Colistin: An Update on the Antibiotic of the 21st Century

Silpak Biswas; Jean-Michel Brunel; Jean-Christophe Dubus; Martine Reynaud-Gaubert; Jean-Marc Rolain


Expert Rev Anti Infect Ther. 2012;10(8):917-934. 

In This Article

Combination Therapy

Colistin is frequently used as combination therapy in order to improve its antibacterial activity. A synergistic effect was reported in different studies to examine the combination of colistin with other antibiotics.[15,125,156] Aoki et al. have demonstrated the effectiveness of polymyxin in combination with rifampicin using a mouse pneumonia model.[157] There are different in vitro synergy testing methods such as time-kill assay, checkerboard assay and Etest assay, which are described in various studies.[158–161] Among these three methods, the time-kill assay is most commonly considered as the reference method.[158,162]

Combination therapy with rifampicin and polymixin is one of the most discussed alternatives for the treatment of MDR Gram-negative bacterial infections.[163–167] Among the various drugs tested for synergy with colistin, the efficacy of rifampicin is notable. The colistin rifampicin combination showed 100% synergy for MDR A.baumannii in most studies.[168–170] However, the same combination showed highly variable synergy (14–100%) for P. aeruginosa.[171] Table3 shows results of various in vitro studies carried out for synergy in combination of drugs with polymyxins.

The available evidence from various studies regarding the comparative effectiveness of colistin monotherapy and colistin combination therapy was reviewed by Petrosillo et al..[125] In this review, a synergistic effect was detected in all of the studies that examined the combination of colistin and rifampicin, whereas carbapenems exhibited a synergistic effect in few studies.[125]

Recent reviews suggest that sulbactam may be considered an option, in association with colistin, in the treatment of MDR A.baumannii infections.[172,173] Song et al. described the effectiveness of colistin and rifampicin in combination for the treatment of patients with VAP caused by carbapenem-resistant A.baumannii strains.[174] Sheng et al. recently demonstrated that the combination of colistin and tigecycline showed good in vitro activity for carbapenem-resistant A. baumannii.[171] A recent study by Liang et al. demonstrated that the combination of colistin and meropenem as well as colistin and minocycline were synergistic in vitro against extensive drug-resistant A. baumannii.[168] Souli et al. using time-kill assay demonstrated synergistic activity of colistin and imipenem combination therapy against K. pneumonia isolates carrying a bla(VIM-1)-type gene.[175] Another study by Arroyo et al. using checkerboard assay showed the synergistic effects of colistin and tigecycline in combination against pan-drug-resistant A. baumannii clinical isolates.[176]

A recent systematic study by Bergen et al. provides important information for optimization of colistin imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations of P. aeruginosa.[177] Another study by Liang et al. demonstrated that combinations of colistin/meropenem, colistin/rifampicin and colistin/minocycline are synergistic in vitro against extensive drug-resistant A. baumannii.[168] Another study by Wareham et al. demonstrated a synergistic effect of colistin in combination with teicoplanin against MDR A. baumannii strains.[178] Glycopeptides also showed synergy with polymyxin in different studies.[156,162]