Evaluation of the Specificity of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Classification for Infective Endocarditis.

BACKGROUND: The 2023 Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) classification is a new diagnostic tool for infective endocarditis, updating the 2000 modified Duke and the 2015 European Society for Cardiology (ESC) classifications. In comparison, its sensitivity is higher; however, its specificity remains to be evaluated and compared to that of the 2 other classifications in endocarditis suspected patients. METHODS: We retrospectively collected the characteristics of patients hospitalized in Bichat University's Hospital, Paris, in 2021, who had been evaluated for clinical suspicion of endocarditis, have had at least a transthoracic echocardiography, 2 pairs of blood cultures, 3-month follow-up and in whom endocarditis diagnosis was finally rejected. All patients were classified by 2000 modified Duke, 2015 ESC and 2023 Duke-ISCVID, as though the endocarditis diagnosis had not been rejected. RESULTS: In total, 130 patients' charts were analyzed. Mean age was 62 years, 84 (64.6%) were male, 39 (30.0%) had prosthetic cardiac valve or valve repair, 21 (16.2%) cardiac implanted electronic device, and 30 (23.1%) other cardiac conditions. Overall, 5, 2, and 5 patients were falsely classified as definite endocarditis with the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID classifications, respectively. The corresponding specificities were 96.2% (95% confidence interval [CI] [90.8%, 98.6%]), 98.5% (95% CI [93.9%, 99.7%]), and 96.2% (95% CI [90.8%, 98.6%]). The rates of possible endocarditis were of 38%, 35%, and 35% in the 3 classifications, respectively. CONCLUSIONS: The 2023 Duke-ISCVID classification is highly specific for ruling out the diagnosis of definite infective endocarditis in patients who had been evaluated for IE.

Wild fish from a highly urbanized river (Orge, France) as vectors of culturable Enterobacterales resistant to antibiotics.

This study shows how wild fishes from urbanized rivers could be involved in the spread of antibiotic-resistant Enterobacterales. Antibiotic resistance profiles and molecular detection of clinical integron (IntI1) were carried out on 105 Enterobacterales isolated from 89 wildfish (skin or gut) belonging to 8 species. The proportion of isolates resistant to at least one antibiotic was independent of fish species and reached 28.3% within the Escherichia coli (E. coli) population and 84.7% in the non-E.coli Enterobacterales. Bacteria involved in nosocomial infections were isolated, such as E. coli, Klebsiella, and Enterobacter, as well as the environmental bacteria (Lelliottia, Butiauxella, and Kluyvera).

Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. METHODS: To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. RESULTS: Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. CONCLUSIONS: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. CLINICAL TRIALS REGISTRATION: NCT02424461; Eudra-CT: 2013-001647-32.

Risk of Bronchial Complications After Lung Transplantation With Respiratory Corynebacteria. Results From a Monocenter Retrospective Cohort Study.

Corynebacterium spp. are associated with respiratory infections in immunocompromised hosts. A link with bronchial complications after lung transplantation (LTx) has been suggested. We aimed to assess the link between respiratory sampling of Corynebacterium spp. and significant bronchial complication (SBC) after LTx. We performed a single center retrospective study. Inclusion of LTx recipients with at least one respiratory Corynebacterium spp. sample (July 2014 to December 2018). Subjects were matched to unexposed LTx recipients. Primary outcome was SBC occurrence after Corynebacterium spp. isolation. Secondary outcomes were Corynebacterium spp. persistent sampling, chronic lung allograft dysfunction (CLAD) onset and all-cause mortality. Fifty-nine patients with Corynebacterium spp. sampling with 59 without isolation were included. Corynebacterium spp. identification was not associated with SBC occurrence (32.4% vs. 21.6%, p = 0.342). Previous SBC was associated with further isolation of Corynebacterium spp. (OR 3.94, 95% CI [1.72-9.05]). Previous SBC and corticosteroids pulses in the last 3 months were the only factors associated with increased risk of Corynebacterium spp. isolation in multivariate analysis. Corynebacterium spp. sampling was significantly associated with CLAD onset (27.1% vs. 6.9%, p = 0.021). Corynebacterium spp. isolation was not associated with SBC but with higher risk of CLAD. Whether CLAD evolution is affected by Corynebacterium spp. eradication remains to be investigated.

Impact of Culture-Positive Preservation Fluid on Early Morbidity and Mortality After Lung Transplantation.

The prevalence, risk factors and outcomes associated with culture-positive preservation fluid (PF) after lung transplantation (LT) are unknown. From January 2015 to December 2020, the microbiologic analyses of PF used to store the cold ischaemia-placed lung graft(s) of 271 lung transplant patients were retrospectively studied. Culture-positive PF was defined as the growth of any microorganism. Eighty-three (30.6%) patients were transplanted with lung grafts stored in a culture-positive PF. One-third of culture-positive PF were polymicrobial. Staphylococcus aureus and Escherichia coli were the most frequently isolated microorganisms. No risk factors for culture-positive PF based on donor characteristics were identified. Forty (40/83; 48.2%) patients had postoperative pneumonia on Day 0 and 2 (2/83; 2.4%) patients had pleural empyema with at least one identical bacteria isolated in culture-positive PF. The 30-day survival rate was lower for patients with culture-positive PF compared with patients with culture-negative PF (85.5% vs. 94.7%, p = 0.01). Culture-positive PF has a high prevalence and may decrease lung transplant recipient survival. Further studies are required to confirm these results and improve understanding of the pathogenesis of culture-positive PF and their management.

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study.

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.

Risk factors for therapeutic failure in the management of post-operative peritonitis: a post hoc analysis of the DURAPOP trial.

BACKGROUND: Therapeutic failure is a frequent issue in the management of post-operative peritonitis. OBJECTIVES: A post hoc analysis of the prospective, multicentre DURAPOP trial analysed the risk factors for failures in post-operative peritonitis following adequate source control and empirical antibiotic therapy in critically ill patients. PATIENTS AND METHODS: Overall failures assessed post-operatively between Day 8 and Day 45 were defined as a composite of death and/or surgical and/or microbiological failures. Risk factors for failures were assessed using logistic regression analyses. RESULTS: Among the 236 analysed patients, overall failures were reported in 141 (59.7%) patients, including 30 (12.7%) deaths, 81 (34.3%) surgical and 95 (40.2%) microbiological failures. In the multivariate analysis, the risk factors associated with overall failures were documented piperacillin/tazobactam therapy [adjusted OR (aOR) 2.10; 95% CI 1.17-3.75] and renal replacement therapy on the day of reoperation (aOR 2.96; 95% CI 1.05-8.34). The risk factors for death were age (aOR 1.08 per year; 95% CI 1.03-1.12), renal replacement therapy on reoperation (aOR 3.95; 95% CI 1.36-11.49) and diabetes (OR 6.95; 95% CI 1.34-36.03). The risk factors associated with surgical failure were documented piperacillin/tazobactam therapy (aOR 1.99; 95% CI 1.13-3.51), peritoneal cultures containing Klebsiella spp. (aOR 2.45; 95% CI 1.02-5.88) and pancreatic source of infection (aOR 2.91; 95% CI 1.21-7.01). No specific risk factors were identified for microbiological failure. CONCLUSIONS: Our data suggest a predominant role of comorbidities, the severity of post-operative peritonitis and possibly of documented piperacillin/tazobactam treatment on the occurrence of therapeutic failures, regardless of their type.

Weekly Sequential Antibioprophylaxis for Recurrent Urinary Tract Infections Among Patients With Neurogenic Bladder: A Randomized Controlled Trial.

BACKGROUND: Recurrent urinary tract infections (R-UTIs) are the main cause of morbidity and hospitalizations in subjects with neurogenic bladder (NB) due to spinal cord injury (SCI). We evaluated the efficacy of weekly oral cyclic antibiotic (WOCA) prophylaxis (ie, the alternate weekly administration of 2 antibiotics) in preventing R-UTIs. METHODS: Randomized (1:1), open-label, superiority-controlled trial compared WOCA prophylaxis to no prophylaxis (control) for 6 months in patients with NB due to SCI, using clean intermittent self-catheterization, and suffering from R-UTIs. Primary outcome was incidence of symptomatic antibiotic-treated UTIs. Secondary outcomes were number of febrile UTIs, number of hospitalizations, WOCA tolerance, antibiotic consumption, number of negative urine cultures, and emergence of bacterial resistance in urinary, intestinal, and nasal microbiota. RESULTS: Forty-five patients were either allocated to the WOCA group (n = 23) or the control group (n = 22). Median (IQR) incidence of symptomatic antibiotic-treated UTIs was 1.0 (0.5-2.5) in the WOCA group versus 2.5 (1.2-4.0) (P = .0241) in the control group. No febrile UTIs were recorded in the WOCA group versus 9 (45.0%) (P < .001) in the control group. The median number of additional antibiotic treatment was 0.0 (IQR, 0.0-2.0) versus 3.0 (2.0-5.0) (P = .004) in the WOCA and control groups, respectively. Only few adverse events were reported. No impact on emergence of bacterial resistance was observed. CONCLUSIONS: WOCA is efficient and well tolerated in preventing R-UTIs in SCI patients. In our study, we did not observe any emergence of antibiotic resistance in digestive and nasal microbiological cultures. CLINICAL TRIALS REGISTRATION: NCT01388413.

Late viral or bacterial respiratory infections in lung transplanted patients: impact on respiratory function.

BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; - 35 mL (IQR; - 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (- 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.

Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens.

Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.).

Clinical characteristics, risk factors, and outcome of tuberculosis in kidney transplant recipients: A multicentric case-control study in a low-endemic area.

OBJECTIVES: Tuberculosis (TB) is a rare but life-threatening infection after solid organ transplant. The present study was undertaken to assess the clinical features, risk factors, and outcome of TB after kidney transplantation in a low-prevalence area. METHODS: We conducted a retrospective study, describing all kidney transplant recipients diagnosed with TB between 2005 and 2015 in 3 French centers. For each TB case, 2 controls without TB were identified and matched by center, age, transplant date, and birth country. Risk factors associated with TB were identified and survival estimated. RESULTS: Thirty-two cases and 64 control patients were included among 3974 transplantations. The prevalence of TB was 0.83%. Median age at the time of diagnosis was 64 years; 75% were born in a high TB prevalence country, but only 3 had received isoniazid prophylaxis for latent TB infection. TB occurred at a median of 22 months after transplantation. On diagnosis, 66% had disseminated infection. Median duration of treatment was 9 months. Immunosuppressive therapy changes were necessary in all patients because of drug-drug interactions. Among cases, 5 deaths occurred during follow-up (median duration: 41 months), one directly related with TB. Survival was significantly lower in transplant recipients with TB, as compared to controls (P = .001). No predictive factors of tuberculosis after transplantation were statistically significant in univariate analysis. CONCLUSION: TB in kidney transplant recipients is a rare and late event, but is associated with significantly reduced survival. Our results emphasize the need for systematic screening for LTBI, followed by IPT in high-risk patients.

Clinical characteristics and prognosis of bacteraemia during postoperative intra-abdominal infections.

BACKGROUND: Bloodstream infections of abdominal origin are usually associated with poor prognosis. We assessed the clinical and microbiological characteristics of critically ill patients admitted to the intensive care unit (ICU) for postoperative intra-abdominal infection (PIAI) and analysed the influence of bacteraemia on their outcome. METHODS: All consecutive PIAI patients admitted to the ICU between 1999 and 2014 were prospectively analysed. Bacteraemic patients (at least one positive blood culture in the 24 h preceding/following surgery) were compared with non-bacteraemic patients. Demographic characteristics, underlying disease, severity scores at the time of reoperation, microbiological results, therapeutic management, outcome, and survival were recorded. Results are expressed as median (interquartile range (IQR)) or proportions. RESULTS: Overall, 343 patients (54% male, 62 (49-73) years old) with PIAI were analysed, including 64 (19%) bacteraemic patients. Immunosuppression and cancer were more frequent in bacteraemic patients (p < 0.001 in both cases). No difference between groups was observed for the characteristics of initial surgery. Time to reoperation, site, and cause of PIAI were similar in both groups. At the time of reoperation, Sequential Organ Failure Assessment (SOFA) score was higher in bacteraemic patients (8 (6-10) versus 7 (4-10); p < 0.05). A predominance of Gram-positive (34%) and Gram-negative (47%) bacteria were recovered from blood cultures (polymicrobial bacteraemia in 9 (14%) patients and bacteraemia involving multidrug-resistant organisms in 14 (22%) patients). In multivariate analysis, risk factors for bacteraemia were immunosuppression or cancer, high SOFA score, and E. coli in peritoneal samples. Bacteraemia did not impact the management (with similar results for the adequacy of antibiotic therapy, anti-infective agents used, de-escalation or duration of therapy in both groups). Neither hospital mortality nor morbidity criteria differed between groups. Risk factors for mortality in multivariate analysis were urgent initial surgery, high Simplified Acute Physiology Score (SAPS) II score and documented antifungal therapy, but not perioperative bacteraemia. CONCLUSIONS: In this ICU population, bacteraemia did not change the overall management of patients with PIAI. Our data suggest that bacteraemic patients do not require a specific management.

Morbidity and mortality related to pneumonia and TRACHEOBRONCHITIS in ICU after lung transplantation.

BACKGROUND: Bacterial respiratory infections (BRI) are major complications contributing to increased morbidity and mortality after lung transplantation (LT). This study analyzed epidemiology and outcome of 175 consecutive patients developing BRI in ICU after LT between 2006 and 2012. METHODS: Three situations were described: colonization determined in donors and recipients, pneumonia and tracheobronchitis during the first 28 postoperative days. Severity score, demographic, bacteriologic and outcome data were collected. RESULTS: 26% of donors and 31% of recipients were colonized. 92% of recipients developed BRI, including at least one episode of pneumonia in 19% of recipients. Only 21% of recipients developed BRI with an organism cultured from the donor's samples, while 40% of recipients developed BRI with their own bacteria cultured before LT. Purulent sputum appears to be an important factor to discriminate tracheobronchitis from pneumonia. When compared to patients with tracheobronchitis, those with pneumonia had longer durations of mechanical ventilation (13 [3-27] vs 3 [29], p = 0.0005) and ICU stay (24 [16-34] vs 14 [9-22], p = 0.002). Pneumonia was associated with higher 28-day (11 (32%) vs 9 (7%), p = 0.0004) and one-year mortality rates (21 (61%) vs 24 (19%), p ≤ 0.0001). CONCLUSIONS: These data confirm the high frequency of BRI right from the early postoperative period and the poor prognosis of pneumonia after LT.

Characteristics and outcomes of anti-infective de-escalation during health care-associated intra-abdominal infections.

BACKGROUND: De-escalation is strongly recommended for antibiotic stewardship. No studies have addressed this issue in the context of health care-associated intra-abdominal infections (HCIAI). We analyzed the factors that could interfere with this process and their clinical consequences in intensive care unit (ICU) patients with HCIAI. METHODS: All consecutive patients admitted for the management of HCIAI who survived more than 3 days following their diagnosis, who remained in the ICU for more than 3 days, and who did not undergo early reoperation during the first 3 days were analyzed prospectively in an observational, single-center study in a tertiary care university hospital. RESULTS: Overall, 311 patients with HCIAI were admitted to the ICU. De-escalation was applied in 110 patients (53%), and no de-escalation was reported in 96 patients (47%) (escalation in 65 [32%] and unchanged regimen in 31 [15%]). Lower proportions of Enterococcus faecium, nonfermenting Gram-negative bacilli (NFGNB), and multidrug-resistant (MDR) strains were cultured in the de-escalation group. No clinical difference was observed at day 7 between patients who were de-escalated and those who were not. Determinants of de-escalation in multivariate analysis were adequate empiric therapy (OR 9.60, 95% CI 4.02-22.97) and empiric use of vancomycin (OR 3.39, 95% CI 1.46-7.87), carbapenems (OR 2.64, 95% CI 1.01-6.91), and aminoglycosides (OR 2.31 95% CI 1.08-4.94). The presence of NFGNB (OR 0.28, 95% CI 0.09-0.89) and the presence of MDR bacteria (OR 0.21, 95% CI 0.09-0.52) were risk factors for non-de-escalation. De-escalation did not change the overall duration of therapy. The risk factors for death at day 28 were presence of fungi (HR 2.64, 95% CI 1.34-5.17), Sequential Organ Failure Assessment score on admission (HR 1.29, 95% CI 1.16-1.42), and age (HR 1.03, 95% CI 1.01-1.05). The survival rate expressed by a Kaplan-Meier curve was similar between groups (log-rank test p value 0.176). CONCLUSIONS: De-escalation is a feasible option in patients with polymicrobial infections such as HCIAI, but MDR organisms and NFGNB limit its implementation.

Toxic Shock Syndrome: A Literature Review.

Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin-1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. Staphylococcal TSS can be menstrual or nonmenstrual. Streptococcal TSS is linked to a severe group A streptococcal infection and, most frequently, to a necrotizing soft tissue infection. Management of TSS is a medical emergency and relies on early detection, immediate resuscitation, source control and eradication of toxin production, bactericidal antibiotic treatment, and protein synthesis inhibiting antibiotic administration. The interest of polyclonal intravenous immunoglobulin G administration as an adjunctive treatment for TSS requires further evaluation. Scientific literature on TSS mainly consists of observational studies, clinical cases, and in vitro data; although more data on TSS are required, additional studies will be difficult to conduct due to the low incidence of the disease.

Long-term Oral Suppressive Antimicrobial Therapy in Infective Endocarditis (SATIE Study): An Observational Study.

Background: The role of suppressive antimicrobial therapy (SAT) in infective endocarditis (IE) management has yet to be defined. The objective of this study was to describe the use of SAT in an IE referral center and the patients' outcomes. Methods: We conducted a retrospective observational study in a French IE referral center (Paris). All patients with IE who received SAT between 2016 and 2022 were included. Results: Forty-two patients were included (36 male [86%]; median age [interquartile range {IQR}], 73 [61-82] years). The median Charlson Comorbidity Index score (IQR) was 3 (1-4). Forty patients (95%) had an intracardiac device. The most frequent microorganisms were Enterococcus faecalis (15/42, 36%) and Staphylococcus aureus (12/42, 29%). SAT indications were absence of surgery despite clinical indication (28/42, 67%), incomplete removal of prosthetic material (6/42, 14%), uncontrolled infection source (4/42, 10%), persistent abnormal uptake on nuclear imaging (1/42, 2%), or a combination of the previous indications (3/42, 7%). Antimicrobials were mainly doxycycline (19/42, 45%) and amoxicillin (19/42, 45%). The median follow-up time (IQR) was 398 (194-663) days. Five patients (12%) experienced drug adverse events. Five patients (12%) presented with a second IE episode during follow-up, including 2 reinfections (different bacterial species) and 3 possible relapses (same bacterial species). Fourteen patients (33%) in our cohort died during follow-up. Overall, the 1-year survival rate was 84.3% (73.5%-96.7%), and the 1-year survival rate without recurrence was 74.1% (61.4%-89.4%). Conclusions: SAT was mainly prescribed to patients with cardiac devices because of the absence of surgery despite clinical indication. Five (12%) breakthrough second IE episodes were reported. Prospective comparative studies are required to guide this empirical practice.

Enterococcal endocarditis management and relapses.

Introduction: Enterococcus faecalis is the third micro-organism causing endocarditis and is associated with a significant relapse rate. The objective of this study was to describe the management of patients with Enterococcus faecalis endocarditis (EE) and its implication for relapses. Methods: We conducted a monocentric, retrospective analysis of all patients hospitalized for EE including endocarditis or infection of cardiac implantable electronic device defined by the modified ESC 2015 Duke criteria in a referral centre in Paris, France. Results: Between October 2016, and September 2022, 54 patients with EE were included, mostly men (n = 40, 74%) with a median age of 75 [68-80] years. A high risk for infective endocarditis (IE) was found in 42 patients (78%), including 14 (26%) previous histories of IE, and 32 (59%) histories of valvular cardiac surgery. The aortic valve was the most frequently affected (n = 36, 67%). Combination therapy was mainly amoxicillin-ceftriaxone during all the curative antibiotic therapy duration (n = 31, 57%). Surgery was indicated for 40 patients (74%), but only 27 (50%) were operated on, mainly due to their frailty. Among the 17 deaths (32%), six (11%) happened during the first hospitalization for EE. A suppressive antibiotic treatment was initiated in 15 (29%) patients, mostly because of not performing surgery. During the 6-year study period an EE relapse occurred in three (6%) patients. Conclusions: EE is a worrying disease associated with a high risk of relapse and significant mortality. Suppressive antibiotic therapy could be a key treatment to limit the occurrence of relapses.

Perturbation and resilience of the gut microbiome up to 3 months after ß-lactams exposure in healthy volunteers suggest an important role of microbial ß-lactamases.

BACKGROUND: Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the ß-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience. RESULTS: While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of ß-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the ß-lactamase activity of the microbiota. The level of ß-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools. CONCLUSIONS: In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous ß-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon. Video Abstract.

Oral DAV131, a charcoal-based adsorbent, inhibits intestinal colonization by ß-lactam-resistant Klebsiella pneumoniae in cefotaxime-treated mice.

Antibiotics excreted into the intestinal tract, such as broad-spectrum cephalosporins, disrupt the indigenous microflora, affect colonization resistance (CR), and promote intestinal colonization by resistant bacteria. We tested whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a cefotaxime (CTX)-resistant Klebsiella pneumoniae strain (PUG-2) in CTX-treated mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days before oral challenge with 10(6) CFU of PUG-2. The fecal CTX concentrations and counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given concomitantly with CTX (P < 0.05), and the area under the curve of PUG-2 fecal density was significantly reduced (P < 0.01). In conclusion, reducing intestinal antibiotic exposure with DAV131 may reduce colonization by resistant strains during treatment compared to treatment with CTX only. This might open new possibilities for decreasing the impact of antibiotics on the intestinal microbiota during treatments.

Lincosamide resistance mediated by lnu(C) (L phenotype) in a Streptococcus anginosus clinical isolate.

OBJECTIVES: Unique resistance to lincosamides (L phenotype) due to the production of nucleotidyltransferases (Lnu) is uncommon among Gram-positive bacteria. The aim of the study was to characterize the L phenotype in a clinical isolate of the Streptococcus milleri group. METHODS: The strain UCN93 was recovered from neonatal specimens and from the mother's vaginal swab. Identification was confirmed by sequencing of the sodA gene. Antimicrobial susceptibility testing was carried out by the disc diffusion method, while MICs were determined using the agar dilution method. Screening for lnu(A), lnu(B), lnu(C) and lnu(D) genes was performed by PCR. Genetic environment and support were determined by thermal asymmetric interlaced PCR and PCR mapping. The transfer of lincomycin resistance was also attempted by conjugation. RESULTS: UCN93 was unambiguously identified as Streptococcus anginosus. It was susceptible to all tested antibiotics, except lincomycin (MIC, 8 mg/L) and tetracycline (2 mg/L). The lnu(C) gene was found to be responsible for the L phenotype. It was shown that lnu(C) was associated with a gene coding for a transposase within a structure similar to the transposon MTnSag1, described once in Streptococcus agalactiae. Since MTnSag1 was found to be mobilized by Tn916 and S. anginosus UCN93 harboured a Tn916 transposon, several attempts at transfer were performed but they all failed. The lnu(C)-containing genetic element was inserted into a chromosomal intergenic sequence of S. anginosus. CONCLUSIONS: Since lnu(C) has been detected in only one S. agalactiae clinical isolate so far, this is its second description among clinically relevant streptococci.