Clayton's Basic Pharmacology for Nurses, 19th Edition - Chapter 45: Drugs Used to Treat Infections

Overview of Antimicrobial Agents and Therapy Principles

• Antimicrobial Classification: Defined by the specific type of pathogen targeted and the chemical family to which the drug belongs.

  • Antibacterial Agents: Specifically target bacteria. Key families mentioned include penicillins, tetracyclines, and aminoglycosides.

  • Antifungal Agents: Specifically target fungi. Key families include azoles and polyenes.

  • Antiviral Agents: Specifically target viruses. Examples include acyclovir and oseltamivir.

• Selection Criteria for Antibiotics:

  • Culture & Sensitivity (C&S): Regarded as the "gold standard" for drug selection. It identifies the exact pathogen and determines which medications effectively inhibit its growth.

  • Empirical Treatment: The initiation of therapy based on the organisms most likely to be causing the infection before C&S results are finalized.

  • Prophylactic Use: Preemptive administration to prevent infection in high-risk individuals or scenarios.

  • Toxicity Factors: Selection is guided by individual patient considerations, including renal and hepatic function and known allergies.

Pre-Therapy Nursing Assessment and Monitoring

• Pre-Therapy Assessment Components:

  • Infection History: Documentation of onset, duration, site, and character of symptoms; recent exposures; and prior infections.

  • Medication History: Review of current medications, previous antimicrobial use, and a thorough check for documented drug allergies.

  • Physical Examination: Establishing baseline vital signs and assessing skin integrity, lymph nodes, and indicators of organ function.

  • Psychosocial Assessment: Evaluating the patient's support system, understanding of their diagnosis, and their likely ability to adhere to the prescribed therapy.

• GI Monitoring: The "Big Three":

  • Symptoms: Nausea, vomiting, and diarrhea.

  • Nursing Actions: Distinguish between antibiotic-related and disease-related symptoms. Closely monitor hydration status. Report persistent diarrhea or abdominal pain, as these may indicate $Clostridioides \, difficile$ ($C. \, diff$) or pseudomembranous colitis.

  • Secondary Infections: Monitor for symptoms such as oral lesions or vaginal/anal itching, which indicate opportunistic infections.

• Allergic Reactions and Anaphylaxis:

  • Timeline: Onset can occur within $30 \, \text{minutes}$ of administration or manifest days into the treatment course.

  • Signs and Symptoms: Laryngeal edema, shock, dyspnea, urticaria (hives), skin rash, and angioedema.

  • High-Risk Observations: Patients with asthma, rhinitis, polypharmacy, or prior allergy histories must be observed for $20\text{--}30 \, \text{minutes}$ post-administration.

Serious Adverse Effects and Organ Toxicities

• Nephrotoxicity:

  • Indicators: Elevated Blood Urea Nitrogen (BUN) and creatinine levels, decreasing urine output, and changes in urinalysis.

  • Nursing Interventions: Monitor Intake & Output (I&O); report urine output less than $30 \, \text{mL/hr}$; maintain aggressive hydration.

• Hepatotoxicity:

  • Indicators: Elevation in liver function tests (LFTs), jaundice, anorexia, nausea, vomiting, or right upper quadrant (RUQ) discomfort.

  • Risk Factors: Preexisting hepatic disease increases susceptibility.

• Ototoxicity:

  • Source: Damage to the 8th cranial nerve (CN VIII).

  • Signs: Tinnitus (ringing in ears), dizziness (vertigo), or hearing loss. Report these symptoms immediately.

• Blood Dyscrasias:

  • Indicators: Sore throat, fatigue, fever, petechiae, and bruising.

  • Nursing Intervention: Monitor the Complete Blood Count (CBC) and report any hemorrhaging in the skin.

• Photosensitivity: Patients must be instructed to wear broad-spectrum sunscreen and avoid prolonged UV exposure to prevent skin damage.

Safe Administration and Implementation

• Allergy Verification: Confirm and document allergy history prior to the first dose.

• Schedule Adherence: Maintain consistent dosing intervals to ensure therapeutic drug levels remain stable in the blood.

• Food Considerations: Clarify if the drug requires an empty stomach; if GI distress occurs, determine if taking with food is permissible.

• IV Site Monitoring: Inspect specifically for signs of phlebitis, infiltration, or redness.

• Infection Precautions: Use standard precautions always; apply transmission-based precautions as specific infections dictate.

Detailed Review of Antibiotic Classes

• Aminoglycosides:

  • Action: Inhibit protein synthesis at the $30S$ ribosomal subunit.

  • Uses: Severe gram-negative infections (meningitis, UTIs, wound infections, septicemia).

  • Toxicity: High risk for ototoxicity and nephrotoxicity.

  • Caution: Do not administer within $72 \, \text{hours}$ of skeletal muscle relaxants used in anesthesia.

• Carbapenems:

  • Action: Inhibit bacterial cell wall synthesis; resistant to beta-lactamase enzymes.

  • Uses: Severe infections caused by multidrug-resistant organisms (MDROs).

  • Serious Effects: Hypersensitivity, bloody diarrhea, and CNS effects (dizziness, confusion, seizures).

• Cephalosporins:

  • Action: Structurally related to penicillins; inhibit cell wall synthesis.

  • Spectrum: Organized into generations; higher generations offer better gram-negative coverage.

  • Specific Agent: Ceftaroline is noted for activity against MRSA and VRSA.

  • Risk: Hypoprothrombinemia (bleeding risk), hepatotoxicity, and secondary infections.

• Glycopeptides (e.g., Vancomycin):

  • Action: Prevent bacterial cell wall synthesis.

  • Uses: Agents include vancomycin, dalbavancin, oritavancin, and telavancin.

  • Serious Effects: Ototoxicity, nephrotoxicity, $QT_{interval}$ prolongation, and coagulation abnormalities.

• Glycylcyclines (Tigecycline):

  • Action: Bacteriostatic; binds to the $30S$ ribosomal subunit.

  • Uses: Broad-spectrum, including MRSA and anaerobic organisms.

• Macrolides:

  • Action: Inhibit protein synthesis; can be bacteriostatic or bactericidal.

  • Uses: Alternative for penicillin-allergic patients; respiratory, GI, and soft-tissue infections.

• Oxazolidinones (Linezolid):

  • Action: Inhibits protein synthesis at the $50S$ ribosome.

  • Serious Effects: Bone marrow suppression, lactic acidosis, seizures, and visual neuropathy.

• Penicillins:

  • Action: Inhibit cell wall synthesis.

  • Risks: Electrolyte imbalances (hyperkalemia or hypernatremia) and hepatotoxicity.

• Quinolones / Fluoroquinolones:

  • Action: Inhibit DNA gyrase, preventing DNA replication.

  • Contraindications: Avoid in patients under $18 \, \text{years}$ old (cartilage development) and pregnant patients (teratogenic).

  • High-Risk Groups: Patients over $60 \, \text{years}$ old on corticosteroids have a significantly elevated risk of tendon rupture.

  • CNS Warnings: Risk for confusion and seizures.

• Streptogramins (Quinupristin-Dalfopristin):

  • Use: Vancomycin-resistant $E. \, faecium$ (VRE) and MRSA.

  • Common Effects: Infusion site pain and arthralgia/myalgia.

• Sulfonamides:

  • Action: Bacteriostatic; inhibit folic acid biosynthesis.

  • Risks: Crystal formation in the urinary tract (hydration is critical) and hematologic reactions.

• Tetracyclines:

  • Interaction: Reduces the effectiveness of oral contraceptives.

  • Serious Effect: Photosensitivity.

Antitubercular Pharmacotherapy

• Regimen Principle: Treatment always involves multi-drug therapy to prevent the development of resistant mycobacteria.

• Ethambutol: Can cause visual toxicity, including changes in red-green color discrimination and blurred vision.

• Isoniazid (INH): Used for active and latent TB. Causes peripheral neuropathy (tingling in extremities). Pyridoxine (Vitamin B6) is co-administered to mitigate this.

• Pyrazinamide: Disrupts replication by lowering intracellular pH; requires LFT monitoring for hepatotoxicity.

• Rifampin: A potent enzyme inducer that reduces the effectiveness of oral contraceptives. It causes a harmless reddish-orange discoloration of urine, sweat, and tears.

Miscellaneous Antibiotics

• Aztreonam: A monobactam safe for penicillin-allergic patients.

• Clindamycin: Carries a high risk for $C. \, diff$-associated diarrhea.

• Daptomycin: A cyclic lipopeptide. It causes rapid depolarization of membranes. Nurses must monitor Creatine Kinase (CK) levels for muscle pain.

• Metronidazole (Flagyl):

  • Action: Bactericidal, trichomonacidal, and protozoacidal.

  • Patient Education: Avoid alcohol during therapy and for $48 \, \text{hours}$ after to avoid a disulfiram-like reaction.

Antifungal and Antiviral Agents

• Systemic Antifungals:

  • Amphotericin B: The gold standard for life-threatening systemic infections, but highly toxic (nephrotoxicity and electrolyte imbalance).

  • Azoles (Fluconazole, Itraconazole): Inhibit fungal P450 enzymes. Itraconazole can cause heart failure.

  • Terbinafine: Used for onychomycosis (nail fungus).

• Antivirals:

  • Herpes Agents: Acyclovir (Zovirax), Famciclovir, and Valacyclovir (improved oral bioavailability).

  • Influenza Agents: Oseltamivir (Tamiflu) and Zanamivir (Relenza). Relenza is inhaled; avoid in asthma/COPD due to bronchospasm risk.

  • Ribavirin: Used for Hepatitis C and RSV. It is teratogenic; pregnant healthcare workers should not handle the aerosol form.

Questions & Discussion

• Question: What are the "Big Three" adverse effects?

  • Answer: Nausea, vomiting, and diarrhea. These are the most frequently reported effects across almost all antimicrobial classes.

• Question: Which statement by a 20-year-old on tetracycline requires more education?

  • Statement: "My boyfriend and I don't usually use protection."

  • Reason: Tetracyclines diminish the effectiveness of oral contraceptives; barrier methods are required to prevent pregnancy.

• Question: What is the most important teaching point for Rifampin?

  • Answer: The medication will turn body secretions (tears, sweat, urine) a reddish-orange color. This is expected and harmless.

• Question: Which drug is a cyclic lipopeptide?

  • Answer: Daptomycin (Cubicin). It works by depolarizing the bacterial cell membrane.

• Question: Which antifungal is reserved for life-threatening infections?

  • Answer: Amphotericin B. Its use is limited by significant toxicity requiring close monitoring.