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.

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study.

OBJECTIVES: A global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection. METHODS: All consecutive patients with a polymerase chain reaction (PCR)-confirmed monkeypox infection seen in a French referral centre were included. RESULTS: Between 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients. CONCLUSION: The current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement.

Novel mutations in antiviral multiresistant HSV-2 genital lesion: A case report.

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

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.

Unplanned admission after ambulatory anaesthesia in France: analysis of a database of 36,584 patients.

BACKGROUND: Unplanned admission (UA) after ambulatory procedures is an unexpected event that has organisational and financial impacts. This study was undertaken to determine the current rate of UA in France and to evaluate the factors associated with the occurrence of this event. METHOD: This is a retrospective analysis of a database of 36,584 patients issued from a private hospital in France. This study received an IRB approval. All of the patients that received ambulatory anaesthesia between April 2015 and June 2017 were included in this database. RESULTS: The overall rate of UA was 1.8% (95%CI: 1.3-2.3]. Hospitalisation after endoscopic procedures (gastrointestinal endoscopy and bronchial fibroscopy) was 1.1% (95%CI: 0.3-1.9), whereas it was 2.5% (95%CI: 1.8-3.2) after surgical procedures (p < 0.01). Organisational concerns, medical reason and surgical complications accounted respectively for one third of the hospitalisations. Pain was liable in 13% of cases, whereas PONV, residual sedation and urinary retention accounted respectively for 6.9%, 2.8% and 2.6% of cases. In a multivariate analysis, age > 60 years, ASA status > 2, general anaesthesia and the type of the procedures were identified risk factors. CONCLUSIONS: In this large cohort of ambulatory patients, the rate of UA remains significant. This is probably related, at least partly, to more invasive procedures scheduled in ambulatory setting. However, organisational problems occurred still frequently. Some factors appear to be easily improvable by appropriate preoperative information, better operating theatre scheduling and better analgesic strategy.

How and why do French medical students choose the specialty of infectious and tropical diseases? A national cross-sectional study.

BACKGROUND: Infectious and tropical diseases (ID) physicians are needed now more than ever to tackle existing and emerging global threats. However, in many countries, ID is not recognized as a qualifying specialty. The creation of ID residency in 2017 in France offers the opportunity to know how and why the specialty is chosen by medical students. METHODS: We first analyzed the choice of specialty of all French medical students in 2017 and 2018 according to their rank at the national exam that ends medical studies. A web questionnaire was then sent in January 2019 to all ID residents in France (n = 100) to assess the factors influencing their choice of specialty and their career plan. RESULTS: We analyzed the choice of 17,087 medical students. ID was the first-chosen specialty with a median national rank of 526/8539, followed by plastic surgery and ophthalmology. The questionnaire was completed by 90% of the French ID residents (n = 100). The most encouraging factors to choose ID were the multi-system approach of the specialty, the importance of diagnostic medicine and having done an internship in ID during medical school. The potential deterrents were the work-life balance, the workload and the salary. CONCLUSIONS: The recent recognition of ID as a qualifying specialty in France can be considered a success insofar as the specialty is the most popular among all medical and surgical specialties. Individuals who choose ID are attracted by the intellectual stimulation of the specialty but express concerns about the working conditions and salaries.

Dynamic Changes in Microbial Composition During Necrotizing Soft-Tissue Infections in ICU Patients.

Introduction: Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries. Materials and Methods: This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses. Results: Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50-68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1-7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including Pseudomonas aeruginosa, staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR (p < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms (p = 0.79) and MDR bacteria (p = 1.0) or the 1-year survival rate. Conclusion: The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.

Robotic-assisted unilateral adrenalectomy: risk factors for perioperative complications in 303 consecutive patients.

BACKGROUND: There is no consensus about the utility of using the robotic platform to perform a unilateral lateral transabdominal adrenalectomy in comparison with conventional laparoscopy. In some groups, obese patients (Body Mass Index > 30 kg/m2) and patients with tumor size > 5 cm have been considered as good candidates for robotic adrenalectomy. However, evaluation of incidence and risk factors for perioperative complications is currently lacking in large series of patients. The aim of this study was to evaluate incidence and predictive factors for intraoperative (conversion and capsular rupture) and postoperative complications (morbidity) after unilateral robotic-assisted transabdominal lateral adrenalectomy. METHODS: From 2001 to 2016, consecutive patients undergoing unilateral lateral transabdominal robotic adrenalectomy were included in a prospectively maintained database and analyzed retrospectively (clinicaltrials.gov NCT03410394). RESULTS: A total of 303 consecutive patients were analyzed. Between the first and last 100 of patients, mean tumor size increased from 2.9 to 4.2 cm (p < 0.001) and mean operating time decreased from 99 to 77 min (p < 0.001). Postoperative complications occurred in 28 patients (9.2%) and no postoperative death was observed. Nine patients (3%) were converted to open laparotomy and capsular rupture was observed in nine patients (3%). BMI was not a significant risk factor for conversion, capsular rupture, or postoperative complication. Tumor size > 5 cm remained the only predictive factor for conversion to laparotomy (OR 7.47, 95% CI 1.81-30.75; p = 0.005). History of upper gastrointestinal surgery was the only predictive factor for capsular rupture (OR 13.6, 95% CI 2.33-80.03; p = 0.004). Conversion to laparotomy (OR 8.35, 95% CI 1.99-35.05; p = 0.003) and patient age (OR 1.039, 95% CI 1.006-1.072; p = 0.019) remained independent predictive factors for postoperative complications. CONCLUSIONS: This study identified independent risk factors for perioperative complications after robotic-assisted unilateral adrenalectomy. These factors should be taken into account when evaluating robotic-assisted transabdominal lateral adrenalectomy.

Safety and efficacy of peri-operative administration of hydroxyethyl starch in children undergoing surgery: A systematic review and meta-analysis.

BACKGROUND: Hydroxyethyl starch (HES) solutions have shown their efficiency for intravascular volume expansion. A safety recommendation limiting their use in adult patients has recently been made. OBJECTIVE: To assess the efficacy and adverse effects of HES when administered intra-operatively to paediatric patients. DESIGN: Systematic review with meta-analyses. Data were analysed using classical mean differences [and their 95% confidence intervals (CIs)] and trial sequential analysis. A Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification was performed for all outcomes. Reviewers extracted valid data, including perioperative total fluid intakes, mortality, renal function, coagulation tests, blood loss and length of hospital and ICU stay. DATA SOURCES: Searches were performed in databases (Pubmed, Embase, Cochrane central register of controlled trials), clinical trials register, and open access journals not indexed in major databases. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) published before December 2016 involving paediatric patients who received 6% low molecular weight HES. RESULTS: Nine RCTs involving 530 peri-operative paediatric patients were analysed. Compared with other fluids, HES did not significantly modify the amount of peri-operative fluid administered [mean difference 0.04; 95% CI (-1.76 to 1.84) ml kg], urine output [mean difference -33; 95% CI (-104 to 38) ml kg] or blood loss [mean difference -0.09; (-0.32 to 0.15) ml kg]. Trial sequential analysis determined that the outcomes for peri-operative fluid and urine output were underpowered. All results were graded as very low quality of evidence. CONCLUSION: Intravascular volume expansion with low molecular weight 6% HES did not appear to modify renal function, blood loss or transfusion when administered to children during the peri-operative period. However, given the lack of statistical power and the very low GRADE quality of evidence, more high-quality RCTs are needed to explore these outcomes.

Time Course of Septic Shock in Immunocompromised and Nonimmunocompromised Patients.

OBJECTIVES: To address the impact of underlying immune conditions on the course of septic shock with respect to both mortality and the development of acute infectious and noninfectious complications. DESIGN: An 8-year (2008-2015) monocenter retrospective study. SETTING: A medical ICU in a tertiary care center. PATIENTS: Patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients were classified in four subgroups with respect to their immune status: nonimmunocompromised and immunocompromised distributed into hematologic or solid malignancies and nonmalignant immunosuppression. Outcomes were in-hospital death and the development of ischemic and hemorrhagic complications and ICU-acquired infections. The determinants of death and complications were addressed by multivariate competing risk analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight hundred one patients were included. Among them, 305 (38%) were immunocompromised, distributed into solid tumors (122), hematologic malignancies (106), and nonmalignant immunosuppression (77). The overall 3-day, in-ICU, and in-hospital mortality rates were 14.1%, 37.3%, and 41.3%, respectively. Patients with solid tumors displayed increased in-hospital mortality (cause-specific hazard, 2.20 [95% CI, 1.64-2.96]; p < 0.001). ICU-acquired infections occurred in 211 of the 3-day survivors (33%). In addition, 95 (11.8%) and 70 (8.7%) patients exhibited severe ischemic or hemorrhagic complications during the ICU stay. There was no association between the immune status and the occurrence of ICU-acquired infections. Nonmalignant immunosuppression and hematologic malignancies were independently associated with increased risks of severe ischemic events (cause-specific hazard, 2.12 [1.14-3.96]; p = 0.02) and hemorrhage (cause-specific hazard, 3.17 [1.41-7.13]; p = 0.005), respectively. CONCLUSIONS: The underlying immune status impacts on the course of septic shock and on the susceptibility to ICU-acquired complications. This emphasizes the complexity of sepsis syndromes in relation with comorbid conditions and raises the question of the relevant endpoints in clinical studies.