Monocentric, Retrospective Study on Infectious Complications within One Year after Solid-Organ Transplantation at a Belgian University Hospital.

The epidemiology, diagnostic methods and management of infectious complications after solid-organ transplantation (SOT) are evolving. The aim of our study is to describe current infectious complications in the year following SOT and risk factors for their development and outcome. We conducted a retrospective study in adult SOT recipients in a Belgian university hospital between 2018 and 2019. We gathered demographic characteristics, comorbidities leading to transplantation, clinical, microbiological, surgery-specific and therapeutic data concerning infectious episodes, and survival status up to one year post-transplantation. Two-hundred-and-thirty-one SOT recipients were included (90 kidneys, 79 livers, 35 lungs, 19 hearts and 8 multiple organs). We observed 381 infections in 143 (62%) patients, due to bacteria (235 (62%)), viruses (67 (18%)), and fungi (32 (8%)). Patients presented a median of two (1-5) infections, and the first infection occurred during the first six months. Nineteen (8%) patients died, eleven (58%) due to infectious causes. Protective factors identified against developing infection were obesity [OR [IC]: 0.41 [0.19-0.89]; p = 0.025] and liver transplantation [OR [IC]: 0.21 [0.07-0.66]; p = 0.007]. Risk factors identified for developing an infection were lung transplantation [OR [IC]: 6.80 [1.17-39.36]; p = 0.032], CMV mismatch [OR [IC]: 3.53 [1.45-8.64]; p = 0.006] and neutropenia [OR [IC]: 2.87 [1.27-6.47]; p = 0.011]. Risk factors identified for death were inadequate cytomegalovirus prophylaxis, infection severity and absence of pneumococcal vaccination. Post-transplant infections were common. Addressing modifiable risk factors is crucial, such as pneumococcal vaccination.

Cardiac Adverse Events and Remdesivir in Hospitalized Patients With COVID-19: A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial.

BACKGROUND: We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. METHODS: This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. RESULTS: Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI], .7-1.5; P = .98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI, .7-1.7; P = .68). CONCLUSIONS: Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT04315948; EudraCT 2020-000936-23.

Incidence and clinical and microbiological features of invasive and probable invasive streptococcal group A infections in children and adults in the Brussels-Capital Region, 2005-2020.

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.

Analysis of a Combined HBHA and ESAT-6-Interferon-γ-Release Assay for the Diagnosis of Tuberculous Lymphadenopathies.

BACKGROUND AND OBJECTIVES: The incidence of tuberculosis lymphadenopathy (TBLA) is increasing, and diagnostic procedures lack sensitivity and are often highly invasive. TBLA may be asymptomatic, and differential diagnosis with other adenopathies (ADPs) is difficult. We evaluated a blood-cell interferon-γ release assay (IGRA) with two different stage-specific mycobacterial antigens for the differential diagnosis of ADP suspected of mycobacterial origin. METHODS: Twenty-one patients were included and divided into three groups: (1) cervical/axillar ADP (n = 8), (2) mediastinal ADP (n = 10), and (3) disseminated ADP (n = 3). The mycobacterial antigens used for the IGRA were the heparin-binding haemagglutinin (HBHA) and the early-secreted antigenic target-6 (ESAT-6), a latency-associated antigen and a bacterial replication-related antigen, respectively. Diagnosis of TBLA based on microbiological results and/or response to anti-TB treatment was obtained for 15 patients. RESULTS: An IGRA profile highly suggestive of active TB (higher IFN-γ response to ESAT-6 compared to HBHA) was found for 3/6 TBLA patients from group 1, and for all the TBLA patients from groups 2 and 3, whereas this profile was not noticed in patients with a final alternative diagnosis. CONCLUSION: These results highlight the potential value of this combined HBHA/ESAT-6 IGRA as a triage test for the differential diagnosis of ADP.

Perioperative antimicrobial prophylaxis in patients undergoing pancreatoduodenectomy: retrospective analysis of bacteriological profile and susceptibility.

BACKGROUND: Pancreatic tumours are frequently associated with obstructive jaundice requiring preoperative biliary drainage (PBD) before pancreatoduodenectomy (PD), exposing patients to infectious complications. This study aims to compare postoperative complications after PD with or without PBD and to analyse bile bacteriology and antibiotic susceptibility. METHODS: All patients undergoing PD between 2014 and 2019 were retrospectively evaluated, and postoperative outcomes were compared according to PBD use. Prophylactic narrow-spectrum antibiotic therapy was given for 24 h, then adapted according to bacteriologic profile. Intraoperative bile cultures and antibiograms were collected. RESULTS: Among 164 patients with intraoperative bile culture during PD (75 PBD+, 89 PBD-), an infected bile was observed in 95% and 70% of PBD + and PBD- groups, respectively (p < 0.001). Postoperative mortality and severe morbidity including infectious complications were similar between groups (5% and 15%). The median duration of antibiotherapy was longer in PBD + compared to PBD- groups (9 vs. 2 days, p = 0.009). Malignant indication and PBD were associated with bile contamination using univariate analysis, and PBD was significantly relevant at multivariate analysis. Most common pathogens identified in bile cultures were Escherichia coli, Klebsiella spp. and Enterobacter spp. Overall antibiotic susceptibility to commonly used antibiotics was decreased, including those used in our local guidelines. CONCLUSIONS: PBD exposes nearly 100% of patients undergoing PD to bile infection and an increased duration of postoperative antimicrobial therapy, without increasing infectious complications in this study. Adaptation of antimicrobial prophylaxis should be further evaluated according to performance of PBD and local epidemiology, in order to avoid overuse of antibiotics.

Immuno-Diagnosis of Active Tuberculosis by a Combination of Cytokines/Chemokines Induced by Two Stage-Specific Mycobacterial Antigens: A Pilot Study in a Low TB Incidence Country.

Active tuberculosis (aTB) remains a major killer from infectious disease, partially due to delayed diagnosis and hence treatment. Classical microbiological methods are slow and lack sensitivity, molecular techniques are costly and often unavailable. Moreover, available immuno-diagnostic tests lack sensitivity and do not differentiate between aTB and latent TB infection (LTBI). Here, we evaluated the performance of the combined measurement of different chemokines/cytokines induced by two different stage-specific mycobacterial antigens, Early-secreted-antigenic target-6 (ESAT-6) and Heparin-binding-haemagglutinin (HBHA), after a short in vitro incubation of either peripheral blood mononuclear cells (PBMC) or whole blood (WB). Blood samples were collected from a training cohort comprising 22 aTB patients, 22 LTBI subjects and 17 non-infected controls. The concentrations of 13 cytokines were measured in the supernatants. Random forest analysis identified the best markers to differentiate M. tuberculosis-infected from non-infected subjects, and the most appropriate markers to differentiate aTB from LTBI. Logistic regression defined predictive abilities of selected combinations of cytokines, first on the training and then on a validation cohort (17 aTB, 27 LTBI, 25 controls). Combining HBHA- and ESAT-6-induced IFN-γ concentrations produced by PBMC was optimal to differentiate infected from non-infected individuals in the training cohort (100% correct classification), but 2/16 (13%) patients with aTB were misclassified in the validation cohort. ESAT-6-induced-IP-10 combined with HBHA-induced-IFN-γ concentrations was selected to differentiate aTB from LTBI, and correctly classified 82%/77% of infected subjects as aTB or LTBI in the training/validation cohorts, respectively. Results obtained on WB also selected ESAT-6- and HBHA-induced IFN-γ concentrations to provided discrimination between infected and non-infected subjects (89%/90% correct classification in the training/validation cohorts). Further identification of aTB patients among infected subjects was best achieved by combining ESAT-6-induced IP-10 with HBHA-induced IL-2 and GM-CSF. Among infected subjects, 90%/93% of the aTB patients were correctly identified in the training/validation cohorts. We therefore propose a two steps strategy performed on 1 mL WB for a rapid identification of patients with aTB. After elimination of most non-infected subjects by combining ESAT-6 and HBHA-induced IFN-γ, the combination of IP-10, IL-2 and GM-CSF released by either ESAT-6 or HBHA correctly identifies most patients with aTB.

Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial.

BACKGROUND: The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. OBJECTIVES: To estimate the effect of remdesivir in blocking viral replication. METHODS: We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells). RESULTS: In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5-3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0-1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8-25-fold) and the median time to viral clearance by 2.4 days (IQR: 0.9-4.5 days). CONCLUSIONS: Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.

BACKGROUND: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. METHODS: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. FINDINGS: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). INTERPRETATION: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. FUNDING: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.

BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2:FiO2) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 µg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 µg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 µg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. FINDINGS: Between April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. INTERPRETATION: Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. FUNDING: Belgian Health Care Knowledge Center and VIB Grand Challenges program.

Clinical Course and Risk Factors for Infection in Severe Forms of Alcohol-Associated Liver Disease.

BACKGROUND AND AIMS: Infection is a major driver of mortality in patients with advanced alcohol-associated liver disease (ALD). The epidemiology and clinical course of patients infected with life-threatening forms of ALD, including severe alcohol-associated hepatitis (sAH) and decompensated alcohol-associated cirrhosis (DAC), and specific risk factors for infection remain mostly unknown. APPROACH AND RESULTS: In this observational study, we assessed all infectious episodes occurring within a 90-day period from diagnosis in all consecutive patients with biopsy-proven sAH (modified Maddrey's discriminant function ≥ 32, Model for End-Stage Liver Disease [MELD] ≥ 18) and DAC (MELD ≥ 18) without alcohol-associated hepatitis in our tertiary hospital between 2003 and 2016. A total of 207 patients were included: 139 with sAH and 68 with DAC. One hundred seventeen (84%) patients with sAH and 41 (60%) patients with DAC experienced at least one infection episode at 90 days (P < 0.001). In multivariable analysis, factors associated with the development of infection were the presence of sAH and baseline MELD score. Bacterial infections represented the most common infection in the two groups, and only the MELD score was independently associated with the occurrence of bacterial infection. In both groups, pneumonia was the most prevalent bacterial infection, and gram-negative bacilli were the main pathogens. Invasive fungal infections (IFI) occurred in 20 (14.5%) patients with sAH and 3 (4.5%) with patients with DAC (P < 0.05). Multivariable regression showed that younger age, higher MELD, and corticosteroid therapy were independently associated with IFI. The 90-day cumulative incidence of death in patients infected with sAH and patients infected with DAC was 46% and 41.5%, respectively (P = 0.43). CONCLUSIONS: Patients with sAH are more susceptible to develop infection than those with DAC. In life-threatening forms of ALD, patients who were infected share a similar mortality rate. Corticosteroid treatment, not sAH, seems to be the main risk factor triggering IFI.

Invasive group B Streptococcus among non-pregnant adults in Brussels-Capital Region, 2005-2019.

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.

Evaluation of total body weight and body mass index cut-offs for increased cefazolin dose for surgical prophylaxis.

French and American guidelines recommend increased dosage regimens of cefazolin (CFZ) for surgical prophylaxis in patients with a body mass index (BMI) ≥ 35 kg/m2 or with a total body weight (TBW) ≥ 120 kg. The objective of this study was to evaluate the accuracy of these cut-offs in identifying patients who require CFZ dose adjustment. A pharmacokinetic study was conducted in patients of varying TBW and BMI who received 2 g of CFZ intravenously for prophylaxis prior to digestive surgery. Adequacy of therapy, defined as a serum concentration of unbound CFZ (fCFZ) ≥ 4 mg/L, was evaluated 180 min (T180) and 240 min (T240) after the start of CFZ infusion. Possible factors associated with insufficient fCFZ levels were also assessed. A P-value of <0.05 was considered statistically significant. A total of 63 patients were included in the study, categorised according to BMI (<35 kg/m2, 20 patients; and ≥35 kg/m2, 43 patients) and TBW (<120 kg, 41 patients; and ≥120 kg, 22 patients). All patients had adequate drug levels at T180 but only 40/63 patients (63%) had adequate levels at T240. At T240, therapy was adequate in 15/20 patients (75%) and 25/43 patients (58%) with BMI <35 kg/m2 and ≥35 kg/m2, respectively (P = 0.20), and in 28/41 patients (68%) and 12/22 patients (55%) with TBW <120 kg and ≥120 kg, respectively (P = 0.28). No factor associated with insufficient fCFZ was identified. In conclusion, current BMI and TBW cut-offs are poor indicators of which patients could benefit from increased CFZ dosage regimens.

Gonococcal aneurysm of the ascending aorta: case report and review of Neisseria gonorrhoeae endovascular infections.

We present the case of a man with a bicuspid aortic valve who presented with persistent fever. Blood cultures yielded Neisseria gonorrhoeae, and the diagnosis of infected mycotic aneurysm was confirmed by detection of the bacterial genome in the aortic wall. The patient was cured with surgery and intravenous ceftriaxone.