CHARACTERIZATION OF CARBAPENEM RESISTANT ACINETOBACTER BAUMANNII ISOLATED IN A TERTIARY CARE HOSPITAL: EPIDEMIOLOGY AND TREATMENT OUTCOME

Objective: Carbapenem resistant Acinetobacter baumannii (CR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Our objectives were to determine the epidemiology and outcome of CR-Ab infections at a tertiary care hospital.Methods: CR-Ab isolates were collected from January to April 2013. MICs were determined and isolates were subjected to screening for carbapenemase production by Modified Hodge test (MHT), metallo-β-lactamase (MBLs) by EDTA disk synergy test and AmpC β-lactamase by AmpC disk test. 15 isolates were subjected to PCR for detection of resistant genes, blaOXA-23, blaVIM and blaNDM. Treatment outcomes of infections were evaluated.Results: 51 CR-Ab isolates from tracheal aspirate (21), blood (15); tissue/wound/drainage (13) and urine samples (2) were collected. Colistin appeared to be the most effective agent with 98% in vitro activity. MHT showed 98% positivity, MBLs production was detected in 94.1% isolates and 64.7% were positive for AmpC β-lactamase production. All 15 isolates carried blaOXA-23 and blaVIM, of these 3 also carried blaNDM gene. Colistin containing combinations were more commonly used (68.3%). Colistin-noncarbapenem combination showed improved clinical response compared to colistin-carbapenem combination against Acinetobacter isolates carrying blaOXA-23 and blaVIM.Conclusion: A stringent infection control practice along with antimicrobial stewardship is needed to prevent emergence of Acinetobacter carrying multiple carbapenemase genes along with blaNDM. Various colistin combinations are preferentially used to treat CR-Ab infections. Identification of antimicrobial combinations with proven in vitro activity that encompass local susceptibility patterns as well as molecular mechanisms of resistance is needed to provide better outcome.Keywords: Acinetobacter baumannii, Carbapenem resistance, Carbapenemases, Colistin combination, metallo-β-lactamase, NDMÂ

Neoantigen landscape supports feasibility of personalized cancer vaccine for follicular lymphoma

Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that polyvalent vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR repertoire from healthy individuals using RNA-seq data. An average of 52 somatic mutations per patient (range, 2-172) were identified, and ≥2 (median, 15) high-quality neoantigens were predicted for 56 of 58 FL samples. The predicted neoantigen peptides were composed of missense mutations (77%), indels (9%), gene fusions (3%), and BCR sequences (11%). Building off of these preclinical analyses, we initiated a pilot clinical trial using personalized neoantigen vaccination combined with PD-1 blockade in patients with relapsed or refractory FL (#NCT03121677). Synthetic long peptide vaccines targeting predicted high-quality neoantigens were successfully synthesized for and administered to all 4 patients enrolled. Initial results demonstrate feasibility, safety, and potential immunologic and clinical responses. Our study suggests that a genomics-driven personalized cancer vaccine strategy is feasible for patients with FL, and this may overcome prior challenges in the field. This trial was registered at www.ClinicalTrials.gov as #NCT03121677

LISA Galactic binaries with astrometry from Gaia DR3

International audienceGalactic compact binaries with orbital periods shorter than a few hours emit detectable gravitational waves at low frequencies. Their gravitational wave signals can be detected with the future Laser Interferometer Space Antenna (LISA). Crucially, they may be useful in the early months of the mission operation in helping to validate LISA's performance in comparison to pre-launch expectations. We present an updated list of 48 candidate LISA binaries with measured properties, for which we derive distances based on Gaia Data release 3 astrometry. Based on the known properties from electromagnetic observations, we predict the LISA detectability after 1, 3, 6, and 48 months with state-of-the-art Bayesian analysis methods. We distinguish between verification and detectable binaries as being detectable after 3 and 48 months respectively. We find 16 verification binaries and 21 detectable sources, which triples the number of known LISA binaries over the last few years. These include detached double white dwarfs, AM CVn binaries, one ultracompact X-ray binary and two hot subdwarf binaries. We find that across this sample the gravitational wave amplitude is expected to be measured to $\approx10\%$ on average, while the inclination is expected to be determined with $\approx15^\circ$ precision. For detectable binaries these average errors increase to $\approx50\%$ and to $\approx40^\circ$ respectively

LISA Galactic binaries with astrometry from Gaia DR3

International audienceGalactic compact binaries with orbital periods shorter than a few hours emit detectable gravitational waves at low frequencies. Their gravitational wave signals can be detected with the future Laser Interferometer Space Antenna (LISA). Crucially, they may be useful in the early months of the mission operation in helping to validate LISA's performance in comparison to pre-launch expectations. We present an updated list of 48 candidate LISA binaries with measured properties, for which we derive distances based on Gaia Data release 3 astrometry. Based on the known properties from electromagnetic observations, we predict the LISA detectability after 1, 3, 6, and 48 months with state-of-the-art Bayesian analysis methods. We distinguish between verification and detectable binaries as being detectable after 3 and 48 months respectively. We find 16 verification binaries and 21 detectable sources, which triples the number of known LISA binaries over the last few years. These include detached double white dwarfs, AM CVn binaries, one ultracompact X-ray binary and two hot subdwarf binaries. We find that across this sample the gravitational wave amplitude is expected to be measured to $\approx10\%$ on average, while the inclination is expected to be determined with $\approx15^\circ$ precision. For detectable binaries these average errors increase to $\approx50\%$ and to $\approx40^\circ$ respectively

LISA Galactic binaries with astrometry from Gaia DR3

International audienceGalactic compact binaries with orbital periods shorter than a few hours emit detectable gravitational waves at low frequencies. Their gravitational wave signals can be detected with the future Laser Interferometer Space Antenna (LISA). Crucially, they may be useful in the early months of the mission operation in helping to validate LISA's performance in comparison to pre-launch expectations. We present an updated list of 48 candidate LISA binaries with measured properties, for which we derive distances based on Gaia Data release 3 astrometry. Based on the known properties from electromagnetic observations, we predict the LISA detectability after 1, 3, 6, and 48 months with state-of-the-art Bayesian analysis methods. We distinguish between verification and detectable binaries as being detectable after 3 and 48 months respectively. We find 16 verification binaries and 21 detectable sources, which triples the number of known LISA binaries over the last few years. These include detached double white dwarfs, AM CVn binaries, one ultracompact X-ray binary and two hot subdwarf binaries. We find that across this sample the gravitational wave amplitude is expected to be measured to $\approx10\%$ on average, while the inclination is expected to be determined with $\approx15^\circ$ precision. For detectable binaries these average errors increase to $\approx50\%$ and to $\approx40^\circ$ respectively

Surgical site infection rates in six cities of India: findings of the International Nosocomial Infection Control Consortium (INICC)

Surgical site infections are a threat to patient safety. However, in India, data on their rates stratified by surgical procedure are not available. From January 2005 to December 2011, the International Nosocomial Infection Control Consortium (INICC) conducted a cohort prospective surveillance study on surgical site infections in 10 hospitals in 6 Indian cities. CDC National Healthcare Safety Network (CDC-NHSN) methods were applied and surgical procedures were classified into 11 types, according to the ninth edition of the International Classification of Diseases. We documented 1189 surgical site infections, associated with 28 340 surgical procedures (4.2%; 95% CI: 4.0-4.4). Surgical site infections rates were compared with INICC and CDC-NHSN reports, respectively: 4.3% for coronary bypass with chest and donor incision (4.5% vs 2.9%); 8.3% for breast surgery (1.7% vs 2.3%); 6.5% for cardiac surgery (5.6% vs 1.3%); 6.0% for exploratory abdominal surgery (4.1% vs 2.0%), among others. In most types of surgical procedures, surgical site infections rates were higher than those reported by the CDC-NHSN, but similar to INICC. This study is an important advancement towards the knowledge of surgical site infections epidemiology in the participating Indian hospitals that will allow us to introduce targeted interventions