CC BY-NC-ND 4.0 · J Pediatr Infect Dis 2022; 17(01): 040-047
DOI: 10.1055/s-0041-1741122
Original Article

Outcome and Risk Factors of Febrile Episodes Treated with Broad Spectrum Antibiotics and Polyclonal IgM–Enriched Immunoglobulin in Pediatric Oncology Hematology Patients: A Retrospective Study

1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Valentina Baretta
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
2   Division of Pediatric Hematology Oncology, Hospital of Bolzano, Bolzano, Italy
,
Massimiliano De Bortoli
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Rita Balter
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Elisa Bonetti
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Ada Zaccaron
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Virginia Vitale
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Giulia Caddeo
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Margherita Mauro
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
Laura Battisti
2   Division of Pediatric Hematology Oncology, Hospital of Bolzano, Bolzano, Italy
,
Gloria Tridello
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
,
1   Department of Mother and Child, Division of Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
› Institutsangaben

Abstract

Objective Preparations with high-titer immunoglobulin-M (HT-IgM) have been used to treat neonatal and adult sepsis as adjuvant to antibiotics. Limited data are available of this use in pediatric oncohematological patients. We retrospectively assessed the characteristics and outcome of febrile episodes treated with broad-spectrum antibiotics and HT-IgM.

Methods This study included febrile episodes diagnosed after chemotherapy or hematopoietic stem cell transplantation (HSCT) treated with antibiotics and HT-IgM. Study period was from January 2011 to March 2019.

Results Seventy febrile episodes in 63 patients were eligible. In 40% of episodes (n = 28), blood cultures identified a causative organism: Gram-negative (n = 15), Gram-positive (n = 8), polybacterial (n = 4), fungi (n = 1). Twenty-six percent of Gram-negatives were extend spectrum β-lactamase (ESBL)-producers. In 44% of episodes, a deep-organ localization was present, mostly pulmonary. Severe or profound neutropenia, hypotension, and hypoxemia were present in 89, 26, and 21% of episodes, respectively; 20% of episodes required intensive care and 20% of episodes required the use of inotropes. Overall, 90-day mortality was 13% and infection-attributable mortality resulted 8.6%. More than half of the patients received HT-IgM within 24 hours from fever onset. HT-IgM-related allergic reactions occurred in three episodes. Risk factors for 90-day mortality were as follows: hypotension and hypoxemia at fever presentation, admission to intensive care unit (ICU), use of inotropes, presence of deep-organ infection, and escalation of antibiotic therapy within 5 days.

Conclusion The combination of broad-spectrum antibiotics and HT-IgM was feasible, tolerated, and promising, being associated with a limited infectious mortality. Further prospective controlled studies are needed to assess the efficacy of this combination over a standard antibiotic approach.



Publikationsverlauf

Eingereicht: 17. Juli 2021

Angenommen: 21. September 2021

Artikel online veröffentlicht:
07. Dezember 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Castagnola E, Fontana V, Caviglia I. et al. A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation. Clin Infect Dis 2007; 45 (10) 1296-1304
  • 2 Lehrnbecher T, Robinson P, Fisher B. et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol 2017; 35 (18) 2082-2094
  • 3 Garbett ND, Munro CS, Cole PJ. Opsonic activity of a new intravenous immunoglobulin preparation: Pentaglobin compared with sandoglobulin. Clin Exp Immunol 1989; 76 (01) 8-12
  • 4 Rossmann FS, Kropec A, Laverde D, Saaverda FR, Wobser D, Huebner J. In vitro and in vivo activity of hyperimmune globulin preparations against multiresistant nosocomial pathogens. Infection 2015; 43 (02) 169-175
  • 5 Ehrenstein MR, Notley CA. The importance of natural IgM: scavenger, protector and regulator. Nat Rev Immunol 2010; 10 (11) 778-786
  • 6 Molnár Z, Nierhaus A, Esen F. Immunoglobulins in sepsis: which patients will benefit the most?. In: Vincent JL. eds. Annual Update in Intensive Care and Emergency Medicine 2013. Berlin, Heidelberg: Springer; 2013: 145-152
  • 7 Shankar-Hari M, Spencer J, Sewell WA, Rowan KM, Singer M. Bench-to-bedside review: immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective. Crit Care 2012; 16 (02) 206
  • 8 Busani S, Damiani E, Cavazzuti I, Donati A, Girardis M. Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness. Minerva Anestesiol 2016; 82 (05) 559-572
  • 9 Domizi R, Adrario E, Damiani E. et al. IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial. Ann Intensive Care 2019; 9 (01) 135
  • 10 Nierhaus A, Berlot G, Kindgen-Milles D, Müller E, Girardis M. Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis. Ann Intensive Care 2020; 10 (01) 132
  • 11 Esen F, Senturk E, Ozcan PE. et al. Intravenous immunoglobulins prevent the breakdown of the blood-brain barrier in experimentally induced sepsis. Crit Care Med 2012; 40 (04) 1214-1220
  • 12 Esen F, Orhun G, Ozcan PE. et al. Neuroprotective effects of intravenous immunoglobulin are mediated through inhibition of complement activation and apoptosis in a rat model of sepsis. Intensive Care Med Exp 2017; 5 (01) 1
  • 13 Rhodes A, Evans LE, Alhazzani W. et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017; 43 (03) 304-377
  • 14 Kakoullis L, Pantzaris ND, Platanaki C, Lagadinou M, Papachristodoulou E, Velissaris D. The use of IgM-enriched immunoglobulin in adult patients with sepsis. J Crit Care 2018; 47: 30-35
  • 15 Cui J, Wei X, Lv H. et al. The clinical efficacy of intravenous IgM-enriched immunoglobulin (pentaglobin) in sepsis or septic shock: a meta-analysis with trial sequential analysis. Ann Intensive Care 2019; 9 (01) 27
  • 16 Kreymann KG, de Heer G, Nierhaus A, Kluge S. Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med 2007; 35 (12) 2677-2685
  • 17 Alejandria MM, Lansang MAD, Dans LF, Mantaring III JB. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev 2013; (09) CD001090
  • 18 Capasso L, Borrelli AC, Parrella C. et al. Are IgM-enriched immunoglobulins an effective adjuvant in septic VLBW infants?. Ital J Pediatr 2013; 39: 63
  • 19 Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane Database Syst Rev 2020; 1 (01) CD001239
  • 20 Mikulska M, Viscoli C, Orasch C. et al; Fourth European Conference on Infections in Leukemia Group (ECIL-4), a joint venture of EBMT, EORTC, ICHS, ELN and ESGICH/ESCMID. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect 2014; 68 (04) 321-331
  • 21 Averbuch D, Tridello G, Hoek J. et al. Antimicrobial resistance in Gram-negative rods causing bacteremia in hematopoietic stem cell transplant recipients: intercontinental prospective study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group. Clin Infect Dis 2017; 65 (11) 1819-1828
  • 22 Freifeld AG, Bow EJ, Sepkowitz KA. et al; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52 (04) 427-431
  • 23 Lehrnbecher T, Averbuch D, Castagnola E. et al; 8th European Conference on Infections in Leukaemia. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol 2021; 22 (06) e270-e280
  • 24 O'Connor D, Bate J, Wade R. et al. Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003. Blood 2014; 124 (07) 1056-1061
  • 25 Sung L, Lange BJ, Gerbing RB, Alonzo TA, Feusner J. Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia. Blood 2007; 110 (10) 3532-3539
  • 26 Lekshminarayanan A, Bhatt P, Linga VG. et al. National trends in hospitalization for fever and neutropenia in children with cancer, 2007-2014. J Pediatr 2018; 202: 231-237.e3
  • 27 Levene I, Castagnola E, Haeusler GM. Antibiotic-resistant Gram-negative blood stream infections in children with cancer: a review of epidemiology, risk factors, and outcome. Pediatr Infect Dis J 2018; 37 (05) 495-498
  • 28 El-Mahallawy HA, El-Wakil M, Moneer MM, Shalaby L. Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer. Pediatr Blood Cancer 2011; 57 (02) 283-288
  • 29 Aljabari S, Balch A, Larsen GY, Fluchel M, Workman JK. Severe sepsis-associated morbidity and mortality among critically ill children with cancer. J Pediatr Intensive Care 2019; 8 (03) 122-129
  • 30 Weiss SL, Fitzgerald JC, Pappachan J. et al; Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015; 191 (10) 1147-1157
  • 31 Pound CM, Johnston DL, Armstrong R, Gaboury I, Menon K. The morbidity and mortality of pediatric oncology patients presenting to the intensive care unit with septic shock. Pediatr Blood Cancer 2008; 51 (05) 584-588
  • 32 Fiser RT, West NK, Bush AJ, Sillos EM, Schmidt JE, Tamburro RF. Outcome of severe sepsis in pediatric oncology patients. Pediatr Crit Care Med 2005; 6 (05) 531-536
  • 33 Carlone G, Torelli L, Maestro A, Zanon D, Barbi E, Maximova N. Pentaglobin efficacy in reducing the incidence of sepsis and transplant-related mortality in pediatric patients undergoing hematopoietic stem cell transplantation: a retrospective study. J Clin Med 2020; 9 (05) 1592
  • 34 El-Nawawy A, El-Kinany H, Hamdy El-Sayed M, Boshra N. Intravenous polyclonal immunoglobulin administration to sepsis syndrome patients: a prospective study in a pediatric intensive care unit. J Trop Pediatr 2005; 51 (05) 271-278