Enhancement of Acinetobacter baumannii biofilm growth by cephem antibiotics via enrichment of protein and extracellular DNA in the biofilm matrices

J Appl Microbiol. 2022 Sep;133(3):2002-2013. doi: 10.1111/jam.15712. Epub 2022 Jul 19.

Abstract

Aims: The aims were to determine the effects of subinhibitory concentrations of eight cephem and carbapenem antibiotics on the biofilm formation of Acinetobacter baumannii cells and examine their effects on pre-established biofilms.

Methods and results: Effects of antibiotics on biofilm formation were assayed using microtitre plates with polystyrene peg-lids. Cefmetazole, ceftriaxone, ceftazidime and cefpirome increased the biomass of pre-established biofilms on pegs in the range of their sub-minimum inhibitory concentrations (MICs), whereas none increased biofilm formation by planktonic cells. Carbapenems had a negative effect. The constituents of antibiotic-induced biofilms were analysed. Ceftriaxone or ceftazidime treatment markedly increased the matrix constituent amounts in the biofilms (carbohydrate, 2.7-fold; protein, 8.9-12.7-fold; lipid, 3.3-3.6-fold; DNA, 9.1-12.2-fold; outer membrane vesicles, 2.7-3.8-fold and viable cells, 6.8-10.1-fold). The antibiotic-enhanced biofilms had increased outer membrane protein A and were resistant to the anti-biofilm effect of azithromycin.

Conclusions: Some cephems increased the biomass of pre-established biofilms in the ranges of their sub-MICs. The antibiotic-enhanced biofilms possessed more virulent characteristics than normal biofilms.

Significance and impact of the study: Incomplete administration of certain cephems following biofilm-related Ac. baumannii infections could adversely cause exacerbated and chronic clinical results.

Keywords: Acinetobacter baumannii; azithromycin; biofilm; carbapenem antibiotics; cephem antibiotics; outer membrane protein A; outer membrane vesicles.

MeSH terms

  • Acinetobacter baumannii*
  • Anti-Bacterial Agents / pharmacology
  • Carbapenems / pharmacology
  • Ceftazidime / pharmacology
  • Ceftriaxone / pharmacology
  • DNA
  • Extracellular Polymeric Substance Matrix

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Ceftriaxone
  • DNA
  • Ceftazidime