Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model
Bibliographic record
Abstract
Combining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibiotics over only 24h and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. To improve the predictivity of in vitro combination assays for bacterial biofilms, we first adapted a previously-described Hollow-fiber (HF) infection model by allowing a Staphylococcus aureus biofilm to form before drug exposure. We then mimicked different concentration profiles of amikacin and vancomycin, similar to the free plasma concentration profiles that would be observed in patients treated daily over 5 days. We assessed the ability of the two drugs, alone or in combination, to reduce planktonic and biofilm-embedded bacterial populations, and to prevent the selection of resistance within these populations. Although neither amikacin nor vancomycin exhibited any bactericidal activity on S. aureus in monotherapy, the combination had a synergistic effect and significantly reduced the planktonic bacterial population by -3.0 to -6.0 log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the addition of vancomycin to amikacin only conferred a further maximum reduction of 0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few bacteria less-susceptible to amikacin were systematically detected before treatment. These resistant bacteria, which were rapidly amplified by exposure to amikacin alone, could be maintained at a low level in the biofilm population and even suppressed in the planktonic population by adding vancomycin. In conclusion, by adapting the HF model, we were able to demonstrate the different bactericidal activities of the vancomycin and amikacin combination on planktonic and biofilm-embedded bacterial populations, suggesting that, for biofilm-associated infections, the efficacy of this combination would not be much greater than with amikacin monotherapy. However, adding vancomycin could reduce possible resistance to amikacin and provide a relevant strategy to prevent the selection of antibiotic-resistant bacteria during treatments.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".