Risk factors for VRE colonization

Risk factors that have been documented to contribute to the acquisition and transmission of VRE in hospitalized patient including ICU admission, length of hospital stay, antibiotic consumption, exposure to invasive procedures  (parentral nutrition, parentral catheter, tracheal intubation, blood transfusion, hemodialysis) and contaminated medical equipments.

By referring to table 4.14, among hospitalized patients, 84.4 % of age group <5 years acquired VRE followed by 80.0% of age group >60 years. While among non-hospitalized individuals, 90.0% of age group >60 years acquired VRE, 52.0% of group age <5 years. This is may be due to the fact that children and elderly are more easily colonized and have lower immunity. They also have the highest rate of infections caused by antibiotic-resistant pathogens .

Among hospitalized patient, 86.1% of patients with VRE were admitted to ICU. This is largely due to the administration of inadequate antimicrobial treatment, which is most often related to bacterial antibiotic resistance. Intensive care units are unique environments because they house seriously ill patients in confined environments where antibiotic use is extremely common. They have been focal points for the emergence and spread of antibiotic resistant pathogens. Studies in the United States dealing with the emergence of VRE revealed that most patients with VRE were in ICUs. The National Nosocomial Infections Surveillance system of the Centers for Disease Control and Prevention reported vancomycin resistance in 28.5% of nosocomial enterococcal intensive care unit infections in 2003.

About 84% of patients included in the present study with VRE were of those with long duration of hospitalization. We considered the length of stay to be particularly important because it represents the duration of the at-risk period for both exposures to antibiotics and acquisition of VRE. In addition, is a correlate of severity of illness. Edmond et al. described among the risk factors that have emerged are longer duration of hospitalization and longer lengths of stay in ICU. 

In this study (Table 4.14), 79.0% of patients carrying VRE were exposed to invasive procedure, and 76.5 % of them were exposed to contaminated medical equipment such as thermometers. This result means that exposure to invasive procedure or contaminated medical equipments may be associated with colonization of VRE. Some studies indicates that the use of internal tube feedings lead to acquiring VRE, and exposure to contaminated medical equipment such as electronic thermometers.   

Other risk factors that have been associated with colonization or infection include previous antimicrobial therapy. Antibiotics, particularly vancomycin, have been ascribed a crucial role in the dissemination of VRE; yet, many publications addressing this subject had small sample sizes or control groups, focused on a limited number of antimicrobial agents, or did not completely control for confounding factors. Thus, the true relationship between vancomycin and VRE and the relative importance of antimicrobial agents other than vancomycin have remained unclear.

Administration of vancomycin or antibiotics such as broad-spectrum cephalosporins is frequently reported as a risk factor for VRE infection or colonization. However, in our study 84.6% of patients with VRE were previously exposed to parenteral vancomycin use. This results means that vancomycin appear to influence selection for VRE in fecal flora (Table 4. 9).

Gordts et al.failed to demonstrate that antibiotic administration to be a reliable cause of the presence of VRE strains in fecal flora. Vancomycin most probably predisposes patients to colonization and infection with VRE by inhibiting the growth of the normal gram-positive bowel flora and by providing a selective advantage for VRE that may be present in small numbers in the individual’s bowel. For example, Van der Auwera et al. found that administration of oral vancomycin or teicoplanin to individuals whose baseline stool specimens contained few or no detectable VRE led to recovery of VRE in large numbers, sometimes as much as 10⁶ to 10⁸ CFU/g of stool. The selective pressure exerted by the increasing use of vancomycin in the United States during the last 10 to 15 years has been extraordinary. For example, the amount of vancomycin used at one university hospital increased 20-fold from 1981 to 1991.

Increased selective pressure is clearly associated with the emergence of transferable glycopeptide resistance in enterococci and is also responsible for plasmid-mediated resistance to two other major groups of antibiotics, cephalosporins in members of the family Enterobacteriaceae and 5-nitroimidazoles in Bacteroides fragilis. Parenteral vancomycin use and receipt of third-generation cephalosporins have been cited by others as risk factors for colonization or infection with VRE.

In this study (table 4.14), 84.6% of hospitalized patients with VRE were previously subjected to parenteral vancomycin, 74.1% of hospitalized patients colonized with VRE were exposed to antibiotic consumption, 81.0% patients colonized with VRE received third-generation cephalosporins, 76.9% of patients with VRE received aminoglycosides, 71.4% of patients with VRE were receiving penicillins and 69.7% of patients with VRE received quinolones. While among non-hospitalized individuals, 59.6% of individuals with VRE were previously   exposed to antibiotic (Table 4. 15). These results mean that vancomycin and other antibiotics including third-generation cephalosporins and ciprofloxacin appear to influence the selection for VRE in fecal flora.

Association between vancomycin use and VRE colonization in this group may reflect the cumulative use of vancomycin. Restriction of vancomycin use to hospitalized patients has the clear advantage of preventing long term VRE fecal colonization. Other study concluded that treatment with intravenous vancomycin does not significantly increase VRE in the stool and therefore does not increase the risk of VRE infection if given over a short period.

The effect of third-generation cephalosporins as a risk factor for acquiring VRE is likely due to their activity against non-enterococcal aerobic enteric flora, leading to decrease in colonization resistance, allowing colonization with VRE. This activity and suppression do not explain the lack of effect of other agents with similar or even broader spectra of activity such as, β-lactamase–inhibitor and combinations. The intense use of third-generation cephalosporins was found to be an important risk factor for VRE. This finding is in line with the recent observation of the striking commonality of risk factors for nosocomial colonization and infection with a diverse array of multiresistant pathogens, in particular, heavy exposure to third generation cephalosporins.

The effects of other risk factors (level of education, animal contact, travel abroad and chronic disease) on acquiring VRE among non-hospitalized individual were examined.

The level of education seems to be crucial for carrying VRE.  77.3% of non-hospitalized individuals carrying VRE were un-educated, while only 14.3% were with higher education. This result suggests that the level of education may be an important factor. Education is usually associated with increased awareness of the dangers of antibiotic use. Un-educated people may not comply with antibiotic use instructions because they either can’t read them or do not understand them.

Contact with animal had no significant impact on VRE carriage. 50.0% of non-hospitalized individuals with VRE were in contact with animals, (P= 0.496). Some studies revealed that animal contact is important risk factor. In Europe, the isolation of VRE from healthy volunteers, animals, and environmental sources indicates that these organisms are part of the normal human flora and suggests that the food chain may be the origin of VRE in these countries. This contradiction may be explained by behavioral differences among our study group and European community. The term animals include a wide range of creatures with wide range differences in normal flora and infections. Dogs are not common in the Palestinian community especially inside houses, while very common in Europe for instance.

In this study, traveling abroad appears to affect VRE carriage probability, 70.0% of non-hospitalized individuals colonized with VRE had traveled abroad (P= 0.021). There is a significant difference. There are no available studies investigating the effect of traveling abroad on acquiring VRE. However, traveling usually expose individuals to new environments and possibly to new sources of infections. Food change, fluctuation of feeding patterns may also disturb gastrointestinal flora leading to a decrease in colonization resistance, therefore, increasing risk of carrying new microbes.   

In this study, having chronic disease also appears to increase the risk (not statistically significant) of acquiring VRE. 71.4% of non-hospitalized individuals with VRE suffered from chronic diseases (P= 0.065). This result means that patients with chronic diseases have lower immunity that increase the risk of colonization with VRE. In some studies, VRE are now being seen with increasing frequency among patients with chronic renal failure.