Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

BACKGROUND: Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. METHODS: This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. RESULTS: Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. CONCLUSION: Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

COVID-19-Associated Fusobacterium nucleatum Bacteremia, Belgium.

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.

West Nile Virus Neuroinvasive Disease Accelerating Probable Dementia With Lewy Bodies.

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.

Population movements and the HIV cascade in recently diagnosed patients at the French Guiana -Suriname border.

Border areas are particular "hot spots" generating high levels of HIV vulnerability and facing great challenges to control epidemics. The objective of this study is to describe the sociodemographic, clinical and biological profiles of newly HIV diagnosed people at the French Guiana - Suriname border, to construct an HIV care cascade and compare it with the Surinamese one. HIV-patients aged over 15 years newly diagnosed in western French Guiana in 2011 and 2012 were included in a retrospective cohort study. Patients were identified using different sources (n = 121). The male-to-female ratio was 0.8, 85% of the patients were of foreign origin, 72% were undocumented migrants, 21% were living in Suriname and 48% had baseline CD4 cell counts <200 cells/mm3. After one year, 34% were lost to follow-up, 54% received treatment, 34% had controlled viremia and 6% died. We observed a disappointing HIV cascade, like that of Suriname, requiring to develop a coordinated healthcare offer on both sides of the border. Targeted efforts through a bi-national collaboration are needed to address the specific issues of cross-border patients to reach the 90*3 UNAIDS's diagnosis, link to care and treatment targets and better control the local epidemic.

Comparative trends of brucellosis serological testing and confirmed brucellosis cases suggest inappropriate prescription habits.

BACKGROUND: Brucellosis is a zoonosis endemic to specific geographical regions. In first line laboratories, diagnosis is made by blood culture or Rose Bengal (RB) serology. METHODS: We compare brucellosis testing between 2012-2021 at two university hospitals in Brussels, Belgium with concomitant national confirmed cases and institutional cases. RESULTS: RB testing increased from 30 to 211 tests/year between 2012-2021. A total of fifty-two national brucellosis cases were notified during the study period, of which fifteen cases in Brussels. No trend was noted nationally or regionally. Epidemiological data indicated travel to endemic regions, confirmed by strain testing. Institutional cases all showed symptomatic presentations with positive travel histories. CONCLUSIONS: Serologic testing inappropriately increases yearly, while annual imported brucellosis cases remain rare, and have positive travel histories and are symptomatic. We therefore support current recommendations of limiting RB testing to symptomatic patients at risk of exposure, meaning predominantly positive recent travel history.

The impact of the COVID-19 pandemic on gram-negative bacteria susceptibility patterns in respiratory samples of intensive care units in the Brussels Capital Region, 2010-2021.

BACKGROUND: The effect of the Coronavirus Disease 2019 (COVID-19) pandemic on gram-negative bacteria nonsusceptibility to antibiotics is unclear. METHODS: Between January 1, 2010, and December 31, 2021, the respiratory samples of intensive care unit patients at 3 University Hospitals in Brussels were retrieved. Based on the nonsusceptibility to antimicrobial classes, drug-resistance patterns were defined as multi-drug-resistant, extensively drug-resistant, and pan-drug-resistant. The study time frame was divided into 6 periods of 2 years each, and the impact of the COVID-19 pandemic (last period: 2020-2021) was assessed. RESULTS: During the current study, 10,577 samples were identified from 5,889 patients. While a significant augmentation of multi-drug-resistant isolates was noticed once comparing 2 prepandemic periods (2012-2013 and 2014-2015), all 3 patterns of nonsusceptibility significantly increased, comparing the years before and throughout the COVID-19 pandemic (2018-2019 and 2020-2021). Globally, the greatest increase in antimicrobial nonsusceptibility, comparing the last 2 periods, was reported for piperacillin-tazobactam (from 28% to 38%). Pseudomonas aeruginosa was the most isolated species, and the most involved in the appearance of resistance, with an augmentation of nonsusceptibility percentage to meropenem of 22% (from 25% to 47%), between the prepandemic and the pandemic periods. CONCLUSIONS: The COVID-19 pandemic was associated with increasing trends of antimicrobial resistance in respiratory samples of patients admitted to the intensive care units in university hospitals with well-implemented antibiotic stewardship programs.

Bacillus Calmette-Guérin (BCG) prostato-epididymitis in a patient treated for a non-invasive urothelial cancer: A case report.

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.

Towards a better detection of patients at-risk of linezolid toxicity in clinical practice: a prospective study in three Belgian hospital centers.

Introduction: Linezolid is a last-resort antibiotic for infections caused by multidrug-resistant microorganisms. It is widely used for off-label indications and for longer than recommended treatment durations, exposing patients at higher risk of adverse drug reactions (ADRs), notably thrombocytopenia. This study aimed to investigate ADR incidence and risk factors, identify thrombocytopenia-related trough levels based on treatment duration, and evaluate the performance of predictive scores for ADR development. Methods: Adult in- and outpatients undergoing linezolid therapy were enrolled in three hospitals and ADRs and linezolid trough levels prospectively monitored over time. A population pharmacokinetic (pop-PK model) was used to estimate trough levels for blood samples collected at varying times. Results: A multivariate analysis based on 63 treatments identified treatment duration ≥10 days and trough levels >8 mg/L as independent risk factors of developing thrombocytopenia, with high trough values correlated with impaired renal function. Five patients treated for >28 days did not develop thrombocytopenia but maintained trough values in the target range (<8 mg/L). The Buzelé predictive score, which combines an age-adjusted Charlson comorbidity index with treatment duration, demonstrated 77% specificity and 67% sensitivity to predict the risk of ADR. Conclusion: Our work supports the necessity of establishing guidelines for dose adjustment in patients with renal insufficiency and the systematic use of TDM in patients at-risk in order to keep trough values ≤8 mg/L. The Buzelé predictive score (if ≥7) may help to detect these at-risk patients, and pop-PK models can estimate trough levels based on plasma samples collected at varying times, reducing the logistical burden of TDM in clinical practice.

Streptobacillus moniliformis right hand abscess and monoarthritis following a rat bite.

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.

Lenacapavir with Fostemsavir in a Multidrug-Resistant HIV-Infected Hemodialysis Patient.

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.

Hematogenous septic arthritis of a non-prosthetic shoulder caused by Capnocytophaga canimorsus: A case report and review of the literature.

Capnocytophaga canimorsus, oral inhabitants of dogs and cats is a cause of zoonotic infections. It is transmitted to humans by bites, scratches, licks, or close exposure to these animals. Infections due to Capnocytophaga canimorsus have a wide range of severity and can sometimes be fatal. We report the case of an 89-years-old man who suffered from a sudden swollen native right shoulder. The blood test revealed an inflammatory syndrome and cytologic evaluation of joint aspiration showed an elevated nucleated cells count suspicious of infection. A Gram-negative bacillus grew after 48 h in the arthrocentesis and was identified as Capnocytophaga canimorsus. After 4 days, blood culture also grew Capnocytophaga canimorsus leading to the diagnosis of hematogenous septic arthritis of a non-prosthetic right shoulder. Antimicrobial therapy was empirically started with cefuroxime then switched to doxycycline for seven weeks with good clinical outcomes. It is important to inquire about patients' environment including their proximity to animals as it can lead to zoonotic infections that can be of high severity. Moreover, hygiene rules must be applied when dog scratches or lick wounds occurred to avoid the spread of zoonotic germs. Prophylactic antibiotic therapy should be given for animal bites.

Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Intravenous Infusions of PF-07304814 (Lufotrelvir) in Participants Hospitalized With COVID-19.

Background: An urgent need remains for antiviral therapies to treat patients hospitalized with COVID-19. PF-07304814-the prodrug (lufotrelvir) and its active moiety (PF-00835231)-is a potent inhibitor of the SARS-CoV-2 3CL protease. Method: Eligible participants were 18 to 79 years old and hospitalized with confirmed COVID-19. This first-in-human phase 1b study was designed with 2 groups: single ascending dose (SAD) and multiple ascending dose (MAD). Participants could receive local standard-of-care therapy. In SAD, participants were randomized to receive a 24-hour infusion of lufotrelvir/placebo. In MAD, participants were randomized to receive a 120-hour infusion of lufotrelvir/placebo. The primary endpoint was to assess the safety and tolerability of lufotrelvir. The secondary endpoint was to evaluate the pharmacokinetics of lufotrelvir and PF-00835231. Results: In SAD, participants were randomized to receive 250 mg lufotrelvir (n = 2), 500 mg lufotrelvir (n = 2), or placebo (n = 4) by continuous 24-hour infusion. In MAD, participants were randomized to receive 250 mg lufotrelvir (n = 7), 500 mg lufotrelvir (n = 6), or placebo (n = 4) by continuous 120-hour infusion. No adverse events or serious adverse events were considered related to lufotrelvir. At doses of 250 and 500 mg, concentrations for the prodrug lufotrelvir and active moiety PF-00835231 increased in a dose-related manner. Unbound concentrations of the lufotrelvir active metabolite reached steady state approximately 2- and 4-fold that of in vitro EC90 following 250- and 500-mg doses, respectively. Conclusions: These safety and pharmacokinetic findings support the continued evaluation of lufotrelvir in clinical studies. Clinical Trials Registration. ClinicalTrials.gov NCT04535167.

Trichinella spiralis-associated myocarditis mimicking acute myocardial infarction.

BACKGROUND: Trichinellosis is a parasitic infection caused by nematodes of the genus Trichinella, and its principal mode of transmission is the consumption of raw or undercooked contaminated meat. Cardiac involvement in trichinellosis is unusual, yet it represents the most frequent cause of death. Here, we report a case in which Trichinella spiralis-associated myocarditis simulated a myocardial infarction. CASE PRESENTATION: A 35-year-old African man with no previous medical history was admitted to the emergency department for acute substernal discomfort at rest described as a pressure with no radiation. The electrocardiogram performed upon admission showed non-specific alterations of repolarization. Blood biology revealed high levels of troponin T and predominant eosinophilic leukocytosis. A transthoracic echocardiography was carried out and found a significant left ventricular concentric hypertrophy with a preserved ejection fraction. The septal and inferior walls, as well as the endocardium were hyperechogenic. The patient was hospitalized for eosinophilic myocarditis. The cause of hypereosinophilia was investigated, and a Trichinella spiralis serology came back strongly positive. A diagnosis of Trichinella spiralis associated-myocarditis was made.The patient was treated with albendazole-prednisolone dual therapy with favorable clinical and biological outcomes. CONCLUSION: The clinical suspicion of trichinellosis is based on suggestive epidemiology associated with the typical clinical presentation and the presence of eosinophilia. Eosinophilic myocarditis is a severe complication of trichinellosis which can result in death due to rhythm disorders. Chest pain, increase in troponins, and electrocardiographic abnormalities are all elements that can mimic a myocardial infarction and mislead clinicians.Abbreviations: ANCA: Anti-Neutrophil Cytoplasmic Antibodies; ANA: Anti-Nuclear Antibodies; ECDC: European Centre for Disease Prevention and Control; ECG: Electrocardiogram; ELISA: Enzyme-Linked ImmunoSorbent Assay; EMF: Endomyocardial Fibrosis; ES: Excretory-Secretory; ICT: International Commission on Trichinellosis; MRI: Magnetic Resonance Imaging.

Efficacy of systematic coronavirus screening by PCR and viral cultures in addition to triage in limiting the spread of SARS-CoV-2 within a hemodialysis unit.

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.

Invasive non-typhoidal Salmonella infection complicated by metastatic infections: Report of three cases.

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.

[Negative impact of COVID-19 pandemic on peritonitis rate in peritoneal dialysis patients: Pleading for a continuous educational training]. / Conséquences de la pandémie de COVID-19 sur le taux de péritonites de dialyse péritonéale : plaidoyer pour une formation continue ininterrompue.

BACKGROUND: Peritonitis is a common complication of chronic peritoneal dialysis treatment contributing to both technique failure and/or death. Little is effectively known about the actual benefits of a continuous training program on peritonitis rates. In the present study, we measured the impact of our patients' training protocol on peritonitis rates. We further studied which consequences the COVID-related disruption of our follow-up program had on peritonitis rates. METHODS: We present our yearly peritonitis rates since our patients' training and retraining program was implemented in 2010. We then focused our study on three consecutive years: 2019, 2020 (emergence of COVID-19), and 2021, collecting microbiological data from each peritonitis episode. Statistical analysis were used to corroborate our findings. RESULTS: Since 2010, peritonitis rates declined linearly (R2=0,6556; df=8; P<0.01) until its nadir in 2019 with 4 peritonitis episodes. The majority of infections were then treated in the outpatient Clinic. In 2020, our continuous technique evaluation decreased by 51% and 28 peritonitis episodes occurred, 47% secondary to strict cutaneous bacteria's, and 31% gastro-intestinal, irrespective of patients' experience or peritoneal dialysis modality. The hospitalization rate reached 71%. Having restored our protocol, we decreased peritonitis rates by 50% in 2021. CONCLUSIONS: Risk factors for peritonitis are identifiable and modifiable and require sustained intervention, continuous visual monitoring and training. These interventions significantly reduce peritonitis rates. Any brief interruption to patients' technique evaluation may elevate peritonitis rates significantly.

Clinical features of Legionnaires' disease at three Belgian university hospitals, a retrospective study.

INTRODUCTION: Legionnaires' disease (LD) is a recognised cause of community-acquired pneumonia. However, Legionella is an overlooked pathogen in hospital-acquired pneumonia. The European Surveillance System 2008-2017 found 23% of the Belgian LD reported cases being healthcare-related, with a higher death-rate than in community-acquired patients. This study aims to describe patients admitted for community-acquired LD or affected by hospital-acquired LD and investigate discriminants associated with lethality. METHODS: Medical records were retrospectively reviewed at three Belgian University Hospitals, between 1 January 2016 up to 31 January 2019. Hospital-acquired LD was defined as symptom onset at 10 days or more after admission, according to the Centres for Disease Control and prevention. Community-acquired LD was defined as diagnosis at admission or within 10 days after admission. RESULTS: Fifty patients were included in the study, among them 26% were diagnosed with hospital-acquired LD. The case-fatality rate was 22%, with eight of the eleven deceased patients (73%) being in the hospital-acquired LD group. Medical history of asthma or chronic obstructive pulmonary disease and higher sequential organ failure assessment (SOFA) score at diagnosis were more frequently observed in the hospital-acquired LD group. Furthermore, significantly lower SOFA score at diagnosis of LD and higher rates of treatment with levofloxacin or moxifloxacin were observed in survivors. CONCLUSION: In the current cohort, LD death-rate was mainly driven by hospital-acquired LD patients. Hospital-acquired LD might especially affect patients with chronic respiratory disease. Respiratory fluoroquinolones treatment and lower SOFA score at diagnosis may be associated with favourable outcomes.

Opportunistic peritonitis in peritoneal dialysis: The example of Paracoccus yeei.

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.

Cytomegalovirus haemorrhagic colitis complicating COVID-19 in an immunocompetent critically ill patient: A case report.

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.