Management Of Neutropenic Patients Research Articles

Necrotizing soft tissue infections in critically ill neutropenic patients: a French multicentre retrospective cohort study

BackgroundNecrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching.Results76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p < 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%, p < 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%, p < 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) [0.23–0.82], p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI [0.22–0.94], p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI [0.09; 0.68], p = 0.006).ConclusionsCritically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival.

The European Guidelines on Diagnosis and Management of Neutropenia in Adults and Children: A Consensus Between the European Hematology Association and the EuNet-INNOCHRON COST Action.

Neutropenia, as an isolated blood cell deficiency, is a feature of a wide spectrum of acquired or congenital, benign or premalignant disorders with a predisposition to develop myelodysplastic neoplasms/acute myeloid leukemia that may arise at any age. In recent years, advances in diagnostic methodologies, particularly in the field of genomics, have revealed novel genes and mechanisms responsible for etiology and disease evolution and opened new perspectives for tailored treatment. Despite the research and diagnostic advances in the field, real world evidence, arising from international neutropenia patient registries and scientific networks, has shown that the diagnosis and management of neutropenic patients is mostly based on the physicians' experience and local practices. Therefore, experts participating in the European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias have collaborated under the auspices of the European Hematology Association to produce recommendations for the diagnosis and management of patients across the whole spectrum of chronic neutropenias. In the present article, we describe evidence- and consensus-based guidelines for the definition and classification, diagnosis, and follow-up of patients with chronic neutropenias including special entities such as pregnancy and the neonatal period. We particularly emphasize the importance of combining the clinical findings with classical and novel laboratory testing, and advanced germline and/or somatic mutational analyses, for the characterization, risk stratification, and monitoring of the entire spectrum of neutropenia patients. We believe that the wide clinical use of these practical recommendations will be particularly beneficial for patients, families, and treating physicians.

AML-199 Radiological Aspects of Pneumonias in Neutropenic Patients

Imaging, such as chest X-ray and chest CT scan, plays a pioneering role in the diagnosis of neutropenic patients with respiratory dysfunction. To analyze radiographic patterns of adults with prolonged neutropenia and pneumonia. An observational, descriptive, and prospective study that analyzed patients admitted to the protected unit (acute myeloid leukemia and aplastic anemia) and transplant unit of Hematology and Pediatric Oncology at August 20th Hospital in Casablanca, from May 1st, 2019 to February 29th, 2020. Patients included were 18 years of age or older receiving chemotherapy and then developed respiratory symptoms during the period of neutropenia. An exploitation form was used to acquire the data then its analysis was performed with IBM SPSS Statistics version 21. Chest X-rays were taken during 20 of the 50 episodes of pneumonia (40%). They were all pathological, including alveolar opacities (90%), excavation (5%), reticulonodular (15%), and effusion syndrome fluid (15%). Chest computed tomography (CT scan) was performed in all patients. The time of its realization from the appearance of signs call clinics was variable ranging from 0 to 8 days, with a median of 2 days. It is important to note that distinct picture radiographs can coexist on the same X-ray and in the same patient. Forty six percent of our patients had condensation hearth and micronodules, nodules (58%), ground-glass opacity (60%), fluid effusion (34%), mediastinal lymphadenopathy (30%), interstitial thickening (22%), and 16% had reticulonodular infiltrates. Eight patients (16%) in our study had Halo sign, 10% had cavity image as well as Atelectasis, 2% with tree-in-bud aspect, and 2% had centrilobular emphysema. Thoracic CT improves the quality of the diagnosis; it also contributes to better management of neutropenic patients when pneumonia is suspected.

Management of neutropenic patients in the intensive care unit (NEWBORNS EXCLUDED) recommendations from an expert panel from the French Intensive Care Society (SRLF) with the French Group for Pediatric Intensive Care Emergencies (GFRUP), the French Society of Anesthesia and Intensive Care (SFAR), the French Society of Hematology (SFH), the French Society for Hospital Hygiene (SF2H), and the French Infectious Diseases

Neutropenia is defined by either an absolute or functional defect (acute myeloid leukemia or myelodysplastic syndrome) of polymorphonuclear neutrophils and is associated with high risk of specific complications that may require intensive care unit (ICU) admission. Specificities in the management of critically ill neutropenic patients prompted the establishment of guidelines dedicated to intensivists. These recommendations were drawn up by a panel of experts brought together by the French Intensive Care Society in collaboration with the French Group for Pediatric Intensive Care Emergencies, the French Society of Anesthesia and Intensive Care, the French Society of Hematology, the French Society for Hospital Hygiene, and the French Infectious Diseases Society. Literature review and formulation of recommendations were performed using the Grading of Recommendations Assessment, Development and Evaluation system. Each recommendation was then evaluated and rated by each expert using a methodology derived from the RAND/UCLA Appropriateness Method. Six fields are covered by the provided recommendations: (1) ICU admission and prognosis, (2) protective isolation and prophylaxis, (3) management of acute respiratory failure, (4) organ failure and organ support, (5) antibiotic management and source control, and (6) hematological management. Most of the provided recommendations are obtained from low levels of evidence, however, suggesting a need for additional studies. Seven recommendations were, however, associated with high level of evidences and are related to protective isolation, diagnostic workup of acute respiratory failure, medical management, and timing surgery in patients with typhlitis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-016-0189-6) contains supplementary material, which is available to authorized users.

Domestic mould exposure and invasive aspergillosis-air sampling of Aspergillus spp. spores in homes of hematological patients, a pilot study.

Aspergillus spp.-related morbidity and mortality remains a major challenge in the management of neutropenic patients. Little is known about the impact of domestic Aspergillus spp. In this controlled prospective study, fungal spores were collected from homes of neutropenic patients. Cases were defined as patients with probable or proven controls as patients with no invasive pulmonary aspergillosis, while patients with possible disease were evaluated as a third group. Forty patients were enrolled and returned questionnaires on high-risk activities and mould exposure. A. fumigatus was detected in concentrations of 0 to 76 cfu/m(3) in every home. A. terreus was detected in nine (18%) homes. Mean Aspergillus spp. cfu/m(3) according to EORTC criteria were: proven/probable IA (15 patients) - 36; possible IA (12 patients) - 42; no IA (13 patients) - 42. Of the seven patients with self-reported moulded walls at home, four had probable and three had possible aspergillosis; the risk ratio of developing IA was 1.65 (95% CI: 1.25-2.17). In conclusion self-reported domestic mould exposure was associated with a high incidence of IA and may be a feasible tool for identifying high-risk patients. There was no correlation between domestic ambient-air spore counts and IA.

23 General management of neutropenic patients

23 General management of neutropenic patients

Laparoscopic cholecystectomy for acalculous cholecystitis in a neutropenic patient after chemotherapy for acute lymphoblastic leukemia

Acute acalculous cholecystitis (ACC) is most frequently reported in critically ill patients following sepsis, extensive injury or surgery. It is rather uncommon as a chemotherapy-induced complication, which is usually life-threatening in neutropenic patients subjected to myelosuppressive therapy. A 23-year-old patient with acute lymphoblastic leukemia was subjected to myelosuppressive chemotherapy (cyclophosphamide, cytarabine, pegaspargase). After the first chemotherapy cycle the patient was neutropenic and feverish; she presented with vomiting and pain in the right epigastrium. Ultrasound demonstrated an acalculous gallbladder with wall thickening up to 14 mm. The ACC was diagnosed. Medical therapy included a broad spectrum antibiotic regimen and granulocyte-colony stimulating factors. On the second day after ACC diagnosis the patient's general condition worsened. Laparoscopic cholecystectomy was performed. The resected gallbladder showed no signs of bacterial or leukemic infiltrates. The postoperative course was uneventful. In the management of neutropenic patients with ACC surgical treatment is as important as pharmacological therapy.

Management of acute perianal sepsis in neutropenic patients with hematological malignancy

In neutropenic patients with acute perianal sepsis in the setting of hematological malignancy, the classical clinical features of abscess formation are lacking. Additionally, the role of surgical intervention is not well established. In this review, we discuss the challenges and controversy regarding diagnosis and optimal management when clear surgical guidelines are absent. In the literature, there is great diversity in the surgical approach to these patients, which leads to a high percentage of diagnostic errors, risks of complications, and unnecessary interventions. We review the literature and assess whether surgical intervention produces better outcomes than a non-surgical approach. Studies published on perianal sepsis in neutropenic cancer patients were identified by searching PubMed using the following key words: "perianal sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological malignancy, cancer". No randomized or prospective studies on the management of acute perianal sepsis in hematological malignancies were found. The largest retrospective study and most comprehensive clinical data demonstrated that 42% of patients were treated successfully without surgical intervention and without morbidity or mortality related to treatment chosen. Small retrospective studies advocated surgical intervention, while the majority of successes were in a non-operative treatment. It is difficult to formulate a conclusion given the small retrospective series on management of neutropenic patients with hematological malignancies. While there is no evidence mandating a routine surgical approach in this category of patients, non-surgical management including careful follow-up to determine whether the patient's condition is deteriorating or treatment has failed is an acceptable approach in selected patients without pathognomonic features of abscess. Comprehensive and well-designed prospective studies are needed to firmly establish the guidelines of treatment protocols.

Infectious Complications In Children With Severe Congenital, Autoimmune Or Idiopathic Neutropenia

We describe the incidence and characteristics of infections in children with severe congenital neutropenia (SCN), autoimmune neutropenia (AN) and idiopathic neutropenia (IN). Data extracted from the Italian Neutropenia Registry on 73 patients with 108 episodes of infections were collected from 2000 to 2009. All SCN patients with SCN and one third of AN and IN experienced at least 1 infectious episode, equating to 5.7 infections/patient in SCN and approximately 0.6 in AN and IN. The rate of infections before diagnosis of neutropenia was 6.35/1000 patient-days at risk in SCN, 0.48 in AN and 0.71 in IN (P < 0.001) and significantly decreased after diagnosis. Skin and subcutaneous abscesses and cellulitis were the most frequent types of infection encountered, followed by pneumonia. Infections are an important clinical issue in the management of neutropenic patients, even in those considered at lower risk.

Clinical experience of granulocyte transfusion in the management of neutropenic patients with haematological malignancies and severe infection

Prolonged chemotherapy-induced neutropenia is a major risk factor for the development of severe bacterial and fungal infections. Infectious manifestations may progress despite adequate anti-infectious treatment and lead to a very high short-term mortality. Granulocyte transfusion (GT) therapy is often considered. However, its efficacy is not well documented. We retrospectively analyzed the clinical characteristics and outcome of a cohort of patients with haematological malignancies receiving GT during neutropenia and severe infection. A total of 30 patients with a median age of 46 y (range 3-82 y) who had received 1 or more GT were included. Acute leukaemia (80%) and non-Hodgkin lymphoma (17%) predominated as the underlying malignancy. All patients had severe and prolonged (median 16 days) neutropenia. The major indications for GT were persistent fever and clinical deterioration despite broad anti-infectious therapy, in combination with progressive pneumonia (n = 16), neutropenic enterocolitis (n = 6), and soft tissue infections (n = 3). GTs were given for a median of 3 transfusions (range 1-14). The median time to fever defervescence after GT was 14 days (range 6-33 days). For 11 patients, the resolution of fever and all signs of infection could directly be related to GT, and 3 of these patients became long-term survivors. Mortality at 30 days post-GT was 40% and at 6 months post-GT was 72%. GT was well tolerated. A substantial proportion of severely ill neutropenic patients appeared to benefit from GT. The results further underline the need for well- designed, randomized, prospective trials to determine the efficacy of this intervention in patients with life-threatening infectious complications.

Pneumonia in neutropenic patients.

Radiologists have a special role in the management of neutropenic patients. The appropriate investigational technique, frequently targeted differential diagnosis, and the special needs of these patients, need to be understood. Early detection of a focus is the major goal in febrile neutropenic patients. As pneumonia is the most common focus, chest imaging is a special radiological task. The sensitivity of chest X-ray, especially in supine position, is known to be low; therefore, the very sensitive high-resolution CT (HRCT) became gold standard in neutropenic hosts and will probably be replaced by thin-section multislice CT (MSCT) in the near future. Costs of high-resolution CT are low in comparison to antibiotics. An infiltrate needs to be localised, so that a physician can utilise this information as a guidance for invasive procedures for further microbiological work-up. The radiological characterisation of infiltrates gives a first and rapid hint to differentiate between different sorts of infectious (typical bacterial, atypical bacterial, fungal) and non-infectious aetiologies. Follow-up investigations need careful interpretation according to disease and concomitant treatment. Due to an increased incidence of fungal infiltrates even with appropriate therapy, follow-up of an infiltrate must use further parameters in addition to lesion size. Temporary exclusion of infectious involvement of the lung with high accuracy remains of special interest for clinicians.

Comparative in vitro Activity of Levofloxacin and Ciprofloxacin against Bacterial Isolates from Neutropenic Patients

Background: Novel fluoroquinolones have been recently introduced in the management of neutropenic patients because of their increased activity against gram-positive and gram-negative micro-organisms. Methods: The activities of levofloxacin and ciprofloxacin were determined by the E test against 223 bacterial isolates from patients with haematological malignancies. Results: In general, the activity of levofloxacin was comparable to that of ciprofloxacin. Levofloxacin was somewhat more active against methicillin-resistant Staphylococcus aureus isolates. All methicillin-susceptible S. aureus isolates were inhibited by ciprofloxacin and levofloxacin at a concentration of ≤0.5 and ≤0.25 µg/ml, respectively. Among gram-negative isolates tested, levofloxacin was significantly (p < 0.001) more active than ciprofloxacin against Stenotrophomonas maltophilia, inhibiting 68 and 53% of these isolates, respectively. Conclusions: Levofloxacin was not superior to ciprofloxacin in its overall antibacterial activity, although small differences between these agents were seen depending on the species tested. In particular, our data suggested that levofloxacin may potentially be used for the management of S. maltophilia infections in neutropenic patients.

Use of G-CSF for granulocyte transfusion therapy.

Patients with neutropenia, especially neutropenia following aggressive myeloablative therapy, are at high risk for developing infectious complications caused by bacteria and opportunistic fungi. Infections remain one of the leading causes of treatment failure in patients with cancer. Thus, new and innovative therapeutic strategies are needed for management of neutropenic patients with infection. Because neutrophils represent the first line of host defense, granulocyte transfusion therapy should be a logical therapeutic approach. Although such therapy has been employed sporadically for several decades, clinical benefit has been compromised by technical problems and low granulocyte yields resulting from inadequate donor stimulation. The discovery of granulocyte colony-stimulating factor (G-CSF) as a means to elevate blood neutrophil counts when administered to normal donors has rekindled interest in granulocyte transfusion therapy. Extensive experience has been gained worldwide with G-CSF in clinical practice, and adverse events have been minimal when G-CSF has been administered to patients or healthy persons in human trials. This review focuses on the use of G-CSF in granulocyte transfusion therapy, including technical considerations of granulocyte leukapheresis and storage, donor selection and stimulation, as well as treatment results and associated risks.

Infection in the neutropenic and stem cell transplant patient

The spectrum of infectious complications in neutropenic patients after stem cell or bone marrow transplant is not very different from that seen in other neutropenic patients, with the possible exception of fungal infections. The prevention and therapy of these infections remain a major challenge. The management of neutropenic patients after stem cell or bone marrow transplant has markedly benefited from the development of new antiviral agents and the use of granulocyte/macrophage colony stimulating factors.

Antibiotic treatment of febrile episodes in neutropenic cancer patients. Clinical and economic considerations.

The increased frequency of infections caused by Gram-positive microorganisms, and the expansion of resistant pathogens resulting from institutional therapeutic practices, represent some of the emerging issues of empirical drug treatment of cancer patients with febrile neutropenia. However, the therapeutic strategies for the treatment of these patients have progressed remarkably over the last decade. Individual therapy in the light of the principal clinical features (in particular, the degree and estimated duration of neutropenia, as well the presence of other potential factors favouring infection such as long-standing intravascular catheters) and local microbial ecology have emerged as the leading concepts. Empirical drug monotherapy has been recognised as a feasible alternative to combination therapy, at least in selected low-risk patients. The indiscriminate use of empirical glycopeptides should be discouraged to prevent the emergence of resistant bacteria, especially in centres where methicillin-resistant staphylococci have not yet become a major issue. Empirical antifungal therapy with amphotericin B is still essential for a successful outcome in case of fever persistence or recurrence. Finally, selected febrile neutropenic patients who exhibit a better prognosis can be handled on an outpatient basis. The prophylactic use of haemopoietic growth factors has been shown to augment cost savings substantially in the management of neutropenic patients via a reduction in the duration and severity of the neutropenia, as well as infectious complications. Although data from economic analyses are not yet available, some cost-containment strategies such as outpatient treatment, monotherapy, and use of more convenient antibiotic combinations may lead to a reduction of therapy expenditures for febrile episodes in these patients.

Empiric amphotericin B therapy: the need for a reappraisal

Neutropenic patients are at high risk of developing invasive fungal diseases. A number of studies, both randomized and historical, have demonstrated that empiric therapy with amphotericin B in neutropenic patients with fever, refractory to antibiotics, results in a decrease in the frequency and mortality of deep fungal infections. Recent years have seen a number of advances in the management of neutropenic patients. Reasonably effective antigungal prophylaxis now exists and in many centres forms part of the routine care of neutropenic patients. Other centres advocate the use of selective decontamination and/or protective isolation. Furthermore the duration of neutropenia can be reduced with the use of haematopoetic growth factors. The impact of empiric amphotericin B in patients already benefiting from such treatments has not been adequately studied. The optimum dose of empiric amphotericin B is not defined. The criteria for commencing amphotericin B therapy in febrile neutropenic patients must therefore be redefined on the basis of further studies carried out in the context of these developments. We offer an approach to the use of empiric amphotericin B based on risk factors and prophylaxis.

Pseudomonas

Although the frequency of infection with P. aeruginosa has declined in many centers treating neutropenic patients with cancer, infections still occur and can be accompanied by considerable morbidity and mortality. Furthermore, patterns of infection can change again, and Pseudomonas may reemerge. Thus, in high-risk, immunocompromised patients, adequate bacterial coverage for P. aeruginosa should be part of any empiric regimen. Third-generation cephalosporins are an important part of the therapeutic armamentarium for the empiric management of neutropenic patients. Assuming a low level of resistance at a given center, however, only ceftazidime and cefoperazone possess sufficient antipseudomonal activity to be used for monotherapy. If other third-generation cephalosporins are used, it is imperative that an aminoglycoside or an antipseudomonal penicillin be added. But even when combined with an aminoglycoside, ceftriaxone would not be a good choice for neutropenic patients. It is an important agent in non-neutropenic hosts or in other immunocompromised patients in whom infection with Pseudomonas is unlikely to occur.

Value of surveillance cultures in the management of neutropenic patients.

To assess whether bacteriological surveillance cultures can be used to predict infection in neutropenic patients, cultures were performed during the period of neutropenia of nose, throat and urine specimens collected once weekly and faeces specimens collected twice weekly. Seventy-six consecutively observed patients undergoing chemotherapy for haematological or non-haematological diseases were investigated. Severe infection including septicaemia, lower respiratory tract infection, anorectal lesion and urinary tract infection occurred in 32 patients. Enterobacter cloacae, Escherichia coli and Pseudomonas aeruginosa were the organisms most commonly involved. In the majority of cases of septicaemia the organisms were isolated from the faeces, often in pure culture, prior to the onset of septicaemia. Most of the isolates of Enterobacter cloacae were resistant to the empiric antibiotic therapy used in the unit and were able to colonise multiple sites, presumably increasing the risk of subsequent infection. Faecal culture is the most useful approach in bacteriological surveillance in neutropenic patients.