What are the best antibiotics for treating Acinetobacter infections?

Treatment of Acinetobacter Infections

First-Line Treatment Based on Susceptibility

For carbapenem-susceptible Acinetobacter, carbapenems (imipenem or meropenem) are the drugs of choice, while for carbapenem-resistant strains, polymyxin-based combination therapy is recommended. 1, 2

Carbapenem-Susceptible Strains

• Imipenem 0.5-1g every 6 hours or meropenem 2g every 8 hours (extended infusion over 40-60 minutes) should be used for susceptible isolates 1, 2, 3
• Carbapenems remain first-line only in areas with low carbapenem resistance rates 1
• Imipenem infusions of 500mg should be given over 20-30 minutes, while 1000mg doses require 40-60 minutes 3

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

Polymyxin-based combination therapy is strongly recommended over monotherapy for severe CRAB infections. 4, 2

Polymyxin Dosing (Colistin)

• Loading dose: 6-9 million IU, followed by 9 million IU/day in 2-3 divided doses 1
• The loading dose is critical because without it, therapeutic levels are not reached for 2-3 days 1
• One million IU of colistin equals 80mg of colistimethate sodium (CMS) 1

Polymyxin B Dosing

• Loading dose: 2-2.5 mg/kg, followed by 1.5-3 mg/kg/day in 2 doses 1
• Unlike colistin, polymyxin B is not a prodrug and dosing cannot be extrapolated between the two agents 1

Site-Specific Treatment Recommendations

Pneumonia/Ventilator-Associated Pneumonia (VAP)

For CRAB pneumonia, use intravenous polymyxin PLUS adjunctive inhaled colistin in combination with another active agent. 4, 2

• Duration: minimum 7 days 4
• Nebulized antibiotics should be delivered using ultrasonic or vibrating plate nebulizers 2
• Avoid tigecycline monotherapy for pneumonia due to poor outcomes 1, 4, 2

Bloodstream Infections

• Colistin with or without carbapenem for 10-14 days 4
• Combination therapy (colistin plus carbapenem, sulbactam, tigecycline, or other agents) showed higher 14-day survival and microbiological eradication rates compared to colistin monotherapy 1

Meningitis/CNS Infections

For Acinetobacter meningitis, use intravenous antimicrobials PLUS intrathecal or intraventricular colistin. 2

• Treatment duration: approximately 3 weeks 2
• Combined IV and intrathecal colistin is a useful and safe option 5
• Imipenem is NOT indicated for meningitis due to lack of safety and efficacy data 3

Alternative Agents

Sulbactam

Sulbactam is preferable to colistin for strains with MIC ≤4 mg/L due to better safety profile and comparable efficacy. 1, 4

• Dose: 9-12 g/day in 3-4 divided doses (consider 4-hour infusion to optimize pharmacokinetics) 1
• Has intrinsic activity against Acinetobacter species independent of beta-lactamase inhibition 1, 4
• Clinical and microbiological response comparable to colistin but with lower nephrotoxicity (15.3% vs 33%) 1

Tigecycline

Tigecycline should NOT be used as monotherapy and is only appropriate in combination therapy for non-pulmonary infections. 1, 4, 2

• For approved indications (complicated skin/soft tissue and intra-abdominal infections): standard dose of 100mg loading, then 50mg every 12 hours may be adequate if MIC ≤1 mg/L 1
• For pneumonia and other severe infections: high-dose regimen of 200mg loading, then 100mg every 12 hours in combination with another active agent 1, 4
• Critical caveat: Tigecycline monotherapy for pneumonia is associated with poor outcomes 1, 4, 6

Minocycline

• Demonstrates 60-80% susceptibility against MDR strains 4
• Should be used in combination rather than monotherapy for serious infections 4
• Consider when isolate is susceptible to minocycline but resistant to other agents 4

Combination vs. Monotherapy

Combination therapy is generally preferred over monotherapy for severe CRAB infections, particularly in patients with septic shock or high risk of death. 1, 4, 2

Evidence for Combination Therapy

• Colistin-carbapenem combinations showed best outcomes in network meta-analyses 4
• Higher 14-day survival and microbiological eradication with combination therapy versus colistin monotherapy in XDR bacteremia 1
• However, colistin plus rifampicin failed to show clinical superiority over colistin alone in randomized trials, despite better microbiological eradication 1

Agents to Avoid in Combination

• Colistin plus rifampicin: No clinical benefit and higher hepatotoxicity 1
• Aminoglycoside monotherapy: Should not be used 2
• Polymyxin-meropenem for high-level carbapenem resistance: Avoid this combination 2

Empiric Coverage Considerations

Empiric coverage for Acinetobacter is justified during outbreaks, endemic situations, or in previously colonized patients. 1, 2

• Include a polymyxin in empiric therapy when carbapenem-resistant Acinetobacter is suspected 1, 2
• In areas with high carbapenem resistance, carbapenems should not be used as monotherapy 1
• Sulbactam and tigecycline should not be used as empiric monotherapy 1

Critical Monitoring and Safety Considerations

Nephrotoxicity with Polymyxins

• Regular renal function monitoring is essential with polymyxin use 1, 2
• Colistin nephrotoxicity rates: 15-33% in clinical studies 1
• Adjust polymyxin dosing in renal impairment 2
• Sulbactam has significantly better safety profile compared to colistin 1

Seizure Risk

• High-dose meropenem (2g every 8 hours) is associated with increased seizure risk 1, 2
• Imipenem is contraindicated in CNS infections due to seizure risk 3

Emerging Therapies

Sulbactam-durlobactam in combination with background carbapenem therapy shows the greatest mortality reduction for CRAB pulmonary infections. 6

• This represents the most promising new combination for CRAB 6
• Multiple novel agents are in Phase 1-3 trials, including zidebactam/WCK-5222 and funobactam/XNW-4107 7

Common Pitfalls to Avoid

• Never use tigecycline monotherapy for pneumonia or bloodstream infections 1, 4, 2, 6
• Do not use aminoglycoside monotherapy despite FDA approval for Acinetobacter 2, 8
• Avoid colistin monotherapy without a loading dose - subtherapeutic levels persist for 2-3 days 1
• Do not extrapolate colistin dosing to polymyxin B - they have different pharmacokinetics 1
• Obtain susceptibility testing before finalizing therapy - resistance patterns vary widely 4, 2
• Consider infectious disease consultation for all MDR Acinetobacter infections 4