Synbiotic Therapy Prevents Nosocomial Infection in Critically Ill Adult Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Based on a Bayesian Framework

Abstract

Background: 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 has been questioned. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) to evaluate and rank the effectiveness of these therapies on NI amongst critically ill adults. Methods: Four electronic databases were systematically searched up to June 30, 2019 for RCTs comparing the administration of probiotics, prebiotics, synbiotics, EPN and TPN in critically ill adults. The primary outcome was NI. The relative efficacy of all outcomes was determined by a Bayesian framework with random effects NMA. We estimated the odds ratio (OR) and mean difference (MD) and ranked the comparative effects of all regimens with the surface under the cumulative ranking probabilities. The study has been registered on PROSPERO (CRD42019147032). Results: Fifty-five RCTs (7,119 patients) were identified. Primary outcome showed that synbiotics had the best effect in preventing NI than EPN (OR 0.37; 95% CrI 0.22-0.61), probiotics followed (OR 0.52; 95% CrI 0.34-0.77), whereas TPN significantly increased NI (OR 2.29; 95% CrI 1.48-3.67). Subgroup analysis showed that TPN significantly increased NI in intensive care unit (ICU) patients (OR 1.57; 95% CrI 1.01-2.56) and severe acute pancreatitis (SAP) patients (OR 3.93; 95% CrI 1.74-9.15). Secondary outcomes showed that synbiotics were more effective in preventing hospital-acquired pneumonia (HAP) (OR 0.34; 95% CrI 0.11-0.85), catheter-related bloodstream infection (OR 0.08; 95% CrI 0.01-0.80), urinary tract infection (OR 0.27; 95% CrI 0.08-0.71) and sepsis (OR 0.34; 95% CrI 0.16-0.70) than EPN. Amongst the treatments, probiotics were most effective for shortening the mechanical ventilation duration (MD -3.93; 95% CrI -7.98 to -0.02), prebiotics were most effective for preventing diarrhea (OR 0.24; 95% CrI 0.05-0.94) and TPN was the least effective in shortening hospital length of stay (MD 4.23; 95% CrI 0.97-7.33). Conclusions: Amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. Take-Home Message: Nosocomial infection is a leading cause of mortality in critically ill patients in the ICU. However, the efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition and total parenteral nutrition in preventing nosocomial infection in critically ill adults has been questioned. The network meta-analysis provides evidence that amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. The results of this study will provide a new scientific basis and a new idea for the debate on the efficacy of synbiotics and other treatments in the improvement of prognosis in critically ill adult patients. Tweet: Synbiotic prevents nosocomial infection in critically ill adults, while total parenteral nutrition has the adverse curative.

Keywords: Bayesian; critical illness; network meta-analysis; nosocomial infection; synbiotic.

Figure 1

Flow diagram of included studies.

Figure 2

Risk bias assessment graph for included studies.

Figure 3

Summary of risk bias assessment for included studies. Studies were classified as having low ROB if none was rated as high ROB, and three or less were rated as unclear risk. Studies had moderate ROB if one was rated as high ROB or none was rated as high ROB but four or more were rated as unclear risk. All other cases were assumed to pertain to high ROB. A = Random sequence generation, B = Allocatin concealment, C = Blinding of participants and personnel, D = Bliding of outcomes assessment, E = Incomplete outcome data, F = Selective reporting, G = Other bias, Q = Quality.

Figure 4

Network plot of all intervention comparisons for nosocomial infection. The size of the nodes corresponds to the total number of participants that study the treatments. The (directly) comparable treatments are linked with a line. The thickness of the line corresponds to the standard error of trials that study this comparison. The colors of the line correspond to the quality of trials that study this comparison. Low risk of bias $[\text{green}]$, moderate risk of bias $[\text{yellow}]$. EPN, Enteral nutrition or adjuvant peripheral parenteral nutrition; TPN, Total parenteral nutrition.

Figure 5

Rankogram and SUCRA ranking curve for nosocomial infection. (A) Rankogram for nosocomial infection. A = Synbiotics. B = Probiotics. C = Probiotics. D = EPN. E = TPN. (B) SUCRA ranking for nosocomial infection. The number on the X-axis represents the rank. As the number goes up, the rating goes down. EPN, Enteral nutrition or adjuvant peripheral parenteral nutrition; TPN, Total parenteral nutrition.

Figure 6

Forest plot of the effect estimate for each active intervention vs. EPN on secondary outcomes. Estimates are presented as odds ratios (OR) and 95% CrI. OR < 1 favor the treatment. BSIs, Bloodstream infections; CrI, credible interval; CRIBS, Catheter-related bloodstream infection; EPN, Enteral nutrition or adjuvant peripheral parenteral nutrition; HAP, Hospital acquired pneumonia; TPN, Total parenteral nutrition; LOS, length of stay; MV, Duration of Mechanical ventilation; UTI, urinary tract infection; VAP, Ventilator-associated pneumonia.