Combination Therapy for Carbapenem-resistant Gram-negative Bacteria

Alexandre P Zavascki; Jurgen B Bulitta; Cornelia B Landersdorfer


Expert Rev Anti Infect Ther. 2013;11(12):1333-1353. 

In This Article

Conceptual Basis of Combination Therapy Against CR GNB

Cornerstone Therapy & Adjuvant Agents

Combination therapy for CR GNB is usually based on a cornerstone antibiotic for which the organism presents in vitro susceptibility, although this is likely not possible for PDR isolates. The main antibiotic is associated with an adjuvant drug to which the organism may be susceptible in vitro or not. It needs to be emphasized that the concept of susceptibility test refers to antibiotic monotherapy. An adjuvant drug, which may cause no bacterial killing in monotherapy, can still be highly beneficial to maximize bacterial killing or prevent resistance.

By far, polymyxins are the antibiotic class for which most CR GNB present in vitro susceptibility, and polymyxin-only-susceptible (POS) isolates account for a significant proportion of CR GNB with XDR profile.[5–11] Therefore, polymyxins (i.e., either colistin or polymyxin B) are the most common cornerstone agents in combination schemes. However, other agents such as tigecycline have also been the main antibiotic in some combination schemes for A. baumannii and Enterobacteriaceae infections. Finally, in some situations even carbapenems have been used as the main agent for the treatment of CR GNB infections.

The most frequently used adjuvant therapies for CR GNB infections are carbapenems, tigecycline, fosfomycin, aminoglycosides and rifampicin. Other agents are discussed later.