What antibiotics are effective against Acinetobacter baumannii infections?

Antibiotics Effective Against Acinetobacter baumannii

For carbapenem-susceptible A. baumannii, carbapenems (imipenem, meropenem, or doripenem) are first-line therapy, while for carbapenem-resistant A. baumannii (CRAB), ampicillin-sulbactam is preferred when the isolate is sulbactam-susceptible (MIC ≤4 mg/L), and colistin is reserved for sulbactam-resistant isolates. 1, 2, 3

Treatment Algorithm Based on Susceptibility

For Carbapenem-Susceptible A. baumannii

• Use carbapenems as first-line agents in areas with low carbapenem resistance rates (<25%) 1, 3
• Effective carbapenems include imipenem, meropenem, and doripenem—ertapenem lacks activity against A. baumannii and must never be used 1, 4
• Avoid carbapenem monotherapy for severe infections in areas with high resistance rates (>25% carbapenem resistance) 1, 3
• Imipenem dosing: 0.5–1 g every 6 hours (extended infusion not possible due to drug instability) 3
• Meropenem dosing: 2 g every 8 hours (high doses carry seizure risk) 3

For Carbapenem-Resistant A. baumannii (CRAB)

First-Line: Ampicillin-Sulbactam (if sulbactam-susceptible)

• Ampicillin-sulbactam is the preferred treatment for CRAB with sulbactam MIC ≤4 mg/L due to superior safety profile and comparable efficacy to polymyxins 2, 3
• Dosing: 3 g sulbactam every 8 hours (9–12 g/day total) administered as 4-hour infusions 1, 2, 3
• Sulbactam demonstrates lower nephrotoxicity compared to colistin (15.3% vs 33%) with significantly higher microbiologic cure rates at day 7 1, 3

Second-Line: Polymyxins (if sulbactam-resistant)

• Colistin is reserved for CRAB showing resistance to all beta-lactams and sulbactam 2, 3
• Colistin dosing: Loading dose of 6–9 million IU, followed by maintenance doses of 4.5 million IU every 12 hours (adjust for renal function) 1, 3
• Polymyxin B alternative: Loading dose of 2–2.5 mg/kg, maintenance doses of 1.5–3 mg/kg/day in 2 divided doses 3
• Polymyxin B is associated with less nephrotoxicity than colistin 3
• Monitor renal function closely—nephrotoxicity occurs in up to 33% of patients receiving colistin 1, 3

Tigecycline Considerations

• Never use tigecycline as monotherapy for bacteremia or primary bloodstream infections due to suboptimal serum concentrations and higher treatment failure rates 1, 3, 5
• Tigecycline may be considered only for approved indications (complicated intra-abdominal infections, complicated skin/soft tissue infections) with secondary bacteremia 3
• High-dose tigecycline (200 mg loading, then 100 mg every 12 hours) may be used for severe infections as part of combination therapy, though not FDA-approved 3
• Avoid tigecycline monotherapy for pneumonia/VAP due to poor lung penetration 3

Combination Therapy for Severe Infections

For severe CRAB infections (septic shock, severe sepsis), combination therapy with two in vitro active agents is recommended to improve clinical outcomes and prevent resistance. 1, 2, 3

Recommended Combinations

• Colistin + high-dose carbapenem (for isolates with meropenem MIC <8 mg/L) 2, 3
• Colistin + sulbactam + tigecycline 3
• Sulbactam or polymyxin + second agent (tigecycline, rifampicin, or fosfomycin) for clinical failures or infections with MIC in the upper limit of susceptibility 6, 1

Combinations to AVOID

• Do not combine colistin plus rifampin routinely—this lacks proven clinical benefit and is associated with higher hepatotoxicity 6, 1
• Avoid colistin plus glycopeptides (vancomycin, telavancin, daptomycin)—this increases nephrotoxicity without added benefit 6, 1, 3
• Avoid polymyxin-meropenem combination for CRAB with high-level carbapenem resistance (MICs >16 mg/L) 1

Evidence Limitations

• There are no convincing data to recommend routine combination therapy over monotherapy for all A. baumannii infections 6
• Combination therapy has not demonstrated consistent mortality benefit in clinical trials, though it may prevent emergence of resistance 6

Treatment Duration

Maintain antimicrobial therapy for 2 weeks for severe infections (VAP, bacteremia with severe sepsis/septic shock). 1, 3

• Shorter durations may be acceptable for less severe infections 1, 3
• Treatment duration should be based on infection site and severity 1

Site-Specific Considerations

Respiratory Infections (HAP/VAP)

• Consider nebulized colistin as adjunctive therapy for MDR A. baumannii pneumonia/VAP 1, 3
• Monitor closely for relapse during treatment—resistance can develop during standard therapy via MDR efflux pump mechanisms 5

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

Bacteremia

• Never use tigecycline as monotherapy 1, 3
• Combination therapy strongly recommended for septic shock 1

Critical Pitfalls to Avoid

• Never use ertapenem for A. baumannii—it lacks activity against this pathogen despite being a carbapenem 1
• Do not delay appropriate therapy while awaiting susceptibility results in critically ill patients with known CRAB colonization or during outbreaks 1
• Avoid carbapenems as monotherapy for severe infections in areas with high CRAB prevalence (>25% resistance rates) 1
• Obtain cultures and susceptibility testing before initiating therapy to guide targeted treatment 1, 2
• Monitor for clinical response and consider repeat blood cultures to document clearance in bacteremia 1