Evaluation of the MTS™ aztreonam-avibactam strip (Liofilchem) on New Delhi metallo-ß-lactamase-producing Enterobacterales.

The combination of ceftazidime-avibactam (CAZ-AVI) and aztreonam (ATM) is used to treat MBL-producing Enterobacterales-related infections. The new combination aztreonam-avibactam (AZA) is currently in development. We compared results obtained with the new MIC test strip (MTS) AZA (Liofilchem) with broth microdilution method (BMD) on 41 MBL-producing Enterobacterales from 41 clinical samples. The MTS AZA was also compared to combination testing method using CAZ-AVI and ATM strips. Compared to BMD, categorical agreement (CA) was 100%. Compared with combination testing method, CA was 97.6%. The MTS AZA can be used to determine MICs levels of AZA or CAZ-AVI/ATM combinations.

Prior participation as a standardized patient improves OSCE scores of third-year medical students: A pilot comparative study at Université Paris Cité Medical School.

OBJECTIVE: Objective structured clinical examinations (OSCE) are one of the main modalities of skills' assessment of medical students. We aimed to evaluate the educational value of the participation of third-year medical students in OSCE as standardized patients. METHODS: We conducted a pilot OSCE session where third-year students participated in sixth-year students' OSCE as standardized patients (cases). Their scores in their own subsequent OSCE exams were compared with third-year students who had not participated (controls). Students' perceptions (stress, preparedness, ease) regarding their OSCE were compared with self-administered questionnaires. RESULTS: A total of 42 students were included (9 cases and 33 controls). Median [IQR] overall score (out of 20 points) obtained by the cases was 17 [16.3-18] versus 14.5 [12.7-16.3] for controls (p < 0.001). Students' perception of their evaluation (difficulty, stress, communication) was not significantly different between cases and controls. Most cases agreed that their participation was beneficial in reducing their stress (67%), increasing their preparedness (78%) and improving their communication skills (100%). All cases agreed that this participation should be offered more widely. CONCLUSION: Students' participation in OSCE as standardized patients led to better performance on their own OSCE and were considered beneficial. This approach could be more broadly generalized to improve student performance.

Use of specific agar plates for early detection of anaerobic bacteria in surgical site infections after spinal surgery: a prospective single centre study.

To determine if additional agar plates could allow earlier detection of anaerobes in spinal surgical site infections (SSIs), we performed a prospective study (November 2017-January 2019) of patients with early spinal SSIs. In addition to routine 14-day cultures, surgical samples were inoculated onto three additional plates (CDC anaerobe agar with 5% sheep blood [CDC], CDC anaerobe laked sheep blood agar with kanamycin/vancomycin [BBL], and Bacteroides bile esculin [BBE] agar with amikacin (BD, USA)) incubated under anaerobic conditions (72 h, 37°C). The primary endpoint was detection of anaerobes by these methods, as compared to routine culture. Anaerobes were identified in 7/61 patients (11%) using the routine procedure and in one extra case with additional plates (overall detection rate 8/61, 13%). Sensitivity was greater for the CDC plate than for the BBL and BBE plates. When routine culture was positive, the CDC plate was always positive, and in three cases showed at least one additional anaerobe. Using additional agar plates, anaerobes were identified in early spinal SSI in 13% of patients. Within 3 days, CDC agar plate enabled detection of anaerobes in one extra case and at least one additional anaerobe in three other cases, compared to routine 14-day culture.

Cytomegalovirus proctitis as a complication of COVID-19 with immunosuppressive treatments.

We report a case of reactivated biopsy-proven cytomegalovirus proctitis complicating the course of severe COVID-19 pneumonia treated with dexamethasone, anakinra and lopinavir/ritonavir. No other contributing factor was found than iatrogenic immunosuppression and COVID-19 immune dysregulation. We draw attention to the immunosuppressive risk when treating severe COVID-19 pneumonia with immunomodulators.

Novel Chromosomal Mutations Responsible for Fosfomycin Resistance in Escherichia coli.

Fosfomycin resistance in Escherichia coli results from chromosomal mutations or acquisition of plasmid-mediated genes. Because these mechanisms may be absent in some resistant isolates, we aimed at decipher the genetic basis of fosfomycin resistance in E. coli. Different groups of isolates were studied: fosfomycin-resistant mutants selected in vitro from E. coli CFT073 (MIC = 1 mg/L) and two groups (wildtype and non-wildtype) of E. coli clinical isolates. Single-nucleotide allelic replacement was performed to confirm the implication of novel mutations into resistance. Induction of uhpT expression by glucose-6-phosphate (G6P) was assessed by RT-qPCR. The genome of all clinical isolates was sequenced by MiSeq (Illumina). Two first-step mutants were obtained in vitro from CFT073 (MICs, 128 mg/L) with single mutations: G469R in uhpB (M3); F384L in uhpC (M4). Second-step mutants (MICs, 256 mg/L) presented additional mutations: R282V in galU (M7 from M3); Q558∗ in lon (M8 from M4). Introduction of uhpB or uhpC mutations by site-directed mutagenesis conferred a 128-fold increase in fosfomycin MICs, whereas single mutations in galU or lon were only responsible for a 2-fold increase. Also, these mutations abolished the induction of uhpT expression by G6P. All 14 fosfomycin-susceptible clinical isolates (MICs, 0.5-8 mg/L) were devoid of any mutation. At least one genetic change was detected in all but one fosfomycin-resistant clinical isolates (MICs, 32 - >256 mg/L) including 8, 17, 18, 5, and 8 in uhpA, uhpB, uhpC, uhpT, and glpT genes, respectively. In conclusion, novel mutations in uhpB and uhpC are associated with fosfomycin resistance in E. coli clinical isolates.

"Chronic Disseminated Aspergillosis," a Novel Fungal Immune Reconstitution Inflammatory Syndrome.

We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting.

A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations.

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.

Smoking as a Risk Factor of Invasive Fungal Disease: Systematic Review and Meta-Analysis.

To investigate the association between smoking and invasive fungal disease (IFD), we searched MEDLINE and Web of Science for studies published until September 2018. Two authors independently performed study selection and data extraction. Relative risks (RRs) were pooled using random-effects meta-analysis. We included 25 studies (18 171 participants; 2527 IFD cases). The meta-analysis showed an increased risk of IFD in smokers (RR 1.41 [95% confidence interval 1.09-1.81]; P = .008). The risk of IFD was higher in retrospective than in prospective studies (RR 1.93 [1.28-2.92] vs. 1.02 [0.78-1.34]; P = .04), in studies with multivariate adjustment compared to studies with univariate analysis (RR 2.15 [1.27-3.64] vs. 1.15 [0.88-1.51]; P = .06), and in studies published after 2002 (RR 2.08 [1.37-3.15] vs. 0.95 [0.75-1.22]; P = .008); other subgroup characteristics did not significantly influence the association in metaregression. Smoking cessation strategies should be implemented, especially in patients who are already at risk for IFD.

More complications in cervical than in non-cervical spine tuberculosis.

Purpose: Cervical spine tuberculosis (CST) is a rare disease that may lead to severe neurological complications. The goal of the study was to compare the characteristics of patients with CST with those of patients with non-cervical spine tuberculosis (NCST).Methods: Between 1997 and 2016, we reviewed all cases of proven tuberculosis from a cohort of spine infections in a tertiary care hospital. Clinical, biological, and imaging data were collected at baseline and after treatment.Results: Fifty-one cases of spine tuberculosis were included: 14 with CST on imaging (27%) and 37 with no cervical localization. Median age was 39 y. Demographic characteristics, duration of symptoms and neurological findings of spine compression were similarly present at presentation in CST and NCST patients. On imaging, lesions were more often multifocal in CST than in NCST patients (9/14 [64%] versus 10/37 [27%], p = .014). Spinal surgery was required in 32/51 (63%) patients. At the end of follow-up (median: 20 months), cure rates were similar in CST and NCST patients but motor and/or sensitive functional sequel were more frequent in CST than NCST patients (6/14 [43%] versus 2/37 [5%], p = .003).Conclusions: Cervical involvement is present in more than a quarter of patients with spinal tuberculosis. Patients with CST had more frequent neurological sequelae than patients with NCST. This was mainly due to a more multifocal disease at presentation. Screening for cervical localization should be systematic in patients with spinal tuberculosis even in the absence of cervical symptoms.

Unexpected Activity of Oral Fosfomycin against Resistant Strains of Escherichia coli in Murine Pyelonephritis.

Fosfomycin tromethamine activity is well established for oral treatment of uncomplicated lower urinary tract infections, but little is known about its potential efficacy in pyelonephritis. Ascending pyelonephritis was induced in mice infected with 6 strains of Escherichia coli (fosfomycin MICs, 1 µg/ml to 256 µg/ml). The urine pH was 4.5 before infection and 5.5 to 6.0 during infection. Animals were treated for 24 h with fosfomycin (100 mg/kg of body weight subcutaneously every 4 h), and the CFU were enumerated in kidneys 24 h after the last fosfomycin injection. Peak (20.5 µg/ml at 1 h) and trough (3.5 µg/ml at 4 h) levels in plasma were comparable to those obtained in humans after an oral dose of 3 g. Fosfomycin treatment significantly reduced the bacterial loads in kidneys (3.65 log10 CFU/g [range, 1.83 to 7.03 log10 CFU/g] and 1.88 log10 CFU/g [range, 1.78 to 5.74 log10 CFU/g] in start-of-treatment control mice and treated mice, respectively; P < 10-6). However, this effect was not found to differ across the 6 study strains (P = 0.71) or between the 3 susceptible and the 3 resistant strains (P = 0.09). Three phenomena may contribute to explain this unexpected in vivo activity: (i) in mice, the fosfomycin kidney/plasma concentration ratio increased from 1 to 7.8 (95% confidence interval, 5.2, 10.4) within 24 h in vitro when the pH decreased to 5, (ii) the fosfomycin MICs for the 3 resistant strains (64 to 256 µg/ml) decreased into the susceptible range (16 to 32 µg/ml), and (iii) maximal growth rates significantly decreased for all strains and were the lowest in urine. These results suggest that local fosfomycin concentrations and physiological conditions may favor fosfomycin activity in pyelonephritis, even against resistant strains.

Evidence of hepatitis E virus transmission by renal graft.

Hepatitis E virus (HEV) can cause chronic infection among immunocompromised patients, especially solid organ transplant recipients, and can evolve to cirrhosis. Several modes of transmission are known. Here we describe the first two cases, to our knowledge, of HEV infection transmitted by a kidney graft from the same infected donor that led to chronic hepatitis. Consequently, systematic screening of donors by HEV serology and HEV RNA detection by polymerase chain reaction, particularly in endemic regions, should be considered.

Sternal Wound Infection after Cardiac Surgery: Management and Outcome.

BACKGROUND: Sternal Wound Infection (SWI) is a severe complication after cardiac surgery. Debridement associated with primary closure using Redon drains (RD) is an effective treatment, but data on RD management and antibiotic treatment are scarce. METHODS: We performed a single-center analysis of consecutive patients who were re-operated for SWI between 01/2009 and 12/2012. All patients underwent a closed drainage with RD (CDRD). Patients with endocarditis or those who died within the first 45 days were excluded from management analysis. RD fluid was cultured twice weekly. Variables recorded were clinical and biological data at SWI diagnosis, severity of SWI based on criteria for mediastinitis as defined by the Centers for Disease Control (CDC), antibiotic therapy, RD management and patient's outcome. RESULTS: 160 patients developed SWI, 102 (64%) fulfilled CDC criteria (CDC+) and 58 (36%) did not (CDC- SWI). Initial antibiotic treatment and surgical management were similar in CDC+ and CDC- SWI. Patients with CDC+ SWI had a longer duration of antibiotic therapy and a mortality rate of 17% as compared to 3% in patients with CDC- SWI (p = 0.025). Rates of superinfection (10% and 9%) and need for second reoperation (12% and 17%) were similar. Failure (death or need for another reoperation) was associated with female gender, higher EuroScore for prediction of operative mortality, and stay in the ICU. CONCLUSION: In patients with SWI, initial one-stage surgical debridement with CDRD is associated with favorable outcomes. CDC+ and CDC- SWI received essentially the same management, but CDC+ SWI has a more severe outcome.