Predictors and patterns of empirical antibiotic therapy and associated outcomes in COVID-19 patients: a retrospective study in a tertiary care facility in South India

Figures & data

Table 1. Characteristics of the study population – demographic, clinical, laboratory, and treatment details (n = 525).

		Empirical Abx initiated (n = 440)		Empirical Abx not initiated (n = 85)
Parameters	Value	Moderate (n = 119)	Severe (n = 321)	Moderate (n = 47)	Severe (n = 38)	p-value^#
Age (years)	60 (48–68)	60 (48.5–69.5)	60 (49–68)	55 (44.5–67)	54 (45–70.75)	0.089^b
Gender Females Males	174(33.1%) 351(66.9%)	46(38.6%) 73(61.3%)	96(29.9) 225(70.1%)	16 (34%) 31 (65.9%)	16 (41%) 22 (59%)	0.378^a
Co-morbidities Diabetes Hypertension Chronic Kidney Disease Chronic Lung Disease Chronic Liver Disease Cardiovascular Disease Immunocompromised Others	284 (54%) 258 (49%) 65 (25.4%) 40 (7.6%) 12 (2.2%) 106 (20.1%) 34 (6.4%) 291 (55.3%)	56 (47.1%) 55 (46.2%) 11 (9.2%) 10 (8.4%) 2 (1.7%) 24 (20.1%) 7 (5.8%) 68 (57.1%)	188 (58.6%) 165 (51.4%) 46 (8.4%) 27 (8.4%) 8 (2.5%) 70 (21.8%) 22 (6.9%) 171 (53.3%)	24 (51.1%) 21 (44.7%) 4 (8.5%) 3 (6.4%) 1 (2.1%) 8 (17%) NA 29 (61.7%)	16 (41%) 17 (43.6%) 4 (10.2%) NA 1 (2.6%) 4 (10.2%) 5 (13.2%) 12 (30.8%)	0.191^a 0.408^a 0.472^a 0.177^a 1^a 0.142^a 1^a NA
Presenting Symptoms Fever Cough Shortness of Breath ARDS Loss of taste/smell Sepsis Manifestation	360 (68.4%) 341 (64.9%) 356 (67.8%) 142 (27%) 15 (2.9%) 25 (4.8%)	84 (70.5%) 68 (54.6%) 65 (54.6%) 1 (0.84%) 6 (5.04%) 1 (0.8%)	216 (67.3%) 212 (66%) 247 (76.9%) 128 (39.9%) 4 (1.2%) 24 (7.5%)	33 (70.2%) 34 (72.3%) 20 (42.5%) 1 (2.1%) 2 (4.2%) NA	27 (69.2%) 27 (71.8%) 24 (64.1%) 12 (33.3%) 3 (7.9%) NA	0.703^a 0.172^a <0.001^a 0.007^a 0.078^a NA
Lab Parameters Absolute Lymphocyte Count (*10^3/μL)   Absolute Neutrophil Count (*10^3/μL)   C-Reactive Protein (mg/L) Creatinine (mg/dL) D-dimer (μ/mL) Ferritin (ng/mL) Lactate Dehydrogenase (IU/L) Platelet (*10^3/μL)   White Blood Cell   Procalcitonin Positive	0.78 (0.47–1.11) 7.38 (4.55–11.25) 73.7 (33.42–132.43) 0.91 (0.75–1.33) 1 (0.5–3.2) 750.6 (359–1417) 518.5 (390–715) 210 (154.25–294.75) 9200 (6200–13600) 185 (35.2%)	0.82 (0.56–1.21) 5.83 (4.07–8.64) 53.06 (23–104.91) 1.05 (0.8–1.65) 0.70 (0.40–1.5) 623 (337.2–1099.5) 406 (327.5–536.75) 196.5 (150–286) 7600 (5300–10200) 33 (27.7%)	0.71 (0.44–1.08) 8.50 (5.30–12.76) 91.68 (47.29–146.1) 1.05 (0.80–1.65) 1.40 (0.6–5.30) 880.5 (441.27–1599) 598 (439–798) 212.5 (157.5–298.25) 10100 (6800–15000) 145 (45.2%)	1.03 (0.79–1.22) 4.11 (2.76–6.65) 35.01 (15.45–81.78) 0.86 (0.76–1.09) 0.50 (0.32–1.25) 428.2 (246.47–667.5) 374 (304.7–450.5) 178.5 (133–281.25) 6250 (4425–7975) 3 (6.4%)	0.77 (0.49–1.06) 8.74 (5.58–11.24) 47.93 (24.5–88.07) 0.87 (0.65–1.22) 1.0 (0.5–2.67) 745.9 (251.2–1335) 529 (436–716) 235 (187.25–312.75) 10700 (6975–13250) 4 (10.5%)	0.058^b   0.001^b   <0.001^b   0.008^b   0.004^b   <0.001^b   <0.001^b   0.925^b   0.001^b   <0.001^a
Co-medications Steroids Remdesivir Anticoagulants Antifungals	486 (92.6%) 358 (68.2%) 469 (89.3%) 74 (14.1%)	99 (83.1%) 60 (50.4%) 97 (81.5%) 4 (3.4%)	308 (95.9%) 237 (73.8%) 293 (91.3%) 62 (19.3%)	44 (93.6%) 30 (63.8%) 43 (91.4%) NA	35 (92.1%) 31 (81.6%) 36 (94.7%) 8 (21.1%)	1^a 0.525^a 0.336^a 0.232^a
Invasive ventilation Yes No	189 (36%) 336 (64%)	6 (5%) 113 (95%)	174 (54.2%) 147 (45.8%)	1 (2.1%) 46 (97.9%)	8 (21.1%) 30 (78.9%)	<0.001^a

^aChi-square test; ^bMann–Whitney U test; Abx: Antibiotics; ^#Statistical tests are performed between the empirical and non-empirical antibiotic group; NA: Not applicable.

Table 2. Predictors for initiation of empirical therapy.

Predictors	Adjusted Odds Ratio (95% CI)	p-value*
Shortness of Breath	2.25(1.30–3.89)	0.003
Invasive ventilation	3.93(1.70–9.09)	0.001
Procalcitonin	3.91(1.66–9.16)	0.001
C-Reactive Protein	1.01(1.00–1.01)	0.005

*Logistic regression.

Figure 1. Pattern of empirical antibiotic usage in moderate and severe manifestation of COVID-19.

Figure 2. Pattern of empirical antibiotics vs antibiotics initiated >48 hours.

Table 3. Prescription pattern of antibiotics based on WHO AWaRe criteria.

Antibiotics by AWaRe criteria (ATC code)	All patients (n = 480)	Moderate (n = 135)	Severe (n = 345)	p-value^a
Access
Amikacin (J01GB06)	2 (0.41%)	1 (0.74%)	1 (0.29%)	0.48
Amoxicillin/clavulanicacid (J01CR02)	5 (1.04%)	2 (1.5%)	3 (0.87%)	0.62
Clindamycin (J01FF01)	17 (3.5%)	5 (3.7%)	12 (3.5%)	1
Doxycycline (J01AA02)	100 (20.8%)	30 (22.2%)	70 (20.3%)	0.7
Metronidazole (P01AB01)	1 (0.21%)	0	1 (0.29%)	1
Sulphamethoxazole/trimethoprim(J01EE01)	3 (0.63%)	1 (0.74%)	2 (0.58%)	1
Watch
Ceftriaxone (J01DD04)	249 (51.9%)	93 (68.9%)	156 (45.2%)	<0.0001
Ceftazidime (J01DD02)	4 (0.83%)	0	4 (1.2%)	0.58
Cefuroxime (J01DC02)	3 (0.63%)	3 (2.2%)	0	0.02
Cefoperazone (J01DD12)	3 (0.63%)	1 (0.74%)	2 (0.58%)	1
Cefpodoxime proxetil (J01DD13)	1 (0.21%)	1 (0.74%)	0	0.28
Cefixime (J01DD08)	1 (0.21%)	0	1 (0.29%)	1
Ciprofloxacin (J01MA02)	2 (0.41%)	0	2 (0.58%)	1
Meropenem (J01DH02)	100 (20.8%)	8 (5.9%)	92 (26.7%)	<0.0001
Piperacillin/tazobactam (J01CR05)	264 (55%)	47 (34.8%)	217 (62.9%)	<0.0001
Teicoplanin (J01XA02)	46 (9.6%)	5 (3.7%)	41 (11.9%)	0.005
Vancomycin (J01XA01)	4 (0.83%)	0	4 (1.2%)	0.58
Reserve
Colistin (J01XB01)	5 (1.04%)	0	5 (1.45%)	0.32
Fosfomycin (J01XX01)	1 (0.21%)	0	1 (0.29%)	1
Linezolid (J01XX08)	6 (1.3%)	1 (0.74%)	5 (1.45%)	1
Polymyxin B (J01XB02)	62 (12.9%)	0	62 (18%)	<0.0001
Tigecycline (J01AA12)	28 (5.8%)	0	28 (8.12%)	0.0001
Not recommended
Cefepime-tazobactam	1 (0.21%)	0	1 (0.29%)	1
Cefoperazone-sulbactam	101 (21.04%)	9 (6.7%)	92 (26.7%)	<0.0001
Meropenem-sulbactam	18 (3.8%)	0	18 (5.2%)	0.002

^aChi-square/Fisher’s T test.

Table 4. Association of empirical therapy with outcomes.

Outcomes	Total (N = 525)	Empirical Therapy Group (n = 440)	Non-empirical Therapy Group (n = 85)	Odds Ratio	p-value
Hospitalisation Days	11 (8–15)	11 (7–16)	11 (8–15)	0.998 (0.96–1.03)	0.724^b
Total Days of Abx Therapy	7 (5–12)	7.5 (5–12)	7 (4–9.25)	1.09 (1.01–1.18)	0.04^b
Invasive ventilation Days	7 (4–13)	7 (4–13)	7 (4–8)	1.08 (0.94–1.24)	0.479^b
Development of Infection (Culture +ve)	125 (23.8%)	110 (25%)	15 (17.6%)	1.25 (0.66–2.49)	0.55^a
Development of Secondary Infection	95 (18.1%)	84 (19.09%)	11 (12.9%)	1.58 (0.79–3.46)	0.218^a
Steroid Days	7 (6–10)	7 (5–10)	7 (6–10)	0.99 (0.93–1.06)	0.754^b
Anticoagulant Days	9 (6–14)	9 (6–14)	10 (7–13)	0.99 (0.95–1.03)	0.408^b
Remdesivir Days	5 (5–5)	5 (5–5)	5 (5–5)	1.14 (0.89–1.46)	0.459^b
Mortality	194 (36.9%)	180 (40.9%)	14 (16.5%)	3.503 (1.88–6.94)	0.00001^a

^aChi-square test; ^bMann–Whitney U test; Abx: Antibiotics.

Data availability statement

The dataset used or analyzed during the current study available from the corresponding author on reasonable request.