Anastomotic Leak is Increased With Clostridium difficile Infection After Colectomy: Machine Learning-Augmented Propensity Score Modified Analysis of 46 735 Patients

Abstract

Background Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). Methods Machine learning-augmented multivariable regression and propensity score (PS)–modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. Results Among 46 735 colectomy patients meeting study criteria, mean age was 61.7 years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). Conclusions This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.

Collagenase-producing bacteria are common in anastomotic leakage after colorectal surgery: a systematic review

“…Most studies (80%) were published from 2019 onwards [ 34 , 35 , 37 , 39 , 41 – 48 ]. The majority of the studies were case–control studies [ 35 , 36 , 38 – 41 , 43 – 48 ], and three were descriptive studies [ 34 , 37 , 42 ].…”

“…The number of patients varied greatly from as few as 19 patients [ 34 ] to more than 46,000 patients [ 35 ]. The total number of patients in all studies was 52,945, of which 1,747 had AL.…”

“…The total number of patients in all studies was 52,945, of which 1,747 had AL. All studies except one [ 35 ] had a majority of male patients. However, one study did not report the sex of the patients [ 42 ].…”

“…However, one study did not report the sex of the patients [ 42 ]. The rate of AL was reported in 14 out of 15 studies [ 35 – 48 ]. The use of antibiotics was reported in nine studies [ 35 – 38 , 40 , 43 , 45 , 46 , 48 ], and information about bowel preparation was presented in eight studies [ 35 – 38 , 40 , 43 – 45 ].…”

Colorectal Anastomosis: The Critical Aspect of Any Colorectal Surgery

“…It happens because collagenase-producing bacteria, particularly E. faecalis, promotes anastomotic leak by degrading healing anastomotic tissue [25]. Furthermore, Clostridium difficile infection can also increase anastomotic leak after colectomy [26].…”