Does Keflex (cephalexin) cover Staphylococcus lugdunensis?

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Does Keflex Cover Staphylococcus lugdunensis?

Yes, Keflex (cephalexin) provides excellent coverage for methicillin-susceptible Staphylococcus lugdunensis, as this organism is uniformly susceptible to first-generation cephalosporins and behaves clinically like methicillin-susceptible S. aureus (MSSA). 1, 2

Microbiological Activity

  • S. lugdunensis is a coagulase-negative staphylococcus that is typically methicillin-susceptible and acts similarly to S. aureus in terms of virulence and antibiotic susceptibility 1
  • First-generation cephalosporins like cephalexin demonstrate good activity against methicillin-susceptible staphylococcal species, including S. lugdunensis 2, 3
  • Unlike other coagulase-negative staphylococci, S. lugdunensis remains susceptible to most antibiotics, with methicillin resistance still rare 4
  • Penicillinase-resistant penicillins (flucloxacillin, dicloxacillin) and first-generation cephalosporins (cefazolin, cephalexin) are appropriate therapeutic options for methicillin-susceptible staphylococcal infections 5

Clinical Application

  • For mild-to-moderate skin and soft tissue infections caused by S. lugdunensis, cephalexin 500 mg orally every 6 hours for 5 days is appropriate 2, 6
  • The WHO Essential Medicines guidelines list cephalexin as a first-choice agent for mild skin and soft tissue infections commonly caused by staphylococcal species 2
  • Cephalexin achieves cure rates of 90% or higher for staphylococcal skin infections and remains effective after decades of clinical use 7

Critical Caveat: Methicillin Resistance

  • This recommendation applies ONLY to methicillin-susceptible S. lugdunensis—if methicillin resistance is suspected or confirmed, alternative agents such as vancomycin, linezolid, or daptomycin must be used 2
  • Although methicillin-resistant strains carrying the mecA gene are rare in S. lugdunensis, they do occur and would render cephalexin ineffective 4
  • Despite in vitro susceptibility results, methicillin-resistant coagulase-negative staphylococci exhibit cross-resistance to cephalosporins, making these agents clinically ineffective 1

Special Considerations for Severe Infections

  • S. lugdunensis causes a substantially more virulent form of infective endocarditis with high rates of perivalvular extension and metastatic infection 1
  • For severe or invasive S. lugdunensis infections (such as endocarditis), intravenous therapy with cefazolin or an anti-staphylococcal penicillin (nafcillin, oxacillin) is recommended rather than oral cephalexin 2
  • The standard regimen for methicillin-susceptible staphylococcal endocarditis includes a semisynthetic β-lactamase-resistant penicillin (nafcillin or oxacillin) intravenously for 4-6 weeks, with cefazolin as an alternative 1
  • S. lugdunensis is always methicillin-susceptible and can be treated with cloxacillin according to European guidelines 1

Common Pitfalls to Avoid

  • Do not assume all coagulase-negative staphylococci are low-virulence organismsS. lugdunensis requires the same aggressive treatment approach as S. aureus 1
  • Do not use cephalexin for catheter-related bloodstream infections caused by S. lugdunensis, as these infections manifest with prominent symptomatology similar to S. aureus-associated CLABSI and require parenteral therapy 1
  • Microbiological differentiation of S. lugdunensis requires specific biochemical assays; initial screening can be done with pyrrolidonyl aminopeptidase hydrolysis testing 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Cephalexin Coverage for Staphylococcus lugdunensis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Antibiotic Treatment for Skin and Soft Tissue Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Staphylococcus lugdunensis: antimicrobial susceptibility and optimal treatment options.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2019

Guideline

Management of Cellulitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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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.

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