Pros: should universal decolonization be performed routinely for critically ill patients?

Healthcare-associated infections (HAI) are associated with long hospital stay, increased rates of death and costs (1,2). Critically ill patients always surfer several invasive treatments which could injury the integrity of skin mucosal, and more critically ill patients have immunocompromise, which increase the risk of infection. Universal decolonization is an important strategy to prevent HAI, such as chlorhexidine bathing, hand hygiene (HH), reverse Intestinal dysbiosis and antibiotic stewardship (3,4).

Chlorhexidine bathing reduces incidence of infection in ICU

Chlorhexidine bathing decreases the risk of bacterial infection. In medical ICU, daily chlorhexidine bathing could decrease incidence density of methicillin-resistant staphylococcus aureus (MRSA) and hospital-associated vancomycin-resistant Enterococcus (VRE) (5,6). In surgical ICU, bathing with 2% chlorhexidine could decrease the risk of HAI by 44.5% (7). Compared with targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers), universal decolonization decreased MRSA culture and bloodstream infection (3). Although a pragmatic cluster-randomized, cross-over study found bathing with chlorhexidine did not reduce the incidence of HAI (4), there are several limitations in this study, first, the study could not be blinded to the chlorhexidine bathing group and the compliance didn’t be monitored; second, end point chosen in this study could be challenged, the effect of daily chlorhexidine bathing on the end point are influenced by several clinical factors, and is relatively weak; third, the overall HAI rates were relatively low (8).

Intestinal dysbiosis needs universal decolonization but not antibiotics

There are numerous bacteria in the gut that do not have any adverse effects. Bacteria barrier is one of the most important barrier of the intestinal epithelium (9). Critically ill patients always have acute gastric injury (AGI) with intestinal dysbiosis. Intestinal dysbiosis could induce bacteria proliferate, luminal bacteria become virulent and injury immune barrier.

Early nutrition (EN) improves intestinal function

EN could not only improve intestinal movement, decrease adherence of microorganisms on intestinal epithelium, decrease bacteria toxin and reduce colonization of pathogenic bacteria, but stimulate intestinal blood flow, maintain intestinal structural integrity and supporting the mass of secretory IgA producing immunocyte (10). The benefits of EN are equal to intestinal universal decolonization.

EN improves prognosis of critically ill patients. A meta-analysis of 21 randomized controlled trials (RCT) compared the provision of early EN versus delayed EN, early EN was associated with a significant reduction in mortality (RR =0.70; 95% CI, 0.49–1.00; P=0.05) and infectious morbidity (RR =0.74; 95% CI, 0.58–0.93; P=0.01) (11). American Society for Parenteral and Enteral Nutrition guideline recommend that early EN should be initiated within 24–48 hours in the critically ill patient who is unable to maintain volitional intake (11).

Probiotics reverse intestinal dysbiosis

Critically ill patients are at high risk for intestinal dysbiosis with high rates of broad spectrum antibiotic use, stress of critical illness, and disease related with intestinal ischemia (12). Probiotics are living microbes, can colonize gastrointestinal tract and be benefits to the patients (13). Probiotic therapy leads to several beneficial effects including augmented release of antimicrobial peptides, IgA production, regulation of immune cell proliferation, reduced gut cell apoptosis and anti-oxidative activity (14).

Probiotics play the role of universal decolonization. The meta-analysis of 14 RCT found that probiotic therapy could reduce the incidence of ventilator associated pneumonia (RR =0.74, 95% CI, 0.61–0.90, P=0.002), and infectious complications in the ICU (RR =0.80, 95% CI, 0.68–0.95, P=0.009) (15). According to Canadian Clinical Practice Guidelines, probiotics should be considered to use in critically ill patients (16).

Universal decolonization is not only patients, but health care staff

Prevention and control of infections have saved a lot of people’s lives, it is also important to protect critically ill patients from HAI.

HH is the important strategy to prevent HAI

HH has been accepted as a crucial component of infection prevention (17). HH has in addition the benefit of being effective for reducing transmission of many resistant or susceptible bacteria. A cost-effectiveness analysis using a Markov model found that universal decolonization include HH is less costly and more effective than screening and isolation of MRSA prevention strategy (18). HH is not only effective on MRSA, but for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) spread. A cost-effectiveness analysis based on dynamic, stochastic transmission model showed that the overall costs (cost of intervention and infections) were the lowest for HH compliance improvement from 55%/60% before/after contact with a patient to 80%/80% (19). HH is effective on HAI prevention, but it depends on compliance improvement.

Antibiotic stewardship is associated with decreasing inappropriate antibiotics usage

Multi-drug-resistant organisms (MDRO) were frequently found in ICU and near half of empiric gram-negative therapy was inappropriate (20). Antimicrobial exposure increases various drug-resistant organisms (21). Numerous studies have demonstrated the association between the use of antimicrobial and MDRO detection (22). Inappropriate therapy was associated with higher costs and long ICU stay (20). Ma et al. conducted a pre-post study and the results showed that the proportion of patients colonized or infected with MDRO decreased along with antimicrobial stewardship (23). A network meta-analysis found that strategies with antimicrobial stewardship program as a core component showed a significant reduction the acquisition of ESBL-PE (24). Antibiotic stewardship is useful to reduce the consumption of antibiotics and the acquisition of MDRO.

Concepts of universal decolonization have developed, the contents include patients, health care workers and infection control. Chlorhexidine bathing, intestinal dysbiosis reverse, HH and antibiotic stewardship have proved be benefit of critically ill patient infection control, more strategies need further studies clarify.

Acknowledgements

Funding: This study was sponsored by Grants [81300043] and [81370180] from National Natural Science Foundation of China and Grant (H201432, Nanjing, China) from Natural Science Foundation of Jiangsu Province.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

1. Kaye KS, Marchaim D, Chen TY, et al. Effect of nosocomial bloodstream infections on mortality, length of stay, and hospital costs in older adults. J Am Geriatr Soc 2014;62:306-11. [Crossref] [PubMed]
2. Roberts RR, Scott RD 2nd, Hota B, et al. Costs attributable to healthcare-acquired infection in hospitalized adults and a comparison of economic methods. Med Care 2010;48:1026-35. [Crossref] [PubMed]
3. Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med 2013;368:2255-65. [Crossref] [PubMed]
4. Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care-associated infections: a randomized clinical trial. JAMA 2015;313:369-78. [Crossref] [PubMed]
5. Kim JS, Chung YK, Lee SS, et al. Effect of daily chlorhexidine bathing on the acquisition of methicillin-resistant Staphylococcus aureus in a medical intensive care unit with methicillin-resistant S aureus endemicity. Am J Infect Control 2016;44:1520-5. [Crossref] [PubMed]
6. Lowe CF, Lloyd-Smith E, Sidhu B, et al. Reduction in hospital-associated methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus with daily chlorhexidine gluconate bathing for medical inpatients. Am J Infect Control 2017;45:255-9. [Crossref] [PubMed]
7. Swan JT, Ashton CM, Bui LN, et al. Effect of Chlorhexidine Bathing Every Other Day on Prevention of Hospital-Acquired Infections in the Surgical ICU: A Single-Center, Randomized Controlled Trial. Crit Care Med 2016;44:1822-32. [Crossref] [PubMed]
8. Pittet D, Angus DC. Daily chlorhexidine bathing for critically ill patients: a note of caution. JAMA 2015;313:365-6. [Crossref] [PubMed]
9. Sansonetti PJ. War and peace at mucosal surfaces. Nat Rev Immunol 2004;4:953-64. [Crossref] [PubMed]
10. Veldhoen M, Brucklacher-Waldert V. Dietary influences on intestinal immunity. Nat Rev Immunol 2012;12:696-708. [Crossref] [PubMed]
11. McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016;40:159-211. [Crossref] [PubMed]
12. Magill SS, Edwards JR, Beldavs ZG, et al. Prevalence of antimicrobial use in US acute care hospitals, May-September 2011. JAMA 2014;312:1438-46. [Crossref] [PubMed]
13. Petrof EO, Dhaliwal R, Manzanares W, et al. Probiotics in the critically ill: a systematic review of the randomized trial evidence. Crit Care Med 2012;40:3290-302. [Crossref] [PubMed]
14. Khailova L, Petrie B, Baird CH, et al. Lactobacillus rhamnosus GG and Bifidobacterium longum attenuate lung injury and inflammatory response in experimental sepsis. PLoS One 2014;9:e97861. [Crossref] [PubMed]
15. Manzanares W, Lemieux M, Langlois PL, et al. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. Crit Care 2016;19:262. [Crossref] [PubMed]
16. Leguina-Ruzzi A. A commentary on the 2015 Canadian Clinical Practice Guidelines in glutamine supplementation to parenteral nutrition. Crit Care 2016;20:7. [Crossref] [PubMed]
17. WHO Guidelines on Hand Hygiene in Health Care: First Global Patient Safety Challenge Clean Care Is Safer Care. WHO Guidelines Approved by the Guidelines Review Committee, Geneva 2009.
18. Whittington MD, Atherly AJ, Curtis DJ, et al. Recommendations for Methicillin-Resistant Staphylococcus aureus Prevention in Adult ICUs: A Cost-Effectiveness Analysis. Crit Care Med 2017;45:1304-10. [Crossref] [PubMed]
19. Kardas-Sloma L, Lucet JC, Perozziello A, et al. Universal or targeted approach to prevent the transmission of extended-spectrum beta-lactamase-producing Enterobacteriaceae in intensive care units: a cost-effectiveness analysis. BMJ Open 2017;7:e017402. [Crossref] [PubMed]
20. Claeys KC, Zasowski EJ, Trinh TD, et al. Antimicrobial Stewardship Opportunities in Critically Ill Patients with Gram-Negative Lower Respiratory Tract Infections: A Multicenter Cross-Sectional Analysis. Infect Dis Ther 2017. [Epub ahead of print]. [Crossref] [PubMed]
21. Williams RJ, Heymann DL. Containment of antibiotic resistance. Science 1998;279:1153-4. [Crossref] [PubMed]
22. Muraki Y, Kitamura M, Maeda Y, et al. Nationwide surveillance of antimicrobial consumption and resistance to Pseudomonas aeruginosa isolates at 203 Japanese hospitals in 2010. Infection 2013;41:415-23. [Crossref] [PubMed]
23. Ma X, Xie J, Yang Y, et al. Antimicrobial stewardship of Chinese ministry of health reduces multidrug-resistant organism isolates in critically ill patients: a pre-post study from a single center. BMC Infect Dis 2016;16:704. [Crossref] [PubMed]
24. Teerawattanapong N, Kengkla K, Dilokthornsakul P, et al. Prevention and Control of Multidrug-Resistant Gram-Negative Bacteria in Adult Intensive Care Units: A Systematic Review and Network Meta-analysis. Clin Infect Dis 2017;64:S51-60. [Crossref] [PubMed]