What is the preferred treatment between Unasyn (ampicillin/sulbactam) and cefepime for Acinetobacter baumannii bacteremia?

Treatment of Acinetobacter baumannii Bacteremia: Unasyn vs Cefepime

Unasyn (ampicillin-sulbactam) is strongly preferred over cefepime for A. baumannii bacteremia, as cefepime has minimal to no intrinsic activity against this pathogen and should not be used. 1, 2

Why Cefepime Should Not Be Used

• Cefepime lacks clinically meaningful activity against A. baumannii and is not recommended for treatment of infections caused by this organism 2
• Cephalosporins as a class show poor activity against A. baumannii, with only 9% susceptibility rates reported for ceftazidime (the most active cephalosporin), making cefepime an inappropriate choice 3
• None of the novel β-lactam/β-lactamase inhibitor combinations recommended for carbapenem-resistant Enterobacterales are clinically active against carbapenem-resistant A. baumannii (CRAB) 4

Sulbactam as the Preferred β-Lactam Option

Sulbactam has intrinsic activity against A. baumannii independent of its β-lactamase inhibitor properties, making ampicillin-sulbactam a viable treatment option 4

Dosing for Bacteremia

• Administer ampicillin-sulbactam as a 4-hour infusion of 3g sulbactam every 8 hours (9-12g/day total) for isolates with MIC ≤4 mg/L 1, 5, 6
• This high-dose regimen optimizes pharmacokinetic/pharmacodynamic parameters for isolates with higher MICs up to 8 mg/L 4

Clinical Evidence Supporting Sulbactam

• Ampicillin-sulbactam demonstrated 88% susceptibility against clinical A. baumannii isolates in comparative studies, second only to polymyxin B 3
• Clinical outcomes with ampicillin-sulbactam were comparable to imipenem for severe A. baumannii infections in small series 4
• Ampicillin-sulbactam showed superior outcomes compared to colistin with lower nephrotoxicity (15.3% vs 33%) and comparable clinical cure rates 4, 5

Treatment Algorithm for A. baumannii Bacteremia

Step 1: Obtain Susceptibility Testing

• Obtain cultures and susceptibility testing immediately before initiating therapy 1
• Determine carbapenem susceptibility status and sulbactam MIC if available 6

Step 2: Assess Carbapenem Susceptibility

For carbapenem-susceptible A. baumannii:

• Use carbapenems (imipenem, meropenem, or doripenem) as first-line therapy in areas with low carbapenem resistance rates 4, 1, 2
• Do NOT use ertapenem as it lacks activity against A. baumannii 1

For carbapenem-resistant A. baumannii (CRAB):

• If sulbactam-susceptible (MIC ≤4 mg/L): Use high-dose ampicillin-sulbactam (9-12g/day) as preferred therapy 6
• If sulbactam-resistant: Use colistin with weight-based dosing (loading dose 9 million IU, then 4.5 million IU every 12 hours, adjusted for renal function) 1, 6

Step 3: Consider Combination Therapy for Severe Infections

• Combination therapy with two in vitro active agents is recommended for severe CRAB bacteremia, especially in cases of septic shock 1, 6
• Sulbactam or polymyxin may be combined with a second agent (tigecycline, rifampin, or fosfomycin) for clinical failures or isolates with MIC at the upper limit of susceptibility 4, 1

Step 4: Avoid Specific Combinations

• Do NOT routinely combine colistin plus rifampin as this lacks proven benefit 4, 1
• Avoid colistin plus glycopeptides (vancomycin) due to increased nephrotoxicity without added benefit 4, 1, 6
• Avoid polymyxin-meropenem combination for CRAB with high-level carbapenem resistance (MICs >16 mg/L) 1, 5

Treatment Duration

• Maintain antimicrobial therapy for 2 weeks for bacteremia, especially in cases manifesting as severe sepsis or septic shock 4, 1, 6
• Duration should be individualized based on clinical response, source control, and severity of infection 4, 1

Monitoring Requirements

• Monitor renal function closely in patients receiving colistin, as nephrotoxicity occurs in up to 33% of patients 1, 5, 6
• Monitor for clinical response and consider repeat blood cultures to document clearance 4
• Watch for emergence of resistance during therapy, particularly with colistin monotherapy 6

Critical Pitfalls to Avoid

• Never use cefepime as monotherapy or empiric therapy for suspected A. baumannii bacteremia as it lacks adequate activity 2, 3
• Do not use tigecycline as monotherapy for bacteremia due to suboptimal serum concentrations and higher treatment failure rates 4
• Avoid carbapenems in monotherapy for severe infections in areas with high CRAB prevalence (>25% resistance rates) 4
• Do not delay appropriate therapy while awaiting susceptibility results in critically ill patients with known CRAB colonization or during outbreaks 4