IgM-enriched immunoglobulin improves colistin efficacy in a pneumonia model by Pseudomonas aeruginosa

Life Sci Alliance. 2022 Jun 21;5(10):e202101349. doi: 10.26508/lsa.202101349. Print 2022 Oct.

Abstract

We evaluated the efficacy of ceftazidime or colistin in combination with polyclonal IgM-enriched immunoglobulin (IgM-IG), in an experimental pneumonia model (C57BL/6J male mice) using two multidrug-resistant Pseudomonas aeruginosa strains, both ceftazidime-susceptible and one colistin-resistant. Pharmacodynamically optimised antimicrobials were administered for 72 h, and intravenous IgM-IG was given as a single dose. Bacterial tissues count and the mortality were analysed. Ceftazidime was more effective than colistin for both strains. In mice infected with the colistin-susceptible strain, ceftazidime reduced the bacterial concentration in the lungs and blood (-2.42 and -3.87 log10 CFU/ml) compared with colistin (-0.55 and -1.23 log10 CFU/ml, respectively) and with the controls. Colistin plus IgM-IG reduced the bacterial lung concentrations of both colistin-susceptible and resistant strains (-2.91 and -1.73 log10 CFU/g, respectively) and the bacteraemia rate of the colistin-resistant strain (-44%). These results suggest that IgM-IG might be useful as an adjuvant to colistin in the treatment of pneumonia caused by multidrug-resistant P. aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Ceftazidime / pharmacology
  • Ceftazidime / therapeutic use
  • Colistin / pharmacology
  • Colistin / therapeutic use
  • Drug Resistance, Multiple, Bacterial
  • Immunoglobulin M
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pneumonia* / drug therapy
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa

Substances

  • Anti-Bacterial Agents
  • Immunoglobulin M
  • Ceftazidime
  • Colistin