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Objective: Clostridium Difficile infections (CDI), the most common infectious colitis, have been increasing in incidence and severity over the last decade. Severe CDI that requires surgical intervention is rare but mortality rate is high and poorly prognosticated. In light of a paucity of level I evidence available to direct clinical decision-making, this study aims to identify factors that may predict mortality from severe CDI.
Methods: A systematic review was performed on 31 published series between 1994 and 2011 describing patients with CDI requiring surgical intervention. Of the 31 studies identified, a meta-analysis was performed on 17 studies that presented comparative data between survivors and non-survivors of surgical CDI. Independent variable analyses were performed for age, gender, preoperative comorbidities, preoperative laboratory values, as well as surgical management (total colectomy end ileostomy or TCEI, segmental colectomy, diverting ostomy, or non-therapeutic laparotomy).
Results: Based on the 31 studies included in the review, the overall rate of surgical intervention for patients diagnosed with CDI was 1.9%. The mean age of surgical CDI patients was 69 years, and 54% were male. 93.2% of the patients with surgical CDI had received antibiotics prior to diagnosis, and 59.3% were initially diagnosed with CDI in-hospital. The mean WBC was 29.6 x103/µL. 49.9% required preoperative vasopressors, and 44.5% had preoperative respiratory failure requiring intubation. Overall, 89.2% of patients received a TCEI for CDI. Overall mortality of surgical CDI patients was 42.5%.
Among the 17 studies included in the meta-analysis, there were a total of 621 patients comprised of 367 (59%) survivors and 254 (40.9%) non-survivors. The mean age of non-survivors was 71.6 years and of survivors was 65.2 years (p=0.001). There was no significant difference between duration of symptom onset to surgery between survivors and non-survivors. Preoperative vasopressor requirement, respiratory failure (RF), acute renal failure (ARF), multi-organ failure (MOF), and recent antibiotic use were independent predictors of postoperative mortality (Table). Non-survivors had a significantly lower preoperative albumin compared to survivors (1.66 vs 2.28 g/dL, p = 0.04). Heart rate, WBC, lactate, creatinine were not significantly different between survivors and non-survivors. Finally, the initial type of surgical intervention was not predictive of survival.
Conclusion: The initial type of surgical intervention was not predictive of survival. Factors that were predictive of mortality from CDI included hypoalbuminemia, septic shock, ARF, RF, and MOF. This study suggests that expeditious surgical intervention prior to end organ failure may lead to improved survival in fulminant CDI.
Table 1: Meta-analysis of surgical Clostridium difficile infection risk factors for mortality

Covariate	No. of studies	Overall Effect (OR and 95% confidence interval)	P	I2 Test for Heterogeneity (%)
Total Colectomy (TCEI)	14	1.5735 (0.8711, 2.8423)	0.13	14.7
Segmental Colectomy	14	0.6526 (0.3541, 1.2026	0.17	24.5
Other Procedure (Not TCEI)	14	0.6355 (0.3518, 1.1480)	0.13	14.7
Gender	10	1.0017 (0.6720, 1.4932)	0.99	0.0
Vasopressors	10	3.8599 (2.6063, 5.7163)	<0.001	12.5
Immunosuppression	9	0.7736 (0.5142, 1.1639)	0.22	0.0
Recent Surgery	7	0.4641 (0.2381, 0.9046)	0.02	17.9
Recent Antibiotic Use	6	4.1599 (1.1733, 14.7486)	0.03	0.0
CRF	6	0.8784 (0.3886, 1.9852)	0.76	0.0
Respiratory Failure	6	6.4230 (3.4633, 11.9121)	<0.001	6.0
ARF	5	3.5793 (1.5789, 8.1142)	0.002	16.7
COPD	4	1.4037 (0.5680, 3.4690)	0.46	0.0
Known Cancer	4	2.0196 (0.7804, 5.2264)	0.15	0.0
MOF	4	7.6396 (3.0764, 18.9715)	<0.001	20.3
Diagnosis Known Pre-Op	3	0.3884 (0.1034, 1.459)	0.16	0.0
Organ Transplant	3	0.3834 (0.1265, 1.1622)	0.09	0.0
Recurrent c diff	3	1.1434 (0.6079, 2.1505)	0.68	0.0