Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes

doi:10.4240/wjgs.v13.i11.1436

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World Journal of Gastrointestinal Surgery

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1948-9366

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

World J Gastrointest Surg. Nov 27, 2021; 13(11): 1436-1447
Published online Nov 27, 2021. doi: 10.4240/wjgs.v13.i11.1436

Table 1 Classification of Clostridium difficile infection severity based on the Infectious Diseases Society of America criteria

Severity	IDSA criteria
Mild	WBC < 15 × 10⁹/L and serum creatinine < 1.5 times premorbid level
Severe	WBC ≥ 15 × 10⁹/L, or serum creatinine ≥ 1.5 times premorbid level
Fulminant (severe, complicated)	Hypotension, shock, ileus, or megacolon

IDSA: Infectious Diseases Society of America; WBC: White blood cell.

Table 2 Baseline information of patients with Clostridium difficile infection compared between patients with appendectomy and no history of appendectomy

Variable	All patients (%)	No prior appendectomy (%)	Prior appendectomy (%)	P value	n
	1580	1382 (87.5)	198 (12.5)
Age	57.1 ± 15.7	57.1 ± 15.6	56.8 ± 17.0	0.812	1580
Gender				0.022	1580
Female	809 (51.2)	692 (50.1)	117 (59.1)
Male	771 (48.8)	690 (49.9)	81 (40.9)
Ethnicity				0.439	1580
African American	611 (38.67)	540 (39.1)	71 (35.9)
Hispanic	262 (16.6)	228 (16.5)	34 (17.2)
Caucasian	58 (3.73)	52 (3.8)	6 (3.03)
Others	10 (0.63)	7 (0.51)	3 (1.52)
Not available	639 (40.4)	555 (40.2)	84 (42.4)
Comorbidities					1580
Hypertension	1210 (76.58)	1022 (73.95)	153 (77.27)	0.815
Diabetes mellitus	741 (46.89)	618 (44.71)	102 (51.51)	0.384
Obstructive lung disease	752 (47.56)	633 (45.80)	95 (47.97)	0.933
Coronary artery disease	480 (30.37)	407 (29.45)	57 (28.78)	0.802
Chronic kidney disease	477 (30.18)	406 (29.37)	56 (28.28)	0.819
Inflammatory bowel diseases					1580
Ulcerative colitis	117 (7.40)	103 (7.45)	9 (4.54)	0.203
Crohn’s disease	42 (2.66)	37 (2.67)	4 (2.02)	0.803
Risk Factor of CDI
Prior use of antibiotics	768 (52.2)	656 (51.3)	112 (58.3)	0.086	1470
Prior use of PPI	429 (29.0)	353 (27.4)	76 (39.4)	0.001	1480
Prior use of steroids	128 (8.73)	110 (8.63)	18 (9.1)	0.838	1467
Prior chemotherapy	50 (3.35)	45 (3.46)	5 (2.59)	0.678	1492
Known malignancy	175 (11.4)	147 (11.0)	28 (14.1)	0.232	1539
Liver cirrhosis	117 (8.42)	98 (8.19)	19 (9.84)	0.531	1389
HIV infection	406 (34.5)	362 (35.2)	44 (29.3)	0.186	1389
C. difficile related complication
Ileus on imaging	52 (3.90)	41 (3.59)	11 (5.67)	0.237	1335
Admission to ICU	615 (40.6)	526 (39.8)	89 (46.1)	0.113	1514
Intubation	298 (19.9)	258 (19.8)	40 (20.7)	0.846	1494
Clinical variable
Body mass index (kg/m²)	27.69 ± 7.7	27.78 ± 7.79	26.70 ± 6.75	0.1890	690
Mean arterial pressure (mmHg)	92.4 ± 18.2	92.6 ± 18.3	90.5 ± 17.5	0.115	1467
Pulse beats per minute	91.7 ± 20.8	91.6 ± 21.0	92.3 ± 20.0	0.700	1464
Laboratory parameters
Hemoglobin g/dL	11.2 ± 2.93	11.2 ± 2.98	11.2 ± 2.58	0.819	1533
White blood cell (cells/mm³)	11.6 ± 8.04	11.4 ± 8.06	13.1 ± 7.71	0.005	1533
Albumin (mg/dL)	3.37 ± 0.82	3.38 ± 0.81	3.31 ± 0.87	0.309	1502
Blood urea nitrogen (mg/dL)	26.9 ± 26.0	26.9 ± 25.8	26.7 ± 27.3	0.925	1531
Serum creatinine (mg/dL)	1.85 ± 2.26	1.85 ± 2.24	1.88 ± 2.43	0.830	1531
Lactic acid (mg/dL)	2.13 ± 2.27	2.16 ± 2.33	1.92 ± 1.82	0.127	1372

C. difficile: Clostridium difficile; CDI: Clostridium difficile infection; PPI: Proton pump inhibitors; HIV: Human immunodeficiency virus; ICU: Intensive care unit.

Table 3 Comparison of the Clostridium difficile infection outcomes based on the prior appendectomy status and the inverse probability of treatment weights analysis

Outcome	Total	No prior appendectomy	Prior appendectomy	OR (95%CI)	P value
n	1580	1382	198
n IP-weighted		1572	1354
Mortality
n (%)	220 (13.9)	193 (14.2)	27 (13.7)	0.97 (0.61-1.47)	0.877
n IP-weighted (%)		218 (14)	207 (15.5)	1.12 (0.65-1.92)	0.685
Recurrence
n (%)	228 (14.4)	199 (14.4)	29 (14.6)	1.02 (0.66-1.54)	0.915
n IP-weighted (%)		228 (14.5)	204 (15.1)	1.05 (0.66-1.67)	0.847
Toxic megacolon
n (%)	7 (0.4)	4 (0.34)	3 (1.57)	4.75 (0.87-22.9)	0.069
n IP-weighted (%)		5 (0.3)	19 (1.5)	4.32 (0.91-20.57)	0.066
Colectomy
n (%)	22 (1.4)	16 (1.19)	6 (3.06)	2.65 (0.93-6.59)	0.067
n IP-weighted (%)		18 (1.2)	24 (1.8)	1.53 (0.55-4.27)	0.413
Severity (IDSA)
Before IPTW				1.32 (1.01-1.75)	0.043
Mild, n (%)	710 (44.9)	634 (45.9)	76 (38.4)
Severe, n (%)	566 (35.8)	489 (35.4)	77 (38.9)
Fulminant, n (%)	304 (19.2)	259 (18.7)	45 (22.7)
After IPTW				1.59 (1.15-2.18)	0.005
Mild, n (%)		724 (46.1)	472 (34.8)
Severe, n (%)		557 (35.4)	526 (38.8)
Fulminant, n (%)		291 (18.5)	356 (26.3)
LOS among survivors
Median (IQR)		9 (5.00; 18.0)	10 (6.50; 20.0)	1.1 (0.94-1.28)	0.233
Median (IQR)-IPTW		10 (5.00; 20.0)	12 (7.00; 23.00)	0.9 (0.74-1.1)	0.318

Data were summarized using counts and percentages before inverse probability of treatment weights (IPTW) and weighed counts and percentages after IPTW. Statistical analysis was performed using logistic regression for categorical variables and Poisson regression for length of stay (LOS). Analysis for LOS included only patients who were discharged. Ordinal logistic regression was used to assess the association between history of appendectomy and Infectious Diseases Society of America severity. CI: Confidence interval; OR: Odds ratio; IQR: Interquartile range; IPTW: Inverse probability of treatment weights; LOS: Length of stay; IDSA: Infectious Diseases Society of America.

Table 4 Association between Clostridium difficile infection outcomes and severity of the presentation

	Severity (IDSA)
Outcomes	Mild (n = 710)	Severe (n = 566)	Fulminant (n = 304)	P value
Mortality (%)	29 (4.1)	44 (7.7)	147 (48.3)	< 0.001
Recurrence (%)	98 (13.8)	81 (14.3)	49 (16.1)	0.063
Toxic megacolon (%)	0	0	7 (2.3)	< 0.001
Colectomy (%)	0	0	22 (7.2%)	< 0.001
Length of stay (median)	8 (4.00; 14.00)	10.0 (6.00; 18.0)	19 (10.0; 30.0)	< 0.001

Counts and percentages were used to summarize categorical variables. The median (interquartile range) was used to summarize length of stay (LOS). Statistical analysis was performed using the Chi-square test of independence. LOS was compared using the Kruskal-Wallis test. Analysis for LOS included only patients who were discharged. IDSA: Infectious Diseases Society of America.

Table 5 Association between body mass index and severity of Clostridium difficile infection presentation

Severity (IDSA)	Body mass index (kg/m²)	P = 0.412
Mild	27.66 ± 7.39
Severe	27.34 ± 7.63
Fulminant	28.4 ± 8.59

IDSA: Infectious Diseases Society of America.

Table 6 Multivariate analysis for primary and secondary outcomes

	Mortality		Recurrence		Toxic megacolon		Need for colectomy
Variable	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI	P value
Age	1.02 (1.01-1.03)	< 0.001	1.00 (0.99-1.01)	0.626			0.99 (0.96-1.02)	0.547
Female gender	Ref		Ref		Ref		Ref
Male gender	1.32 (0.97-1.81)	0.079	0.91 (0.67-1.22)	0.518	0.86 (0.17-4.00)	0.846	1.36 (0.55-3.46)	0.501
Prior appendectomy = no	Ref		Ref		Ref		Ref
Prior appendectomy = yes	1.03 (0.64-1.59)	0.905	0.92 (0.58-1.42)	0.727	5.37 (1.03-25.09)	0.031	2.77 (0.95-7.17)	0.044
Prior antibiotics (no)	Ref		Ref		Ref		Ref
Prior antibiotics (yes)	1.04 (0.76-1.43)	0.788	1.07 (0.79-1.44)	0.668	0.13 (0.01-0.81)	0.065	1.58 (0.62-4.31)	0.348
Prior steroids (no)	Ref		Ref		Ref		Ref
Prior steroids (yes)	0.72 (0.37-1.30)	0.309	1.08 (0.63-1.77)	0.774	1.99 (0.10-12.38)	0.533	0.41 (0.02-2.07)	0.391
Prior PPI (no)	Ref		Ref		Ref		Ref
Prior PPI (yes)	0.89 (0.62-1.27)	0.530	1.05 (0.74-1.46)	0.790	1.08 (0.15-5.38)	0.933	1.83 (0.71-4.60)	0.196
Prior chemotherapy (no)	Ref		Ref		Ref		Ref
Prior chemotherapy (yes)	0.92 (0.34-2.07)	0.851	0.76 (0.26-1.79)	0.570	-		4.26 (0.65-16.24)	0.063

Multivariate analysis for mortality and recurrence was performed using binomial logistic regression. Chemotherapy was not included in the analysis of toxic megacolon due to convergence issues. OR: Odds ratio; CI: Confidence interval; PPI: Proton pump inhibitors.

Citation: Shaikh DH, Patel H, Munshi R, Sun H, Mehershahi S, Baiomi A, Alemam A, Pirzada U, Nawaz I, Naher K, Hanumanthu S, Nayudu S. Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes. World J Gastrointest Surg 2021; 13(11): 1436-1447
URL: https://www.wjgnet.com/1948-9366/full/v13/i11/1436.htm
DOI: https://dx.doi.org/10.4240/wjgs.v13.i11.1436