Table 2.

Therapeutic approaches to carbapenem-resistant Acinetobacter baumannii (CRAb)

Approach	Advantages	Limitations	References
Monotherapy
Polymyxins	Highly active in vitro Mainstay against CRAb	Nephrotoxicity of colistin + calcineurin inhibitors Unclear pharmacokinetics and dosing regimen Emergence of resistance with monotherapy	(43, 44)
Tigecycline	Highly active in vitro Large volume of distribution Tissue penetration	Increased mortality Resistance during therapy Inadequate serum and urine concentrations	(22, 29, 45)
Sulbactam	Comparable to carbapenems for susceptible strains Optimized with high dose and prolonged infusion	Co-resistance of sulbactam in CRAb	(46)
Combination therapy
Carbapenem + polymyxins	Favorable meta-analysis of in vitro data Successful in organ transplant recipients	Controlled trials needed	(22, 47)
Polymyxins + rifampin	Randomized controlled trial: increased bacterial clearance	No difference in 30-day mortality Rifampin interacts vs. azoles, calcineurin/mTOR inhibitors	(48)
Polymyxins + fosfomycin	Randomized controlled trial: favorable microbiological response	Not powered to detect differences in clinical outcomes IV fosfomycin not available in the US	(49)

mTOR, mammalian target of rapamycin; IV, intravenous; US, United States of America.