What is a good alternative to Augmentin (amoxicillin/clavulanate)?

Alternative Antibiotics to Augmentin (Amoxicillin-Clavulanate)

For most respiratory tract infections requiring an alternative to Augmentin, cefdinir, cefpodoxime proxetil, or cefuroxime axetil are the preferred first-line alternatives, with respiratory fluoroquinolones (levofloxacin or moxifloxacin) reserved for patients with recent antibiotic exposure or significant comorbidities. 1

Primary Alternatives Based on Clinical Context

For Respiratory Tract Infections (Sinusitis, Otitis Media, Pneumonia)

Second/Third-Generation Cephalosporins (Preferred):

• Cefdinir is the most preferred alternative due to excellent patient acceptance (particularly in children), good activity against S. pneumoniae comparable to second-generation agents, and activity against H. influenzae similar to cefuroxime axetil 1
• Cefpodoxime proxetil is often regarded as the preferred treatment when high-dose amoxicillin or amoxicillin-clavulanate fails or is intolerable, with activity similar to cefuroxime axetil and cefdinir against S. pneumoniae but greater activity against H. influenzae 1
• Cefuroxime axetil provides broad-spectrum coverage with activity against S. pneumoniae similar to cefdinir and cefpodoxime, though the clinical utility of the suspension formulation for children is often limited by poor taste 1

Respiratory Fluoroquinolones (Second-Line):

• Levofloxacin (750 mg daily) or moxifloxacin should be reserved for patients with comorbidities, recent antimicrobial use (within 4-6 weeks), or risk factors for drug-resistant S. pneumoniae 1
• These agents should not be used as first-line therapy in otherwise healthy patients due to concerns about promoting fluoroquinolone resistance 1

For Patients with Penicillin Allergy

Non-Type I Hypersensitivity (e.g., rash):

• Cefdinir, cefpodoxime proxetil, or cefuroxime axetil are appropriate due to negligible cross-reactivity with penicillins 1, 2
• Cefdinir is preferred in this scenario based on high patient acceptance 1

Type I Hypersensitivity (immediate/anaphylactic reactions):

• Azithromycin or clarithromycin are recommended alternatives, though they have limited effectiveness against major pathogens with bacterial failure rates of 20-25% possible 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) is an option but similarly has limited effectiveness 1
• These patients may require desensitization, sinus cultures, or other ancillary procedures 1

Algorithm for Selecting Alternatives

Step 1: Assess Disease Severity and Recent Antibiotic Use

Mild Disease WITHOUT Recent Antibiotics (past 4-6 weeks):

• Use cefpodoxime proxetil, cefuroxime axetil, or cefdinir as first choice 1
• For children, cefdinir is preferred due to palatability 1

Mild Disease WITH Recent Antibiotics OR Moderate Disease:

• Use cefpodoxime proxetil, cefuroxime axetil, or cefdinir 1
• Consider respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin) for adults with comorbidities 1

Severe Disease or Treatment Failure:

• Ceftriaxone 50 mg/kg/day IM or IV for 5 days is appropriate, particularly in children 1
• Combination therapy may be considered: high-dose amoxicillin or clindamycin plus cefixime, or high-dose amoxicillin or clindamycin plus rifampin (rifampin should not be used as monotherapy or for longer than 10-14 days due to rapid resistance development) 1

Step 2: Consider Pathogen Coverage

For Drug-Resistant S. pneumoniae (DRSP) Coverage:

• High-dose amoxicillin (90 mg/kg/day in children; 1g three times daily in adults) targets ≥93% of S. pneumoniae 1
• Respiratory fluoroquinolones provide excellent DRSP coverage 1
• Cefdinir, cefpodoxime, and cefuroxime have activity against penicillin-susceptible pneumococci but variable activity against DRSP 1

For β-Lactamase-Producing H. influenzae and M. catarrhalis:

• Cefpodoxime proxetil has the greatest activity against H. influenzae among oral cephalosporins 1
• Cefdinir and cefuroxime axetil provide adequate coverage 1
• Respiratory fluoroquinolones provide excellent coverage 1

Step 3: Reassess at 72 Hours

• Failure to respond after 72 hours should prompt either a switch to alternate antimicrobial therapy or reevaluation of the patient 1
• Consider CT scan, fiberoptic endoscopy, or sinus aspiration and culture if symptoms persist despite appropriate antibiotic therapy 1

Common Pitfalls and Caveats

Avoid These Agents as Augmentin Alternatives:

• Cefaclor has poor activity against H. influenzae, fair activity against penicillin-susceptible pneumococci, and no activity against DRSP, resulting in poor overall efficacy 1
• Cefixime has potent activity against H. influenzae but limited gram-positive coverage including S. pneumoniae, no activity against staphylococci, and may fail against even penicillin-susceptible pneumococci 1
• Macrolides as monotherapy (azithromycin, clarithromycin, erythromycin) are not recommended for patients with significant risk of DRSP infection due to high resistance rates 1

Important Considerations:

• When changing antibiotic therapy, consider the limitations in coverage of the initial agent 1
• Agents in the same class as the patient had been receiving previously should not be used 1
• For hospitalized patients with community-acquired pneumonia, combination therapy with a β-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone demonstrates significant mortality reduction compared to cephalosporin alone 1

Specific Clinical Scenarios

Acute Bacterial Sinusitis in Adults:

• Cefpodoxime proxetil, cefuroxime axetil, or cefdinir for mild-moderate disease 1
• Respiratory fluoroquinolone for patients with recent antibiotic exposure or comorbidities 1

Acute Otitis Media in Children:

• Cefdinir (14 mg/kg/day in 1-2 doses), cefpodoxime (10 mg/kg/day in 2 divided doses), or cefuroxime axetil 2
• Azithromycin (30 mg/kg single dose or 12 mg/kg/day for 5 days) for penicillin-allergic patients, though clinical success against macrolide-resistant S. pneumoniae is only 67% 2

Community-Acquired Pneumonia (Outpatient):

• For patients without comorbidities: doxycycline or a macrolide (though macrolide monotherapy not recommended if DRSP risk) 1
• For patients with comorbidities or recent antibiotic use: respiratory fluoroquinolone OR combination of high-dose amoxicillin (or ceftriaxone if parenteral feasible) plus a macrolide 1