Transplant Cell Ther. 2021 Dec 19:S2666-6367(21)01443-3. doi: 10.1016/j.jtct.2021.12.008. Online ahead of print.
ABSTRACT
BACKGROUND: The utility of weekly rectal swab surveillance cultures (RSSC) as a resource to identify gut colonisation with Extended Spectrum Beta-Lactamase (ESBL)-producing E Coli or Klebsiella pneumoniae carbapenemase (KPC) producing organisms, to guide empirical antibiotic therapy in HSCT patients continues to be a subject of interest. There is urgency to assess and justify modifications to empirical antibiotics based upon regional epidemiology and patient groups.
OBJECTIVE: To study the utility of weekly rectal swab surveillance cultures (RSSC) to guide empirical antibiotics therapy and the impact of gut colonisation on transplant outcomes.
STUDY DESIGN: This is a retrospective analysis of 317 successive first transplants done in three pediatric bone marrow transplant centres in Indian sub-continent, mainly for hemoglobinopathies, between April 2016 and April 2021. Transplantation, infection control and febrile neutropenia management protocols are identical among the three centres. First line antibiotics were chosen based on RCCS reports i.e. meropenem and high dose meropenem with colistin for ESBL and carbapenemase resistant colonisation respectively for first half of the study and no adjustment was made in the second half. Clinical response to antibiotics, long term outcomes, antibiotic-resistant bacteraemia and acute GVHD were analysed. Log-rank test, Chi-squared test and Wilcoxon test were used to compare data using R Statistical software.
RESULTS: Of all 871 weekly RSSC done, 162 were positive for ESBL- or KPC-resistant organism. RCCS were ESBL-positive in 106 patients (33%) and KPC-positive in 10 patients (3%). Within 97 ESBL-positive patients for whom antimicrobial susceptibility testing (AST) report was available, only 22 (25%) demonstrated clinical resistance of Pip-Taz. Within the 10 KPC-positive patients’ clinical resistance was observed only in 4 (40%) to Pip-Taz and 3 (30%) to meropenem. For ESBL-positive RSSC where 1st line empirical antibiotics were used, 66% of the patients responded clinically. Even within the 15 who were resistant to 1st line empirical antibiotics (Pip-Taz) on RSSC reports, 67% responded to Pip-Taz clinically. Within these patients 27 (56%) never needed any carbapenems. Using Pip-Taz empirically in ESBL-positive patients did not prolong meropenem use within 100 days of transplantation (p=0.18). For KPC-positive RSSC where 1st line empirical antibiotics were used, all patients clinically responded, including 4 who were resistant to Pip-Taz and 3 patients who were meropenem resistant on RCCS. Comparing patients who were ESBL-positive, KPC-positive and neither, no statistically significant difference was seen in overall survival (p=0.95), disease free survival (p=0.45), transplant related mortality (p=0.97), rejection (p=0.68) and rate of acute GVHD grade II-IV (p=0.78). Comparing the ESBL-positive patients who did and did not get higher-level empirical antibiotics, no statistical difference was seen in overall survival (p=0.32), disease free survival (p=0.64), transplant related mortality (p=0.65), rejection (p=0.46), acute GVHD grade II-IV (p=0.26) or antibiotic resistant bacteraemia (p=0.3).
CONCLUSIONS: In context of transplantation for non-malignant HSCTs, empiric antibiotic choice based on rectal swab surveillance cultures is not justified, even in regions with a high prevalence of antimicrobial resistance. Antimicrobial susceptibility testing (AST) reports in surveillance cultures did not correlate with in-vivo clinical response. Colonisation reported on weekly surveillance rectal swab cultures showed no correlation with clinical outcomes.
PMID:34936930 | DOI:10.1016/j.jtct.2021.12.008