Rapid identification from rectal swabs of the clinically most relevant carbapenemase genes from gram-negative bacteria using the BD MAX Check-Points CPO Assay.

We conducted an international multicentre evaluation to assess the clinical performance characteristics of the new multiplex PCR-based BD MAX Check-Points CPO assay to detect the 5 major carbapenemase families: KPC, VIM/IMP (tested simultaneously), NDM and OXA-48 compared to a reference method consisting of 2 culture methods (to improve recovery of CPO isolates from the rectal swabs), followed by carbapenem susceptibility testing and sequencing of target carbapenemase genes. Tests were performed from rectal swab specimens in ESwab collection and transport devices. Positive percent agreement (PPA) for BD MAX Check-Points CPO for KPC and OXA-48 were 88.2% (95% CI:72.6-96.7) and 96.2% (95% CI:80.4-99.9), respectively. Negative percent agreement was ≥99% for each gene. Insufficient samples (≤10) were positive for VIM/IMP or NDM tests to calculate meaningful PPA values. The BD MAX Check-Points CPO assay represents an accurate tool for rapid recognition of patients with rectal colonization by the most commonly encountered CPOs.

Comparison of an Automated Plate Assessment System (APAS Independence) and Artificial Intelligence (AI) to Manual Plate Reading of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus CHROMagar Surveillance Cultures.

The automated plate assessment system (APAS Independence; Clever Culture System, Bäch, Switzerland) is an automated imaging station linked with interpretive software that detects target colonies of interest on chromogenic media and sorts samples as negative or presumptive positive. We evaluated the accuracy of the APAS to triage methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus cultures using chromogenic medium compared to that by human interpretation. Patient samples collected from the nares on ESwabs were plated onto BD BBL CHROMagar MRSA II and BD BBL CHROMagar Staph aureus and allowed to incubate for 20 to 24 h at 37°C in a non-CO2 incubator. Mauve colonies are suggestive of S. aureus and were confirmed with latex agglutination. Following incubation, samples were first interrogated by APAS before being read by a trained technologist blinded to the APAS interpretation. The triaging by both APAS and the technologists was compared for accuracy. Any discordant results required further analysis by a third reader. Over a 5-month period, 5,913 CHROMagar MRSA cultures were evaluated. Of those, 236 were read as concordantly positive, 5,525 were read as concordantly negative, and 152 required discordant analysis. Positive and negative percent agreements (PPA and NPA, respectively) were 100% and 97.3%, respectively. The APAS detected 5 positive cultures that were missed by manual reading and determined to be true positives. In a separate analysis, 744 CHROMagar Staph aureus plates were read in parallel. Of these, 133 were concordantly positive, 585 were concordantly negative, and 26 required discordant analysis. PPA and NPA were 95.7% and 96.7%, respectively. This study confirmed the high sensitivity of digital image analysis by the APAS Independence such that negative cultures can be reliably reported without technologist intervention (negative predictive values [NPVs] of 100% for CHROMagar MRSA and 99.0% for CHROMagar Staph aureus). Triaging using the APAS Independence may provide great efficiency in a laboratory with high throughput of MRSA and S. aureus surveillance cultures.

A randomized trial of dapagliflozin and metformin, alone and combined, in overweight women after gestational diabetes mellitus.

BACKGROUND: Women with a history of gestational diabetes mellitus are at a substantially increased risk of gestational diabetes mellitus recurrence and type 2 diabetes. Weight gain, particularly increased central adiposity after delivery, is strongly associated with deterioration of pancreatic beta cell compensation for insulin resistance. Weight management after gestational diabetes mellitus could have a significant benefit in these women who are at a high risk of developing type 2 diabetes. OBJECTIVE: This study aimed to evaluate the treatment efficacy of dapagliflozin and metformin, alone and in combination, on body weight and anthropometric, cardiovascular, and metabolic parameters in overweight women with a recent history of gestational diabetes mellitus. STUDY DESIGN: This was a prospective, single-blind, randomized, outpatient clinical trial with 3 parallel treatment groups. Overweight or obese (body mass index>25) females (n=66; ≥18-45 years) with gestational diabetes mellitus in pregnancy in the past 12 months were randomized in a single-blind manner to dapagliflozin, metformin, or dapagliflozin-metformin for 24 weeks. Body weight, height, body mass index, waist circumference, waist-to-height ratio, and blood pressure were determined at baseline and trial completion. Oral glucose tolerance tests were performed at baseline and 24 weeks to assess glycemia and mean blood glucose and calculate insulin sensitivity and secretion measures. Plasma lipid fractions, thyroid-stimulating hormone, and liver enzymes were also assessed in the fasting sample at the beginning and completion of the study trial. RESULTS: The study was completed by 49 participants (74%). Significant reduction of weight, waist circumference, and waist-to-height ratio and improved glycemia and insulin sensitivity index derived from oral glucose tolerance test were found with dapagliflozin-metformin vs metformin monotherapy. Both dapagliflozin and dapagliflozin-metformin therapy were superior to metformin in increasing high-density lipoprotein levels, reducing triglyceride concentrations, lowering the triglyceride-to-high-density lipoprotein cholesterol ratio, and improving glucose excursion after an oral glucose tolerance test. The early insulin response to a glucose challenge significantly improved with only dapagliflozin-metformin compared with single-drug treatments. CONCLUSION: This is the first report comparing the efficacy of a sodium-glucose cotransporter 2 inhibitor alone and in combination with metformin in this patient population. We found that combination dapagliflozin-metformin treatment over a 24-week period had a greater positive effect on body weight, waist circumference, and glycemic, cardiovascular, and metabolic parameters than metformin monotherapy in overweight or obese at-risk women with a recent history of gestational diabetes mellitus.

Postpartum treatment with liraglutide in combination with metformin versus metformin monotherapy to improve metabolic status and reduce body weight in overweight/obese women with recent gestational diabetes: A double-blind, randomized, placebo-controlled study.

BACKGROUND: Gestational diabetes (GDM) imparts a high risk of developing diabetes postpartum. Insulin resistance appears to be the major contributor. Liraglutide, a glucagon-like peptide-1 analogue, improves peripheral glucose disposal and reduces body weight. We evaluated whether liraglutide in combination with metformin (MET-LIRA) is more effective than metformin monotherapy (MET-P) in improving insulin action and reducing body weight in overweight prior GDM (pGDM) women. METHODS: Women (n = 153; body mass index (BMI) ≥25 kg/m2; 18-45 y; GDM within 12 months) with metabolic abnormalities were randomized to MET-LIRA (MET-2000 mg, LIRA 1.8 mg SC QD) or MET-P (MET-2000 mg, Placebo QD). Study visits at baseline, 36-40, 56-60 and 80-84 weeks included body weight (BW), BMI, waist circumference and waist-to-height ratio measures. Oral glucose tolerance tests (OGTTs) were performed to assess glycemia, mean blood glucose (MBG), lipids, and compute insulin sensitivity and secretion measures. FINDINGS: Seventy-two (47%) participants completed the study. MET-LIRA therapy was significantly better in improving MBG and insulin sensitivity indices [SIOGTT MET-LIRA from 4.6 (3.2) to 5.9 (2.9) vs. MET-P 5.5 (3.0) to 5.4 (3.2)] and reducing BW and central adiposity [BMI MET-LIRA from 37.2 (8.3) to 33.8 (5.2) vs MET-P 33.8(5.2) to 32.8(6)]. MET-LIRA therapy but not MET-P decreased triglycerides (TRG) and TRG/high density lipoprotein cholesterol (HDL-C) ratios. INTERPRETATION: MET-LIRA treatment demonstrated superior efficacy in correcting the metabolic status of pGDM women over 84 weeks of therapy. The addition of liraglutide to metformin therapy resulted in a more dramatic decrease in BW and central adiposity than metformin alone. FUNDATION: Supported by an unrestricted investigator initiated grant from Novo Nordisk, Inc. awarded to K.E.H. MEETING PRESENTATION: The results from preliminary analyses of this study were presented at 76th meeting of the American Diabetes Association, June 10-14, 2016 New Orleans, LA, and 77th meeting of the American Diabetes Association, June 9-12, 2017San Diego, CA.

Differentiating Streptococcus pseudoporcinus from GBS: could this have implications in pregnancy?

BACKGROUND: Streptococcus agalactiae (GBS) is a common pathogen known to cause neonatal and maternal infectious morbidity. Streptococcus pseudoporcinus (S pseudoporcinus) is a separate, recently identified ß-hemolytic gram-positive coccus that can cause false-positive results on standard GBS agglutination testing assays. OBJECTIVE: To determine the prevalence and clinical implications of Streptococcus pseudoporcinus colonization in pregnancy. MATERIALS AND METHODS: This is a 2-year retrospective cohort study comparing pregnant women colonized with GBS to those colonized with S. pseudoporcinus. A proteomics method of identification, namely, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, was used to distinguish between S. pseudoporcinus and GBS colonization. Antibiotic susceptibility testing was carried out on all specimens. Maternal and neonatal chart reviews were conducted to identify predictors of S. pseudoporcinus colonization and to compare maternal and neonatal outcomes. RESULTS: S. pseudoporcinus colonization occurred in 1.6% of all pregnancies. A total of 2.5% of all GBS-positive results by agglutination assay were false positive, instead reflecting S. pseudoporcinus colonization. Clindamycin resistance among S. pseudoporcinus isolates is uncommon. S. pseudoporcinus colonization in pregnancy is independently associated with African American race, tobacco use, and body mass index ≥35. Preterm premature rupture of membranes or spontaneous preterm birth was more common in patients colonized with S. pseudoporcinus. CONCLUSION: Although the prevalence of S. pseudoporcinus colonization is low, it primarily occurs in African American women and is associated with preterm premature rupture of membranes or spontaneous preterm birth when compared to individuals colonized with GBS.

Glycal Metallanitrenes for 2-Amino Sugar Synthesis: Amidoglycosylation of Gulal-, Allal-, Glucal-, and Galactal 3-Carbamates.

The rhodium(II)-catalyzed oxidative cyclization of glycal 3-carbamates with in situ incorporation of an alcohol nucleophile at the anomeric position provides access to a range of 2-amino sugars having 1,2-trans-2,3-cis stereochemistry, a structural motif present in compounds of medicinal and biological significance such as the streptothricin group of antibiotics and the Chitinase inhibitor allosamidin. All of the diastereomeric d-glycal 3-carbamates have been investigated, revealing significant differences in anomeric stereoselectivity depending on substrate stereochemistry and protecting groups. In addition, some substrates were prone to forming C3-oxidized dihydropyranone byproducts under the reaction conditions. Allal- and gulal 3-carbamates provided uniformly high stereo- and chemoselectivity, while for glucal substrates, acyclic, electron-withdrawing protecting groups at the 4 O and 6 O positions were required. Galactal 3-carbamates have been the most challenging substrates; formation of their amidoglycosylation products is most effective with an electron-withdrawing 6 O-Ts substituent and a sterically demanding 4 O-TBS group. These results suggest a mechanism whereby conformational and electronic factors determine the partitioning of an intermediate acyl nitrenoid between alkene addition, leading to amidoglycosylation, and C3-H insertion, providing the dihydropyranone byproduct. Along the amidoglycosylation pathway, high anomeric selectivity results when a glycosyl aziridine intermediate is favored over an aziridine-opened oxocarbenium donor.

Recognition of Streptococcus pseudoporcinus Colonization in Women as a Consequence of Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Group B Streptococcus Identification.

During a 14-month period of using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for group B streptococcus (GBS) identification, we recovered 32 (1%) Streptococcus pseudoporcinus isolates from 3,276 GBS screening cultures from female genital sources (25 isolates from pregnant women and 7 from nonpregnant women). An additional two S. pseudoporcinus isolates were identified from a urine culture and a posthysterectomy wound culture. These isolates were found to cross-react with three different GBS antigen agglutination kits, PathoDx (Remel) (93%), Prolex (Pro-Lab Diagnostics) (38%), and Streptex (Remel) (53%). New approaches to bacterial identification in routine clinical microbiology laboratories may affect the prevalence of S. pseudoporcinus.

PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts.

Missense mutations that reduce or abrogate myeloid cell expression of the F-BAR domain protein, proline serine threonine phosphatase-interacting protein 2 (PSTPIP2), lead to autoinflammatory disease involving extramedullary hematopoiesis, skin and bone lesions. However, little is known about how PSTPIP2 regulates osteoclast development. Here we examined how PSTPIP2 deficiency causes osteopenia and bone lesions, using the mouse PSTPIP2 mutations, cmo, which fails to express PSTPIP2 and Lupo, in which PSTPIP2 is dysfunctional. In both models, serum levels of the pro-osteoclastogenic factor, MIP-1α, were elevated and CSF-1 receptor (CSF-1R)-dependent production of MIP-1α by macrophages was increased. Treatment of cmo mice with a dual specificity CSF-1R and c-Kit inhibitor, PLX3397, decreased circulating MIP-1α and ameliorated the extramedullary hematopoiesis, inflammation, and osteopenia, demonstrating that aberrant myelopoiesis drives disease. Purified osteoclast precursors from PSTPIP2-deficient mice exhibit increased osteoclastogenesis in vitro and were used to probe the structural requirements for PSTPIP2 suppression of osteoclast development. PSTPIP2 tyrosine phosphorylation and a functional F-BAR domain were essential for PSTPIP2 inhibition of TRAP expression and osteoclast precursor fusion, whereas interaction with PEST-type phosphatases was only required for suppression of TRAP expression. Thus, PSTPIP2 acts as a negative feedback regulator of CSF-1R signaling to suppress inflammation and osteoclastogenesis.

Masterful precepting: using the BECOME method to enhance clinical teaching.

Staff development educators are actively engaged in the mentoring of preceptors and the orientation of new nursing staff. They are consulted by preceptors to assist in reconciling orientation conflicts. This assistance can range from diagnosing performance problems to resolving intrapersonal conflicts between preceptor and orientee. This article describes the development of a framework, known by the acronym BECOME. The purpose of this framework is to provide educators with a repertoire of strategies for educating and mentoring preceptors.