Antimicrobials

Drugs for Treating Infections

Terminology

  • Antimicrobial

    • Definition: Any drug used to treat any organism.

    • Categories: Includes antibacterials, antifungals, and antivirals.

Microorganisms

  • Bacteria

    • Characteristics: Single cell with a rigid outer cell wall in addition to the cell membrane.

    • Treatment Strategy: Exploit differences between bacterial and human cells for treatment.

  • Fungi

  • Viruses

Classification of Antimicrobials

  • Classification by Susceptible Organism

    • Narrow Spectrum: Effective against a limited range of organisms.

    • Broad Spectrum: Effective against a wide range of organisms.

    • Types of Antimicrobials:

    • Antibiotics

    • Antifungals

    • Antivirals

Selection of Antimicrobial

  • Factors to Consider:

    • Identity of Microorganism: Confirm the specific microbe causing infection or rely on probable cause.

    • Site of Infection: Drug must penetrate to the site of infection to be effective.

    • Patient-Specific Factors:

    • Immune system function

    • Health conditions

    • Age

    • Pregnancy and lactation status

    • Allergies

Gram + vs. Gram - Bacteria

  • Gram Positive Characteristics:

    • Structure:

    • Plasma membrane

    • Peptidoglycan layer

  • Gram Negative Characteristics:

    • Structure:

    • Plasma membrane, thin peptidoglycan layer

    • Outer membrane containing lipopolysaccharide and protein

First Classification of Antibiotics

  • Bactericidal vs. Bacteriostatic:

    • Bactericidal Action: Antibiotics directly kill bacteria during treatment.

    • Bacteriostatic Action: Antibiotics inhibit bacterial growth; bacteria die naturally after their normal life span.

    • Summary of Actions:

    • No Antibiotic → Normal bacterial growth

    • Administration of Bactericidal Antibiotic → Direct killing of bacteria

    • Administration of Bacteriostatic Antibiotic → Inhibited growth keeps bacteria alive until the drug is discontinued; eventually leads to bacterial death.

Second Classification of Antibiotics

  • Mechanism of Action:

    • Cell Wall Synthesis Inhibitors:

    • Penicillins

    • Cephalosporins

    • Protein Synthesis Inhibitors:

    • Macrolides

    • Tetracyclines

Third Classification of Antibiotics

  • Chemical Structure:

    • Penicillins

    • Sulfonamides

    • Others

Antibiotic Drugs

Beta-Lactam Antibiotics

  • Includes:

    • Penicillins

    • Cephalosporins

  • Action: Inhibit bacterial cell wall synthesis.

  • Classification: Bactericidal.

Penicillins

  • Impact: Over 200 million lives saved; significantly changed the course of modern medicine.

  • Therapeutic Uses:

    • More effective against Gram+ than Gram-.

    • Variety of infections treated: UTI’s, RTI’s, Otitis, Syphilis, Endocarditis.

Penicillin Examples

  • Drug Name & Spectrum:

    • Penicillin G: Spectrum - sensitive, narrow.

    • Amoxicillin: Spectrum - sensitive, broad.

    • Amoxicillin/Clavulanate: Spectrum - resistant, broad.

    • Ticarcillin: Spectrum - sensitive, extended.

Penicillins Specifics

  • Penicillin G:

    • Natural penicillin.

    • Unstable in stomach acid; better absorbed on an empty stomach.

    • Narrow spectrum and inactivated by penicillinase.

    • Dosage measured in units.

    • PenVK: Created synthetically in 1941.

Penicillins Adverse Effects

  • Allergic reactions occur in about 1-2% of the population.

  • Symptoms can range from skin rash to anaphylaxis.

  • Note: Prior penicillin exposure is usually required for reactions to occur.

Cephalosporins

  • Characteristics:

    • Similar structure to penicillins, also contain beta-lactam.

    • Inhibit bacterial cell wall synthesis.

  • Allergies: About 10% of those allergic to penicillin may also experience cross-reactivity (approximately 0.1% to 0.2% of the population).

Cephalosporin Examples

  • Drug Name & Grouping:

    • Cephalexin: First generation, oral (PO).

    • Cefaclor: Second generation, oral (PO).

    • Ceftriaxone: Third generation, parenteral (IM, IV).

    • Cefepime: Fourth generation, parenteral (IM, IV).

Cephalosporins Generational Differences

  • Progression from 1st to 4th Generation:

    • Broader antibacterial spectrum with each generation, starting with effective coverage against Gram+ and gradually adding Gram- coverage.

    • Increased resistance to beta-lactamase.

Cephalosporins Adverse Effects

  • Allergic reactions similar to penicillins.

  • Patients with a history of severe allergic reactions to penicillin should not receive a cephalosporin.

Carbapenems

  • Administration: Parenteral (hospital use only).

  • Characteristics:

    • Broad spectrum beta-lactam antibiotics.

    • Mechanism: Inhibit bacterial cell wall synthesis.

    • Generally well tolerated and bactericidal.

Carbapenem Examples

  • Drug Names:

    • Imipenem (Primaxin)

    • Meropenem (Merrem)

    • Ertapenem (Invanz)

    • Doripenem (Doribax)

Tetracyclines

  • Characteristics:

    • Not beta-lactams; different chemical structure.

    • Inhibit bacterial protein synthesis and are bacteriostatic.

    • Broad spectrum which has declined in use due to resistance and better alternatives.

Tetracycline Examples

  • Drug Name, Lipid Solubility, Half-life, Oral Absorption:

    • Tetracycline: Intermediate, 9 hours, intermediate absorption.

    • Doxycycline: High, 20 hours, high absorption.

    • Minocycline: High, 15 hours, high absorption.

Tetracyclines Therapeutic Uses

  • Indications:

    • Used for certain infectious diseases such as:

    • Rocky Mountain Spotted Fever

    • Lyme disease

    • Pneumonia caused by Mycoplasma pneumoniae

    • Acne (lower daily doses)

    • Peptic ulcer disease (in combination).

Tetracyclines Drug and Food Interactions

  • Interactions:

    • Tetracyclines bind to minerals (positively charged) and should not be taken with dairy products, supplements, laxatives, and antacids.

    • Recommendation: Administer 1 hour before or 2 hours after taking these substances.

Tetracyclines Adverse Effects

  • Risks Include:

    • Tooth discoloration and altered bone development.

    • Not recommended for children under age 8 or pregnant/nursing women.

    • Other effects: Gastrointestinal disturbances and photosensitivity.

Macrolides

  • Mechanism of Action: Inhibit protein synthesis.

  • Spectrum of Activity: Similar to penicillins but varies with each drug.

Macrolides Adverse Effects

  • Common Side Effects: Most commonly gastrointestinal disturbances; can be minimized by taking with food.

  • Examples:

    • Erythromycin

    • Azithromycin (Zithromax, Z-Pak)

    • Clarithromycin (Biaxin, Biaxin XL)

Macrolides Pharmacokinetics of Erythromycin

  • Characteristics:

    • Unstable in gastric acid and incompletely absorbed.

    • Food decreases drug absorption.

    • Can be administered as a prodrug (EES) or with an acid-resistant coating to improve absorption (Erythromycin Base Filmtab).

Sulfonamides

  • Characteristics:

    • Known as "sulfa drugs."

    • Broad spectrum and bacteriostatic.

    • Usage has declined due to resistance and the development of newer antibiotics.

Sulfonamides Types

  • Types of Sulfonamides:

    • Systemic Sulfonamides: Sulfamethoxazole

    • Topical Sulfonamides:

    • Sulfacetamide

    • Silver sulfadiazine

    • Sulfamethoxazole/trimethoprim (Bactrim)

Sulfonamides Mechanism

  • PABA & Pathways:

    • Sulfonamides inhibit the conversion of PABA into dihydrofolate, interrupting the pathway leading to folic acid synthesis.

    • This effectively inhibits the production of tetrahydrofolate needed by humans.

Sulfonamides Uses

  • Common Uses:

    • Urinary tract infections, burns, and eye infections.

  • Adverse Effects:

    • Risks include renal damage, hypersensitivity (about 3% of the population), and increased free concentration of bilirubin.

    • Not recommended for infants, near-term pregnant women, or nursing mothers.

Fluoroquinolones

  • Characteristics:

    • Broad spectrum and bactericidal; inhibit bacterial DNA synthesis.

    • Effective in penetrating many tissues.

Fluoroquinolones Drug Interactions

  • Examples:

    • Certain minerals (calcium, iron, magnesium) reduce absorption and should not be taken simultaneously.

    • Common drugs include:

    • Levofloxacin

    • Ciprofloxacin

    • Ofloxacin

    • Moxifloxacin

Fluoroquinolones Adverse Effects

  • Associated Risks:

    • Tendonitis and tendon rupture, especially in patients over 60 or those taking corticosteroids.

    • Discontinue use if tendonitis occurs.

    • Contraindicated in children under 10 and pregnant women.

    • Other effects: phototoxicity and settling of growth plates.

Clindamycin

  • Mechanism of Action: Inhibits protein synthesis.

  • Pharmacokinetics:

    • Widely concentrated in tissues (including bones) and body fluids.

    • Effective against Gram+ cocci, including penicillin-resistant Staphylococcus and many anaerobes (especially Bacteroides).

    • Ineffective against Gram- aerobes.

Clindamycin Clinical Uses

  • Limited Uses:

    • Risk of pseudomembranous colitis (potentially fatal).

    • Used for anaerobic infections, osteomyelitis, Staphylococcal joint and bone infections, conjunctivitis, diabetic foot infections, and acne (as topical gel/lotion).

  • Adverse Effects:

    • Main side effect: GI disturbances, particularly diarrhea.

    • Other potentials include hepatotoxicity and bone marrow suppression (rare).

Metronidazole (Flagyl)

  • Usage:

    • Effective for certain sexually transmitted diseases (STDs) as well as other systemic infections (e.g., C. diff).

  • Mechanism: Affects DNA function in microorganisms.

  • Adverse Effects:

    • Typically gastrointestinal disturbances such as nausea and vomiting; may cause urine discoloration and a disulfiram reaction.

Aminoglycosides

  • Characteristics:

    • Bactericidal, narrow spectrum antibiotics primarily targeting Gram-negative bacteria.

  • Adverse Effects:

    • Risks include ototoxicity and nephrotoxicity.

    • Required parenteral administration for systemic effect; can be used topically.

Aminoglycosides Examples

  • Drug Names:

    • Streptomycin

    • Gentamicin

    • Tobramycin

    • Amikacin

    • Neomycin (not for parenteral use).

Topical Antibiotics

  • Bacitracin: Bactericidal, inhibits cell wall synthesis; effective against Gram-positive bacteria.

  • Neomycin: Bactericidal aminoglycoside; effective against Gram-negative and some Staphylococcus strains; risk of possible allergies.

  • Polymyxin B: Alters cell membrane structure; effective against Gram-negative bacteria.

Superinfections

  • Definition: Infections that develop during the treatment of an initial infection, allowing resistant microorganisms to cause new infections.

  • Examples: C. diff, candidiasis, UTI.

Resistance

  • Definition: Microorganisms that become less sensitive to previously exposed antimicrobials.

    • Mechanism: Changes in genetic make-up due to spontaneous random mutation and transfer of genetic material.

    • Nosocomial or Hospital-acquired Infections: Major sources of resistant strains.

Resistance and Overuse of Antibiotics

  • Problem: Overuse of antibiotics, particularly broad-spectrum ones, promotes the development of resistant strains.

  • Example: Beta-Lactamase enzyme inhibits the activity of beta-lactam antibiotics.

Antifungal Agents

Systemic Fungal Infections

  • Action Mechanism: Most disrupt fungal cell membrane causing cellular content leakage.

  • Cell Membrane Active Antifungals:

    • Polyene antibiotics:

    • Amphotericin B (especially lipid formulations)

    • Nystatin (topical)

    • Azole antifungals:

    • Ketoconazole

    • Itraconazole

    • Fluconazole

    • Voriconazole

    • Miconazole and Clotrimazole (topicals).

The Azole Antifungals

  • Adverse Effects:

    • Generally well tolerated but may cause gastrointestinal disturbances, headaches, and hepatotoxicity.

Topical Antifungals

  • Drug Names, OTC or Rx, Dosage Form:

    • Miconazole (Monistat): OTC; vaginal suppositories, cream.

    • Tolnaftate (Tinactin): OTC; cream, powder, solution, spray.

    • Butenafine (Mentax): Rx; cream.

Superficial Fungal Infections

  • Tinea Pedis (Athlete’s Foot): Characterized by cracking and itching between toes, treatment usually takes 2 to 6 weeks to resolve and can be treated with OTC products.

  • Tinea Capitis: Affects scalp, more common in children; systemic antifungal therapy for 1 to 3 months is usually required.

  • Tinea Corporis: Occurs on the skin of trunk and limbs; can be treated with topical or systemic antifungals.

  • Tinea Cruris (Jock Itch): Treatment for 1 to 2 weeks for redness and itching in the groin area and inner thigh.

  • Tinea Unguium: Fungal nail infection; may require systemic treatments lasting between 6 weeks to 12 months for effectiveness.

  • Vaginal Candidiasis (Yeast Infection): Treatable with either topical or systemic therapy, typically resolving in 1 to 2 weeks.

  • Oral Candidiasis (Oral Thrush): Yeast infection of the mucous membranes of the mouth, treated with topical therapy lasting 1 to 2 weeks.

Antiviral Agents

Viruses

  • Composition: Contain DNA or RNA within a protein coat.

  • Types:

    • DNA Viruses: E.g., Small pox, chicken pox, shingles, herpes simplex.

    • RNA Viruses: E.g., Common cold, influenza, rabies.

    • Retroviruses: E.g., HIV.

Antiviral Agents Characteristics

  • Properties:

    • Narrow spectrum and mechanism of action varies by agent.

    • Can possess a wide range of adverse effect potentials, including oral, parenteral, and topical therapy forms.

Herpes Simplex and Varicella Zoster Treatment

  • Acyclovir (Zovirax) and Valacyclovir (Valtrex): For herpes simplex (genital herpes, encephalitis) and varicella-zoster (chicken pox, shingles).

  • Famciclovir (Famvir): Topical treatment for herpes simplex keratitis.

  • Other Treatments: Idoxuridine, vidarabine, and trifluridine; Penciclovir for cold sores.

Influenza Treatment

  • Oseltamivir (Tamiflu): For the prevention and treatment of influenza A and B.

Other Antimicrobials

  • Genital Warts:

    • Podofilox (Condylox)

    • Imiquimod (Aldara)

  • Lice:

    • Permethrin (Elimite, Nix)

Role of the Athletic Trainer

  • Education Responsibilities:

    • Promoting appropriate antibiotic use.

    • Ensuring patient compliance with medication regimens.

    • Monitoring for allergic reactions and other adverse effects.

    • Evaluating the overall effectiveness of antibiotic treatments.