What is the coverage and dosage of Unasyn (ampicillin/sulbactam) for various infections?

Unasyn (Ampicillin/Sulbactam) Coverage and Dosing

Antimicrobial Spectrum

Unasyn provides broad-spectrum coverage against gram-positive cocci (including most S. aureus), gram-negative organisms (E. coli, Klebsiella species), and anaerobes (including Bacteroides fragilis), making it particularly effective for polymicrobial infections. 1, 2

The sulbactam component irreversibly inactivates beta-lactamases from most beta-lactamase-producing organisms, extending ampicillin's activity to include organisms that would otherwise be resistant 3, 2. Key coverage includes:

• Gram-positive organisms: Staphylococcus aureus (non-MRSA), Streptococcus species (groups B, C, G), Peptostreptococcus species 4, 1
• Gram-negative organisms: Escherichia coli, Klebsiella species, Proteus species 1, 5
• Anaerobes: Bacteroides fragilis and other anaerobic bacteria 1, 2
• Special consideration: Sulbactam has intrinsic activity against Acinetobacter baumannii, making it valuable for multidrug-resistant infections 2, 6

Standard Dosing Regimens

Adults with Normal Renal Function

The FDA-approved adult dosage is 1.5-3 g IV every 6 hours (representing 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam), with a maximum sulbactam dose of 4 grams per day. 1

• Administer by slow IV injection over 10-15 minutes, or as IV infusion over 15-30 minutes in 50-100 mL compatible diluent 1
• Treatment duration should not routinely exceed 14 days 1

Pediatric Patients (≥1 Year)

• Recommended dose: 300 mg/kg/day IV divided every 6 hours (representing 200 mg ampicillin/100 mg sulbactam per kg per day) 1
• Children weighing ≥40 kg should receive adult dosing 1
• Maximum sulbactam dose: 4 grams per day 1

Renal Impairment Adjustments

The FDA label provides specific dosing based on creatinine clearance 1:

• CrCl ≥30 mL/min: 1.5-3 g every 6-8 hours 1
• CrCl 15-29 mL/min: 1.5-3 g every 12 hours 1
• CrCl 5-14 mL/min: 1.5-3 g every 24 hours 1

Clinical Indications

FDA-Approved Indications

Unasyn is approved for infections caused by beta-lactamase-producing bacteria 1:

• Intra-abdominal infections 1, 2
• Skin and skin structure infections 1, 2
• Gynecological infections 1, 2

Additional Guideline-Supported Uses

For necrotizing soft tissue infections (mixed polymicrobial), ampicillin-sulbactam 1.5-3 g every 6-8 hours IV is recommended as first-line therapy, often combined with clindamycin 600-900 mg every 8 hours IV and ciprofloxacin 400 mg every 12 hours IV. 4

Other well-supported indications include:

• Lower respiratory tract infections and aspiration pneumonia 2
• Diabetic foot infections 2
• Urogenital infections (95% clinical/bacteriological efficacy in acute pyelonephritis) 5
• Pediatric infections: acute epiglottitis, periorbital cellulitis 2
• Surgical prophylaxis for abdominal and gynecological procedures 7, 8

Special Considerations for Resistant Organisms

Acinetobacter baumannii Infections

For multidrug-resistant Acinetobacter baumannii, high-dose sulbactam therapy (9-12 g/day divided every 8 hours with 4-hour extended infusions) is recommended, particularly for isolates with MIC ≤4 mg/L. 6, 9

• Sulbactam-containing regimens show lower nephrotoxicity rates compared to polymyxin-based therapies 4, 6
• Combination therapy with tigecycline, polymyxin, doxycycline, or minocycline may be added based on susceptibility testing 4, 9
• For CRAB bloodstream infections, cefoperazone-sulbactam combined with imipenem-cilastatin showed significantly lower mortality than monotherapy 4, 9

Important Limitations

• Not effective against MRSA - requires alternative agents 4
• Standard doses (<9 g/day sulbactam) may be insufficient for severe resistant infections 9, 6
• Increasing macrolide resistance in group A streptococci necessitates combination therapy for necrotizing fasciitis 4

Common Pitfalls to Avoid

• Underdosing sulbactam for resistant organisms: Doses <9 g/day may fail for severe CRAB infections 9, 6
• Ignoring local resistance patterns: Susceptibility varies geographically, particularly for Acinetobacter species 9
• Inadequate infusion time for high-dose therapy: Extended 4-hour infusions optimize pharmacokinetics for resistant pathogens 9, 6
• Failing to adjust for renal impairment: Both ampicillin and sulbactam are renally eliminated with similar kinetics 1
• Exceeding 14-day IV course without reassessment: Prolonged therapy increases adverse event risk 1

Safety Profile

• Generally well-tolerated with adverse effects primarily attributed to the ampicillin component 7, 3
• Lower nephrotoxicity compared to polymyxin-based regimens for resistant infections 4, 6
• Pain at injection site is the most commonly reported adverse effect 5
• Monitor renal function during high-dose therapy, especially in patients with baseline renal impairment 9, 6