Delafloxacin

Aka: Delafloxacin, Baxdela

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II. Indications

  1. Conditions
    1. Acute Skin and Soft Tissue Infections
    2. Second-Line Agent for refractory covered infections
      1. Should be reserved for resistant infections refractory to other agents
  2. Activity
    1. See Below
    2. Broad spectrum Antibiotic FDA approved in 2017 for acute Bacterial Skin Infections
    3. Increased Gram Positive coverage (including MRSA) over other Quinolones
    4. Broad Gram Positive Bacteria coverage (including otherwise Quinolone resistant organisms)
      1. Methicillin Resistant Staphylococcus Aureus (MRSA, as well as MSSA)
      2. Staphylococcus Haemolyticus
      3. Staphylococcus lugdunensis
      4. Streptococcus Pyogenes
      5. Streptococcus agalactiae
      6. Streptococcus anginosus (as well as Streptococcus intermedius and StreptococcusConstellatus)
      7. Enterococcus faecalis
    5. Gram Negative Bacteria
      1. Escherichia coli
      2. Enterobacter cloacae
      3. KlebsiellaPneumoniae
      4. Pseudomonas aeruginosa

III. Contraindications

  1. See Fluoroquinolone
  2. Fluoroquinolone Hypersensitivity

IV. Mechanism

  1. Inhibition of Bacterial enzymes (DNA Replication, transcription, repair, recombination)
    1. Bacterial Topoisomerase 4
    2. DNA gyrase (Topoisomerase 2)

V. Dosing

  1. Oral
    1. Delafloxacin 450 mg orally every 12 hours for 5-14 days
  2. Parenteral
    1. Delafloxacin 300 mg IV over 60 minutes every 12 hours
    2. Decrease dose to 200 mg IV every 12 hours if GFR 15-30 ml/min
    3. Transition to oral dosing when able
  3. Renal
    1. Adjust IV dose for GFR 15-30 ml/min (see above)
    2. Avoid Delafloxacin for GFR <15 ml/min (End Stage Renal Disease)

VI. Pharmacokinetics

  1. Protein binding: 84%
  2. Oral Bioavailability: 84%
  3. Hepatic metabolism (Glucuronidation)
  4. Excreted in urine and stool, partially metabolized
  5. IV Half-Life: 3.7 hours after a single IV dose
  6. Oral Half-Life: 4 to 8 hours after multiple doses

VII. Adverse Effects

  1. See Fluoroquinolone
  2. Common
    1. Nausea or Vomiting (8%)
    2. Diarrhea (8%)
    3. Headache (3%)
  3. Serious
    1. See Fluoroquinolone
    2. Fluoroquinolones have several serious warnings (e.g. tendon rupture, Neuropathy, Aortic Dissection)
    3. QT Prolongation has NOT been seen with Delafloxacin

VIII. Safety

  1. Fluoroquinolones are generally avoided in pregnancy
    1. Cartilage damage risk
  2. Unknown Safety in Lactation
    1. However, Fluoroquinolones are associated with risk of pediatric Arthropathy

IX. Resources

  1. Delafloxacin (DailyMed)
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208610s000,208611s000lbl.pdf

X. References

  1. (2018) Med Lett Drugs Ther 60(1543): 49-51
  2. (2017) Presc Lett 24(11): 66
  3. LoVecchio (2021) Crit Dec Emerg Med 35(3): 24
  4. Smith and LoVecchio (2017) Crit Dec Emerg Med 31(11):24

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