Running head: PROPHYLACTIC PROBIOTIC THERAPY

Decreasing Ventilator-associated Pneumonia Among Ventilated Patients Using Prophylactic

Probiotic Therapy
Haralambos Vavlas
University of South Florida

PROPHYLACTIC PROBIOTIC THERAPY

Abstract
Clinical Problem: Patients who are placed on mechanical ventilation have a great risk of
acquiring ventilator-associated pneumonia (VAP), which is associated with high mortality rates
and increased healthcare costs for both patients and hospitals.
Objective: To discuss whether prophylactic probiotics decrease the occurrence of VAP in patients
that are placed on mechanical ventilation in the intensive care unit (ICU). PubMed,
ScienceDirect, and CINAHL were analyzed to obtain randomized controlled trials regarding
probiotics and the prevention of VAP. Search terms used were ventilator-associated pneumonia,
VAP, VAP prevention, and prophylactic probiotics.
Results: Banupriya, Biswal, Srinivasaraghavan, Narayanan, and Mandal (2015) found that
mechanically ventilated patients who were given probiotics showed a significant decrease in the
occurrence of VAP (p<.001). Morrow, Kollef, and Casale (2010), Zeng et al. (2016), and
Kontzampassi, Giamarellos-Bourboulis, Voudouris, Kazamias, and Eleftheriadis (2006)
exhibited a significantly lower occurrence of VAP in mechanically ventilated patients given
prophylactic probiotics compared to those who were not (p<.001, p=.031, and p=.01
respectively).
Conclusion: Mechanically ventilated patients who receive prophylactic probiotics have a
decreased occurrence of VAP and healthcare costs. Mortality rates did not show a significant
decrease with probiotic administration. Further research is needed to determine whether a
correlation exists between probiotics and mortality rates to maintain order in terms of severity in
patients with VAP. In addition, further research is needed to establish a protocol for the specific
strains of probiotics used in addition to a dosing regimen.

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Decreasing Ventilator-associated Pneumonia Among Ventilated Patients Using Prophylactic

Probiotic Therapy
One of the most common hospital acquired infections (HAI) that is found in up to 78% of
patients that are mechanically ventilated is ventilator-associated pneumonia (VAP) (Zeng et al.,
2016). VAP is as a new onset of pneumonia that has occurred after a patient has begun
mechanical ventilation (Zeng et al., 2016). VAP is a life threatening disease, with mortality rates
of 16-94% compared to 0.2-51% in patients without VAP (Banupriya, Biswal,
Srinivasaraghavan, Narayanan, & Mandal, 2015). Furthermore, VAP causes an increased length
of hospital stay, an increase in costs for both patients and hospitals, and has been shown to
complicate the vital care of a large percentage (30%) of mechanically ventilated patients
(Morrow, Kollef, & Casale, 2010). In order to decrease the occurrence of VAP in the
mechanically ventilated population, researchers and clinicians have studied the effects of
probiotic therapy. Probiotics are beneficial to their host in multiple ways including, increasing
the function of the protective layer in the gut, preventing the settling of disease-causing bacteria,
enhancing the normal bacterial flora, and strengthening immunity (Zeng et al., 2016). To date, no
guidelines have been established that include probiotics as an intervention to decrease and
prevent VAP, however studies have shown probiotics to be a feasible and effective practice
(Oliveira, Zagalo, & Cavaco-Silva, 2014). This paper assesses whether or not probiotics are an
effective intervention in decreasing the occurrence of VAP. In intubated patients (P), do
prophylactic probiotics (I), compared to no probiotics (C), decrease the occurrence of VAP (O),
over a three-month period (T)? The expected outcome measure will be occurrence of VAP.
Literature Search

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PubMed, ScienceDirect, and CINAHL were accessed to gather peer reviewed

randomized controlled trials on probiotics and the prevention of VAP. Search terms used were
VAP, ventilator-associated pneumonia, VAP prevention, and prophylactic probiotics. The years
that were used to search for randomized controlled trials were between 2005 to 2016.
Literature Review
Four randomized-controlled trials were analyzed to determine the efficacy of
prophylactic probiotics on the occurrence of ventilator-associated pneumonia (VAP). Banupriya
et al. (2015) conducted an open-labeled, randomized, controlled trial, which investigated whether
or not probiotics prevented VAP in patients that are mechanically ventilated. A total of 150
mechanically ventilated patients, ages 12 years old or less, were randomized to a control or
intervention group by a computerized system, which generated a random number list. Seventyfive patients were randomized to both groups. Patients that were assigned to the probiotics group
received two capsules per day containing probiotics. Patients assigned to the control group
received standard care and no probiotics. The outcomes of this study showed a significantly
lower occurrence of VAP in the intervention group (p<.001). There were twelve patients (17.1%)
in the probiotic group that acquired VAP compared to 35 patients (48.6%) in the control group.
The strengths of this study included randomization of patients generated by a computerized
system, which was concealed from the individuals who first enrolled patients into the study by
sealed numbered envelopes. In addition, the patients also had similar demographics (p>.05) and
patients were monitored until they were discharged from the hospital, which gave the researchers
enough time to study the effects of the probiotics on VAP. Further strengths of this study were
rational was given by the researchers as to why patient attrition occurred and the control group
was appropriate in that it was similar to the intervention group in terms of ethnicity, age, and sex.

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A limitation of this study was that the patients and the providers were not blinded to the
interventions given to the study groups. Another limitation of this study was that this study was
completed at a single site, which may render results that cannot be generalized to other patient
populations. In summary, this study exhibited that probiotics decreased the occurrence of VAP in
mechanically ventilated patients.
Kontzampassi, Giamarellos-Bourboulis, Voudouris, Kazamias, and Eleftheriadis (2006)
investigated whether probiotics decrease the incidence of infections, including VAP, in patients
that are placed on mechanical ventilation. The design of this study was a randomized, doubleblind, controlled, trial. A total of 77 mechanically ventilated patients, ages 18 years old or
greater, were randomized into a control or intervention group. Forty-one patients were randomly
assigned into the intervention group and 36 patients were randomly assigned to the control
group. Patients assigned to the intervention group received 12 grams of probiotics daily. Patients
assigned to the control group did not receive probiotics and were given a 12-gram placebo
capsule. The outcomes of this study showed that patients allocated to the intervention group
showed a significant decrease (p=.01) in the incidence of infection rate (63%), including VAP,
compared to 90% found in the control group. The patients who received probiotics also showed a
decrease incidence of respiratory tract infections (54%) compared to patients that did not (80%),
which was also statistically significant (p=.03). The strengths of this study were randomization
of patients into their respective groups by a list that was blinded by the study personnel, the
control and intervention groups were similar in terms of injury severity, illness, and baseline
demographics, and that this was a double-blinded study. Further strengths of this study include
reasons were given for patient attrition and follow-up assessments were conducted until the
patient was discharged from the hospital, therefore the intervention was conducted long enough

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to test whether probiotics decreased the occurrence of VAP. The main weaknesses of this study
were that this study was performed in a single location and the population sample was small,
therefore the results cannot be generalized to other patient populations. In summary,
administration of probiotics was effective and showed a significant decreased occurrence of
overall infection including VAP.
Morrow et al. (2010) performed a blinded, randomized, controlled trial, to determine
whether prophylactic probiotic therapy decreased the occurrence of ventilator-associated
pneumonia (VAP), in patients placed on mechanical ventilation. There were 146 mechanically
ventilated patients, ages 19 years old or greater, randomly assigned to the control or intervention
group. The process of randomization was done in a 1:1 ratio by permutation blocks. Seventythree patients were randomized into both the control and intervention groups. The control group
received a placebo capsule twice daily, and the intervention group received a probiotic capsule,
twice daily. Patients in both groups also received standard care. Twenty-five percent of patients
that received probiotics acquired VAP compared to 47.1% of patients in the control group,
diagnosed by clinical criteria. The intervention groups showed a significant decrease (p<.001) in
the occurrence of VAP. In addition, 28 (40%) patients in the control group compared to 13
(19.1%) patients in the intervention group also had microbiologically confirmed VAP, which was
also statistically significant (p=.007). The strengths of this study were that patients were
randomized into either a control or intervention group by permutation blocks, patients and
personnel were blinded to group assignments and interventions, and rationale for patient attrition
was given. Another strength of this study was that the control group was appropriate and was
similar to the intervention group based on patient demographics. The main limitation of this
study was that it was performed in a single location, therefore the results cannot be generalized

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to other patient populations. In summary, probiotic therapy was effective and showed a decreased
occurrence of VAP.
Zeng et al. (2016) studied whether probiotics reduce the occurrence of VAP in patients
that are mechanically ventilated. The design of this study was an open-labeled, randomized,
controlled multicenter study, which incorporated 11 intensive care units (ICU). There were 250
mechanically ventilated patients, ages 18 years old or older, that were randomly assigned to a
control (n=125) or intervention group (n=125). The intervention group was given three capsules
containing probiotics daily, which was administered through a nasogastric tube in addition to
standard care. The control group was given standard care. The outcomes of this study showed a
significant decrease (p=.031) in the occurrence of VAP in the patients that received probiotics
(36.4%) compared to the patients that did not (50.4%). The strengths of this study included
randomization of patients to the intervention and control groups, rationale for patient attrition
was given, and the study continued until the patients were extubated, discharged, or death
occurred, therefore the assessments were done for a sufficient amount of time to test the efficacy
of the probiotics. Further strengths include the control group was appropriate in that it was
similar to the intervention group in terms of race, age, and sex, and this was a multicenter study,
which involved multiple ICUs. The main weaknesses of this study was that it was an open-label
study. Therefore, the patients and the providers knew which treatments were being given to each
group. In addition, this study was conducted for 14 days, and these results cannot be generalized
to long term mechanically ventilated patients. In summary, this study exhibited that probiotic
therapy significantly decreased the occurrence of VAP in patients placed on mechanical
ventilation.
Synthesis

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Banupriya et al. (2015) demonstrated that prophylactic probiotics significantly decreased

the occurrence of VAP in patients that are mechanically ventilated compared to mechanically
ventilated patients who were not given probiotics (p<.001). Additionally, Kotzampassi et al.
(2006) reported a significant reduction in the occurrence of overall infection, including the
occurrence of VAP (p=.01) and respiratory tract infections (p=.03), in mechanically ventilated
patients given probiotics. Morrow et al. (2010) demonstrated a significant reduction in the
occurrence of VAP diagnosed by clinical criteria in mechanically ventilated patients treated with
probiotics (p<.001). Of these, Morrow et al. (2010) showed a decrease in the occurrence of
microbiologically confirmed VAP, which was also statistically significant (p=.007). Finally, Zeng
et al. (2016) showed a significant decrease (p=.031) in the occurrence of VAP in mechanically
ventilated patients who received probiotics compared to mechanically ventilated patients who
did not.
Research has demonstrated that probiotics significantly decreases the occurrence of VAP
in the mechanically ventilated population. Due to decreased occurrence of VAP, healthcare costs
for both patients and hospitals should also subsequently decrease. Despite these promising
results, clinical guidelines have yet to be made that incorporate the use of probiotics in patients
receiving mechanical ventilation. Oliveira and Cavaco-Silva (2014) showed that as of 2013, no
guidelines exist that implement probiotics in the prevention of VAP, however deem probiotics as
a feasible and effective preventive measure. Despite the significant reduction in the incidence of
VAP, only Kotzampassi et al. (2006) showed a corresponding decline in mortality rates in the
intervention group. One possible explanation for the lack of decreased mortality rates may be
attributed to the multiple complications critically ill and immobile patients face in the clinical
setting such as, pressure sores and blood clots, which may lead to death. In addition, the strain of

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probiotic has a lot to do with the organism that it affects. Most VAP probiotics were effective
against pseudomonas. Kotzampassi et al. (2006) used a combination of four different probiotics
in their intervention group, which may have been more effective against a more deadly organism.
Therefore, in the other studies, death may have occurred as a result of an organism that was not
covered by the strain of probiotic used. This is an area for additional research. In addition, more
research is also needed to determine a specific protocol on the strain and the amount of
probiotics used to best treat patients with VAP. Various types of probiotics and dosing regimens
were used in each study with no sense of homogeneity.
Clinical Recommendation
Although no guidelines have incorporated the use of probiotics to reduce or prevent VAP,
research has confirmed that prophylactic probiotics are a feasible and effective practice that
should be incorporated into clinical guidelines. In addition, research has showed that
prophylactic probiotics significantly reduced the occurrence of VAP in the mechanically
ventilated population. Further research is needed in order to establish a protocol for the specific
strain of probiotics used in addition to a dosing regimen. Probiotics are an innovative treatment
that decrease the occurrence of VAP, improve patient outcomes, and decrease healthcare costs.

References
Banupriya, B., Biswal, N., Srinivasaraghavan, R., Narayanan, P., & Mandal, J. (2015). Probiotic

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