Neutrophil Ratio of White Blood Cells as a Prognostic Predictor of Clostridioides difficile Infection

Figures & data

Table 1 Underlying Diseases and Prior Medications in Hospitalized Adults with Clostridioides Difficile Infection (CDI) Stratified by the in-Hospital Outcome

Variables	Totaln=235	Outcome		P value
		Survival, n=177	Fatality, n=58
Age, years	75.7 ± 12.8	75.8 ± 12.4	75.5 ± 13.9	0.87
Gender, male	114 (48.5)	93 (52.5)	21 (36.2)	0.04
Underlying disease
Hypertension	150 (63.8)	113 (63.8)	37 (63.8)	1.00
Diabetes mellitus	111 (47.2)	81 (45.8)	30 (51.7)	0.45
Chronic kidney disease	104 (44.3)	79 (44.6)	25 (43.1)	0.88
Old stroke	87 (37.0)	65 (36.7)	22 (37.9)	0.88
Dementia	62 (26.4)	46 (26.0)	16 (27.6)	0.86
Coronary artery disease history	41 (17.4)	34 (19.2)	7 (12.1)	0.24
Congestive heart failure	35 (14.9)	24 (13.6)	11 (19.0)	0.40
Parkinsonism	27 (11.5)	21 (11.9)	6 (10.3)	1.00
Solid organ malignancy	29 (12.3)	25 (14.1)	4 (6.9)	0.17
Chronic obstructive pulmonary disease	24 (10.2)	20 (11.3)	4 (6.9)	0.47
Liver cirrhosis	7 (3.0)	5 (2.8)	2 (3.4)	0.68
Recent medication within one month before CDI onset
Antimicrobial therapy
Cephalosporins	120 (51.1)	89 (50.3)	31 (53.4)	0.76
Cefazolin, iv	3 (1.3)	3 (1.7)	0	1.00
Cefuroxime, iv/o	20 (8.5)	18 (10.2)	2 (3.4)	0.17
Ceftazidime or ceftriaxone, iv	73 (31.1)	54 (30.5)	19 (32.8)	0.75
Cefepime, iv	34 (14.5)	23 (13.0)	11 (19.0)	0.28
Penicillins, iv	28 (11.9)	17 (9.6)	11 (19.0)	0.06
Carbapenem, iv	49 (20.9)	37 (20.9)	12 (20.7)	1.00
Fluoroquinolones, iv/o	11 (4.7)	7 (4.0)	4 (6.9)	0.47
Glycopeptide, iv	34 (14.5)	25 (14.1)	9 (15.5)	0.83
Proton pump inhibitors, iv/o	60 (25.5)	41 (23.2)	19 (32.8)	0.17
H2-receptor antagonists, iv/o	36 (15.3)	26 (14.7)	10 (17.2)	0.68
Steroid, iv/o	61 (26.0)	45 (25.4)	16 (27.6)	0.73
VRE colonization during hospitalization	32 (13.6)	12 (14.1)	7 (12.1)	0.83
ICU-onset CDI	35 (14.9)	23 (13.0)	12 (20.7)	0.20

Note: Data are presented as patient numbers (%) or means ± standard deviations.

Abbreviations: iv, intravenous; o, oral; VRE, vancomycin-resistant enterococci; ICU, intensive care unit.

Figure 1 The mortality of patients with Clostridioides difficile infection (CDI) was stratified according to the severity grading of IDSA/SHEA.

Notes: *Severe CDI: blood leukocyte ≥ 15,000 cells/mL or serum creatinine > 1.5 mg/dL; non-severe CDI: blood leukocyte ≤ 15,000 cells/mL and serum creatinine < 1.5 mg/dL, according to the IDSA/ SHEA criteria⁶.

Table 2 Laboratory Characteristics and Antimicrobial Therapy in Patients with Clostridioides Difficile Infection (CDI) Stratified by the in-Hospital Outcome

Variables	Totaln=235	Outcome		P value
		Survival, n=177	Fatality, n=58
Blood leukocyte count, x1000 cells/mL	12.1 ± 6.9	11.6 ± 6.6	13.5 ± 7.8	0.06
Leukocyte count ≥ 15,000 cells/mL	62 (26.4)	41 (23.2)	21 (36.2)	0.06
Neutrophil ratio, %	75.4 ± 13.1	74.1 ± 13.3	79.6 ± 11.2	0.005
Neutrophil ratio >75%	131 (55.7)	87 (49.2)	44 (75.9)	<0.001
Neutrophil count, cells/mL	9435.6 ± 6231.1	8892.8 ± 5901.2	11,092.1 ± 6939.7	0.02
Monocyte ratio, %	6.4 ± 3.0	6.6 ± 3.1	5.7 ± 2.4	0.03
Monocyte count, cells/mL	711.9 ± 494.7	698.6 ± 416.7	752.7 ± 682.8	0.47
Eosinophil ratio, %	2.2 ± 3.3	2.4 ± 3.2	1.5 ± 3.7	0.09
Eosinophil count, cells/mL	215.9 ± 350.0	233.7 ± 342.4	161.5 ± 370.0	0.17
Lymphocyte ratio, %	14.9 ± 10.0	15.8 ± 10.3	12.3 ± 8.5	0.02
Lymphocyte count, cells/mL	1495.3 ± 1012.3	1538.9 ± 1084.1	1362.2 ± 744.6	0.25
Neutrophil/lymphocyte ratio	9.3 ± 10.1	8.8 ± 10.0	11.0 ± 10.0	0.15
Serum creatinine > 1.5 mg/L	27 (11.5)	16 (9.0)	11 (19.3)	0.06
CDI caused by an isolate with tcdC deletion*	20 (11.8)	11 (8.5)	9 (22.0)	0.03
18 base-pair deletion	5 (2.9)	3 (2.3)	2 (4.9)	0.60
39 base-pair deletion	15 (8.8)	8 (6.2)	7 (17.1)	0.05
Drug therapy for CDI
Metronidazole, iv/o	123 (52.3)	93 (52.5)	30 (51.7)	1.00
Vancomycin, o	9 (3.8)	4 (2.3)	5 (8.6)	0.04

Notes: Data are presented as patient numbers (%) or means ± standard deviations; iv = intravenous; o = oral. *Only 170 C. difficile isolates were available: 129 in the survival group and 41 in the fatality group.

Table 3 The Multivariate Analysis of Clinical Variables Associated with in-Hospital Mortality in 235 Patients with Clostridioides Difficile Infection (CDI), with the Inclusion of Blood Leukocyte > 15,000 Cells/mL (Model A) or Neutrophil Ratio > 75% (Model B)

Clinical Variables	Odds Ratio	95% Confidence Interval	P value
Model A
Serum creatinine > 1.5 mg/L	3.59	1.24–10.44	0.02
CDI caused by an isolate with tcdC deletion	3.34	1.24–9.04	0.02
Oral vancomycin therapy for CDI	3.27	0.56–19.10	0.19
Blood leukocyte > 15,000 cells/mL	1.66	0.75–3.71	0.21
Prior penicillin exposure	1.49	0.50–4.42	0.48
Gender, male	0.61	0.28–1.35	0.22
Model B
CDI caused by an isolate with tcdC deletion	3.54	1.28–9.83	0.02
Serum creatinine > 1.5 mg/L	3.42	1.15–10.22	0.03
Oral vancomycin therapy CDI	3.03	0.50–18.53	0.23
Neutrophil ratio > 75%	2.65	1.15–6.09	0.02
Prior penicillin exposure	1.61	0.54–4.81	0.40
Gender, male	0.63	0.28–1.39	0.25

Table 4 Clinical and Microbiological Characteristics in Patients with Clostridioides Difficile Infection (CDI) Stratified by a Neutrophil Ratio ≤ 75% or > 75%

Variables	Neutrophil Ratio		P value
	<75%, n=104	>75%, n=131
Age, years	75.1 ± 11.7	76.2 ± 13.6	0.51
Gender, male	53 (51.0)	70 (53.4)	0.51
Underlying disease
Hypertension	64 (61.5)	86 (65.6)	0.59
Diabetes mellitus	50 (48.1)	61 (46.6)	0.90
Chronic kidney disease	44 (42.3)	60 (45.8)	0.60
Old stroke	37 (35.6)	50 (38.2)	0.79
Dementia	29 (27.9)	33 (25.2)	0.66
Coronary artery disease history	22 (21.2)	19 (14.5)	0.23
Congestive heart failure	14 (13.5)	21 (16.0)	0.71
Parkinsonism	14 (13.5)	13 (9.9)	0.42
Chronic obstructive pulmonary disease	10 (9.6)	14 (10.7)	0.83
Malignancy	9 (8.7)	20 (15.3)	0.16
Liver cirrhosis	3 (2.9)	4 (3.1)	1.00
Blood leukocyte count ≥ 15,000 cells/mL	12 (11.5)	50 (38.2)	<0.001
Serum creatinine > 1.5 mg/L	10 (9.9)	17 (13.1)	0.54
CDI caused by an isolate with tcdC deletion*	9 (12.7)	11 (11.1)	0.81
18 base-pair deletion	2 (1.9)	3 (2.3)	1.00
39 base-pair deletion	7 (9.9)	8 (8.1)	0.79

Notes: Data are presented as patient numbers (%) or means ± standard deviations. *Only 170 C. difficile isolates available: 73 from those with neutrophil <75% and 97 from those with neutrophil >75%.

Figure 2 Clinical outcomes of 235 patients with Clostridioides difficile infection (CDI) stratified by neutrophil ratio. The association of the neutrophil ratio and mortality rate was marginal (P = 0.06, by Fisher’s test).

Note: *Treatment success rate was assessed in 130 patients who received metronidazole or vancomycin therapy.

McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:987–994.

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