Serial measurement of circulating calprotectin as a prognostic biomarker in COVID-19 patients in intensive care setting.

OBJECTIVES: Circulating calprotectin (cCLP) has been shown to be a promising prognostic marker for COVID-19 severity. We aimed to investigate the prognostic value of serial measurements of cCLP in COVID-19 patients admitted to an intensive care unit (ICU). METHODS: From November 2020 to May 2021, patients with COVID-19, admitted at the ICU of the OLV Hospital, Aalst, Belgium, were prospectively included. For sixty-six (66) patients, blood samples were collected at admission and subsequently every 48 h during ICU stay. On every sample (total n=301), a cCLP (EliA™ Calprotectin 2, Phadia 200, Thermo Fisher Scientific; serum/plasma protocol (for Research Use Only, -RUO-) and C-reactive protein (CRP; cobas c501/c503, Roche Diagnostics) analysis were performed. Linear mixed models were used to associate biomarkers levels with mortality, need for mechanical ventilation, length of stay at ICU (LOS-ICU) and medication use (antibiotics, corticosteroids, antiviral and immune suppressant/modulatory drugs). RESULTS: Longitudinally higher levels of all biomarkers were associated with LOS-ICU and with the need for mechanical ventilation. Medication use and LOS-ICU were not associated with variations in cCLP and CRP levels. cCLP levels increased significantly during ICU hospitalization in the deceased group (n=21/66) but decreased in the non-deceased group (n=45/66). In contrast, CRP levels decreased non-significantly in both patient groups, although significantly longitudinally higher CRP levels were obtained in the deceased subgroup. CONCLUSIONS: Serial measurements of cCLP provides prognostic information which can be useful to guide clinical management of COVID-19 patients in ICU setting.

A case report: septic shock due to (tropical) pyomyositis and multiple metastatic embolisms caused by Panton Valentine Leukocidin-positive methicillin-sensitive staphylococcus aureus in a 12-year-old boy.

CASE REPORT: A 12-year-old boy, of Congolese roots and without medical history, first presented to our Emergency Department 3 days after blunt trauma of the left ankle. The boy represented on two more occasions in the next 3 days due to ongoing pain. On the last occasion he presented with severe hypoglycaemia. He was diagnosed with severe septic shock, secondary to subperiosteal abscess formation / osteomyelitis of the ankle. The patient was transferred to the paediatric intensive care unit where appropriate medical care was provided, including broad-spectrum antibiotic therapy, high dose vasopressor / inotropic support, surgical debridement of abscesses and below-knee amputation. PANTON VALENTINE LEUKOCIDIN TOXIN AND PYOMYOSITIS TROPICALIS: The causative organism was a methicillin-susceptible S. aureus, which upon further identification was a carrier of the PVL (Panton Valentine leukocidin) toxin. This pathogen is responsible for severe musculoskeletal infections. In children these infections are often associated with more severe clinical course requiring a higher need for surgical intervention and longer hospital stay.Tropical pyomyositis is a disease caused by Staphylococcus aureus, often seen in tropical countries, and classically presented with muscle abscesses. Young males between the ages of 10-40 years old are the most susceptible, and often present with a history of blunt trauma. Treatment generally requires a combination of an anti-staphylococcal agent, and an anti-toxic agent blocking bacterial protein-synthesis of PVL. Source control by surgical debridement also plays a major role in the treatment of PVL-infection. Despite agressive treatment, mortality still varies from 0.5% to 2%.

Importance of In-Hospital Prospective Registry and Infectious Endocarditis Heart Team to Monitor and Improve Quality of Care in Patients with Infectious Endocarditis.

AIM: To investigate the value of prospective in-hospital registry data and the impact of an infectious endocarditis heart team approach (IEHT) on improvement in quality of care and monitor outcomes in hospitalized patients with IE. METHODS: Between December 2014 and the end of 2019, 160 patients were hospitalized in one centre with the definite diagnosis of infectious endocarditis (IE) and entered in a prospective registry. From 2017, an IEHT was introduced. Propensity score matching was used to assess the impact of an IEHT approach on clinical outcomes. RESULTS: Median age was 72.5 y (62.75-80.00), diabetes was present in 33.1%, chronic kidney disease in 27.5%, COPD in 17.5%, and a history of ischaemic heart disease in 30.6%. Prosthetic valve IE was observed in 43.8% and device-related IE in 16.9% of patients. Staphylococcus (37.5%) was the most frequent pathogen followed by streptococcus (24.4%) and enterococcus (23.1%). Overall, 30-day and 1-year mortality were 19.4% and 37.5%, respectively. The introduction of prospective data collection and IE heart team was associated with a trend towards reduction of adjusted 1-year mortality (26.5% IEHT vs. 41.2% controls, p = 0.0699). An IEHT clinical decision-making approach was independently associated with a shorter length of stay (p = 0.04). CONCLUSIONS: Use of a prospective registry of IE coupled with a heart team approach was associated with more efficient patient management and a trend towards lower mortality. Prospective data collection and dedicated IEHT have the potential to improve patient care and clinical outcomes.

Bacteremia and complicated parapneumonic effusion caused by Bordetella holmesii in an elderly patient.

We describe a case of bacteremia and a complicated parapneumonic effusion caused by Bordetella holmesii, in an elderly patient with underlying chronic hepatitis C infection.

Are VIDAS® anti-HEV IgM and IgG assays fit for reliable diagnosis of hepatitis E virus infections? Comparison & case story telling.

Objectives: Hepatitis E virus (HEV) genotype 3 is an emerging pathogen in developed countries. We evaluated the performance of two new serological assays for the detection of HEV, VIDAS® anti-HEV IgM and IgG. Methods: VIDAS® assays were performed on 77 clinical samples: 68 samples from patients suspected for HEV infection and 9 samples which previously tested positive for HEV IgM, IgG or HEV PCR. All samples were also tested using Wantai HEV assays. Cross-reactivity was assessed. To get a better view on the natural course of HEV infections, three clinical cases are described. Results: The concordance rate between VIDAS® and Wantai assays was good for HEV IgM (0.75,CI 0.52-0.98) and very good for HEV IgG (0.85,CI 0.72-0.98). Four samples tested borderline/positive with Wantai IgM but negative with VIDAS® IgM. All of these samples were HEV RNA negative, HEV IgG was positive in 2/4 samples. Five samples produced conflicting HEV IgG results. These tested positive with VIDAS® but negative with Wantai IgG. All five samples were HEV IgM and RNA negative. We detected no cross-reactivity. The clinical cases illustrate that HEV serology can still be negative in the very beginning of an acute infection. Conclusions: There is a good agreement between VIDAS® and Wantai anti-HEV IgM and IgG assays. Discrepant HEV IgM results probably reflect false positive Wantai IgM results (RNA-/IgG- samples) and longer-lasting positive Wantai IgM (RNA-/IgG+ samples). Discrepant HEV IgG results, could either represent resolved HEV infections (false negative Wantai IgG results) or false positive VIDAS® HEV IgG results.

Epidemiology of RSV and hMPV in Belgium: a 10-year follow-up.

Objectives: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are important respiratory pathogens. Both viral pathogens have similar clinical manifestations. The epidemiology of RSV is well known, that of hMPV is less clear. We reviewed the results of 10 consecutive years of molecular testing for RSV and hMPV in respiratory samples of Flemish patients. Methods: In the laboratory of the OLV hospital Aalst, Belgium, multiplex RT-PCR assays are used for the detection of RSV and hMPV. The lab receives invasive and noninvasive respiratory samples of patients from all over Flanders. Results: Between September 2006 and August 2016, 16,826 respiratory samples were analyzed for RSV and hMPV. Of these samples, 18% tested positive for RSV and 7.3% for hMPV. RSV consistently peaked in November/December each year within a very narrow time frame. The occurrence of hMPV was less predictable and spreaded more widely throughout the winter and spring. Both viruses were mainly found in samples from young children. RSV was most frequently detected in samples from infants <3 months, while hMPV peaked between 6 and 9 months. After the age of 1 year, RSV rapidly dropped. hMPV dropped a little later and slower. Both viruses slightly increased again at older age (>50 years). Conclusions: Despite their similarities, some of the epidemiologic characteristics of hMPV and RSV differ. The most striking difference is the annual distribution of RSV and hMPV infections.

How is the Xpert MRSA Gen 3 assay (Cepheid) performing on pooled eSwab medium?

The performance of the Xpert MRSA Gen 3 was compared to the Xpert MRSA on pooled eSwab media from nose, throat, and perineum using broth enriched cultured as gold standard. A lower specificity was found for the Xpert MRSA Gen 3 compared to the Xpert MRSA (91.8% versus 97.9%; P<0.05).

Multicenter evaluation of BD Veritor System and RSV K-SeT for rapid detection of respiratory syncytial virus in a diagnostic laboratory setting.

The recently introduced BD Veritor System RSV laboratory kit (Becton Dickinson, Sparks, MD, USA) with automatic reading was evaluated and compared with the RSV K-SeT (Coris BioConcept, Gembloux, Belgium) for the detection of respiratory syncytial virus (RSV) using 248 nasopharyngeal aspirates of children younger than 6 years old with respiratory tract infection. Compared to reverse transcriptase polymerase chain reaction as gold standard, both tests had an identical sensitivity of 78.1% and a specificity of 96.8% and 95.8% for the BD Veritor System and RSV K-SeT, respectively. Both antigen tests can be used to reliably confirm RSV in young children. However, a negative result does not definitively exclude the presence of RSV.

Characterisation of a collection of Streptococcus pneumoniae isolates from patients suffering from acute exacerbations of chronic bronchitis: in vitro susceptibility to antibiotics and biofilm formation in relation to antibiotic efflux and serotypes/serogroups.

The correlation between Streptococcus pneumoniae serotypes, biofilm production, antibiotic susceptibility and drug efflux in isolates from patients suffering from acute exacerbations of chronic bronchitis (AECB) remains largely unexplored. Using 101 isolates collected from AECB patients for whom partial (n=51) or full (n=50) medical details were available, we determined serotypes (ST)/serogroups (SG) (Quellung reaction), antibiotic susceptibility patterns [MIC (microdilution) using EUCAST and CLSI criteria] and ability to produce biofilm in vitro (10-day model; crystal violet staining). The majority of patients were 55-75 years old and <5% were vaccinated against S. pneumoniae. Moreover, 54% showed high severity scores (GOLD 3-4), and comorbidities were frequent including hypertension (60%), cancer (24%) and diabetes (20%). Alcohol and/or tobacco dependence was >30%. Isolates of SG6-11-15-23, known for large biofilm production and causing chronic infections, were the most prevalent (>15% each), but other isolates also produced biofilm (SG9-18-22-27 and ST8-20 being most productive), except SG7, SG29 and ST5 (<2% of isolates each). Resistance (EUCAST breakpoints) was 8-13% for amoxicillin and cefuroxime, 35-39% for macrolides, 2-8% for fluoroquinolones and 2% for telithromycin. ST19A isolates showed resistance to all antibiotics, ST14 to all except moxifloxacin, and SG9 and SG19 to all except telithromycin, moxifloxacin and ceftriaxone (SG19 only). Solithromycin and telithromycin MICs were similar. No correlation was observed between biofilm production and MIC or efflux (macrolides, fluoroquinolones). S. pneumoniae serotyping may improve AECB treatment by avoiding antibiotics with predictable low activity, but it is not predictive of biofilm production.

The preanalytical optimization of blood cultures: a review and the clinical importance of benchmarking in 5 Belgian hospitals.

Bloodstream infections remain a major challenge in medicine. Optimal detection of pathogens is only possible if the quality of preanalytical factors is thoroughly controlled. Since the laboratory is responsible for this preanalytical phase, the quality control of critical factors should be integrated in its quality control program. The numerous recommendations regarding blood culture collection contain controversies. Only an unambiguous guideline permits standardization and interlaboratory quality control. We present an evidence-based concise guideline of critical preanalytical determinants for blood culture collection and summarize key performance indicators with their concomitant target values. In an attempt to benchmark, we compared the true-positive rate, contamination rate, and collected blood volume of blood culture bottles in 5 Belgian hospital laboratories. The true-positive blood culture rate fell within previously defined acceptation criteria by Baron et al. (2005) in all 5 hospitals, whereas the contamination rate exceeded the target value in 4 locations. Most unexpected, in each of the 5 laboratories, more than one third of the blood culture bottles were incorrectly filled, irrespective of the manufacturer of the blood culture vials. As a consequence of this shortcoming, one manufacturer recently developed an automatic blood volume monitoring system. In conclusion, clear recommendations for standardized blood culture collection combined with quality control of critical factors of the preanalytical phase are essential for diagnostic blood culture improvement.

Performance of a new chromogenic medium, BBL CHROMagar MRSA II (BD), for detection of methicillin-resistant Staphylococcus aureus in screening samples.

Two chromogenic media for the detection of MRSA were compared: BBL CHROMagar MRSA II (BD) and MRSA ID agar (bioMérieux). Following overnight nonselective enrichment, 1,919 screening samples were inoculated on both chromogenic agars. After 24 h, the sensitivities of both media were high and comparable. Both media showed an important decrease in specificity after 48 h of incubation (decreases of 8% for MRSA II and 10% for MRSA ID), but MRSA II was significantly more specific at both time points.

First case of Staphylococcus pseudintermedius infection in a human.

We present the first clinical report of a Staphylococcus pseudintermedius infection in a human. Biochemically, S. pseudintermedius can be easily misidentified as S. aureus. Therefore, the final microbiological identification requires the combination of phenotypic and genotypic tests.

Prevalence and correlates of nonadherence to antiretroviral therapy in a population of HIV patients using Medication Event Monitoring System.

Nonadherence to antiretroviral therapy (ART) jeopardizes good clinical outcome in people living with HIV. In a single-center prospective study, prevalence and correlates of nonadherence were investigated in 43 patients on ART. Nonadherence was assessed using Medication Event Monitoring System (MEMS), self-report and collateral report of treating physicians. Based on MEMS data, median taking adherence, dosing adherence, and timing adherence was 98% (interquartile range [IQR] = 5.3), 91.5% (IQR = 18), and 86% (IQR = 31.5), respectively. The median number of drug holidays per 100 days was 0.8 (IQR = 4.8). The prevalence of nonadherence measured by MEMS was 40%. Self-reported nonadherence and collateral report of nonadherence by physicians varied from 5% to 41% and 24% to 28%, respectively. Patients were categorized as adherent or nonadherent based on a clinically validated algorithm derived from MEMS parameters. Nonadherent patients used significantly more escaping coping strategies (p = 0.003) and planned problem solving strategies (p = 0.049), were prescribed significantly more antiretroviral medications (p = 0.02) and were significantly longer on ART (p = 0.04) than adherent patients. Identified correlates of nonadherence may help clinicians in detecting patients with HIV at risk for nonadherence and can support the development of adherence enhancing interventions.

A combination of poor adherence and a low baseline susceptibility score is highly predictive for HAART failure.

The relationship between adherence, virological response to highly active antiretroviral therapy (HAART) and the presence and development of genotypic resistance was assessed in 41 HIV-infected patients on HAART. Four adherence parameters (drug taking adherence, dosing adherence, timing adherence and drug holidays) were scored prospectively using electronic event monitoring. Genotypic resistance at baseline and after therapy failure was scored retrospectively and a genotype-based susceptibility score was calculated. Overall median adherence rates were high. All adherence parameters were better in virological responders (n=31) compared to non-responders (n=10), drug taking adherence and number of drug holidays being significantly different. Responders had a significantly higher susceptibility score. Stepwise logistic regression showed that the number of drug holidays and a low susceptibility score were highly predictive for therapy failure. Despite the presence of a limited number of baseline resistance mutations, perfectly adherent patients can control virus replication for a prolonged period.

Nonadherence to highly active antiretroviral therapy: clinically relevant patient categorization based on electronic event monitoring.

Adherence to highly active antiretroviral therapy (HAART) is crucial, but which aspects of drug-taking behavior are important remain largely unknown. In a prospective observational study, 43 HIV-1-infected patients taking HAART underwent electronic event monitoring (EEM). Taking adherence was defined as the percentage of doses taken compared with the number prescribed, dosing adherence was defined as the percentage of days on which all doses were taken, and timing adherence was defined as the percentage of doses taken within 1 hr of the time prescribed. Drug holidays were defined as periods of no drug intake for >24 hr. Cluster analysis, including the four EEM parameters, was used and refined to construct an algorithm to discriminate patients. Patients were categorized as nonadherent if they had a taking adherence of <90%, or a dosing adherence of <75% and at least 1 drug holiday, or a timing adherence of <80% and at least 1 drug holiday, or >6 drug holidays per 100 days. All four EEM parameters differed significantly (p < 0.0001) between the two groups. Adherent patients had a better outcome, as shown by a larger drop in viral load (p = 0.011) and rise in CD4+ cell count (p = 0.035), showing that the algorithm-based categorization is clinically relevant.