Antimicrobials Drugs: Disrupt DNA or Folate Metabolism

Fluroquionolones Function

• Inhibit bacterial DNA gyrase and topoisomerase IV

• Prevents bacterial DNA from unwinding and resealing correctly

• Disrupts DNA replication

• Bactericidal

Fluroquinolones Prototype

Ciprofloxacin (Cipro)

Ciprofloxacin (Fluroquinolones) Common uses

• Complicated urinary infections

• Gastrointestinal infections

• Bone and joint infections

• Serious gram-negative infections

• Infections involving susceptible Pseudomonas

Ciprofloxacin (Fluroquinolones) Adverse Effects

• Tendinitis and tendon rupture

• Peripheral neuropathy

• Central nervous system effects

• Dysglycemia

• QT-interval prolongation

• Nausea, diarrhea, C.diff

• Photosensitivity

Ciprofloxacin (Fluroquinolones) High tendon-injury risk

• Older age

• Concurrent corticosteroid therapy

• Kidney, heart, or lung transplantation

• Kidney impairment

Ciprofloxacin (Fluroquinolones) Drug Interactions

• Aluminum, calcium, iron, magnesium, and zinc can reduce oral ciprofloxaic absorption → antacids, mineral supplements, multivitamins

• Tizanidine is contraindicated with ciprofloxacin

• Other meds that prolong the QT interval → high dysrhythmia risk

Ciprofloxacin (Fluroquinolones) Before administrating

• Review kdiney function and ordered dose

• Review medication and supplement list

• Asses tendon, neurologic, glucose, and cardiac risk factors

Ciprofloxacin (Fluroquinolones) Patient teaching

• Separate ciprofloxacin from other mineral products

• Proper hydration

• Use sun protection

• Report tendon pain or swelling promptly

• Report numbness, tingling, burning pain, weakness, confusion, or severe dizziness

Nitromidazoles Function

• Enters susceptible anaerobic organisms

• Becomes converted into reactive compounds

• Damages bacterial DNA

• Prevents DNA replication and repair

• Bactericidal against susceptible bacteria

Nitromidazoles Prototype

Metronidazole (Flagyl)

Metronidazole (Nitromidazoles) Common Uses

• Anaerobic bacterial infections

• Intra-abdominal or pelvic infections involving anaerobes

• Bacterial vaginosis

• Selected protozoal infections

Metronidazole (Nitromidazoles) Adverse effects

• Nausea and abdominal discomfort

• Metallic taste

• Headache

• Darkened urine

• Peripheral neuropathy, especially with prolonged therapy

• Rare seizures or encephalopathy

Metronidazole (Nitromidazoles) Drug interactions

• Alcohol and products containing propylene glycol

• Warfarin and other coumarin anticoagulants

• Disulfiram

• Metronidazole may increase the anticoagulant effect of warfarin

Metronidazole (Nitromidazoles) Nursing implications

• Assess neurologic status with prolonged therapy or new symptoms

• Monitor bleeding when prescribed with warfarin

• Monitor for therapeutic response and significant diarrhea

• Report new numbness, tingling, difficulty walking, confusion, or seizures

Metronidazole (Nitromidazoles) Patient teaching

• Avoid alcohol and products containing propylene glycol during treatment and at least 3 days after final dose

Folate Antagonists Function

• Sulfamethoxazole inhibits an early step in bacterial folate synthesis

• Trimethoprim inhibits a later step

• Combination prevents production of nucleic acids

• Combination is generally bactericidal against susceptible organisms

Folate Antagonists Prototype

Trimethoprim-Sulfamethoxazole (TMP-SMX; Bactrim)

Trimethoprim-Sulfamethoxazole (Folate Antagonist) Common uses

• Urinary tract infections

• Skin infections, selected community-associated MRSA infections

• Gastrointestinal infections

• Pneumocystis jirovecii pneumonia

Trimethoprim-Sulfamethoxazole (Folate Antagonist) Common Adverse Effects

• Nausea and vomiting

• Rash

• Photosensitivity

Trimethoprim-Sulfamethoxazole (Folate Antagonist) Serious Adverse Effects

• Stevens-Johnson syndrome or toxic epidermal necrolysis

• Blood dyscrasias and bone marrow suppression

• Hyperkalemia

• Kidney injury or crystalluria

• Severe hepatic reactions

Trimethoprim-Sulfamethoxazole (Folate Antagonist) Higher-Risk Patients

• Kidney impairment

• Folate Deficiency

• Older age

• Prolonged or high-dose treatment

• Concurrent medications that increase potassium

Trimethoprim-Sulfamethoxazole (Folate Antagonist) Drug Interactions

• Warfarin: TMP-SMX can increase anticoagulant effect and bleeding risk

• Medications that increase potassium: ace inhibitors, angiotensin receptor blockers, potassium-sparing diuretics

Trimethoprim-Sulfamethoxazole (Folate Antagonist) Before Administrating

• Clarify history of sulfonamide reactions

• Review kidney function and potassium

• Review CBC when indicated

Trimethoprim-Sulfamethoxazole (Folate Antagonist) During Treatment

• Monitor for therapeutic response

• Assess rash or mucosal lesions

• Monitor potassium, kidney function, and CBC

• Monitor INR more closely when used with warfarin

Trimethoprim-Sulfamethoxazole (Folate Antagonist) Patient Teaching

• Maintain appropriate fluid intake unless contraindicated

• Use sun protection

• Report rash, unusual bleeding, severe weakness, palpitations, or reduced urine output