Alarming Upward Trend in Multidrug-Resistant Bacteria in a Large Cohort of Immunocompromised Children: A Four-Year Comparative Study

Simple Summary Infection is the second leading cause of death in patients with cancer. The emergence of multidrug resistant bacteria is an ongoing problem, leading to difficulties in the treatment of antibiotic resistant bacterial infections. Our main objective was to document the evolution of multidrug resistant bacteria in a tertiary centre in Lyon, France, which was initially stable between 2014 and 2017 in a study conducted by Raad C. et al. (2021). Following 2017, multidrug resistant bacteria seem to increase gradually in bloodstream infections and in digestive colonisations in a similar cohort in the same tertiary centre, considering that the antibiotic management did not change over the eight years. We want to raise awareness among health practitioners and to incite other similar centres to study their tendencies of multidrug resistant bacteria in order to avoid dangerous multidrug resistant infections in immunocompromised children with a rather good prognostic otherwise. Abstract Documenting bacteremia at the onset of fever in immunosuppressed children is challenging; therefore, it leads to the early administration of broad-spectrum antibiotics. We aimed to analyse the evolution of antibiotic resistance profiles of bacterial bloodstream infections (BSI) and gut colonisations in a large cohort of immunocompromised children carrying a central venous catheter, in comparison with a prior, similar study conducted in our centre from 2014 to 2017. A retrospective, observational cohort study was conducted from January 2018 to December 2021, in a tertiary centre for paediatric immuno-haematology and oncology. Empirical antibiotic therapy was adapted to the immunosuppression risk group and prior bacterial colonisation. There was a mean of 6.9 BSI/1000 patient bed days. Multidrug-resistant bacteria (MDRB) associated BSI accounted for 35/273 (12.8%). The incidence of MDRB gum/gut colonisation and MDRB associated BSI increased annually and correlated with the level of immunosuppression (p = 0.024). One third (34.7%) of the BSI episodes were not associated with neutropenia. As compared to the previous study, an alarming emergence of MDRB responsible for gut colonisations and BSI in immunosuppressed children was reported over the last four years. The degree of immunosuppression directly correlates with the risk of having an MDRB gut colonisation or MDRB BSI.

[1]  K. Bochennek,et al.  Infections during Non-Neutropenic Episodes in Pediatric Cancer Patients—Results from a Prospective Study in Two Major Large European Cancer Centers , 2022, Antibiotics.

[2]  A. Gennery,et al.  Biomarkers for Diagnosing Febrile Illness in Immunocompromised Children: A Systematic Review of the Literature , 2022, Frontiers in Pediatrics.

[3]  M. Elhadi,et al.  Infectious diseases as a cause of death among cancer patients: a trend analysis and population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results database , 2021, Infectious agents and cancer.

[4]  V. Fowler,et al.  Antibiotic resistance in the patient with cancer: Escalating challenges and paths forward , 2021, CA: a cancer journal for clinicians.

[5]  Zhezhen Jin,et al.  Bacteremia in Febrile, Non-neutropenic, and Well-appearing Children With Cancer , 2021, Journal of pediatric hematology/oncology.

[6]  Saira A Khan,et al.  Epidemiology and prognostic factors of pediatric brain tumor survival in the US: Evidence from four decades of population data. , 2021, Cancer epidemiology.

[7]  Y. Bertrand,et al.  Trends in bacterial bloodstream infections and resistance in immuno-compromised patients with febrile neutropenia: a retrospective analysis , 2021, European Journal of Pediatrics.

[8]  L. Klesse,et al.  Recent progress in the treatment of cancer in children , 2021, CA: a cancer journal for clinicians.

[9]  K. Krull,et al.  Rethinking Success in Pediatric Oncology: Beyond 5-Year Survival. , 2021, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  B. Alexander,et al.  Editorial: Infections of the immunocompromised host: a musing on the changing times. , 2020, Current opinion in infectious diseases.

[11]  W. Jastaniah,et al.  A clinical approach to non-neutropenic fever in children with cancer , 2020, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[12]  K. Bochennek,et al.  Recent advances and future directions in the management of the immunocompromised host. , 2020, Seminars in oncology.

[13]  F. Pane,et al.  A Frontline Approach With Peripherally Inserted Versus Centrally Inserted Central Venous Catheters for Remission Induction Chemotherapy Phase of Acute Myeloid Leukemia: A Randomized Comparison , 2019, Clinical lymphoma, myeloma & leukemia.

[14]  L. Khedmat,et al.  The Prevalence of Risk Factors for the Development of Bacteraemia in Children , 2018, Open access Macedonian journal of medical sciences.

[15]  Y. Bertrand,et al.  Increased Risk of Thrombosis Associated with Peripherally Inserted Central Catheters Compared with Conventional Central Venous Catheters in Children with Leukemia , 2018, The Journal of pediatrics.

[16]  E. Larson,et al.  Risk for Health Care–Associated Bloodstream Infections in Pediatric Oncology Patients With Various Malignancies , 2017, Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses.

[17]  Jae Wook Lee,et al.  Prognostic factors and treatment of pediatric acute lymphoblastic leukemia , 2017, Korean journal of pediatrics.

[18]  A. Martinot,et al.  Risk‐stratification management of febrile neutropenia in pediatric hematology‐oncology patients: Results of a French nationwide survey , 2016, Pediatric blood & cancer.

[19]  Priyanka Singh,et al.  Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study , 2016, Journal of pathogens.

[20]  Y. Bertrand,et al.  Improvement in the Outcome of Invasive Aspergillosis in a Pediatric Hematology Department: A 10-Year Review , 2015, Journal of pediatric hematology/oncology.

[21]  L. Pagano,et al.  Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[22]  L. Öhrmalm,et al.  Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia , 2013, PloS one.

[23]  W. Kamps,et al.  Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia—species distribution and susceptibility patterns , 2013, Supportive Care in Cancer.

[24]  F. Pane,et al.  Early ultrasonographic finding of septic thrombophlebitis is the main indicator of central venous catheter removal to reduce infection-related mortality in neutropenic patients with bloodstream infection. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[25]  S. Esposito,et al.  Catheter-related infections in pediatric patients with cancer , 2012, European Journal of Clinical Microbiology & Infectious Diseases.

[26]  G. Lamprecht,et al.  Neue Erkenntnisse zur Sepsis durch bakterielle Translokation , 2012, Zentralblatt für Chirurgie.

[27]  D. Relman,et al.  Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation , 2010, Proceedings of the National Academy of Sciences.

[28]  Y. Bertrand,et al.  Low incidence of sepsis due to viridans streptococci in a ten‐year retrospective study of pediatric acute myeloid leukemia , 2006, Pediatric blood & cancer.

[29]  Y. Bertrand,et al.  Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report , 2005, Leukemia.

[30]  G. Can,et al.  Bacteremia in childhood cancer. , 2002, Journal of tropical pediatrics.

[31]  J. Palmblad,et al.  Empiric therapy of bacterial infections in severe neutropenia , 1997 .