Synergistic Activity of Colistin plus Rifampin against Colistin-Resistant KPC-Producing Klebsiella pneumoniae

Abstract

f Infections caused by carbapenem-resistant KPC-producing Klebsiella pneumoniae are responsible for high rates of 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-producing K. pneumoniae isolates (colistin MIC range of 8 to 128 mg/liter). 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/liter) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/liter. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin, and tigecycline showed variously synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC-producing K. pneumoniae isolates (colistin MIC range of 0.5 to 2 mg/liter) and 4/4 ertapenem-resistant extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates (ertapenem MIC range of 16 to 32 mg/liter). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing K. pneumoniae isolates, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant K. pneumoniae and may possibly slow the selection of heteroresistant subpopulations during colistin therapy.

Colistin-Resistant Klebsiella pneumoniae: Report of a Cluster of 24 Cases from a New Oncology Center in Eastern India

“…Case series have been documented from Italy, the United States, Hungary, and Greece. [4][5][6][7][8][9][10] However, such reports are rare, although we suspect underreporting of cases. One of the challenges faced in the developing world is lack of isolation facilities in adequate numbers and the lack of adequate awareness, which makes infection control a priority.…”

Colistin-Resistant Klebsiella pneumoniae: Prevalence of Integrons and Synergistic Out Turn for Colistin-Meropenem

“…We are now in a state to prohibit the emergence of future resistance and are made workable with the ease of combination therapy using different classes of antibiotics for the betterment in efficacy (13). In addition, it is necessary to have knowledge in selecting antibiotics with appropriate synergistic activity (14). Combination of colistin with carbapenem is studied in detail to at least save the last resort of available antibiotics.…”

KPC-Producing Klebsiella pneumoniae Strains That Harbor AAC(6′)-Ib Exhibit Intermediate Resistance to Amikacin

“…Finally, AMK and COL demonstrated synergy, but exclusively against COL-resistant CR-Kp strains. Previous studies among COL-resistant CR-Kp strains identified combinations of COL plus rifampin (19,20) or doxycycline (19) as potentially synergistic. These combinations may be more attractive for subsequent studies given the potential additive toxicities of AMK and COL combination therapy.…”