Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates.

Infections due to drug-resistant Acinetobacter baumannii strains are increasing and cause significant morbidity and mortality, especially in hospitalized and critically ill patients. A. baumannii rapidly develops resistance to numerous antibiotics, and antibiotics traditionally used against this deadly pathogen have been failing in recent years, highlighting the need to identify new treatment strategies. Treatment options that have shown promise include revisiting common antibiotics not typically used against A. baumannii, evaluating new antibiotics recently introduced to market, and identifying combinations of antibiotics that display synergistic interactions. In this study, we characterized the antibiotic susceptibility profiles of extensively (XDR) and pandrug-resistant (PDR) A. baumannii patient isolates. We examined the potency of 22 standard-of-care antibiotics and the newer antibiotics eravacycline, omadacycline, and plazomicin against these strains. Furthermore, we examined combinations of these antibiotics against our collection to identify synergistic effects. We found that this collection is highly resistant to most or all standard-of-care antibiotics, except for minocycline and rifampin. We show that eravacycline and omadacycline are effective against these strains based on minimum inhibitory concentrations. We also identified two highly effective combinations, cefepime and amikacin and cefepime and ampicillin-sulbactam, which exhibited high rates of synergy against this collection. This information is valuable in our battle against highly drug resistant and virtually untreatable A. baumannii infections.

What Does Minimally Invasive Mitral Valve Surgery Really Mean? Defining Totally Endoscopic Mitral Valve Surgery Through Meta Analysis.

INTRODUCTION: Minimally invasive approaches to mitral valve surgery are being performed with increasing frequency; however, many of these procedures still involve rib spreading and large incisions. The heterogeneity of self-reported "minimally invasive" approaches limits analysis of outcomes. This review aims to formally define totally endoscopic mitral valve surgery (TEMVS) and assess outcomes. MATERIALS AND METHODS: A comprehensive literature search in Pub-Med, Cochrane Library, and EMBASE was used to find studies reporting outcomes on totally endoscopic mitral valve surgery. "Totally endoscopic" was defined as incisions less than 3cm and the avoidance of rib spreading. The primary outcome was 30-day mortality and secondary endpoints included postoperative myocardial infarction (MI), stroke, early reoperation, wound infection, renal failure, and prolonged ventilation. Perioperative patient characteristics were also recorded and analyzed. RESULTS: Thirty-three studies (6031 patients) were included in our meta-analysis. The 30-day mortality rate was 0.33%, p=0.88. The most frequent complications were early reoperation (2.12%, p=0.44) and prolonged ventilation (1.46% p=<0.01). Rates of MI, stroke, and renal failure were each less than 1%. Patient characteristics including age, body mass index (BMI), and ejection fractions were also analyzed. CONCLUSIONS: We propose a formal definition of TEMVS, which is performed through incisions less than 3cm and without rib spreading. Thirty-day mortality and other adverse sequelae of TEMVS are uncommon.

Thermodynamic destabilization of azurin by four different tetramethylguanidinium amino acid ionic liquids.

The thermal unfolding of the copper redox protein azurin was studied in the presence of four different amino acid-based ionic liquids (ILs), all of which have tetramethylguanidium as cation. The anionic amino acid includes two with alcohol side chains, serine and threonine, and two with carboxylic acids, aspartate and glutamate. Control experiments showed that amino acids alone do not significantly change protein stability and pH changes anticipated by the amino acid nature have only minor effects on the protein. With the ILs, the protein is destabilized and the melting temperature is decreased. The two ILs with alcohol side chains strongly destabilize the protein while the two ILs with acid side chains have weaker effects. Unfolding enthalpy (ΔHunf°) and entropy (ΔSunf°) values, derived from fits of the unfolding data, show that some ILs increase ΔHunf°while others do not significantly change this value. All ILs, however, increase ΔSunf°. MD simulations of both the folded and unfolded protein conformations in the presence of the ILs provide insight into the different IL-protein interactions and how they affect the ΔHunf° values. The simulations also confirm that the ILs increase the unfolded state entropies which can explain the increased ΔSunf° values.

Effects of Ionic Liquids on Metalloproteins.

In the past decade, innovative protein therapies and bio-similar industries have grown rapidly. Additionally, ionic liquids (ILs) have been an area of great interest and rapid development in industrial processes over a similar timeline. Therefore, there is a pressing need to understand the structure and function of proteins in novel environments with ILs. Understanding the short-term and long-term stability of protein molecules in IL formulations will be key to using ILs for protein technologies. Similarly, ILs have been investigated as part of therapeutic delivery systems and implicated in numerous studies in which ILs impact the activity and/or stability of protein molecules. Notably, many of the proteins used in industrial applications are involved in redox chemistry, and thus often contain metal ions or metal-associated cofactors. In this review article, we focus on the current understanding of protein structure-function relationship in the presence of ILs, specifically focusing on the effect of ILs on metal containing proteins.