1. Clinical Infectious Diseases 2012;55(6):764–70 Jan Vydra,1 Ryan M. Shanley,2 Ige George,1 Celalettin Ustun,1 Angela R. Smith,4 Daniel J. Weisdorf,1 and Jo-Anne H. Young3 Journal conference R1 강현준, Prof. 이미숙

2.  Enterococci : important cause of healthcare-associated infections  Vancomycin-resistant enterococci (VRE) : commonly isolated from blood and other sites in recipients of hematopoietic stem cell transplantation (HSCT) : directly attributable mortality of preengraftment VRE bloodstream infections (BSIs)

3.  VRE infection may actually serve as a marker of concomitant severe illness  reviewed cases of enterococcal bloodstream infections among allogeneic HSCT recipients  analyzed risk factors for enterococcal BSI and the association of these infections with outcomes

4.  Patients and Data Collection : Patients receiving their first allogeneic HSCT at the University of Minnesota between 1 January 2004 and 31 December 2008  VRE Screening : All patients were screened at admission for VRE by culture using perirectal swabs : Surveillance cultures - performed periodically, generally weekly, throughout the initial hospitalization : Patients who were found to be colonized or infected with VRE were placed under contact isolation.

5.  Blood cultures : a tunneled central venous line or peripherally inserted central catheter in all patients with new onset of fever or with other signs of infection : After the positive blood culture, blood cultures were generally drawn daily until 2 consecutive cultures were negative and the patient had defervesced.  Definitions : Enterococcal bloodstream infection - any blood culture growing Enterococcus species : (MIC) of ≥32 μ g/mL – VRE, (MIC) of ≤8 μ g/mL – VSE : “VRE BSI” group vs “VSE BSI” group vs “No enterococcal BSI” group(1 st year) : VRE colonized - VRE isolated from a surveillance culture or from any other nonsterile body : neutrophil recovery to <500/ μ L by day 42 - graft failure.

6.  752 patients underwent their first allogeneic transplant within this 5- year timeframe The median follow up was 47 months, with a minimum follow-up of 1 year. Colonization : 173 (23%) of patients were colonized with VRE Of these, 25% had been known to be VRE colonized prior to their transplant underlying diagnosis of leukemia 2.4 > lymphoma or nonmalignancy myelodysplastic syndrome 2.6 > lymphoma or nonmalignancy patients aged >60 years 2.0 > younger adults

7. 93 patients had enterococcal BSIs during the first year following transplantation 14% of patients colonized with VRE developed VRE BSI, VRE bacteremia was only 4% in the noncolonized group. The cumulative incidence of first enterococcal BSI : 6.6% for VRE BSI, 5.7% for VSE BSI during the first year after transplantation Most of the infections occurred in the first 60 days None of the patients with VSE bacteremia subsequently developed a VRE bacteremia Rates of vancomycin resistance among bloodstream isolates : 66% in adults and 31% in children

8. The rate of VRE colonization increased from 13% in 2004 to 30% in 2008 incidence of VRE BSI among colonized patients decreased significantly

9. Most of the infections occurred in the first 60 days

10. Risk factors for VRE BSI : (1) colonization with VRE (2) delay in engraftment day 21 4.5% 22–28 6.3% 29–35 11.9% 36–42 15.0% more than 42 25% (3) severe acute GVHD

11. VRE vs VSE BSI ① In adult patients, the 30-day mortality : 38% and 38% ② In pediatric patients, the 30-day mortality : 20% and 4.5% ③ Median time to resolution of BSI : 3 and 1 days ④ In adult patients, 1-year survival : 20% and 48% ⑤ In pediatric patients, 1-year survival : 60% and 86% ⑥ In overall survival 1 year after infection between VRE BSI occurring before and after day 60 : no difference

13. Enterococcal bacteremia and time to engraftment (in 1-week intervals) -> the only variables associated with survival

14. 1. The high risk of VRE bloodstream infection : VRE colonized patients > patients not colonized 2. The risk of VRE bacteremia increased with delay in engraftment : the highest – delay by day 42 3. The rate of vancomycin resistance : adult patients > pediatric patients 4. VRE BSI was associated with inferior overall survival at 1 year after transplant 5. Both VRE and VSE bloodstream infections occurred at similar rates throughout the first year after transplant

15. Vancomycin-resistant enterococci have emerged as important pathogens in healthcare-associated infections over the last 2 decades Most of these infections occurred during the preengraftment period The rate of vancomycin resistance for enterococcal bloodstream isolates among our adult patients was 66%, whereas the isolates from pediatric patients had a lower resistance rate of 31% While restriction of vancomycin use has been suggested as a means of reducing the rate of VRE infections, a systematic review was not able to confirm this effect

16. Barrier precautions and contact isolation have not been clearly shown previously to be effective in preventing VRE colonization but are widely used in HSCT recipients. Equivalent & high, all-cause mortality 30 days after infection in patients with VRE and VSE bacteremia : enterococcal BSIs preferentially occur in patients with delayed engraftment and other significant medical conditions > enterococcal bacteremia per se

17. A metaanalysis of studies of mortality : VRE BSI > VSE BSI -> most studies were published before widespread use of antibiotics against VRE -> recently published analysis : mortality : VRE BSI = VSE BSI similar short-term mortality of VSE and VRE bacteremia, but increased nonrelapse mortality at 1 year after HSCT of the VRE vs VSE vs “no enterococcal bacteremia” groups -> support the opinion that VRE infections may serve as a marker of severity of underlying medical condition High rates of vancomycin resistance and significant mortality with enterococcal infections -> further efforts to optimize prevention and management of these infections