What is the recommended treatment approach for a patient suspected of having an Acinetobacter baumannii infection, particularly in a healthcare setting or with risk factors for hospital-acquired infections?

Treatment of Acinetobacter baumannii Infections

For carbapenem-susceptible A. baumannii, use carbapenems (imipenem, meropenem, or doripenem) as first-line therapy; for carbapenem-resistant A. baumannii (CRAB), high-dose ampicillin-sulbactam is the preferred agent when sulbactam MIC ≤4 mg/L, with polymyxins (colistin or polymyxin B) reserved for isolates resistant to all other options. 1, 2

Initial Assessment and Empirical Therapy

Obtain cultures and susceptibility testing immediately before starting antibiotics. 1 The choice of empirical therapy depends critically on:

• Local resistance patterns in your institution—if carbapenem resistance rates exceed 25%, avoid carbapenem monotherapy for severe infections 1, 2
• Patient colonization status—if the patient is known to be colonized with CRAB or during an outbreak, include colistin empirically 3
• Infection severity—severe sepsis, septic shock, or ventilator-associated pneumonia warrant immediate combination therapy 1, 2

Treatment Algorithm Based on Susceptibility

For Carbapenem-Susceptible A. baumannii

Use carbapenems as first-line monotherapy in areas with low resistance rates (<25%). 1, 2 Specific dosing:

• Imipenem: 0.5-1 g IV every 6 hours (cannot use extended infusion due to drug instability) 2
• Meropenem: 2 g IV every 8 hours (high doses carry seizure risk, particularly in renal dysfunction or CNS pathology) 2
• Doripenem: standard dosing per institutional protocols 1

Critical caveat: Never use ertapenem for A. baumannii—it completely lacks activity against this pathogen. 1

For Carbapenem-Resistant A. baumannii (CRAB)

First-Line Option: High-Dose Ampicillin-Sulbactam

Ampicillin-sulbactam is the preferred agent for CRAB when sulbactam MIC ≤4 mg/L. 1, 2 This recommendation is based on:

• Superior safety profile compared to polymyxins (15.3% vs 33% nephrotoxicity) 1, 2
• Comparable clinical cure rates to imipenem in severe infections 1
• Significantly higher microbiologic cure rates at day 7 compared to colistin 2

Dosing: 3 g sulbactam (9 g ampicillin-sulbactam) IV every 8 hours as a 4-hour infusion (total 9-12 g sulbactam daily). 1, 4, 2

Second-Line Option: Polymyxins

When sulbactam is not an option (MIC >4 mg/L or resistance), use colistin or polymyxin B. 3, 2

Colistin dosing (colistimethate sodium):

• Loading dose: 6-9 million IU IV 3, 2
• Maintenance: 4.5 million IU IV every 12 hours for creatinine clearance >50 mL/min 3, 2
• Adjust maintenance dose based on creatinine clearance for CrCl <50 mL/min 3
• For continuous renal replacement therapy: at least 9 million IU/day 3
• For intermittent hemodialysis: 2 million IU every 12 hours with normal loading dose; perform dialysis toward end of dosing interval 3

Critical pharmacokinetic consideration: Colistin requires a loading dose because steady-state plasma concentrations are not reached for 2-3 days without it, leaving patients with suboptimal levels during the critical early treatment period. 3

Polymyxin B dosing (alternative with less nephrotoxicity):

• Loading dose: 2-2.5 mg/kg IV 3, 2
• Maintenance: 1.5-3 mg/kg/day IV divided into 2 doses 3, 2
• No dose adjustment needed for renal replacement therapy 3, 2

Third-Line Option: Tigecycline

Tigecycline should NEVER be used as monotherapy for bacteremia or primary bloodstream infections due to suboptimal serum concentrations. 1, 2 However, it may be considered in specific circumstances:

For approved indications only (complicated intra-abdominal infections, complicated skin/soft tissue infections) with tigecycline MIC ≤1 mg/L: 3

• Standard dose: 100 mg IV loading, then 50 mg IV every 12 hours 3

For severe non-approved indications (especially pneumonia) when other options are exhausted and MIC ≤1 mg/L: 3

• High-dose regimen: 200 mg IV loading, then 100 mg IV every 12 hours 3, 1, 2
• Must be used in combination with another active agent 3

Important limitation: Tigecycline has poor lung penetration with very low epithelial lining fluid concentrations (0.01-0.02 mg/L), making it suboptimal for pneumonia even at high doses. 3

Combination Therapy for Severe Infections

For severe CRAB infections (septic shock, severe sepsis, ventilator-associated pneumonia), use combination therapy with two in vitro active agents. 1, 2

Recommended combinations: 1, 2

• Colistin + high-dose carbapenem (even if resistant, for synergy)
• Colistin + sulbactam + tigecycline (triple therapy for critically ill)
• Sulbactam or polymyxin + tigecycline, rifampicin, or fosfomycin

Combinations to AVOID: 3, 1

• Colistin + rifampin (routine use not recommended; lacks proven clinical benefit despite microbiologic eradication, and increases hepatotoxicity) 3
• Colistin + vancomycin or other glycopeptides (significantly increased nephrotoxicity without added benefit) 3, 1
• Polymyxin + meropenem for high-level carbapenem resistance (MIC >16 mg/L; ineffective) 1

For monotherapy vs combination in non-severe infections: Monotherapy with an active agent is generally sufficient for uncomplicated infections when the isolate is susceptible. 4

Site-Specific Considerations

Ventilator-Associated Pneumonia (VAP)

• Consider nebulized colistin as adjunctive therapy to systemic treatment for MDR A. baumannii pneumonia/VAP 1, 2
• Never use tigecycline monotherapy for VAP due to poor lung penetration 1, 2
• Treatment duration: 2 weeks for severe infections with sepsis/septic shock 1, 2

Bacteremia

• Maintain therapy for 2 weeks, especially with severe sepsis or septic shock 1, 2
• Obtain repeat blood cultures to document clearance 1
• Never use tigecycline monotherapy—only consider if part of combination for secondary bacteremia from approved indication sites 1, 2

Urinary Tract Infections

• Remove or replace urinary catheter when possible 4
• For uncomplicated UTI with susceptible isolates: 7 days of monotherapy 4
• For complicated UTI or systemic symptoms: up to 14 days, consider combination therapy 4
• Preferred agents: Ampicillin-sulbactam (3 g sulbactam every 8 hours) for sulbactam-susceptible; colistin (6-9 million IU loading, then 9 million IU/day) for resistant isolates 4

Critical Monitoring Requirements

Monitor renal function closely in all patients receiving colistin—nephrotoxicity occurs in up to 33% of patients. 1, 4, 2 Check serum creatinine at baseline and at least every 2-3 days during therapy.

Monitor for clinical response and consider repeat cultures to document microbiological clearance, particularly important for A. baumannii given reports of resistance development during therapy. 1, 5

Watch for seizures in patients receiving high-dose meropenem, especially those with renal dysfunction or CNS pathology. 2

Common Pitfalls to Avoid

• Do not delay appropriate therapy while awaiting susceptibility results in critically ill patients with known CRAB colonization or during outbreaks—start empirical combination therapy immediately 1
• Do not use carbapenems as monotherapy for severe infections in high-resistance areas (>25% carbapenem resistance) 1, 2
• Do not forget the loading dose for colistin—without it, therapeutic levels are not achieved for 2-3 days 3
• Do not use tigecycline monotherapy for bacteremia or pneumonia—suboptimal drug levels lead to treatment failure 1, 2
• Do not combine colistin with rifampin routinely—no proven clinical benefit and increased hepatotoxicity 3, 1

Resistance Surveillance

A. baumannii has high propensity for developing resistance during therapy, particularly via MDR efflux pumps. 5 If clinical relapse is suspected:

• Obtain repeat cultures immediately 5
• Test all isolates for susceptibility to tigecycline and other antimicrobials 5
• Consider switching to combination therapy or alternative agents 5