Epidemiology and risk factors for bacterial infections (BI) in children and adolescents after allogeneic hematopoietic stem cell transplantation (allo-HSCT)

Summary

Introduction

Infections are the most common complications in allo-HSCT. Over recent years, the origins of infectious complications have undergone some changes associated with extended indications, usage of alternative HSC sources, introduction of new drugs, e.g., monoclonal antibodies (MAbs) and cytotoxic drugs, which exhibit specific immunosuppressive effects. The aim of present study was to epidemiological survey, evaluation of frequency, and specific features of BI occuring in children and adolescents, during the first year after allo-HSCT of different types. Materials and methods. The study included 155 pediatric and adolescent patients observed following allo-HSCT. Prevention of infectious complications in the allo-HSC recipients was performed in accordance with Recommendations of the European Conference on Infectious Complications in Leukemia (ECIL 1-4th Edition). Identification of the microbial isolates was performed using an automatic analyzer «VITEK-2» (BioMerieux, France). Results. Development of BI after allo-HSCT was registered in 80% of the patients. The five-year overall survival rate among patients undergoing BI versus BI-free patients was, respectively, 36,3% and 87,1% (p<0,001). When analysing pattern of the isolated pathogens, we have revealed an increased proportion of gram-positive (GP) bacteria with time (47% in 2010-2013 vs 42% in 2008-2009, p<0,001), at the expense of Enterococcus spp. (14% in 2008-2009 vs 19,5% in 2010-2013, p=0,015), vancomycin-resistant enterococci (VRE) (4% in 2008-2009 vs 9,5% in 2010-2013, p=0,049). A growing proportion of Enterococcus spp. over 2010-2013 was due to increased number of E.faecalis strains (from 10% to 13%), E.faecium (VRE), from 17,1% to 24,7%, respectively, for 2011 and 2013 (p=0,05). The spectrum of the BI pathogens proved to be dependent on the time period post-HSCT, i. e., Gram-positive agents were prevalent before the HSC engraftment (p=0,037). At the later terms, all the pathogens were found at lower rates, especially, E.coli, Enterobacter spp., Acinetobacter spp., Citrobacter (p=0,001). The BI clinical patterns, generally, did not depend on the period post-HSCT, most often presented with bacteremia (38,7%), respiratory infections (22,5%), ORL-, and soft tissue lesions (14%). Nevertheless, the urinary tract infections proved to be more common at the earlier post-transplant terms as compared to the later period (p = 0,004). The most significant underlying risk factors for BI were as follows: acute leukemia (p=0,044); severe infectious complications preceding allo-HSCT (p=0,001); oral cavity colonization with pathogenic and opportunistic microflora (e. g., Enterococcus spp., Gram-negative bacteria, p=0,015); acute GVHD of grade III-IV (p=0,002); prolonged corticosteroids for treatment of acute GVHD (p=0,008); administration of immunosuppressive MAbs in chronic GVHD (p=0,036); severe hypogammaglobulinemia requiring IVIG replacement therapy (p<0,001); CMV and/or HSV infection after allo-HSCT (resp., p=0,001, and p=0,043). The rate of microbial resistance to ciprofloxacin was 38% over the period of 2008-2009, then followed by increased resistance over 2010-2013 – 65% (p<0,001), especially for Kl.pneumoniae (p<0,001) and Enterobacter spp. (p=0,005), E.coli (p<0,001), as well as GP cocci, i.e., S.epidermidis (p<0,001). Conclusions. There are several important clinical factors associated with the risk of BI observed after allo-HSCT. Epidemiological monitoring of specific pathogens should be also performed. Changes in the microbial pattern and sensitivity to antibiotics among the BI pathogens makes it necessary to revise the intestinal decontamination programs, since gut is a reservoir for 90% of the multidrug-resistant strains. The strategy of empirical and targeted antimicrobial prescription should be considered as well.

Keywords

Risk factors, Аllogeneic hematopoietic stem cell transplantation, bacterial infections, epidemiology, antibiotic resistance