511. The cefazolin (CZ) and piperacillin-tazobactam (TZP) inoculum effects (IEs) are persistent amongst serial isolates of methicillin-sensitive <i>Staphylococcus aureus</i> (MSSA) derived from the sputum of persons with cystic fibrosis (pwCF) despite variation in other phenotypes.
Bibliographic record
Abstract
Abstract Background Phenotypic diversity among chronically infecting pathogens within the airways of pwCF is increasingly recognized, limiting susceptibility testing-directed decision-making (Somayaji, 2019, JCF). While it is an important outcome determinant in infection (Miller, 2018, OFID), the IE has generally only been studied in acute infection models. Herein, we sought to establish if variation in the presence of the IE to beta-lactams exists among CF-derived MSSA. Methods Single sputum cultures from 10 pwCF with chronic MSSA infection of ≥ 10 years in duration were collected, and 10 unique colonies from each were selected and confirmed as MSSA for a total of 100 isolates. Individual isolates were subjected to susceptibility testing at standard (SI: 105 CFU/mL) and high inoculum (HI: 107 CFU/mL) against CZ and TZP and assessed for protease (PRO) and hyaluronidase (HA) production in triplicate. The presence of the IE was defined if a ≥ 4-fold difference in MIC between SI and HI existed. All 100 strains were typed using pulsed-field gel electrophoresis. Results Patients included had a median age of 30.5 years, forced vital capacity of 93%, forced expiratory volume in one second of 66% predicted, and a BMI of 21.5 kg/m2. Median sputum MSSA burden was 106 CFU/ml. The IE was overall more common with TZP than CZ: 47% vs 33%, respectively. Median MIC50 for CZ increased between SI and HI: 0.5 to 1µg/mL, and TZP: 2 to 4µg/mL (p< 0.0001 for both). The most prevalent pulsotypes identified corresponded to multilocus sequence types (ST)-5 (20%), ST-30 (15%), and ST-1 (5%), where ST-30 isolates were more likely to exhibit the CZ and TZP IE (p< 0.0001 for both). Eight out of 10 patients had all isolates belonging to the same pulsogroup. Of patients infected with a single strain, discordance between IE phenotype was not noted, though PRO and HA production varied. Among these patients, the standard deviation of zone clearance diameter ranged from 0-0.9cm (mean range: 0-1.4cm) and 0-1.8cm (mean range: 0-7.2cm), respectively, between individual isolates. Conclusion Phenotypic diversity in chronic MSSA exists within the airways of pwCF. However, we observed the IE for CZ and TZP to be strain dependent, without variable penetrance. Disclosures All Authors: No reported disclosures.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".