Deciphering Unexpected Vascular Locations of Scedosporium spp. and Lomentospora prolificans Fungal Infections, France.

Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease--related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.

Campylobacter coli enteritis associated with Campylobacter fetus bacteremia, spondylodiscitis, and late CIED-related endocarditis, a case report.

Campylobacter sp. is widely considered a leading causative agent of bacterial food-borne gastrointestinal illness. Discitis and endocarditis caused by Campylobacter spp. are extremely rare. We describe the case of a 94-year-old man who was admitted for recent lumbar pain, diarrhea, and fever. C. fetus and C. coli were identified by MALDI-TOF from blood and stool samples respectively. MRI of the spine showed L5-S1 discitis. Patient was treated with 6 weeks of amoxicillin with clinical and microbiological response until cardiac implantable electronic device (CIED) related endocarditis occurred four weeks after the end of the antibiotic treatment. He was treated with another 6 weeks amoxicillin regimen, with a favorable outcome after a 6-month follow-up. Enteric infection with Campylobacter spp. in a debilitated patient should raise the possibility of a co-infection with another more invasive species such as C. fetus, leading to systemic invasion. In case of Campylobacter fetus bacteremia, a search for endocarditis and spondylodiscitis is recommended even in the absence of specific clinical signs.

Effectiveness of third-generation cephalosporins or piperacillin compared with cefepime or carbapenems for severe infections caused by wild-type AmpC ß-lactamase-producing Enterobacterales: A multi-centre retrospective propensity-weighted study.

BACKGROUND: The optimal treatment regimen for infections caused by wild-type AmpC ß-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to the type of definitive antibiotic therapy: third-generation cephalosporin (3GC), piperacillin ± tazobactam, cefepime or carbapenem. METHODS: All cases of BSI and pneumonia caused by wild-type AmpC ß-lactamase-producing Enterobacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin ± tazobactam (piperacillin group), or cefepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups. RESULTS: In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half (n=271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin ± tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI. CONCLUSION: Treatment of included BSI or pneumonia caused by wild-type AmpC ß-lactamase-producing Enterobacterales with 3GC or piperacillin ± tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem.

Invasive bacillary angiomatosis in a kidney transplant recipient: A challenging case on belatacept immunosuppression.

Bacillary angiomatosis is a disseminated vascular proliferative disease caused by aerobic gram-negative bacilli Bartonella henselae or Bartonella quintana. Bacillary angiomatosis is mostly described in immunosuppressed patients with HIV infection and organ transplant recipients. We describe the case of a female aged 75 years who is a kidney transplant recipient who was admitted for a 3-month history of intermittent fever, chills, vomiting, and a 12-kg weight loss. The maintenance immunosuppression was based on prednisone, mycophenolate, and monthly infusions of belatacept. Physical examination was unremarkable. Laboratory investigations revealed elevated blood acute phase proteins but all blood cultures were negative. Serological tests for Bartonella were negative. Thoracoabdominal computed tomography scan and transesophageal echocardiography were normal. A Positron Emission Tomography scan showed a hypermetabolic mass in the duodenopancreatic region, with multiple hepatic and splenic lesions. Histological findings of spleen and pancreatic biopsies were not conclusive. The histopathological examination of a celiac lymph node biopsy finally demonstrated bacillary angiomatosis. The diagnosis of bacillary angiomatosis in immunocompromised patients is most often delayed in the absence of skin involvement. A high index of clinical suspicion is needed when interpreting negative results.

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.

Clinical Added Value of SARS-CoV-2 Antigen Detection in Blood Samples.

This study evaluated the performances of immunoassays (LFIA and ELISA) designed for SARS-CoV-2 Antigen (Ag)-detection in nasopharyngeal (NP) and serum samples in comparison to RT-PCR. NP samples from patients with respiratory symptoms (183 RT-PCR-positive and 74 RT-PCR-negative samples) were collected from March to April and November to December 2020. Seroconversion and antigen dynamics were assessed by symptom onset and day of RT-PCR diagnosis. Serum samples from 87 COVID-19 patients were used to investigate the added value of Ag quantification, at diagnosis and during follow-up. The sensitivity of COVID-VIRO-LFIA on samples with Ct ≤ 33, considered as the contagious threshold, was 86% on NPs (CI 95%: 79-90.5) and 76% on serum samples (CI 95%: 59.4-88), with a specificity of 100%. Serum N-Ag was detected during active infection as early as day two from symptom onset, with a diagnostic sensitivity of 81.5%. Within one week of symptom onset, diagnostic sensitivity and specificity reached 90.9% (95% CI, 85.1%-94.6%) and 98.3% (95% CI, 91.1%-99.9%), respectively. Serum N-Ag concentration closely correlated with disease severity. Longitudinal analysis revealed the simultaneous increase of antibodies and decrease of N-Ag. Sensitivities of COVID-VIRO-LFIA and COV-QUANTO-ELISA tests on NP and serum samples were close to 80%. They are suitable COVID-19-laboratory diagnostic tests, particularly when blood samples are available, thus reducing the requirement for NP sampling, and subsequent PCR analysis. ELISA titers may help to identify patients at risk of poor outcomes.

Clinical Features and Outcome of Multidrug-Resistant Osteoarticular Tuberculosis: A 12-Year Case Series from France.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2-6) for a mean duration of 20 months (range, 13-27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

One-Year Sequelae and Quality of Life in Adults with Meningococcal Meningitis: Lessons from the COMBAT Multicentre Prospective Study.

INTRODUCTION: COMBAT is a prospective, multicentre cohort study that enrolled consecutive adults with community-acquired bacterial meningitis (CABM) in 69 participating centres in France between February 2013 and July 2015 and followed them for 1 year. METHODS: Patients aged at least 18 years old, hospitalised with CABM were followed during their hospitalisation and then contacted by phone 12 months after enrolment. Here we present the prevalence of sequelae at 12 months in a subgroup of patients with meningococcal meningitis. RESULTS: Five of the 111 patients with meningococcal meningitis died during initial hospitalisation and two died between discharge and 12 months, leaving 104 patients alive 1 year after enrolment, 71 of whom provided 12-month follow-up data. The median age was 30.0 years and 54.1% of the patients had no identified risk factor for meningitis. More than 30% reported persistent headache, more than 40% were not satisfied with their sleep and 10% had concentration difficulties. Hearing loss was present in about 15% of the patients and more than 30% had depressive symptoms. About 13% of the patients with a previous professional activity had not resumed work. On the SF-12 Health Survey, almost 50% and 30% had physical component or mental component scores lower than the 25th percentile of the score distribution in the French general population. There was a non-significant improvement in the patients' disability scores from hospital discharge to 12 months (p = 0.16), but about 10% of the patients had residual disability. CONCLUSIONS: Although most patients in our cohort survive meningococcal meningitis, the long-term burden is substantial and therefore it is important to ensure a prolonged follow-up of survivors and to promote preventive strategies, including vaccination. TRIAL REGISTRATION: ClinicalTrial.Gov identification number NCT01730690.

Aztreonam plus Clavulanate, Tazobactam, or Avibactam for Treatment of Infections Caused by Metallo-ß-Lactamase-Producing Gram-Negative Bacteria.

Metallo-ß-lactamase (MBL)-producing Gram-negative bacteria are often extremely resistant, leading to a real therapeutic dead end. Here, we evaluated the in vitro and in vivo efficacy of aztreonam in combination with ceftazidime-avibactam, ceftolozane-tazobactam, or amoxicillin-clavulanate for the treatment of infections caused by MBL-producing Enterobacteriaceae, MBL-producing Pseudomonas aeruginosa, and extremely drug-resistant Stenotrophomonas maltophilia First, we report two clinical cases, namely, a urinary tract infection caused by an NDM-5-producing Escherichia coli isolate and a pulmonary infection caused by a S. maltophilia isolate efficiently treated with the association of aztreonam-ceftazidime-avibactam and aztreonam-amoxicillin-clavulanate, respectively. Then, a total of 50 MBL-producing Enterobacteriaceae isolates, 3 MBL-producing P. aeruginosa isolates, and 5 extremely drug-resistant S. maltophilia isolates were used to test aztreonam susceptibility in combination with ceftolozane-tazobactam, ceftazidime-avibactam, or amoxicillin-clavulanate. The Etest strip superposition method was used to determine the MICs of the aztreonam/inhibitor combinations. According to CLSI breakpoints, aztreonam susceptibility was fully restored for 86%, 20%, and 50% of the MBL-producing Enterobacteriaceae isolates when combined with ceftazidime-avibactam, ceftolozane-tazobactam, and amoxicillin-clavulanate, respectively. In P. aeruginosa, the aztreonam-ceftazidime-avibactam combination was the most potent, even though the reduction in MICs was at most 2-fold. With the 5 S. maltophilia isolates, aztreonam-ceftazidime-avibactam and aztreonam-amoxicillin-clavulanate were found to be equal (100% susceptibility). Overall, aztreonam-ceftazidime-avibactam was the most potent combination to treat infections caused by MBL producers compared with aztreonam-amoxicillin-clavulanate and aztreonam-ceftolozane-tazobactam. However, in many cases aztreonam-amoxicillin-clavulanate was found to be as efficient as aztreonam-ceftazidime-avibactam, offering the main advantage to be markedly cheaper. We also confirmed the validity of Etest superpositions as a very simple method to determine MICs of aztreonam combinations.

Germs of thrones - spontaneous decolonization of Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) in Western Europe: is this myth or reality?

Background: In France, Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) are considered as Extensively Drug-Resistant (XDR) bacteria. Their management requires reinforcement of hospital's hygiene policies, and currently there is few consistent data concerning the spontaneous decolonization in XDR colonized patients. Our aim is to study the natural history of decolonization of XDR carriers over time in a hospital setting in a low prevalence country. Material and methods: Retrospective multicenter study over 2 years (2015-2016) in 2 different tertiary care hospital sites and units having an agreement for permanent cohorting of such XDR carriers. We gathered the type of microorganisms, risk factors for colonization and rectal swabs from patient's follow-up. We also evaluated patient care considering isolation precautions. Results: We included 125 patients, aged 63+/-19y, including 72.8% of CRE (n = 91), 24.8% of VRE (n = 31) and 2.4% (n = 3) co-colonized with CRE and VRE. CRE were mainly E. coli (n = 54), K. pneumoniae (n = 51) and E. cloacae (n = 6). Mechanisms of resistance were mainly OXA-48 (n = 69), NDM-1 (n = 11), OXA-232 (n = 8) and KPC (n = 3).Prior antibiotic therapy was reported in 38.4% (n = 48) of cases. Conversely, 17.6% (n = 22) received antibiotics during follow-up.Spontaneous decolonization occurred within the first 30 days in 16.4% (n = 19/116) of cases and up to 48.2% after day-90 with a median follow-up of 96 days (0-974).We estimated that XDR carriage was associated with a larger care burden in 13.6% (n = 17) of cases, especially due to a prolongation of hospitalization of 32.5 days (15-300). Conclusions: Our study shows that spontaneous decolonization is increasing over time (up to 48.2%). We can regret that only few patients underwent screening after 1 year, emphasizing the need for more monitoring and prospective studies.

First Occurrence of OXA-72-Producing Acinetobacter baumannii in Serbia.

Here, we characterized the first OXA-72-producing Acinetobacter baumannii isolate (designated MAL) recovered from a urine sample from a Serbian patient. Antimicrobial susceptibility testing, plasmid analysis, and whole-genome sequencing (WGS) were performed to fully characterize the resistome of the A. baumannii MAL clinical isolate. The isolate was multidrug resistant and remained susceptible only to colistin and tigecycline. PCR analysis revealed the presence of the carbapenemase OXA-72, an OXA-40 variant. Extraction by the Kieser method revealed the presence of two plasmids, and one of these, a ca. 10-kb plasmid, harbored the blaOXA-72 gene. WGS revealed 206 contigs corresponding to a genome of 3.9 Mbp in size with a G+C content of 38.8%. The isolate belonged to sequence type 492 and to worldwide clone II (WWCII). Naturally occurring ß-lactamase-encoding genes (blaADC-25 and blaOXA-66) were also identified. Aminoglycoside resistance genes encoding one aminoglycoside adenyltransferase (aadA2), three aminoglycoside phosphatases (strA, strB, aphA6), and one 16S RNA methylase (armA) conferring resistance to all aminoglycosides were identified. Resistance to fluoroquinolones was likely due to mutations in gyrA, parC, and parE Of note, the resistome matched perfectly with the antibiotic susceptibility testing results.

Fatal measles pneumonitis during Hodgkin's lymphoma.

The treatment of measles pneumonitis in immunocompromised adults is not established. We describe a patient with Hodgkin's lymphoma who developed acute pneumonia during a measles infection. On day 13, intravenous ribavirin and immunoglobulins were administrated. On day 18, the patient developed acute respiratory failure. An examination of transbronchial pulmonary biopsies showed Warthin-Finkeldey giant cells that are pathognomonic of measles pneumonitis. The patient died despite aggressive supportive care. Our case and a review of literature show that measles pneumonitis is routinely fatal in patients with cancer. We suggest that antiviral drugs should be considered as soon as the diagnosis has been established.

Eradication of an outbreak of vancomycin-resistant Enterococcus (VRE): the cost of a failure in the systematic screening.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are still a concern in hospital units tending to seriously ill patients. However, the cost-effectiveness of active surveillance program to identify asymptomatically VRE colonized patient remains debatable. This work aims at evaluating the cost of a failure in the active surveillance of VRE that had resulted in an outbreak in a French University Hospital. FINDINGS: A VRE outbreak was triggered by a failure in the systematic VRE screening in a medico-surgical ward specialised in liver transplantation as a patient was not tested for VRE. This failure was likely caused by the reduction of healthcare resource. The outbreak involved 13 patients. Colonized patients were grouped in a dedicated part of the infectious diseases unit and tended by a dedicated staff. Transmission was halted within two months after discovery of the index case.The direct cost of the outbreak was assessed as the cost of staffing, disposable materials, hygiene procedures, and surveillance cultures.The loss of income from spare isolation beds was computed by difference with the same period in the preceding year. Payments were drawn from the hospital database. The direct cost of the outbreak (2008 Euros) was €60 524 and the loss of income reached €110 915. CONCLUSIONS: Despite this failure, the rapid eradication of the VRE outbreak was a consequence of the rapid isolation of colonized patient. Yet, eradicating even a limited outbreak requires substantial efforts and resources. This underlines that special attention has to be paid to strictly adhere to active surveillance program.

Characteristics of B-cell lymphomas in HIV/HCV-coinfected patients during the combined antiretroviral therapy era: an ANRS CO16 LYMPHOVIR cohort study.

Hepatitis C virus (HCV) infection is frequent among HIV-infected patients. We describe, the characteristics of 6 HIV/HCV-coinfected patients with B-cell non-Hodgkin lymphoma (NHL) included in a prospective cohort study of HIV-related lymphomas. Five of the 6 cases had features of marginal zone/lymphoplasmacytic NHL versus 1 of 33 HIV only-infected patients. Remarkably, anti-HCV treatment led to a hematological response in a patient with splenic marginal zone lymphoma. This supports the role of chronic antigenic stimulation by HCV on lymphomagenesis and further evaluation of HCV antiviral therapy in coinfected patients with NHL.

Acute liver failure due to antitubercular therapy: Strategy for antitubercular treatment before and after liver transplantation.

The standard antitubercular treatment (ATT), which consists of isoniazid (INH), rifampicin (RIF), ethambutol, and pyrazinamide (PZA), is the best available treatment for tuberculosis (TB). However, the hepatotoxicity of INH and PZA can be severe, and even after drug withdrawal, patients may require liver transplantation (LT). In these cases, the strategy for the treatment of TB is poorly defined. Between 1986 and 2008, 14 patients presented at our department with severe hepatitis secondary to INH and PZA treatment. Four of these patients were immunosuppressed: 2 after renal transplantation and 2 because of human immunodeficiency virus infection. In seven of the 14 patients an alternative ATT was begun on admission, which was well tolerated. Hepatitis improved spontaneously in 5 patients, and alternative ATT was continued for 9.3 ± 4.2 months; 1 patient deteriorated and underwent LT, and 1 patient died. ATT was stopped definitively in 2 patients. Six patients required urgent LT, and alternative ATT was started after transplantation and was successful. Five patients receiving RIF had an episode of acute rejection. In conclusion, hepatitis secondary to ATT can be successfully treated with alternative anti-TB regimens. The use of RIF in LT patients may lead to acute rejection. RIF should therefore be avoided in these patients.

Cerebrovascular diseases in HIV-infected patients.

Cerebrovascular disease (CVD) has early been recognized in HIV-infected patients, including infectious arteritis, inflammatory vasculitis, aneurismal and small-vessel arteriopathy, to which adds now the premature atherosclerotic cerebral arteriopathy associated with the highly active antiretroviral therapy (HAART)-induced metabolic disorders. As a result of the increased life-expectancy associated with HAART, HIV patients grow older and are exposed to the combined vascular risk of antiviral-induced metabolic changes and advancing age. Several studies have documented subclinical cervical artery atherosclerosis, as assessed by intima-media thickness, ultrasound detection of carotid artery plaques and intracerebral small-vessel disease, all being associated with the induced metabolic changes. This suggests that vascular prevention should be performed on a long-term basis.

Efficacy of etravirine for treatment of acute HIV meningoencephalitis.

We describe a patient with human immunodeficiency virus (HIV) and hepatitis C virus coinfection who experienced recurrent episodes of acute HIV meningoencephalitis. The addition of etravirine to the therapeutic regimen completely resolved symptoms, and HIV was no longer detected in cerebrospinal spinal fluid specimens. Etravirine has a satisfactory safety profile and, in this case, was a durable alternative therapy for HIV meningoencephalitis.

HIV-associated vascular diseases: structural and functional changes, clinical implications.

After more than two decades of AIDS epidemic, the spectrum of HIV-associated vascular diseases has mainly evolved from infectious and inflammatory vasculitides to premature atherosclerosis, its related contributing conditions (metabolic syndrome, dyslipidemia, insulin resistance syndrome) and complications (acute coronary and cerebrovascular syndromes). Today, as the AIDS epidemic further progresses worldwide and as the life expectancy of HIV-infected patients treated with effective antiviral regimens has dramatically increased, more than 10% of patients experience cardiovascular manifestations. The complex interplay between viral infection, inflammatory and cytokines pathways, protease inhibitors-induced hyperlipidemia and direct effects on endothelial cells has not, by far, been integrated in a single comprehensive pathogenesis network. However, recognition of its main components has resulted in a broader appreciation of cardiovascular risk and risk factors in HIV-infected/treated patients. Cardiovascular prevention is required in more than one half of HIV-infected/treated patients to achieve a reliable effectiveness of modern antiretroviral therapy. As the prognosis of HIV patients improves continuously, this rate is also likely to increase in the future.