• Clinical science

Overview of antibiotic therapy

Summary

Antibiotics are employed against bacterial as well as some parasitic infections. They have either a bacteriostatic or a bactericidal effect and can be effective against a small group of bacteria (narrow-spectrum) or a wide range of pathogens (broad-spectrum). Most antibiotics work by inhibiting cell wall synthesis, protein synthesis, or nucleic acid synthesis in bacteria. Common side effects include allergies and cross-reacting hypersensitivities, as well as nephrotoxic and hepatotoxic effects. Many antibiotics are contraindicated in certain patient groups (e.g., children, pregnant or lactating women). In the case of severe infections, early initiation of one or more antibiotics without waiting for a microbiological confirmation is indicated (empirical antibiotic therapy), with the aim of targeting the most likely pathogen(s). Because of widespread use of antibiotics (often misuse!), antibiotic-resistant pathogens have emerged (e.g., MRSA, Pseudomonas).

Basic mechanisms of antibiotic action

Beta-lactam antibiotics

Beta-lactamase inhibitors

Beta-lactamase inhibitors (CAST): Clavulanic Acid, Sulbactam, Tazobactam

Penicillins

Natural penicillins

Anti-staphylococcal penicillins

Aminopenicillins

Aminopenicillin therapy HHELPSSS destroy enterococci.

AMinoPenicillins are AMPed-up penicillins.

AmOxicillin is administered Orally, while amPicillin is administered via a Prick!

Ureidopenicillins

  • Drugs
  • Clinical use: extended spectrum
    • Gram-negative bacilli
      • Especially Pseudomonas
      • Also anaerobes, i.e., Bacteroides fragilis
    • Gram-positive aerobes

Carboxypenicillins

For antipseudomonals: A TICk kills Pseudomonas with a PIPE bomb in a CAR. (ticarcillin, piperacillin, carbenicillin)
References:[1]

Carbapenems

I'm a pen” that crosses out allthe bacteria.

Monobactams

Cephalosporins

First generation cephalosporins

First generation cephalosporins: PEcK

Second generation cephalosporins

Second generation cephalosporins: HEN PEcKS

Third generation cephalosporins

Fourth generation cephalosporins

Fifth generation cephalosporins

Cephalosporins can be LAME because they don't act against Listeria, Atypical organisms (Chlamydia, Mycoplasma), MRSA , and Enterococci!

Adverse effects

References:[1]

Glycopeptides

References:[1]

Epoxides

Lipopeptides

Polymyxins

Aminoglycosides

Mean GNATScaNNOT kill anaerobes. (AMINoglycosides; Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin; Nephrotoxicity, Neuromuscular blockade, Ototoxicity, Teratogenic)
References:[1][2]

Tetracyclines

References:[1][3]

Glycylcyclines

  • Drugs: tigecycline
  • Mechanism of action
  • CNS penetration: poor
  • Route of elimination: mostly biliary
  • Clinical use
  • Adverse effects
    • GI upset
    • Hepatotoxicity
    • Deposition in bones and teeth
    • Damage to mucous membranes (these antibiotics should be taken with a lot of water)
    • Photosensitivity
  • Contraindications
    • Pregnancy
    • Hepatic failure (relative contraindication)
    • Should be used with caution for children < 8 years and lactating women

References:[4][5][6]

Macrolides

References:[1]

Lincosamides

Clindamycin is indicated for anaerobes above the diaphragm and metronidazole treats anaerobes below it!

Oxazolidinones

Amphenicols

References:[1]

Fluoroquinolones

  • Mechanisms of resistance
    • Bacterial mutations can occur in genes that mediate:
      • DNA gyrase and topoisomerase IV enzymes
      • Cell wall permeability
      • Efflux pumps

References:[7][8]

Nitroimidazoles

GET GAP on the Metro! (Giardia, Entamoeba, Trichomonas, Gardnerella, Anaerobes (Clostridium, Bacteroides), H. Pylori → Metronidazole)

Clindamycin is indicated for anaerobes above the diaphragm and metronidazole treats anaerobes below it!
References:[1][9][10]

Sulfonamides and trimethoprim

Trimethoprim (TMP) Treats Marrow Poorly.

References:[1][11][12]

Nitrofurans

Antimycobacterial drugs

Compare drugs below with tuberculosis therapy for an overview

The four drugs used as first-line treatment are “RIPE”: Rifampin, Isoniazid, Pyrazinamide, and Ethambutol.

Rifamycins

The 4Rs' of rifampin: RNA polymerase inhibition, Ramping up of cytochrome P450 activity, Red or orange colored urine, and Rapid developement of resistance if used alone
References:[4][13]

Isoniazid (INH)

INH Injures Neurons and Hepatocytes!

Neurotoxicity and lupus may be prevented by supplementing with pyridoxine (vitamin B6)!References:[14]

Pyrazinamide

  • Mechanism of action
    • Not completely understood.
    • Bactericidal
  • CNS penetration: only when meninges are inflamed
  • Route of elimination: renal
  • Clinical use: M. tuberculosis
  • Adverse effects
  • Contraindications
    • Hepatic failure (relative contraindication)
    • Pregnancy (relative contraindication)

Ethambutol

  • Mechanism of action
    • Prevents cell wall synthesis by inhibiting arabinosyltransferase
    • Bacteriostatic
  • CNS penetration: only when meninges are inflamed
  • Route of elimination: primarily renal
  • Clinical use
  • Adverse effects
    • Optic neuritis, retrobulbar neuritis ↓ visual acuity and red-green color-blindness→ can result in irreversible blindness
    • Resistance develops rapidly if used as a monotherapy.
  • Contraindications
    • Children (relative contraindication)

EYEthambutol causes optic neuropathy!
References:[15]

Dapsone