Antibiotics Targeting DNA / RNA Replication

Generic Name

Fluoroquinolones

(ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin)

  • Contraindicated in Pregnancy
Dosing and Formulations
  • Ciprofloxacin
  • Levofloxacin
  • Moxifloxacin Norfloxacin
  • Ofloxacin
Mechanism of Action
  • Interferes with bacterial replication through inhibition of Topoisomerase II and IV
  • Gram negative with some gram positive (including MRSA)
  • Ciprofloxacin is the most active for Pseudomonas
Indications
  • Folliculitis, hot-tub folliculitis (ciprofloxacin), abscesses, cellulitis, infected ulcers, wound infections, donovanosis, chancroid, anthrax
Adverse Effects
  • Gastrointestinal: nausea, vomiting, diarrhea, severe hepatotoxicity (moxifloxacin, levofloxacin)
  • neurologic: headaches, dizziness, agitation, sleep disturbance, seizures, psychosis, hallucinations, depression, peripheral neuropathy, exacerbation of myasthenia gravis 
  • MSK: tendonitis, tendon rupture
  • cardiovascular: can induce aortic dissection/rupture
  •  skin: hypersensitivity and photosensitivity, pseudoporphyria, photo-onycholysis 

Drug interactions:

  • decreased bioavailability of fluoroquinolones with antacids containing Ca, Mg, Al
  • ↑ levels of theophylline, caffeine, warfarin, and cyclosporine (due to inhibition of CYP 1A2)
  • caution with medications causing ↑ QT
Other

Caution in following settings

  • Pregnancy
  • Children < 18 years of age (arthropathy / tendinopathy)
  • Hypokalemia, hypomagnesemia 
  • QT prolonging meds
  • Peripheral neuropathy 
  • Myasthenia gravis

Generic Name

Rifampin

  • Pregnancy Category C
Dosing and Formulations
  • 300-600 mg / day (adult);
  • 10mg/kg/day (600 mg max for children)
Mechanism of Action
  • Binds β-subunit of bacterial DNA-dependent RNA polymerase, blocking RNA synthesis 
  • Broad spectrum and good for intracellular organisms, mycobacterium
  • Rifamycin family includes rifampin, rifabutin and rifapentine
Indications

FDA

  • Tuberculosis

Off label

  • Infections: leprosy, mycobacterium avium complex, bartonella, CA-MRSA, MSSA, leishmaniasis, rhinoscleroma, aspergillosis, brucellosis, tularemia, chlamydia, gonorrhea; 
  • Non-infectious: pruritis associated with biliary disease
Adverse Effects
  • Skin: orange/red discoloration of body excretions, LABD, PF, PV, DRESS
  • Neurologic: headache, drowsiness, ataxia, dizziness, inability to concentrate, fatigue
  • GI: elevated LFTs, hepatotoxicity 
  • others: DVT, pulmonary fibrosis, ocular toxicity, decreased effectiveness of OCPs
  • Potent inducer of CYP 1A2, 2C9, 2C19, 2D6 and 3A4 (decreased effectiveness of medications metabolized by these CYP)
Other
  • Resistance quickly develops when used as monotherapy

Generic Name

Trimethoprim Sulfamethoxazole (TMP-SMX)

  • Pregnancy Category D
Dosing and Formulations

Dosage

  • 160/800 DS capsule BID

Other sulfonamides:

  • sulfasalazine
  • sulfisoxazole
Mechanism of Action
  • Trimethoprim (TMP)
    • dihydrofolate reductase inhibitor 
  • Sulfamethoxazole (SMX)
    • dihydropteroate synthetase inhibitor
  • Both TMP and SMX synergistically inhibit the production of tetrahydrofolic acid, which inhibits thymidine synthesis 🡪 ↓DNA synthesis 
  • Broad spectrum including gram positive, gram negatives and pseudomonas
Indications
  • Acne, CA-MRSA skin infections, hidradenitis suppurativa, granuloma inguinale, mycobacterium avium complex, actinomycetoma, cat-scratch disease, glanders

Contraindications

  • Allergy
  • Pregnancy (3rd trimester) and lactation
  • Porphyria
  • Megaloblastic anemia
  • Folate deficiency
  • G6PD deficiency
  • Caution in those with hepatic abnormalities, renal abnormalities or heme abnormalities
Adverse Effects
  • Skin: (cutaneous eruptions in 4-5% of healthy individuals, 15% in HIV): morbilliform drug eruptions, urticaria, Sweets, fixed drug eruption, DRESS, SJS/TEN, precipitates porphyria & pseudoporphyria, photosensitivity
  • Nails: Beau’s lines, paronychia, partial leukonychia, photo-onycholysis
  • Gastrointestinal: nausea, vomiting, loss of appetite, diarrhea, hepatitis
  • Kidney: interstitial nephritis, hyperkalemia, nephro- or uro- lithiasis
  • Neurologic: headaches, dizziness, tinnitus
  • Hematologic (especially if G6PD): agranulocytosis > immune thrombocytopenic purpura, neutropenia, hemolytic or aplastic anemia
Other
  • Increased levels of dapsone, oral hypoglycemic agents, potassium, phenytoin, warfarin, 
  • Blood dyscrasias with methotrexate; reduces cyclosporine

Monitoring

  • CBC at baseline then monthly for long-term treatment

Generic Name

Metronidazole

  • Pregnancy Category B
Dosing and Formulations

  • 500 mg QID

Mechanism of Action
  • DNA strand break: protozoa and anaerobes
Indications
  • Trichomonas, amoeba, skin anaerobic infections
Adverse Effects
  • Gastrointestinal: metallic taste, xerostomia, disulfiram reaction with alcohol
  • Skin: morbilliform eruption
  • Hematologic: thrombophlebitis, transient leukopenia
  • Neurologic: headaches, confusion, syncope, seizures, sensory neuropathy  
Other
  • Increase level of cyclosporine, warfarin
  • Avoid in liver dysfunction