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Response to “Reassessing the death risk related to probiotics in critically ill patients”

The Original Article was published on 29 November 2016

We would like to thank Dr. Maraolo for his valuable and careful analysis [1] of the data of our recently published systematic review and meta-analysis on probiotic and synbiotic therapy in the critically ill [2]. As Dr. Maraolo has observed we have made an error in the calculation of the pooled risk ratio (RR) and 95% confidence interval (CI) for the effect of probiotics on hospital mortality. When we abstracted mortality data from the Besselink et al. [3] study we included correct data in both arms (24 of 152 and 9 of 144 patients in the probiotic and placebo groups, respectively). Nonetheless, we made a mistake creating the forest plot. Please, accept our sincere apologies.

Currently, after including the correct data from the Besselink et al. study using the random effect model in the software RevMan 5.3 (Cochrane IMS, Oxford, UK), we found that the revised effect of probiotics and synbiotics therapy on overall mortality is 1.02 (95% CI 0.85,1.22; p = 0.83, I2 = 0%; Fig. 1). Notwithstanding, at this point we respectfully disagree with Dr. Maraolo. Certainly, after reassessing the RR this new result does not change the direction of the effect against the use of probiotics in the critically ill. Our previous data showed that the RR was 0.98 with a CI similar to the present one (0.85, 1.22). Moreover, the p value was 0.83 and we cannot thus affirm that a trend against probiotics on mortality exists, as we defined trend with a p value <0.10. So far, clinical trials evaluating the effects of probiotics (excluding Saccharomyces boulardii, which should not be considered as a probiotic in the critical care setting) [4] in different ICU patient populations have documented safety and clinical benefits, as we recently demonstrated in our systematic review.

Fig. 1
figure 1

Effect of Probiotics and Synbiotics Therapy on Hospital Mortality

Having said that, the conclusion of our meta-analysis remains unchanged. According to our findings probiotic therapy may be associated with a significant reduction in overall new infections, including new episodes of ventilator-associated pneumonia. However, no benefits in terms of reduction in mortality or another relevant clinical outcome for critically ill patients have been pointed out.



Confidence interval


Risk ratio.


  1. Maraolo AE. Reassessing the death risk related to probiotics in critically ill patients. Crit Care. 2016;20:338.

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  2. Manzanares W, Lemieux M, Langlois PL, Wischmeyer PE. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. Crit Care. 2016;20:262.

    Article  PubMed Central  Google Scholar 

  3. Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, Van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG, Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind,placebo-controlled trial. Lancet. 2008;371:651–9.

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  4. Urben LM, Wiedmar J, Boettcher E, Cavallazzi R, Martindale RG, McClave SA. Bugs or drugs: are probiotics safe for use in the critically ill? Curr Gastroenterol Rep. 2014;16:388.

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Authors´ contribution

WM and PW wrote and edited the letter. Both authors read and approved the final version of the manuscript.

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The authors declare that they have no competing interests.

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Correspondence to Paul E. Wischmeyer.

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See related Letter by Maraolo,

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Manzanares, W., Wischmeyer, P.E. Response to “Reassessing the death risk related to probiotics in critically ill patients”. Crit Care 21, 43 (2017).

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  • Critical Care
  • Risk Ratio
  • Hospital Mortality
  • Random Effect Model
  • Forest Plot