Impact of Surveillance Stool Culture Guided Selection of Antibiotics in Allogeneic Hematopoietic Stem Cell Transplant Patients
Authors: Paul Davinder , Gokarn Anant Ganesh , Bhat Vasudev , Bhat Vivek , Bonda Avinash , Zanwar Saurabh , Mathew Libin , Kannan Sadhana , Susan Deepa , Saikia Tapan , Khattry Navin 
Published: October 2019

Abstract
INTRODUCTION
Allogeneic stem cell transplant (allo-SCT) patients are at high risk for severe life threatening bacterial infections. Although the prevalence and pattern of resistance varies among centres and countries, there is a growing global problem of resistance to antibiotics. The consequent increased use of broad spectrum antibiotics and injudicious antibiotic policies have contributed to the selection of multidrug resistant (MDR) pathogens. Translocation of organisms which normally colonize the gut into the bloodstream during the febrile neutropenia (FN) has long been postulated as a pathogenic factor for life threatening gram negative infections. This hypothesis had led to utilization of various methods of peritransplant gut decontamination. Our centre has a policy of performing surveillance stool cultures for all patients prior to transplant. While initially our antibiotic policy was independent of any surveillance culture, over recent years stool surveillance culture sensitivity has guided our choice of first line antibiotics in the post transplant FN. This retrospective analysis is aimed at comparing the outcomes of empirical versus surveillance stool culture guided selection of antibiotics in the immediate post allo-SCT FN.
METHODOLOGY
This was a retrospective analysis of 190 allo SCT patients from January 2008 to December 2014 at our centre. During the post transplant FN, patients were categorized into two groups. Group-1 (Empirical: n=48) received first line broad spectrum antibiotics as per our hospital policy i.e. cefoperazone + sulbactum combination with amikacin. Group-2 (Surveillance based: n=119) received first line antibiotics based on sensitivity pattern of stool surveillance culture. In both groups, escalation to second line antibiotics (carbapenems with or without colistin or tigecycline) was done if defervescence did not occur in 24-48 hours or blood cultures grew a resistant organism or if there was any clinical deterioration. The primary endpoint was defervescence rate after first line antibiotics in both groups. Secondary endpoints were need for second line antibiotics, duration of total antibiotic use, concordance between blood and surveillance stool culture, incidence and causes of mortality, prevalence of MDR organisms in stool surveillance culture and change in trend of resistant organisms in stool surveillance cultures over last 7 years.
RESULTS
One ninety patients underwent allo-SCT from January 2008 to December 2014.The median age of the cohort was 26 years (range 3-57 years) with 136 males and 54 females. The diagnoses were AML-75, ALL-46, CML-19, aplastic anemia-18, MDS-12 and others-20. Group 1 (Empirical) had 48 patients, while 119 were in Group 2 (Surveillance based). Twenty three patients did not have any growth in stool surveillance.
In group 1, defervescence to first line antibiotics occurred in 23 (48 %) patients, whereas in group 2, it occurred in 78 (66 %) patients (P= 0.05). Defervescence within 24 hours was seen in 18 (37.5 %) patients in group 1 and 67 (56.3 %) patients in group 2 (P= 0.0425). In group 2, 34.5 % patients required escalation to second line antibiotics, compared to 54 % patients in group 1 (P = 0.0294). The median duration of total antibiotic use was 17.5 days in group 1 and 18 days in group 2 (P= NS). The concordance between blood culture and surveillance stool culture was seen in 3 (1.76 %) patients. There was no significant difference in infection related mortality between the two groups as shown in the figure 1.
The prevalence of resistant organisms in the baseline surveillance stool culture changed between the periods 2008-2011 and 2012-2014. The incidence of extended spectrum beta lactamase (ESBL) organisms decreased from 79.66 % in 2008-2011 to 62.1 % in 2012-2014 (P = 0.0351). The incidence of carbapenem resistant (15.25 % vs. 25.26 %), colistin resistant (1.69 % vs. 2.1 %) and vancomycin resistant enterococcus (VRE: 3.38 % vs. 10.52 %) increased from 2008-2011 to 2012-2014 period. The increase in the combined incidence of carbapenem resistant, colistin resistant and VRE was from 20.32 % to 37.86 % (P = 0.0351).
CONCLUSION
Stool surveillance guided antibiotic usage leads to earlier defervescence in higher number of patients, while also reducing the need for second line antibiotics in patients undergoing allo-SCT. A randomized study is required to prove the importance of stool surveillance in this setting.

Disclosures
No relevant conflicts of interest to declare.