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The literature regarding COVID-19-associated pulmonary aspergillosis (CAPA) has shown conflicting observations, including survival of CAPA patients not receiving antifungal therapy and discrepancy between CAPA diagnosis and autopsy findings. To gain insight into the pathophysiology of CAPA, we performed a case-control study in which we compared Aspergillus test profiles in CAPA patients and controls in relation to intensive care unit (ICU) mortality. This was a multinational case-control study in which Aspergillus test results, use of antifungal therapy, and mortality were collected from critically ill COVID-19 patients. Patients were classified using the 2020 European Confederation for Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus case definitions. We analyzed 219 critically ill COVID-19 cases, including 1 proven, 38 probable, 19 possible CAPA cases, 21 Aspergillus-colonized patients, 7 patients only positive for serum (1,3)-ß-d-glucan (BDG), and 133 cases with no evidence of CAPA. Mortality was 53.8% in CAPA patients compared to 24.1% in patients without CAPA (P = 0.001). Positive serum galactomannan (GM) and BDG were associated with increased mortality compared to serum biomarker-negative CAPA patients (87.5% versus 41.7%, P = 0.046; 90.0% versus 42.1%, P = 0.029, respectively). For each point increase in GM or 10-point BDG serum concentration, the odds of death increased (GM, odds ratio [OR] 10.208, 95% confidence interval [CI], 1.621 to 64.291, P = 0.013; BDG, OR, 1.247, 95% CI, 1.029 to 1.511, P = 0.024). CAPA is a complex disease, probably involving a continuum of respiratory colonization, tissue invasion, and angioinvasion. Serum biomarkers are useful for staging CAPA disease progression and, if positive, indicate angioinvasion and a high probability of mortality. There is need for a biomarker that distinguishes between respiratory tract colonization and tissue-invasive CAPA disease.
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COVID-19 , Aspergilose Pulmonar Invasiva , Animais , Aspergillus , Estudos de Casos e Controles , Estado Terminal , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas , SARS-CoV-2RESUMO
We describe four secondary fungal infections caused by Mucorales species in COVID-19 patients. Three COVID-19 associated mucormycosis (CAM) occurred in ICU, one outside ICU. All were men aged >â¯50 years, three died. Clinical presentations included pulmonary, rhino-orbital cerebral and disseminated infection. Infections occurred in patients with and without diabetes mellitus. CAM is an emerging disease and our observations underscore the need to be aware of invasive mucormycosis, including in COVID-19 patients without (poorly controlled) diabetes mellitus and outside ICU.
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COVID-19 , Mucorales , Mucormicose , Feminino , Humanos , Masculino , Mucormicose/diagnóstico , Países Baixos/epidemiologia , SARS-CoV-2RESUMO
BACKGROUND: Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%-100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking. METHODS: A 5-year retrospective cohort study (2011-2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated. RESULTS: Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), despite switching to appropriate antifungal therapy after a median of 10 days. CONCLUSIONS: Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality.
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Aspergillus fumigatus/genética , Doenças Autoimunes/tratamento farmacológico , Farmacorresistência Fúngica/genética , Neoplasias Hematológicas/tratamento farmacológico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Voriconazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/patogenicidade , Doenças Autoimunes/complicações , Doenças Autoimunes/microbiologia , Doenças Autoimunes/mortalidade , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/microbiologia , Neoplasias Hematológicas/mortalidade , Humanos , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/microbiologia , Aspergilose Pulmonar Invasiva/mortalidade , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoAssuntos
Aspergilose , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Aspergillus , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Aspergilose Pulmonar/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Pandemias , Aspergilose Pulmonar/virologia , SARS-CoV-2RESUMO
BACKGROUND: Contact precautions (CP) are recommended when caring for patients with carbapenemase-producing Enterobacterales (CPE), carbapenemase-producing Pseudomonas aeruginosa (CPPA), and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E). AIM: Our aim was to determine the interpretation of CP and associated infection prevention and control (IPC) measures in the non-ICU hospital setting for patients with CPE, CPPA or ESBL-E in 11 hospitals in the Southwest of the Netherlands. METHODS: A cross-sectional survey was developed to collect information on all implemented IPC measures, including use of personal protective equipment, IPC measures for visitors, cleaning and disinfection, precautions during outpatient care and follow-up strategies. All eleven hospitals were invited to participate between November 2020 and April 2021. FINDINGS: The survey was filled together with each hospital. All hospitals installed isolation precautions for patients with CPE and CPPA during inpatient care and day admissions, whereas ten hospitals (90.9%) applied isolation precautions for patients with ESBL-E. Gloves and gowns were always used during physical contact with the patient in isolation. Large variations were identified in IPC measures for visitors, cleaning and disinfection products used, and precautions during outpatient care. Four hospitals (36.4%) actively followed up on CPE or CPPA patients with the aim to declare them CPE- or CPPA-negative as timely as possible, and two hospitals (20.0%) actively followed up on ESBL-E patients. CONCLUSION: CP are interpreted differently between hospitals, leading to regional differences in IPC measures applied in clinical settings. Harmonizing infection-control policies between the hospitals could facilitate patient transfers and benefit collective efforts of preventing transmission of MDR-GNB.
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BACKGROUND: The risk of urinary tract infections is increased by the inappropriate placement and unnecessary prolongation of the use of indwelling urinary catheters. Sustained behavior change in infection prevention could be promoted by empowering patients through a smartphone app. OBJECTIVE: The aim of this study is to assess the feasibility and efficacy of implementation actions on patients' use of the Participatient app on a clinical ward and to compare 3 survey methods for urinary catheter use. METHODS: Participatient was introduced for all admitted patients at the surgical nursing ward in a university hospital in the Netherlands. Over a period of 3 months, the number of new app users, days of use, and sessions were recorded. In a comparison of urinary catheter use before and after the implementation of the app, 3 methods for point prevalence surveys of catheter use were tested. Surveys were conducted through manual parsing of the text in patients' electronic medical records, parsing a survey of checkbox items, and parsing nursing notes. RESULTS: In all, 475 patients were admitted to the ward, 42 (8.8%) installed the app, with 1 to 5 new users per week. The actions with the most ensuing app use were the kick-off with the clinical lesson and recruiting of the intake nurse. Between the survey methods, there was considerable variation in catheter use prevalence. Therefore, we used the standard method of manual parsing in further analyses. Catheter use prevalence decreased from 38% (36/96) to 27% (23/86) after app introduction (OR 0.61, 95% CI 0.32-1.14). CONCLUSIONS: The clinical application of Participatient, the infection prevention app for patients, could be feasible when implementation actions are also used. For surveying indwelling urinary catheter use prevalence, manual parsing is the best approach.
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PURPOSE: Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This study aims to conduct a systematic review and an individual patient-level image analysis of CT findings of COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: A systematic literature search was conducted to identify studies reporting CT findings of CAPA as of January 7, 2021. We summarized study-level clinical and CT findings of CAPA and collected individual patient CT images by inviting corresponding authors. The CT findings were categorized into four groups: group 1, typical appearance of COVID-19; group 2, indeterminate appearance of COVID-19; group 3, atypical for COVID-19 without cavities; and group 4, atypical for COVID-19 with cavities. In group 2, cases had only minor discrepant findings including solid nodules, isolated airspace consolidation with negligible ground-glass opacities, centrilobular micronodules, bronchial abnormalities, and cavities. RESULTS: The literature search identified 89 patients from 25 studies, and we collected CT images from 35 CAPA patients (mean age 62.4 ± 14.6 years; 21 men): group 1, thirteen patients (37.1%); group 2, eight patients (22.9%); group 3, six patients (17.1%); and group 4, eight patients (22.9%). Eight of the 14 patients (57.1%) with an atypical appearance had bronchial abnormalities, whereas only one (7.1%) had an angio-invasive fungal pattern. In the study-level analysis, cavities were reported in 12 of 54 patients (22.2%). CONCLUSION: CAPA can frequently manifest as COVID-19 pneumonia without common CT abnormalities of pulmonary aspergillosis. If abnormalities exist on CT images, CAPA may frequently accompany bronchial abnormalities.
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COVID-19 , Aspergilose Pulmonar , Idoso , COVID-19/complicações , Análise de Dados , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Critically ill COVID-19 patients have proven to be at risk for developing invasive fungal infections. However, the incidence and impact of possible/probable COVID-19-associated pulmonary aspergillosis (CAPA) in severe COVID-19 patients varies between cohorts. We aimed to assess the incidence, risk factors, and clinical outcome of invasive pulmonary aspergillosis in a regional cohort of COVID-19 intensive care patients. METHODS: We performed a regional, multicentre, retrospective cohort study in the intensive care units (ICUs) in North Brabant, The Netherlands. We included adult patients with rt-PCR-confirmed SARS-CoV-2 infection (COVID-19), requiring mechanical ventilation for acute respiratory distress syndrome. Demographics, clinical course, biomarker value, and treatment outcomes were compared between the groups with possible/probable CAPA from the main study centre and the regional centres, and without signs of CAPA from the main study centre as controls. The primary aim was to assess the regional impact of possible/probable CAPA in COVID-19 ICU patients, measured as all-cause mortality at 30 days after ICU admission. Secondary outcomes were risk factors for developing CAPA, based on underlying host factors and to identify the value of the mycological arguments for the diagnosing of CAPA. RESULTS: Between 1 March and 30 April 2020, we included 123 patients with severe COVID-19: 29 patients (30.9%) in the main ICU with possible/probable CAPA, and 65 (69.1%) with no signs of CAPA; 29 patients in the regional ICUs with signs of CAPA. Patients' characteristics and risk factors did not differ for CAPA and non-CAPA patients. Patients with COPD and/or chronic steroid medication developed CAPA more frequently, although this was not statistically significant. CAPA patients were admitted to the ICU earlier, had lower PF-ratios, and more often required renal replacement therapy. All-cause 30-day mortality was significantly higher in mechanically ventilated COVID-19 patients with possible/probable CAPA 39.7% (23/58) compared to patients without evidence for CAPA 16.9% (11/65) (OR 3.2 [95% CI 1.4-7.4] p = 0.005). CONCLUSION: The high incidence of possible and probable CAPA in critically ill COVID-19 patients is alarming. The increase in 30-day mortality in CAPA highlights the need for active surveillance and management strategies in critically ill COVID-19 patients.
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BACKGROUND: SARS-CoV-2 has spread globally. Currently, literature of SARS-CoV-2 in neonates is scarce. We present a case of a neonate with a high viral load and prolonged virus shedding. METHODS: Epidemiology, clinical characteristics, treatment, laboratory data and follow-up information and the treatment of a neonate with COVID-19 were recorded. RESULTS: A 7-day-old boy was admitted to the hospital with fever, lethargy and apnoea. He was found SARS-CoV-2 RNA positive with an exceptionally high viral load in nasopharyngeal swab and stool. The father and two maternity nurses at home had detectable SARS-CoV-2 RNA as well. Sequencing showed all strains belonged to the same cluster. The father was asymptomatic and the maternity nurses developed symptoms after visiting. In the mother, no SARS-CoV-2 RNA could be found. Six days after admission, the neonate was discharged after clinical improvement with oral antibiotics because of a possible pyelonephritis. Monitoring the course of this infection showed that SARS-CoV-2 RNA was detectable in the nasopharynx until day 19 and in stool until day 42 after symptom onset. CONCLUSIONS: This case shows that neonates can have a high viral load of SARS-CoV-2 and can shed the virus for over one month in stool. Despite the high viral load in the neonate, the mother and a sibling did not get infected.
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COVID-19/diagnóstico , SARS-CoV-2 , COVID-19/complicações , COVID-19/virologia , Diagnóstico Diferencial , Febre/etiologia , Humanos , Recém-Nascido , Masculino , Carga Viral , Eliminação de Partículas ViraisRESUMO
Importance: On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. Objective: To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. Design, Setting, and Participants: This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. Main Outcomes and Measures: The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase-polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Results: Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. Conclusions and Relevance: Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.
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Betacoronavirus/isolamento & purificação , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Adulto , Idoso , COVID-19 , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pandemias , Prevalência , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. METHODS: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. FINDINGS: Between March 2 and March 12, 2020, 1796 (15%) of 12â022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. INTERPRETATION: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. FUNDING: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
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Betacoronavirus/genética , Infecções Comunitárias Adquiridas/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/epidemiologia , Pessoal de Saúde , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Adulto , Idoso , COVID-19 , Infecções Comunitárias Adquiridas/virologia , Infecções por Coronavirus/virologia , Infecção Hospitalar/virologia , Estudos Transversais , Feminino , Variação Genética , Hospitais de Ensino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
BACKGROUND: Relapsing fever is an infectious disease caused by Spirochaetes. The presentation is characterised by recurrent episodes of fever. CASE DESCRIPTION: At the end of her trip through South Africa and Botswana, a 54-year-old woman had symptoms of fever and dry cough. Back in the Netherlands, physical examination at the emergency department did not reveal any abnormalities besides fever. Laboratory investigation found thrombocytopenia and elevated infection markers. Thick blood smear revealed the presence of Spirochaetes. Following a working diagnosis of 'relapsing fever', the patient was treated with doxycycline. There was no Jarisch-Herxheimer reaction. At a follow-up outpatient appointment two weeks later, the patient had fully recovered. CONCLUSION: Relapsing fever is a rare disease without specific symptoms. The diagnosis is therefore easily overlooked. Untreated, mortality is high. During episodes of fever, the diagnosis can be established with a thick blood smear.
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Febre Recorrente/diagnóstico , Febre Recorrente/tratamento farmacológico , Viagem , Anti-Infecciosos/uso terapêutico , Borrelia/isolamento & purificação , Tosse/etiologia , Doxiciclina/uso terapêutico , Feminino , Febre/etiologia , Humanos , Pessoa de Meia-Idade , Países Baixos , Doenças Raras , Febre Recorrente/complicaçõesRESUMO
We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient who was treated with chemotherapy for acute myeloid leukemia. We discuss the clinical manifestations, diagnosis, and treatment of this unusual infection in neutropenic patients.