Antibiotic Prescriptions in Critically Ill Patients with Bloodstream Infection Due to ESBL-Producing Enterobacteriaceae: Compliance with the French Guidelines for the Treatment of Infections with Third-Generation Cephalosporin-Resistant Enterobacteriaceae-A Multicentric Retrospective Cohort Study.

National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum ß-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303-1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI.

Infectious hazards of tatami mats.

A 16-year old girl consulted for repeated axillary abscesses. The bacteriological culture yielded monomicrobial Staphylococcus aureus. Faced with these recurrent abscesses in an immunocompetent patient playing a close contact sport, the biologist suspected the strain to harbor a virulence factor explaining these recurrences.

Relationship between COVID-19 and ICU-Acquired Bloodstream Infections Related to Multidrug-Resistant Bacteria.

A bloodstream infection (BSI) is a severe ICU-acquired infection. A growing proportion is caused by multidrug-resistant bacteria (MDRB). COVID-19 was reported to be associated with a high rate of secondary infections. However, there is a lack of data on the relationship between COVID-19 and the incidence of MDRB ICU-acquired BSI. The aim of this study was to evaluate the relationship between COVID-19 and ICU-acquired BSI related to MDRB. This retrospective study was conducted in a single-center ICU during a one-year period. All adult patients admitted for more than 48 h were included. The cumulative incidence of ICU-acquired BSI related to MDRB was estimated using the Kalbfleisch and Prentice method. The association of COVID-19 status with the risk of ICU-acquired BSI related to MDRB was assessed using cause-specific Cox's proportional hazard model. Among the 1320 patients included in the analysis, 497 (37.65%) had COVID-19. ICU-acquired BSI related to MDRB occurred in 50 patients (36 COVID patients (7%) and 14 non-COVID patients (1.6%)). Extended-spectrum beta-lactamase Enterobacteriacae (46%) and carbapenem-resistant Acinetobacter baumannii (30%) were the most commonly isolated MDRB. COVID-19 was significantly associated with a higher risk of MDRB ICU-acquired BSI (adjusted cHR 2.65 (1.25 to 5.59) for the whole study period). However, this relationship was only significant for the period starting at day 15 after ICU admission. ICU-acquired BSI related to MDRB was significantly associated with ICU mortality (HR (95%CI) 1.73 (1-3)), although COVID-19 had no significant impact on this association (p het 0.94). COVID-19 is significantly associated with an increased risk of ICU-acquired BSI related to MDRB, mainly during the period starting at day 15 after ICU admission.

An unusual case of native aortic endocarditis due to Corynebacterium pseudodiphtheriticum.

Corynebacterium pseudodiphtheriticum, a Gram-positive rod belonging the oropharynx microbiota, is usually described in pulmonary infections, especially in immunocompromised patients. This paper describes a rare case of native aortic infectious endocarditis (IE) and reviews the literature on similar cases. A 62-year-old man with rheumatic fever since childhood was hospitalized for surgical treatment of a febrile IE due to C. diphtheriticum with a large vegetation (15.8 X 8.3 mm). MALDI-TOF-MS from strain isolated in positive blood cultures identified C. pseudodiphtheriticum (2.34), and 16S rRNA sequencing from the valve sample confirmed the identification. The summary of 25 cases shows that the outcome of an IE due to C. pseudodiphtheriticum is bad. The review of the literature shows that this agent found in blood cultures in a cardiovascular context deserves to be explored meticulously because an unfavorable prognosis is frequent.

Sepsis-like Energy Deficit Is Not Sufficient to Induce Early Muscle Fiber Atrophy and Mitochondrial Dysfunction in a Murine Sepsis Model.

Sepsis-induced myopathy is characterized by muscle fiber atrophy, mitochondrial dysfunction, and worsened outcomes. Whether whole-body energy deficit participates in the early alteration of skeletal muscle metabolism has never been investigated. Three groups were studied: "Sepsis" mice, fed ad libitum with a spontaneous decrease in caloric intake (n = 17), and "Sham" mice fed ad libitum (Sham fed (SF), n = 13) or subjected to pair-feeding (Sham pair fed (SPF), n = 12). Sepsis was induced by the intraperitoneal injection of cecal slurry in resuscitated C57BL6/J mice. The feeding of the SPF mice was restricted according to the food intake of the Sepsis mice. Energy balance was evaluated by indirect calorimetry over 24 h. The tibialis anterior cross-sectional area (TA CSA), mitochondrial function (high-resolution respirometry), and mitochondrial quality control pathways (RTqPCR and Western blot) were assessed 24 h after sepsis induction. The energy balance was positive in the SF group and negative in both the SPF and Sepsis groups. The TA CSA did not differ between the SF and SPF groups, but was reduced by 17% in the Sepsis group compared with the SPF group (p < 0.05). The complex-I-linked respiration in permeabilized soleus fibers was higher in the SPF group than the SF group (p < 0.05) and lower in the Sepsis group than the SPF group (p < 0.01). Pgc1α protein expression increased 3.9-fold in the SPF mice compared with the SF mice (p < 0.05) and remained unchanged in the Sepsis mice compared with the SPF mice; the Pgc1α mRNA expression decreased in the Sepsis compared with the SPF mice (p < 0.05). Thus, the sepsis-like energy deficit did not explain the early sepsis-induced muscle fiber atrophy and mitochondrial dysfunction, but led to specific metabolic adaptations not observed in sepsis.

High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.

Evolution of antibiotic susceptibility profiles of staphylococci from osteoarticular infections: A 10-year retrospective study.

BACKGROUND: Knowledge of the antibiotic susceptibility profiles of the bacteria responsible for osteoarticular infections is crucial for choosing the appropriate empirical antibiotic regimen. Wide use of broad spectrum antibiotics in these infections may have lead to selection of resistant bacteria. The aim of our study was to answer to these questions: (1) Did the bacterial pathogens isolated from osteoarticular infections (OAIs) and their antibiotic susceptibility profile change over the 10-year period in our University Hospital, particularly for Staphylococcus aureus and Coagulase negative staphylococci? (2) Are the antibiotics used for post-operative antibiotic therapy still effective against staphylococci involved in OAIs? (3) Are the antibiotics used for documented therapy still effective against staphylococci involved in OAIs? HYPOTHESIS: We hypothetise that bacterial epidemiology and antibiotic resistance rates have changed little thanks to a reasoned prescription of antibiotics in our Center. MATERIALS AND METHODS: We performed a retrospective study describing the antibiotic susceptibility profile of bacteria isolated from osteoarticular infections over 10years in our University Hospital, with a focus on the Staphylococcus genus. RESULTS: A total of 3474 staphylococci were included (2373 coagulase negative staphylococci and 1101 S. aureus), 34.8% (1207/3469) of which were resistant to methicillin. Antibiotic susceptibility profiles remained quite stable between 2010 and 2019, except for rifampicin (14.1% (45/318) versus 5.7% (23/401), p=0.0001) and fluoroquinolones (35.3% (109/309) versus 20.3% (81/399), p=0.000008) for which resistance rates significantly decreased even among methicillin-resistant strains. DISCUSSION: In spite of wide use of antibiotics in orthopaedic units, overall resistance rates did not increase over the last 10years. The prescription of these molecules in combination regimens guided by the antibiotic susceptibility patterns performed on reliable samples and on the basis of multidisciplinary discussions may explain these results. LEVEL OF EVIDENCE: IV, retrospective study.

Bacterial Aspiration Pneumonia in Generalized Convulsive Status Epilepticus: Incidence, Associated Factors and Outcome.

Suspicion of bacterial aspiration pneumonia (BAP) is frequent during generalized convulsive status epilepticus (GCSE). Early identification of BAP is required in order to avoid useless antibiotic therapy. In this retrospective monocentric study, we aimed to determine the incidence of aspiration syndrome and BAP in GCSE requiring mechanical ventilation (MV) and factors associated with the occurrence of BAP. Patients were older than 18 years and had GCSE requiring MV. To distinguish BAP from pneumonitis, tracheal aspirate and quantitative microbiological criterion were used. Out of 226 consecutive patients, 103 patients (46%) had an aspiration syndrome, including 54 (52%) with a BAP. Staphylococcus aureus represented 33% of bacterial strains. No relevant baseline characteristics differed, including serum levels of CRP, PCT, and albumin. The median duration of treatment for BAP was 7 days (5-7). Patients with BAP did not have a longer duration of MV (p = 0.18) and ICU stay (p = 0.18) than those with pneumonitis. At 3 months, 24 patients (44%) with BAP and 10 (27%) with pneumonitis had a poor functional outcome (p = 0.06). In conclusion, among patients with GCSE, half of the patients had an aspiration syndrome and one-quarter suffered from BAP. Clinical characteristics and biomarkers were not useful for differentiating BAP from pneumonitis. These results highlight the need for a method to rapidly differentiate BAP from pneumonitis, such as polymerase-chain-reaction-based techniques.

Apyretic pulmonary oedema revealing Cardiobacterium hominis endocarditis: Case report and review of literature.

Cardiobacterium hominis is a member of the HACEK group of bacteria, responsible for infective endocarditis, mainly in patients with damaged or prosthetic valves. The low virulence of this organism can explain the insidious presentation and subacute or chronic progression of C. hominis infective endocarditis. Here, a 41-year-old man with a past history of surgery for a Waldhausen type aortic coarctation was hospitalised with dyspnea and chest pains revealing an acute pulmonary oedema, without fever. Transesophageal echocardiography indicated a 20 mm vegetation on biscuspid aortic valve. Six sets of blood culture were positive with Cardiobacterium hominis. In case of lack of fever, the diagnosis of infectious endocarditis is difficult because other symptoms are non-specific and biological markers of inflammatory syndrome are quiet or non-existent. This is the first case of C. hominis infectious endocarditis with a clinical presentation of acute pulmonary oedema in the literature. We report here an apyretic pulmonary oedema revealing C. hominis endocarditis and a review of the literature on apyretic infective endocarditis due to C. hominis.

Short communication: dog bite and back pain.

Capnocytophaga canimorsus is a Gram-negative rod commensal of oral cavity of dogs and cats. It can cause sepsis, septic shock, endocarditis, and meningitis associated with bites or licking wounds, especially in immunocompromised patients. Herein, we report a case of C. canimorsus spondylodiscitis linked to a dog bite in a previously healthy patient and review the literature on this pathogen.

Evaluation of the new BL-RED (ß-Lactamase Rapid Electrochemical Detection) test in positive blood culture broths.

The rapid detection of extended-spectrum ß-lactamase Enterobacterales (ESBL-E) in a positive blood culture is important in order to initiate an appropriate antibiotic therapy and thus decrease mortality. We evaluated the new BL-RED (ß-Lactamase Rapid Electrochemical Detection) test in 100 positive blood culture broths to detect (in ten minutes) the presence or absence of ESBL-E. The BL-RED test appears to be an easy, rapid and reliable test to detect the presence of ESBL directly in Gram negative bacilli-positive blood culture broths, with good performances (sensibility =97.3%, specificity =90.5%, predictive positive value =85.7% and predictive negative value =98.3%). This test could be useful for therapeutic decisions and adjustments of sepsis empirical antibiotic therapy, particularly in wards where the ecology is unfavorable, such as in intensive care units.

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

OBJECTIVE: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. METHODS: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. RESULTS: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. CONCLUSIONS: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

Stable Incidence of Invasive Pneumococcal Disease in Children in Northern France From 2014 Through 2018.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in France since June 2010. The aim of this study was to evaluate the trends in the incidence of invasive pneumococcal disease (IPD) resulting in hospitalization of children younger than 18 years of age, to identify the vaccination status of these patients and to analyze the serotypic evolution of the pneumococci involved in the various types of IPD. METHODS: This multicenter retrospective study reviewed all admissions of children younger than 18 years of age for IPD from 2014 through 2018 in all hospitals with a pediatric or neonatal unit in northern France. Data completeness was obtained by matching 3 independent databases. The incidence of IPD resulting in hospitalization was calculated per age group. The clinical course and the vaccine and nonvaccine types were described overall and by the IPD type. RESULTS: One hundred thirty cases of IPD were identified: 51 with bacteremia, 45 meningitis, 28 pneumonia or pleuropneumonia and 6 arthritis. The IPD incidence ranged from 2.4 to 3.0/100,000 in children under 18 years of age (95% confidence intervals, 1.4-3.3 and 1.9-4.1, respectively), and from 9.5 to 15.9/100,000 in children under 2 years of age, with no significant differences over time. Nonvaccine types were predominant (81%), mainly 24F, 23B and 10A. Vaccine serotype 3 was involved in 10 cases of IPD, 2 of which were in correctly vaccinated children. Two cases of IPD could have been prevented by vaccination. Neurologic sequelae affected 26% of these children (62% of those with meningitis). Six children died from IPD (5%). CONCLUSION: The incidence of IPD resulting in hospitalization remained stable in northern France during the study period, with no significant increase in nonvaccine types. Further surveillance is needed to adjust the vaccination strategy if necessary.

Diagnostic accuracy of the BJI InoPlex™ (Diaxonhit) immunoassay on blood samples for periprosthetic joint infection in complex microbiological situations. Preliminary results of 24 cases in a French Reference Center for Complex Bone and Joint Infection (CRIOAC).

BACKGROUND: While joint aspiration is the benchmark for diagnosing periprosthetic joint infections (PJI), the results can be flawed because certain bacteria are difficult to culture, the patient is on concurrent antibiotic therapy or in some cases, repeated joint aspirations confer conflicting results. The BJI InoPlex™ (Diaxonhit) is a multiplex ELISA (Enzyme Linked Immunosorbent Assay) that measures the immune response (presence of specific IgG) to certain bacterial species from three families: Staphylococcus (8 antigens) epidermidis, aureus and lugdunensis, Streptococcus B (4 antigens) and Cutibacterium acnes (4 antigens). This assay is done with peripherally collected blood. However, there are few published studies about this assay, especially if the microbiological diagnosis is in doubt in cases of suspected chronic PJI. This led us to conduct a retrospective study in a French tertiary care center to determine 1) the sensitivity and specificity of the BJI InoPlex™, 2) its positive (PPV) and negative predictive value (NPV) and 3) what causes diagnostic errors. HYPOTHESIS: The BJI InoPlex has a sensitivity/specificity and PPV/NPV above 75%. MATERIALS AND METHODS: The BJI InoPlex was used 24 times on 24 patients between January 2016 and January 2017 in scenarios where the microbiological diagnosis was difficult: 1 with on-going antibiotic therapy, 13 conflicting repeat joint aspirations, 10 negative cultures with history of infection and/or clinical evidence of a PJI. The series consisted of 11 hip arthroplasty and 13 knee arthroplasty cases. The results of the BJI InoPlex test were compared to the MusculoSkeletal Infection Society (MSIS) the criteria for a joint infection. RESULTS: For the bacterial species covered by the test, the sensitivity of the BJI InoPlex for diagnosing a chronic PJI based on the 2018 MSIS criteria was 50%, the specificity was 56%, the PPV was 36% and the NPV was 69%. DISCUSSION: While innovative, minimally invasive, and rapid (results in a few hours), the BJI InoPlex does not provide an effective diagnosis of chronic PJI in complex microbiological situations. In this study, we used the test in the most difficult situations possible and on a small number of patients, which may explain why the results were not as good as in other studies. Its current performance and cost mean there is no role for it in our algorithm for treating patients with a suspected PJI, contrary to other biomarkers. Its spectrum must include other bacterial strains involved in chronic PJI. Knowledge of the specific infectious agent increases its diagnostic value, it could be used to monitor the outcome of a PJI, although other studies would be needed to support this use. LEVEL OF EVIDENCE: IV-Retrospective diagnostic study.