Reversal of the in vitro susceptibility of enterococci to trimethoprim-sulfamethoxazole by folinic acid
Open accessAbstract
The in vitro susceptibilities of 21 clinical isolates of Streptococcus faecalis to trimethoprim (TMP) in combination with sulfamethoxazole (SMX) was evaluated in Mueller-Hinton broth (MHB) in the presence and absence of folinic acid as well as in urine. The mean MIC and MBC in MHB, expressed as the TMP concentration, was 0.13 and 0.32 micrograms of TMP-SMX per ml, respectively. In MHB supplemented with folinic acid, the mean MIC and MBC was 3.3 and 5.5 micrograms of TMP-SMX per ml, respectively. In urine the mean MIC of TMP-SMX for these isolates was 8.1 micrograms/ml (range, 1.6 to 50 micrograms/ml). All isolates were inhibited by less than 0.01 micrograms of TMP-SMX per ml when methotrexate was added to the urine.
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Enterococci can use another bypass strategy by incorporating exogenous tetrahydrofolic acid and folinic acid when these are added to the media, and this ability is correlated with up to a 25-fold increase in TMP-SMX MICs and is thought to impair antimicrobial activity in vivo.
“Interestingly, enterococci use another “bypass” strategy by incorporating exogenous tetrahydrofolic acid and folinic acid when added to the media. This ability to use folate from different sources is correlated with up to 25-fold increase in the MICs of TMP-SMX and are thought to impair the antimicrobial activity in vivo (84, 85).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [85]
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Mechanisms of Antibiotic Resistance
Munita, J. M., & Arias, C. A. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.vmbf-0016-2015 · Cited by 2,782 · see citing works
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Mechanisms of antibiotic resistance
Munita, J. M., & Arias, C. A. (2016) · Virulence Mechanisms of Bacterial Pathogens · doi:10.1128/9781555819286.ch17 · Cited by 421 · see citing works
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- Authors
- Zervos, M. J., & Schaberg, D. R.
- Affiliations
- University of Michigan (US)
- ORCID
- Zervos, M J
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1985-09
- Volume
- 28
- Issue
- 3
- Pages
- 446-448
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC180272
- OpenAlex
- W2031422931
- Cited by
- 68
- References
- 13
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 1 · 2014: 9 · 2012: 1
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Epidemiology › Urinary Tract Infections Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Keywords
- Enterococcus faecalis, Enterococcus, trimethoprim-sulfamethoxazole, leucovorin, methotrexate, antimicrobial susceptibility, minimum inhibitory concentration, minimum bactericidal concentration, urine, drug interactions, sulfonamide resistance
- MeSH terms
- Leucovorin, Drug Combinations, Microbial Sensitivity Tests, Enterococcus faecalis, Sulfamethoxazole, Trimethoprim, In Vitro Techniques
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