Colistin Resistance Emerges in Multidrug-Resistant Gram-Negative Bacteria

Strategic Insights -

Researchers from Monash University in Clayton, Australia, have reported the emergence of colistin resistance in multidrug-resistant Gram-negative bacteria, specifically Klebsiella pneumoniae. The study, published in the Journal of Antimicrobial Chemotherapy, examined the in vitro pharmacodynamic properties of colistin against 21 multidrug-resistant clinical isolates of K. pneumoniae from 16 different clinical sites worldwide.

Key Takeaways:

  • The study found that six isolates were colistin-resistant, with MICs of ≥ 32 mg/L, while 15 of the 16 isolates considered colistin-susceptible based on MICs showed colistin heteroresistance.
  • Colistin exhibited extremely rapid killing against susceptible isolates, but regrowth was observed as early as 2 h after treatment, and substantial regrowth at 24 h even at concentrations up to 64x MIC for some isolates.
  • The study suggests that monotherapy with colistin methanesulfonate and long dosage intervals may be problematic for the treatment of infections caused by multidrug-resistant K. pneumoniae, particularly for colistin-heteroresistant strains.
  • Colistin exhibited no or very modest post-antibiotic effect (PAE) against the isolates tested.
  • The researchers conclude that further investigation on combination therapy of colistin with other antibiotics is warranted.

Statistics:

  • 21 multidrug-resistant clinical K. pneumoniae isolates from 16 different clinical sites worldwide were employed in the study.
  • 18 different PFGE groups were identified among the 22 isolates.
  • For susceptible isolates, colistin MICs ranged from 0.125 to 1 mg/L.
  • 15 of the 16 isolates considered colistin-susceptible by MIC showed colistin heteroresistance.
  • Colistin-regrowth was observed in 6 of the 7 isolates tested at 24 h, with some isolates showing substantial regrowth even at concentrations up to 64x MIC.

Sources:

  • A. Poudyal et al., Monash University, "In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae," Journal of Antimicrobial Chemotherapy, 2008;62(6):1311-1318.
  • News release, Monash University, "Resistance to colistin emerging in multidrug-resistant Gram-negative bacteria," 2009.