Pharmacology of Anti-Infective Drugs: Cell Wall Disruptors and Protein Synthesis Inhibitors

Foundations of Anti-Infective Therapy

• Definition of Bacterial Infection: An invasion of the body by bacteria that leads to physiological changes and symptoms. Indicators are categorized as localized or systemic.
• Signs and Symptoms of Infection (Must Know):
  • Localized Symptoms: Redness, swelling, warmth, pain, and purulent drainage (characterized as cloudy or colored).
  • Systemic Symptoms: Fever, chills, malaise, fatigue, elevated White Blood Cell (WBC) count, and hypotension (which may indicate sepsis).
  • Non-Infectious Indicators: Afebrile status (no fever) and clear drainage are generally NOT signs of infection.
• Culture & Sensitivity (C&S):
  • Order of Operations: A C&S must be ordered and collected BEFORE the administration of any antibiotic.
  • Sensitivity: Indicates the organism is successfully killed by the specific drug, meaning the drug will be effective.
  • Resistance: Indicates the organism is not killed by the drug, meaning the drug will be ineffective.
  • Empiric Therapy: Often, a broad-spectrum antibiotic is administered first; once C&S results are available, the provider may switch to a more specific drug.

Cell Wall Disruptors: Penicillins (PCN)

• Mechanism of Action: These drugs interfere with bacterial cell wall synthesis, leading to cell death (bactericidal).
• The Four Penicillin Groups:
  • Natural Penicillins: Examples include Penicillin G and Penicillin V.
  • Penicillinase-Resistant Penicillins: Examples include Nafcillin and Oxacillin.
  • Aminopenicillins: Examples include Amoxicillin and Ampicillin.
  • Extended-Spectrum Penicillins: Example includes Piperacillin-Tazobactam.
• Clinical Uses: Urinary Tract Infections (UTIs), septicemia, meningitis, Sexually Transmitted Infections (STIs) such as syphilis, respiratory infections, and soft tissue infections.
• Prophylactic Uses: Dental or oral procedures, rheumatic fever, and recurring ear infections.
• Patient Teaching and Administration:
  • Timing: Take on an empty stomach ($1$ hour before or $2$ hours after meals). If Gastrointestinal (GI) upset occurs, it may be taken with food.
  • Fluid Intake: Must be taken with a full glass of water. Avoid taking with milk or antacids as they interfere with absorption.
  • Adherence: Complete the entire prescribed course even if symptoms improve.
  • Missed Doses: Do not increase the next dose if a dose is missed.
  • Contraception: PCN can reduce the effectiveness of estrogen-based birth control pills. Advise the use of a backup contraception method.
  • Pre-assessment: Before administering Augmentin (Amoxicillin/Clavulanate), specifically ask the patient about Penicillin allergies.
• Adverse Reactions:
  • Common: Glossitis (tongue inflammation), stomatitis (mouth inflammation), nausea, vomiting, diarrhea, gastritis, dry mouth, abdominal pain, and phlebitis (for IV) or pain at the IM injection site.
  • Serious/Reportable: Anaphylactic shock (hypersensitivity) is the priority. Bloody diarrhea and cramping should be reported. Hematopoietic changes include anemia, thrombocytopenia, and leukopenia.
  • Superinfection: A fungal overgrowth such as Candida, characterized by bright red oral mucosa with white patches. This requires reaching out to the provider immediately.
• Nursing Alerts:
  • Anaphylaxis Risk: In outpatient settings, clients must wait $30$ minutes after an IM injection to be assessed for reactions.
  • Cross-Sensitivity: Exercise caution with Cephalosporins, as approximately $10 \%$ of patients with a PCN allergy also react to Cephalosporins.

Cell Wall Disruptors: Cephalosporins

• Mechanism of Action: Contains a beta-lactam ring that disrupts the bacterial cell wall; these are bactericidal drugs and are chemically related to penicillins.
• The Five Generations: Progression to higher generations indicates increased coverage of gram-negative bacteria.
  • 1st Generation: Focus on gram-positive bacteria (e.g., Cephalexin, Cefazolin).
  • 2nd Generation: Covers gram-positive and some gram-negative (e.g., Cefuroxime).
  • 3rd Generation: Broad gram-negative coverage (e.g., Ceftriaxone).
  • 4th Generation: Broadest gram-negative coverage (e.g., Cefepime).
  • 5th Generation: Includes coverage for MRSA (e.g., Ceftaroline), though it is not first-line treatment.
• Adverse Reactions:
  • Nausea, vomiting, diarrhea, headache, dizziness, malaise, heartburn, and fever.
  • Nephrotoxicity: Indicated by an increase in serum creatinine and a decrease in urine output.
  • Administration Issues: Thrombophlebitis via IV (requires stopping infusion and notifying the charge nurse) and pain/inflammation via IM.
• Nursing Implementation:
  • Monitor serum creatinine and Blood Urea Nitrogen (BUN), especially in elderly or renal-impaired patients.
  • Report urine output levels less than $300$ mL/day or $500$ mL/day as signs of potential nephrotoxicity.
  • Disulfiram-like Reaction: Consuming alcohol within $72$ hours of taking Cephalosporins can cause flushing, throbbing, respiratory difficulty, vomiting, hypotension, chest pain, and sweating. Advise total abstinence from alcohol.
  • Give Cefuroxime with food if the patient experiences GI upset.

Cell Wall Disruptors: Carbapenems and Vancomycin

• Carbapenems (Imipenem, Meropenem, Doripenem):
  • Inhibit cell wall synthesis; used for serious/resistant infections like endocarditis, meningitis, and septicemia.
  • Contraindications: Allergy to PCN or Cephalosporins, renal failure, and children younger than $3$ years old.
• Vancomycin:
  • Uses: Drug of choice for Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE). Treats C. diff (pseudomembranous colitis) and other gram-positive infections resistant to other drugs.
  • Red Man Syndrome: A reaction causing flushing, hypotension, and tingling/burning from the neck and face upward. Caused by rapid IV infusion. Prevention involves slow infusion over at least $60$ minutes.
  • Ototoxicity: Ringing in the ears (tinnitus), hearing loss, or dizziness. Contraindicated in patients with pre-existing hearing loss. Risk increases when combined with Diuretics.
  • Nephrotoxicity: Monitor BUN/creatinine. Report urine output less than $750$ mL/day.

Protein Synthesis Inhibitors: Tetracyclines

• Mechanism: Inhibit bacterial protein synthesis. They are broad-spectrum, affecting both gram-positive and gram-negative organisms.
• Examples: Tetracycline, Doxycycline, Minocycline, Tigecycline.
• Clinical Uses: Used if the client is allergic to PCN/Cephalosporins. Treatments include acne vulgaris, respiratory infections, E. coli, Chlamydia, Rickettsial diseases, intestinal amebiasis, and H. pylori (in combination with metronidazole and bismuth).
• Contraindications:
  • Children under $9$ years old: Causes permanent yellow-gray-brown discoloration of developing teeth.
  • Pregnancy/Lactation: Category D (potential fetal risk).
• Interactions and Teaching:
  • Bleeding Risk: Tetracycline + Warfarin increases the risk of bleeding.
  • Absorption Blockers: Do not take with dairy (milk), antacids, laxatives, or iron products. Calcium, magnesium, aluminum, and iron block absorption. Space these $2$ hours apart from the drug.
  • Photosensitivity: Severe risk of sunburn; wear protective clothing and avoid tanning beds. Sunscreen may be insufficient.
  • Take on an empty stomach with a full glass of water, except for Minocycline and Tigecycline, which can be taken with food.

Protein Synthesis Inhibitors: Aminoglycosides, Macrolides, and Lincosamides

• Aminoglycosides (Gentamicin, Neomycin, Tobramycin, Amikacin, Streptomycin):
  • The 3 Toxicities (RON):
    1. Nephrotoxicity: Monitor I&O, daily weight, and encourage fluid intake of $2$ L/day.
    2. Ototoxicity: Tinnitus and dizziness; contraindicated in pre-existing hearing loss.
    3. Neurotoxicity: Indicated by circumoral (around the mouth) numbness, tingling, peripheral paresthesia, tremors, and respiratory paralysis.
  • Contraindications: Myasthenia gravis and Parkinson's disease.
• Macrolides (Erythromycin, Azithromycin, Clarithromycin):
  • Side Effects: High incidence of GI distress (nausea, vomiting, diarrhea, abdominal cramping). Risk of pseudomembranous colitis.
  • Timing: Erythromycin and Azithromycin should be taken on an empty stomach ($1$ hour before/$2$ hours after meals).
• Lincosamides (Clindamycin, Lincomycin):
  • Used for serious infections when PCN/Erythromycin are ineffective.
  • Major Risk: High risk for C. diff. Monitor stools closely.
  • Clindamycin: Unique in that it can be taken with food or water.
• Miscellaneous Agents:
  • Daptomycin: For complicated skin infections and Staph aureus bacteremia.
  • Linezolid: For MRSA and VREF. Contraindicated in Phenyketonuria (PKU) and pregnancy.
  • Quinupristin/Dalfopristin: For VREF. Must flush IV lines with D5W only (not saline or heparin).

Nursing Process Summary

• Pre-administration Assessment:
  • Check vital signs (temp, HR, RR, BP) and skin condition.
  • Verify C&S results and baseline labs (BUN, Creatinine, CBC).
  • Perform a hearing test if administering Aminoglycosides.
  • Identify allergies, current medications (especially oral contraceptives), and medical history.
• Universal Implementation Rules:
  • Administer with a full glass of water.
  • Do not double up missed doses.
  • Complete the full course.
• Evaluating Therapeutic Response:
  • Patient is afebrile.
  • Drainage resolves or clears.
  • WBC count trends downward.
  • Improved energy and decreased pain.
• Evaluating Hypersensitivity:
  • Monitor for wheezing, angioedema (face/airway swelling), and rashes.