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Proposed alternative antibiotic regimens for completing treatment of right-sided endocarditis due to Staphylococcus aureus among patients who are unable to complete standard parenteral therapy

Proposed alternative antibiotic regimens for completing treatment of right-sided endocarditis due to Staphylococcus aureus among patients who are unable to complete standard parenteral therapy
Regimen Comments

Dicloxacillin 1 g orally every 6 hours

plus

Rifampin 600 mg orally every 12 hours
  • For treatment of MSSA infection only.
  • Rifampin reduces methadone levels and concurrent use may require methadone dose adjustments.[1] In patients on methadone, consider alternative regimens; do not prioritize rifampin over methadone.
  • Regimen studied in POET trial.[2]

Linezolid 600 mg orally every 12 hours

plus

Rifampin* 600 mg orally every 12 hours
  • Rifampin reduces methadone levels and concurrent use may require methadone dose adjustments.[1] In patients on methadone, consider alternative regimens, including linezolid monotherapy; do not prioritize rifampin over methadone.
  • For linezolid administration longer than one to two weeks, laboratory monitoring is warranted.
  • Risk of serotonin syndrome in patients receiving linezolid with other serotonergic medications (eg, tramadol, SSRI, MAOI). Consider alternative regimens when possible.
  • Regimen studied in POET trial.[2]

Ciprofloxacin 750 mg orally every 12 hours

plus

Rifampin 300 mg orally every 8 hours
  • For use only if ciprofloxacin susceptibility is confirmed; if susceptibility data are not available, the regimen should not be used for treatment of MRSA infection.
  • Rifampin reduces methadone levels and concurrent use may require methadone dose adjustments.[1] In patients on methadone, consider alternative regimens; do not prioritize rifampin over methadone.
  • Fluoroquinolones may cause significant QT interval prolongation and torsades de pointes; risk is increased with concurrent methadone and other QT-prolonging medications; obtain baseline ECG and monitor.
  • Combination studied in a small prospective cohort.[3]
Trimethoprim-sulfamethoxazole 2 double-strength tablets (160 mg/800 mg per tablet) orally every 12 hours
  • Kidney function monitoring may be warranted.
  • No randomized trial data for treatment of IE are available.
Doxycycline 100 mg orally every 12 hours
  • May be considered for patients who are intolerant of other antibiotic regimens.
  • Risk for photosensitivity.
  • No randomized trial data for treatment of IE are available.

Dalbavancin 1000 mg IV loading dose, then 500 mg IV once weekly

or

1500 mg IV loading dose, then 1000 mg IV once every other week
  • May be considered for patients in whom oral absorption of medications is limited or there are other contraindications to oral antibiotics.
  • No randomized trial data for treatment of IE are available.
Oritavancin 1200 mg IV weekly
  • May be considered for patients in whom oral absorption of medications is limited or there are other contraindications to oral antibiotics.
  • No randomized trial data for treatment of IE are available.
Dosing in this table is intended for adult patients with normal organ (ie, kidney, liver) function. For dose adjustments, refer to the Lexicomp drug monographs included with UpToDate. Refer to UpToDate topic on right-sided endocarditis for guidance regarding duration of treatment.

MSSA: methicillin-susceptible S. aureus; POET: Partial Oral Versus Intravenous Antibiotic Treatment trial; SSRI: selective serotonin reuptake inhibitor; MAOI: monoamine oxidase inhibitor; ECG: electrocardiogram; MRSA: methicillin-resistant S. aureus; IE: infectious endocarditis; IV: intravenously.

* In areas where fusidic acid is available, fusidic acid (750 mg orally every 12 hours) may be used instead of rifampin.

¶ Refer to the UpToDate topic on linezolid for further discussion.
References:
  1. Badhan RKS, Gittins R, Al Zabit D. The optimization of methadone dosing whilst treating with rifampicin: A pharmacokinetic modeling study. Drug Alcohol Depend 2019; 200:168.
  2. Iversen K, Ihlemann N, Gill SU, et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Engl J Med 2019; 380:415.
  3. Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med 1996; 101:68.

Adapted from: Baddour LM, Weimer MB, Wurcel AG, et al. Management of infective endocarditis in people who inject drugs: A scientific statement from the American Heart Association. Circulation 2022; 146:e187.

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