Antibiotics Study Guide

Antibiotics

• Chemicals that inhibit specific bacteria.
• Made in three ways:
  • By living microorganisms.
  • By synthetic manufacture.
  • In some cases, through genetic engineering.

Types of Antibiotics

• Bacteriostatic:
  • Inhibit the growth of bacteria.
• Bactericidal:
  • Kill bacteria directly.

Signs of Infection

• Fever
• Lethargy
• Elevated white blood cell count
• Classic signs of inflammation:
  • Redness
  • Swelling
  • Heat
  • Pain

Goal of Antibiotic Therapy

• Decrease the population of the invading bacteria to a point at which the human inflammatory/immune system can effectively deal with the pathogen.

Selecting Treatment

• Culture:
  • Identification of the causative organism.
• Sensitivity testing:
  • Determination of which antibiotic will best kill or control the organism.

Bacteria Classification

• Gram-positive:
  • The cell wall retains a stain or resists decolorization with alcohol.
• Gram-negative:
  • The cell wall loses a stain or is decolorized by alcohol.
• Aerobic:
  • Depend on oxygen for survival.
• Anaerobic:
  • Do not use oxygen.

Bacteria and Resistance to Antibiotics

• Bacteria adapt to their environment.
• The longer an antibiotic has been in use, the greater the chance that the bacteria will develop into a resistant strain.
• Use of antibiotics may result in the development of superinfections or overgrowth of resistant pathogens.

Aminoglycosides

• A group of antibiotics used to treat serious infections caused by primarily aerobic gram-negative bacilli.
• Common medications:
  • Amikacin (Amikin)
  • Gentamicin (Garamycin)
  • Neomycin (Mycifradin)
  • Plazomicin (Zemdri)
  • Streptomycin (generic)
  • Tobramycin (Bethkis, TOBI, Tobrex)
• Bactericidal.
• Actions:
  • Inhibit protein synthesis in susceptible strains of aerobic gram-negative bacteria.
  • Irreversibly bind to a unit of the bacteria ribosomes, leading to misreading of the genetic code and cell death.
• Pharmacokinetics:
  • Poorly absorbed from the GI tract, but rapidly absorbed after IM injection, reaching peak level within 1 hour.
  • Widely distributed throughout the body, cross the placenta, and enter human milk.
  • Excreted unchanged in the urine.
• Contraindications and cautions:
  • Known allergy to any aminoglycosides, renal disease, preexisting hearing loss, myasthenia gravis, or parkinsonism.
  • Use caution during pregnancy; use lower doses with patient who have renal impairment.
  • Risk for nephrotoxicity and ototoxicity.
• Adverse effects (Serious and limit usefulness):
  • CNS effects
  • Renal toxicity
  • GI effects
  • Cardiac effects
  • Hypersensitivity reactions
• Drug–drug interactions:
  • Synergistic bactericidal effect with penicillins or cephalosporins.
  • Use caution with nephrotoxic medications.
  • Increased neuromuscular blockade with certain drugs.

Carbapenems

• Broad-spectrum antibiotics effective against gram-positive and gram-negative bacteria.
• Common medications:
  • Doripenem (Doribax)
  • Ertapenem (Invanz)
  • Imipenem–cilastatin (Primaxin)
  • Imipenem–cilastatin–relebactam (Recarbrio)
  • Meropenem (Merrem IV)
  • Meropenem–vaborbactam (Vabomere)
• Bactericidal.
• Actions:
  • Inhibit cell membrane synthesis, leading to cell death.
• Indications:
  • Treatment of serious infections caused by susceptible bacteria.
  • Treatment of serious intra-abdominal, urinary tract, skin and skin structure, bone and joint, and gynecological infections.
• Pharmacokinetics:
  • Rapidly absorbed if given IM and reach peak level at the end of the infusion if given IV.
  • Widely distributed throughout the body.
  • Ability to cross the placenta or to enter human milk varies by drug.
  • Excreted unchanged in the urine.
  • Average half-life of 1 to 4 hours.
• Contraindications and cautions:
  • Known allergy to any of the carbapenems or beta-lactams.
  • Use caution during pregnancy and lactation.
  • Test renal function regularly.
• Adverse effects:
  • GI tract effects
  • Superinfections
  • CNS effects
• Drug–drug interactions:
  • Consider alternative if patient is taking valproic acid.
  • Avoid concurrent use of imipenem with ganciclovir.

Cephalosporins

• Similar to the penicillins in structure and activity.
• Common medications:
  • First generation: cefazolin (generic), cefadroxil (generic), cephalexin (Keflex)
  • Second: cefaclor (Ceclor), cefotetan (generic), cefoxitin (generic), cefprozil (generic), cefuroxime (Zinacef)
  • Third: cefdinir (Omnicef), cefotaxime (Claforan), cefpodoxime (generic), ceftazidime (Ceptaz, Tazicef), ceftriaxone (Rocephin)
  • Fourth and other: cefepime (Maxipime), cefiderocol (Fetroja), ceftaroline (Teflaro), ceftazidime–avibactam (Avycaz), ceftolozane–tazobactam (Zerbaxa)
• Bactericidal and bacteriostatic depending on dose and specific drug.
• Action:
  • Interfere with the cell wall–building ability of bacteria when they divide.
• Indications:
  • Treatment of infections caused by susceptible bacteria.
• Pharmacokinetics:
  • Primarily excreted unchanged in the urine.
  • Eliminated primarily by the liver.
  • Cross the placenta and enter human milk.
• Contraindications and cautions:
  • Allergies to cephalosporins or penicillins.
  • Hepatic or renal impairment.
  • Pregnancy or lactation.
  • Reserve for appropriate situations due to resistance.
• Adverse effects:
  • GI tract most common
  • CNS symptoms
  • Nephrotoxicity
  • Superinfections
• Drug–drug interactions:
  • Increased nephrotoxicity risk with concurrent administration with aminoglycosides.
  • Increased bleeding possible with warfarin.

Fluoroquinolones

• Synthetic class of antibiotics with a broad spectrum of activity.
• Common medications:
  • Ciprofloxacin (Cipro)
  • Delafloxacin (Baxdela)
  • Levofloxacin (Levaquin)
  • Moxifloxacin (Avelox)
  • Ofloxacin (generic)
• Bactericidal.
• Actions:
  • Enter bacterial cell by passive diffusion.
  • Interfere with action of DNA enzymes, leading to cell death.
• Indications:
  • Treating infections caused by susceptible strains of gram-positive and gram-negative bacteria.
  • Urinary tract, respiratory tract, skin infections.
  • Some prevent or treat postexposure of anthrax infection.
• Pharmacokinetics:
  • Absorbed from the GI tract.
  • Metabolized in the liver.
  • Excreted in urine and feces.
  • Widely distributed in the body; cross the placenta and enter human milk.
• Contraindications and cautions:
  • Some have warnings related to potential serious adverse effects.
  • Known allergy to any fluoroquinolone.
  • Not recommended for use in pregnant or lactating patients except in specific circumstances.
  • Renal dysfunction.
  • Associated with damage to developing cartilage.
• Adverse effects:
  • Most serious: tendinitis, tendon rupture, peripheral neuropathy, CNS effects, prolonged QT interval, C. difficile diarrhea, liver toxicity.
  • Common: headache, dizziness, insomnia, depression.
  • GI and immunological effects.
• Drug–drug interactions:
  • Therapeutic effect decreased with iron salts, sucralfate, multivitamins, calcium or magnesium supplements, antacids.
  • Drugs that increase QTc interval; warfarin, NSAIDs.

Penicillins and Penicillinase-Resistant Antibiotics

• First antibiotic introduced for clinical use.
• Natural penicillins:
  • Penicillin G benzathine (Bicillin L.A., Permapen)
  • Penicillin G potassium (Pfizerpen)
  • Penicillin G procaine
  • Penicillin V (Penicillin-VK)
• Aminopenicillins:
  • Amoxicillin (Amoxil)
  • Ampicillin (generic)
  • Combination medications
• Bactericidal.
• Action:
  • Interfere with the ability of susceptible bacteria to build their cell walls.
• Indications:
  • Treatment of streptococcal infections, pneumococcal infections, staphylococcal infections, etc.
  • Antipseudomonal penicillins have widest spectrum.
• Pharmacokinetics:
  • Rapidly absorbed from the GI tract.
  • Excreted unchanged in the urine.
  • Enter human milk.
• Contraindications and cautions:
  • Allergies to penicillin or other allergens.
  • Renal disease.
  • Patients who are pregnant or lactating.
• Adverse effects:
  • GI tract
  • Superinfections
• Drug–drug interactions:
  • Parenteral aminoglycosides

Sulfonamides

• Drugs that inhibit folic acid synthesis.
• Medications:
  • sulfadiazine (generic)
  • cotrimoxazole or trimethoprim–sulfamethoxazole (Septra, Bactrim)
• Bacteriostatic.
• Action:
  • Block para-aminobenzoic acid to prevent synthesis of folic acid in susceptible bacteria.
• Indications:
  • Treatment of infections caused by gram-negative and gram-positive bacteria.
  • Inexpensive and effective treatment for UTIs and trachoma.
• Pharmacokinetics:
  • Teratogenic
  • Distributed into human milk
  • Absorbed from the GI tract
  • Metabolized in the liver
  • Excreted in the urine
• Contraindications and cautions:
  • Known allergy to any sulfonamide or to thiazide or loop diuretics.
  • Pregnancy and lactation.
  • Renal disease or history of kidney stones.
  • Older adults.
• Adverse effects:
  • GI effects
  • Renal effects
  • CNS effects
  • Bone marrow depression
  • Dermatological effects
• Drug–drug interactions:
  • Antidiabetic agents
  • Medications that increase hyperkalemia risk
  • Cyclosporine

Tetracyclines

• Developed as semisynthetic antibiotics based on the structure of a common soil mold.
• Most common medications:
  • Tetracycline (generic)
  • Demeclocycline (generic)
  • Doxycycline (Doryx, Acticlate)
  • Eravacycline (Xerava)
  • Omadacycline (Nuzyra)
  • Minocycline (Arestin, Minocin)
  • Sarecycline (Seysara)
• Bacteriostatic.
• Action:
  • Inhibit protein synthesis in a wide range of bacteria, leading to the inability of bacteria to multiply
  • Toxic to humans at high concentrations.
• Indications:
  • Treatment of various infections caused by susceptible strains of bacteria.
  • Infections when penicillin is contraindicated.
• Pharmacokinetics:
  • Absorbed adequately from the GI tract.
  • Concentrated in the liver, excreted unchanged in the urine.
  • Cross the placenta and pass into human milk.
• Contraindications and cautions:
  • Known allergy to tetracyclines.
  • Pregnancy and lactation.
  • Children younger than 8 years.
• Adverse effects:
  • GI tract
  • Skeletal effects
  • Superinfections
  • Local effects
• Drug–drug interactions
  • Concurrent tetracycline use
  • Oral combinations that decrease absorption
• Drug-food interactions
  • Administer on empty stomach with water

Antimycobacterials

• Mycobacteria include pathogens causing TB and leprosy.
• First-line drugs for treating tuberculosis:
  • Isoniazid (generic), rifampin (Rifadin), pyrazinamide (generic), ethambutol (Myambutol), rifabutin (Mycobutin), rifapentine (Priftin)
• Leprostatic drug:
  • Dapsone (generic)
• Action:
  • Most act on the DNA of the bacteria, leading to a lack of growth and eventual bacterial death.
• Indications:
  • Treatment of TB and leprosy.
• Pharmacokinetics:
  • Generally well absorbed from the GI tract.
  • Metabolized in the liver.
  • Excreted in the urine.
  • Cross the placenta and enter human milk.
• Contraindications and cautions:
  • Known allergy to these agents.
  • Severe renal or hepatic failure.
  • Pregnancy
• Adverse effects:
  • CNS effects
  • GI irritation
• Drug–drug interactions:
  • Combinations that increase risk of hepatotoxicity.
  • Histamine reactions

Other Antibiotics

• Lincosamides:
  • Bacteriostatic
  • clindamycin (Cleocin), lincomycin (Lincocin)
• Lipoglycopeptides:
  • Bactericidal
  • telavancin (Vibativ), dalbavancin (Dalvance), oritavancin (Orbactiv), vancomycin (Vancocin, Firvanq)
• Macrolides:
  • Bactericidal or bacteriostatic
  • erythromycin (Ery-Tab, Eryc), azithromycin (Zithromax), clarithromycin (Biaxin), fidaxomicin (Dificid)
• Oxazolidinones:
  • tedizolid (Sivextro), linezolid (Zyvox)
• Monobactam antibiotic:
  • Bactericidal
  • aztreonam (Azactam)

Miscellaneous Antibiotics

• Daptomycin
• Tigecycline (Tygacil)
• Streptogramins
• Rifaximin (Xifaxan)