Microbiome-Based Strategies for Preventing Hospital-Acquired Infections in Critical Care

Nosocomial infections (NI)—meaning hospital-acquired— are common complications and the leading cause of mortality in intensive care unit (ICU) hospitalized patients with serious illness. Severe trauma, complex surgery, antibiotic use, and mechanical ventilation are a few events that make hospitalized patients more susceptible to infections.

Moreover, critically ill patients admitted to the ICU demonstrate significant and rapid dysbiosis in microbiota from different body sites. Intestinal microbiota dysbiosis has been shown to increase susceptibility to NI and significantly affect outcomes. Modulating the intestinal microbiota to prevent NI has become a therapy of great interest.

This blog will explore the evidence regarding microbiome-based interventions for preventing hospital-acquired infections in critical care.

Hospital-acquired infections, in brief

As the name indicates, these infections are usually acquired after hospitalization and manifest two days after admission with the risk higher in the ICU. Facility practices, patient immunity, and local pathogen prevalence determine risk. The likelihood of contracting a hospital-acquired infection also hinges on the patient’s immunosuppression, age, comorbidities, healthcare visits, invasive procedures, and ICU stay. Recent intravenous antibiotic use increases antimicrobial resistance to multiple drugs.

Common nosocomial infections are ventilator-associated pneumonias, central-line-associated bloodstream infections, catheter-associated urinary tract infections, surgical site infections, and Clostridium difficile infections.

The treatment of nosocomial infections is complicated by frequent antibiotic use (71% of ICU patients in one study) which not only kills pathogens but also beneficial microbes and can lead to antibiotic resistance.

Dysbiosis in the ICU

Critical illness and its accompanying physiological stress lead to rapid disruptions in gut integrity and changes to the microbiome, including loss of diversity and overgrowth of pathogenic bacteria.

Researchers report that “fecal ICU samples tend to have a lower relative abundance of Firmicutes and increased relative abundance of Proteobacteria.” Considerable depletions in anti-inflammatory microbes and increases in well-known pathogens have been observed.

Strikingly, dysbiosis can take hold within hours from some insults such as trauma and burns. Antibiotics and other therapies can further aggravate the microbiota.

Furthermore, intestinal dysbiosis in critical illness can drive a systemic inflammatory response and distant organ failure regardless of the location of the initial infection.

Modulation of the gut microbiome: outcomes

Researchers believe that restoring a healthy microbiome holds potential as a valuable intervention for critical illnesses. A variety of approaches to modify the microbiome have been employed in the ICU, showing differing levels of success.

Probiotics

Probiotics may be beneficial by restoring non-pathogenic microbiota, which competes with hospital-acquired pathogens, curbing their excessive growth, regulating both local and systemic immune responses, and enhancing the integrity of the gut barrier.

A 2016 systematic review and meta-analysis of 30 trials enrolling 2972 patients found that probiotic administration (Saccharomyces boulardii, Lactobacillus spp., and Bifidobacterium spp) was associated with a reduction in ICU-acquired infections, including ventilator-associated pneumonia (VAP), the most common new infection in the ICU.

However, not all studies confirm a beneficial role for probiotics. For example, in a 2021 study of patients with critical illness requiring mechanical ventilation, the use of a strain of Lacticaseibacillus rhamnosus did not show any significant variance in the occurrence of ventilator-associated pneumonia compared to a placebo. As always, probiotic effects are predicated on specific strains.

Several meta-analyses published in 2022 found that probiotics were associated with a decrease in the incidence of ICU infections, notably VAP:

Based on a meta-analysis involving 4893 patients, probiotics were found to decrease the incidence of VAP, reduce ICU length of stay, and shorten the duration of antibiotic therapy.
A meta-analysis of 8339 patients from 31 studies reported that probiotic-supplemented enteral nutrition(EPN) compared to EPN alone was more effective in alleviating VAP and preventing diarrhea; mixed probiotic strain therapy and low-dose probiotics were also more beneficial in reducing VAP incidence than EPN alone.
Another meta-analysis of nine studies with 860 critically ill patients also reported that probiotic supplementation led to a reduction in ICU-acquired infections.

Antibiotic-associated diarrhea (AAD) is often caused by hospital-acquired Clostridium difficile infection (CDI), a growing global health threat. Recurrent CDI particularly can lead to more ICU admissions and increased morbidity and mortality.

A recent literature review found that strains of lactobacilli, Bifidobacterium, and Saccharomyces demonstrated efficacy in the prevention of AAD, with the strains of Saccharomyces boulardii performing best.

Fecal microbiota transplantation

Fecal microbiota transplantation (FMT) (stools from a healthy donor are delivered to a dysbiotic patient) has been proven to be highly effective (clinical success rates ranging from 83% to 100%) in recurrent CDI. In addition, FMT has been successful in case reports of critically ill patients with dysbiosis-induced diarrhea not caused by CDI. The ability of FMT to restore gut microbiota balance and immune response in sepsis demonstrates another potential therapy for use in critically ill patients.

Synbiotics

When prebiotics are combined with probiotics, a complementary synbiotic effect may result (the precise definition is evolving).

Mechanistically, synbiotics may enhance gut microbiota, provide nutritional support to host epithelial cells via increased short-chain fatty acids utilization , preserve gut epithelial barrier by inhibiting intraluminal toxins, and regulate immune system function, potentially beneficial in reducing the development of NI.

Synbiotics have been studied in the prevention of NI:

A 2022 meta-analysis included 25 studies (5049 patients) with seven using synbiotics and the other 18 using probiotic therapy. The incidence of ICU-acquired infections was significantly reduced by the synbiotics therapy. One study reported that synbiotics were more effective than probiotics in reducing infections and length of hospital stay.
In a meta-analysis of 55 studies involving 7119 patients, researchers sought to rank “the efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition (EPN) and total parenteral nutrition (TPN) in preventing nosocomial infection (NI)” in critically ill adults. The results showed that synbiotics demonstrated the best effect in preventing NI compared to EPN followed by probiotics while TPN significantly increased the risk of NI. Synbiotics outperformed EPN in preventing hospital-acquired pneumonia, catheter-related bloodstream infections, urinary tract infections, and sepsis according to secondary outcomes.

Caution!

Researchers advise caution, however, because of a higher risk of bacteremia and fungemia infection resulting from probiotics and synbiotics in immuno-compromised critically ill patients. There are also reports of drug-resistant Escherichia coli bacteremia following FMT.

Takeaway

Hospital-acquired infections remain a significant challenge in critical care settings, often leading to mortality among seriously ill patients. Intestinal microbiota dysbiosis has emerged as a key contributor to susceptibility and outcomes. Manipulating the gut microbiome through probiotics, synbiotics, and fecal transplantation shows promise in preventing several of these infections. However, the application of these interventions requires careful consideration, especially in immuno-compromised critically ill patients. Further research is needed to refine and establish these therapies for effective and safe use in the complex context of critical care settings.

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