First report of Acinetobacter pittii acute community-acquired pneumonia in an immunocompetent patient in France following a heat wave.

BACKGROUND: In recent years, Acinetobacter baumannii-calcoaceticus complex (ABC) infections have attracted attention, mainly because of the impact of carbapenem-resistant isolates in hospital-acquired infections. However, acute community-acquired ABC infections are not uncommon in warm and humid countries, where they are responsible for community-acquired infections with specific clinical features. To date, such infection has not been reported in France. CASE PRESENTATION: We report the case of a 55-year-old non-immunocompromised patient living in France with no known risk factors for community-acquired ABC infections who presented pneumonia with bloodstream infection due to wild-type A. pittii. The outcome was favorable after 7 days of antibiotic treatment with cefepime. We confirmed bacterial identification with whole-genome sequencing, and we examined the A. pitii core-genome phylogeny for genomic clusters. CONCLUSIONS: This situation is uncommon in Europe and occurred after a heat wave in France with temperatures above 38 °C. Herein, we discuss the possibility that this pneumonia may be emerging in the current context of global warming.

Ampicillin-susceptible Enterococcus faecium infections: clinical features, causal clades, and contribution of MALDI-TOF to early detection.

Enterococcus faecium, a common resident of the human gastrointestinal tract, is also a major pathogen. Prompt initiation of appropriate treatment is essential to improve patient outcome in disseminated E. faecium infections. However, ampicillin resistance is frequent in this species, rendering treatment difficult. We used a comprehensive approach, including clinical data review, whole-genome sequencing, and mass spectrometry, to characterize ampicillin-susceptible (EFM-S) and ampicillin-resistant (EFM-R) isolates. We included all patients with culture-confirmed E. faecium infection attending our hospital over a 16-month period. A comparison of 32 patients infected with EFM-S strains and 251 patients infected with EFM-R strains revealed that EFM-R isolates were strongly associated with a longer hospital stay, history of prior hospitalization, and the carriage of multidrug-resistant organisms. An analysis of the genomes of 26 EFM-S and 26 EFM-R isolates from paired patients revealed a population structure almost perfectly matching ampicillin susceptibility, with resistant isolates in clade A1, and susceptible isolates in clades A2 and B. The clade B and A2 isolates mostly came from digestive or biliary tract samples, whereas clade A1 isolates were mostly obtained from urine and blood. Finally, we built a custom database for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which differentiated between clade B and clade A1/A2 strains with high-positive and high-negative predictive values (95.6% and 100%, respectively). This study provides important new insight into the clinical features and clades associated with EFM-S and EFM-R isolates. In combination with MALDI-TOF MS, these data could facilitate the rapid initiation of the most appropriate treatment.IMPORTANCEEnterococcus faecium is an important human pathogen in which the prevalence of ampicillin resistance is high. However, little is known about the clinical characteristics of patients infected with ampicillin-resistant and ampicillin-susceptible strains. Indeed, current knowledge is based on genus-wide studies of Enterococcus or studies of very small numbers of susceptible isolates, precluding robust conclusions. Our data highlight specific clinical features related to the epidemiology of EFM-S and EFM-R strains, such as length of hospital stay, history of prior hospitalization, carriage of multidrug-resistant organisms, and type of sample from which the isolate was obtained. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with a custom-built database may make it possible to distinguish clade B isolates, which are typically susceptible to ampicillin, from clade A1/A2 isolates (A1 being typically resistant), thereby facilitating the management of these infections.

Evaluation of the contribution of shotgun metagenomics in the microbiological diagnosis of liver abscesses.

BACKGROUND: Shotgun metagenomics (SMg) sequencing has gained a considerable interest, as it enables the detection of any microorganisms through a single analysis. Due to the limitations of standard microbiological approaches, the microbial documentation of liver abscesses (LA), which is crucial for their medical management, can be difficult. Here we aimed to compare the performance of SMg with standard approaches for the microbiological documentation of LA. METHODS: In this retrospective study conducted at two centers, we compared the results of standard microbiology with metagenomics analysis of consecutive LA samples. For samples tested positive for Klebsiella pneumoniae, we compared the analysis of virulence and resistance genes using metagenomics data to whole-genome sequencing of corresponding isolates obtained in culture. RESULTS: Out of the 62 samples included, standard approaches and SMg yielded documentation in 80.6% and 96.8%, respectively. In 37.1% (23/62) of cases, both methods showed identical results, whereas in 43.5% (27/62) of cases, the samples were positive by both methods, but SMg found additional species in 88.9% (24/27), mostly anaerobes. When the standard approaches were negative, the SMg was able to detect microorganisms in 80.0% of cases (8/10). Overall, SMg identified significantly more microorganisms than culture (414 vs.105; p<0.05). K. pneumoniae genome analysis was able to detect resistance and virulence genes with a level of sensitivity depending on the depth of sequencing. DISCUSSION: Overall, we showed that SMg had better performance in detecting and identifying microorganisms from LA samples and could help characterizing strain's resistome and virulome. Although still costly and requiring specific skills and expensive equipment, MGs methods are set to expand in the future.

Vasoplegic Syndrome after Cardiac Surgery for Infective Endocarditis.

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

Overly broad-spectrum antibiotic treatment of wild-type Pseudomonas aeruginosa infections in relation to the EUCAST new definition of susceptibility testing categories, a retrospective multicentre cohort study.

Objectives: EUCAST changed the definition of the 'intermediate' (I) category in 2019, now defined as 'susceptible, increased exposure'. This new definition could lead to an increased prescription of antibiotics still reported as 'S', compared with those now reported as 'I'. The objective of this study was to evaluate the influence of this definition on the use of overly broad-spectrum antibiotics for the treatment of infections caused by WT Pseudomonas aeruginosa. Methods: A retrospective observational multicentre study was conducted, involving five hospitals. Two 15 month study periods were defined, before and after the implementation of the new definition. All patients with an infection caused by WT P. aeruginosa treated by ß-lactams were included. The main endpoint was the proportion of patients treated by an overly broad-spectrum antibiotic treatment by meropenem or ceftolozane/tazobactam. Results: Two hundred and ninety-one patients were included. No difference between groups was found, in terms of infection, microbiology or demographic characteristics. Two overly broad-spectrum antibiotic treatments by meropenem or ceftolozane/tazobactam were observed in Period 1 (1.2%), versus 13 in Period 2 (10.8%; P < 0.001). No overly broad-spectrum treatment was observed when the antimicrobial stewardship team had given advice. Conclusions: This new definition can cause a negative impact on the use of overly broad-spectrum antibiotic treatment due to misunderstanding by clinicians. Its successful implementation requires adaptation of software for reporting antibiotic susceptibility, a sustained strong information campaign by microbiologists and support by an antimicrobial stewardship team.

Health status and healthcare trajectory of vulnerable asylum seekers hosted in a French Reception Center.

BACKGROUND: Europe lacks studies related to asylum-seekers' health. METHODS: We described the health status, healthcare and follow-up of men seeking asylum, accommodated in a primary reception center in Paris (CPA). This observational study included volunteer patients presenting for care at the CPA primary care unit (PCU) from January to March 2018. They could be referred to on-site GPs and psychiatrists or to surrounding healthcare facilities. After their asylum application, patients were transferred to other French accommodation centers. PCU healthcare professionals could make referrals for close medical reassessments after transfer. RESULTS: The 728 included men came mostly from Central Asia or Middle East (65%) and Africa (34%). Seventy percent reported violence during migration. Seventy-five percent (547/728) were referred to on-site GPs, 20% to psychiatrists. During patients' stay at CPA, 67% (144/214) of referrals to surrounding healthcare facilities led to performed consultations. Seven percent of all the included patients (49/728) were referred for frequent communicable infectious diseases screening. Final diagnoses (n = 1108) included 31% infectious diseases and 7% psychiatric disorders. When post-transfer accommodation centers could be reached, 69% (33/48) of the medical referrals had led to a scheduled appointment. CONCLUSIONS: The healthcare trajectory at CPA could benefit from optimization of infectious and psychiatric screenings, and improved coordination of care and follow-up.

Blood Cultures for the Diagnosis of Infective Endocarditis: What Is the Benefit of Prolonged Incubation?

To assess the need for prolonged incubation of blood culture bottles beyond five days for the diagnosis of infectious endocarditis (IE), we conducted a retrospective cohort study of 6109 sets of two blood culture bottles involving 1211 patients admitted to the Henri Mondor University Hospital for suspicion of IE between 1 January 2016 and 31 December 2019. Among the 322 patients with IE, 194 had positive blood cultures in our centre. Only one patient with a time-to-positivity blood culture of more than 120 h (5 days) was found. The main cause for the 22 patients with positive blood cultures after five days was contamination with Cutibacterium acnes. Our results do not support extending the duration of incubation of blood culture bottles beyond five days for the diagnosis of infectious endocarditis, with the exception of patients with risk factors for C. acnes infection.

Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19.

OBJECTIVE: To assess post-discharge persistent symptoms and health-related quality of life (HRQoL) of patients hospitalized in a COVID-19 ward unit more than 100 days after their admission. METHODS: All eligible patients were contacted by phone by trained physicians and were asked to answer to a dedicated questionnaire. Patients managed in hospital ward without needing intensive care were compared with those who were transferred in intensive care units (ICU). RESULTS: We included 120 patients after a mean (±SD) of 110.9 (±11.1) days following admission. The most frequently reported persistent symptoms were fatigue (55%), dyspnoea (42%), loss of memory (34%), concentration and sleep disorders (28% and 30.8%, respectively). Comparisons between ward- and ICU patients led to no statistically significant differences regarding those symptoms. In both group, EQ-5D (mobility, self-care, pain, anxiety or depression, usual activity) was altered with a slight difference in pain in the ICU group. CONCLUSION: Most patients requiring hospitalization for COVID-19 still have persistent symptoms. While there were few differences between HRQoL between ward and ICU patients, our findings must be confirmed in larger cohorts, including more severe patients.

A nomogram to predict the risk of unfavourable outcome in COVID-19: a retrospective cohort of 279 hospitalized patients in Paris area.

OBJECTIVE: To identify predictive factors of unfavourable outcome among patients hospitalized for COVID-19. METHODS: We conducted a monocentric retrospective cohort study of COVID-19 patients hospitalized in Paris area. An unfavourable outcome was defined as the need for artificial ventilation and/or death. Characteristics at admission were analysed to identify factors predictive of unfavourable outcome using multivariable Cox proportional hazard models. Based on the results, a nomogram to predict 14-day probability of poor outcome was proposed. RESULTS: Between March 15th and April 14th, 2020, 279 COVID-19 patients were hospitalized after a median of 7 days after the first symptoms. Among them, 88 (31.5%) patients had an unfavourable outcome: 48 were admitted to the ICU for artificial ventilation, and 40 patients died without being admitted to ICU. Multivariable analyses retained age, overweight, polypnoea, fever, high C-reactive protein, elevated us troponin-I, and lymphopenia as risk factors of an unfavourable outcome. A nomogram was established with sufficient discriminatory power (C-index 0.75), and proper consistence between the prediction and the observation. CONCLUSION: We identified seven easily available prognostic factors and proposed a simple nomogram for early detection of patients at risk of aggravation, in order to optimize clinical care and initiate specific therapies. KEY MESSAGES Since novel coronavirus disease 2019 pandemic, a minority of patients develops severe respiratory distress syndrome, leading to death despite intensive care. Tools to identify patients at risk in European populations are lacking. In our series, age, respiratory rate, overweight, temperature, C-reactive protein, troponin and lymphocyte counts were risk factors of an unfavourable outcome in hospitalized adult patients. We propose an easy-to-use nomogram to predict unfavourable outcome for hospitalized adult patients to optimize clinical care and initiate specific therapies.

Applicability of the CURB-65 pneumonia severity score for outpatient treatment of COVID-19.

OBJECTIVES: The CURB-65 is a severity score to predict mortality secondary to community acquired pneumonia and is widely used to identify patients who can be managed as outpatients. However, whether CURB-65 can be applicable to COVID-19 patients for the decision of outpatient treatment is still unknown. METHODS: We conducted a retrospective single-centre study assessing the performance of the CURB-65 to predict the risk of poor outcome, defined as the need for mechanical ventilation and/or death, among patients hospitalized for COVID-19. The association between the CURB-65 and the outcome was assessed by a univariable Cox proportional hazard regression model. RESULTS: A total of 279 patients were hospitalized between March 15th and April 14th, 2020. According to the CURB-65, 171 (61.3%) patients were considered at low risk (CURB-65 01), 66 (23.7%) at intermediate risk (CURB-65=2), and 42 (15.1%) had high risk of 30-day mortality (CURB-65 35). During the study period, 88 (31.5%) patients had a poor outcome. The CURB-65 was strongly associated with a poor outcome (Pfor linear trend <0.001). However, among patients with a CURB-65 of 01, thus considered at low risk, 36/171 (21.1%) had a poor outcome. CONCLUSIONS: Our study suggests that the applicability of CURB-65 to guide the decision of inpatient or outpatient care is scarce, as it does not safely identify patients who could be managed as outpatients.

Implementation and evaluation of a therapeutic patient education programme during a clinical trial in Yaoundé, Cameroon - Trial ANRS-12286/MOBIDIP.

OBJECTIVES: High adherence is needed to maintain antiretroviral therapy efficacy. Few attempts at therapeutic patient education (TPE) have been made in sub-Saharan Africa. We describe patients' achievements before intervention and identified needs, TPE programme implementation and evaluation, and patients' satisfaction. METHODS: The TPE programme was proposed to patients in the ANRS-12286/MOBIDIP trial. Beforehand, a directory of competences to manage HIV infection was designed. Patients' HIV-related knowledge and skills assessment was realised, leading to an educational contract. Evaluation was performed using a standardised collection form and a satisfaction survey. RESULTS: Of 154 patients, 146 underwent TPE. During a median of 1.8 years, 47% of patients had ≥3 consultations. Educational assessment revealed limited knowledge about HIV disease. Conversely, patients had frequently managed issues of adherence or disclosure. A median of 12 objectives were considered per patient, and 75% were attained. Objectives from the cognitive domain were less frequently attained. Patients appeared satisfied with the intervention: more emphasis was placed on psycho-affective aspects or experience-sharing than on the acquisition of knowledge. CONCLUSION: Active listening, know-how and a space for discussion appear more important for patients than knowledge on disease or treatments. PRACTICE IMPLICATIONS: In HIV care, the directory of learning objectives should be revised to include more objectives concerning practical skills for disease management.

Psoas abscess and chronic Q fever: a contiguous or hematogenous complication? A case report and literature review.

Few cases of psoas abscesses (PA) during chronic Q fever have been reported, and the route of transmission remains unknown. Here, we report a new case and have performed a systematic literature review to determinate the spreading route of this complication. Medline, EMBASE and Web of Science were searched. Local spreading was supported by endocarditis exclusion, evidence of vascular infection and absence of distantly infected sites. Among 275 retrieved references, 179 were initially rejected, and 85 additional references were rejected after full-text review. A total of 11 studies, reporting 13 cases, were included. Additionally, we reported one new case. A total of 14/14 cases reached Q fever vascular infection diagnostic criteria, and 7/14 provided adequate evidence supporting a causal relationship between Q fever vascular infection and PA. All patients presented aorta defects. In conclusion, Q fever PA results from the spreading of a local infection and occurs specifically in patients presenting a vascular graft or an abdominal aortic aneurysm.

Tertiary Lymphoid Organs in Takayasu Arteritis.

OBJECTIVE: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. METHODS: Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment, and follow-up data were extracted from medical records. RESULTS: Aorta specimens from Bentall procedures were available from seven patients (5 females, aged 22-57 years) with TA. Surgical treatment was performed at TA diagnosis (n = 4) or at a median of 108 months (84-156) after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient. Of note, ectopic follicles containing CD21(+) FDCs were found in all patients (4/4) with increased aortic (18)F-fluoro-deoxyglucose (FDG) uptake before surgery but were absent in all but one patients (2/3) with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center-like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells. CONCLUSION: Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

Presentation and impact of catheter-associated thrombosis in patients with infected long-term central venous catheters: a prospective bicentric observational study.

BACKGROUND: Catheter-associated thrombosis (CAT) in patients with infected long-term central venous catheter (LTCVC) has been poorly studied. METHODS: We prospectively included patients with infected LTCVC and collected clinical data. Doppler ultrasound was systematically performed to screen for CAT. Outcome (death or infection relapse) was evaluated 12 weeks after infection diagnosis. RESULTS: 90 patients were included and CAT was diagnosed in 27 (30%). Local signs suggesting infection were more frequent in patients with CAT than without (11/27 versus 8/63, p = 0.03). Outcome was similar in patients with and without CAT. However, median duration of antimicrobials was longer (18 versus 14 days, p = 0.02), catheter removal tended to be more frequent (24/27 versus 46/63, p = 0.08), and anticoagulant therapy more often prescribed (17/27 versus 6/63, p < 0.01) in patients with CAT than without. Patients with occlusive thrombosis were more likely to have Staphylococcus aureus infections (4/7 versus 1/17, p = 0.02) and prolonged positivity of blood-cultures (3/7 versus 1/15, p = 0.02), than patients with non-occlusive thrombosis. CONCLUSION: CAT is associated with local signs suggesting infection. A more aggressive treatment in CAT cases allowed a similar outcome at 12 weeks between patients with and without CAT. Occlusive thrombosis represented a subgroup of patients at risk of delayed clearance of bacteremia.

Incidence of infectious morbidity events after second-line antiretroviral therapy initiation in HIV-infected adults in Yaoundé, Cameroon.

BACKGROUND: Since antiretroviral therapy (ART), HIV-infected individuals experience mainly non-AIDS-related conditions, among which infectious events are prominent. We aimed to estimate incidence and describe overall spectrum of infectious events, including all grade events, among HIV-1-infected adults failing first-line ART in Yaoundé, Cameroon. METHODS: All patients from Cameroon enrolled in the second-line ART 2LADY trial (ANRS12169) were included in this secondary analysis. Medical files were reviewed with predefined criteria for diagnosis assessment. Incidence rates (IR) were estimated per 100 person-years (% PY). RESULTS: A total of 302 adult patients contributing 840 PY experienced 596 infectious events (IR 71% PY). Only 29 (5%) events were graded as severe. Most frequent infections were upper respiratory tract infections (15% PY), diarrhoea (9% PY) and malaria (9% PY). A total of 369 (62%) infections occurred during the first year (IR 130% PY) followed by a persistent lower incidence during the following 3 years. Higher IR were observed in patients with CD4+ T-cell count <200 cells/mm3 for all infectious events except for mycobacterial and parasitic infections. IR of viral, bacterial and parasitic infectious events were lower in case of co-trimoxazole use in patients with CD4+ T-cell count <200 cells/mm3. CONCLUSIONS: Infectious events are common and mainly occur during the first year after treatment initiation. Second-line ART initiation had a positive impact on the entire spectrum of infectious morbidity.