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Increased Antibiotic Susceptibility of Gram-Positive Bacteria in Cerebrospinal Fluid Compared to Broth
Jennifer S Wirth1,2, Marija Djukic1,2, Katrin Biesner1,2
1Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, 37075 Göttingen, Germany.
Abstract:
Background: In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens that are effective in vivo in spite of reduced in vitro susceptibility in culture media. Methods: Antibiotic susceptibility was tested in cerebrospinal fluid (CSF) and Mueller-Hinton broth (Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis) or brain-heart infusion (Streptococcus pneumoniae). Results: Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were either lower in CSF than in broth or equal in CSF and broth. The difference between MICs in CSF and broth was prominent with gentamicin, levofloxacin, linezolid (staphylococci), and vancomycin (staphylococci and pneumococcus), whereas it was absent with ampicillin (E. faecalis), penicillin G (S. pneumoniae), linezolid (enterococcus and pneumococcus), and vancomycin (enterococcus). In no case was the MIC or MBC higher in CSF than in broth. Conclusions: Several antibiotics possess an antibacterial effect in CSF at lower concentrations than the MICs determined in broth, i.e., MICs in broth underestimate in situ susceptibility in CSF.
Insights
Antibiotic susceptibility testing in cerebrospinal fluid (CSF) reveals that standard broth methods often underestimate bacterial susceptibility. This finding is crucial for optimizing treatments against resistant Gram-positive bacteria in central nervous system infections.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Resistant Gram-positive bacteria pose a growing challenge for treating hospital- and community-acquired central nervous system (CNS) infections.
- Current therapeutic strategies often struggle to identify effective antibiotic regimens for multi-drug resistant pathogens.
- There is a need to improve methods for predicting in vivo efficacy despite reduced in vitro susceptibility.
Purpose of the Study:
- To evaluate antibiotic susceptibility in cerebrospinal fluid (CSF) compared to standard culture media.
- To determine if in vitro susceptibility testing in broth accurately reflects antibiotic effectiveness within the CNS environment.
- To identify antibiotics that show improved efficacy in CSF compared to broth-based minimum inhibitory concentrations (MICs).
Main Methods:
- Antibiotic susceptibility testing was performed on key pathogens including Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae.
- Testing was conducted in both cerebrospinal fluid (CSF) and standard culture broths (Mueller-Hinton or Brain-Heart Infusion).
- Minimal Inhibitory Concentrations (MICs) and Minimal Bactericidal Concentrations (MBCs) were determined for various antibiotics.
Main Results:
- MICs and MBCs were found to be lower in CSF compared to broth for several antibiotic-pathogen combinations.
- Significant differences were observed with gentamicin, levofloxacin, linezolid (against staphylococci), and vancomycin (against staphylococci and pneumococci).
- In no instance were antibiotic concentrations higher in CSF than in broth, indicating broth MICs may underestimate in situ susceptibility.
Conclusions:
- Standard broth-based MICs can underestimate the actual in situ susceptibility of bacteria within the CSF.
- Several antibiotics demonstrate antibacterial activity in CSF at concentrations lower than those predicted by standard in vitro testing.
- These findings suggest a need to reconsider standard susceptibility testing methods for CNS infections to optimize antibiotic selection.
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