What antibiotic is effective for treating Acinetobacter baumannii infections?

Antibiotic Treatment for Acinetobacter baumannii

First-Line Treatment Based on Susceptibility

For carbapenem-susceptible A. baumannii, carbapenems (imipenem, meropenem, or doripenem) are the drugs of choice in areas with low carbapenem resistance rates. 1 However, carbapenems should not be used as monotherapy for severe infections in areas with high resistance rates (>25% carbapenem resistance). 1

Carbapenem Dosing for Susceptible Isolates:

• Imipenem: 0.5–1 g every 6 hours (extended infusion not possible due to drug instability) 1
• Meropenem: 2 g every 8 hours (high doses associated with seizure risk) 1
• Note: Ertapenem lacks activity against A. baumannii and should never be used 2

Treatment for Carbapenem-Resistant A. baumannii (CRAB)

Sulbactam-Based Therapy (Preferred When Susceptible):

For CRAB with sulbactam MIC ≤4 mg/L, ampicillin-sulbactam is preferable to polymyxins due to superior safety profile and comparable efficacy. 1 Sulbactam has intrinsic bactericidal activity against A. baumannii independent of its β-lactamase inhibitor properties. 2

Dosing: 9–12 g/day of sulbactam in 3 daily doses, administered as 4-hour infusions (3 g sulbactam every 8 hours) 1

• Clinical studies demonstrate comparable outcomes to imipenem for severe infections 1
• Lower nephrotoxicity compared to colistin (15.3% vs 33%) 1
• Microbiologic cure rates at day 7 significantly higher than colistin 1

Polymyxin Therapy (For Sulbactam-Resistant CRAB):

Colistin should be reserved for CRAB showing resistance to all beta-lactams and sulbactam. 1

Colistin Dosing:

• Loading dose: 6–9 million IU 1
• Maintenance: 4.5 million IU every 12 hours in critically ill patients with creatinine clearance >50 mL/min 1
• Renal adjustment: Dose individually adjusted according to creatinine clearance 1
• CRRT: At least 9 million IU/day 1
• Intermittent hemodialysis: 2 million IU every 12 hours with normal loading dose 1

Polymyxin B Alternative:

• Loading dose: 2–2.5 mg/kg 1
• Maintenance: 1.5–3 mg/kg/day in 2 doses 1
• Associated with less nephrotoxicity than colistin 1
• No dose adjustment needed for CRRT 1

Tigecycline Considerations

Tigecycline should NOT be used as monotherapy for bacteremia or primary bloodstream infections due to suboptimal serum concentrations. 1, 2 Standard dosing (100 mg loading, then 50 mg every 12 hours) achieves Cmax of only 0.87 mg/L, insufficient for intravascular infections. 1

When Tigecycline May Be Considered:

• For approved indications only (complicated intra-abdominal infections, complicated skin/soft tissue infections) with secondary bacteremia 1
• High-dose regimen (200 mg loading, then 100 mg every 12 hours) may be used for severe infections as part of combination therapy, though not FDA-approved 1
• Avoid for pneumonia/VAP: Cure rates significantly lower than imipenem (47.9% vs 70.1%) and poor ELF concentrations 1

Combination Therapy

For severe CRAB infections (septic shock, severe sepsis), combination therapy with two in vitro active agents is recommended. 2, 3

Recommended Combinations:

• Colistin + high-dose carbapenem (if carbapenem MIC ≤32 mg/L) 3
• Colistin + sulbactam + tigecycline 3
• Sulbactam or polymyxin + second agent (tigecycline, rifampicin, or fosfomycin) for clinical failures or isolates with MIC at upper limit of susceptibility 1

Combinations to AVOID:

• Colistin + rifampin: Routine use not recommended (lacks proven benefit) 1, 2
• Colistin + glycopeptides (vancomycin): Discouraged due to increased nephrotoxicity without added benefit 1, 2, 4

Treatment Duration

For severe infections (VAP, bacteremia with severe sepsis/septic shock), maintain antimicrobial therapy for 2 weeks. 1, 2 Shorter durations may be acceptable for less severe infections. 1

Site-Specific Considerations

Pneumonia/VAP:

• Consider nebulized colistin as adjunctive therapy for MDR A. baumannii 2
• Avoid tigecycline monotherapy due to poor lung penetration 1

Urinary Tract Infections:

• Ampicillin-sulbactam 3 g sulbactam every 8 hours for sulbactam-susceptible isolates 3
• Colistin (6-9 million IU loading, then 9 million IU/day) for sulbactam-resistant isolates 3

Critical Monitoring

• Renal function: Monitor closely in all patients receiving colistin (nephrotoxicity occurs in up to 33% of patients) 2, 4
• Resistance emergence: More frequent monitoring for relapse in Acinetobacter infections, as resistance can develop during standard treatment via MDR efflux pumps 5
• Repeat cultures: Obtain blood and other specimens if relapse suspected 5

Common Pitfalls to Avoid

• Never use ertapenem for A. baumannii (lacks activity) 2
• Never use tigecycline monotherapy for bacteremia (suboptimal serum levels) 2, 6
• Avoid carbapenems in monotherapy in high-resistance areas 1
• Do not delay appropriate therapy in critically ill patients with known CRAB colonization or during outbreaks 2