ANTIMICROBIALS

Antimicrobial: Any agent that can kill or suppress microorganisms, which include bacteria, fungi, viruses, and protozoa.

Pathogens and Disease

• Pathogens: Microbes that cause disease

  • Bacteria

  • Viruses

  • Fungi

  • Protozoa

  • Fleas and mites

• Pathogenicity: The inherent ability of an organism to cause infection.

• Virulence: The degree to which a pathogen can cause disease, even in small numbers.

How Pathogens Cause Disease

• Invasiveness: Pathogens can grow rapidly, damaging surrounding tissues.

• Toxin Production: Even minimal amounts of toxins can impair normal cellular functions, resulting in damage or cell death.

Bacteria

• Gram Staining:
     - Gram-positive: Retain purple stain due to thick cell wall.
     - Gram-negative: Lose purple stain, indicating a thinner cell wall.

• Shape:
     - Bacilli: Rod-shaped.
     - Cocci: Spherical.
     - Spirilla: Spiral-shaped.

• Oxygen Requirement:
     - Aerobic: Thrives in oxygen-rich environments.
     - Anaerobic: Prefers oxygen-free environments.
     - Facultative: Can function in both oxygen-rich and oxygen-free environments.

Antibiotics

Antibiotics: Chemical substances produced by or derived from microorganisms that can kill or inhibit bacteria.

Classification of Antibiotics

• By Mechanism of Action:

  • Bactericidal: kills bacteria (People Can Vote Against Farts)

    • Cell Wall Weakening: e.g., Penicillins, Cephalosporins.

    • Cell Wall Synthesis Inhibitors: e.g., Vancomycin.

    • Lethal Inhibitors of Protein Synthesis: e.g., Aminoglycosides.

    • Inhibitors of DNA Synthesis: e.g., Fluoroquinolones, Nitroimidazole

  • Bacteriostatic: slows bacterial growth and replication, allowing immune system to eliminate bacteria (Mom Types Really Slow)

    • Nonlethal Inhibitors of Protein Synthesis: e.g., Macrolides, Tetracyclines.

    • Inhibitors of RNA Synthesis: e.g., Rifampin.

    • Antimetabolites: e.g., Sulfonamides.

• By Coverage:

  • Broad Spectrum Antibiotics: Used initially until laboratory results provide information; effective against a variety of pathogens.

  • Narrow Spectrum Antibiotics: Used once specific pathogens are identified; have lesser effects on the normal flora.

Selection of Antibiotics

• Laboratory Tests:
    - Identification of pathogen through samples (urine, stool, blood).
    - Culture and sensitivity testing.
    - Direct antigen detection.

• Prophylactic

  • Broad spectrum to prevent infection (surgery, dental work that carries risk of bacterial endocarditis, neutropenia)

• Empiric

  • Prescribed before C&S, based on clinical evaluation and knowledge of likely pathogens

• Host Factors

  • Immune System: Weakened immunity (e.g. AIDS, immunosuppressive therapy) may necessitate aggressive treatment.

  • Tissue Conditions: Injury or inflammation may impact the efficacy of antibiotics.

  • Blood Brain Barrier and Placental Barrier: Antibiotic choice must consider penetration through barriers.

  • Allergy History: Any past allergic reactions to drugs must be documented.

  • Age Factors: Infants and the elderly may struggle to metabolize and eliminate antibiotics effectively.

  • Dosage Size and Duration: Antibiotics should be present at the infection site for an adequate period; premature discontinuation can lead to treatment failure. Patients must be taught to complete the full prescribed course.

Adverse Effects of Antibiotics

• Superinfections: New infections that develop during treatment for a primary infection. Occurs when antibiotics disrupt normal flora, allowing secondary infections to prosper (e.g., fungal infections).
    - Example: Vaginal Candida infection can arise in females treated with broad-spectrum antibiotics for urinary tract infection.

• Opportunistic Infections: Happen when the immune system is suppressed.

Special Considerations in Antibiotic Use

• Pregnancy: Certain antibiotics like Tetracyclines can harm the fetus, leading to teeth discoloration and impaired bone growth.

• Genetics: Some individuals may lack enzymes (e.g., G6PD) necessary to process specific drugs (e.g., sulfonamides can cause hemolysis in these individuals).

• Breastfeeding: Some antibiotics can affect infant hearing (e.g., Aminoglycosides).

Antibiotic Combinations

• Effects of Combination Therapy: Can be additive, potentiative, or antagonistic.

• Indications for Combination: Utilized for mixed infections, preventing resistance, minimizing toxicity, and enhancing bacterial action.

• Disadvantages: Resistance to antibiotics can develop.

Monitoring of Antimicrobial Therapy

• Monitor clinical responses and laboratory results, including CBC, CRP (C-Reactive Protein), and ESR (Erythrocyte Sedimentation Rate).

• Increase the frequency of monitoring with the severity of the infection.

• Assess serum drug levels for toxicity, specifically peak and trough levels.

• Evaluate clinical indicators of success: reduction of fever, alleviation of related symptoms, and normalization of lab test results.

Peak and Trough Levels for Antibiotics

• Peak Level: The highest concentration of a drug measured shortly after administration (typically 30–60 minutes post-dose) to ensure therapeutic levels.

• Trough Level: The lowest concentration of a drug before the next dose, ensuring that levels stay above the minimum effective threshold and averting toxicity.

• Common Antibiotics Requiring Monitoring:
    - Vancomycin (to prevent nephrotoxicity and ototoxicity).
    - Aminoglycosides (e.g., Gentamicin, Tobramycin, Amikacin).

Bactericidal

Cell Wall Weakening

Penicillins

• The first mass-produced antibiotic, isolated from the Penicillium fungus in 1941.

• Primarily targets gram-positive organisms (e.g., Streptococci, Staphylococci) and some gram-negatives (e.g., Amoxicillin).

• Mechanism of Action: Binds to penicillin-binding proteins (PBPs), disrupting cell wall structure and causing water influx, leading to cell lysis.

• Key Component: Beta-lactam ring

• Common Infections Treated with Penicillin

  • Strep throat

  • Syphilis

  • Ear infections (otitis media)

  • Meningitis

  • Pneumonia

  • Skin infections

  • Gonorrhea

  • Dental abscesses

• Nursing Implications

  • Administration: Via IV or IM route (oral absorption is limited).

    • May cause GI upset and nausea; if PO take with food depending on form

  • Contraindications: Hypersensitivity to penicillin or related drugs; caution required for those with renal disease.

  • Resistance: Some bacteria produce beta-lactamase or penicillinase, which breaks the beta-lactam ring, conferring resistance.

  • Allergy

    • Types of Reactions:
        - Immediate: 2 to 30 minutes post-exposure.
        - Accelerated: 1 to 72 hours post-exposure.
        - Delayed: Days to weeks post-exposure.

    • Considerations:
        - Monitor for: Anaphylaxis, laryngeal edema, bronchoconstriction, severe hypotension, rash, hives
        - Treatment: Epinephrine, respiratory support as necessary; consider skin testing prior to administration, especially in those with a history of mild reactions.

    • Cross-Sensitivity: Patients allergic to penicillin may react to cephalosporins.

  • Superinfection (C. Diff, oral thrush, vaginal yeast infection)

Cephalosporins

• Cefazolin, Cefepime, Cefotaxime, and Cephalexin.

• Mechanism of Action: inhibit cell wall synthesis and cause cell lysis; categorized as beta-lactam antibiotics.

• Generational Resistance: First-generation agents are more susceptible to beta-lactamases; subsequent generations demonstrate increased resistance.

  • First Generation: Cephazolin is commonly used for surgical prophylaxis; rarely indicated for active infections.

  • Second Generation: Rarely used for active infection.

  • Third Generation: Cetriaxone preferred for various infections; penetrates the blood-brain barrier effectively.

  • Fourth Generation: Cefepime commonly treats pneumonia and resistant organisms like Pseudomonas.

  • Fifth Generation: Ceftaroline addresses methicillin-resistant Staphylococcus aureus (MRSA).

• Monitoring:

  • Creatinine/BUN due to potential nephrotoxicity

  • Avoid ethanol during treatment and up to 72 hours post-treatment to preclude disulfiram-like reactions.

  • C. difficile infections characterized by watery diarrhea and fever.

  • Hypersensitivity reactions, particularly for those with a penicillin allergy

  • Observe for bleeding risk

Cell Wall Synthesis Inhibitors

Carbapenems

• Imipenem, Meropenem, Ertapenem, and Cilastatin.

• Mechanism of Action: Inhibit cell wall synthesis

• Broad-spectrum activity against gram-positive, gram-negative pathogens, and anaerobes.

• Adverse Effects: May lower platelet counts and can cause drug fever.

• Common Uses: Meningitis, intra-abdominal infections, and other severe infections.

Vancomycin

• Classification: Glycopeptide antibiotic effective against gram-positive organisms, including resistant strains.

• Mechanism of Action: Inhibits bacterial cell wall synthesis, demonstrating a bactericidal effect.

• Administration: IV (administered over 60 mins); PO form is prescribed for C. difficile as it is not absorbed into the bloodstream.

• Adverse Effects:

  • Ototoxicity (which may be permanent)

  • Nephrotoxicity

  • “Red man” syndrome

  • Thrombophlebitis

  • Allergic rash.

• Nursing Implications

  • Trough Levels: Monitor to ensure levels remain between 10–20 mcg/mL to reduce risk of toxicity.

  • Administration Tips: Infusion should be slow to prevent infusion-related reactions.

  • Adverse Effects Monitoring:

    • Check BUN and creatinine (nephrotoxicity)

    • Watch for changes in hearing (ototoxic)

    • Warning signs of C. difficile

Inhibitors of Protein Synthesis

Aminoglycosides

• Gentamicin, Neomycin, Amikacin, Tobramycin.

• Mechanism of Action: inhibit protein synthesis and cause production of faulty proteins (bactericidal)

• Narrow-spectrum

• Target aerobic gram-negative microorganisms

• Adverse Effects:

  • Nephrotoxicity

  • Ototoxicity

  • Neuro-muscular blockade.

• Nursing Considerations:

  • Serum peak and trough levels

  • Renal function

  • Effectiveness through WBC counts and fever reduction.

Inhibitors of DNA Synthesis

Fluoroquinolones

• Effective against a wide range of bacteria, primarily gram-negative pathogens.

• Mechanism of Action: Inhibit bacterial DNA replication and division.

• Adverse Effects: Tendonitis and potential for tendon rupture, particularly in older adults or those on corticosteroids.

Metronidazole (Flagyl)

• Effective against anaerobic bacteria and certain protozoal infections.

• Mechanism of Action: Damages DNA and halts protein synthesis in microbes.

• Adverse Effects: Nausea, metallic taste, peripheral neuropathy.

Bacteriostatic

Tetracyclines

• Includes: Tetracycline, Demeclocycline, Doxycycline, Minocycline.

• Mechanism of Action: Inhibit bacterial protein synthesis by binding to 30S ribosomal subunits, exerting bacteriostatic effects.

• Usage: Effective for infections like acne, STIs (Chlamydia, Syphilis), Lyme disease.

• Adverse Effects: Gastrointestinal irritation, tooth discoloration, superinfections, hepatotoxicity, and photosensitivity.

Macrolides

• Includes: Erythromycin.

• Mechanism of Action: Inhibit protein synthesis; mainly bacteriostatic.

• Therapeutic Uses: Effective against whooping cough, chlamydial infections, and as alternatives for penicillin-allergic patients.

• Adverse Effects: Gastrointestinal effects, QT prolongation.

Clindamycin

• Similar to macrolides in terms of action, effective against anaerobes.

• Serious Adverse Effects: Risk of pseudomembranous colitis due to C. difficile.

Sulfonamides and Trimethoprim

• Broad-spectrum agents targeting gram-positive and gram-negative bacteria.

• Mechanism of Action: Inhibit folic acid synthesis, displaying bacteriostatic properties.

• Adverse Effects: Hypersensitivity reactions, hematologic effects, renal damage from crystalluria.

RNA Synthesis Inhibitors

• Includes Rifaximin, Rifapentine, Rifampicin.

• Mechanism of Action: Inhibit RNA polymerase, impacting RNA synthesis.

Antifungal Agents

• Classes: Polyenes, Azoles, Echinocandins, etc.

Polyenes (Amphotericin B)

• Mechanism: Binds fungal membranes, resulting in electrolyte leakage and cell death.

• Nursing Considerations: Monitor renal function, electrolyte balance, and for infusion-related reactions.

Azoles (Fluconazole)

• Mechanism: Inhibit ergosterol synthesis in fungi.

• Clinical Uses: Effective for various candidiasis and cryptococcal meningitis.

Antiviral Agents

• Development Challenges: Viral reliance on host cells complicates the creation of effective antiviral agents.

• Drugs: Includes Amantadine (Influenza), Acyclovir (Herpes simplex), Ganciclovir (CMV).