Pharm 4.2

OBJECTIVE 4.2: ANTIBIOTICS, ANTIVIRALS & ANTIFUNGALS

BACTERIA

• Gram Staining: A method used to categorize bacteria and aid in determining appropriate antibiotic treatment.
  • Gram-positive bacteria: Turn purple when stained.
  • Gram-negative bacteria: Turn red when stained.

TYPES OF INFECTIONS

• Community-acquired infections:

  • Definition: Infections acquired by individuals who have not been hospitalized or undergone medical procedures in the past year.

• Health care-associated infections:

  • Definition: Infections contracted in a health care facility, which were not present or incubating upon admission.
  • Occur more than 48 hours after admission.
  • Considered one of the top 10 causes of death in Canada.
  • Treatment is complicated due to drug resistance and virulence.
  • Examples include:
    • Methicillin-resistant Staphylococcus aureus (MRSA) (most common).
    • Vancomycin-resistant Enterococcus (VRE, previously known as a nosocomial infection).

GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA

• Importance of Cultures:
  • Cultures must be taken from appropriate sites before starting antibiotic therapy.
  • Sent to labs for culture and sensitivity (C&S) studies to guide therapy.

ANTIBIOTIC THERAPY

• Types of Antibiotic Therapy:

  • Empiric therapy: Treatment given before specific culture information is available.
  • Definitive therapy: Tailored antibiotic therapy based on cultured organism results.
  • Prophylactic therapy: Antibiotics used to prevent infection (e.g., in surgery or trauma cases).

• Therapeutic Response:

  • Observed as a decrease in signs and symptoms (e.g., fever, increased WBCs, pain).

• Subtherapeutic Response:

  • No improvement in signs and symptoms.

ANTIBIOTIC THERAPY CONSIDERATIONS

• Concerns:

  • Pseudomembranous colitis associated with Clostridium difficile.
  • Risk of superinfection and secondary infections.
  • Development of drug resistance.
  • Considerations of food-drug interactions.
  • Factors such as age, pregnancy, liver and kidney function, genetics, and allergies impact therapy.

• Allergic Reactions:

  • Common allergies involve penicillins and sulfonamides, which can lead to severe reactions (e.g., anaphylaxis, breathing difficulties, severe rash).

CLASSES OF ANTIBIOTICS

• Major Classes:
  • Sulfonamides
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Macrolides
  • Quinolones
  • Aminoglycosides
  • Tetracyclines

MECHANISM OF ACTION

• Antibiotics work through different mechanisms:
  • Interfering with cell wall synthesis.
  • Interfering with protein synthesis.
  • Interfering with DNA replication.
  • Acting as metabolites to disrupt bacterial metabolism.

ACTIONS OF ANTIBIOTICS

• Bactericidal: Kill bacteria.
• Bacteriostatic: Inhibit the growth of bacteria, leading to eventual death.

SULFONAMIDES

• Characteristics:

  • One of the first antibiotics, often combined with other drugs (e.g., sulfamethoxazole with trimethoprim).

• Mechanism of Action:

  • Bacteriostatic; inhibits folic acid synthesis in bacteria, crucial for their growth and function without affecting human cells.

• Efficacy:

  • Effective against gram-positive and gram-negative bacteria.
  • Indications for use: urinary tract infections, certain pneumonias, upper respiratory infections, outpatient Staphylococcus infections linked to MRSA.

• Nursing Implications:

  • Hydration: Patients should consume 2,000 to 3,000 mL of fluid daily.
  • Administer orally with food.
  • Instruct patients to report adverse effects: abdominal pain, diarrhea, hematuria, rash, respiratory difficulty.

ß-LACTAM ANTIBIOTICS

• Classes Include:
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams

PENICILLINS

• Types:

  • Natural Penicillins: Penicillin G, Penicillin V
  • Aminopenicillins: Amoxicillin, Ampicillin
  • Extended-spectrum: Pipercillin, Ticarcillin
  • Penicillinase-resistant: Cloxacillin.

• Mechanism of Action:

  • Enter bacteria, bind to penicillin-binding proteins disrupting cell wall synthesis leading to cell lysis.

• Indications:

  • Treat infections caused by susceptible bacteria (mainly gram-positive).

• Contraindications and Concerns:

  • Generally well-tolerated, but allergic reactions can occur (0.7% to 4%), leading to urticaria, pruritus, angioedema.
  • History of throat swelling or hives from penicillin precludes cephalosporins.

• Common Adverse Effects:

  • Nausea, vomiting, diarrhea, abdominal pain.

• Drug Interactions:

  • Interactions with NSAIDs, oral contraceptives (which may decrease contraceptive effectiveness), warfarin (increased effect), and tetracyclines (decrease penicillin effectiveness).

• Nursing Implications:

  • Oral doses should be taken with water, not juice.
  • Monitor for allergic reactions post-administration.

CEPHALOSPORINS

• Characteristics:

  • Semisynthetic antibiotics, similar to penicillins, with broad spectrum of activity.

• Generations:

  • Divided into first, second, third, fourth, and fifth generations (the fifth not available in Canada).

• Mechanism of Action:

  • Interfere with bacterial cell wall synthesis, leading to cell lysis.

• Adverse Effects:

  • Generally similar to those of penicillins; mild diarrhea, rash, concern for cross-sensitivity in penicillin-allergic patients.

• Nursing Implications:

  • Assess for penicillin allergy and administer with food to mitigate GI upset.

MACROLIDES

• Examples:

  • Erythromycin, azithromycin, clarithromycin.

• Mechanism of Action:

  • Prevent protein synthesis within bacterial cells; generally bacteriostatic but can be bactericidal at high concentrations.

• Indications:

  • Treat strep infections, pneumonia, syphilis, gonorrhea, chlamydia, and others.

• Adverse Effects:

  • GI effects are common, especially with erythromycin; hepatotoxicity possible; better safety profile for azithromycin and clarithromycin.

• Nursing Implications:

  • Monitor interactions due to high protein binding.
  • Administer oral erythromycin on an empty stomach to enhance absorption while being cautious about GI upset.

TETRACYCLINES

• Examples:

  • Doxycycline, minocycline, tigecycline.

• Mechanism of Action:

  • Bacteriostatic, inhibit protein synthesis, disrupt essential bacterial functions.

• Indications:

  • Broad-spectrum, effective against various organisms including some gram-negative, protozoa, Rickettsia, and others.

• Adverse Effects:

  • Not recommended for children under 8 years and pregnant women due to risks of tooth discoloration; may also cause gastric upset and alteration of intestinal flora.

• Nursing Implications:

  • Avoid dairy products, iron preparations, and antacids that bind with the drug.
  • Take with sufficient fluids, and avoid sun exposure due to photosensitivity.

MULTIDRUG-RESISTANT ORGANISMS (MDROs)

• Definition: Organisms resistant to one or more classes of antimicrobial drugs.

  • Notable examples include MRSA, VRE, ESBL producers, and KPC producers.

• MRSA:

  • Not confined to hospitals; significant prevalence in community-acquired infections.

• VRE:

  • Often linked with UTIs.
  • Development of new antibiotics targeting resistant strains.

AMINOGLYCOSIDES

• Examples:

  • Gentamicin, streptomycin, tobramycin, amikacin.

• Mechanism of Action:

  • Bactericidal; prevent protein synthesis, primarily effective against gram-negative bacteria; usually given parenterally due to poor oral absorption.

• Indications:

  • Effective against gram-negative infections, used synergistically for resistant gram-positive infections.

• Adverse Effects:

  • Nephrotoxicity and ototoxicity are serious concerns. Requires monitoring of drug levels to avoid toxicity.

• Therapeutic Drug Monitoring:

  • Monitor peak and trough serum levels to manage toxicity risks.

QUINOLONES

• Examples:

  • Ciprofloxacin, norfloxacin, levofloxacin, moxifloxacin.

• Mechanism of Action:

  • Bactericidal; alter bacterial DNA preventing reproduction.

• Indications:

  • Treats infections from both gram-negative and gram-positive organisms, including complicated UTIs and respiratory infections.

• Interactions:

  • Avoid antacids, calcium, magnesium, iron, and zinc preparations as they interfere with absorption; timing of medications is critical.

MISCELLANEOUS ANTIBIOTICS

• Examples:

  • Clindamycin, linezolid, metronidazole, nitrofurantoin, vancomycin.

• Clindamycin:

  • Used for severe infections, associated with risk of pseudomembranous colitis.

• Metronidazole:

  • Effective for anaerobes and protozoal infections; alcohol must be avoided during treatment.

• Nitrofurantoin:

  • Primarily for UTIs; caution in those with impaired renal function.

• Vancomycin:

  • Treatment of choice for MRSA; requires monitoring for therapeutic drug levels, risks of ototoxicity and nephrotoxicity, and may cause red man syndrome if infused too quickly.

ANTITUBERCULAR DRUGS

• Tuberculosis (TB):

  • Caused by Mycobacterium tuberculosis, characterized by granulomas primarily in the lungs.

• Transmission:

  • Spread through droplets expelled when coughing or sneezing.

• Treatment:

  • First-line drugs include isoniazid, rifampin, ethambutol, and pyrazinamide; second-line drugs include amikacin and levofloxacin.

• Therapeutic Effectiveness:

  • Depends on proper dosing, duration, adherence to the regimen, and effective drug combinations.

GENERAL PRINCIPLES OF VIROLOGY

• Viral Replication:

  • Viruses cannot replicate independently; they hijack host cells for reproduction, utilizing their mechanisms to synthesize essential components.

• Viral Illnesses Examples:

  • Smallpox, influenza, HIV/AIDS, herpes, and hepatitis infections.

• Antiviral Drugs:

  • Reduce virus virulence and replication ability; include drugs for CMV, hepatitis viruses, herpes viruses, and influenza.

• Key Characteristics:

  • Effectiveness is higher in patients with competent immune systems, as antiviral drugs work best when the immune system is robust.

OPPORTUNISTIC INFECTIONS

• Occur in immunocompromised patients, requiring comprehensive prophylaxis and therapeutic approaches.