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Assess the incidence, risk factors, clinical and microbiological features, and outcome of both probable invasive and invasive group A Streptococcus (GAS) infections in children and adults in the BrusselsCapital Region between 2005 and 2020. A retrospective, multicentric study was performed in three university hospitals in Brussels. Patients were identified through the centralized laboratory information system. Epidemiological and clinical data were collected from patients' hospital records. A total of 467 cases were identified. Incidence has increased from 2.1 to 10.9/100,000 inhabitants between 2009 and 2019 in non-homeless adults while it was above 100/100,000 on homeless in years with available denominators. Most of GAS were isolated from blood (43.6%), and the most common clinical presentation was skin and soft tissue infections (42.8%). A third of all the patients needed surgery, a quarter was admitted to the intensive care unit, and 10% of the adult patients died. Wounds and chickenpox disease were the main risk factors for children. Tobacco, alcohol abuse, wounds or chronic skin lesion, being homeless, and diabetes were identified as major predisposing factors for adults. The most common emm clusters were D4, E4, and AC3; 64% of the isolates were theoretically covered by the 30-valent M-protein vaccine. The burden of invasive and probable invasive GAS infections is on the rise in the studied adult population. We identified potential interventions that could contribute to decrease this burden: appropriate care of wounds, specifically among homeless and patients with risk factors such as diabetes and systematic chickenpox vaccination for children.
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Varicela , Infecções Estreptocócicas , Criança , Humanos , Adulto , Estudos Retrospectivos , Incidência , Streptococcus pyogenes , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologiaRESUMO
BACKGROUND: Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness. METHODS: In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4â units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT50)) ≥1/320 was the product of choice for the study. RESULTS: Between 2 May 2020 and 26 January 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median (interquartile range) volume of 884 (806-906)â mL) convalescent plasma was administered and 80.68% of the units came from donors with neutralising antibody titres (NT50) ≥1/320. Median time from onset of symptoms to randomisation was 7â days. The proportion of patients alive and free of mechanical ventilation on day 15 was not different between both groups (convalescent plasma 83.74% (n=267) versus control 84.05% (n=137)) (OR 0.99, 95% CI 0.59-1.66; p=0.9772). The intervention did not change the natural course of antibody titres. The number of serious or severe adverse events was similar in both study arms and transfusion-related side-effects were reported in 19 out of 320 patients in the intervention group (5.94%). CONCLUSIONS: Transfusion of 4â units of convalescent plasma with high neutralising antibody titres early in hospitalised COVID-19 patients did not result in a significant improvement of clinical status or reduced mortality.
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Anticorpos Antivirais/sangue , COVID-19 , Imunização Passiva , Adulto , Anticorpos Neutralizantes/sangue , COVID-19/terapia , Hospitalização , Humanos , Estudos Prospectivos , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
INTRODUCTION: Invasive candidiasis or candidemia is a severe infection affecting more than 250,000 people worldwide every year. It is present in up to 16% of ICU patients. The prognosis of these infections is unfavorable, with global death estimated around 50,000 per year, which corresponds to up to 40% depending on patient severity and comorbidities. Therapeutic failure is not rare due to the emergence of multiresistant strains and of new species poorly responsive to current therapies like Candida auris. AREAS COVERED: We first review the positioning of antifungal drugs used to treat candidiasis, namely polyenes, azoles, echinocandins and pyrimidine analogues. We then discuss the progresses brought by new formulations, new derivatives within these classes, compounds acting on new targets or repurposed drugs in terms of pharmacokinetic profile, spectrum of activity, potency, safety or risk of drug-drug interactions. EXPERT OPINION: While new formulations (amphotericin B cochleate) improve oral bioavailability of the corresponding drugs, new azoles or echinocandins offer higher potency including against strains resistant to former generations of drugs. Repurposed drugs show synergism with current therapies in vitro. Results from ongoing and future clinical trials will be decisive to establish the interest for these drugs in our arsenal.
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Candidemia , Candidíase Invasiva , Humanos , Candidemia/tratamento farmacológico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Azóis/farmacologia , Azóis/uso terapêuticoRESUMO
We report 4 cases of Fusobacterium nucleatum bacteremia associated with coronavirus disease (COVID-19). Three cases occurred concomitantly with COVID-19 diagnosis; 1 occurred on day 15 of intensive care. None of the patients had known risk factors for F. nucleatum bacteremia. F. nucleatum infection could represent a possible complication of COVID-19.
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COVID-19/complicações , Infecções por Fusobacterium/complicações , Adulto , Idoso , Bacteriemia , Bélgica , COVID-19/epidemiologia , Fusobacterium nucleatum/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
To assess the incidence, clinical, microbiological features and outcome of invasive Streptococcus agalactiae (GBS) infections in non-pregnant adults in three tertiary hospitals of the Brussels-Capital Region. All bacterial cultures positive for GBS, from 2005 to 2019 from 3 hospitals of the Brussels-Capital Region, were extracted, and only cases of invasive diseases were included. Medical files were retrospectively retrieved for risk factors, clinical manifestations and outcome and also antibiotic-susceptibility testing and GBS serotypes. Incidence rates were calculated based on the hospitals catchment populations. A total of 337 cases of GBS-invasive infections were included. The incidence of invasive GBS for the 3 hospitals increased from 3.7 to 8.2 cases per 100.000 inhabitants between 2009 and 2018 (p = 0.04). The most frequently identified risk factors were diabetes (36.8%), obesity (35.0%), cancer (21.7%), renal disease (20.8%), and advanced age (≥ 65 years; 47.2%). Isolated bacteremia (22%), osteoarticular infection (21.4%), abscesses (13.9%), and skin and soft tissue infections (18.4%) were the most frequent manifestations. Intensive care unit admission was required in 21.7% and overall mortality was 9.4%. All strains remained susceptible to penicillin over the years. Up to 20% of strains were resistant to clindamycin. Serotypes Ia, Ib, II, III, IV, and V represented 96.8% of the available serotypes (60/62). As reported in several countries, invasive GBS disease in non-pregnant adults represents an increasing burden, particularly among diabetic, obese, and elderly patients. Almost all serotypes identified are included in the upcoming hexavalent GBS conjugate vaccine.
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Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bélgica/epidemiologia , Farmacorresistência Bacteriana , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sorogrupo , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/classificação , Streptococcus agalactiae/efeitos dos fármacos , Centros de Atenção TerciáriaRESUMO
We describe a case of dementia with Lewy bodies immediately following encephalitis due to West Nile virus (WNV). The patient had rapid eye movement-sleep behavior disorder and constipation before the onset of encephalitis, which suggests that he would have ultimately developed dementia with Lewy bodies even without WNV infection. Our case illustrates the interactions between α-synuclein and WNV, as observed in mouse models, wherein synuclein expression augments after WNV infection and protects neurons against the virus.
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Clonazepam/uso terapêutico , Disfunção Cognitiva , Encefalite/complicações , Moduladores GABAérgicos/uso terapêutico , Doença por Corpos de Lewy , Febre do Nilo Ocidental/complicações , Idoso , Confusão/etiologia , Febre/etiologia , Humanos , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/tratamento farmacológico , Masculino , República da Macedônia do Norte , Vírus do Nilo Ocidental/isolamento & purificaçãoAssuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , COVID-19 , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Pandemias , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Pontuação de Propensão , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: Severe alcoholic hepatitis (AH) has a poor short-term prognosis. Although infections are frequent complications of AH, the incidence of invasive aspergillosis (IA) and its impact on outcome remain unknown. METHODS: We prospectively followed 94 biopsy-proven severe AH episodes for 3 months. We retrospectively reviewed our diagnosis of IA based on EORTC/MSG and AspICU criteria, except for host factors. RESULTS: Fifteen IA (6 proven, 8 probable, and 1 possible) were diagnosed after a median delay of 26 days following diagnosis of AH. The sites of infection were the lungs (n=11) and central nervous system (n=2), while IA was disseminated in 2 cases. Baseline MELD score ≥24 and ICU admission were independent risk factors for IA. Thirteen IA occurred in the context of corticosteroids, and 2 had received no specific treatment for AH. Non-response to corticosteroids at day 7 was not a risk factor for IA, but IA was associated with absence of liver improvement at day 28. Despite antifungal treatment, 3-month transplant-free survival of patients with IA was 0% compared to 53% in those without IA. IA, Lille score ≥0.45, and overt encephalopathy were independent predictors of transplant-free mortality. CONCLUSIONS: IA is a frequent complication of severe AH and carries a very high risk of mortality. Systematic screening for IA should be recommended in these patients. Further studies are needed to identify high-risk populations requiring antifungal prophylactic treatment.
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Aspergilose/etiologia , Hepatite Alcoólica/complicações , Corticosteroides/efeitos adversos , Adulto , Idoso , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Estudos de Coortes , Feminino , Galactose/análogos & derivados , Hepatite Alcoólica/tratamento farmacológico , Humanos , Estimativa de Kaplan-Meier , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Introduction: The Bacillus Calmette-Guérin (BCG) used as anti-tuberculous vaccine is also a well-known therapy for superficial urothelial cancer. Local or general side effects can occur, although it is generally well tolerated. Case: We present the case of a 65 year-old caucasian man consulting for gross hematuria and lower urinary tract symptoms. Magnetic resonance imaging (MRI) demonstrated a non-invasive urothelial carcinoma (NMIBC) and Prostate Imaging-Reporting and Data System (PIRADS) IV lesions. Transurethral resection of the bladder tumor revealed a non-invasive transitional cell carcinoma. Intravesical Bacillus Calmette Guerin (BCG) therapy was provided. After 6 intravesical instillations, the patient presented with prostato-epididymitis. Forthcoming BCG instillations were canceled, and cancer treatment was switched to epirubicine. Treatment with ethambutol, rifampicin and isoniazid was started with rapid resolution of the symptoms. Urinary and semen cultures grew Mycobacterium tuberculosis complex strain BCG. As prostate specific antigen (PSA) rose, prostate's biopsies were performed showing extensive necrosis boarded by granulomas without signs of malignancy. Discussion: BCGitis is a rare complication in patients treated for non-invasive urothelial cancer. Several risk factors, local and systemic, should be considered prior to this immunotherapy. BCGitis (local or disseminated) or hypersensitivity reactions to BCG must be included in the differential diagnosis even if therapy was administered several years before the symptoms. Adequate treatment must be started as fast as possible to avoid serious complications.
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Streptobacillus moniliformis is a zoonotic agent associated with rat bites. We present a patient with cellulitis, subcutaneous abscess, and septic mono-arthritis after a rat bite of the right hand. The patient had no systemic features of rat bite fever (RBF). S. moniliformis was cultured from purulent drainage of a thumb abscess. This case illustrates an unusual clinical presentation of streptobacillary infection after a rat bite.
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We report a hemodialysis MDR HIV-infected patient switched to fostemsavir with lenacapavir plus lamivudine for more than a year. She maintained a suppressed viral replication and did not present any clinical or biological drug-related side effects. The combination of lenacapavir plus fostemsavir looks promising in terms of safety and efficacy even in patients with end-stage renal disease awaiting renal transplant. Both drugs are first in class ARVs so that there is no cross resistance with previous drugs, maintaining their efficacy against MDR HIV.
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BACKGROUND: Patients with end-stage-renal-disease (ESRD) undergoing hemodialysis (HD) represent a vulnerable population for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, due to their intrinsic fragility and increased exposure to the virus. Therefore, applying effective screening strategies and infection control measures is essential to control the spread of the epidemic within hemodialysis centers. OBJECTIVE: Description and evaluation of the efficacy of systematic screening by rt-PCR and viral cultures, in addition to triage to limit the spread of the epidemic. Evaluation of the performance of these tests using "post-hoc" SARS-CoV-2 serology as a surrogate marker of infection. METHODS: One hundred and forty-four patients undergoing hemodialysis in the Nephrology-Hemodialysis center of CHU Brugmann, Brussels, benefited from systematic virological screening using viral cultures in asymptomatic patients, or molecular tests (rt-PCR) for symptomatic ones, in addition to general prevention measures. Post-hoc serology was performed in all patients. RESULTS: Thirty-eight (26.3%) individuals were infected with SARS-CoV-2. Seventeen infected patients (44.7%) were asymptomatic and thus detected by viral culture. Our strategy allowed us to detect and isolate 97.4% of the infected patients, as proven by post-hoc serology. Only one patient, missed by clinical screening and sequential viral cultures, had a positive serology. CONCLUSION: The implementation of a control and prevention strategy based on a systematic clinical and virological screening showed its effectiveness in limiting (and shortening) the spread of the SARS-CoV-2 epidemic within our hemodialysis unit.
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COVID-19 , SARS-CoV-2 , Unidades Hospitalares de Hemodiálise , Humanos , Reação em Cadeia da Polimerase , Diálise Renal/efeitos adversos , TriagemRESUMO
Early evidence during the coronavirus disease 2019 (COVID-19) pandemic indicated high levels of interleukin (IL)-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic. While the monoclonal antibody blocks IL-6 pathway, its effect on other inflammatory cytokines remains poorly described. To better understand the effect of TCZ on the biological inflammatory profile, we monitored a large panel of inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Twenty-three patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were included in the study, among which 15 patients received TCZ and 8 patients did not. Serum samples were collected for 8 days, before and following TCZ administration or hospital admission for the control group. Serum profile of 12 cytokines (IL-1ß, -2, -4, -6, -8, -10, -12, -13, -17, -18, tumor necrosis factor α (TNF-α), interferon-gamma (IFN-γ), and sIL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1ß, -2, -4, -10, -12p70, -18, and sIL-6R levels in the treated patients with maximal values reaching 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. Our results suggested that some inflammatory pathways escape IL-6R blockade and even appeared amplified. This finding highlights an old observation of the anti-inflammatory effects of IL-6 as already suggested over 20 years ago. Clinical Trial Registration number: NCT04346017.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Tratamento Farmacológico da COVID-19 , Citocinas/sangue , Estado Terminal , Humanos , Interleucina-6/antagonistas & inibidores , SARS-CoV-2RESUMO
Non-typhoidal Salmonella (NTS) disease is usually a self-limiting infection presenting with digestive symptoms. However, disseminated presentation with involvement of secondary infectious sites is observed. We report diagnostic specificities and challenges related to the management of three patients with invasive NTS (iNTS) and secondary infectious locations. Among the seven patients (age range 46 - 83 years), four (two with extra-digestive infectious sites) had at least one immune debilitating condition. Two patients were incidentally discovered with iNTS and deceased after developing a septic shock despite antimicrobial treatment. Two individuals recovered under medical treatment without complications. Three other patients presented with secondary infectious sites. Case 1 suffered from urinary tract infection and dorsolumbar spondylodiscitis that responded well to antimicrobials and surgery. Abdominal prosthetic aortic aneurysm was diagnosed in case 2 and medical treatment only was applied. After four years of follow-up, he remains under antimicrobial treatment. Case 3 presented with conjoint thoracic aortic aneurysm and cutaneous abscesses managed with antimicrobials and surgery. Atherosclerosis and previous vascular intervention were the predisposing events for vascular involvement. iNTS is a serious disease carrying a high risk of mortality or secondary locations. Secondary locations can be managed by long duration antimicrobial therapy combined with surgery. Spine and aortitis are the most frequent secondary locations. Multi-drug resistant NTS represent an additional risk of mortality. Public health measures should be implemented to limit the spread of NTS to humans and the emergence of drug resistance.
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Paracoccus yeei, a Gram-negative coccobacillus, is an emergent opportunistic pathogen. It originates from soil and water. VITEK and MALDI-TOF are used for identification. There are few reports of peritoneal dialysis peritonitis. Its presentation is usually indolent. It can be successfully treated with several antibiotics: ß-lactams, aminoglycosides, without removing the catheter.
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Among the challenges in controlling tuberculosis, a rapid and accurate diagnostic test for the detection of Mycobacterium tuberculosis complex (MTBc) and its resistance to first line therapies is crucial. We evaluated the performance of the Xpert MTB/RIF Ultra assay (Xpert Ultra) for the rapid detection of MTBc and rifampicin resistance (RR) in 1120 pulmonary and 461 extra-pulmonary clinical specimens and compared it with conventional phenotypic techniques. The Xpert Ultra assay detected MTBc in 223 (14.1%) samples with an overall sensitivity and specificity, using culture as the "gold standard", of 91.1% (95% CI, 85.6-95.1) and 94.5% (95% CI, 93.1-95.6), respectively. The sensitivity of the Xpert Ultra test for smear-negative extra-pulmonary specimens was high (87.1%), even higher than with smear-negative pulmonary specimens (81.8%). But this enhanced sensitivity came with a low overall specificity of smear-negative extra-pulmonary specimens (66.7%). For 73 patients, 79/1423 (3.4%) negative mycobacterial culture samples were found to be positive with Xpert Ultra. Clinical data was necessary to correctly interpret potential false-positive results, especially trace-positive results. Sensitivity of the Xpert Ultra to detect RR compared to drug susceptibility testing was 100% (95% CI, 29.2-100) and specificity was 99.2% (95% CI, 95.8-100). We concluded that the Xpert Ultra test is able to provide a reliable TB diagnosis within a significantly shorter turnaround time than culture. This is especially true for paucibacillary samples such as smear-negative pulmonary specimens and extra-pulmonary specimens.
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Testes Diagnósticos de Rotina/métodos , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/diagnóstico , Adulto , Antibióticos Antituberculose/farmacologia , Bélgica , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Laboratórios Hospitalares , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologiaRESUMO
Suspicion threshold for opportunistic coinfections should be lowered in severe COVID-19. Serum CMV polymerase chain reaction and colonoscopy should be discussed in presence of persistent digestive disturbances.
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PURPOSE: To report multimodal imaging findings in two cases of AIDS-related cryptococcal chorioretinitis associated with uveitis and vasculitis. METHODS: Findings on clinical examination, color fundus photography, fluorescein and indocyanine green angiographies, and optical coherence tomography. Patients. Both patients were diagnosed with Cryptococcus neoformans meningitis in the setting of untreated HIV infection with CD4+ T cell count < 100/mm3. Ocular manifestations occurred during the course of the antifungal therapy for meningitis. RESULTS: In both cases, fundus showed vitritis. Fluorescein angiography allowed the characterization of vasculitis lesions, and indocyanine green angiography indicated choroidal involvement. In combination with optical coherence tomography, ICG and FA allowed the assessment of treatment response. CONCLUSION: These two cases reveal the potential of C. neoformans to infect almost all ocular structures and the critical role of multimodal imaging in baseline evaluation and in the follow-up of patients.
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BACKGROUND: Susceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection. METHODS: After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies. RESULTS: We found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls. CONCLUSION: In this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.
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Sistema ABO de Grupos Sanguíneos/imunologia , Anticorpos/sangue , COVID-19/sangue , Polissacarídeos/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/virologia , Suscetibilidade a Doenças , Células Epiteliais/imunologia , Epitopos/imunologia , Feminino , Galactosiltransferases , Humanos , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Risco , Adulto JovemRESUMO
Background and Objectives: SARS-CoV-2-induced ARDS is a new entity that should be characterized as it appears to be different from standard ARDS. Hypernatremia is a biological alteration that seems to occur very often in this population without any clear cause. The present study aims to clarify the possible causes of hypernatremia and evaluate its impact on patient outcome. Patients and Methods: We conducted a retrospective one-day prevalence study in 2 intensive care units, which only treated COVID-19 patients with moderate to severe ARDS. We measured blood and urine electrolytes in all the patients. Patients with chronic renal failure or renal replacement therapy were excluded from the study. Hypernatremia was defined as plasma sodium levels above 145 mmol/L. Results: Inclusion criteria were met in 17 out of 24 patients. Hypernatremia was present in 52% patients. All had a natriuresis higher than 20 mmol/L and a urine osmolality above 600 mOsm/L. Hypernatremia was acquired in ICU as all the patients had a normal serum sodium level at admission. Conclusion: The incidence of hypernatremia was elevated and appears to be linked to significant insensible water losses. This should trigger us to optimize the maintenance fluid therapy in critically ill patients with SARS-CoV-2-induced ARDS.