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Updated: Jan 25, 2026

Listeria monocytogenes Infection of the Brain
Published on: October 2, 2018
Effect of subinhibitory concentrations of ampicillin on Listeria monocytogenes
Ángel Rodríguez-Villodres1, José Antonio Lepe1, Jesús Blázquez2
1Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain; Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Abstract:
Listeria monocytogenes is an important cause of meningoencephalitis associated with high mortality. The treatment of choice for listeriosis is ampicillin alone or in combination with gentamicin or penicillin G. However, only low ampicillin concentrations are recorded in the central nervous system (CNS). In this study, we analysed the effect of subinhibitory concentrations of ampicillin on the morphology, growth and survival of L. monocytogenes. The non-inhibitory concentration (NIC), the minimum inhibitory concentration (MIC) and the MIC/NIC ratio were determined. Gram and Live/Dead staining showed aggregates of L. monocytogenes cells when grown at subinhibitory concentrations of ampicillin, with >90% of viable cells. The L. monocytogenes strains tested showed an intermediate heteroresistance to ampicillin, characterised by a MIC/NIC ratio of 4. Our results seem to indicate that both intermediate heteroresistance and the formation of aggregates could play a role in the clinical failure of ampicillin in the treatment of CNS infections caused by L. monocytogenes. However, more studies are necessary to elucidate this question.
Insights
Subinhibitory ampicillin concentrations cause Listeria monocytogenes to form aggregates and exhibit heteroresistance. This may explain ampicillin treatment failures in central nervous system (CNS) listeriosis.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Listeria monocytogenes causes severe meningoencephalitis with high mortality.
- Ampicillin is the primary treatment for listeriosis, but achieves low concentrations in the central nervous system (CNS).
Purpose of the Study:
- To investigate the effects of subinhibitory ampicillin concentrations on Listeria monocytogenes morphology, growth, and survival.
- To determine the non-inhibitory concentration (NIC), minimum inhibitory concentration (MIC), and MIC/NIC ratio for L. monocytogenes.
Main Methods:
- Gram staining and Live/Dead staining were used to assess bacterial morphology and viability.
- Determination of NIC, MIC, and MIC/NIC ratio for ampicillin against L. monocytogenes strains.
Main Results:
- Subinhibitory ampicillin concentrations induced the formation of L. monocytogenes aggregates.
- Over 90% of cells within these aggregates remained viable.
- L. monocytogenes strains displayed intermediate heteroresistance to ampicillin, with a MIC/NIC ratio of 4.
Conclusions:
- Intermediate heteroresistance and aggregate formation in L. monocytogenes may contribute to ampicillin treatment failure in CNS infections.
- Further research is needed to confirm the clinical implications of these findings.
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