Can Levofloxacin and Augmentin Be Taken Together?
Yes, levofloxacin and Augmentin (amoxicillin-clavulanate) can be taken together safely, and this combination is specifically recommended by major medical societies for certain serious infections including neutropenic fever, complicated diabetic foot infections, and animal bites. 1, 2, 3
Evidence-Based Indications for Combined Use
Approved Combination Scenarios
The Infectious Diseases Society of America explicitly recommends ciprofloxacin (a fluoroquinolone like levofloxacin) plus amoxicillin-clavulanate as oral empirical treatment for low-risk neutropenic patients with fever. 1, 3 This demonstrates that fluoroquinolones and beta-lactam/beta-lactamase inhibitor combinations are not only safe together but therapeutically synergistic for specific conditions.
For complicated diabetic wound infections and animal bites, guidelines support using fluoroquinolones together with amoxicillin-clavulanate in complex cases requiring broad-spectrum coverage. 3
Mechanism of Complementary Coverage
The combination provides rational antimicrobial coverage because:
Levofloxacin covers gram-negative organisms (including Pseudomonas at 750 mg dosing), atypical pathogens (Mycoplasma, Chlamydophila, Legionella), and both penicillin-susceptible and resistant Streptococcus pneumoniae. 4
Augmentin provides enhanced coverage against beta-lactamase producing organisms, anaerobes, and gram-positive cocci including Staphylococcus aureus (methicillin-sensitive). 5
Together, they provide comprehensive coverage against mixed aerobic-anaerobic infections and resistant organisms. 3
Important Clinical Considerations
When This Combination Makes Sense
Use this combination when you need:
- Empirical coverage for neutropenic fever in low-risk patients who can take oral medications 1
- Treatment of polymicrobial infections (diabetic foot infections, complex intra-abdominal infections, severe animal bites) 3
- Coverage for both typical and atypical respiratory pathogens plus anaerobes in severe community-acquired pneumonia 1
Critical Warnings and Contraindications
Do NOT use levofloxacin if the patient is already receiving fluoroquinolone prophylaxis, as this promotes resistance. 3 The Infectious Diseases Society of America specifically warns against fluoroquinolone use in patients on fluoroquinolone prophylaxis.
The FDA has issued boxed warnings for fluoroquinolones including levofloxacin regarding: 6
- Tendinopathy and tendon rupture risk
- Aortic aneurysm rupture or dissection (especially in elderly patients)
- Central nervous system effects
- Peripheral neuropathy
Reserve this broad-spectrum combination for specific indications rather than routine use to promote antimicrobial stewardship and prevent resistance. 2, 3
Practical Prescribing Algorithm
Step 1: Verify the Indication
- Is this neutropenic fever, complicated diabetic foot infection, severe polymicrobial infection, or animal bite requiring broad coverage?
- If yes, proceed. If no, consider narrower-spectrum monotherapy.
Step 2: Check Contraindications
- Patient already on fluoroquinolone prophylaxis? If yes, do NOT add levofloxacin 3
- History of tendon disorders, aortic aneurysm, or severe CNS reactions to fluoroquinolones? If yes, avoid levofloxacin 6
- Severe renal impairment? Adjust doses of both agents appropriately
Step 3: Dose Appropriately
- Levofloxacin: 750 mg once daily for severe infections (provides better anti-pseudomonal coverage than 500 mg) 1, 4
- Augmentin: 875 mg/125 mg twice daily for adults, or high-dose formulations (2000 mg/125 mg twice daily) for resistant organisms 5
Step 4: Plan Duration and De-escalation
- Most infections: 7-10 days 1
- Obtain cultures before starting therapy when possible 1
- De-escalate to narrower-spectrum monotherapy once culture results and clinical response allow 1
Common Pitfalls to Avoid
Do not use this combination routinely for simple community-acquired infections where monotherapy would suffice. 2, 3 Guidelines emphasize that inappropriate use of broad-spectrum combinations promotes antimicrobial resistance.
Do not continue both agents for the full course if cultures reveal a pathogen susceptible to a single agent. 1 Switch to targeted monotherapy as soon as microbiologic data permit.
Monitor for Clostridioides difficile infection, as both agents can disrupt normal gut flora, and the combination increases this risk. 6
Counsel patients about fluoroquinolone risks, particularly tendon pain (stop immediately if this occurs) and avoid in patients with risk factors for aortic dissection. 6