�Son efectivos los probi�ticos para prevenir la diarrea del viajero?

Pinos, Yazm�n; Castro-Guti�rrez, Victoria; Rada, Gabriel

doi:10.5867/medwave.2016.6807

Res�menes Epistemonikos

Medwave 2016; 16(Suppl5):e6807 doi: 10.5867/medwave.2016.6807

�Son efectivos los probi�ticos para prevenir la diarrea del viajero?

Are probiotics effective to prevent traveler�s diarrhea?

Yazm�n Pinos, Victoria Castro-Guti�rrez, Gabriel Rada

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Abstract

La diarrea aguda es la enfermedad m�s com�n que afecta a los viajeros, principalmente aquellos que se dirigen a regiones de alto riesgo. El uso de probi�ticos podr�a prevenir su aparici�n, sin embargo, los datos que apoyan su uso no son consistentes y no se recomiendan en las gu�as cl�nicas actuales. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante b�squedas en m�ltiples bases de datos, identificamos cuatro revisiones sistem�ticas que en conjunto incluyen siete estudios aleatorizados pertinentes a esta pregunta. Realizamos un metan�lisis y tablas de resumen de los resultados utilizando el m�todo GRADE. Concluimos que los probi�ticos podr�an prevenir la diarrea del viajero, pero la certeza de la evidencia es baja.

Problem

Acute diarrhea is the most common disease that affects travelers heading to at-risk areas. Although preventive measures related to hygiene have reduced the risk in many destinations, this is still high in some others [1].

The use of probiotics as prophylaxis for traveler's diarrhea seems attractive because of their beneficial effects over intestinal flora, and the reduction in colonization by pathogenic bacteria, in addition to their safety. However, data supporting their use are not consistent [2].

Methods

We used Epistemonikos database, which is maintained by screening multiple databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

Probiotics might prevent traveler’s diarrhea but the certainty of the evidence is low.

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We found four systematic reviews [3],[4],[5],[6], that included seven randomized controlled trials [7],[8],[9],[10],[11],[12],[13].
What types of patients were included	Three studies only included adults [7],[11],[13]. One study included patients aged 10 to 80 years [10]. In three studies, the age range was not specified [8],[9],[12]. The included patients traveled to different destinations: From the United Kingdom to Belize [7] From Austria to Turkey/North Africa [8] From Denmark to Egypt [9] From Finland to Turkey [10] To warm climates [12] not specified From the United States to Mexico [13] One trial included several destinations [11]
What types of interventions were included	The trials used different probiotics and in different doses: Lactobacillus fermentum 10¹¹ CFU per day during three weeks or until the appearance of diarrhea [7]. Lactobacillus acidophilus 10¹¹ CFU per day during three weeks or until the appearance of diarrhea [7] (subgroup of study above). Saccharomyces boulardi 5 X 10⁹ and 2 X 10¹⁰during three weeks [8]. Combination of L. acidophilus + L. bulgaricus + bifidobacterium bifidum + streptococcus thermophilus 3 x 10⁹ per two weeks [9]. Lactobacillus rhamnosus GG 2 x 10⁹ CFU per day during 1-2 weeks [10]. Lactobacillus rhamnosus GG 20 x 10⁹ CFU per day during 1-3 weeks [11]. Saccharomyces cereviciae 2.5 x 10⁹ or 5 x 10⁹ and Lactobacillus acidophilus 2 x 10⁸ or 2 x 10⁹ during the travel (average 10 days for Saccharomyces and 12 days for Lactobacillus) [12]. Lactobacillus acidophilus + lactobacillus bulgaricus 30 x 10⁷ at 60 x 10⁷ lactobacilli per tablet, four tablets in each meal for eight days and during 28 days [13]. All of the trials compared against placebo or standard treatment.
What types of outcomes were measured	The outcome was the development of diarrhea during the trip, defined as more than three stools per day for at least two days, or more than five stools in 48 hours.

Both trials evaluated the use of tetrahydrocannabinol capsules administered orally. In one trial, the dose was 5 mg, 7.5 mg or 10 mg once [9], and in the other trials, the dose was not specified [8].

Both trials compared against placebo.

Summary of findings

The information on the effects of probiotics to prevent traveler's diarrhea is based on seven randomized trials including 4,025 patients. All of the trials measured the outcome of diarrhea during the trip, defined as more than three stools per day for at least two days or more than five stools in 48 hours.

The summary of findings is as follows:

Probiotics might prevent traveler’s diarrhea but the certainty of the evidence is low.

Follow the link to access the interactive version of the Summary of Findings (iSoF) table

Other considerations for decision-making

To whom this evidence does and does not apply

The evidence presented in this summary applies to people traveling to various destinations.
Although the trials used different probiotics, the overall certainty of the existing evidence is low, so any conclusion regarding differences between different types of probiotics is not reliable.

About the outcomes included in this summary

We only included the development of diarrhea as the critical outcome for decision-making, which in general agrees with the guidelines and reviews identified.

Balance between benefits and risks, and certainty of the evidence

It is not possible to make an adequate balance between benefits and risks due to the existing uncertainty
If the benefit were real, there would be important variation in this balance depending on different risk areas.

What would patients and their doctors think about this intervention

Probiotics constitute a generally acceptable and well tolerated intervention by patients, although it is associated with costs.
Patients and physicians putting more value on an uncertain benefit would probably be inclined to use this intervention. Those who place a higher value on the certainty of the evidence or costs would probably abstain from its use.
In any case it is important to inform about the limitations of existing evidence.

Resource considerations

The cost of probiotics could be an important factor in the decision, especially in situations where resources are limited.
It is not possible to make an adequate cost / benefit balance due to the existing uncertainty.

Differences between this summary and other sources

The systematic reviews identified differ in their conclusions, so this summary partially agrees with them, especially in recognizing that the existing evidence is limited.
The evidence presented in this summary is consistent with one of the main clinical guidelines, which makes a conditional recommendation against its use, based on evidence similar to what is discussed in this article [14].

Could this evidence change in the future?

The probability that future evidence would change the conclusions of this article is very high, due to the existing uncertainty.
None of the identified systematic reviews is sufficiently updated, so a new review could shed some additional light on this topic.

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Probiotics for prevention of traveler's diarrhea

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

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