Synergistic Activity of Colistin plus Rifampin against Colistin-Resistant KPC-producing Klebsiella pneumoniae.
Antimicrob Agents Chemother. 2013 Jun 10;
Authors: Tascini C, Tagliaferri E, Giani T, Leonildi A, Flammini S, Casini B, Lewis R, Ferranti S, Rossolini GM, Menichetti F
Infections caused by carbapenem-resistant KPC-producing Klebsiella pneumoniae are responsible for high mortality and represent a major therapeutic challenge especially when the isolates are also resistant to colistin. We used the checkerboard method to evaluate the synergistic activity of 10 antibiotic combinations against 13 colistin-resistant KPC K. pneumoniae (colistin MIC range: 8-128 mg/l). Colistin plus rifampin was the only combination that demonstrated consistent synergistic bacteriostatic activity against 13/13 strains tested, reducing the colistin MIC below the susceptibility breakpoint (MIC ≤ 2 mg/l) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/l. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin and tigecycline showed variable synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC K. pneumoniae (colistin MIC range: 0.5-2 mg/l), and 4/4 ertapenem-resistant, ESBL producing K. pneumoniae (ertapenem MIC range: 16-32 mg/l). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing K. pneumoniae, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant K. pneumoniae, and possibility slow the selection of hetero-resistant subpopulations during colistin therapy.
PMID: 23752510 [PubMed - as supplied by publisher]