Sub-minimum inhibitory concentrations in ceftazidime exacerbate the formation of Acinetobacter baumannii biofilms

Bipin Yadav1, Anjali Jaiswal1, Durgesh Kumar1

  • 1Laboratory of Applied Microbiology and Cancer Remedies, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.

Microbial Pathogenesis
|December 15, 2024
PubMed

Insights

Low-dose antibiotics, like ceftazidime (CAZ) at sub-minimum inhibitory concentrations (sub-MICs), can unexpectedly promote Acinetobacter baumannii growth and biofilm formation, contributing to antibiotic resistance. This highlights environmental antibiotic contamination risks.

Area of Science:

  • Microbiology
  • Environmental Science
  • Pharmacology

Background:

  • Acinetobacter baumannii is a Gram-negative coccobacillus frequently causing nosocomial infections, particularly in immunocompromised individuals within healthcare settings.
  • Antibiotic resistance is exacerbated by the presence of antibiotics at sub-minimum inhibitory concentrations (sub-MICs) in various environmental settings, including wastewater and natural water bodies.
  • Third-generation cephalosporins, such as ceftazidime (CAZ), are commonly prescribed in India to treat A. baumannii infections.

Purpose of the Study:

  • To investigate the effects of ceftazidime (CAZ) at sub-minimum inhibitory concentrations (sub-MICs) on the A. baumannii KSK1 strain.
  • To assess the impact of CAZ sub-MICs on bacterial adhesion, growth, morphology, and biofilm formation.
  • To understand the implications of environmental antibiotic contamination by sub-MICs on antibiotic resistance and bacterial persistence.

Main Methods:

  • Exposure of A. baumannii KSK1 strain to ceftazidime (CAZ) at sub-minimum inhibitory concentrations (sub-MICs).
  • Evaluation of bacterial adhesion to lung epithelial cells.
  • Monitoring of bacterial growth kinetics and morphology.
  • Assessment of bacterial aggregate formation and in vitro biofilm formation.

Main Results:

  • CAZ sub-MICs reduced initial adhesion to lung epithelial cells and temporarily slowed A. baumannii KSK1 growth, but the bacteria eventually resumed growth.
  • Exposure to CAZ sub-MICs altered the morphology of planktonic A. baumannii KSK1 cells, inducing the formation of aggregates resembling biofilms.
  • CAZ sub-MICs significantly increased in vitro biofilm formation by A. baumannii KSK1.

Conclusions:

  • Sub-minimum inhibitory concentrations (sub-MICs) of ceftazidime (CAZ) can paradoxically promote A. baumannii persistence and biofilm formation, posing a significant challenge.
  • Environmental contamination with antibiotics at sub-MIC levels, particularly in wastewater, may contribute to the selection and persistence of antibiotic-resistant strains.
  • The findings emphasize the need to consider the impact of sub-MIC antibiotics in both clinical therapy and environmental monitoring to combat antibiotic resistance.