Clinical, virological, and operational aspects of a single-center Belgian experience with in-hospital infusions of casirivimab/imdevimab and sotrovimab for mild/moderate COVID-19.

OBJECTIVES: To describe the clinical and virological characteristics of COVID-19 patients treated in a hospital with casirivimab/imdevimab and sotrovimab between June 2021 and April 2022 and to report the logistics for administering these monoclonal antibodies (mAbs). METHODS: All COVID-19 adult patients treated with mAbs at CHU Charleroi (Belgium) were included. A multidisciplinary monoclonal antibodies team (MMT) was dedicated to identify eligible patients and coordinate the administration of mAbs in a temporary structure created within the hospital. RESULTS: A total of 69 COVID-19 patients were treated with casirivimab/imdevimab (11.6%) and sotrovimab (88.4%) within a median of 4 days of symptom onset, mainly during the Omicron B.1.1.529 period (71%); no severe adverse events occurred. Thirty-eight (55%) were outpatients, and among the 31 inpatients, 42% were nosocomial COVID-19. The median age was 65 years [IQR, 50-73], and 53.6% were male. The most common risk factors for progression to severe COVID-19 were immunosuppression (72.5%), arterial hypertension (60.9%) and age>65 years (47.8%). One fifth were SARS-CoV-2-unvaccinated patients. The median Belgian MASS score for patient prioritization was 6 [IQR, 4-8]. On Day 29, 10.5% of the outpatients were hospitalized, and 1.4% were admitted to an intensive care unit (ICU); there were no COVID-19-related deaths. General practitioners referred 19.4% of the outpatients. CONCLUSIONS: In our experience, mAbs were prescribed in very high-risk patients with no adverse events, few progressions to severe COVID-19, and no related deaths. Our MMT has improved coordination of COVID-19 treatment and contribute to enhance communication with primary care.

Epidemiology and outcome of anaerobic bacteremia in a tertiary hospital.

Despite a low incidence, anaerobic bacteremia remains a serious and often underestimated condition. This retrospective study aims to describe the epidemiology of anaerobic bacteremia and to identify risk factors affecting mortality and the impact of treatment. We included all positive anaerobic blood cultures from January 2018 to December 2019 at the University Hospital of Charleroi (Belgium). We identified 105 episodes of clinically significant anaerobic bacteremia (mean age of patients: 66.4 +/- 16.8 years). The main comorbidities were hypertension, chronic kidney disease, and diabetes. Bacteremia was community-acquired in 70.5% of the episodes. Two thirds of the blood cultures were mono-microbial, and the commonest bacteria found were Bacteroides fragilis group (31.4%), Fusobacterium spp. (17.1%) and Clostridium spp. (15.2%). The main sources of bacteremia were abdominal (35.2%), urinary (17.1%), osteoarticular (14.2%) and pulmonary (12.3%). Surgery within 30 days before hospitalization was more frequent in patients with nosocomial bacteremia (45.2% vs 2.7%, p < 0.0001). An appropriate empirical antibiotic therapy was initiated in 74.7% of patients, and the median duration of antibiotic therapy was 10 [5 - 15] days. One third of patients had a surgical management. Patients who did not survive at day 30 (n = 23 [21.9%]) had significantly lower time to positivity (TTP) values than patients alive at day 30, presented more often with sepsis, had higher Charlson scores and chronic kidney disease, and were more likely to suffer from Clostridium spp. bacteremia. In a Cox proportional hazard analysis, sepsis (OR: 7.32 [95% CI: 2.83- 18.97], p< 0.0001) was identified as an independent risk factors for 30-day mortality, whereas time to positivity ≥ 30 h (OR: 0.24 [95% CI: 0.07 - 0.84], p = 0.025) and an adequate empirical antibiotic therapy (OR: 0.37 [95% CI: 0.15 - 0.94], p = 0.037) were associated with better outcomes. Anaerobic bacteremia has a high mortality rate which justifies the maintenance of empirical antibiotic therapy.

Impact of collaborative physician-pharmacist stewardship strategies on prophylactic antibiotic practices: a quasi-experimental study.

BACKGROUND: An effective use of surgical antibiotic prophylaxis (SAP) appears essential to prevent the development of infections linked to surgery while inappropriate and excessive prescriptions of prophylactic antibiotics increase the risk of adverse effects, bacterial resistance and Clostridium difficile infections. In this study, we aimed to analyze SAP practices in an acute secondary hospital in Belgium during the years 2016-2021 in order to evaluate the impacts of combined stewardship interventions, implemented thanks to a physician-pharmacist collaboration. METHODS: A quasi-experimental study on SAP practices was conducted during 5 years (2016-2021) in a Belgian University Hospital. We first performed a retrospective observational transversal study on a baseline group (2016.1-2016.4). Then, we constituted a group of patients (2017.1-2017.4) to test a combined intervention strategy of stewardship which integrated the central role of a pharmacist in antibiotic stewardship team and in the pre-operative delivery of nominative kits of antibiotics adapted to patient factors. After this test, we collected patient data (2018.1-2018.4) to evaluate the sustained effects of stewardship interventions. Furthermore, we evaluated SAP practices (2019.1-2019.4) after the diffusion of a computerized decision support system. Finally, we analyzed SAP practices in the context of the COVID-19 pandemic (2020.1-2020.4 and 2021.1-2021.4). The groups were compared from year to year in terms of compliance to institutional guidelines, as evaluated from seven criteria (χ2 test). RESULTS: In total, 760 surgical interventions were recorded. The observational study within the baseline group showed that true penicillin allergy, certain types of surgery and certain practitioners were associated with non-compliance (p < 0.05). Compared with the baseline group, the compliance was significantly increased in the test group for all seven criteria assessed (p < 0.05). However, the effects were not fully sustained after discontinuation of the active interventions. Following the diffusion of the computerized decision support system, the compliance to guidelines was not significantly improved. Finally, the COVID-19 pandemic did not appear to affect the practices in terms of compliance to guidelines. CONCLUSIONS: This study shows that optimization of SAP practices is achievable within a proactive multidisciplinary approach including real-time pharmaceutical interventions in the operating area and in the care units practicing SAP.

Mitral endocarditis caused by Achromobacter xylosoxidans in an older patient: Case report and literature review.

We report a rare case of recurrent Achromobacter xylosoxidans bacteremia in an older woman in 2014 and 2020. During the more recent bacteremia, a diagnosis of mitral endocarditis was made. The patient could not have surgery because of severe comorbidities and a high operative risk. Combined antibiotic therapy was given with piperacillin/tazobactam and trimethoprim/sulfamethoxazole (TMP/SMX). Antibiotic therapy was administered for six weeks with a good response, but the patient relapsed after six days with A. xylosoxidans bacteremia and cardiac decompensation. Antibiotic therapy was resumed, using meropenem and TMP/SMX, but the patient died one month after the recurrence. We review the 22 cases of A. xylosoxidans endocarditis that have been described in the literature.

Antibiotic use in patients with Coronavirus disease 2019 (COVID-19): outcomes and associated factors.

OBJECTIVES: To characterise the factors, outcomes and infections associated with antibiotic use in COVID-19 patients. METHODS: Records of patients with RT-PCR-confirmed COVID-19, hospitalized at the CHU Charleroi (Belgium) between 11 March and 3 May 3 2020, were retrospectively reviewed. Factors associated with antibiotic treatment, outcomes and bacterial infections were analysed. RESULTS: Among the 164 hospitalized COVID-19 patients (median age 60.5 years [IQR] 46-79), twenty-five (15.2%) were admitted to the ICU. Twenty-six (15.9%) died in the hospital. One hundred (61%) received antibiotic treatment. Combination therapies with macrolides were more common in the early part of the study period (26/67, 38.8%). Twenty-eight patients (17.1%) had a confirmed infection, mostly of the urinary tract (18/28, 64.3%). Only 2 (1.2%) had a documented respiratory coinfection. Six of the 7 ICU infections (85.7%) were superinfections. Gram-negative bacteria were most frequently isolated. In multivariate analysis, six factors were associated with antibiotic use: being hospitalized in the ICU (OR: 4.59; 95% CI 1.07-19.71), age > 65 years (OR: 4.16; 95% CI 1.72-10.05), arrival from a nursing home (OR: 4.59; 95% CI 1.11-19.71), diabetes (OR: 4.35; 95% CI 1.26-14.93), bilateral consolidation on chest CT (OR: 9.92; 95% CI 2.40-41.06) and a C-reactive protein level > 60 mg/L (OR:2.46; 95% CI 1.13-5.37). Antibiotic treatment did not reduce the length of stay or the mortality rate. CONCLUSION: Antibiotics have been overused during the COVID-19 pandemic, despite a low rate of coinfections . Integrating the antimicrobial stewardship (AMS) programme into the COVID-19 response is essential.

Ulnar infected pseudoaneurysm in the course of extended-spectrum beta-lactamase Escherichia coli septicemia.

We describe the first case of proximal ulnar pseudoaneurysm due to extended-spectrum beta-lactamase-producing Escherichia coli. We performed an open ligation of the ulnar artery and partial excision of the aneurysmal sac. This article discusses the etiology and surgical management of ulnar-infected pseudoaneurysms according to the literature data.

Food poisoning due to a TSST1-producing Staphylococcus aureus.

Toxic Shock Syndrome (TSS) is a very rare and severe complication of Staphylococcus aureus infections. However, bacteremia is very uncommon in this disease. We present here the case of a healthy 15-year old boy who presented septic shock and diffuse exanthema four hours after eating in a fast food restaurant. Blood cultures were positive for a TSST-1 producing Staphylococcus aureus. The patient was treated with antibiotics and fully recovered.

Corrigendum: CSF HIV RNA Escape in Opsoclonus-Myoclonus-Ataxia Syndrome: Case Report and Review of the Literature.

[This corrects the article DOI: 10.3389/fneur.2020.585527.].

CSF HIV RNA Escape in Opsoclonus-Myoclonus-Ataxia Syndrome: Case Report and Review of the Literature.

Background: Human immunodeficiency viruses (HIV) infection is associated with a broad range of neurological manifestations, including opsoclonus-myoclonus ataxia syndrome (OMAS) occurring in primary infection, immune reconstitution syndrome or in case of opportunistic co-infection. Case: We report the exceptional case of a 43-year-old female under HIV treatment for 10 years who presented initially with suspected epileptic seizure. Although the clinical picture slightly improved under anti-epileptic treatment, it was rapidly attributed to OMAS. The patient exhibited marked opsoclonus, mild dysarthria, upper limbs intermittent myoclonus, ataxia in 4 limbs, truncal ataxia, and a severe gait ataxia (SARA score: 34). The diagnostic work-up showed radiological and biological signs of central nervous system (CNS) inflammation and cerebral venous sinus thromboses. The HIV viral load was higher in cerebrospinal fluid (CSF) than in the blood (4,560 copies/ml vs. 76 copies/ml). She was treated for 5 days with pulsed corticotherapy. Dolutegravir and anticoagulation administration were initiated. Follow-ups at 2 and 4 months showed a dramatic improvement of clinical neurologic status (SARA score at 4 months: 1), reduction of CNS inflammation and revealed undetectable CSF and serum viral loads. Conclusion: This case underlines the importance of the evaluation of the CSF viral load in HIV patients developing OMAS and suggests CSF HIV RNA escape as a novel cause for OMAS.

Infectious Mononucleosis Resulting in Acute Necrotizing Mediastinitis: A Case Report and Literature Review.

The serological prevalence of Epstein-Barr virus (EBV) among young adults exceeds 90% worldwide. Even though EBV primary infection is usually benign, severe complications can occur in adolescents and young adults and so the disease must be promptly diagnosed. The development of an oropharyngeal abscess leading to a descending necrotizing mediastinitis (DNM) is exceptional and potentially lethal, so early diagnosis with a CT scan, appropriate antibiotics and surgery are essential. The authors present a case where DNM was associated with reactive hemophagocytic syndrome as a result of infectious mononucleosis, as well as a review of similar cases in the English literature. LEARNING POINTS: The incidence of serious complications in Epstein-Barr virus (EBV) primary infection increases with age.Respiratory symptoms (e.g., pleuritic pain, dyspnoea) and unusually prolonged fever (>10 days) in patients with infectious mononucleosis could be 'red flags' for life-threatening complications such as empyema and descending necrotizing mediastinitis.The threshold for performing cervical and chest computed tomography in septic patients with infectious mononucleosis should be low.

Outcome of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia: impact of diabetes.

The aim of this study was to describe the epidemiology of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia in a diabetic and a non-diabetic population of the University Hospital of Charleroi and to analyze medical outcomes, including risk of metastatic infection and mortality. Descriptive and multivariable analyses were performed using MedCalc 18.9 (MedCalc Software bvba, Ostend, Belgium). A total of 248 patients with MSSA bacteremia were identified between 1st January 2012 and 28th June 2017 out of which 32.7% were diabetic. Within the diabetic patients, we observed more prolonged hospital duration of stay (p = 0.034), more secondary bacteremia of cutaneous sources (including cellulitis, diabetic foot and ulcer) (p = 0.037), and more metastatic infection (p = 0.002). The overall 30-day mortality was 24.2% with no difference between the two groups. With a logistic regression analysis, it was demonstrated that age ≥ 60 years (odds ratio (OR), 2.20 (95% CI, 1.03-4.67)) and Charlson Comorbidity Index (CCI) ≥ 3 (OR, 2.95 (95% CI, 1.51-5.79)) were the only independent risk factors of mortality, while removal of the primary site of infection was a protective factor (OR, 0.27 (95% CI, 0.12-0.62)). Risk of developing metastatic infection was increased with diabetes (OR, 2.08 (95% CI, 1.12-3.90)), while early empirical antibiotic therapy (OR, 0.38 (95% CI, 0.20-0.71)) decreased this risk. Diabetes was not associated with increased 30-day mortality after MSSA bacteremia. However, diabetes increased significantly the risk of metastatic infection. An aggressive treatment of MSSA bacteremia seems crucial to improve the outcome of diabetic patients.

[Large granular lymphocytic leukemia CD3-CD56-: a challenge for the biologist and the physician]. / Leucémie à grands lymphocytes granuleux CD3-CD56- : un défi pour le biologiste et le clinicien.

Large granular lymphocyte leukemia (LGL) are chronic lymphoproliferative disorders classified into three main groups: T-cell LGL leukemia (T-LGL), aggressive NK-cell leukemia and chronic lymphoproliferative disorder of NK cells (NK-LGL). Patients with LGL leukemia exhibit chronic (>3 months) and moderate (<1G/L) to substantial monoclonal expansion of large granular lymphocytes in the peripheral blood. Cytologically, large granular lymphocytes are medium to large cells which are further characterized by an eccentric nucleus and a slightly basophilic cytoplasm containing azurophilic granules. Typically, T-LGL (CD3-and mostly CD8+) can be differentiated from NK-LGL disorders (CD3-) based on flow cytometry analysis. However, distinction between LGL leukemias can be tricky. We report here the case of a 47-year-old woman patient diagnosed with large granular lymphocytes leukemia associated with atypical CD3-CD56- immunophenotyping and clinical manifestations of pseudo-Felty's syndrome.

Genetic characteristics and antimicrobial resistance of Staphylococcus epidermidis isolates from patients with catheter-related bloodstream infections and from colonized healthcare workers in a Belgian hospital.

BACKGROUND: Staphylococcus epidermidis is a pathogen that is frequently encountered in the hospital environment. Healthcare workers (HCWs) can serve as a reservoir for the transmission of S. epidermidis to patients. METHODS: The aim of this study was to compare and identify differences between S. epidermidis isolated from 20 patients with catheter-related bloodstream infections (CRBSIs) and from the hands of 42 HCWs in the same hospital in terms of antimicrobial resistance, biofilm production, presence of the intercellular adhesion (ica) operon and genetic diversity (pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome (SCC) mec typing). RESULTS: S. epidermidis isolates that caused CRBSI were resistant to significantly more non-betalactam drugs than were isolates collected from HCWs. Among the 43 mecA positive isolates (26 from HCWs), the most frequent SCCmec type was type IV (44%). The ica operon was significantly more prevalent in CRBSI isolates than in HCWs (P < 0.05). Weak in vitro biofilm production seemed to correlate with the absence of the ica operon regardless of the commensal or pathogenic origin of the isolate. The 62 isolates showed high diversity in their PFGE patterns divided into 37 different types: 19 harbored only by the CRBSI isolates and 6 shared by the clinical and HCW isolates. MLST revealed a total of ten different sequence types (ST). ST2 was limited to CRBSI-specific PFGE types while the "mixed" PFGE types were ST5, ST16, ST88 and ST153. CONCLUSION: One third of CRBSI episodes were due to isolates belonging to PFGE types that were also found on the hands of HCWs, suggesting that HCW serve as a reservoir for oxacillin resistance and transmission to patients. However, S. epidermidis ST2, mecA-positive and icaA-positive isolates, which caused the majority of clinically severe CRBSI, were not recovered from the HCW's hands.

A multicenter quasi-experimental study: impact of a central line infection control program using auditing and performance feedback in five Belgian intensive care units.

BACKGROUND: We analyzed the impact associated with an intervention based on process control and performance feedback to decrease central line-associated bloodstream infection (CLABSI) rates.This study was conducted from March 2011 to September 2012 in five adult intensive care units (ICU) located in two Belgian tertiary hospitals A and B, with a total of 53 beds. METHODS: This study was divided in three phases: P1 (baseline), P2 (intervention) and P3 (post intervention).During P2, external monitoring of five central venous catheters (CVC) care critical processes and monthly reporting (meetings and feedbacks reports posted) of performance indicators (CLABSI rate, CVC utilization ratio, compliance rate with each care process, and insertion site) to ICU workers were performed. The external monitoring of process measures was assessed by the same trained research nurse.A Poisson regression analysis was used to compare CLABSI incidence density rate per phase. Statistical significance was achieved with 2-sided p-value of <0.05. For the analysis, we separated the five ICU in hospital A and B when appropriate. RESULTS: Significantly improved total mean compliance was achieved for hand hygiene, CVC handling and CVC dressing. CLABSI rate declined from 4.00 (95% confidence interval (CI): 1.94-6.06) to 1.81 (0.46-3.17) per 1,000 CVC-days in P2 with an incidence rate ratio (IRR) of 0.49 (0.24-0.98, p = 0.043). A better response was observed in hospital A where the nurse participation at the monthly meeting was significantly higher than in hospital B (p < 0.001) as the percentage of feedbacks reports posted in ICU (p < 0.001). The decline in the CLABSI rate observed during P2 in comparison with P1 was independent of the insertion site (femoral or non-femoral; p = 0.054). The overall CLABSI rate increased to 2.73 (1.17-4.29) per 1,000 CVC-days with IRR of 0.67 (0.36-1.26, p = 0.212) in P3 compared to P1, but a high nursing turnover was observed in both hospitals. CONCLUSIONS: Our intervention focused on external auditing and performance feedback resulted in significant reduction in rates of CLABSI. Investigation continues regarding the most effective way to sustain CLABSI prevention practices and to improve the culture of safety in healthcare.

Variations in catheter-related bloodstream infections rates based on local practices.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) surveillance serves as a quality improvement measure that is often used to assess performance. We reviewed the total number of microbiological samples collected in three Belgian intensive care units (ICU) in 2009-2010, and we described variations in CRBSI rates based on two factors: microbiological documentation rate and CRBSI definition which includes clinical criterion for coagulase-negative Staphylococcus (CNS) episode. FINDINGS: CRBSI rates were 2.95, 1.13 and 1.26 per 1,000 estimated catheter-days in ICUs A, B and C, respectively. ICU B cultured fewer microbiological samples and reported the lowest CRBSI rate. ICU C had the highest documentation rate but was assisted by support available from the laboratory for processing single CNS positive blood cultures. With the exclusion of clinical criterion, CRBSI rates would be reduced by 19%, 45% and 0% in ICUs A, B and C, respectively. CONCLUSION: CRBSI rates may be biased by differences of blood culture sampling and CRBSI definition. These observations suggest that comparisons of CRBSI rates in different ICUs remain difficult to interpret without knowledge of local practices.

Management and outcome of high-risk peritonitis: a retrospective survey 2005-2009.

OBJECTIVES: To describe the clinical and microbiological aspects of high-risk peritonitis and to analyze their impact on its outcome. METHODS: This was a retrospective review of all culture-positive peritonitis between October 1, 2005 and September 30, 2009. In accordance with recent Infectious Diseases Society of America (IDSA) guidelines, a group of high-risk peritonitis patients was selected based on age, severity of illness, underlying diseases, and acquisition of the infection. RESULTS: Ninety-three patients with high-risk peritonitis were studied; these patients were divided into subgroups of those with community-associated disease (14%) and those with healthcare-associated disease (86%). The median age of patients was 66 (interquartile range (IQR) 22-95) years. The 30-day mortality rate was 25%. Subgroups differed in age (p=0.011), degree of comorbidity (p=0.023), severity of peritonitis (p=0.036), admission to the intensive care unit (ICU) (p=0.002), length of ICU stay (p<0.001), length of hospital stay (p<0.001), cure at day 30 (p=0.001), and adequate treatment (p=0.042). The microbiological etiology and resistance profiles were similar between the patient groups. Adequate empirical treatment was not related to a better outcome. Severity of disease (p=0.005) and the presence of enterococci (p=0.044) were independently associated with mortality. CONCLUSIONS: The mode of acquisition influences severity and certain parameters of outcome in high-risk peritonitis, but not its microbiological etiology. The outcome seems to depend primarily on severity of peritonitis and much less on the adequacy of treatment.

Upper gastrointestinal bleeding related to emphysematous cholecystitis due to Clostridium perfringens.

We describe the case of a 46-year-old man admitted for upper gastrointestinal bleeding in the context of cirrhosis. A deep bleeding duodenal ulcer was treated by sclerotherapy. Abdominal pain and fever lead us to perform an abdominal computed tomography, which demonstrated emphysematous cholecystitis. An emergency cholecystectomy was performed and antimicrobial therapy initiated. The patient recovered uneventfully. Links between ulcers and emphysematous cholecystitis are discussed.