Persistent Nocardia beijingensis infection in a patient with postoperative abscess and misuse of antibiotics in China.

Here we describe the first case of abscess infection caused by Nocardia beijingensis in China. The patient was immunocompetent but suffered from postoperative abscess for 6 years. This study highlights the necessity of long-term infected foci to be thoroughly examined to identify the pathogen, as well as the importance of accurate Nocardia identification and antimicrobial susceptibility tests for understanding the pathogen's epidemiology, clinical significance, and treatment strategy.

Zona pellucida removal by acid Tyrode's solution affects pre- and post-implantation development and gene expression in mouse embryos†.

The zona pellucida plays a crucial role in the process of fertilization to early embryonic development, including cellular arrangement and communication between blastomeres. However, little is known regarding the role of the zona pellucida in pre- and post-implantation embryonic development associated with gene expression. We investigated the effect of zona pellucida removal on pre- and post-implantation development of mouse embryos. After zona pellucida removal of two-cell stage embryos was performed by acid Tyrode's solution, which is commonly used for zona pellucida treatment, compaction occurred earlier in zona pellucida-free than zona pellucida-intact embryos. In addition, the expression of differentiation-related genes in the inner cell mass and trophectoderm was significantly altered in zona pellucida-free blastocyst compared with zona pellucida-intact embryos. After embryo transfer, the rate of implantation and live fetuses was lower in zona pellucida-free embryos than in control embryos, whereas the fetal weight at E17.5 was not different. However, placental weight significantly increased in zona pellucida-free embryos. RNA-sequencing analysis of the placenta showed that a total of 473 differentially expressed genes significantly influenced the biological process. The present study suggests that zona pellucida removal by acid Tyrode's solution at the two-cell stage not only disturbs the expression pattern of inner cell mass-/trophectoderm-related genes but affects the post-implantation development of mouse embryos. Overall, this study provides deeper insight into the role of the zona pellucida during early embryonic development and the viability of post-implantation development.

Pharmacokinetic and pharmacodynamic profiles of a novel phospholipid-aspirin complex liquid formulation and low dose enteric-coated aspirin: results from a prospective, randomized, crossover study.

Low dose enteric-coated aspirin (EC-ASA) is routinely used for secondary cardiovascular event prevention. However, absorption of EC tablets is poor, which can result in subtherapeutic antiplatelet effects. Phospholipid-aspirin liquid filled capsules (PL-ASA) are a novel FDA-approved immediate-release formulation designed to reduce gastrointestinal (GI) injury by limiting direct contact with the stomach lining. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of PL-ASA versus EC-ASA at a low dose. This randomized, open-label, crossover study assessed PK and PD following a single 81-mg dose of PL-ASA versus EC-ASA under fasting conditions in 36 volunteers without cardiovascular disease between 18 and 75 years of age. Volunteers were randomly assigned 1:1 to either PL-ASA then EC-ASA or vice versa with a minimum 14-day washout. Assessments included PK parameters for acetylsalicylic acid and salicylic acid, platelet aggregation in response to arachidonic acid (AA), and serum thromboxane B2 (TxB2) assessments over 24 h. PL-ASA was rapidly absorbed. PL-ASA reached Tmax 3 h earlier (1.01 vs. 4.00 h, p < 0.0001), with almost double the Cmax (720 vs. 368 ng/mL, p < 0.0001) and overall 44% higher exposure of acetylsalicylic acid (AUC0-t: 601 vs. 416 h*ng/mL, p = 0.0013) compared with EC-ASA. Within 1 h of dosing, PL-ASA achieved significantly lower residual platelet aggregation, which persisted for the full 24 h (median AA-LTA was 47% with PL-ASA vs. 80.5% with EC-ASA; p = 0.0022 at hour-24). Treatment with PL-ASA also resulted in significantly lower serum TxB2 concentrations at each time point compared with EC-ASA (all p-values < 0.05). PL-ASA resulted in faster and more complete aspirin absorption paralleled by more prompt and potent platelet inhibition compared with EC-ASA after a single 81 mg dose. PL-ASA represents an attractive novel aspirin formulation for the secondary prevention of cardiovascular events.Clinical Trial Registration ClinicalTrials.gov identifier: NCT04811625.

The use of a two-step removal protocol and optimized culture conditions improve development and quality of zona free mouse embryos.

The zona pellucida (ZP) plays an important role in both the fertilization and embryonic development. For the successful handling of early stage blastomeres for differentiation analysis, the production of identical twins or quadruplets, nuclear transfer or gene introduction requires the removal of the ZP (ZPR). Although single use of either acidic Tyrode's solution or pronase are commonly used for ZPR, long-term exposure to these agents can result in the inhibition of development with the collapse of the three-dimensional blastomere structure. Here, we demonstrate the benefits of using a two-step combined ZPR method, which relies upon a customized well-of-well (cWOW) system with smaller well size, on developmental competence and the quality of the zona free (ZF) mouse embryos. We first isolated 2-cell embryos using acid Tyrode's solution and then cultured these embryos using either commercially available or cWOW, which had a smaller microwell size. The rate of blastocyst was significantly increased by use of cWOW when compared to other culture systems. Then we evaluated the use of a two-step ZPR protocol, relying on acid Tyrode's solution and proteinase K, and subsequent culture in the cWOW system. Although acid Tyrode's solution treatment alone reduced ZPR time, blastomere morphology became wrinkled, significant decrease in blastocyst rate associated with increased number of apoptotic cells and increased expression of apoptosis-related genes were observed. Using proteinase K alone increased ZPR time and significantly decreased the blastocyst rate, but did not induce an increase in apoptotic cell number or apoptosis-related gene expression. In contrast, two-step method significantly reduced ZPR time and improved blastocyst rate by increasing the total number of cells in these wells an reducing the number of apoptotic cells in these experiments. These results suggest that the two-step ZPR protocol is beneficial for reducing the toxic effects of zona removal on ZF embryo development and quality when combined with a suitable culture system.

Expression of the Tas1r3 and Pept1 genes in the digestive tract of wagyu cattle.

Animals have precise recognition systems for amino acids and peptides that regulate their feeding behavior as well as metabolic responses. Because of their particular gastrointestinal structure, ruminants are expected to have unique mechanisms of amino acid regulation in the digestive tract. To better understand these mechanisms in the ruminant digestive tract, the expression of Tas1r3 and Pept1 was studied along the gastrointestinal tract of Japanese Black cattle through quantitative RT-PCR and immunohistochemistry. Tas1r3 mRNA was detected ubiquitously along the gastrointestinal tract, and the most predominant expression was observed in the reticulum. In addition, the presence of Tas1r3 receptor was confirmed in the rumen through immunohistochemistry. The expression level of Pept1 mRNA was higher in the forestomach (rumen, reticulum, and omasum) and small intestine (duodenum) than that in the tongue, and predominant expression was observed in the rumen. By contrast, a negligible amount of Pept1 mRNA was detected in the abomasum and large intestine. Further studies on the roles of Tas1r3 and Pept1 in the digestive tract, in particular, in the four components of the stomach, will help us to understand the mechanisms of amino acids regulation in ruminants and provide the basis for formulating cattle diets to improve the health and productivity of cattle.

Bioavailability of aspirin in fasted and fed states of a novel pharmaceutical lipid aspirin complex formulation.

Dyspeptic symptoms are common with aspirin and clinicians frequently recommend that it be taken with food to reduce these side effects. However, food can interfere with absorption, especially with enteric-coated aspirin formulations. We evaluated whether food interferes with the bioavailability of a new, pharmaceutical lipid-aspirin complex (PL-ASA) liquid-filled capsule formulation. In this randomized, open label, crossover study, 20 healthy volunteers fasted for ≥ 10 h and then randomized as either "fasted", receiving 650 mg of PL-ASA, or as "fed", with a standard high-fat meal and 650 mg of PL-ASA 30 min later. After a washout of 7 days, participants crossed over to the other arm. The primary outcome was comparison of PK parameters of the stable aspirin metabolite salicylic acid (SA) between fasted and fed states. Mean age of participants was 36.8 years and 55% were male. The ratios for the fed to fasted states of the primary SA PK parameters of AUC0-t and AUC0-∞ were 88.7% and 88.8% respectively, with 90% confidence intervals between 80 and 125%, which is consistent with FDA bioequivalence guidance. Mean peak SA concentration was about 22% lower and occurred about 1.5 h later in the fed state. Food had a modest effect on peak SA levels and the time required to reach them after PL-ASA administration, but did not impact the extent of exposure (AUC) compared with intake in a fasted state. These data demonstrate that PL-ASA may be co-administered with food without significant impact on aspirin bioavailability.Clinical Trial Registration:http://www.clinicaltrials.gov Unique Identifier: NCT01244100.

RGB-D SLAM Using Point-Plane Constraints for Indoor Environments.

Pose estimation and map reconstruction are basic requirements for robotic autonomous behavior. In this paper, we propose a point-plane-based method to simultaneously estimate the robot's poses and reconstruct the current environment's map using RGB-D cameras. First, we detect and track the point and plane features from color and depth images, and reliable constraints are obtained, even for low-texture scenes. Then, we construct cost functions from these features, and we utilize the plane's minimal representation to minimize these functions for pose estimation and local map optimization. Furthermore, we extract the Manhattan World (MW) axes on the basis of the plane normals and vanishing directions of parallel lines for the MW scenes, and we add the MW constraint to the point-plane-based cost functions for more accurate pose estimation. The results of experiments on public RGB-D datasets demonstrate the robustness and accuracy of the proposed algorithm for pose estimation and map reconstruction, and we show its advantages compared with alternative methods.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.

BACKGROUND: Carbapenem resistance is a growing concern. Applying a novel algorithm, we examined epidemiology and outcomes of carbapenem resistance among gram-negative pathogens in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). METHODS: In a retrospective cohort design within the Premier Research database (2009-2016), all hospitalized adult patients with a gram-negative organism in a respiratory or blood culture specimen who fit criteria for HAP/VAP based on International Classification of Diseases, Ninth Revision, Clinical Modification, codes were included in the study. RESULTS: Among 8,969 patients with HAP/VAP, 1,059 isolates (11.8%) were carbapenem-resistant (CR) organisms. Patients with CR organisms were more likely female (41.4% vs 33.2%; P < .001) and medical admissions (33.8% vs 27.4%, P < .001) than those with carbapenem-susceptible (CS) organisms. Patients with carbapenem resistance had higher comorbidity burden than those with carbapenem susceptibility (median [interquartile range] Charlson Comorbidity Index score, 3 [1-4] vs 2 [1-4]; P < .001). Pseudomonas aeruginosa was the most common gram-negative pathogen overall (24.9%) and among CS organisms (23.5%), and was second to Stenotrophomonas maltophilia (44.0%) among CR organisms (35.3%). Acinetobacter baumannii accounted for 11.8% of CR organisms and 2.5% of CS organisms (P < .001). Patients with carbapenem resistance were more likely than those with carbapenem susceptibility to receive inappropriate empiric therapy (25.8% vs 10.0%; P < .001). Carbapenem resistance did not affect adjusted mortality (22.9% CR vs 21.6% CS) or postinfection length of stay (except among survivors of VAP), but it was associated with excess costs ($8,921; 95% CI, 3,864-13,977). CONCLUSIONS: Using administrative data, our novel algorithm identified patients with pneumonia at high risk for death, consistent with HAP/VAP. Among them, carbapenem resistance occurred in 12% of all cases and was associated with substantial excess in hospital costs.

Emergency of fungemia cases caused by fluconazole-resistant Candida auris in Beijing, China.

We describe the microbiological characterization and clinical presentation of two fungemia cases caused by fluconazole-resistant Candida auris in neonatal intensive care unit of a hospital in Beijing, China. We advocate for the need of guidelines or recommendations to improve identification, surveillance, and implementation of infection control measures in Chinese hospitals.

Development and validation of a bedside instrument to predict carbapenem resistance among gram-negative pathogens in complicated urinary tract infections.

We developed a bedside instrument to predict carbapenem resistance in complicated urinary tract infections. A model assigning weighted points for admission from an extended care facility (1), history of weight loss (1), early mechanical ventilation (1), age <50 years (2), male gender (3), catheter-associated urinary tract infection (4), prior antibiotics treatment (4), and prior carbapenem-resistant infection (8) exhibited good discrimination (C statistic, 0.721).

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

BACKGROUND: Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. METHODS: PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. RESULTS: IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). CONCLUSIONS: IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI.

A Retrospective Cohort Analysis Shows that Coadministration of Minocycline with Colistin in Critically Ill Patients Is Associated with Reduced Frequency of Acute Renal Failure.

Nonclinical studies have suggested that oxidative damage, caspase-mediated apoptosis, and inducible nitric oxide synthase levels may be involved in the pathogenesis of colistin (CST)-associated acute renal failure. MIN inhibits caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the hypothesis that coadministration of CST with MIN (CST-MIN) may reduce the incidence of acute renal failure as well as produce additive or synergistic antimicrobial effects. A multicenter retrospective cohort study was conducted using the Premier Research database to examine the impact of CST-MIN on acute renal failure. Inclusion criteria were as follows: age of ≥18 years, intensive care unit admission at CST initiation, primary International Classification of Diseases 9 (ICD-9) diagnosis of pneumonia or sepsis, nondialysis at hospital admission, and discharge between January 2010 and December 2015. ICD-9 code 584.XX or ICD-10 code N17 was used to define acute renal failure. Baseline comparisons, 1:8 propensity score matching, and confirmatory logistic regression analyses were conducted. In total, 4,817 patients received CST and met inclusion criteria; 93 received CST-MIN. Unadjusted frequency of acute renal failure was significantly lower in patients receiving CST-MIN than CST (11.8% versus 23.7%, P = 0.007). Similar results were seen in propensity score matching (12.0% versus 22.3%, P = 0.031) and logistic regression analyses (odds ratio of 0.403, P = 0.006). Mortalities and 30-day readmission rates were similar between groups. The acute renal failure rate was not impacted by prevalence of baseline renal disease. CST-MIN in critically ill patients may reduce CST-associated acute renal failure. Further evaluation of this combination in prospective clinical studies is warranted.

30-day readmission, antibiotics costs and costs of delay to adequate treatment of Enterobacteriaceae UTI, pneumonia, and sepsis: a retrospective cohort study.

Background: Enterobacteriaceae are common pathogens in pneumonia, sepsis and urinary tract infection (UTI). Though rare, carbapenem resistance (CRE) among these organisms complicates efforts to ensure adequate empiric antimicrobial therapy. In turn this negatively impacts such outcomes as mortality and hospital costs. We explored proportion of total costs represented by antibiotics, 30-day readmission rates, and per-day costs of inadequate antimicrobial coverage among patients with Enterobacteriaceae pneumonia, sepsis and/or UTI in the context of inappropriate (IET) vs. appropriate empiric (non-IET) therapy and carbapenem resistance (CRE) vs. susceptibility (CSE). Methods: We conducted a retrospective cohort study in the Premier Research database (2009-2013) of 175 US hospitals. We included all adult patients admitted with a culture-confirmed UTI, pneumonia, or sepsis as principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure. Patients with hospital acquired infections or transfers from other acute facilities were excluded. IET was defined as failure to administer an antibiotic therapy in vitro active against the culture-confirmed pathogen within 2 days of admission. Results: Among 40,137 patients with Enterobacteriaceae infections (54.2% UTI), 4984 (13.2%) received IET. CRE (3.1%) was more frequent in patients given IET (13.0%) than non-IET (1.6%, p < 0.001). The proportions of total costs represented by antibiotics were similar in IET and non-IET (3.3% vs. 3.4%, p = 0.01), and higher among the group with CRE than CSE (4.2% vs. 3.4%, p < 0.001). The 30-day readmission rates were higher in both IET than non-IET (25.6% vs. 21.1%, p < 0.001) and CRE than CSE (29.7% vs. 21.5%, p < 0.001) groups. Each additional day of inadequate therapy cost an additional $766 (95% CI $661, $870, p < 0.001) relative to adequate treatment. Conclusions: In this large US cohort of Enterobacteriaceae infections, the cost of antibiotics was a small component of total costs, irrespective of whether empiric treatment was appropriate or whether a CRE was isolated. In contrast, each extra day of inadequate treatment added >$750 to hospital costs. Both CRE and IET were associated with an increased risk of readmission within 30 days.

Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

BACKGROUND: Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. METHODS: We conducted a retrospective cohort study in Premier Perspective database (2009-2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. RESULTS: Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/-2.0 vs. 1.9+/-2.1, p = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p < 0.001) in costs. CONCLUSIONS: In this large US database, the prevalence of CRE among patients with Enterobacteriaceae UTI, pneumonia or sepsis was comparable to other national estimates. Infection with CRE was associated with a four-fold increased risk of receiving IET, which in turn increased mortality, LOS and costs.

Single-Dose Oritavancin Compared to Standard of Care IV Antibiotics for Acute Bacterial Skin and Skin Structure Infection in the Outpatient Setting: A Retrospective Real-World Study.

INTRODUCTION: Cost-containment strategies are shifting the treatment of acute bacterial skin and skin structure infections (ABSSSI) from inpatient to outpatient settings. Current standard of care (SoC) requires multiple-dose regimens, which are associated with high hospitalization rates and high costs. Oritavancin, a new single-dose antibiotic for ABSSSI, may be suitable for outpatient therapy. This analysis evaluates the effectiveness, costs, and resource utilization of oritavancin vs. SoC in a real-world, outpatient setting. METHODS: A single-site, retrospective chart review was conducted of 118 adult patients diagnosed with ABSSSI and treated with either single-dose oritavancin or multi-dose SoC therapy between 6 August 2014 and 30 June 2015. Patients were assigned to two matched cohorts: oritavancin and SoC. Primary clinical effectiveness endpoints was the success (cured or improved) at 5-30 days after the course of antibiotic therapy has been completed. Secondary economic endpoints were total costs and healthcare resource utilization. RESULTS: Oritavancin showed comparable clinical effectiveness vs. multi-dose SoC in the outpatient setting. A similar percentage of patients in the oritavancin (90.2%) and SoC cohorts (77.4%) achieved successful outcomes ("cure" or "improved"), with the cure rate higher for oritavancin (73.2%) vs. SoC (48.4%; P = 0.0315). Oritavancin's clinical effectiveness was consistent across patient subgroups with varying demographic, clinical, and ABSSSI characteristics. Oritavancin was consistently associated with lower costs (per-patient savings $2319) and reduced resource utilization measures, and it required just 1.0 day of therapy vs. 7.2 days for SoC. CONCLUSION: Oritavancin is well suited for the outpatient treatment of ABSSSI. Compared with SoC, oritavancin offers comparable effectiveness, is more economical, and requires fewer healthcare resources.

Exploring second coordination sphere effects in nitric oxide synthase.

Second coordination sphere (SCS) effects in proteins are modulated by active site residues and include hydrogen bonding, electrostatic/dipole interactions, steric interactions, and π-stacking of aromatic residues. In Cyt P450s, extended H-bonding networks are located around the proximal cysteinate ligand of the heme, referred to as the 'Cys pocket'. These hydrogen bonding networks are generally believed to regulate the Fe-S interaction. Previous work identified the S(Cys) → Fe σ CT transition in the high-spin (hs) ferric form of Cyt P450cam and corresponding Cys pocket mutants by low-temperature (LT) MCD spectroscopy [Biochemistry 50:1053, 2011]. In this work, we have investigated the effect of the hydrogen bond from W409 to the axial Cys ligand of the heme in the hs ferric state (with H4B and L-Arg bound) of rat neuronal nitric oxide synthase oxygenase construct (nNOSoxy) using MCD spectroscopy. For this purpose, wt enzyme and W409 mutants were investigated where the H-bonding network with the axial Cys ligand is perturbed. Overall, the results are similar to Cyt P450cam and show the intense S(Cys) → Fe σ CT band in the LT MCD spectrum at about 27,800 cm-1, indicating that this feature is a hallmark of {heme-thiolate} active sites. The discovery of this MCD feature could constitute a new approach to classify {heme-thiolate} sites in hs ferric proteins. Finally, the W409 mutants show that the hydrogen bond from this group only has a small effect on the Fe-S(Cys) bond strength, at least in the hs ferric form of the protein studied here. Low-temperature MCD spectroscopy is used to investigate the effect of the hydrogen bond from W409 to the axial Cys ligand of the heme in neuronal nitric oxide synthase. The intense S(Cys) → Fe σ-CT band is monitored to identify changes in the Fe-S(Cys) bond in wild-type protein and W409 mutants.

Multidrug resistance, inappropriate empiric therapy, and hospital mortality in Acinetobacter baumannii pneumonia and sepsis.

BACKGROUND: The relationship between multidrug resistance (MDR), inappropriate empiric therapy (IET), and mortality among patients with Acinetobacter baumannii (AB) remains unclear. We examined it using a large U.S. METHODS: We conducted a retrospective cohort study using the Premier Research database (2009-2013) of 175 U.S. hospitals. We included all adult patients admitted with pneumonia or sepsis as their principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, along with antibiotic administration within 2 days of admission. Only culture-confirmed infections were included. Resistance to at least three classes of antibiotics defined multidrug-resistant AB (MDR-AB). We used logistic regression to compute the adjusted relative risk ratio (RRR) of patients with MDR-AB receiving IET and IET's impact on mortality. RESULTS: Among 1423 patients with AB infection, 1171 (82.3 %) had MDR-AB. Those with MDR-AB were older (63.7 ± 15.4 vs. 61.0 ± 16.9 years, p = 0.014). Although chronic disease burden did not differ between groups, the MDR-AB group had higher illness severity than those in the non-MDR-AB group (intensive care unit 68.0 % vs. 59.5 %, p < 0.001; mechanical ventilation 56.2 % vs. 42.1 %, p < 0.001). Patients with MDR-AB were more likely to receive IET than those in the non-MDR-AB group (76.2 % MDR-AB vs. 13.8 % non-MDR-AB, p < 0.001). In a regression model, MDR-AB strongly predicted receipt of IET (adjusted RRR 5.5, 95 % CI 4.0-7.7, p < 0.001). IET exposure was associated with higher hospital mortality (adjusted RRR 1.8, 95 % CI 1.4-2.3, p < 0.001). CONCLUSIONS: In this large U.S. database, the prevalence of MDR-AB among patients with AB infection was > 80 %. Harboring MDR-AB increased the risk of receiving IET more than fivefold, and IET nearly doubled hospital mortality.

Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.

INTRODUCTION: Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. METHODS: SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. RESULTS: Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). CONCLUSION: Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. FUNDING: The Medicines Company, Parsippany, NJ, USA. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II).