RESUMEN
Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS-CoV-2 infection in immunocompromised patients, particularly in the management of persistent SARS-CoV-2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti-CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS-CoV-2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.
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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Huésped Inmunocomprometido , SARS-CoV-2 , Humanos , Antivirales/uso terapéutico , SARS-CoV-2/inmunología , COVID-19/inmunología , Quimioterapia Combinada , Anticuerpos Neutralizantes/uso terapéuticoRESUMEN
BACKGROUND: Sepsis occurs in 12-27% of patients with haematological malignancy within a year of diagnosis. Sepsis mortality has improved in non-cancer patients in the last two decades, but longitudinal trends in patients with haematological malignancy are not well characterised. We aimed to compare outcomes, including temporal changes, in patients with and without a haematological malignancy admitted to ICU with a primary diagnosis of sepsis in Australia and New Zealand over the past two decades. METHODS: We performed a retrospective cohort study of 282,627 patients with a primary intensive care unit (ICU) admission diagnosis of sepsis including 17,313 patients with haematological malignancy, admitted to 216 intensive care units (ICUs) in Australia or New Zealand between January 2000 and December 2022. Annual crude and adjusted in-hospital mortality were reported. Risk factors for in-hospital mortality were determined using a mixed methods logistic regression model and were used to calculate annual changes in mortality. RESULTS: In-hospital sepsis mortality decreased in patients with haematological malignancy, from 55.6% (95% CI 46.5-64.6%) in 2000 to 23.1% (95% CI 20.8-25.5%) in 2021. In patients without haematological malignancy mortality decreased from 33.1% (95% CI 31.3-35.1%) to 14.4% (95% CI 13.8-14.8%). This decrease remained significant after adjusting for mortality predictors including age, SOFA score and comorbidities, as estimated by adjusted annual odds of in-hospital death. The reduction in odds of death was of greater magnitude in patients with haematological malignancy than those without (OR 0.954, 95% CI 0.947-0.961 vs. OR 0.968, 95% CI 0.966-0.971, p < 0.001). However, absolute risk of in-hospital mortality remained higher in patients with haematological malignancy. Older age, higher SOFA score, presence of comorbidities, and mechanical ventilation were associated with increased mortality. Leukopenia (white cell count < 1.0 × 109 cells/L) was not associated with increased mortality in patients with haematological malignancy (p = 0.60). CONCLUSIONS: Sepsis mortality has improved in patients with haematological malignancy admitted to ICU. However, mortality remains higher in patients with haematological malignancy than those without.
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Neoplasias Hematológicas , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Sepsis , Humanos , Sepsis/mortalidad , Neoplasias Hematológicas/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios Retrospectivos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Nueva Zelanda/epidemiología , Estudios de Cohortes , Mortalidad Hospitalaria/tendencias , Australia/epidemiología , Adulto , Modelos Logísticos , Factores de Riesgo , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: The infection risk in patients receiving ibrutinib, idelalisib or venetoclax for chronic lymphocytic leukaemia (CLL) or B-cell lymphoma treated outside of clinical trials is incompletely defined. We sought to identify the severe infection rate and associated risk factors in a 'real-world' cohort. METHODS: We conducted a retrospective cohort study of adult patients with CLL or lymphoma treated with ibrutinib, idelalisib or venetoclax. RESULTS: Of 67 patients identified (ibrutinib n = 53, idelalisib n = 8 and venetoclax n = 6), 32 (48%) experienced severe infection. Severe infection occurred at a rate of 65 infections per 100 person-years, with a median of 17.8 months of therapy. Median time to first infection (IQR) was 5.4 months (1.4-15.9). Poor baseline Eastern Cooperative Oncology Group (ECOG) performance status and high Charlson Comorbidity Index (CCI) score associated with increased risk of severe infection [hazard ratios (95% CI) 1.57 (1.07-2.31, p = .018) and 1.3 (1.05-1.62, p = .016) respectively]. CONCLUSION: The severe infection rate for patients receiving ibrutinib, idelalisib or venetoclax for lymphoma and CLL exceeded those reported in clinical trials. Patients with poor ECOG or high CCI should be closely monitored for early signs of infection and prevention strategies actively pursued. Further prospective research is required to define optimal antimicrobial prophylaxis recommendations.
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Leucemia Linfocítica Crónica de Células B , Linfoma de Células B , Adulto , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Estudios Retrospectivos , Linfoma de Células B/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Coronavirus disease 2019 (COVID-19) in immunocompromised patients can lead to severe and prolonged illness. Data are limited with regard to management of COVID-19 in this setting, particularly in persistent or recrudescent infection. The authors conducted an online survey among infectious diseases doctors to determine current approaches to treatment across Australasia. There was marked variability in responses relating to the diagnostic modalities and use of antiviral agents in patients with immunocompromise, highlighting the need for high-quality studies to guide treatment decisions in this group.
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COVID-19 , Humanos , Antivirales/uso terapéutico , Huésped Inmunocomprometido , Encuestas y Cuestionarios , Australasia/epidemiologíaRESUMEN
OBJECTIVE: To identify barriers and enablers to COVID-19 vaccination in renal transplant recipients who are undecided about vaccination. METHODS: An online survey was distributed to 876 adult kidney transplant recipients at a tertiary referral service, who had not been vaccinated against COVID-19. The survey assessed willingness to be vaccinated, attitudes toward COVID-19 vaccines, and barriers and enablers to proceeding with vaccination. RESULTS: The survey response rate was 54% (473/876). Three hundred and forty-six (73.1%) participants planned to receive vaccination (yes group), 105 (22.2%) were undecided, and 22 (4.7%) refused vaccination. The undecided group were younger but were not different in other demographic characteristics to the yes group. The undecided group were less positive toward (34.29% vs. 91.3%, p < .001) and more concerned about (93.3% vs. 25.1%, p < .001) vaccination than the yes group. Their concerns related to vaccine safety (including harm to their transplant), poor efficacy, and a lack of rigorous testing in transplant recipients. Undecided recipients had received less vaccine-specific information from medical specialists than the yes group. Most undecided participants (95.1%) were willing to proceed with vaccination with appropriate supports. The most desired supports were information and a recommendation to proceed with vaccination from their treating transplant specialist and team. CONCLUSION(S): Concerns about vaccine safety (including harm to transplant), poor vaccine efficacy, and lack of rigorous testing were barriers to vaccine uptake. Most undecided recipients would proceed with vaccination with specific recommendations and vaccine information provided by their transplant specialist/team. These simple interventions can be readily implemented to optimize vaccine uptake.
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COVID-19 , Trasplante de Riñón , Vacunas , Adulto , Actitud , Vacunas contra la COVID-19 , Humanos , Trasplante de Riñón/efectos adversos , SARS-CoV-2 , Receptores de Trasplantes , VacunaciónRESUMEN
Patients with invasive fungal disease (IFD) are at significant risk of morbidity and mortality. A productive partnership between patients, their carers/families, and the multidisciplinary team managing the infection and any underlying conditions, is essential. Sharing information and addressing knowledge gaps are required to ensure those at risk of IFD avoid infection, while those with suspected or confirmed infection optimise their therapy and avoid toxicities. This new addition to the Australian and New Zealand consensus guidelines for the management of IFD and antifungal use in the haematology/oncology setting outlines the key information needs of patients and their carers/families. It specifically addresses risk factor reduction, antifungal agents and adherence, and the risks and benefits of complementary and alternative therapies. Knowledge gaps are also identified to help inform the future research agenda.
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Hematología , Micosis , Antifúngicos/uso terapéutico , Australia/epidemiología , Humanos , Oncología Médica , Micosis/prevención & control , Factores de RiesgoRESUMEN
BACKGROUND: Individuals splenectomised for trauma have lower infection rates than those splenectomised for other conditions. Residual functional splenic tissue (FST) after splenectomy may provide ongoing immunological protection. AIMS: To quantify the prevalence and volume of residual FST post-splenectomy using standard testing. METHODS: Splenectomised adults were recruited from the Spleen Australia clinical registry. Eligible individuals had been splenectomised at least 1 year prior to their visit and resided in Victoria. Splenic function was identified by evaluating Howell-Jolly bodies and IgM memory B cells. A 99m-Technetium-labelled, heat-denatured erythrocyte scintigraphic scan was performed if splenic function was detected. RESULTS: Initially, 75 splenectomised individuals (all cause) were recruited, with a median of 58 years of age and who were splenectomised a median of 14 years previously. The most common indications for splenectomy were trauma (30.7%) and haematological disease (28.0%). Scintigraphy identified FST in nine individuals (12.0%). Eight had been splenectomised for trauma. In this cohort, 34.8% of individuals splenectomised for trauma had residual FST. To explore our findings further, 45 additional individuals were recruited, predominately individuals splenectomised for trauma. Twenty-five individuals completed assessments by December 2018. An additional 11 individuals had FST, of whom 9 had been splenectomised for trauma. Overall, we identified 20 individuals with residual FST. Volumes ranged from 2.2 to 216.0 cc. We saw individuals with accessory spleens and splenotic nodules and an individual with both. Seventeen individuals had been splenectomised for trauma. CONCLUSIONS: Residual FST is commonly seen in individuals splenectomised for trauma. It can present in varying distributions and of varying volume. The clinical significance is unclear.
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Esplenectomía , Enfermedades del Bazo , Adulto , Humanos , Prevalencia , Esplenectomía/efectos adversos , VictoriaRESUMEN
INTRODUCTION: Multimodal interventions (MMI) are frequently used in various healthcare settings to encourage change in healthcare personnel practices and improve patient safety. In 2013, an MMI conducted in an Australian metropolitan ED used clinician champions, guidelines, education sessions and promotional materials to encourage a reduction in unused and inappropriate peripheral intravenous cannulas (PIVC). A 60-day postintervention demonstrated a successful reduction in the number of unused PIVCs without changes in appropriate insertions. We aimed to investigate if this MMI produced a sustained effect in reducing the frequency of unused PIVCs inserted in this ED. METHODS: A single-centre retrospective cohort study of adult patients presenting to the above ED in Victoria, Australia, was conducted in April 2018. A random sample of 380 patients with a PIVC inserted in ED was assessed to determine if the PIVC was used (termed 'Long-term follow-up'). The appropriateness of unused PIVCs was assessed. Our findings were compared with previously collected data in 2013 ('Pre-Intervention' and 'Immediately Post-Intervention') to determine a sustained reduction in the frequency of unused PIVC insertions was achieved. Long-term analysis of the MMI, including the overall frequency of PIVC insertions in ED before and after the MMI, was also collected. RESULTS: In our Long-term follow-up cohort, 101 of 373 (27.1%, 95% CI 22.6% to 31.9%) PIVCs were unused (seven cases excluded). This was significantly lower than the Pre-Intervention cohort (139/376, 37.0%, 95% CI 32.1% to 42.1%). While not significant, the frequency of unused PIVCs in the Post-Intervention cohort was lower in comparison (73/378, 19.3%, 95% CI 15.4% to 23.7%). No significant change in the appropriateness of unused PIVCs was observed between the Post-Intervention and Long-term follow-up. The overall proportion of patients receiving a PIVC has remained low since the MMI. CONCLUSION: An MMI aimed at reducing unused PIVC insertions in ED has been effective in eliciting sustained change. Unused but appropriately inserted PIVCs seem unaffected by the intervention.
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Cateterismo Periférico/normas , Servicio de Urgencia en Hospital/normas , Mejoramiento de la Calidad , Adulto , Anciano , Estudios Controlados Antes y Después , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , VictoriaRESUMEN
The aim of this study was to determine if natural killer cell number (CD3- /CD16± /CD56± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.
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Infecciones por Citomegalovirus/complicaciones , Trasplante de Riñón/efectos adversos , Células Asesinas Naturales/citología , Receptores de Trasplantes , Área Bajo la Curva , Citomegalovirus , Infecciones por Citomegalovirus/sangre , Femenino , Humanos , Inmunosupresores/farmacología , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Curva ROC , Análisis de Regresión , RiesgoRESUMEN
BACKGROUND: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. METHODS: We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. RESULTS: Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). CONCLUSION: Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.
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Infecciones/diagnóstico , Trasplante de Riñón/efectos adversos , Receptores de Trasplantes , Biomarcadores/análisis , Linfocitos T CD4-Positivos/inmunología , Femenino , Humanos , Inmunoglobulinas/análisis , Terapia de Inmunosupresión , Trasplante de Riñón/estadística & datos numéricos , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Factores de RiesgoRESUMEN
Cytomegalovirus (CMV) infection represents a major cause of morbidity and mortality in immunocompromised hosts. Skin ulceration is a rare manifestation of tissue-invasive disease, with the anogenital region being the most typical site of involvement. We present a case of CMV ulceration on the right leg occurring 16 years following renal transplantation and 1 year after adjuvant radiotherapy for a Marjolin ulcer at this site. We suggest radiotherapy may provide a mechanism for local reactivation of the virus in the skin of seropositive patients.
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Carcinoma de Células Escamosas/radioterapia , Infecciones por Citomegalovirus/diagnóstico , Úlcera de la Pierna/virología , Neoplasias Cutáneas/radioterapia , Receptores de Trasplantes , Anciano , Anticuerpos Antivirales/sangre , Carcinoma de Células Escamosas/cirugía , Cicatriz/patología , Citomegalovirus/inmunología , Humanos , Huésped Inmunocomprometido , Inmunoglobulina G/sangre , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Masculino , Radioterapia Adyuvante , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: Conjugated pneumococcal vaccine is recommended for kidney transplant recipients, however, their immunogenicity and potential to trigger allograft rejection though generation of de novo anti-human leukocyte antigen antibodies has not been well studied. METHODS: Clinically stable kidney transplant recipients participated in a prospective cohort study and received a single dose of 13-valent conjugate pneumococcal vaccine. Anti-pneumococcal IgG was measured for the 13 vaccine serotypes pre and post vaccination and functional anti-pneumococcal IgG for 4 serotypes post vaccination. Anti-human leukocyte antigen antibodies antibodies were measured before and after vaccination. Kidney transplant recipients were followed clinically for 12 months for episodes of allograft rejection or invasive pneumococcal disease. RESULTS: Forty-five kidney transplant recipients participated. Median days between pre and post vaccination serology was 27 (range 21-59). Post vaccination, there was a median 1.1 to 1.7-fold increase in anti-pneumococcal IgG antibody concentrations for all 13 serotypes. Kidney transplant recipients displayed a functional antibody titer ≥1:8 for a median of 3 of the 4 serotypes. Post vaccination, there were no de novo anti-human leukocyte antigen antibodies, no episodes of biopsy proven rejection or invasive pneumococcal disease. CONCLUSION: A single dose of 13-valent conjugate pneumococcal vaccine elicits increased titers and breadth of functional anti-pneumococcal antibodies in kidney transplant recipients without stimulating rejection or donor-specific antibodies.
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Trasplante de Riñón , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/efectos adversos , Vacunas Neumococicas/farmacología , Anticuerpos Antibacterianos/sangre , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , VacunaciónRESUMEN
INTRODUCTION: The impact of medical student psychological distress on academic performance has not been systematically examined. This study provided an opportunity to closely examine the potential impacts of workplace and study related stress factors on student's psychological distress and their academic performance during their first clinical year. METHODS: This one-year prospective cohort study was performed at a tertiary hospital based medical school in Melbourne, Australia. Students completed a questionnaire at three time points during the year. The questionnaire included the validated Kessler psychological distress scale (K10) and the General Health Questionnaire-28 (GHQ-28), as well as items about sources of workplace stress. Academic outcome scores were aggregated and correlated with questionnaire results. RESULTS: One hundred and twenty six students participated; 126 (94.7%), 102 (76.7%), and 99 (74.4%) at time points one, two, and three, respectively. 33.1% reported psychological distress at time point one, increasing to 47.4% at time point three. There was no correlation between the K10 scores and academic performance. There was weak negative correlation between the GHQ-28 at time point three and academic performance. Keeping up to date with knowledge, need to do well and fear of negative feedback were the most common workplace stress factors. CONCLUSIONS: Poor correlation was noted between psychological distress and academic performance.
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Rendimiento Académico/psicología , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Estudiantes de Medicina/psicología , Adulto , Femenino , Humanos , Masculino , Estudios Prospectivos , Facultades de Medicina , Encuestas y Cuestionarios , Victoria/epidemiología , Adulto JovenRESUMEN
A cross-sectional survey of 265 adult patients with haematological malignancy, haemoglobinopathy or human immunodeficiency virus was performed to determine the potential risk of infection from animal exposures. One hundred and thirty-seven (52%) owned an animal; the majority were dogs (74%) and cats (39%), but 14% owned birds and 3% reptiles. Eighty percent engaged in behaviour with their animals that potentially put them at risk of zoonotic infections. The most frequent behaviours were picking up animal faeces 72 (52%), cleaning animal areas 69 (50%) and allowing animals to sleep in the same bed 51 (37%). Twenty-eight percent allowed the animal to lick their face. Of all patients, 80 (30%) had been bitten or scratched by an animal. Only 16% of those who owned pets could recall receiving education regarding safe behaviours around animals. These immunocompromised patients are at risk of infection through exposure to pets. Our study highlights the need for increased education of patients regarding how to remain safe around their pets.
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Conocimientos, Actitudes y Práctica en Salud , Huésped Inmunocomprometido , Educación del Paciente como Asunto , Mascotas/microbiología , Mascotas/virología , Zoonosis/prevención & control , Zoonosis/transmisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Australia , Aves/microbiología , Aves/virología , Gatos , Estudios Transversales , Perros , Femenino , Infecciones por VIH/inmunología , Neoplasias Hematológicas/inmunología , Hemoglobinopatías/inmunología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto Joven , Zoonosis/inmunologíaAsunto(s)
Pruebas Diagnósticas de Rutina/métodos , Lupus Eritematoso Sistémico/diagnóstico , Bazo/fisiopatología , Enfermedades del Bazo/diagnóstico , Australia/epidemiología , Inclusiones Eritrocíticas/inmunología , Humanos , Programas de Inmunización/normas , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Tamizaje Masivo/normas , Estudios Prospectivos , Sepsis/epidemiología , Enfermedades del Bazo/complicaciones , Enfermedades del Bazo/prevención & control , Trombosis/epidemiologíaRESUMEN
Two cases of disseminated enteroviral infection occurred in patients who received the CD20 monoclonal antibody obinutuzumab. Clinical features included hepatitis, edema, and a dermatomyositis-like syndrome. These manifestations may be unfamiliar to clinicians and are possibly responsive to intravenous immunoglobulin. Clinicians should remain vigilant for enteroviral infections in patients receiving obinutuzumab.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Infecciones por Enterovirus/diagnóstico , Meningoencefalitis/diagnóstico , Adulto , Diagnóstico Diferencial , Infecciones por Enterovirus/etiología , Femenino , Humanos , Linfoma/tratamiento farmacológico , Meningoencefalitis/etiología , Persona de Mediana EdadRESUMEN
We report a case of Acanthamoeba encephalitis diagnosed from an antemortem brain biopsy specimen, where the organism was first isolated in mycobacterial liquid medium and first identified by using a sequence generated by a commercial panfungal sequencing assay. We correlate susceptibility results with clinical outcome.
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Acanthamoeba/clasificación , Acanthamoeba/aislamiento & purificación , Encéfalo/parasitología , Infecciones Protozoarias del Sistema Nervioso Central/diagnóstico , Genotipo , Acanthamoeba/genética , Anciano , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Infecciones Protozoarias del Sistema Nervioso Central/parasitología , ADN Protozoario/química , ADN Protozoario/genética , Histocitoquímica , Humanos , Imagen por Resonancia Magnética , Masculino , Técnicas Microbiológicas , Microscopía , Datos de Secuencia Molecular , Radiografía , Análisis de Secuencia de ADNAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Infecciones Fúngicas Invasoras/etiología , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Scedosporium/aislamiento & purificación , Antifúngicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Farmacorresistencia Fúngica Múltiple , Sustitución de Medicamentos , Resultado Fatal , Neutropenia Febril/complicaciones , Neutropenia Febril/tratamiento farmacológico , Femenino , Filgrastim/uso terapéutico , Fluconazol/uso terapéutico , Humanos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/microbiología , Persona de Mediana Edad , Combinación Piperacilina y Tazobactam/uso terapéutico , Purinas/administración & dosificación , Purinas/efectos adversos , Quinazolinonas/administración & dosificación , Quinazolinonas/efectos adversos , Recurrencia , Rituximab/administración & dosificación , Rituximab/efectos adversos , Scedosporium/efectos de los fármacos , Triazoles/uso terapéutico , Valaciclovir/uso terapéutico , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
Background: Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized. Aims: To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis. Methods: Retrospective cohort study of all patients admitted to ICU in Australia or New Zealand between January 2000 and December 2022 with a primary admission diagnosis of sepsis and total white cell count <1.0 × 109 cells/L. Results: We identified 8617 ICU admissions with neutropenic sepsis (hematological malignancy n = 4660; metastatic solid cancer n = 1034; no cancer n = 2800). Patients with hematological malignancy were younger (median, 61.5 years) with low rates of chronic comorbidities (4.7%) and were usually admitted to ICU from the ward (67.4%). Mechanical ventilation rates were 20.2% and in-hospital mortality was 30.6%. Patients with metastatic solid cancers were older (median, 66.3 years), with higher rates of chronic comorbidities (9.9%), and were usually admitted to the ICU from the emergency department (50.8%). Mechanical ventilation rates were 16.9% and in-hospital mortality was 42.4%. Patients with no documented cancer had highest rates of mechanical ventilation (41.7%) and mortality (46.3%). Neutropenia was independently associated with mortality among patients with solid cancers or no cancer but did not confer increased risk among patients with hematological malignancy (odds ratio, 0.98; 95% confidence interval, .90-1.06; P = .60). Conclusions: Patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis constitute 3 distinct clinical groups. Management approaches should be tailored accordingly.
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Objectives: Despite vaccination strategies, people with chronic kidney disease, particularly kidney transplant recipients (KTRs), remained at high risk of poor COVID-19 outcomes. We assessed serological responses to the three-dose COVID-19 vaccine schedule in KTRs and people on dialysis, as well as seroresponse predictors and the relationship between responses and breakthrough infection. Methods: Plasma from 30 KTRs and 17 people receiving dialysis was tested for anti-Spike receptor binding domain (RBD) IgG and neutralising antibodies (NAb) to the ancestral and Omicron BA.2 variant after Doses 2 and 3 of vaccination. Results: After three doses, KTRs achieved lower anti-Spike RBD IgG levels (P < 0.001) and NAb titres than people receiving dialysis (P = 0.002). Seropositive cross-reactive Omicron neutralisation levels were achieved in 11/27 (40.7%) KTRs and 11/14 (78.6%) dialysis recipients. ChAdOx1/viral-vector vaccine type, higher mycophenolate dose (> 1 g per day) and lower absolute B-cell counts predicted poor serological responses in KTRs. ChAdOx-1 vaccine type and higher monocyte counts were negative predictors in dialysis recipients. Among ancestral NAb seroresponders, higher NAb levels positively correlated with higher Omicron neutralisation (R = 0.9, P < 0.001). More KTRs contracted SARS-CoV-2 infection (14/30; 47%) than dialysis recipients (5/17; 29%) and had more severe disease. Those with breakthrough infections had significantly lower median interdose incremental change in anti-Spike RBD IgG and ancestral NAb titres. Conclusion: Serological responses to COVID-19 vaccines in KTRs lag behind their dialysis counterparts. KTRs remained at high risk of breakthrough infection after their primary vaccination schedule underlining their need for booster doses, strict infection prevention measures and close surveillance.