Antimicrobial Stewardship during COVID-19 Outbreak: A Retrospective Analysis of Antibiotic Prescriptions in the ICU across COVID-19 Waves
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Primary Outcome
2.3. Secondary Outcomes
2.3.1. Empirical Antibiotic Treatment Appropriateness in the COVID-19 Group
2.3.2. Antimicrobial Resistance in the Overall COVID-19 Group
2.3.3. Clinical Outcomes in the COVID-19 Group
2.4. Control Group
3. Discussion
4. Materials and Methods
4.1. Study Design and Population
4.2. Extracted Data
4.3. Definitions
4.4. Outcomes
4.5. Control Group
4.6. Ethical Considerations
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Overall (Superinfected Patients) (n= 170) | No Empirical Antibiotic Treatment (n = 29) | Empirical Antibiotic Treatment (n = 141) | ||||
---|---|---|---|---|---|---|
De-escalation (n = 47) | Escalation (n = 5) | Continuation (n = 89) | p-Value | |||
Age | ||||||
Mean (SD) | 63.3 (12.6) | 63.2 (14.6) | 63.5 (9.51) | 62.6 (7.47) | 63.3 (13.7) | 0.548 |
Median [IQR] | 66.0 [57.0–72.0] | 68.0 [58.0–74.0] | 63.0 [56.5–69.5] | 65.0 [58.0–68.0] | 67.0 [57.0–74.0] | |
Gender | ||||||
F | 46 (27.1%) | 14 (48.3%) | 8 (17.0%) | 1 (20.0%) | 23 (25.8%) | 0.5 |
H | 124 (72.9%) | 15 (51.7%) | 39 (83.0%) | 4 (80.0%) | 66 (74.2%) | |
BMI | ||||||
Mean (SD) | 30.0 (5.84) | 29.9 (6.67) | 30.4 (6.24) | 27.9 (4.76) | 30.0 (5.46) | 0.53 |
Median [IQR] | 29.0 [26.0–33.4] | 29.0 [26.4–31.5] | 28.9 [26.4–35.0] | 26.8 [26.0–27.0] | 29.3 [26.0–33.1] | |
Missing | 11 (6.5%) | 2 (6.9%) | 5 (10.6%) | 0 (0%) | 4 (4.5%) | |
Obesity | ||||||
0 | 91 (53.5%) | 17 (58.6%) | 24 (51.1%) | 4 (80.0%) | 46 (51.7%) | 0.473 |
1 | 71 (41.8%) | 11 (37.9%) | 18 (38.3%) | 1 (20.0%) | 41 (46.1%) | |
Missing | 8 (4.7%) | 1 (3.4%) | 5 (10.6%) | 0 (0%) | 2 (2.2%) | |
Immunosuppression * | ||||||
0 | 149 (87.6%) | 26 (89.7%) | 40 (85.1%) | 5 (100%) | 78 (87.6%) | 0.626 |
1 | 21 (12.4%) | 3 (10.3%) | 7 (14.9%) | 0 (0%) | 11 (12.4%) | |
Invasive procedures as outpatients | ||||||
0 | 169 (99.4%) | 29 (100%) | 47 (100%) | 5 (100%) | 88 (98.9%) | 0.745 |
1 | 1 (0.6%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (1.1%) | |
Previous hospitalization < 90 days | ||||||
0 | 151 (88.8%) | 26 (89.7%) | 42 (89.4%) | 5 (100%) | 78 (87.6%) | 0.686 |
1 | 19 (11.2%) | 3 (10.3%) | 5 (10.6%) | 0 (0%) | 11 (12.4%) | |
Prior antibiotic course < 90 days | ||||||
0 | 124 (72.9%) | 22 (75.9%) | 33 (70.2%) | 4 (80.0%) | 65 (73.0%) | 0.872 |
1 | 46 (27.1%) | 7 (24.1%) | 14 (29.8%) | 1 (20.0%) | 24 (27.0%) | |
Myocardial infarction | ||||||
0 | 143 (84.1%) | 23 (79.3%) | 43 (91.5%) | 5 (100%) | 72 (80.9%) | 0.163 |
1 | 27 (15.9%) | 6 (20.7%) | 4 (8.5%) | 0 (0%) | 17 (19.1%) | |
Congestive heart failure | ||||||
0 | 165 (97.1%) | 28 (96.6%) | 47 (100%) | 5 (100%) | 85 (95.5%) | 0.3 |
1 | 5 (2.9%) | 1 (3.4%) | 0 (0%) | 0 (0%) | 4 (4.5%) | |
Vascular peripheral disease | ||||||
0 | 161 (94.7%) | 27 (93.1%) | 45 (95.7%) | 5 (100%) | 84 (94.4%) | 0.822 |
1 | 9 (5.3%) | 2 (6.9%) | 2 (4.3%) | 0 (0%) | 5 (5.6%) | |
Stroke | ||||||
0 | 162 (95.3%) | 29 (100%) | 47 (100%) | 5 (100%) | 81 (91.0%) | 0.0839 |
1 | 8 (4.7%) | 0 (0%) | 0 (0%) | 0 (0%) | 8 (9.0%) | |
Dementia | ||||||
0 | 168 (98.8%) | 29 (100%) | 47 (100%) | 4 (80.0%) | 88 (98.9%) | 0.0014 |
1 | 2 (1.2%) | 0 (0%) | 0 (0%) | 1 (20.0%) | 1 (1.1%) | |
Chronic respiratory failure | ||||||
0 | 148 (87.1%) | 26 (89.7%) | 41 (87.2%) | 5 (100%) | 76 (85.4%) | 0.639 |
1 | 22 (12.9%) | 3 (10.3%) | 6 (12.8%) | 0 (0%) | 13 (14.6%) | |
Connective tissue disease | ||||||
0 | 168 (98.8%) | 29 (100%) | 46 (97.9%) | 5 (100%) | 88 (98.9%) | 0.862 |
1 | 2 (1.2%) | 0 (0%) | 1 (2.1%) | 0 (0%) | 1 (1.1%) | |
Gastric ulcer | ||||||
0 | 167 (98.2%) | 28 (96.6%) | 47 (100%) | 5 (100%) | 87 (97.8%) | 0.553 |
1 | 3 (1.8%) | 1 (3.4%) | 0 (0%) | 0 (0%) | 2 (2.2%) | |
Mild liver disease | ||||||
0 | 166 (97.6%) | 28 (96.6%) | 46 (97.9%) | 5 (100%) | 87 (97.8%) | 0.944 |
1 | 4 (2.4%) | 1 (3.4%) | 1 (2.1%) | 0 (0%) | 2 (2.2%) | |
Moderate to severe liver disease | ||||||
0 | 168 (98.8%) | 29 (100%) | 47 (100%) | 5 (100%) | 87 (97.8%) | 0.553 |
1 | 2 (1.2%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (2.2%) | |
Kidney disease | ||||||
0 | 160 (94.1%) | 26 (89.7%) | 45 (95.7%) | 5 (100%) | 84 (94.4%) | 0.822 |
1 | 10 (5.9%) | 3 (10.3%) | 2 (4.3%) | 0 (0%) | 5 (5.6%) | |
Diabetes—without complications | ||||||
0 | 118 (69.4%) | 23 (79.3%) | 28 (59.6%) | 4 (80.0%) | 63 (70.8%) | 0.344 |
1 | 52 (30.6%) | 6 (20.7%) | 19 (40.4%) | 1 (20.0%) | 26 (29.2%) | |
Diabetes—with complications | ||||||
0 | 164 (96.5%) | 28 (96.6%) | 46 (97.9%) | 5 (100%) | 85 (95.5%) | 0.707 |
1 | 6 (3.5%) | 1 (3.4%) | 1 (2.1%) | 0 (0%) | 4 (4.5%) | |
Solid cancer without metastasis < 5 years | ||||||
0 | 148 (87.1%) | 24 (82.8%) | 42 (89.4%) | 5 (100%) | 77 (86.5%) | 0.623 |
1 | 22 (12.9%) | 5 (17.2%) | 5 (10.6%) | 0 (0%) | 12 (13.5%) | |
Solid cancer with metastasis | ||||||
0 | 166 (97.6%) | 28 (96.6%) | 46 (97.9%) | 5 (100%) | 87 (97.8%) | 0.944 |
1 | 4 (2.4%) | 1 (3.4%) | 1 (2.1%) | 0 (0%) | 2 (2.2%) | |
Leukemia | ||||||
0 | 167 (98.2%) | 29 (100%) | 46 (97.9%) | 5 (100%) | 87 (97.8%) | 0.944 |
1 | 3 (1.8%) | 0 (0%) | 1 (2.1%) | 0 (0%) | 2 (2.2%) | |
Lymphoma | ||||||
0 | 167 (98.2%) | 28 (96.6%) | 46 (97.9%) | 5 (100%) | 88 (98.9%) | 0.862 |
1 | 3 (1.8%) | 1 (3.4%) | 1 (2.1%) | 0 (0%) | 1 (1.1%) | |
Hypertension | ||||||
0 | 86 (50.6%) | 10 (34.5%) | 24 (51.1%) | 2 (40.0%) | 50 (56.2%) | 0.695 |
1 | 84 (49.4%) | 19 (65.5%) | 23 (48.9%) | 3 (60.0%) | 39 (43.8%) | |
Tobacco consumption | ||||||
0 | 126 (74.1%) | 22 (75.9%) | 36 (76.6%) | 4 (80.0%) | 64 (71.9%) | 0.797 |
1 | 44 (25.9%) | 7 (24.1%) | 11 (23.4%) | 1 (20.0%) | 25 (28.1%) | |
COVID-19 wave | ||||||
wave1 | 30 (17.6%) | 6 (20.7%) | 8 (17.0%) | 0 (0%) | 16 (18.0%) | 0.244 |
wave2 | 51 (30.0%) | 8 (27.6%) | 17 (36.2%) | 2 (40.0%) | 24 (27.0%) | |
wave3 | 72 (42.4%) | 13 (44.8%) | 14 (29.8%) | 2 (40.0%) | 43 (48.3%) | |
wave4 | 17 (10.0%) | 2 (6.9%) | 8 (17.0%) | 1 (20.0%) | 6 (6.7%) | |
Charlson Score | ||||||
Mean (SD) | 4.59 (2.28) | 4.79 (2.50) | 4.30 (1.99) | 3.20 (0.837) | 4.76 (2.38) | 0.137 |
Median [IQR] | 4.00 [3.00–6.00] | 5.00 [3.00–6.00] | 4.00 [3.00–5.00] | 3.00 [3.00–4.00] | 4.00 [3.00–6.00] | |
SAPS II at ICU admission | ||||||
Mean (SD) | 41.1 (15.7) | 41.1 (15.6) | 43.9 (14.2) | 29.4 (5.03) | 40.3 (16.6) | 0.0274 |
Median [IQR] | 38.0 [29.0–49.0] | 39.0 [29.0–50.0] | 41.0 [33.0–50.0] | 29.0 [29.0–31.0] | 36.0 [29.0–46.0] | |
SOFA at ICU admission | ||||||
Mean (SD) | 5.09 (2.95) | 4.45 (2.57) | 5.68 (3.07) | 4.00 (1.22) | 5.06 (3.04) | 0.366 |
Median [IQR] | 4.00 [3.00–8.00] | 3.00 [3.00–6.00] | 4.00 [3.00–8.00] | 4.00 [4.00–5.00] | 4.00 [2.00–8.00] | |
Prophylactic antibiotic therapy | ||||||
0 | 102 (60.0%) | 16 (55.2%) | 25 (53.2%) | 3 (60.0%) | 58 (65.2%) | 0.395 |
1 | 68 (40.0%) | 13 (44.8%) | 22 (46.8%) | 2 (40.0%) | 31 (34.8%) | |
Dexamethasone | ||||||
0 | 32 (18.8%) | 6 (20.7%) | 9 (19.1%) | 0 (0%) | 17 (19.1%) | 0.557 |
1 | 138 (81.2%) | 23 (79.3%) | 38 (80.9%) | 5 (100%) | 72 (80.9%) | |
Vasopressors | ||||||
0 | 91 (53.5%) | 20 (69.0%) | 14 (29.8%) | 2 (40.0%) | 55 (61.8%) | 0.0016 |
1 | 79 (46.5%) | 9 (31.0%) | 33 (70.2%) | 3 (60.0%) | 34 (38.2%) | |
Mechanical ventilation | ||||||
0 | 21 (12.4%) | 6 (20.7%) | 3 (6.4%) | 1 (20.0%) | 11 (12.4%) | 0.442 |
1 | 149 (87.6%) | 23 (79.3%) | 44 (93.6%) | 4 (80.0%) | 78 (87.6%) | |
Meduri corticosteroids protocol ** | ||||||
0 | 146 (85.9%) | 27 (93.1%) | 40 (85.1%) | 5 (100%) | 74 (83.1%) | 0.592 |
1 | 24 (14.1%) | 2 (6.9%) | 7 (14.9%) | 0 (0%) | 15 (16.9%) | |
Hydroxychloroquine | ||||||
0 | 147 (86.5%) | 21 (72.4%) | 43 (91.5%) | 5 (100%) | 78 (87.6%) | 0.578 |
1 | 23 (13.5%) | 8 (27.6%) | 4 (8.5%) | 0 (0%) | 11 (12.4%) | |
Lopinavir/ritonavir | ||||||
0 | 156 (91.8%) | 26 (89.7%) | 43 (91.5%) | 5 (100%) | 82 (92.1%) | 0.796 |
1 | 14 (8.2%) | 3 (10.3%) | 4 (8.5%) | 0 (0%) | 7 (7.9%) | |
Anti-IL1 (Kineret) | ||||||
0 | 165 (97.1%) | 29 (100%) | 44 (93.6%) | 5 (100%) | 87 (97.8%) | 0.421 |
1 | 5 (2.9%) | 0 (0%) | 3 (6.4%) | 0 (0%) | 2 (2.2%) | |
Anti-JAK2 (Jakavi) | ||||||
0 | 162 (95.3%) | 28 (96.6%) | 43 (91.5%) | 5 (100%) | 86 (96.6%) | 0.369 |
1 | 8 (4.7%) | 1 (3.4%) | 4 (8.5%) | 0 (0%) | 3 (3.4%) | |
Tocilizumab | ||||||
0 | 134 (78.8%) | 24 (82.8%) | 35 (74.5%) | 4 (80.0%) | 71 (79.8%) | 0.441 |
1 | 4 (2.4%) | 1 (3.4%) | 2 (4.3%) | 0 (0%) | 1 (1.1%) | |
Missing | 32 (18.8%) | 4 (13.8%) | 10 (21.3%) | 1 (20.0%) | 17 (19.1%) | |
In-hospital immunosuppressors | ||||||
0 | 132 (77.6%) | 26 (89.7%) | 33 (70.2%) | 4 (80.0%) | 69 (77.5%) | 0.368 |
1 | 35 (20.6%) | 3 (10.3%) | 13 (27.7%) | 0 (0%) | 19 (21.3%) | |
Missing | 3 (1.8%) | 0 (0%) | 1 (2.1%) | 1 (20.0%) | 1 (1.1%) | |
Acquired resistance—Overall *** | ||||||
0 | 161 (94.7%) | 29 (100%) | 42 (89.4%) | 4 (80.0%) | 86 (96.6%) | 0.115 |
1 | 9 (5.3%) | 0 (0%) | 5 (10.6%) | 1 (20.0%) | 3 (3.4%) | |
Rectal swab MDR | ||||||
0 | 167 (98.2%) | 29 (100%) | 45 (95.7%) | 5 (100%) | 88 (98.9%) | 0.458 |
1 | 3 (1.8%) | 0 (0%) | 2 (4.3%) | 0 (0%) | 1 (1.1%) | |
Acquired resistance in other samples | ||||||
0 | 162 (95.3%) | 29 (100%) | 43 (91.5%) | 4 (80.0%) | 86 (96.6%) | 0.173 |
1 | 8 (4.7%) | 0 (0%) | 4 (8.5%) | 1 (20.0%) | 3 (3.4%) | |
Total duration of antibiotic treatment (days) | ||||||
Mean (SD) | 8.86 (28.5) | 18.6 (67.4) | 10.2 (10.6) | 12.0 (5.34) | 4.82 (3.05) | 0.001 |
Median [IQR] | 6.00 [3.00–7.00] | 7.00 [6.00–7.00] | 7.00 [6.00–9.00] | 10.0 [10.0–12.0] | 4.00 [3.00–7.00] | |
Relapse of infection | ||||||
0 | 155 (91.2%) | 26 (89.7%) | 41 (87.2%) | 3 (60.0%) | 85 (95.5%) | 0.0095 |
1 | 14 (8.2%) | 2 (6.9%) | 6 (12.8%) | 2 (40.0%) | 4 (4.5%) | |
Missing | 1 (0.6%) | 1 (3.4%) | 0 (0%) | 0 (0%) | 0 (0%) | |
Recurrence of infection | ||||||
0 | 143 (84.1%) | 26 (89.7%) | 34 (72.3%) | 2 (40.0%) | 81 (91.0%) | 0.001 |
1 | 26 (15.3%) | 2 (6.9%) | 13 (27.7%) | 3 (60.0%) | 8 (9.0%) | |
Missing | 1 (0.6%) | 1 (3.4%) | 0 (0%) | 0 (0%) | 0 (0%) | |
Mechanical ventilation (days) | ||||||
Mean (SD) | 21.9 (16.5) | 15.7 (9.77) | 24.4 (15.8) | 45.8 (24.7) | 21.4 (17.1) | 0.0547 |
Median [IQR] | 17.0 [11.0–30.0] | 13.0 [8.00–19.0] | 20.0 [12.0–36.0] | 47.5 [37.3–56.0] | 16.0 [11.0–27.0] | |
Missing | 13 (7.6%) | 2 (6.9%) | 2 (4.3%) | 1 (20.0%) | 8 (9.0%) | |
ICU length of stay (d) | ||||||
Mean (SD) | 27.7 (19.7) | 18.2 (10.1) | 33.3 (21.9) | 43.4 (30.3) | 26.9 (18.9) | 0.183 |
Median [IQR] | 21.0 [15.0–35.5] | 15.0 [12.0–19.0] | 25.0 [18.5–46.5] | 52.0 [15.0–68.0] | 21.0 [15.0–31.0] | |
Hospital length of stay (d) | ||||||
Mean (SD) | 35.1 (21.3) | 24.3 (12.8) | 43.3 (24.7) | 49.6 (29.3) | 33.4 (19.3) | 0.0562 |
Median [IQR] | 29.5 [20.0–46.0] | 20.0 [17.0–28.0] | 37.0 [24.5–54.5] | 60.0 [23.0–75.0] | 30.0 [20.0–45.0] | |
Sepsis to ICU discharge (d) | ||||||
Mean (SD) | 28.1 (20.3) | 18.6 (10.1) | 34.1 (23.1) | 43.4 (30.9) | 27.1 (19.4) | 0.159 |
Median [IQR] | 21.0 [15.0–35.5] | 17.0 [12.0–20.0] | 25.0 [18.5–46.5] | 52.0 [15.0–67.0] | 21.0 [15.0–32.0] | |
Sepsis to hospital discharge (d) | ||||||
Mean (SD) | 34.7 (23.7) | 22.8 (12.9) | 43.5 (26.3) | 49.4 (29.6) | 33.1 (22.8) | 0.0393 |
Median [IQR] | 29.0 [19.0–43.8] | 19.0 [14.0–26.0] | 37.0 [25.0–55.5] | 60.0 [23.0–75.0] | 29.0 [18.0–43.0] | |
Withdrawal or withholding of care | ||||||
0 | 156 (91.8%) | 25 (86.2%) | 45 (95.7%) | 5 (100%) | 81 (91.0%) | 0.486 |
1 | 14 (8.2%) | 4 (13.8%) | 2 (4.3%) | 0 (0%) | 8 (9.0%) | |
ICU mortality | ||||||
0 | 124 (72.9%) | 17 (58.6%) | 41 (87.2%) | 4 (80.0%) | 62 (69.7%) | 0.0729 |
1 | 46 (27.1%) | 12 (41.4%) | 6 (12.8%) | 1 (20.0%) | 27 (30.3%) | |
In-hospital mortality | ||||||
0 | 123 (72.4%) | 17 (58.6%) | 40 (85.1%) | 4 (80.0%) | 62 (69.7%) | 0.136 |
1 | 47 (27.6%) | 12 (41.4%) | 7 (14.9%) | 1 (20.0%) | 27 (30.3%) | |
Day 28 Mortality | ||||||
0 | 124 (72.9%) | 17 (58.6%) | 40 (85.1%) | 4 (80.0%) | 63 (70.8%) | 0.174 |
1 | 46 (27.1%) | 12 (41.4%) | 7 (14.9%) | 1 (20.0%) | 26 (29.2%) | |
Day 90 Mortality | ||||||
0 | 123 (72.4%) | 17 (58.6%) | 40 (85.1%) | 4 (80.0%) | 62 (69.7%) | 0.136 |
1 | 47 (27.6%) | 12 (41.4%) | 7 (14.9%) | 1 (20.0%) | 27 (30.3%) |
n (%) | |
---|---|
Replacement of an empirical antimicrobial agent with a narrower-spectrum antibiotic | 29/47 (61.7) |
Stopping one or more components of an empirical combination therapy | 18/47 (38.2) |
Cases of microbiologically confirmed infection, causative pathogen is covered by concomitant antimicrobial therapy | 5/18 |
Cases of non-microbiologically confirmed infection | 13/18 |
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Lakbar, I.; Delamarre, L.; Curtel, F.; Duclos, G.; Bezulier, K.; Gragueb-Chatti, I.; Martin-Loeches, I.; Forel, J.-M.; Leone, M. Antimicrobial Stewardship during COVID-19 Outbreak: A Retrospective Analysis of Antibiotic Prescriptions in the ICU across COVID-19 Waves. Antibiotics 2022, 11, 1517. https://doi.org/10.3390/antibiotics11111517
Lakbar I, Delamarre L, Curtel F, Duclos G, Bezulier K, Gragueb-Chatti I, Martin-Loeches I, Forel J-M, Leone M. Antimicrobial Stewardship during COVID-19 Outbreak: A Retrospective Analysis of Antibiotic Prescriptions in the ICU across COVID-19 Waves. Antibiotics. 2022; 11(11):1517. https://doi.org/10.3390/antibiotics11111517
Chicago/Turabian StyleLakbar, Ines, Louis Delamarre, Fanny Curtel, Gary Duclos, Karine Bezulier, Ines Gragueb-Chatti, Ignacio Martin-Loeches, Jean-Marie Forel, and Marc Leone. 2022. "Antimicrobial Stewardship during COVID-19 Outbreak: A Retrospective Analysis of Antibiotic Prescriptions in the ICU across COVID-19 Waves" Antibiotics 11, no. 11: 1517. https://doi.org/10.3390/antibiotics11111517