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Susceptibility Testing of Colistin for Acinetobacter baumannii: How Far Are We from the Truth?
Federica Sacco1,2, Paolo Visca3, Federica Runci3
1Department of Molecular Medicine, University of Rome "La Sapienza", 00161 Rome, Italy.
Abstract:
Acinetobacter baumannii is involved in life-threatening nosocomial infections, mainly in the intensive care units (ICUs), and often colistin may represent the last therapeutic opportunity. The susceptibility to colistin of 51 epidemiologically typed A. baumannii strains isolated in 2017 from clinical samples of patients hospitalized in the ICU of a tertiary care academic hospital was investigated. All isolates were carbapenem-resistant due to the presence of the bla OXA-23 gene in sequence group 1 (international clonal lineage II) and sequence group 4 (related to international clonal lineage II) isolates, and to the bla OXA-24/40 gene in sequence group 2 (international clonal lineage I) isolates. Vitek®2, agar diffusion, and broth microdilution tests showed major discordancy (≥2 dilution factors) in the minimum inhibitory concentration (MIC) values for colistin in 24 out of 51 isolates, resulting in erroneous reporting of qualitative susceptibility data for eight isolates. In growth kinetics experiments in the presence of colistin, five isolates grew with drug concentrations above the susceptibility breakpoint when incubated for >12 h, and three isolates showed the presence of heteroresistant subpopulations. This study highlights that the high frequency of isolation of carbapenem-resistant A. baumannii strains in high-risk infectious wards requires an accurate application of methods for detecting susceptibility to antibiotics, in particular to colistin, so as to ensure a correct therapeutic approach.
Insights
Carbapenem-resistant Acinetobacter baumannii infections are a critical threat. Accurate colistin susceptibility testing is vital for effective treatment, as standard methods can yield misleading results in these challenging cases.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Acinetobacter baumannii is a significant cause of hospital-acquired infections, particularly in intensive care units (ICUs).
- Colistin is often the last-resort antibiotic for treating multidrug-resistant A. baumannii infections.
- Carbapenem resistance in A. baumannii is frequently mediated by OXA-type carbapenemases (blaOXA-23, blaOXA-24/40).
Purpose of the Study:
- To evaluate colistin susceptibility testing methods for carbapenem-resistant Acinetobacter baumannii (CRAB) strains.
- To investigate the accuracy of standard antimicrobial susceptibility testing (AST) methods in CRAB.
- To identify potential sources of error in colistin susceptibility reporting for CRAB.
Main Methods:
- Epidemiological typing and molecular characterization of 51 CRAB isolates.
- Phenotypic susceptibility testing using Vitek 2, agar diffusion, and broth microdilution.
- Minimum Inhibitory Concentration (MIC) determination and analysis of discordancy.
- Growth kinetics experiments to assess heteroresistance and growth at higher drug concentrations.
Main Results:
- All 51 A. baumannii isolates were carbapenem-resistant, with blaOXA-23 or blaOXA-24/40 genes identified.
- Major discordancy (≥2 log2 dilution factors) in colistin MICs was observed in 24 out of 51 isolates.
- Erroneous qualitative susceptibility reporting occurred for eight isolates due to testing discrepancies.
- Growth kinetics revealed heteroresistant subpopulations in three isolates and growth above susceptibility breakpoints in five isolates after 12 hours.
Conclusions:
- Standard colistin susceptibility testing methods demonstrate significant discordancy for CRAB isolates.
- Inaccurate susceptibility reporting can compromise therapeutic decisions for life-threatening infections.
- Robust and accurate AST methods are crucial for guiding appropriate antibiotic use against CRAB.
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