Is amoxicillin (amoxicillin) and linezolid (linezolid) synergistic?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 12, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Synergistic Properties of Amoxicillin and Linezolid

Amoxicillin and linezolid do not demonstrate significant synergistic activity against most pathogens, with their combination showing predominantly indifferent effects in clinical settings. 1

Evidence on Synergistic Activity

  • Linezolid combinations with other antibiotics predominantly show indifferent effects (72% of interactions) rather than synergy when tested against various pathogens, including Enterococcus species 1
  • When linezolid is combined with beta-lactams like amoxicillin, there is limited evidence supporting synergistic activity against common pathogens 1
  • Specific combinations of linezolid with other agents have shown varying degrees of interaction:
    • Linezolid with rifampin (20.4% synergism) and fosfomycin (19.0% synergism) show the highest rates of synergy 1
    • Antagonistic effects are rare but have been reported in approximately 2% of linezolid combination interactions 1

Specific Pathogen Considerations

  • For methicillin-resistant Staphylococcus aureus (MRSA), linezolid combined with carbapenems (imipenem) has demonstrated synergistic activity, but this does not extend to amoxicillin specifically 2
  • Against Mycobacterium abscessus complex, linezolid shows frequent synergism with amikacin and tigecycline, but rarely exhibits synergy with beta-lactams like cefoxitin 3
  • For multidrug-resistant tuberculosis, neither amoxicillin-clavulanate nor linezolid are recommended in combination with each other, though both may be used separately in specific MDR-TB regimens 4

Clinical Applications and Recommendations

  • Amoxicillin-clavulanate is primarily recommended in combination with carbapenems for specific infections like XDR tuberculosis, rather than with linezolid 4
  • Guidelines for treating vancomycin-resistant enterococci (VRE) recommend linezolid monotherapy (600 mg IV/PO every 12 hours) rather than combination therapy with beta-lactams like amoxicillin 4
  • For diabetic foot infections, linezolid and amoxicillin-clavulanate have been studied as separate treatment options, not in combination 5
  • In severe infections requiring combination therapy, other combinations such as linezolid with rifampin or daptomycin with beta-lactams are preferred over linezolid with amoxicillin 4

Potential Concerns

  • Combining antibiotics without proven synergy may increase the risk of adverse effects without providing additional clinical benefit 4
  • The clinical choice of linezolid in combination with other antibiotics should be guided by targeted therapy based on microbiological results rather than an intended synergistic effect 1
  • Unnecessary antibiotic combinations may contribute to antimicrobial resistance and violate antimicrobial stewardship principles 4

In conclusion, while specific antibiotic combinations with linezolid may demonstrate synergy against certain pathogens, the combination of amoxicillin and linezolid specifically lacks substantial evidence supporting synergistic activity in clinical practice.

References

Research

Synergistic properties of linezolid against Enterococcus spp. isolates: a systematic review from in vitro studies.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2024

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treating foot infections in diabetic patients: a randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.