RESUMEN
PURPOSE: Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever. METHODS: This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge. RESULTS: We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia. CONCLUSION: In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.
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Fiebre , Mucositis , Neutropenia , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Mucositis/etiología , Neutropenia/etiología , Neutropenia/complicaciones , Anciano , Fiebre/etiología , Adulto , Países Bajos , Índice de Severidad de la Enfermedad , Candidemia/etiología , Candidemia/epidemiología , Neoplasias Hematológicas/complicacionesRESUMEN
AIMS: In Tunisia, limited research has focused on characterizing clinical vancomycin-resistant Enterococcus faecium (VREfm). This study aimed to bridge this knowledge gap by molecular characterization of antimicrobial resistance, determining the genetic elements mediating vancomycin-resistance, and whole-genome sequencing of one representative VREfm isolate. METHODS AND RESULTS: Over 6 years (2011-2016), a total of eighty VREfm isolates responsible for infection or colonization were identified from hospitalized patients, with the incidence rate increasing from 2% in 2011 to 27% in 2016. All of these strains harbored the vanA gene. The screening for antimicrobial resistance genes revealed the predominance of ermB, tetM, and aac(6')-Ie-aph(2'')-Ia genes and 81.2% of strains harbored the Tn1545. Pulsed-field gel electrophoresis identified seven clusters, with two major clusters (belonging to ST117 and ST80) persisting throughout the study period. Seven Tn1546 types were detected, with type VI (truncated transposon) being the most prevalent (57.5%). Whole-genome sequencing revealed a 3 028 373 bp chromosome and five plasmids. Mobile genetic elements and a type I CRISPR-cas locus were identified. Notably, the vanA gene was carried by the classic Tn1546 transposon with ISL3 insertion on a rep17pRUM plasmid. CONCLUSION: A concerning trend in the prevalence of VREfm essentially attributed to CC17 persistence and to horizontal transfer of multiple genetic variants of truncated vanA-Tn1546.
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Elementos Transponibles de ADN , Enterococcus faecium , Variación Genética , Infecciones por Bacterias Grampositivas , Neutropenia , Enterococos Resistentes a la Vancomicina , Secuenciación Completa del Genoma , Humanos , Enterococcus faecium/genética , Enterococcus faecium/aislamiento & purificación , Enterococcus faecium/efectos de los fármacos , Túnez , Enterococos Resistentes a la Vancomicina/genética , Enterococos Resistentes a la Vancomicina/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/epidemiología , Elementos Transponibles de ADN/genética , Neutropenia/microbiología , Neutropenia/complicaciones , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Pruebas de Sensibilidad Microbiana , Electroforesis en Gel de Campo Pulsado , Resistencia a la Vancomicina/genética , Vancomicina/farmacologíaRESUMEN
Phaeohyphomycoses are infections caused by dark-walled dematiaceous fungi. Alternaria and Curvularia are two genera of dematiaceous molds known to cause invasive fungal rhinosinusitis, particularly in immunocompromised patients. Co-infection with two dematiaceous fungi is rarely reported in the literature. This report describes a case of biopsy proven invasive fungal rhinosinusitis with Alternaria spp. and Curvularia spp. co-infection in a neutropenic host. The infection characteristics, microbiologic findings, and treatment are described.
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Alternaria , Ascomicetos , Coinfección , Huésped Inmunocomprometido , Neutropenia , Feohifomicosis , Humanos , Feohifomicosis/microbiología , Feohifomicosis/diagnóstico , Feohifomicosis/complicaciones , Feohifomicosis/tratamiento farmacológico , Coinfección/microbiología , Coinfección/diagnóstico , Alternaria/aislamiento & purificación , Neutropenia/complicaciones , Neutropenia/microbiología , Ascomicetos/aislamiento & purificación , Masculino , Alternariosis/microbiología , Alternariosis/complicaciones , Alternariosis/diagnóstico , Antifúngicos/uso terapéutico , Persona de Mediana Edad , Sinusitis/microbiología , Sinusitis/complicaciones , Sinusitis/diagnóstico , Rinitis/microbiología , Rinitis/complicacionesRESUMEN
PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.
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Antibacterianos , Bacteriemia , Infecciones por Enterobacteriaceae , Neutropenia , Humanos , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Bacteriemia/mortalidad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Neutropenia/complicaciones , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/mortalidad , Infecciones por Enterobacteriaceae/microbiología , Adulto , Anciano , Enterobacteriaceae/efectos de los fármacos , Resultado del Tratamiento , Tiempo de Internación , Neoplasias Hematológicas/complicaciones , Adulto JovenRESUMEN
Introduction. Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have the highest likelihood of benefiting from prophylactic antimicrobials is important for antimicrobial stewardship (AMS).Hypothesis. We aimed to identify groups of HCT recipients that have the highest likelihood of benefiting from prophylactic fluroquinolones.Methods. All admissions for HCT in a tertiary centre between January 2020 and December 2022 (N = 400) were retrospectively studied. Allogeneic HCT (allo-HCT) recipients had prophylaxis with ciprofloxacin during the chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. Bacteraemias were recorded when non-contaminant bacterial pathogens were isolated in blood cultures.Results. Allo-HCT was performed for 43.3â% (173/400) of patients and auto-HCT was performed for 56.7â% (227/400). A bacteraemia was documented in 28.3â% (113/400) of cases. Allo-HCT recipients were more likely to have a Gram-positive bacteraemia (20.8%, 36/173, vs 10.1%, 23/227, P = 0.03), while a difference was not observed for Gram-negative bacteraemias (18.5%, 32/173 vs 18.1%, 41/227, P = 0.91). Among auto-HCT recipients not receiving ciprofloxacin prophylaxis, patients with germ cell tumours had the highest probability (P for trend 0.09) of recording any bacteraemia (43.5%, 10/23) followed by patients with lymphomas (32.5%, 13/40), other auto-HCT indications (22.2%, 2/9), multiple myeloma (22.1%, 29/131) and multiple sclerosis (12.5%, 3/24). The higher number of bacteraemias in patients with germ cell tumours was primarily driven by Gram-negative pathogens.Conclusions. Ciprofloxacin prophylaxis was associated with a reduced incidence of Gram-negative bacteraemias in allo-HCT recipients. Auto-HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of bacteraemias and represent a possible target group for this intervention.
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Antibacterianos , Profilaxis Antibiótica , Bacteriemia , Ciprofloxacina , Trasplante de Células Madre Hematopoyéticas , Neoplasias de Células Germinales y Embrionarias , Humanos , Ciprofloxacina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Estudios Retrospectivos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Persona de Mediana Edad , Femenino , Adulto , Profilaxis Antibiótica/métodos , Antibacterianos/uso terapéutico , Bacteriemia/prevención & control , Bacteriemia/microbiología , Anciano , Adulto Joven , Neutropenia/complicaciones , Programas de Optimización del Uso de los Antimicrobianos , AdolescenteRESUMEN
BACKGROUND: Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting. There is a paucity of data describing the risk of IE in patients with hematologic malignancy who develop bacteremia while neutropenic. METHODS: Adult patients on the hematology ward from January 2018 to December 2020 with hematologic malignancy and bacteremia were evaluated retrospectively for endocarditis by applying the 2023 Duke-ISCVID criteria. Charts of possible cases were evaluated 90 days after the initial BSI for new infectious complications that could indicate missed IE. Descriptive statistics compared patients admitted for hematopoietic stem cell transplantation (HSCT) to those admitted for alternative reasons (non-HSCT). RESULTS: Among the 1005 positive blood cultures initially identified, there were 66 episodes in 65 patients with hematologic malignancy and at least grade 3 neutropenia for a mean duration of 11.4 days during their admission. Transthoracic echocardiography (TTE) was performed in 34.8% of BSIs, and transesophageal echocardiography (TEE) in 6.1%. There were no new infectious complications in possible cases 90 days after their initial BSI. No cases of endocarditis were identified. CONCLUSIONS: Endocarditis is rare amongst patients with hematologic malignancy, bacteremia, and neutropenia, and no cases were identified in this cohort. The use of routine TTE in this setting seems unwarranted, and the addition of TEE is unlikely to improve patient-centered outcomes.
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Bacteriemia , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Neutropenia , Humanos , Neutropenia/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hematológicas/complicaciones , Estudios Retrospectivos , Bacteriemia/microbiología , Bacteriemia/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Endocarditis/microbiología , Endocarditis/complicaciones , Anciano , Ecocardiografía , Ecocardiografía TransesofágicaRESUMEN
Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer ß-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.
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Anfotericina B , Antifúngicos , Glicósidos , Mucormicosis , Neutropenia , Triterpenos , Animales , Anfotericina B/uso terapéutico , Anfotericina B/farmacología , Mucormicosis/tratamiento farmacológico , Ratones , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Triterpenos/farmacología , Triterpenos/uso terapéutico , Neutropenia/tratamiento farmacológico , Neutropenia/complicaciones , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Rhizopus/efectos de los fármacos , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/microbiología , Mucor/efectos de los fármacos , Triazoles/uso terapéutico , Triazoles/farmacologíaRESUMEN
Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in ELANE, impacting neutrophil maturation and leading to high risk of life-threatening infections. Most patients with ELANE-mutant SCN can achieve safe neutrophil counts with chronic Granulocyte-Colony Stimulating Factor (G-CSF). However, up to 10% of patients have neutropenia refractory to G-CSF and require allogeneic stem cell transplant. Traditional conditioning for these patients includes busulfan and cyclophosphamide which is associated with significant toxicities. We present five patients with SCN without myeloid malignancy transplanted using a reduced toxicity regimen of busulfan, fludarabine and thymoglobulin. 5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. All patients had MSDs and no evidence of MDS. Conditioning consisted of PK-adjusted busulfan, fludarabine, and thymoglobulin, with calcineurin inhibitor and mycophenolate mofetil GVHD prophylaxis. With median follow-up of 48.4 months, overall and event-free survival were 100%. There was no acute GVHD and one instance of chronic limited GVHD. Patients exhibited >95% donor myeloid chimerism at 5 years post-BMT. Two patients experienced CMV reactivation without end-organ disease, and no other viral reactivation or significant infections occurred. MSD-BMT with reduced toxicity myeloablation for SCN provides excellent outcomes while minimizing toxicity. These data suggest that busulfan, fludarabine, and ATG can be considered an efficacious, low-toxicity standard of care regimen for patients with SCN undergoing MSD-BMT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Neutropenia , Neutropenia/congénito , Humanos , Niño , Trasplante de Médula Ósea/efectos adversos , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Busulfano/uso terapéutico , Busulfano/farmacología , Trasplante de Células Madre Hematopoyéticas/métodos , Hermanos , Estudios Prospectivos , Neutropenia/complicaciones , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Factor Estimulante de Colonias de Granulocitos/uso terapéuticoRESUMEN
BACKGROUND: Stenotrophomonas maltophilia (S. maltophilia) is a nosocomial pathogen causing life-threatening invasive infections with a high mortality rate in some patient populations, especially those who are severely ill or immunocompromised. There is a need for data on mortality in patients with S. maltophilia bacteremia. OBJECTIVE: In this meta-analysis, we aimed to investigate risk factors for mortality in S. maltophilia bacteremia. METHODS: Studies comparing patients who died from S. maltophilia bacteremia with patients who survived were considered for inclusion. Studies were included if they reported one or more risk factors for mortality. Mortality risk factors included clinical predisposing factors, predisposing comorbidities and appropriateness of antibiotic therapy. RESULTS: Nineteen studies with 1248 patients were included in the meta-analysis. Five hundred and six (40.5%) patients died. The following risk factors for mortality were identified: ICU admission, septic shock, need for mechanical ventilation, indwelling central venous catheter, neutropenia, comorbid hematological malignancies, chronic kidney disease, inappropriate antimicrobial therapy and prior antibiotic use. CONCLUSIONS: Appropriate antimicrobial therapy had a protective effect against mortality in S. maltophilia bacteremia. Indwelling central venous catheter, neutropenia, hematological malignancies and chronic kidney disease were also risk factors for mortality.
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Bacteriemia , Infección Hospitalaria , Infecciones por Bacterias Gramnegativas , Neoplasias Hematológicas , Neutropenia , Insuficiencia Renal Crónica , Stenotrophomonas maltophilia/inmunología , Humanos , Estudios Retrospectivos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Factores de Riesgo , Antibacterianos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Infección Hospitalaria/tratamiento farmacológico , Neutropenia/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
Hematologic abnormalities are common manifestations of SLE, although neutropenia is observed less frequently and is not included in the classification criteria. Nonetheless, neutropenia is a risk factor for infections, especially those caused by bacteria or fungi. We aimed to evaluate the impact of neutropenia in SLE through a systematic investigation of all infections in a large cohort of well-characterized patients, focusing on neutropenia, lymphopenia, and hypocomplementemia. Longitudinal clinical and laboratory parameters obtained at visits to the Rheumatology Unit, Linköping University Hospital, and linked data on all forms of healthcare utilization for all the subjects included in our regional SLE register during 2008-2022 were assessed. Data regarding confirmed infections were retrieved from the medical records. Overall, 333 patients were included and monitored during 3,088 visits to a rheumatologist during the study period. In total, 918 infections were identified, and 94 occasions of neutropenia (ANC < 1.5 × 109/L) were detected in 40 subjects (12%). Thirty neutropenic episodes in 15 patients occurred in association with infections, of which 13 (43%) required in-hospital care, 4 (13%) needed intensive care, and 1 (3%) resulted in death. Bayesian analysis showed that patients with ≥ 1 occasion of neutropenia were more likely to experience one or more infections (OR = 2.05; probability of association [POA] = 96%). Both invasiveness (OR = 7.08; POA = 98%) and severity (OR = 2.85; POA = 96%) of the infections were significantly associated with the present neutropenia. Infections are common among Swedish SLE patients, 12% of whom show neutropenia over time. Importantly, neutropenia is linked to both the invasiveness and severity of infections. Awareness of the risks of severe infections in neutropenic patients is crucial to tailor therapies to prevent severe illness and death.
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Lupus Eritematoso Sistémico , Neutropenia , Humanos , Prevalencia , Suecia/epidemiología , Teorema de Bayes , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Neutropenia/epidemiología , Neutropenia/complicacionesRESUMEN
PURPOSE: Sepsis is the main cause of nonrelapse mortality, and there are no published data on applicability of supportive care protocols from high-income countries such as Sri Lanka. The aim of the study was to investigate management and mortality of neutropenic episodes among Hemato-Oncology patients. MATERIALS AND METHODS: Retrospective analysis of clinical characteristics, management, morbidity, and mortality of neutropenic Hemato-Oncology patients presented to the Lanka Hospital Blood Cancer Centre from January 1, 2019 to December 31, 2019 was performed. RESULTS: A total of 169 neutropenic episodes were identified; 115 (68%) of such episodes were related to chemotherapy. Acute leukemia, lymphoproliferative disorders, and plasma cell disorders accounted for 23%, 69%, and 8% of patients, respectively. The median age of patients who had sepsis was 56 years, whereas that of those who had no sepsis was 53 years (P = .49). The median time to neutropenia was 9 days for those in the sepsis group compared with 8 days in the group that had no sepsis (0.64). The median neutrophil count in the group that had sepsis was 0.06, whereas it was 0.69 in the group that had no sepsis (P ≤ .05). The median time to commencement of antibiotics was 20 minutes. CONCLUSION: To our knowledge, this is the only documented study related to outcome and successful applicability of western supportive care protocols to Sri Lankan patients with neutropenia. In this study, we have shown that neutropenic sepsis can be successfully managed in the setting of limited resources with service development, following guidelines and staff training.
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Neoplasias Hematológicas , Neoplasias , Neutropenia , Sepsis , Humanos , Persona de Mediana Edad , Sri Lanka/epidemiología , Estudios Retrospectivos , Configuración de Recursos Limitados , Neoplasias/complicaciones , Sepsis/terapia , Sepsis/tratamiento farmacológico , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Neutropenia/inducido químicamente , Neutropenia/diagnóstico , Neutropenia/complicacionesRESUMEN
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) was associated with potentially life-threatening complications. Among patients supported by extracorporeal membrane oxygenation (ECMO), those who underwent HSCT had a worse prognosis than those who did not. Advances in HSCT and critical care management have improved the prognosis of ECMO-supported HSCT patients. CASE: The patient in the remission stage of lymphoma after 22 months of allogeneic hematopoietic stem cell transplantation, suffered from ARDS, severe neutropenia, thrombocytopenia, and long-term COVID-19. We evaluated the benefits and risks of ECMO for the patient, including the possibility of being free from ECMO, the status of malignancy, the interval from HSCT to ARDS, the function of the graft, the amount of organ failure, and the comorbidities. ECMO was ultimately used to save his life. CONCLUSIONS: We did not advocate for the general use of ECMO in HSCT patients and we believed that highly selected patients, with well-controlled tumors, few comorbidities, and fewer risk factors for death, tended to benefit from ECMO with well ICU management.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Neutropenia , Síndrome de Dificultad Respiratoria , Trombocitopenia , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , COVID-19/terapia , COVID-19/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Trombocitopenia/terapia , Trombocitopenia/complicaciones , Neutropenia/complicaciones , Neutropenia/terapia , Neoplasias/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Although mucormycosis is an important cause of morbidity and mortality in children with cancer, our understanding of the typical characteristics of these infections is incomplete. We reviewed all cases of mucormycosis diagnosed at a single pediatric cancer center over 5 decades to identify the clinical features of mucormycosis in pediatric oncology patients and to identify risk factors for mortality. There were 44 cases of mucormycosis diagnosed between 1970-2019. Most patients (89%) had hematological malignancies and a history of prolonged and severe neutropenia (91%). In this series, hyperglycemia and exposure to corticosteroids were common. Pulmonary (36%) and disseminated infections (32%) were most common; rhino-orbital-cerebral infections were relatively infrequent (11%). Rhizopus spp. was the most common etiological agent (40%) followed by Mucor spp. (31%), and Cunninghamella spp. (19%). Overall mortality was 44% and 51% and attributable mortality was 39% and 41% at the end of antifungal therapy and end of follow up, respectively. Attributable mortality fell to 18% in 2010-2019, from 58-60% in previous decades; adjunctive surgery was associated with decreased mortality. Mortality remains unacceptably high despite aggressive antifungal therapy and adjunctive surgery, suggesting novel therapeutic strategies are needed.
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Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Mucormicosis , Neutropenia , Humanos , Niño , Mucormicosis/diagnóstico , Antifúngicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios de Cohortes , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Neutropenia/complicacionesRESUMEN
Despite modern antimicrobial treatments, bacterial and fungal infections remain major complications in neutropenic patients. Granulocyte transfusions appeared in the 1950s-60s but first clinical trials were limited by the difficulty of transfusing enough viable granulocytes. The refinement of apheresis techniques as well as donor pretreatment with corticosteroids and/or granulocyte colony-stimulating growth factor (G-CSF) have led to improved collection yield. Despite this, uncertainties remain regarding the real clinical usefulness of granulocyte transfusions. Few studies have been carried out since the G-CSF era and the quality of scientific evidence remains low, mainly because of small case series. The largest prospective randomized controlled study published so far failed to demonstrate any benefit of therapeutic granulocyte transfusions on mortality or infection control. However, the quality of this trial is limited due to its low statistical power (insufficient patient recruitment). Moreover, granulocyte transfusions are complex procedures, burdensome for the donor, expensive and associated with a significant risk of adverse effects. Therefore, the current place of granulocyte transfusion in clinical practice is guided by the experience of each center. With the increasing emergence of multi-resistant germs, it is likely that granulocyte transfusion will become interesting in the coming years. Standardization of collection and administration procedures and the final proof of their (in)effectiveness will remain the challenges for the future.
En dépit des traitements antimicrobiens modernes, les infections bactériennes et fongiques restent des complications majeures chez les patients neutropéniques. Les transfusions de granulocytes (TG) sont apparues dans les années 1950-1960, mais les premiers essais cliniques ont été limités par la difficulté de transfuser un nombre suffisant de granulocytes viables. Le perfectionnement des techniques d'aphérèse ainsi que la stimulation pharmacologique du donneur par corticostéroïdes et/ou facteur de croissance granulocytaire (G-CSF) ont permis d'améliorer le rendement des collectes. Malgré cela, des incertitudes subsistent quant à la réelle utilité clinique des TG. Peu d'études ont été réalisées depuis l'ère du G-CSF et la qualité des preuves scientifiques reste faible. La plus large étude prospective contrôlée randomisée publiée à ce jour n'a pas pu démontrer de bénéfice des TG sur la mortalité ou le contrôle des infections. Cependant, la valeur de cet essai est limitée en raison de sa faible puissance statistique (recrutement de patients insuffisant). De plus, les TG sont des procédures complexes, lourdes pour le donneur, coûteuses et associées à un risque non négligeable d'effets indésirables. Par conséquent, la place actuelle des TG dans la pratique clinique est principalement guidée par l'expérience de chaque centre. Avec l'émergence croissante de germes multirésistants, il est probable que les TG suscitent à nouveau l'intérêt dans les années à venir. Les défis seront de parvenir à une détermination définitive de leur (in)efficacité et d'uniformiser les procédures de collecte et d'administration.
Asunto(s)
Neutropenia , Humanos , Neutropenia/complicaciones , Neutropenia/terapia , Estudios Prospectivos , Donantes de Tejidos , Granulocitos , Factor Estimulante de Colonias de Granulocitos/uso terapéuticoRESUMEN
Cytopenia is a common finding in patients admitted to internal medicine wards and the clinical workup may be long and time-consuming. In this single-center observational study, we analyzed a series of 151 inpatients who received hematologist referral due to cytopenia observed during hospital admission. Patients were mainly elderly (median 71 years, 15-96) and 87% had at least one comorbidity. Anemia was the most common cytopenia (91%), followed by thrombocytopenia (51%), and neutropenia (22%); 73 (48%) patients had a bicytopenia and 5 (3%) pancytopenia. Cytopenias were mainly severe, 66% of cases required RBC transfusions, and 21% platelet pools. During a median hospital stay of 15 days (1-166), 53 subjects (35%) received a hematologic discharge diagnosis, whilst the two-thirds had secondary cytopenia mainly due to associated comorbidities. Only about 34% of 2,728 diagnostic tests performed (including laboratory, imaging, and histology) clearly informed the discharge diagnosis in this heterogenous setting. Specifically, bone-marrow evaluation indicated in 46 (30%) patients, was diagnostic in 32 (69.6%). Eleven percent of patients died due to progression of the oncohematologic disease (29%), sepsis (24%), and solid tumor progression (24%). In conclusion, cytopenias in the internal medicine setting are mainly severe, more frequently secondary to associated comorbidities (2/3 of patients) and deserve proper workup before second/third-level tests (immune-hematological assays and CT scan or PET and bone-marrow evaluation, respectively).
Asunto(s)
Medicina Interna , Pancitopenia , Trombocitopenia , Humanos , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Medicina Interna/métodos , Persona de Mediana Edad , Adulto , Anemia/etiología , Adolescente , Neutropenia/complicaciones , CitopeniaRESUMEN
Neutropenia can be caused by a variety of congenital and acquired factors, with Chemotherapy-induced myelosuppression being the most common cause. Neutropenia significantly affects oral health, leading to the manifestation of oral lesions such as ulcers, fungal and viral infections, and mucositis. This study aims to investigate oral lesions in patients with hematological malignancies who developed neutropenia after chemotherapy. This cross-sectional study included 50 patients with hematological malignancies. The participants were divided into 2 groups: the first group consisted of 25 patients with hematological malignancies who developed chemotherapy-induced neutropenia and the second group consisted of 25 patients with hematological malignancies who did not develop chemotherapy-induced neutropenia. Patients were assigned to one of the groups based on the absolute neutrophil count (ANC). Full oral clinical examination was performed to determine the presence of oral lesions. In the Chemotherapy-Induced Neutropenia group, the most common lesion was ulceration, observed in 12 patients (48%). Fungal infections were the second most common, present in 5 patients (20%), followed by viral infections in 4 patients (15%), and mucositis, which occurred in a single patient (4%). A statistically significant association was found between neutropenia and the presence of oral ulcers (P valueâ =â .015). In contrast, in the Chemotherapy group, oral changes were less frequent. Fungal infections were the most common, occurring in 4 patients (15%), followed by oral mucositis in 3 patients (12%). Ulceration and viral infections were the least common, each observed in 1 patient (4%). The frequency of various forms of oral ulcers increases with the severity of neutropenia. However, there was no significant increase in other oral lesions in patients with neutropenia.
Asunto(s)
Antineoplásicos , Neoplasias Hematológicas , Mucositis , Micosis , Neutropenia , Úlceras Bucales , Virosis , Humanos , Estudios Transversales , Mucositis/inducido químicamente , Úlceras Bucales/tratamiento farmacológico , Siria , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Neutropenia/complicaciones , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Micosis/tratamiento farmacológico , Antineoplásicos/efectos adversos , Virosis/complicacionesRESUMEN
AIM: WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome is a rare combined primary immunodeficiency disease caused by gain-of-function (GOF) mutations in the chemokine receptor CXCR4 and includes severe neutropenia as a common feature. Neutropenia is a known risk factor for periodontitis; however, a detailed periodontal evaluation of a WHIM syndrome cohort is lacking. This study aimed to establish the evidence base for the periodontal status of patients with WHIM syndrome. MATERIALS AND METHODS: Twenty-two adult WHIM syndrome patients and 22 age- and gender-matched healthy volunteers (HVs) were evaluated through a comprehensive medical and periodontal examination. A mouse model of WHIM syndrome was assessed for susceptibility to naturally progressing or inducible periodontitis. RESULTS: Fourteen patients with WHIM syndrome (63.6%) and one HV (4.5%) were diagnosed with Stage III/IV periodontitis. No WHIM patient presented with the early onset, dramatic clinical phenotypes typically associated with genetic forms of neutropenia. Age, but not the specific CXCR4 mutation or absolute neutrophil count, was associated with periodontitis severity in the WHIM cohort. Mice with a Cxcr4 GOF mutation did not exhibit increased alveolar bone loss in spontaneous or ligature-induced periodontitis. CONCLUSIONS: Overall, WHIM syndrome patients presented with an increased severity of periodontitis despite past and ongoing neutrophil mobilization treatments. GOF mutations in CXCR4 may be a risk factor for periodontitis in humans.
Asunto(s)
Síndromes de Inmunodeficiencia , Neutropenia , Enfermedades Periodontales , Periodontitis , Enfermedades de Inmunodeficiencia Primaria , Verrugas , Adulto , Humanos , Animales , Ratones , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/complicaciones , Enfermedades de Inmunodeficiencia Primaria/genética , Verrugas/genética , Verrugas/terapia , Neutropenia/complicaciones , Neutropenia/genética , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/genética , Periodontitis/complicaciones , Periodontitis/genéticaRESUMEN
Background and Objectives: There is a need for information regarding the clinical picture of hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in patients with hematologic malignancies. In this study, we aimed to investigate the risk factors associated with hemorrhagic pneumonia caused by Stenotrophomonas maltophilia. Materials and Methods: A review of the clinical picture of hemorrhagic pneumonia based on reported cases in the literature was performed. In addition, patients with hematologic malignancies who had a Stenotrophomonas maltophilia infection were included in the meta-analysis to evaluate risk factors for hemorrhagic pneumonia. Results: A total of 91 patients had hemorrhagic pneumonia. Acute myeloid leukemia was present in 57 patients (62.6%). Those with bacteremia accounted for 94%, while those with neutropenia accounted for 95% and those with thrombocytopenia accounted for 86.7%. Hemorrhagic pneumonia was a risk factor for mortality of Stenotrophomonas maltophilia infection in patients with hematologic malignancies. Neutropenia and thrombocytopenia were identified as risk factors for hemorrhagic pneumonia. Conclusions: Stenotrophomonas maltophilia bacteremia with hemorrhagic pneumonia in patients with hematologic malignancies is a situation with rapid development and high mortality. Neutropenia and thrombocytopenia were risk factors for hemorrhagic pneumonia in patients with hematologic malignancies and with Stenotrophomonas maltophilia bacteremia; thus, these patients should be managed with caution.
Asunto(s)
Infecciones por Bacterias Gramnegativas , Neoplasias Hematológicas , Neutropenia , Neumonía , Stenotrophomonas maltophilia , Trombocitopenia , Humanos , Neutropenia/complicaciones , Neoplasias Hematológicas/complicacionesRESUMEN
BACKGROUND: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described. METHODS: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations. RESULTS: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed. CONCLUSIONS: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted.