Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption.

Background: The advent of anti-tumor necrosis factor α (anti-TNFα) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNFα. Methods: This French retrospective study (2010-2022) included all TB cases in patients with IBD who were treated with anti-TNFα in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNFα exposure. Results: Thirty-six patients were included (median age, 35 years; IQR, 27-48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18-80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60-42.82; P = .015). Anti-TB treatment was longer in this population (median [IQR], 9 [9-12] vs 6 [6-9] months; P = .049). Anti-TNFα was resumed in 66% after a median 4 months (IQR, 3-10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNFα were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21-90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNFα were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery). Conclusions: TB with anti-TNFα treatment is often complicated by IRIS of varying severity. Restarting anti-TNFα is a safe and effective strategy.

Prediction of 30-day mortality after surgery for infective endocarditis using risk scores: Insights from a European multicenter comparative validation study.

BACKGROUND: It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). METHODS: Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and five specific risk scores for early mortality after surgery for IE - (1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intra-cardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intra-cardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa) - was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised. RESULTS: A total of 1,012 patients from five European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs. 0.693 or less, p=0.01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%. CONCLUSION: EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than five established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.

Efficacy of vancomycin lock therapy for totally implantable venous access port-related infection due to coagulase-negative staphylococci in 100 patients with cancer.

OBJECTIVES: Data on the efficacy of vancomycin catheter lock therapy (VLT) for conservative treatment of totally implantable venous access port-related infections (TIVAP-RI) due to CoNS are scarce. The aim of this study was to evaluate the effectiveness of VLT in the treatment of TIVAP-RI due to CoNS in cancer patients. METHODS: This prospective, observational, multicentre study included adults with cancer treated with VLT for a TIVAP-RI due to CoNS. The primary endpoint was the success of VLT, defined as no TIVAP removal nor TIVAP-RI recurrence within 3 months after initiation of VLT. The secondary endpoint was 3 month mortality. Risk factors for VLT failure were also analysed. RESULTS: One hundred patients were included [men 53%, median age 63 years (IQR 53-72)]. Median duration of VLT was 12 days (IQR 9-14). Systemic antibiotic therapy was administered in 87 patients. VLT was successful in 44 patients. TIVAP could be reused after VLT in 51 patients. Recurrence of infection after completion of VLT occurred in 33 patients, among which TIVAP was removed in 27. Intermittent VLT (antibiotic solution left in place in the TIVAP lumen part of the time) was identified as a risk factor for TIVAP-RI recurrence. At 3 months, 26 deaths were reported; 1 (4%) was related to TIVAP-RI. CONCLUSIONS: At 3 months, success of VLT for TIVAP-RI due to CoNS was low. However, removing TIVAP was avoided in nearly half the patients. Continuous locks should be preferred to intermittent locks. Identifying factors of success is essential to select patients who may benefit from VLT.

Vasoplegic Syndrome after Cardiac Surgery for Infective Endocarditis.

Purpose: Post-operative vasoplegic syndrome is a dreaded complication in infective endocarditis (IE). Methods and Results: This retrospective study included 166 consecutive patients referred to cardiac surgery for non-shocked IE. Post-operative vasoplegic syndrome was defined as a persistent hypotension (mean blood pressure < 65 mmHg) refractory to fluid loading and cardiac output restoration. Cardiac surgery was performed 7 (5−12) days after the beginning of antibiotic treatment, 4 (1−9) days after negative blood culture and in 72.3% patients with adapted anti-biotherapy. Timing of cardiac surgery was based on ESC guidelines and operating room availability. Most patients required valve replacement (80%) and cardiopulmonary bypass (CPB) duration was 106 (95−184) min. Multivalvular surgery was performed in 43 patients, 32 had tricuspid valve surgery. Post-operative vasoplegic syndrome was reported in 53/166 patients (31.9%, 95% confidence interval of 24.8−39.0%) of the whole population; only 15.1% (n = 8) of vasoplegic patients had a post-operative documented infection (6 positive blood cultures) and no difference was reported between vasoplegic and non-vasoplegic patients for valve culture and the timing of cardiac surgery. Of the 23 (13.8%) in hospital-deaths, 87.0% (n = 20) occurred in the vasoplegic group and the main causes of death were multiorgan failure (n = 17) and neurological complications (n = 3). Variables independently associated with vasoplegic syndrome were CPB duration (1.82 (1.16−2.88) per tertile) and NTproBNP level (2.11 (1.35−3.30) per tertile). Conclusions: Post-operative vasoplegic syndrome is frequent and is the main cause of death after IE cardiac surgery. Our data suggested that the mechanism of vasoplegic syndrome was more related to inflammatory cardiovascular injury rather than the consequence of ongoing bacteremia.

Should We Quantify Valvular Calcifications on Cardiac CT in Patients with Infective Endocarditis?

BACKGROUND: Evaluate the impact of valvular calcifications measured on cardiac computed tomography (CCT) in patients with infective endocarditis (IE). METHODS: Seventy patients with native IE (36 aortic IE, 31 mitral IE, 3 bivalvular IE) were included and explored with CCT between January 2016 and April 2018. Mitral and aortic valvular calcium score (VCS) were measured on unenhanced calcium scoring images, and correlated with clinical, surgical data, and 1-year death rate. RESULTS: VCS of patients with mitral IE and no peripheral embolism was higher than those with peripheral embolism (868 (25-1725) vs. 6 (0-95), p < 0.05). Patients with high calcified mitral IE (mitral VCS > 100; n = 15) had a lower rate of surgery (40.0% vs.78.9%; p = 0.03) and a higher 1-year-death risk (53.3% vs. 10.5%, p = 0.04; OR = 8.5 (2.75-16.40) than patients with low mitral VCS (n = 19). Patients with aortic IE and high aortic calcifications (aortic VCS > 100; n = 18) present more frequently atypical bacteria on blood cultures (33.3% vs. 4.8%; p = 0.03) than patients with low aortic VCS (n = 21). CONCLUSION: The amount of valvular calcifications on CT was associated with embolism risk, rate of surgery and 1-year risk of death in patients with mitral IE, and germ's type in aortic IE raising the question of their systematic quantification in native IE.

Diagnostic Performance of Transesophageal Echocardiography and Cardiac Computed Tomography in Infective Endocarditis.

BACKGROUND: Multimodality imaging is essential for infective endocarditis (IE) diagnosis. The aim of this work was to evaluate the agreement between transesophageal echocardiography (TEE) and cardiac computed tomography (CT) findings in patients with surgically confirmed IE. METHODS: Sixty-eight patients (mean age 63 ± 2 years) with a definite diagnosis of left-side IE according to the modified European Society of Cardiology Duke criteria, on both native and prosthetic valves, underwent TEE and cardiac CT before surgery. The presence of valvular (vegetations, erosion) and paravalvular (abscess, pseudoaneurysm) IE-related lesions were compared between both modalities. Perioperative inspection was used as reference. RESULTS: TEE performed better than CT in detecting valvular IE-related lesions (TEE area under the curve [AUCTEE] = 0.881 vs AUCCT = 0.720, P = .02) and was similar to CT with respect to paravalvular IE-related lesions (AUCTEE = 0.830 vs AUCCT = 0.816, P = .835). The ability of TEE to detect vegetation was significantly better than that of CT (AUCTEE = 0.863 vs AUCCT = 0.693, P = .02). The maximum size of vegetations was moderately correlated between modalities (Spearman's rho = 0.575, P < .001). Computed tomography exhibited higher sensitivity than TEE for pseudoaneurysm detection (100% vs 66.7%, respectively) but was similar with respect to diagnostic accuracy (AUCTEE = 0.833 vs AUCCT = 0.984, P = .156). CONCLUSIONS: In patients with a definite diagnosis of left-side IE according to the modified European Society of Cardiology Duke criteria, TEE performed better than CT for the detection of valvular IE-related lesions and similar to CT for the detection of paravalvular IE-related lesions.

Clinical relevance and impact of Corynebacterium isolation in lower respiratory tract of critically ill patients requiring mechanical ventilation.

PURPOSE: Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. METHODS: We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007-2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. RESULTS: Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34-60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. CONCLUSION: Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated.

Impact of a multidisciplinary care bundle for necrotizing skin and soft tissue infections: a retrospective cohort study.

BACKGROUND: Necrotizing skin and soft tissue infections (NSTIs) require both prompt medical and surgical treatment. The coordination of multiple urgent interventions by care bundles has improved outcome in other settings. This study aimed to assess the impact of a multidisciplinary care bundle on management and outcome of patients with NSTIs. METHODS: Patients with NSTIs admitted between 2006 and 2017 were compared according to admission before or after bundle implementation (2012-2013). This bundle consisted mainly in (1) the creation of a multidisciplinary task force; (2) management guidelines on empirical antibiotics, intensive care unit admission criteria, a triage algorithm to accelerate operating room access; and (3) an active communication policy. Patient recruitment and management were compared between pre- and post-implementation periods. Main outcome was day 60-censored hospital survival. RESULTS: Overall, 224 patients were admitted: 60 before, 35 during, and 129 after bundle implementation. Admission after implementation was associated with increased yearly admissions (10 [8-13] vs 30 [24-43] patients/year, p = 0.014) and decreased mortality (30 vs 15%, HR = 0.49 [0.26-0.92]; p = 0.026) but was no longer a protective factor for mortality after adjustment on confounding factors (adjusted HR = 0.90 [0.43-1.88], p = 0.780). There was no significant difference regarding time to surgery (0 [0-1] vs 0 [0-1] days, p = 0.192) or rate of antibiotic treatment within 24 h (98% vs 99%, p > 0.99). CONCLUSIONS: Implementation of a multidisciplinary care bundle for NSTIs was feasible, but in a retrospective study from an already experienced center was not associated with significantly increased survival after adjustment.

Infective endocarditis without biological inflammatory syndrome: Description of a particular entity.

BACKGROUND: Bacterial infective endocarditis (IE) is rarely suspected in patients with a low C-reactive protein (CRP) concentration. AIMS: To address the incidence, characteristics and outcome of left-sided valvular IE with low CRP concentration. METHODS: This was a retrospective analysis of cases of IE discharged from our institution between January 2009 and May 2017. The 10% lowest CRP concentration (<20mg/L) was used to define low CRP concentration. Right-sided cardiac device-related IE, non-bacterial IE, sequelar IE and IE previously treated by antibiotics were excluded. RESULTS: Of the 469 patients, 13 (2.8%; median age 68 [61-76] years) had definite (n=8) or possible (n=5) left-sided valvular IE with CRP<20mg/L (median 9.3 [4.7-14.2] mg/L). The median white blood cell count was 6.3 (5.3-7.5) G/L. The main presentations were heart failure (n=7; 54%) and stroke (n=3; 23%). Transthoracic echocardiography (TTE) showed vegetations (n=5) or isolated valvular regurgitation (n=4). Overall, eight patients (62%) had severe valvular lesions on transoesophageal echocardiography (TOE), and nine patients (69%) underwent cardiac surgery. All patients survived at 1-year follow-up. Bacterial pathogens were documented in eight patients (streptococci, coagulase-negative Staphylococcus, Corynebacteriumjeikeium, HACEK group, Coxiella burnetii, Bartonella henselae) using blood cultures, serology or valve culture and/or polymerase chain reaction analysis. CONCLUSIONS: Left-sided valvular IE with limited or no biological syndrome is rare, but is often associated with severe valvular and paravalvular lesions. TOE should be performed in presence of unexplained heart failure, new valvular regurgitation or cardioembolic stroke when TTE is insufficient to rule out endocarditis, even in patients with a low CRP concentration.

De-escalation and discontinuation strategies in high-risk neutropenic patients: an interrupted time series analyses of antimicrobial consumption and impact on outcome.

Febrile neutropenia (FN) is the main reason for antibiotic prescription in hematology wards where, on the other hand, antibiotic stewardship (AS) is poorly explored. The objectives of the present study were to evaluate (1) the impact of an AS intervention on antibiotic consumption and (2) the applicability and acceptance rate of the intervention and its clinical impact. A persuasive AS intervention based on European Conference on Infection in Leukaemia (ECIL) guidelines for FN was implemented in a high-risk hematology ward in a tertiary referral public university hospital. This included the creation and diffusion of flow charts on de-escalation and discontinuation of antibiotics for FN, and the introduction in the team of a doctor dedicated to the implementation of flow charts and to antibiotic prescription revision. All consecutive patients receiving antibiotics during hospitalization were included. A segmented linear regression model was performed for the evaluation of antibiotic consumption, taking into account 1-year pre-intervention period and 6-month intervention period. Overall, 137 consecutive antibiotic prescriptions were re-evaluated, 100 prescriptions were for FN. A significant reduction of the level of carbapenem consumption was observed during the intervention period (level change (estimate coefficient ± standard error) = - 135.28 ± 59.49; p = 0.04). Applicability and acceptability of flow charts were high. No differences in terms of intensive care unit transfers, bacteremia incidence, and mortality were found. A persuasive AS intervention in hematology significantly reduced carbapenem consumption without affecting outcome and was well accepted. This should encourage further applications of ECIL guidelines for FN.

Utility of ultra-deep sequencing for detection of varicella-zoster virus antiviral resistance mutations.

We report the first application of ultra-deep sequencing (UDS) to varicella-zoster virus (VZV) genotypic antiviral testing in a case of acyclovir-resistant VZV infection initially detected by Sanger sequencing within a deeply immunocompromised heart transplant recipient. As added-value compared to Sanger analysis, UDS revealed complex dynamics of viral population under antiviral pressure. Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus affecting populations worldwide. VZV is commonly acquired in youth whose primary infection usually manifests as benign varicella (chickenpox). After the initial infection, the virus establishes lifelong latency in sensory ganglia leading to a risk of subsequent reactivation. Reactivation usually results in the development of localized herpes zoster (HZ) lesions, a painful skin rash commonly known as shingles (Cohen, 2013). The incidence and severity of HZ increase with impaired specific cell-mediated immunity mainly as a result of increasing age, malignancy, immunodeficiency, organ transplantation, or immunosuppressive drug therapy (Cohen, 2013; Koo et al., 2014; Pavlopoulou et al., 2015). In particular, HZ remains a significant cause of morbidity among solid organ transplant (SOT) recipients, especially in patients undergoing heart transplantation (HT) compared with liver, kidney, or lung transplant recipients (Carby et al., 2007; Koo et al., 2014; Pavlopoulou et al., 2015). These particular individuals are at increased risk of primary infection, reactivation followed by dissemination with visceral involvement and associated with bacterial superinfection, and chronic recurrences (Cohen, 2013). VZV infections may also engender debilitating neuralgia among highly immunocompromised patients (Sampathkumar et al., 2009). HT is also associated with the risk of reactivation of other latent viruses belonging to the Herpesviridae family as herpes simplex virus (HSV). Currently licensed drugs to prevent or to cure HSV- or VZV-associated diseases target the viral DNA polymerase (Pol). Acyclovir (ACV) and its prodrug valacyclovir (VACV) are considered as the first-line therapy, whereas foscarnet (FOS) or cidofovir (CDV) constitute alternative options. After primophosphorylation by the viral thymidine kinase (TK), ACV targets the viral DNA polymerase and inhibits the viral genome replication by a chain termination mechanism. According to this mechanism of action, viral mutations conferring resistance to ACV have been mapped both in TK and Pol encoding genes. Viral mutations conferring resistance to FOS and CDV are only detected in Pol gene. VZV ACV-resistance is mostly mediated by TK alterations, consisting in either translational frameshifts, sometimes associated with premature stop codon, or amino acid substitutions. In the remaining cases, amino acid substitutions are detected within Pol (De et al., 2015; Piret and Boivin, 2014). Classically, Sanger sequencing has been recognized as the gold standard for the detection of drug resistance mutations (DRMs) within VZV TK and Pol genes (Perrier et al., 2016; Piret and Boivin, 2014). However, this approach cannot detect minor variants present at a frequency below 20%. Ultra-deep sequencing (UDS) has an enhanced sensitivity compared to Sanger method and allows quantitative evaluation of the viral mutants (Chin et al., 2013). We report here a case of VZV resistant infection in an HT recipient. Our retrospective study aimed at showing the utility of UDS for DRM detection as a complement of Sanger method.