesn't just slow the growth of bacteria, it kills bacteria

  2. Penicillin is bactericidal
• Peptidoglycans


  • Both gram-positive and gram-negative bacteria possess them in their cell walls
  • They are composed of repeating disaccharide units cross-linked with amino-acids (peptides)
• Transpeptidase


  The enzyme that catalyzes the cross-linking of the peptidoglycan units
• How penicillin works


  1. Penicillin must evade the bacterial defenses and penetrate the outer cell-wall layers to the inner cytoplasmic membrane, where the transpeptidase enzymes are located

  2. The penicillin beta-lactam ring binds to and competitively inhibits the transpeptidase enzyme

  3. This arrests cell wall synthesis and the bacteria dies
• Porins


  Channels in the outer membrane of gram-negative bacteria where penicillin must pass through
• Penicillin-binding protein


  Enzyme where penicillin binds to transpeptidase, arresting cell wall synthesis
• Requirements for penicillin to be effective

  • Penetrate the cell layer
  • Keep its beta-lactam ring intact
  • Bind to the transpeptidase (penicillin-binding protein)
• Ways bacteria defend against beta-lactam antibiotics

  • Gram-negative: Prevent penicillin from penetrating by altering porins
  • Both: Produce beta-lactamase enzymes that cleave the beta-lactam ring
  • Alter the molecular structure of the transpeptidase so the antibiotic can't bind
  • Actively pump out the beta-lactam before it can bind
• All penicillins can cause anaphylactic (allergic) reactions
• Penicillins can cause diarrhea by destroying the natural GI flora and allowing resistant pathogenic bacteria (such as Clostridioides difficile) to grow
• Types of penicillin


  • Penicillin G
  • Aminopenicillins
  • Penicillinase-resistant penicillins
  • Anti-Pseudomonal penicillins
  • Cephalosporins
  • Carbapenems
• Penicillin G


  The original penicillin discovered by Fleming, sensitive to beta-lactamase enzymes
• Penicillin V


  Oral form of penicillin, acid stable in the stomach, used for streptococcus pharyngitis
• Aminopenicillins (Ampicillin, Amoxicillin)


  Have a broader spectrum than Penicillin G, hitting more gram-negative organisms, but still inhibited by penicillinase
• Amoxicillin is more effectively absorbed orally than ampicillin, so it is frequently used for outpatient treatment of bronchitis, otitis media, and sinusitis
• Ampicillin is commonly used with aminoglycosides (gentamicin) for broad gram-negative coverage, especially for serious urinary tract infections
• Penicillinase-resistant penicillins (Methicillin, nafcillin, oxacillin)


  Can kill Staphylococcus aureus, usually given IV
• Methicillin use has been discontinued in the US due to interstitial nephritis, but its name is still used in reference to sensitivity testing (MRSA)
• Nafcillin


  Drug of choice for serious Staphylococcus aureus infections
• Cloxacillin and dicloxacillin


  Not good against gram-negative organisms, used for gram-positive bacteria that produce penicillinase
• MRSA (methicillin-resistant Staphylococcus aureus) is now prevalent both in hospital-acquired and community-acquired infections
• Anti-Pseudomonal penicillins (Carboxypenicillins, Ureidopenicillins)


  Have expanded gram-negative coverage, especially against Pseudomonas aeruginosa, also active against anaerobes
• Carbenicillin has certain disadvantages like lower activity, high sodium load, platelet dysfunction, and hypokalemia, so it has been replaced by ticarcillin or ureidopenicillins
• Beta-lactamase inhibitors (Clavulanic acid, Sulbactam, Tazobactam)


  Can be combined with penicillins to create beta-lactamase resistant combinations
• Cephalosporins


  • More resistant to beta-lactamases than penicillins
  • Have a new R-group side chain allowing for more spectrum variations
• Generations of cephalosporins


  • First generation: More effective against gram-positive, less effective against gram-negative
  • Second generation: More effective against gram-negative
  • Third generation: Used for serious infections like pneumonia, meningitis, pyelonephritis
  • Fourth generation: Extended spectrum third generation
  • Fifth generation: First with activity against MRSA
• MRSA and Enterococci are resistant to all cephalosporins
• First generation cephalosporins


  • CEFADROXIL
  • CEFAZOLIN
  • CEFALEXIN
  • CEPHALOTHIN
  • CEPHAPIRIN
  • CEPHRADINE
• Second generation cephalosporins


  • Cover more gram-negative rods than first-generation cephalosporins
  • Cefuroxime has good coverage against Streptococcus pneumoniae and Haemophilus influenzae
• Second generation cephalosporins


  • CEFACLOR
  • CEFPROZIL
  • CEFUROXIME
  • CEFOXITIN
  • CEFAMANDOLE
  • CEFMETAZOLE
  • CEFONICID
  • CEFOTETAN
• Third generation cephalosporins


  • Used primarily for inpatient treatment of community-acquired pneumonia, meningitis, and pyelonephritis
• Third generation cephalosporins


  • CEFDINIR
  • CEFIXIME
  • CEFOTAXIME
  • CEFTAZIDIME
  • CEFTIBUTEN
  • CEFTIZOXIME
  • CEFTRIAXONE
  • CEFDITOREN
  • CEFPODOXIME
• Fourth generation cephalosporins


  Sometimes called an extended spectrum 3rd-generation cephalosporin
• Fourth generation cephalosporins


  • CEFEPIME
• Fifth generation cephalosporins


  • CEFTAROLINE
  • CEFIDEROCOL
• Carbapenems


  • Imipenem, Meropenem, Doripenem, and Ertapenem
  • Constitute one of the newer classes of antibiotics with some of the broadest coverage
  • Resistant to beta-lactamases, including Extended Spectrum Beta-Lactamases
• Imipenem


  Has the broadest antibacterial activity of any antibiotic known<|>Kills gram-negatives, gram-positives, and anaerobes<|>Stable to beta-lactamases<|>Can pass through porin channels to the periplasmic space<|>Notable for making seizures more likely by lowering seizure threshold
• Meropenem and Doripenem


  As powerful as imipenem<|>Stable against dehydropeptidase, so cilastatin is not needed<|>Have less potential for causing seizures relative to imipenem