La prise en charge de la neutropénie fébrile chez les enfants et les adolescents immunocompétents.

La neutropénie fébrile est une manifestation clinique fréquente en pédiatrie, qui peut être associée à une infection bactérienne invasive. Cependant, le risque de ce type d'infection est faible chez les enfants et les adolescents autrement en santé qui font de la fièvre et présentent une neutropénie, la plupart des cas étant causés par une infection virale. Les enfants âgés de six mois à 18 ans qui ont l'air bien, ne souffrent pas d'un cancer, sont considérés comme immunocompétents et présentent un premier épisode de neutropénie, sans autres facteurs de risque, n'ont généralement pas besoin d'antibiotiques empiriques. Cependant, une évaluation approfondie est indiquée, y compris une anamnèse et un examen physique complets, de même qu'une hémoculture lorsque la numération absolue des neutrophiles est inférieure à 0,5 × 109/L. Il est recommandé d'assurer un suivi étroit, de reprendre l'hémogramme et de donner des conseils préventifs stricts.

Nose-to-brain delivery of paliperidone palmitate poloxamer-guar gum nanogel: Formulation, optimization and pharmacological studies in rats.

Oral delivery of paliperidone palmitate (PPD), a potent antipsychotic agent, has been reported with a potential risk of very serious drug-induced adverse events such as tachycardia, hyperprolactinemia, sexual dysfunction, and neutropenia. Alternatively, the potential of nasal delivery has also been explored to treat CNS complications by delivering the medicines directly to the brain bypassing the blood-brain barrier. Hence, the objectives of current work were to formulate, design, optimize, and investigate the therapeutic potency of PPD-loaded intranasal in-situ gel (PPGISG) in the treatment of schizophrenia. PPD-nanoemulsion (PNE) was fabricated using water titration technique, was further optimized via Box-Behnken design. Furthermore, the optimized PNE was evaluated for parameters such as globule size, polydispersity index, zeta potential, and % entrapment efficiency were found to be 21.44±1.58nm, 0.268±0.02, -25.56±1.6mV, and 99.89±0.25%, respectively. PNE was further converted to PPGISG utilizing two polymers, poloxamer, and guar gum. Simultaneously, ex-vivo permeation for PNE, PPGISG, and PPD-suspension was found to be 211.40±4.8, 297.89±3.9 and 98.66±1.6µg/cm2, respectively. While PPGISG nanoparticles showed 1.58 and 5.65-folds more Jss than PNE and PPD-suspension. Behavioral studies confirmed that no extrapyramidal symptoms were observed in experimental animals post intranasal administration. Finally, the outcomes of the in-vivo hemato-compatibility study proved that intranasal formulation did not cause any alteration in leukocytes, RBCs, and neutrophils count. Therefore, intranasal delivery of PPGISG can be considered a novel tool for the safe delivery of PPD in schizophrenic patients.

Early subcutaneous drainage of skin and soft tissue infections in patients with febrile neutropenia: A new treatment option.

OBJECTIVES: Patients with febrile neutropenia presenting a cutaneous portal of entry for an infectious agent are at high risk of death (19-32%). If medical management is well codified, surgical management represents a therapeutic dilemma because the only available option is an aggressive debridement of the infected area which is associated with a high morbidity rate. Our objective was to implement a low-risk technique that is quick to perform and does not delay major surgical debridement if the latter turns out to be necessary. PATIENTS AND METHODS: We performed an early subcutaneous drainage of the infected areas by percutaneous approach in order to avoid the evolution towards skin and subcutaneous necrosis. Five consecutive patients were treated with this technique associated with the recommended medical treatment between March and September 2017. This technique is based on the mechanical concept of the evacuation of the edema from the inflammatory area which would allow a better efficiency of the antibiotic treatment thanks to a better blood perfusion and a higher tissue concentration of antibiotics. RESULTS: Of the 5 patients managed in the department, no skin necrosis occurred, no surgical debridement was necessary, and no patient died during the episode of febrile neutropenia. CONCLUSION: Early subcutaneous drainage by percutaneous approach of an area of skin infection in a patient with febrile neutropenia may be considered as an interesting option. This technique allows without loss of chance for the patient to increase survival and decrease the number of aggressive surgical debridement and their high morbidity.

[Clozapine rechallenge after neutropenia in resistant schizophrenia: A review]. / Réintroduction de la clozapine après neutropénie dans la schizophrénie résistante : revue des données de la littérature.

INTRODUCTION: Clozapine is an atypical antipsychotic known for its efficacy in refractory schizophrenia. One of the adverse effects is neutropenia. This dysplasia is a rare but major side effect which leads to a discontinuation and constitutes further contraindication. Thereafter, therapeutic options decrease dramatically. Mechanisms involved are not well known at this time and can be combined. A toxic hypothesis may be more likely than an immune-allergic one. METHODS: We have reviewed publications on Medline describing procedures that allowed clozapine rechallenge after blood dyscrasia in refractory schizophrenia. Three different procedures were found: simple rechallenge, rechallenge with lithium and rechallenge with Granulocyte - colony stimulating factor (G-CSF). Rechallenge could be simple or multiple. RESULTS: These past years, clozapine have been rechallenged successfully after neutropenia thanks to different procedures, the different options being simple rechallenge, rechallenge with lithium and/or rechallenge with G-CSF. Lithium as G-CSF are used to increase neutrophil blood rate and prevent neutropenia recurrence after clozapine rechallenge. G-CSF was first used within the context of chemotherapy and extends now to clozapine-induced neutropenia. Both for lithium and G-CSF, numerous procedures are reviewed and cannot be compared. DISCUSSION: Publications are limited but increasing, and they point out that a careful rechallenge can be successful. However, interesting data can be extracted. First, clozapine is more likely to be incriminated in neutropenia when patients receive many drugs, but a careful study could prevent some discontinuation. Indeed, other drugs or a hematologic disease could be involved. Moreover, several contributing factors have been found such as HLA group and drug interaction. Ethnic origin also affects neutrophil rate. That is why, in Great Britain, a subgroup of patients "benign ethnic neutropenia" has been introduced to enlarge threshold and allow these patients to access clozapine despite lower blood counts. Then, rechallenge choice has to be done on a case-by-case basis and only after considering the benefits and risks of such a treatment. Most of the time, clinical advice of rechallenge arises from the inefficiency of other antipsychotics and even sismotherapy failure. Patients and sometimes families have to be informed and give their consent. Preventive measures have been found such as taking a hematologic recommendation and doing twice-a-week blood sample monitoring. With regards lithium and G-CSF, some efficient doses are assumed (lithium: 0,4-1,1 mEq/L and G-CSF>0,3 mg/week). Lithium as G-CSF may have other adverse effects which need to be considered. There is no successful rechallenge reported after agranulocytosis. Some publications highlight that if neutropenia occurs on rechallenge, it will do so more quickly and more severe than at the time of initial trial of clozapine. CONCLUSION: There is emerging evidence of successful clozapine rechallenging. However, further investigations are required as randomized controlled trials to reassess guidelines and establish the safety and effectiveness of the different procedures. Because of the practical and ethical difficulties of designing such studies, referral hospitals could be elected, and common background writing proposed in order to ease data comparison.

Risk of Neutropenia in Adults Treated with Piperacillin-Tazobactam or Cefazolin: A Retrospective Cohort Study.

Background: Neutropenia is an adverse effect associated with the use of several antibiotics, including piperacillin-tazobactam (P/T). Previous findings have suggested that the risk of neutropenia in children is significantly higher with P/T than with ticarcillin-clavulanate. Objectives: To compare the risk of neutropenia associated with P/T and with cefazolin in an adult population and to describe the characteristics of neutropenia episodes observed. Methods: This descriptive retrospective study involved patients aged 18 years or older who received a minimum of 10 days of treatment with P/T or cefazolin between January 2009 and December 2013. Patients who experienced neutropenia (absolute neutrophil count < 1.5 × 109/L) were compared, using univariate and multivariate logistic regression models, between those who received P/T and those who received cefazolin. Results: A total of 207 patients were included (104 who received P/T and 103 who received cefazolin). Ten episodes of neutropenia were observed, 5 with each antibiotic (4.8% and 4.9%, respectively; odds ratio 0.99, 95% confidence interval 0.278-3.527). The mean cumulative dose of piperacillin was 290.4 g among patients who experienced neutropenia and 247.0 g among all patients treated with P/T, and the mean treatment duration was 24.0 days and 21.0 days, respectively. The average time before the onset of neutropenia was slightly longer with P/T than with cefazolin (22.0 versus 17.2 days, p = 0.38). Conclusions: Although these results require confirmation in a larger clinical trial (to lessen possible attribution bias), the risk of neutropenia appeared to be similar between P/T and cefazolin.

Contexte: La neutropénie est un effet indésirable associé à l'utilisation de plusieurs antibiotiques, dont la pipéracilline-tazobactam (P/T). Des données récentes indiquent que le risque de neutropénie chez les enfants est significativement plus élevé avec la P/T qu'avec l'association ticarcilline-clavulanate. Objectifs: Comparer le risque de neutropénie associé à la P/T et à la céfazoline chez une population adulte et décrire les caractéristiques des épisodes de neutropénie observés. Méthodes: Cette étude rétrospective descriptive impliquait des patients âgés d'au moins 18 ans ayant reçu un traitement d'au moins 10 jours par P/T ou céfazoline entre janvier 2009 et décembre 2013. Les patients ayant présenté une neutropénie (nombre absolu de neutrophiles < 1,5 × 109/L) ont été comparés, à l'aide de modèles de régression logistique univariée et multivariée, entre ceux qui ont reçu de la P/T et ceux qui ont reçu de la céfazoline. Résultats: Au total, 207 patients ont été inclus (104 ayant reçu de la P/T et 103 ayant reçu de la céfazoline). Dix épisodes de neutropénie ont été observés, 5 avec chaque antibiotique (4,8 % et 4,9 %, respectivement; rapport des cotes 0,99; intervalle de confiance à 95 % 0,278­3,527). La dose cumulée moyenne de pipéracilline était de 290,4 g chez les patients ayant présenté une neutropénie et de 247,0 g chez tous les patients traités par P/T. La durée moyenne du traitement était de 24,0 jours et 21,0 jours, respectivement. Le délai moyen avant l'apparition de la neutropénie était légèrement plus long avec la P/T qu'avec la céfazoline (22,0 contre 17,2 jours, p = 0,38). Conclusions: Bien que ces résultats nécessitent une confirmation dans un essai clinique de plus grande envergure (afin de réduire d'éventuels biais d'attribution), le risque de neutropénie semble être similaire chez les personnes ayant reçu de la P/T et ceux ayant reçu de la céfazoline.

Granulocyte transfusions collected after steroid priming for severe infections during neutropenia: A single center experience.

BACKGROUND: There is no universally accepted opinion on the use of granulocyte transfusions collected using apheresis (GTA) in neutropenic patients and severe infection. PATIENTS AND METHODS: The efficacy and safety of GTAs transfused at a single center over 10 years were analyzed retrospectively. GTAs were harvested from voluntary unrelated donors after priming with methylprednisolone using continuous apheresis and hydroxyethylstarch as sedimentation agent. RESULTS: 41 patients with neutropenia and hematologic malignancy (15 females and 26 males aged 22-69 (median 45.5)) were given a median 3.5 GTAs per patient (range: 1-17) containing a median 1.39×1010 granulocyte/GTA (range: 0.65-2.81). The indications for GTA use were soft tissue inflammation, sepsis, and pneumonia in 30, 22, and 14 cases, respectively. After GTA complete (30 patients: 73.2%) or partial (6 patients: 14.6%) healing of the infection was achieved. The success rate was 91.7% in soft tissue infections, 66.7% in invasive fungal infections, and 68% in sepsis. Septic shock (documented in 12 cases) was associated with a poor response (P<0.03; Chi-square test). Clinical worsening was observed in six cases (14.6%); four patients died. No significant short-term side effects of GTA treatment were recorded. CONCLUSIONS: In our study GTAs collected after steroid priming and used for the treatment of infection during severe neutropenia have shown comparable efficacy with several previously reported trials. However retrospective fashion of our study and inhomogeneous group of patients do not allow any firm conclusions. Prospective studies (including patients' registries) are needed for the better clarification of the role and the dose of GTAs necessary for the successful infection management during neutropenia.

[Preparation of pooled granulocytes concentrates from whole blood buffy coats (PGC) as an alternative to apheresis]. / Le mélange de concentré de granulocytes de sang total (MCGST) comme alternative au concentré de granulocytes d'aphérèse (CGA).

BACKGROUND: The collection of granulocytes by apheresis requires volunteer donor stimulation by corticoids and the use of HES, a compound which is currently challenged by potential safety issues. Preparation of pooled granulocytes concentrates from whole blood buffy coats (PGC) represent an alternative to apheresis with a better benefit/risk for the donors. METHOD: Whole blood is collected in a bottom and top blood bag for buffy coat preparation. After centrifugation and separation, buffy coat are obtained. Twenty ABO matched buffy coats are selected for processing into one PGC. Four pools of five buffy coats were made, platelet additive solution is added to each pool, mixed gently and centrifuged. The red cell residue, supernatant and granulocyte rich layer are separated. Two granulocyte rich layers are pooled and added with 70mL of ABO matched plasma from the initial donations (=PGC10). The final PGC (=PGC20) is obtained by pooling two PGC10 into a platelet storage bag. Neutrophil content and in-vitro functionality are assessed at day of preparation (D1) and at expiry hour, 48 hours after collection (D2). RESULTS: On N=18, mean: Volume=408±4mL, 2.2*1010±0.24 neutrophils, Hematocrit=18%±3%, 4.7*1011platelets. Viability is well preserved: 95%±6% day of PGC preparation, 85%±7% after 24h of storage (D2). Functionality (ROS production measurement) is well preserved: 1.36±0.25 at D1 and 1.38±0.18 at D2. Expression and modulation of adhesion molecules after stimulation are normal at D1 and slightly decreased at D2 but still normal. CONCLUSIONS: PGC20 in vitro characteristics are in conformance with the EDQM guide (V19) and similar to apheresis for granulocytes content and hematocrit. The viability and two mean indicators which explore neutrophil function are well maintained during PGC preparation and after 24 hours of storage.

[Invasive pulmonary aspergillosis]. / Aspergillose pulmonaire invasive.

INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in a wide range of patients. Early recognition and diagnosis have become a major focus in improving the management and outcomes of this life-threatening disease. BACKGROUND: IPA typically occurs during a period of severe and prolonged neutropenia. However, solid organ transplant recipients, patients under immunosuppressive therapy or hospitalized in intensive care units are also at risk. The diagnosis is suspected in the presence of a combination of clinical, biological and CT scan evidence. The microbiological diagnostic strategy should be adapted to the patient's profile. Conventional methods with culture and species identification remain the standard but early diagnosis has been improved by the use of biomarkers such as galactomannan antigen in serum or in bronchoalveolar lavage. OUTLOOK: The epidemiology of IPA should change with the increased use of antifungal prophylactic regimens and the arrival of targeted therapies. Other microbiological tools, such as PCR and other biomarkers, are currently being assessed. CONCLUSIONS: IPA must be considered in a wide range of patients. Its prognosis remains poor despite progress in the microbiological diagnosis and therapeutic management.

[Retrospective study of 25 cases of pulmonary mucormycosis in acute leukaemia]. / Mucormycoses pulmonaires au cours des traitements de leucémies aiguës. Analyse rétrospective d'une série de 25 patients.

INTRODUCTION: In acute leukaemia (AL), the occurrence of pulmonary mucormycosis (PM), the incidence of which is increasing, as a result of chemotherapy induced marrow aplasia, remains a life threatening complication. METHODS: Analysis of clinical, biological and thoracic CT characteristics of patients with PM developing during the treatment of AL between 2000 and 2015. Day 0 (D0) was defined as the day with first CT evidence of PM. RESULTS: Among 1193 patients, 25 cases of PM were recorded during 2099 episodes of bone marrow aplasia. At time of diagnosis of PM, 24/25 patients had been neutropenic for a median of 12 days. None of the patients had diabetes mellitus. On initial CT (D0), the lesion was solitary in 20/25 cases and a reversed halo sign (RHS) was observed in 23/25 cases. From D1 to D7, D8 to D15 and after D15, RHS was seen in 100 %, 75 % and 27 % of cases, respectively. A tissue biopsy was positive in 17/18 cases. The detection of circulating Mucorales DNA in serum was positive in 23/24 patients and in 97/188 serum specimens between D-9 and D9. Bronchoalveolar lavage contributed to diagnosis in only 3/21 cases. The antifungal treatment was mainly based on liposomal amphotericin B combined with, or followed by, posaconazole. A pulmonary surgical resection was performed in 9/25 cases. At 3 months, 76 % of patients were alive and median overall survival was 14 months. CONCLUSION: In AL, early use of CT could improve the prognosis of PM. The presence of a RHS on CT suggests PM and is an indication for prompt antifungal treatment.

[Febrile neutropenia: is ambulatory care possible]? / Neutropénie fébrile : le traitement ambulatoire est-il possible ?

Febrile neutropenia: is ambulatory care possible ? Outpatient treatment of neutropenic fever post chemotherapy is possible for patients at low risk of complications. Thorough clinical evaluation at presentation and close follow-up are essential. The patient's comorbidities, their specific cancer diagnosis, the expected duration and severity of neutropenia, their adherence and access to healthcare facilities should be assessed before proposing outpatient management. Empirical treatment with oral amoxicillin/clavulanic acid with ciprofloxacin are prescribed for the duration of neutropenia, in the absence of a clinical or microbiological diagnosis.

Neutropénie fébrile : le traitement ambulatoire est-il possible ? Le traitement antibiotique ambulatoire chez un patient neutropénique fébrile après une chimiothérapie est possible pour les malades à faible risque de complications (patient éligible à cette prise en charge selon une évaluation initiale rigoureuse et suivi médical rapproché). Le terrain sous-jacent, la nature de la pathologie cancéreuse, la profondeur et la durée de la neutropénie, la gravité du tableau clinique ainsi que la compréhension par le patient et ses conditions de vie et d'accès aux soins sont les critères qui doivent être impérativement pris en compte pour autoriser cette prise en charge en ville. Une association d'antibiotiques par voie orale (amoxicilline-acide clavulanique et ciprofloxacine) est prescrite jusqu'à la sortie d'aplasie (en l'absence d'infection documentée).

[French recommendations on control measures to reduce the infectious risk in immunocompromised patients]. / Quelles mesures pour maîtriser le risque infectieux chez les patients immunodéprimés ? Recommandations formalisées d'experts.

The increase use of immunosuppressive treatments in patients with solid cancer and/or inflammatory diseases requires revisiting our practices for the prevention of infectious risk in the care setting. A review of the literature by a multidisciplinary working group at the beginning of 2014 wished to answer the following 4 questions to improve healthcare immunocompromised patients: (I) How can we define immunocompromised patients with high, intermediate and low infectious risk, (II) which air treatment should be recommended for this specific population? (III) What additional precautions should be recommended for immunocompromised patients at risk for infection? (IV) Which global environmental control should be recommended? Based on data from the literature and using the GRADE method, we propose 15 recommendations that could help to reduce the risk of infection in these exposed populations.

Practices of infectious control management during neutropenia: A survey from 149 French hospitals.

OBJECTIVE OF THE STUDY: Neutropenic patients represent a growing and fragile population in our hospitals. Numerous treatments induce neutropenia in haematology wards and elsewhere. Although strict isolation is recommended during post-haematopoietic stem cell transplantation neutropenia, this may not be the current practice in other situations. In this study, our objective was to analyse what protective measures are applied in neutropenic patients in a French survey. MATERIELS AND METHODS: A questionnaire was sent out to infection control teams of 400 public and private French hospitals to enquire about their local recommendations regarding infection prevention in neutropenic patients. RESULTS: Among the 166 (41%) responders, 134 (81%) managed neutropenic patients. All of the centres recommended protective isolation for neutropenic patients. However, only 46 (34%) had clearly defined patients warranting specific isolation measures in terms of the level of neutropenia. All of the centres recommended several barrier measures, but these were highly variable according to the type of air treatment in the wards (note that only 72% of haematology wards are equipped with air treatment). Gowns, gloves, masks, hats and shoe covers were respectively recommended in 128 (95%), 79 (59%), 132 (98%), 87 (65%), and 34 (25%) of the establishments. Surprisingly, the recommendations vary both among hospitals and within the same hospital among different clinical wards. CONCLUSION: In conclusion, protective measures for neutropenic patients are applied variably and urgently require a consensus to homogenize practices.

[Clinical burden caused by hospitalization for febrile neutropenia in France in 2010-2011: An analysis of the PMSI database]. / Hospitalisations pour neutropénie fébrile chimio-induite en France en 2010-2011 : impact clinique et caractéristiques des patients à partir des données de la base PMSI.

INTRODUCTION: Febrile neutropenia (FN) is a severe complication of chemotherapy in terms of morbidity and mortality. Using data from the PMSI database, the objective of this work was to estimate the clinical burden caused by hospitalization for FN in France, assessed by number of patients, number of stays and hospital mortality. METHODS: Using the PMSI database (which includes all hospitalizations occurring annually in France), an algorithm was used to select newly-diagnosed patients treated by chemotherapy in 2010/2011 who were hospitalized for FN within the 30 days following each administration of chemotherapy during their first year of treatment. The number, characteristics and comorbidities of patients were described, as well as the number and length of stay and mortality in hospitalized patients. RESULTS: In 2010-11, 10,229 patients were hospitalized for FN, representing a hospitalization rate of 7.4% in newly-diagnosed patients receiving chemotherapy. A total of 13,559 stays were identified, with an average duration of 6.3±8.7 days (median=4 days). A total of 720 deaths occurred during the hospital stays, corresponding to a mortality rate of 7%. Among patients hospitalized for FN, there were 14% of patients with diabetes, 8 % with heart failure, 34% with hypertension and 41% with at least one of these three comorbidities. DISCUSSION: With 10,299 hospitalized patients and 13,559 stays in 2010-11, the clinical burden induced by febrile neutropenia in cancer patients treated with chemotherapy is considerable.

[Prognosis prediction of febrile neutropenia by MASCC score: A retrospective study]. / Prédiction de la gravité des neutropénies fébriles par le score de MASCC : une étude de cohorte rétrospective.

INTRODUCTION: The score of the MASCC, by means of clinical criteria, estimates the risk of serious complications in patients with neutropenic fever induced by chemotherapy. METHODS: We retrospectively studied a cohort of patients hospitalized for a neutropenic fever and analyzed complications according to the criteria defined by the MASCC. RESULTS: Eighty-one neutropenic fevers in 71 patients were identified. Microbiological documentation was obtained in 33% of cases only. Fifty-eight patients (72%) presented with a MASCC score≥21 and were considered as low risk of complications. In the total population, 10 patients died during their hospitalizations for neutropenic fever, 7 in the high-risk group versus 3 in the low risk group, including 2 patients suffering from significant comorbidities not taken into account by MASCC score. Within the low risk group, presence of a metastatic disease and existence of 2 or more comorbidities were associated with a longer duration of hospitalization. CONCLUSION: This analysis suggests that the criteria of the MASCC are not always enough to thoroughly identify which patients were at risk of complications or could be treated through outpatient management. By better taking into account the comorbidities and tumoral stage, a better selection of the patients who are likely to receive an ambulatory treatment could be made. To date, hospitalization remains frequently necessary in neutropenic fevers, at least in its initial steps, and the place of the general practitioner remains to be better defined.

[Antithyroid agents related agranulocytosis: Literature review]. / Agranulocytoses aux antithyroïdiens de synthèse : revue de la littérature.

The antithyroid agents (carbimazole, methimazole, thiamazole, propylthiouracil and benzylthiouracile) are the drug class that is associated with a high risk of agranulocytosis. Acute and profound (<0.5×10(9)/L) isolated neutropenia occurring in a subject treated with antithyroid agents should be considered as a drug-induced agranulocytosis, until proven otherwise. The clinical spectrum ranges from discovery of acute severe but asymptomatic neutropenia, to isolated fever, localized infections (especially ear, nose and throat, or pulmonary) or septicemia. With an optimal management (discontinuation of antithyroid agents, antibiotics in the presence of fever or a documented infection, or use of hematopoietic growth factor) the current mortality is close to 2%.

[Granulocyte- colony stimulating factor (G-CSF) use in clinical practice in patients receiving chemotherapy for breast cancer: The Opaline Study]. / Description des modalités pratiques de prescription d'un facteur de croissance de la lignée granulocytaire (G-CSF) chez les patientes recevant une chimiothérapie pour un cancer du sein : étude Opaline.

OBJECTIVES: To describe the French routine use of G-CSF in patients treated for breast cancer as per the EORTC recommendations. PATIENTS AND METHODS: A prospective multicenter observational study conducted between February 2008 and September 2009 in 869 breast cancer patients treated by chemotherapy (CT) and for whom G-CSF treatment will be delivered in primary (PP) or secondary prophylaxis. RESULTS: The mean age was 55 years. A total of 80.3% of CT was in neoadjuvant/adjuvant setting (NAS). PP was delivered in 78.9% of the NAS patients and 67.5% in metastatic situation. Of the 702 evaluable patients, incidences of severe (SN) and febrile neutropenias (FN) in patients who received PP were 9.3% and 4.2%, respectively. In patients who did not received G-CSF at first cycle, SN and FN were 12.4% and 7.3%, respectively. The use of PP was mainly driven by the type of CT for patients treated in the NAS and by patient or disease related risk factors in the locally advanced/metastatic setting. CONCLUSION: This study has shown that the use of G-CSF was in accordance with the 2010 updates of the EORTC recommendations. However, G-CSF appears more widely used in the routine practice.

[Febrile neutropenia in onco-hematology patients hospitalized in Intensive Care Unit]. / Prise en charge de la neutropénie fébrile chez le patient d'onco-hématologie admis en réanimation.

Febrile neutropenia in cancer patients is associated with a high mortality. Patients are frequently admitted to Intensive Care Unit (ICU) for severe sepsis or septic shock. Empirical antibiotic treatment, including monotherapy ß-lactam covering Pseudomonas aeruginosa, must be prompt. The ICU management is slightly different, due to a particular microbial ecology. A standardized approach to obtain a microbiological documentation is the cornerstone in these patients, leading to an adapted antimicrobial treatment. Systematic reassessment of initial antibiotic regimen should be realised. Neutropenic patients with severe sepsis or septic shock should receive promptly a ß-lactam-aminoglycoside combination, as well as glycopeptides in case of severity or absence of documented infection. Early catheter removal should be considered widely. In the actual context of growing resistance, antibiotics saving became a major concern. According to context and microbial documentation, an escalade or de-escalade approach is recommended, to take into account multi-resistant pathogens. The addition of antifugal treatment is also a major issue in these patients and has well-defined indications. In neutropenic patients admitted in the ICU for severe sepsis or septic shock, controlling local microbial epidemiology and the emergence of multi-resistant bacteria are the key issues.

Antifungal prophylaxis with itraconazole oral solution in neutropenic patients.

The role of itraconazole in anti-fungal prophylaxis has been limited by the low bioavailability of the capsule formulation but the bioavailability of the oral solution is much improved. Three multi-centre studies using itraconazole solution (5 mg/kg/day) have recently been completed. The UK trial compared itraconazole solution with fluconazole suspension (100 mg/day). No invasive aspergillosis occurred in the itraconazole arm and there were more fungal deaths due to proven/suspected infection in the fluconazole group than in the itraconazole group (0 versus 7, p = 0.024). An Italian study compared itraconazole solution with placebo. Proven, suspected and superficial fungal infections were fewer in the itraconazole arm compared with placebo, with significant differences in proven and suspected systemic fungal infections (itraconazole 24% versus placebo 33 %, p = 0.035). The third study compared itraconazole with amphotericin B capsules (2 g/day). There were more invasive fungal infections, Aspergillus infections and fungal deaths in the amphotericin B arm than with itraconazole but none of these differences were statistically significant. Azole prophylaxis in neutropenic patients may reduce the incidence of Candida infections, empirical amphotericin B usage, and the incidence of proven fungal infections. Itraconazole may be more effective than fluconazole in preventing invasive aspergillosis. All of these effects are more pronounced in high risk patients.

Early empiric antifungal therapy of infections in neutropenic patients comparing fluconazole with amphotericin B/flucytosine.

We compared the efficacy and tolerability of fluconazole (FCA) with amphotericin B/flucytosine (ABF) in neutropenic patients with haematological malignancies. Antifungal therapy started on day 4 when fever was unresponsive to antibiotics or on day 1 together with the antibiotics, if there was evidence of mycosis. If patients did not respond to FCA after 7 days they switched to ABF. 98 patients, 51 FCA and 47 ABF were included in the study. Response to fever was achieved in 28/51 FCA patients and in another 16 after switching to ABF. So in overall 44/51 (86.2%) of the FCA and 37/47 (78.8%) of the ABF group defervescence was observed. 46 patients (21 FCA, 25 ABF) developed radiological signs of pneumonia. Resolution of infiltrates was achieved in 5/21 FCA and 20/25 ABF patients, and another 10 of 15 initially not responding patients showed regression when switched to ABF, 5 of these had highly suspected aspergillosis. Adverse events occured in 19.6% of FCA and 97.9% of ABF patients. In conclusion fluconazole and amphotericin B/flucytosine seem to be equally effective. In view of its lower toxicity fluconazole may be preferred as first line empiric antifungal agent, but in case of nonresponse, pneumonia or aspergillosis it may be replaced by amphotericin B combined with flucytosine.