What alternative to ampicillin‑sulbactam (Unasyn) is recommended for treating Acinetobacter nosocomialis infection when Unasyn is unavailable?

Alternative Antimicrobial Therapy for Acinetobacter nosocomialis When Ampicillin-Sulbactam Is Unavailable

Carbapenems (imipenem, meropenem, or doripenem) are the preferred alternative to ampicillin-sulbactam for Acinetobacter nosocomialis infections in areas with low carbapenem resistance, while polymyxins (colistin or polymyxin B) should be used when carbapenem resistance is documented or highly suspected. 1

Treatment Algorithm Based on Local Resistance Patterns

Step 1: Assess Local Carbapenem Susceptibility

In areas with low carbapenem resistance (<20% of isolates resistant):

• First choice: Carbapenems 1
  • Imipenem 0.5-1 g IV every 6 hours 2
  • Meropenem 2 g IV every 8 hours as extended infusion (preferred for optimal pharmacodynamics) 2
  • Doripenem is an acceptable alternative with similar efficacy 2
• Carbapenems remain the drugs of choice for Acinetobacter infections when susceptibility is preserved 1
• More than 85% of Acinetobacter isolates historically remain susceptible to carbapenems, though resistance is increasing 1

In areas with high carbapenem resistance (>20% of isolates resistant) or documented carbapenem-resistant isolates:

• Polymyxins become the primary option 1, 2
  • Polymyxin B: Loading dose 2-2.5 mg/kg IV, then maintenance 1.5-3 mg/kg/day divided into two doses or continuous infusion 3
  • Colistin: Loading dose 6-9 million IU, then 9 million IU/day in 2-3 divided doses with renal adjustment 3
• Polymyxins have the greatest level of in vitro activity against multidrug-resistant Acinetobacter 1

Step 2: Consider Combination Therapy for Severe Infections

For severe infections (septic shock, bacteremia, ventilator-associated pneumonia):

• Combine polymyxin with a second active agent 3, 2
  • Polymyxin + high-dose carbapenem (2 g meropenem every 8 hours) even if resistant, for potential synergy 2
  • Polymyxin + tigecycline (200 mg loading dose, then 100 mg every 12 hours) 3, 2
  • Polymyxin + rifampicin (600 mg/day) 3
  • Polymyxin + fosfomycin (12-24 g/day divided into 3-4 doses) 3
• Combination therapy with two in vitro active agents is recommended for severe carbapenem-resistant Acinetobacter infections 2

Step 3: Alternative Agents When Standard Options Fail

Tigecycline-based regimens:

• Use when polymyxin resistance is documented or strongly suspected 3
• Tigecycline 200 mg loading dose, then 100 mg every 12 hours combined with high-dose meropenem or rifampicin 3
• Critical limitation: Tigecycline should not be used as monotherapy for empirical treatment 1

Cefoperazone-sulbactam (if available regionally):

• Provides sulbactam component with intrinsic anti-Acinetobacter activity 4
• Dose: 3 g/3 g IV every 8 hours for severe infections 4
• Particularly effective in regions where this formulation is available (more common outside the United States) 4

Site-Specific Considerations

For ventilator-associated pneumonia:

• Add nebulized antibiotics as adjunctive therapy in non-responding cases 2
  • Nebulized colistin 2 million IU every 8-12 hours (up to 5 million IU every 8 hours for refractory cases) 2
  • Nebulized aminoglycosides (tobramycin or amikacin) based on susceptibility 2
• Nebulized therapy should never be used for colonization without documented infection 2

For meningitis/ventriculitis:

• Consider intrathecal aminoglycosides (amikacin) in addition to systemic therapy 5
• Treatment duration: 3 weeks 2

Treatment Duration

• Severe infections (VAP, bacteremia with septic shock): 14 days 3, 2
• Less severe infections: 7-10 days may be acceptable 2
• Meningitis/ventriculitis: 21 days 2

Critical Safety Monitoring

Nephrotoxicity surveillance with polymyxins:

• Monitor renal function closely—nephrotoxicity occurs in up to 33% of patients receiving colistin 3, 2
• Continuous infusion of polymyxin B may reduce nephrotoxicity risk compared to intermittent dosing 3
• Polymyxins demonstrate significantly higher nephrotoxicity than sulbactam-based regimens (33% vs 15.3%) 3, 2

Common Pitfalls to Avoid

• Never use ertapenem for Acinetobacter infections—it lacks activity against this organism 1, 2
• Avoid aminoglycoside monotherapy—inadequate tissue penetration limits efficacy 1, 2
• Do not delay appropriate therapy in critically ill patients with known carbapenem-resistant Acinetobacter colonization or during outbreaks 2
• Avoid empirical polymyxin use in areas with low carbapenem resistance—this exposes patients to unnecessary toxicity and promotes resistance 1
• Do not use third-generation cephalosporins—Acinetobacter species demonstrate high rates of resistance 1