Probiotics for Clostridium Difficile

We saw it coming, but could we have prevented it?

An older gentleman developed septic shock on post injury day 2, so empiric vancomycin and piperacillin/tazobactam was clearly indicated.  His abdomen was morbid: multiple transabdominal gunshot wounds and hypovolemic shock, status post massive transfusion protocol, damage control laparotomy with right hemicolectomy, small bowel resection, cholecystectomy, four stapled bowel repairs (duodenum, jejunum, ileum, and sigmoid colon), with ligations at the small and large bowel mesenteries, left in discontinuity in small and large bowel, with Bogota bag. But in such a state of bowel flora disarray, no one was surprised that after 9 days of vanc/zosyn, his green diarrhea returned a positive Clostridium difficile toxin.

No other cases of C diff had been seen recently in the unit at the time; all rooms in the ICU are routinely cleaned and disinfected, and rates of glove use and appropriate hand hygiene in the Trauma ICU are generally high. Could we have prevented his infection with prophylactic probiotics?

The literature is conflicted. The most recent authoritative 2010 clinical practice guidelines from the Infectious Disease Society of America do not recommend the use of probiotics because data showed no benefit to outweigh the theoretical risk of infection from the probiotics themselves. The latest Cochrane Review (2013) reverse the previous Cochrane review (2008) by finding probiotics reduce the risk of C diff by 64%. In 23 studies of n=4213 patients, RR was 0.36; 95% CI 0.26 to 0.51. A 2010 RCT n=68 found less ventilator acquired pneumonia (40.0 vs. 19.1%; P = 0.007) and diminished C diff incidence (18.6 vs. 5.8%; P = 0.02) with lactobacillus administration. However a very large RCT in Lancet (2013) of n=2981 inpatients ≥ 65 y/o on antibiotics found no significant reduction in antibiotic associated diarrhea with or without C.diff infection; RR was 1.04; 95% CI 0.84 to 1.28.  Lastly, a word on safety. Although the literature is full of case reports of Lactobacillus bacteremia and Saccharomyces fungemia secondary to probiotics, a recent 2013 single center retrospective review found the incidence of such events to be 2 of 1176 patients, or 0.2%. These patients were similarly sick to our patient, with moderate to severe immunosuppression (47%), impaired intestinal integrity (33%), and requiring an echocardiogram (62%).

Our patient’s GI flora has continued to deteriorate. Amidst the over 14 washouts, attempted abdominal closures, and subtotal colectomy with intermittent high fevers, ventilator and vasopressor requirements, he began to need more and more antibiotics at the recommendation of our Infectious Disease consultants. Post injury day 27 he was on metronidazole, vancomycin (both IV and PO), imipenem, amikacin, and caspofungin for intraabdominal sepsis and pneumonia. 

We stopped short of fecal transplant to reestablish the GI flora, when the C. diff finally responded to the metronidazole and vancomycin.

References

1.  Allen SJ, et al. 2013. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and clostridium difficile diarrhoea in older inpatients (PLACIDE): A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 382(9900):1249-57.

2.  Cohen SH, et al. 2010. Clinical practice guidelines for clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of america (SHEA) and the infectious diseases society of america (IDSA). Infect Control Hosp Epidemiol 31(5):431-55.

3.  Goldenberg JZ, et al. 2013. Probiotics for the prevention of clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 5:CD006095.

4.  Morrow LE, et al. 2010. Probiotic prophylaxis of ventilator-associated pneumonia: A blinded, randomized, controlled trial. Am J Respir Crit Care Med 182(8):1058-64.

5.  Pillai A and Nelson R. 2008. Probiotics for treatment of clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev (1):CD004611. doi(1):CD004611.

6.  Simkins J, et al. 2013. Investigation of inpatient probiotic use at an academic medical center. Int J Infect Dis 17(5):e321-4.

By: Andy Tully, MS4