What are the recommended antibiotics for treating Multi-Drug Resistant (MDR) Acinetobacter infections?

Treatment of Multidrug-Resistant Acinetobacter Infections

For MDR Acinetobacter infections, colistin-based combination therapy is the recommended first-line treatment, with specific regimens tailored to infection site: colistin plus carbapenem (with or without adjunctive inhaled colistin) for pneumonia, and colistin-carbapenem combinations for bloodstream infections. 1

First-Line Treatment by Infection Site

Pneumonia (Hospital-Acquired/Ventilator-Associated)

• Colistin with or without carbapenem, plus adjunctive inhaled colistin for at least 7 days 1, 2
• Colistin dosing: 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h 1
• Adding inhaled colistin significantly improves clinical cure rates (57.4% vs 37.0%, p=0.003) 3
• Tigecycline monotherapy is strongly contraindicated for pneumonia due to poor outcomes and increased mortality 1, 2

Bloodstream Infections

• Colistin-carbapenem combination therapy for 10-14 days 1, 2
• Same colistin dosing as above with loading dose mandatory 1
• Combination therapy reduces mortality compared to monotherapy 2
• Tigecycline monotherapy associated with 2.73-fold increased mortality (OR 2.73,95% CI 1.53-4.87) 4

Complicated Urinary Tract Infections

• Colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h for 5-7 days 1
• Aminoglycosides may be considered if susceptible 1

Alternative Treatment Options

Sulbactam-Based Regimens

• Sulbactam 9-12 g/day IV in 3-4 divided doses for severe infections 1
• FDA-approved for Acinetobacter calcoaceticus in skin/soft tissue infections 5, 6
• Preferable to colistin for strains with MIC ≤4 mg/L due to better safety profile 2
• 4-hour infusion recommended to optimize pharmacokinetics 1

Tigecycline (Only in Combination)

• High-dose tigecycline required: 200 mg IV loading dose, then 100 mg IV q12h 4
• Never use as monotherapy - associated with significantly increased mortality 1, 2, 4
• Only use when isolate MIC ≤0.5 mg/L 4
• Must be combined with colistin or carbapenem 1, 2
• Standard dosing (100 mg loading, 50 mg q12h) is inadequate and associated with higher mortality 4

Minocycline

• Alternative when other options limited or contraindicated 2
• Demonstrates 60-80% susceptibility against MDR strains 2
• Must be used in combination, never as monotherapy for serious infections 2

Critical Dosing Considerations

Colistin Loading Dose

• Loading dose is mandatory - without it, therapeutic levels take 2-3 days to achieve 1
• 6-9 million IU loading dose, then 9 million IU/day in 2-3 doses 1
• One million IU colistin = 80 mg colistimethate sodium (CMS) 1
• Plasma concentrations often suboptimal with standard dosing, associated with higher mortality 1

Carbapenem Optimization

• Extended infusion (3-4 hours) recommended for high MIC strains (≥8 mg/L) 1
• Meropenem 2 g IV q8h by extended infusion 1
• Imipenem cannot use extended infusion due to drug instability 1

Treatment Duration by Site

• Pneumonia: At least 7 days, typically 10-14 days 1, 2
• Bloodstream infections: 10-14 days 1, 2
• Complicated UTI: 5-7 days 1
• Intra-abdominal infections: 5-7 days 1

Combination vs. Monotherapy

Combination therapy is strongly preferred over monotherapy for all severe MDR Acinetobacter infections 2. Colistin-carbapenem combinations show the best outcomes in network meta-analyses 2. Monotherapy is only acceptable for uncomplicated urinary tract infections with documented susceptibility 1.

Critical Pitfalls to Avoid

1. Never use tigecycline monotherapy for pneumonia or bloodstream infections - documented increased mortality 1, 2, 4
2. Never omit the colistin loading dose - delays therapeutic levels by 2-3 days 1
3. Never use standard-dose tigecycline (50 mg q12h) for serious infections - high-dose required 4
4. Monitor for resistance development during treatment, particularly with Acinetobacter - obtain repeat cultures if clinical deterioration occurs 7
5. Expect high nephrotoxicity with colistin - AKI develops in 53.7% of patients 3

Essential Ancillary Measures

• Infectious disease consultation is highly recommended for all MDR Acinetobacter infections 1
• Obtain susceptibility testing before finalizing therapy - resistance patterns vary widely 1, 2
• Monitor renal function closely - colistin nephrotoxicity is common and dose-dependent 1, 3
• Consider source control - duration should account for adequacy of drainage/debridement 1