Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY
Abstract
:1. Introduction
2. Results
2.1. Study Participants
2.2. Antibiotic Exposure and Severe COVID-19 Outcome
2.3. Sensitivity Analysis for Antibiotic Exposure Interaction
3. Discussion
4. Materials and Methods
4.1. Data Sources
4.2. Study Design
4.3. Matching
4.4. Antibiotic Exposure
4.5. Confounding
4.6. Random Forest Model
4.7. Statistical Analysis
4.8. Sensitivity Analysis
4.9. Software and Reproducibility
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Case (n 1 = 67,515) | Control (n 1 = 375,330) | |||
---|---|---|---|---|
n 1 | % | n 1 | % | |
Age group | ||||
18–29 | 1665 | 2.5 | 9115 | 2.4 |
30–39 | 3205 | 4.7 | 18,350 | 4.9 |
40–49 | 4735 | 7.0 | 27,040 | 7.2 |
50–59 | 8310 | 12.3 | 48,065 | 12.8 |
60–69 | 11,070 | 16.4 | 63,885 | 17.0 |
70–79 | 16,535 | 24.5 | 94,630 | 25.2 |
80+ | 21,995 | 32.6 | 114,245 | 30.4 |
Sex | ||||
male | 36,555 | 54.1 | 207,450 | 55.3 |
female | 30,960 | 45.9 | 167,880 | 44.7 |
Ethnicity | ||||
White | 57,400 | 85.0 | 305,410 | 81.4 |
South Asian | 5495 | 8.1 | 28,565 | 7.6 |
Black | 1310 | 1.9 | 4135 | 1.1 |
Mixed | 560 | 0.8 | 2605 | 0.7 |
Other | 1145 | 1.7 | 4760 | 1.3 |
Unknown | 1600 | 2.4 | 29,860 | 8.0 |
BMI category 2 | ||||
Healthy weight (<18.5 kg/m2) | 13,490 | 20.0 | 82,845 | 22.1 |
Underweight (18.5–24.9 kg/m 2) | 1580 | 2.3 | 7275 | 1.9 |
Overweight (25–29.9 kg/m 2) | 16,935 | 25.1 | 109,010 | 29.0 |
Obese (≥30 kg/m2) | 24,730 | 36.6 | 112,190 | 29.9 |
Unknown | 10,780 | 16.0 | 64,010 | 17.1 |
CCI group 3 | ||||
No comorbidities (0) | 19,830 | 29.4 | 164,015 | 43.7 |
Low (1–2) | 36,765 | 54.5 | 177,195 | 47.2 |
Medium (3–4) | 9685 | 14.3 | 30,845 | 8.2 |
High (5–6) | 1185 | 1.8 | 3085 | 0.8 |
Very high (≥ 7) | 50 | 0.1 | 195 | 0.1 |
Smoking status 4 | ||||
Never | 22,425 | 33.2 | 142,935 | 38.1 |
Current | 6145 | 9.1 | 34,385 | 9.2 |
Former | 38,790 | 57.4 | 196,805 | 52.4 |
Unknown | 160 | 0.2 | 1215 | 0.3 |
IMD 5 | ||||
1 (least deprived) | 9370 | 13.9 | 62,170 | 16.6 |
2 | 11,470 | 17.0 | 70,280 | 18.7 |
3 | 13,420 | 19.9 | 77,720 | 20.7 |
4 | 14,380 | 21.3 | 77,020 | 20.5 |
5 (most deprived) | 17,605 | 26.1 | 79,830 | 21.3 |
Unknown | 1265 | 1.9 | 8305 | 2.2 |
Care home residents | 3010 | 4.5 | 31,875 | 8.5 |
COVID-19 vaccine 6 | 29,100 | 43.1 | 181,090 | 48.2 |
Flu vaccine 7 | 46,285 | 68.6 | 261,090 | 69.6 |
Probability of COVID-19 Hospitalisation | Conditional Logistic Regression Model 1 | |||
---|---|---|---|---|
Risk Level | RF Estimated | Observed | OR | 95% CI |
Decile 1 (lowest) | 0.09 | 0.08 | ref | |
Decile 2 | 0.11 | 0.10 | 1.3 | 1.2–1.3 |
Decile 3 | 0.12 | 0.11 | 1.5 | 1.4–1.5 |
Decile 4 | 0.13 | 0.12 | 1.6 | 1.5–1.7 |
Decile 5 | 0.14 | 0.13 | 1.7 | 1.6–1.8 |
Decile 6 | 0.15 | 0.14 | 1.9 | 1.8–2.0 |
Decile 7 | 0.16 | 0.16 | 2.1 | 2.1–2.2 |
Decile 8 | 0.17 | 0.18 | 2.6 | 2.5–2.7 |
Decile 9 | 0.19 | 0.22 | 3.1 | 3.0–3.2 |
Decile 10 (highest) | 0.25 | 0.30 | 4.8 | 4.6–5.0 |
Variables 1,2,3 | Decile 1 (Lowest Risk) | Decile 2 | Decile 3 | Decile 4 | Decile 5 | Decile 6 | Decile 7 | Decile 8 | Decile 9 | Decile 10 (Highest Risk) |
---|---|---|---|---|---|---|---|---|---|---|
Total antibiotics (count) 4 | 2 (2, 3) | 2 (2, 3) | 3 (2, 3) | 3 (2, 4) | 3 (2, 5) | 4 (3, 6) | 5 (4, 7) | 7 (5, 9) | 10 (7, 14) | 20 (13, 35) |
Level 1 (2) (lowest) | 73.1% | 58.5% | 48.8% | 38.8% | 26.4% | 15.1% | 7.6% | 2.1% | 0.2% | 0% |
Level 2 (3) | 25.6% | 37.7% | 43.3% | 45.9% | 45.3% | 41.4% | 30.3% | 16.6% | 5.6% | 0.6% |
Level 3 (6) | 1.3% | 3.5% | 7.2% | 13% | 22.3% | 32% | 39.5% | 38.6% | 68.5% | 6.6% |
Level 4 (13) (highest) | 0% | 0.3% | 0.6% | 2.3% | 6% | 11.5% | 22.6% | 42.7% | 23.7% | 92.8% |
Antibiotic types (count) 5 | 2 (1, 2) | 2 (1, 2) | 2 (1, 2) | 2 (2, 3) | 2 (2, 3) | 2 (2, 3) | 2 (2, 3) | 3 (2, 4) | 3 (3, 4) | 4 (3, 6) |
Level 1 (2) (lowest) | 91.9% | 83.9% | 78.7% | 73.6% | 64.1% | 53.8% | 44.9% | 33.7% | 23.7% | 14.8% |
Level 2 (3) | 7.2% | 14.1% | 17.2% | 19.3% | 23.4% | 28.8% | 31.5% | 31.6% | 27.3% | 18.7% |
Level 3 (4) (highest) | 0.8% | 2.0% | 4.2% | 7.1% | 12.5% | 17.4% | 23.6% | 34.8% | 49.0% | 66.5% |
Broad-spectrum antibiotics (count) 6 | 0 (0, 0) | 0 (0, 0) | 0 (0, 0) | 0 (0, 0) | 0 (0, 0) | 0 (0, 0) | 0 (0, 1) | 0 (0, 1) | 0 (0, 1) | 1 (0, 3) |
Level 1 (0) (lowest) | 91.1% | 85.3% | 83.5% | 82.6% | 80.6% | 77.0% | 71.5% | 64.0% | 55.9% | 39.3% |
Level 2 (1) | 7.2% | 12.1% | 13.3% | 13.6% | 14.3% | 15.8% | 17.3% | 19.9% | 21.4% | 18.8% |
Level 3 (3) (highest) | 1.7% | 2.6% | 3.2% | 3.8% | 5.1% | 7.2% | 11.3% | 16.1% | 22.7% | 41.9% |
Time between (day) 7 | 120 (11, 367) | 264 (58, 478) | 325 (116, 561) | 419 (180, 666) | 539 (268, 472) | 615 (402, 797) | 686 (477, 864) | 785 (583, 925) | 899 (743, 991) | 1010 (897, 1057) |
Level 1 (75) (lowest) | 63.1% | 48.9% | 42.0% | 32.9% | 23.9% | 15.4% | 10.3% | 7.3% | 4.0% | 2.1% |
Level 2 (423) | 24.9% | 33.2% | 35.1% | 34.9% | 31.8% | 30.7% | 26.3% | 17.9% | 9.3% | 6.2% |
Level 3 (728) | 10.0% | 14.5% | 18.5% | 25.9% | 32.5% | 36.4% | 37.0% | 36.6% | 26.9% | 12.1% |
Level 4 (977) (highest) | 2.0% | 3.4% | 4.4% | 6.3% | 11.8% | 17.4% | 26.3% | 38.2% | 59.8% | 79.5% |
Recent antibiotics (day) 8 | 637 (388, 817) | 499 (292, 697) | 416 (252, 638) | 340 (199, 538) | 270 (150, 420) | 210 (188, 371) | 165 (95, 303) | 132 (80, 241) | 94 (62, 158) | 62 (51, 85) |
Level 1 (65) (lowest) | 2.5% | 3.6% | 4.8% | 7.4% | 13.1% | 20.0% | 27.4% | 36.0% | 53.5% | 82.8% |
Level 2 (155) | 6.8% | 12.9% | 17.5% | 24.0% | 30.3% | 33.9% | 37.1% | 38.0% | 33.6% | 14.8% |
Level 3 (334) | 23.6% | 30.0% | 34.4% | 37.0% | 36.8% | 32.7% | 26.0% | 18.5% | 9.8% | 1.9% |
Level 4 (678) (highest) | 67.1% | 53.5% | 43.3% | 31.6% | 19.8% | 13.4% | 9.6% | 7.5% | 3.0% | 0.5% |
Prescribing intervals average (day) 9 | 98 (10, 238) | 151 (45, 314) | 175 (76, 324) | 190 (92, 316) | 186 (101, 306) | 170 (102, 284) | 145 (95, 236) | 122 (80, 174) | 94 (66, 138) | 50 (31, 76) |
Level 1 (30) (lowest) | 43.7% | 29.8% | 22.2% | 17.2% | 13.3% | 11.6% | 11.8% | 14.6% | 22.0% | 63.8% |
Level 2 (93) | 13.5% | 15.3% | 16.6% | 17.1% | 19.1% | 23.4% | 29.8% | 38.4% | 47.2% | 29.6% |
Level 3 (171) | 17.6% | 20.6% | 24.2% | 26.3% | 29.2% | 31.3% | 33.5% | 34.1% | 27.1% | 6.0% |
Level 4 (363) (highest) | 25.1% | 34.3% | 37.0% | 39.4% | 38.5% | 33.7% | 24.9% | 12.8% | 3.7% | 0.6% |
Prescribing intervals deviation (day) 9 | 0 (0, 0) | 0 (0, 78) | 0 (0, 126) | 41 (0, 162) | 90 (0, 187) | 111 (40, 202) | 117 (63, 199) | 112 (71, 175) | 96 (62, 149) | 51 (25, 83) |
Level 1 (0) (lowest) | 77.0% | 62.1% | 52.2% | 41.2% | 27.8% | 16.1% | 8.6% | 2.9% | 0.7% | 0.2% |
Level 2 (37) | 7.6% | 11.7% | 12.8% | 14.8% | 16.3% | 18.0% | 18.2% | 20.0% | 27.9% | 64.1% |
Level 3 (103) | 6.0% | 10.7% | 14.0% | 16.8% | 22.4% | 28.3% | 35.0% | 43.0% | 46.2% | 27.6% |
Level 4 (226) (highest) | 9.4% | 15.5% | 21.0% | 27.2% | 33.5% | 37.6% | 38.2% | 34.2% | 25.3% | 8.2% |
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Yang, Y.-T.; Wong, D.; Zhong, X.; Fahmi, A.; Ashcroft, D.M.; Hand, K.; Massey, J.; Mackenna, B.; Mehrkar, A.; Bacon, S.; et al. Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY. Antibiotics 2024, 13, 566. https://doi.org/10.3390/antibiotics13060566
Yang Y-T, Wong D, Zhong X, Fahmi A, Ashcroft DM, Hand K, Massey J, Mackenna B, Mehrkar A, Bacon S, et al. Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY. Antibiotics. 2024; 13(6):566. https://doi.org/10.3390/antibiotics13060566
Chicago/Turabian StyleYang, Ya-Ting, David Wong, Xiaomin Zhong, Ali Fahmi, Darren M. Ashcroft, Kieran Hand, Jon Massey, Brian Mackenna, Amir Mehrkar, Sebastian Bacon, and et al. 2024. "Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY" Antibiotics 13, no. 6: 566. https://doi.org/10.3390/antibiotics13060566