Antimicrobial Resistance as Risk Factor for Recurrent Bacteremia after Staphylococcus aureus, Escherichia coli, or Klebsiella spp. Community-Onset Bacteremia.

We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.

Primary Invasive Cutaneous Fusariosis in Patients with STAT3 Hyper-IgE Syndrome.

Dominant negative (DN) mutations in signal transducer and activator of transcription 3 (STAT3) are known to cause hyper-IgE syndrome, a rare primary immunodeficiency. STAT3 DN patients are prone to develop fungal infections, including chronic mucocutaneous candidiasis due to impaired IL-17-mediated immunity, and pulmonary aspergillosis. Despite having preserved phagocyte functions, STAT3 DN patients present connective tissue abnormalities and a defect in the immunological skin barrier. Fusarium species are ubiquitous molds, whose potential to infect humans depends on the host's innate and cellular immune status. Our aim was to describe four STAT3 DN patients with fusariosis confined to the skin. Medical records were reviewed and summarized. Four patients, aged 4, 11, 30, and 33 years, presented with chronic skin lesions which started in the extremities. Two patients had remote lesions, and none had systemic involvement. Skin biopsies showed mycelial threads with deep inflammatory-occasionally granulomatous-infiltrates, reaching the dermis; cultures grew Fusarium solani. Response to treatment was heterogeneous, often requiring multimodal therapies, including topical antifungal preparations. In this work, we describe primary invasive cutaneous fusariosis as a syndromic entity in four STAT3 DN patients.

Antimicrobial Resistance and Mortality in Hospitalized Patients with Bacteremia in the Greater Paris Area from 2016 to 2019.

Purpose: Antibiotic-resistant bacteremia is a leading global cause of infectious disease morbidity and mortality. Clinical data warehouses (CDWs) allow for the secure, real-time coupling of diverse data sources from real-world clinical settings, including care-based medical-administrative data and laboratory-based microbiological data. The main purpose of this study was to assess the contribution of CDWs in the epidemiological study of antibiotic resistance by constructing a database of bacteremia patients, BactHub, and describing their main clinico-microbiological features and outcomes. Patients and Methods: Adult patients with bacteremia hospitalized between January 1, 2016 and December 31, 2019 in 14 acute care university hospitals from the Greater Paris area were identified; their first bacteremia episode was included. Data describing patients, episodes of bacteremia, bacterial isolates, and antimicrobial resistance were structured. Results: Among 29,228 patients with bacteremia, 41% of episodes were community-onset (CO) and 59% were hospital-acquired (HA). Thirty-day and ninety-day mortality rates were 15% and 20% in CO episodes, and 18% and 36% in HA episodes. Overall resistance rates were high, including third-generation cephalosporin resistance among Klebsiella pneumoniae (CO 21%, HA 37%) and Escherichia coli (CO 13%, HA 17%), and methicillin resistance among Staphylococcus aureus (CO 11%, HA 14%). Annual incidence rates increased significantly from 2017 to 2019, from 20.0 to 20.9 to 22.1 stays with bacteremia per 1000 stays (p < 0.0001). Conclusion: The Bacthub database provides accurate clinico-microbiological data describing bacteremia across France's largest hospital group. Data from Bacthub may inform surveillance and the clinical decision-making process for bacteremia patients, including choice of antimicrobial therapy. The database also offers opportunities for research, including analysis of hospital care pathways and significant patient outcomes such as mortality and recurrence of infection.

Vasculitis and familial Mediterranean fever: Description of 22 French adults from the juvenile inflammatory rheumatism cohort.

Objective: The frequency of vasculitis may be increased in patients with Familial Mediterranean Fever (FMF), according to several studies. Our aim was to assess the characteristics of French adult patients with both diseases. Methods: Patients with vasculitis were selected from patients followed for FMF in the French JIR-cohort. Results: Twenty-two patients were included [polyarteritis nodosa (PAN) n = 10, IgA vasculitis n = 8, unclassified vasculitis n = 2, granulomatosis with polyangiitis n = 1, and microscopic polyangiitis n = 1]. Pathogenic mutations in exon 10 were found in all 21 patients (96%) for which MEFV testing results were available, and 18 (82%) had two pathogenic mutations. Histology showed vasculitis in 59% of patients. Most patients with FMF-associated PAN were HBV-negative and had an inactive FMF before PAN onset, and 40% had a peri-renal or central nervous system bleeding. Most patients with FMF-associated IgA vasculitis had an active FMF before vasculitis onset, and 25% had digestive bleeding. Both patients with unclassified vasculitis had ischemic and/or hemorrhagic complications. Conclusion: This study confirms the predominance of PAN and IgA vasculitis in patients with FMF and the high frequency of bleeding in FMF-associated PAN. FMF should be considered in case of persistent symptoms and/or inflammatory syndrome despite vasculitis treatment in Mediterranean patients.

Antimicrobial stewardship in high-risk febrile neutropenia patients.

BACKGROUND: The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients. METHODS: We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January-October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death. RESULTS: Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15-0.53, p < 0.001). CONCLUSION: Implementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes.

From Pathophysiological Hypotheses to Case-Control Study Design: Resistance from Antibiotic Exposure in Community-Onset Infections.

Antimicrobial resistance is a global public health concern, at least partly due to the misuse of antibiotics. The increasing prevalence of antibiotic-resistant infections in the community has shifted at-risk populations into the general population. Numerous case-control studies attempt to better understand the link between antibiotic use and antibiotic-resistant community-onset infections. We review the designs of such studies, focusing on community-onset bloodstream and urinary tract infections. We highlight their methodological heterogeneity in the key points related to the antibiotic exposure, the population and design. We show the impact of this heterogeneity on study results, through the example of extended-spectrum ß-lactamases producing Enterobacteriaceae. Finally, we emphasize the need for the greater standardization of such studies and discuss how the definition of a pathophysiological hypothesis specific to the bacteria-resistance pair studied is an important prerequisite to clarify the design of future studies.

An Educational Game Evening for Medical Residents: A Proof of Concept to Evaluate the Impact on Learning of the Use of Games.

Insufficient knowledge of bacteria and antimicrobials leads to the emergence of multidrug-resistant-bacterium infections. Diversification of the teaching forms, such as the use of games, could be a solution. We organized an event around 3 games (Bacteria Game, KROBS, and Dawaa) to collect student feedback on the evening and assess their knowledge before and after the evening using multiple-choice questions. The preliminary results suggest a positive effect of this event, but due to the low number of participants, we see this report more as a proof of concept to assess the impact of games on the learning.

Anti-RNP positivity in primary Sjögren's syndrome is associated with a more active disease and a more frequent muscular and pulmonary involvement.

Objectives: To describe and compare the clinical and biological characteristics of subjects with primary Sjögren's syndrome (pSS) with and without anti-RNP antibodies. Methods: Patients fulfilling the American College of Rheumatology (ACR)/EULAR 2016 criteria for pSS and having anti-RNP antibodies, without other connective tissue disease diagnosed and no anti-dsDNA antibodies were retrieved from the database from our French National Reference Center. These patients were compared with all other patients with pSS with negative anti-Sm, anti-RNP and anti-dsDNA antibodies. Results: Overall, 21 patients with pSS positive for anti-RNP antibodies and 446 negative for anti-RNP antibodies were retrieved. Anti-RNP-positive patients had a lower median age at onset of pSS symptoms (41.0 vs 50.0 years, p=0.01), a higher median EULAR Sjögren's syndrome disease activity index at inclusion (8.0 vs 3.0, p<0.01), more frequently constitutional symptoms (14.3% vs 0.01%, p<0.01), myositis (19.0% vs 2.3%, p<0.01) and pulmonary (19.0% vs 5.7%, p=0.04) involvement. Moreover, anti-RNP-positive patients had higher median gammaglobulin levels (22.5 vs 13 g/L, p<0.01), more frequently anti-SSA antibodies (90.5% vs 67.1%, p=0.03), but less frequent lymphocytic sialadenitis with a focus score ≥1 (66.7% vs 85.5%, p=0.03). If the analysis is restricted to anti-SSA-positive patients, anti-RNP positivity is associated with the same clinicobiologic features except the pulmonary involvement. Conclusion: Patients with pSS with anti-RNP antibodies displayed a more active systemic disease, with more frequent muscular and pulmonary involvement, and increased gammaglobulin level, compared with anti-RNP-negative patients.

Association of Vasculitis and Familial Mediterranean Fever.

Certain types of vasculitis occur more frequently and present differently in patients with familial Mediterranean fever (FMF). We assessed the characteristics of patients with FMF and systemic vasculitis through a systematic review of the literature. Medline was searched by two independent investigators until December 2017. We screened 310 articles and selected 58 of them (IgA vasculitis n = 12, polyarteritis nodosa (PAN) n = 25, Behçet's disease (BD) n = 7, other vasculitis n = 14). Clinical case reports were available for 167 patients (IgA vasculitis n = 46, PAN n = 61, BD n = 46, other vasculitis n = 14), and unavailable for 45 patients (IgA vasculitis n = 38, PAN n = 7). IgA vasculitis was the most common vasculitis in FMF patients with a prevalence of 2.7-7%, followed by PAN with a prevalence of 0.9-1.4%. Characteristics of FMF did not differ between patients with and without vasculitis. Patients with FMF and IgA vasculitis displayed more intussusception (8.7%) and possibly less IgA deposits on histological analysis than patients with IgA vasculitis alone. Patients with FMF and PAN had a younger age at vasculitis onset (mean age = 17.9 years), as well as more perirenal hematomas (49%) and CNS involvement (31%) than patients with PAN alone. Glomerular involvement was noted in 33% of patients diagnosed with PAN, suggesting an alternative diagnosis. Sequencing of the MEFV gene confirmed the presence of two pathogenic variants in 73% of FMF patients with IgA vasculitis or PAN. The majority of patients with BD were from one case series, and presented more skin, gastrointestinal, and CNS involvement than patients with isolated BD. In conclusion, FMF, particularly when supported by two pathogenic MEFV mutations, could predispose to IgA vasculitis, or a PAN-like vasculitis with more perirenal bleeding and CNS involvement.

Impact of a multimodal strategy combining a new standard of care and restriction of carbapenems, fluoroquinolones and cephalosporins on antibiotic consumption and resistance of Pseudomonas aeruginosa in a French intensive care unit.

This study aimed to assess whether post-prescription review and feedback (PPRF) of all antibiotics, with restriction of carbapenems, fluoroquinolones and third-generation cephalosporins (3GCs), along with a change in medical standard of care impacted antibiotic consumption and bacterial antimicrobial resistance in a French medical/surgical intensive care unit (ICU). A 4-year before (2007-2010) and after (2011-2014) retrospective comparative study was performed. Antibiotic consumption was evaluated in defined daily doses per 1000 patient-days. The rates of Pseudomonas aeruginosa resistance to piperacillin, ceftazidime, ciprofloxacin, imipenem and amikacin and of AmpC-hyperproducing group 3 Enterobacteriaceae were assessed. Consumption of fluoroquinolones decreased by -85%, carbapenems by -58%, 3GCs by -50% and glycopeptides by -66% (P ≤ 0.0001). Consumption of penicillins with and without ß-lactamase inhibitors increased by +72% and +78%, sulfonamides by +172% and macrolides by +267% (P < 0.0001). Pseudomonas aeruginosa resistance rates for all antibiotics tested and the proportion of AmpC-hyperproducing group 3 Enterobacteriaceae decreased (P ≤ 0.01). The median length of stay, use of vasopressors and invasive mechanical ventilation decreased, and the use of renal replacement therapy increased (P < 0.05). The initial severity score (SAPS II) increased (P < 0.01) due to changes in practice, with no impact on in-hospital mortality (P = 0.07). In conclusion, changes in medical care along with PPRF and a restriction of high ecological impact antibiotics were associated with a shift towards the consumption of low ecological impact antibiotics in an ICU. Rates of resistant P. aeruginosa and of AmpC-hyperproducing group 3 Enterobacteriaceae decreased simultaneously.

Symptomatic muscular sarcoidosis: Lessons from a nationwide multicenter study.

OBJECTIVES: To describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study. METHODS: Patients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations. RESULTS: Forty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18-71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe. CONCLUSION: This nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.

Association of hidradenitis suppurativa and familial Mediterranean fever: A case series of 6 patients.

OBJECTIVES: Familial mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Hidradenitis suppurativa (HS) is an inflammatory cutaneous disease. Those diseases can occur simultaneously among the same individual. Our objective was to describe the features of patients displaying both FMF and HS. METHODS: We screened the French adult FMF reference center for FMF patients with HS. RESULTS: Six patients out of 151 (4%) with a median age of 36 years old were concerned. Among them, FMF was symptomatic at a median age of 11.5years old and colchicine was introduced at a median age of 20.5years old. HS was diagnosed at a median age of 31.5years old. An elderly patient displayed AA amyloidosis in the outcome of FMF, with a late diagnosis of HS, with response to anakinra. There was no temporal relation between FMF and HS attacks. Some patients had a persistent inflammatory syndrome under treatment. CONCLUSION: FMF and HS are both inflammatory diseases involving young patients, with HS possibly being an autoinflammatory disease. Although their association seems to be fortuitous, both can induce an important inflammation state that could lead to AA amyloidosis and require a close monitoring of clinical signs and acute-phase reactants. Anakinra was successful in treating the only patient with both HS, FMF and amyloidosis.