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Challenges in the Management of Infectious Complications in Neutropenic Cancer...
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Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 5962

Special Issue Editor

Dr. Carlota Gudiol

E-Mail Website
Guest Editor
Infectious Diseases Department, Bellvitge University Hospital, Institute for Biomedical Research (IDIBELL), University of Barcelona, Hospitalet de Llobregat, 08907 Barcelona, Spain
Interests: bacteremia; antibiotic resistance; infections in onco-hematological patients; fungal infections

Special Issue Information

Dear Colleagues,

Microorganisms is now soliciting manuscripts for a Special Issue on “Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients”, with Guest Editor Carlota Gudiol. The issue is targeted towards understanding and managing the complications of microbial infections in neutropenic patients with cancer.

Due to the underlying malignancy and chemotherapy-induced neutropenia, neutropenic cancer patients are at high risk for severe infections, especially bloodstream infections (BSIs), one of the most common life-threatening complications in these patients.

This Special Issue aims to collect papers on infectious complications in neutropenic cancer patients to better define the management and treatment of those diseases. Topics of interest include elucidating the epidemiology of infection, and accurate diagnosing pathogenic pathogens and their resistance phenotypes, and all as related to infectious complications in neutropenic cancer patients.

We will consider original scientific research articles, comprehensive reviews, comments, commentaries, and perspectives for publication. All manuscripts will be peer-reviewed.

Dr. Carlota Gudiol
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neutropenia
  • cancer
  • leukaemia
  • neutropenia-related complications
  • infectious complications
  • microbial infections
  • bloodstream infection
  • bacteremia

Published Papers (5 papers)

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Research

Jump to: Review, Other

13 pages, 299 KiB  
Article
Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy
by Cristina Royo-Cebrecos, Júlia Laporte-Amargós, Marta Peña, Isabel Ruiz-Camps, Carolina Garcia-Vidal, Edson Abdala, Chiara Oltolini, Murat Akova, Miguel Montejo, Malgorzata Mikulska, Pilar Martín-Dávila, Fabián Herrera, Oriol Gasch, Lubos Drgona, Hugo Manuel Paz Morales, Anne-Sophie Brunel, Estefanía García, Burcu Isler, Winfried V. Kern, Zaira R. Palacios-Baena, Guillermo Maestr de la Calle, Maria Milagro Montero, Souha S. Kanj, Oguz R. Sipahi, Sebnem Calik, Ignacio Márquez-Gómez, Jorge I. Marin, Marisa Z. R. Gomes, Philipp Hemmatii, Rafael Araos, Maddalena Peghin, Jose L. Del Pozo, Lucrecia Yáñez, Robert Tilley, Adriana Manzur, Andrés Novo, Jordi Carratalà and Carlota Gudioladd Show full author list remove Hide full author list
Microorganisms 2024, 12(4), 705; https://doi.org/10.3390/microorganisms12040705 - 30 Mar 2024
Viewed by 970
Abstract
This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for [...] Read more.
This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population. Full article
(This article belongs to the Special Issue Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients)
16 pages, 850 KiB  
Article
Ceftazidime–Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia
by Fabián Herrera, Diego Torres, Ana Laborde, Rosana Jordán, Noelia Mañez, Lorena Berruezo, Sandra Lambert, Nadia Suchowiercha, Patricia Costantini, Andrea Nenna, María Laura Pereyra, José Benso, María Luz González Ibañez, María José Eusebio, Laura Barcán, Nadia Baldoni, Lucas Tula, Inés Roccia Rossi, Martín Luck, Vanesa Soto, Verónica Fernández and Alberto Ángel Carenaadd Show full author list remove Hide full author list
Microorganisms 2024, 12(1), 195; https://doi.org/10.3390/microorganisms12010195 - 18 Jan 2024
Viewed by 1054
Abstract
Few studies have evaluated the efficacy of ceftazidime–avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance [...] Read more.
Few studies have evaluated the efficacy of ceftazidime–avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan–Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18–11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58–30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01–0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients. Full article
(This article belongs to the Special Issue Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients)
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12 pages, 259 KiB  
Article
Invasive Fungal Infections in Children with Acute Leukemia: Epidemiology, Risk Factors, and Outcome
by Tamar Ruth Gal Etzioni, Nurit Fainshtain, Adi Nitzan-Luques, Gal Goldstein, Sigal Weinreb, Violeta Temper, Maya Korem and Dina Averbuch
Microorganisms 2024, 12(1), 145; https://doi.org/10.3390/microorganisms12010145 - 11 Jan 2024
Viewed by 1043
Abstract
Invasive fungal infections (IFI) cause morbidity and mortality in children with acute leukemia (AL). We retrospectively collected data on febrile neutropenic episodes (FNE) in AL children (2016–2021) and assessed factors associated with proven/probable IFI. Ninety-three children developed 339 FNE. Seventeen (18.3%) children developed [...] Read more.
Invasive fungal infections (IFI) cause morbidity and mortality in children with acute leukemia (AL). We retrospectively collected data on febrile neutropenic episodes (FNE) in AL children (2016–2021) and assessed factors associated with proven/probable IFI. Ninety-three children developed 339 FNE. Seventeen (18.3%) children developed 19 proven/probable IFI (11 yeast; eight molds). The proven/probable yeast IFI rate was 6/52 (11.5%) in children who belong to the high risk for IFI category (HR-IFI-AL: high-risk acute lymphocytic leukemia (ALL), acute myeloid leukemia, relapse); and 5/41 (12.2%) in the non-HR-IFI-AL category (standard/intermediate risk ALL). The proven/probable mold IFI rate was 7/52 (13.5%) in HR-IFI-AL children and 1/41 (2.4%) in the non-HR-IFI-AL category. In the multivariable analysis, underlying genetic syndrome, oral mucositis, and older age were significantly associated with proven/probable IFI, while a longer time since AL diagnosis was protective. Two of 13 (15.4%) HR-IFI-AL children died because of IFI. The elevated risks of proven/probable mold IFI and the associated mortality in HR-IFI-AL children, and high risk of invasive candidiasis in the non-HR-IFI-AL group, emphasize the need for the close monitoring of local epidemiology and the adjustment of practices accordingly. Full article
(This article belongs to the Special Issue Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients)

Review

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36 pages, 433 KiB  
Review
High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies
by Giovanni Mori, Sara Diotallevi, Francesca Farina, Riccardo Lolatto, Laura Galli, Matteo Chiurlo, Andrea Acerbis, Elisabetta Xue, Daniela Clerici, Sara Mastaglio, Maria Teresa Lupo Stanghellini, Marco Ripa, Consuelo Corti, Jacopo Peccatori, Massimo Puoti, Massimo Bernardi, Antonella Castagna, Fabio Ciceri, Raffaella Greco and Chiara Oltolini
Microorganisms 2024, 12(1), 117; https://doi.org/10.3390/microorganisms12010117 - 6 Jan 2024
Viewed by 1487
Abstract
Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) [...] Read more.
Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non-Aspergillus invasive mold diseases. Here, we perform a narrative review, discussing the major advances of the last decade on prophylaxis, the diagnosis of and the treatment of IFDs in patients with high-risk neutropenic fever undergoing remission induction chemotherapy for AML/MDS and allo-HSCT. Then, we present our single-center retrospective experience on b-IFDs in 184 AML/MDS patients undergoing high-dose chemotherapy while receiving posaconazole (n = 153 induction treatments, n = 126 consolidation treatments, n = 60 salvage treatments). Six cases of probable/proven b-IFDs were recorded in six patients, with an overall incidence rate of 1.7% (6/339), which is in line with the literature focused on MAP with azoles. The incidence rates (IRs) of b-IFDs (95% confidence interval (95% CI), per 100 person years follow-up (PYFU)) were 5.04 (0.47, 14.45) in induction (n = 2), 3.25 (0.0013, 12.76) in consolidation (n = 1) and 18.38 (3.46, 45.06) in salvage chemotherapy (n = 3). Finally, we highlight the current challenges in the field of b-IFDs; these include the improvement of diagnoses, the expanding treatment landscape of AML with molecular targeted drugs (and related drug–drug interactions with azoles), evolving transplantation techniques (and their related impacts on IFDs’ risk stratification), and new antifungals and their features (rezafungin and olorofim). Full article
(This article belongs to the Special Issue Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients)

Other

Jump to: Research, Review

36 pages, 686 KiB  
Systematic Review
Usefulness of 18F-FDG PET-CT in the Management of Febrile Neutropenia: A Retrospective Cohort from a Tertiary University Hospital and a Systematic Review
by Andrea Gutiérrez-Villanueva, Claudia Quintana-Reyes, Elena Martínez de Antonio, Begoña Rodríguez-Alfonso, Karina Velásquez, Almudena de la Iglesia, Guiomar Bautista, Cristina Escudero-Gómez, Rafael Duarte and Ana Fernández-Cruz
Microorganisms 2024, 12(2), 307; https://doi.org/10.3390/microorganisms12020307 - 31 Jan 2024
Viewed by 833
Abstract
Febrile neutropenia (FN) is a complication of hematologic malignancy therapy. An early diagnosis would allow optimization of antimicrobials. The 18F-FDG-PET-CT may be useful; however, its role is not well established. We analyzed retrospectively patients with hematological malignancies who underwent 18F-FDG-PET-CT as [...] Read more.
Febrile neutropenia (FN) is a complication of hematologic malignancy therapy. An early diagnosis would allow optimization of antimicrobials. The 18F-FDG-PET-CT may be useful; however, its role is not well established. We analyzed retrospectively patients with hematological malignancies who underwent 18F-FDG-PET-CT as part of FN management in our university hospital and compared with conventional imaging. In addition, we performed a systematic review of the literature assessing the usefulness of 18F-FDG-PET-CT in FN. A total of 24 cases of FN underwent 18F-FDG-PET-CT. In addition, 92% had conventional CT. In 5/24 episodes (21%), the fever was of infectious etiology: two were bacterial, two were fungal, and one was parasitic. When compared with conventional imaging, 18F-FDG-PET-CT had an added value in 20 cases (83%): it diagnosed a new site of infection in 4 patients (17%), excluded infection in 16 (67%), and helped modify antimicrobials in 16 (67%). Antimicrobials could be discontinued in 10 (41.6%). We identified seven publications of low quality and one randomized trial. Our results support those of the literature. The available data suggest that 18F-FDG-PET-CT is useful in the management of FN, especially to diagnose fungal infections and rationalize antimicrobials. This review points out the low level of evidence and indicates the gaps in knowledge. Full article
(This article belongs to the Special Issue Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients)
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