Duration from start of antibiotic exposure to onset of Clostridioides difficile infection for different antibiotics in a non-outbreak setting

Figures & data

Figure 1. Kaplan-Meyer Curve showing the number of days elapsed from start of antibiotic exposure to CDI. For comparison between curves see below.

Table

Comparison (log rank)	Cephalosporin	Piperacillin/tazobactam	Cloxacillin/Flucloxacillin	Clindamycin	Quinolone
Cephalosporins	n/a	P < 0.001	P < 0.001	P < 0.001	P < 0.001
Piperacillin/tazobactam	n/a	n/a	P = 0.14	P = 0.015	P = 0.004
Cloxacillin/Flucloxacillin	n/a	n/a	n/a	P = 0.24	P = 0.12
Clindamycin	n/a	n/a	n/a	n/a	P = 0.95
Quinolones	n/a	n/a	n/a	n/a	n/a

Table

Comparison (log rank)	Cephalosporin	Piperacillin/tazobactam	Cloxacillin/Flucloxacillin	Clindamycin	Quinolone
Cephalosporins	n/a	P < 0.001	P < 0.001	P < 0.001	P < 0.001
Piperacillin/tazobactam	n/a	n/a	P = 0.14	P = 0.015	P = 0.004
Cloxacillin/Flucloxacillin	n/a	n/a	n/a	P = 0.24	P = 0.12
Clindamycin	n/a	n/a	n/a	n/a	P = 0.95
Quinolones	n/a	n/a	n/a	n/a	n/a

Table 1. Patient characteristics.

Patient characteristics	1 Cephalosporins (n = 131)	2 Piperacillin/tazobactam (n = 64)	3 Cloxacillin/ flucloxacillin (n = 41)	4 Quinolones (n = 29)	5 Clindamycin (n = 28)	All patients (n = 385)	Head-to head analysis
	Mean ± SD or n/N (%)						P-value (if significant in any comparison)
Risk factors
Age (years)	75 ± 15	74 ± 14	77 ± 15	74 ± 11	74 ± 16	75 ± 15
Female gender n (%)	59 (45)	35 (55)	27 (66)	15 (52)	14 (50)	204 (53)	0.02 (1 and 3)
Inhospital days before onset of CDI (days)	10 ± 6	15 ± 8	13 ± 8	13 ± 10	10 ± 8		<0.001 (1 and 2)
Haematological malignancy n (%)	4 (3)	4 (6)	1 (2)	2 (7)	4 (14)	22 (6)	0.03 (1 and 5)
Inflammatory bowel disease n (%)	3 (2)	3 (5)	3 (7)	0 (0)	0 (0)	10 (3)
Renal insufficiency n (%)	23 (18)	17 (27)	4 (10)	4 (14)	5 (18)	68 (18)	0.05 (2 and 3)
Diabetes mellitusn (%)	29 (22)	13 (20)	13 (32)	4 (14)	8 (29)	91 (24)
Corticosteroid treatment n (%)	25 (19)	11 (17)	6 (15)	4 (14)	7 (25)	66 (17)
Proton pump inhibitor treatment n (%)	63 (48)	35 (55)	22 (54)	16 (55)	9 (32)	189 (49)
Number of prescribed drugs at admission n (%)	9 ± 5	10 ± 5	10 ± 5	9 ± 6	9 ± 6	10 ± 5
Outcome
Severe CDI n (%)	61 (47)	37 (58)	15 (37)	7 (24)	12 (43)	172 (44)	0.003 (2 and 4)
ICU care n (%)	0.1 ± 0.9	1 ± 6	0.1 ± 0,5	0	0	0.4 ± 3
Death within 30 days after positive test n (%)	28 (9)	11 (17)	4 (1)	4 (14)	3 (11)	65 (17)
Recurrence n (%)	17 (13)	14 (22)	6 (15)	4 (14)	4 (14)	63 (16)

Patient characteristics for all patients included and the largest antibiotic groups separated. The results from the head-to-head comparisons for inclusion in multivariable comparison in the right column.

Table 2. Days from start of antibiotic exposure to CDI and onset during ongoing antibiotic treatment.

Antibiotic	N	Days to CDI, mean ± SD	HR with 95% CI, Univariate model^a	HR with 95% CI, Multivariate model A^b	HR with 95% CI, Multivariate model B^c
Cephalosporins	131	7,6 ± 5,6
Piperacillin/tazobactam	64	13,7 ± 9,1	0.42 (0.31–0.57)	0.48 (0.35–0.66)	0.48 (0.35–0.65)
Cloxacillin/Flucloxacillin	41	16,6 ± 9,4	0.33 (0.23–0.47)	0.33 (0.22–0.47)	0.33 (0.22–0.47)
Quinolones	29	22,0 ± 7,8	0.25 (0.16–0.37)	0.23 (0.15–0.35)	0.24 (0.15–0.36)
Clindamycin	28	19,1 ± 10,3	0.26 (0.17–0.39)	0.22 (0.14–0.34)	0.21 (0.14–0.34)
PcV/PcG	17	16,5 ± 9,4	0.37 (0.22–0.62)	0,35 (0,21–0,59)	0.35 (0.21–0.58)
Carbapenems	17	12,7 ± 9,7	0.46 (0.28–0.77)	0.67 (0.40–1.14)	0.66 (0.39–1.12)
Trimethoprim/sulfa	16	17,38 ± 8,9	0.32 (0.19–0.53)	0.25 (0.15–0.44)	0.25 (0.15–0.44)
Amoxicillin/Ampicillin	11	13,2 ± 8,1	0.46 (0.25–0.86)	0.36 (0.19–0.68)	0.35 (0.18–0.66)
Mecillinam	10	11,0 ± 8,0	0.55 (0.29–1.04)
Amoxicillin/clavulanic acid	8	17,6 ± 10,2	0.29 (0.14–0.60)	0.21 (0.10–0.43)	0.20 (0.10–0.42)
Doxycycline	4	7,8 ± 3,9	1.04 (0.38–2.80)
Lymecycline	3	30,0 ± 0,0	0.13 (0.04–0.40)	0.09 (0.03–0.30)	0.09 (0.03–0.30)
Nitrofurantoin	2	17,5 ± 7,8	0.39 (0.10–1.60)
Trimethoprim	2	21,5 ± 12,0	0.21 (0.05–0.84)	0.30 (0.07–1.24)	0.31 (0.08–1.28)
Azithromycin	2	30,0 ± 0,0	0.13 (0.03–0.52)	0.10 (0.02–0.41)	0.10 (0.02–0.43)
Total	385	13,4 ± 9,4
Antibiotic	N	Onset during antibiotic treatment, n (%)	OR with 95% CI, Univariate model^d	OR with 95% CI, Multivariate model A^e	OR with 95% CI, Multivariate model B^f
Cephalosporins	131	106 (80,9)
Piperacillin/tazobactam	64	24 (37,5)	0.14 (0.073–0.28)	0.16 (0.081–0,32)	0.16 (0.08–0.32)
Cloxacillin/Flucloxacillin	41	21 (51,2)	0.25 (0.12–0.53)	0.27 (0.13–0.59)	0.29 (0.13–0.63)
Quinolones	29	4 (13,8)	0.04 (0.012–0.12)	0.04 (0.01–0.13)	0.04 (0.01–0.14)
Clindamycin	28	11 (39,3)	0.15 (0.064–0.37)	0.16 (0.06–0.38)	0.16 (0.06–0.39)
PcV/PcG	17	7 (41,2)	0.17 (0.057–0.48)	0.17 (0.06–0.50)	0.18 (0.06–0.53)
Carbapenems	17	11 (64,7)	0.43 (0.15–1.28)
Trimethoprim/sulfa	16	7 (43,8)	0.18 (0.062–0.54)	0.19 (0.06–0.56)	0.19 (0.06–0.56)
Amoxicillin/Ampicillin	11	5 (45,5)	0.20 (0.056–0.70)	0.17 (0.05–0.61)	0.16 (0.05–0.59)
Mecillinam	10	4 (40)	0.16 (0.041–0.60)	0.15 (0.04–0.58)	0.16 (0.04–0.61)
Amoxicillin/clavulanic acid	8	4 (50)	0.24 (0.055–1.01)
Doxycycline	4	4 (100)	n/a
Lymecycline	3	3 (100)	n/a
Nitrofurantoin	2	0 (0)	n/a
Trimethoprim	2	0 (0)	n/a
Azithromycin	2	0 (0)	n/a
Total	385	211 (54,8)

Compared to cephalosporins in all comparisons.

^aCox-regression, all antibiotic groups compared to cephalosporins.

^bCox-regression including variables with significant differences between the five biggest antibiotic groups (gender, haematological malignancy, renal insufficiency, in-hospital days 30 days before onset of CDI).

^cSensitivity analysis adding severe CDI to cox-regression.

^dBinary logistic regression, all antibiotic groups compared to cephalosporins.

^eBinary logistic regression including variables with significant differences between the five biggest antibiotic groups (gender, haematological malignancy, renal insufficiency, in-hospital days 30 days before onset of CDI).

^fSensitivity analysis adding severe CDI to cox-regression.

Table 3. Severe CDI.

Antibiotic	N	Severe CDI N (%)	OR with 95% CI, Univariate model^a	OR with 95% CI, Multivariate model^b
Cephalosporins	131	61 (47)
Piperacillin/tazobactam	64	37 (58)	1.57 (0.86–2.88)
Cloxacillin/Flucloxacillin	41	15 (37)	0.66 (0.32–1.36)
Quinolones	29	7 (24)	0.37 (0.15–0.91)	0.34 (0.13–0.88)
Clindamycin	28	12 (43)	0.86 (0.38–1.96)
PcV/PcG	17	6 (35)	0.63 (0.22–1.79)
Carbapenems	17	11 (65)	2.10 (0.74–6.03)
Trimethoprim/sulfa	16	8 (50)	1.15 (0.41–3,24)
Amoxicillin/Ampicillin	11	7 (64)	2.01 (0.56–7.19)
Mecillinam	10	4 (40)	0.77 (0.21–2.84)
Amoxicillin/clavulanic acid	8	3 (38)	0,69 (0.16–3.00)
Doxycycline	4	0 (0)	n/a
Lymecycline	3	1 (33)	0.57 (0.05–6.48)
Nitrofurantoin	2	0 (0)	n/a
Trimethoprim	2	0 (0)	n/a
Azithromycin	2	0 (0)	n/a
Total	385	172 (45)

Percentages of severe CDI in all antibiotic groups. Compared to cephalosporins in all comparisons.

^aBinary logistic regression, all antibiotic groups compared to cephalosporins.

^bBinary logistic regression including variables with significant differences between the five biggest antibiotic groups (gender, haematological malignancy, renal insufficiency, in-hospital days 30 days before onset of CDI).

Data availability statement

Data will be available upon reasonable request to corresponding author.