Novel substituted (pyridin-3-yl)phenyloxazolidinones: antibacterial agents with reduced activity against monoamine oxidase A and increased solubility.

PubMed

Reck, Folkert; Zhou, Fei; Eyermann, Charles J; Kern, Gunther; Carcanague, Dan; Ioannidis, Georgine; Illingworth, Ruth; Poon, Grace; Gravestock, Michael B

2007-10-04

Oxazolidinones represent a new and promising class of antibacterial agents. Current research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Oxazolidinones bearing a (pyridin-3-yl)phenyl moiety (e.g., 3) generally show improved antibacterial activity compared to linezolid but suffer from potent monoamine oxidase A (MAO-A) inhibition and low solubility. We now disclose the finding that new analogues of 3 with acyclic substituents on the pyridyl moiety exhibit excellent activity against Gram-positive pathogens, including linezolid-resistant Streptococcus pneumoniae. Generally, more bulky substituents yielded significantly reduced MAO-A inhibition relative to the unsubstituted compound 3. The MAO-A SAR can be rationalized on the basis of docking studies using a MAO-A/MAO-B homology model. Solubility was enhanced with incorporation of polar groups. One optimized analogue, compound 13, showed low clearance in the rat and efficacy against S. pneumoniae in a mouse pneumonia model.

Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes.

PubMed

Santini, Alessandro; Ronchi, Dario; Garbellini, Manuela; Piga, Daniela; Protti, Alessandro

2017-07-01

Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion: Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes. The inhibition of mitochondrial protein synthesis diminishes the respiratory chain enzyme content and thus limits aerobic energy production. As a result, anaerobic glycolysis and lactate generation accelerate independently from tissue hypoxia. In the absence of any confirmatory test, linezolid-induced lactic acidosis should be suspected only after exclusion of other, more common, causes of lactic acidosis such as hypoxemia, anemia or low cardiac output. Normal-to-high whole-body oxygen delivery, high venous oxygen saturation and lack of response to interventions that effectively increase tissue oxygen provision all suggest a primary defect in oxygen use at the mitochondrial level. During prolonged therapy with linezolid, blood drug and lactate levels should be regularly monitored. The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal to reverse mitochondrial intoxication and intercurrent life support.

Outbreak of linezolid-resistant Staphylococcus haemolyticus in an Italian intensive care unit.

PubMed

Mazzariol, A; Lo Cascio, G; Kocsis, E; Maccacaro, L; Fontana, R; Cornaglia, G

2012-04-01

We report an outbreak of linezolid-resistant Staphylococcus haemolyticus strains (MIC 32 mg/L) in patients admitted to the Verona University Hospital Intensive Care Unit. The strains proved to be clonally related at pulsed field gel electrophoresis. All the strains showed the G2576T mutation responsible for linezolid-resistance and retained their resistance even after several passages on antibiotic-free medium. After a decade of linezolid use, multifocal emergence of linezolid resistance in coagulase-negative staphylococci has become an important matter of concern and mandates stricter control over the use of this antibiotic in order to preserve its clinical utility.

Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

PubMed

Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

2013-01-01

To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

A simple high-performance liquid chromatography for the determination of linezolid in human plasma and saliva.

PubMed

Hara, Shuuji; Uchiyama, Masanobu; Yoshinari, Masami; Matsumoto, Taichi; Jimi, Shiro; Togawa, Atsushi; Takata, Tohru; Takamatsu, Yasushi

2015-09-01

Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. A practical high-performance liquid chromatography method was developed for the determination of linezolid in human plasma and saliva. Linezolid and an internal standard (o-ethoxybenzamide) were extracted from plasma and saliva with ethyl acetate and analyzed on a Capcell Pak C18 MG column with UV detection at 254 nm. The calibration curve was linear through the range 0.5-50 µg/mL using a 200 μL sample volume. The intra- and interday precisions were all <6.44% for plasma and 5.60% for saliva. The accuracies ranged from 98.8 to 110% for both matrices. The mean recoveries of linezolid were 80.8% for plasma and 79.0% for saliva. This method was used to determine the plasma and saliva concentrations of linezolid in healthy volunteers who were orally administered a 600 mg dose of linezolid. Our liquid-liquid extraction procedure is easy and requires a small volume of plasma or saliva (200 μL). This small volume can be advantageous in clinical pharmacokinetic studies, especially if children participate. Copyright © 2015 John Wiley & Sons, Ltd.

Accumulation of multiple mutations in linezolid-resistant Staphylococcus epidermidis causing bloodstream infections; in silico analysis of L3 amino acid substitutions that might confer high-level linezolid resistance.

PubMed

Ikonomidis, Alexandros; Grapsa, Anastasia; Pavlioglou, Charikleia; Demiri, Antonia; Batarli, Alexandra; Panopoulou, Maria

2016-12-01

Fifty-six Staphylococcus epidermidis clinical isolates, showing high-level linezolid resistance and causing bacteremia in critically ill patients, were studied. All isolates belonged to ST22 clone and carried the T2504A and C2534T mutations in gene coding for 23SrRNA as well as the C189A, G208A, C209T and G384C missense mutations in L3 protein which resulted in Asp159Tyr, Gly152Asp and Leu94Val substitutions. Other silent mutations were also detected in genes coding for ribosomal proteins L3 and L22. In silico analysis of missense mutations showed that although L3 protein retained the sequence of secondary motifs, the tertiary structure was influenced. The observed alteration in L3 protein folding provides an indication on the putative role of L3-coding gene mutations in high-level linezolid resistance. Furthermore, linezolid pressure in health care settings where linezolid consumption is of high rates might lead to the selection of resistant mutants possessing L3 mutations that might confer high-level linezolid resistance.

Modeling the economic impact of linezolid versus vancomycin in confirmed nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.

PubMed

Patel, Dipen A; Shorr, Andrew F; Chastre, Jean; Niederman, Michael; Simor, Andrew; Stephens, Jennifer M; Charbonneau, Claudie; Gao, Xin; Nathwani, Dilip

2014-07-22

We compared the economic impacts of linezolid and vancomycin for the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA)-confirmed nosocomial pneumonia. We used a 4-week decision tree model incorporating published data and expert opinion on clinical parameters, resource use and costs (in 2012 US dollars), such as efficacy, mortality, serious adverse events, treatment duration and length of hospital stay. The results presented are from a US payer perspective. The base case first-line treatment duration for patients with MRSA-confirmed nosocomial pneumonia was 10 days. Clinical treatment success (used for the cost-effectiveness ratio) and failure due to lack of efficacy, serious adverse events or mortality were possible clinical outcomes that could impact costs. Cost of treatment and incremental cost-effectiveness per successfully treated patient were calculated for linezolid versus vancomycin. Univariate (one-way) and probabilistic sensitivity analyses were conducted. The model allowed us to calculate the total base case inpatient costs as $46,168 (linezolid) and $46,992 (vancomycin). The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with lower costs ($824 less) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA nosocomial pneumonia). Approximately 80% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). The results of our probabilistic sensitivity analysis indicated that linezolid is the cost-effective alternative under varying willingness to pay thresholds. These model results show that linezolid has a favorable incremental cost-effectiveness ratio compared to vancomycin for MRSA-confirmed nosocomial pneumonia, largely attributable to the higher clinical trial response rate of patients treated with linezolid. The higher drug acquisition cost of linezolid was offset by lower treatment failure-related costs and fewer days of hospitalization.

Serotonin toxicity as a consequence of linezolid use in revision hip arthroplasty.

PubMed

Mason, Lyndon W; Randhawa, Kiran S; Carpenter, Eleanor C

2008-11-01

Linezolid is the first in a new group of antibiotics called oxazolidinones. As a potent antimicrobial, it has activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, penicillin-resistant Streptococcus pneumoniae, and macrolide-resistant streptococci. There are several documented case reports of serotonin toxicity when used with selective serotonin reuptake inhibitors. The symptoms of serotonin syndrome are alteration of mental state, autonomic dysfunction, and neuromuscular disorders. This article presents a case of an interaction of the serotonin reuptake inhibitor venlafaxine and linezolid and the possible diagnostic problems that can occur. A 58-year-old woman presented with signs of systemic infection. Her medical history included bladder resection for transitional cell carcinoma, bilateral total hip arthroplasty (THA), and depression, for which she was on venlafaxine. Serological and imaging investigations revealed MRSA infection of the bilateral THA. The patient was started on vancomycin and rifampicin intravenously. As intravenous access was becoming problematic and long-term antibiotics were needed, treatment was changed to oral linezolid and oral rifampicin. Four days after the commencement of linezolid, the patient was acutely disorientated with generalized cerebellar signs and no autonomic dysfunction. A computed tomography scan of the head and lumbar puncture revealed no abnormal findings. A diagnosis of serotonin toxicity was made. The patient recovered when linezolid and venlafaxine were discontinued and supportive measures were provided. Linezolid is a popular choice of antibiotic, especially for the treatment of orthopedic-related MRSA infections. Patients who commonly require linezolid as an antimicrobial are those with complex infections where other antibiotic treatment has failed. It is therefore important to be vigilant with linezolid use. Physicians should be aware of the nonspecific presentation of serotonin symptoms and the treatment.

Linezolid-resistant mucoid Staphylococcus haemolyticus from a tertiary-care centre in Delhi.

PubMed

Matlani, M; Shende, T; Bhandari, V; Dawar, R; Sardana, R; Gaind, R

2016-05-01

We report an unusual morphological mucoid variant of Staphylococcus haemolyticus associated with linezolid resistance from a patient with sepsis. Linezolid resistance and mucoid character together made this pathogen difficult to treat. To our knowledge this is the first such report.

Linezolid-induced optic neuropathy with a rare pathological change in the inner retina.

PubMed

Ishii, Nobuhito; Kinouchi, Reiko; Inoue, Masatomo; Yoshida, Akitoshi

2016-12-01

We report a case of linezolid-induced optic neuropathy with transient microcystic spaces in the inner retina. We observed the retina using Fourier-domain optical coherence tomography (FD-OCT) in a patient with linezolid-induced optic neuropathy. A 49-year-old woman presented to our department with a 1-week history of bilateral photophobia. At the first visit, her best-corrected visual acuity (VA) was 0.6 in the right eye and 0.5 in the left eye. She had moderate optic disk edema and central scotomas bilaterally. FD-OCT showed bilateral microcystic spaces in the retina. Microcystic spaces were seen in the retinal nerve fiber layer (RNFL) and at the border of the RNFL and the retinal ganglion cell layer. Magnetic resonance imaging and laboratory tests showed no positive findings except for an elevated lactic acid level. One week after the first visit, the VA levels decreased to 0.06 and 0.07 in the right and left eyes, respectively. Because the patient had a 7-month history of linezolid treatment for persistent pyogenic arthritis, we suspected linezolid-induced optic neuropathy and immediately terminated treatment with this drug. The optic disk edema and the microcystic spaces in the retina resolved, and the VA improved to 1.2 at 6 weeks after linezolid withdrawal. Microcystic spaces, which resolved with linezolid withdrawal, were observed in linezolid-induced optic neuropathy. The microcystic spaces in the inner retina can be the first retinal sign of some optic neuropathies.

[Impact of rational use of antibiotics in a third level clinic in Colombia].

PubMed

Pallares, Christian J; Cataño, Juan C

2017-06-01

The increasing resistance of bacteria to antibiotics threatens the survival of patients and health costs. To determine the impact of an antimicrobial stewardship program in bacterial resistance and antibiotic consumption. Quasi experimental study in a third level clinic in the city of Medellin, that evaluate in two time periods (pre-intervention between October 2012 and September 2013 and post intervention between October 2013 and September 2014) the impact of an antimicrobial stewardship program in terms of antibiotic consumption and bacterial ecology. Adherence to institutional guidelines for management of infections in the post-intervention period was 82%. Antibiotic consumption of meropenem, ceftriaxone, vancomycin and colistin decreased, and imipenem, daptomycin and linezolid was increased. A significant decrease in antibiotic resistance in Pseudomonas aeruginosa was observed, including carbapenems. An increase of extended spectrum beta lactamase production (ESBL) in Enterobacteriaceae (especially E. coli) and piperacillin/tazobactam resistance was observed. The construction and implementation of a strategy in hospitals with guidelines for managing infectious diseases, restrictions in antibiotic use, a permanent monitoring system for the formulation of antibiotics, achieved a positive impact on reducing antibiotic use and bacterial resistance.

Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin.

PubMed

Kollef, Marin H; Rello, Jordi; Cammarata, Sue K; Croos-Dabrera, Rodney V; Wunderink, Richard G

2004-03-01

To assess the effect of baseline variables, including treatment, on clinical cure and survival rates in patients with Gram-positive, ventilator-associated pneumonia (VAP). Retrospective analysis of two randomized, double-blind studies. Multinational study with 134 sites. 544 patients with suspected Gram-positive VAP, including 264 with documented Gram-positive VAP and 91 with methicillin-resistant S. aureus (MRSA) VAP. Linezolid 600 mg or vancomycin 1 g every 12 h for 7-21 days, each with aztreonam. Clinical cure rates assessed 12-28 days after the end of therapy and excluding indeterminate or missing outcomes significantly favored linezolid in the Gram-positive and MRSA subsets. Logistic regression showed that linezolid was an independent predictor of clinical cure with odds ratios of 1.8 for all patients, 2.4 for Gram-positive VAP, and 20.0 for MRSA VAP. Kaplan-Meier survival rates favored linezolid in the MRSA subset. Logistic regression showed that linezolid was an independent predictor of survival with odds ratios of 1.6 for all patients, 2.6 for Gram-positive VAP, and 4.6 for MRSA VAP. Initial linezolid therapy was associated with significantly better clinical cure and survival rates than was initial vancomycin therapy in patients with MRSA VAP.

Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections.

PubMed

Plosker, Greg L; Figgitt, David P

2005-01-01

Linezolid (Zyvox), the first available oxazolidinone antibacterial agent, has good activity against Gram-positive pathogens, including multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Randomised multicentre trials in patients with various types of serious Gram-positive infections showed that clinical cure rates with linezolid were similar to those with vancomycin or teicoplanin. In some subgroup analyses, which must be interpreted with a degree of caution, clinical advantages were noted for linezolid (e.g. versus vancomycin in confirmed MRSA nosocomial pneumonia and MRSA-complicated skin and soft tissue infections). Although generally well tolerated, gastrointestinal adverse effects are relatively common with linezolid and it has been associated with thrombocytopenia and myelosuppression. The oral bioavailability of linezolid is approximately 100%, thus allowing sequential intravenous-to-oral administration without changing the drug or dosage regimen. Healthcare resource use data from various countries indicate that this practical advantage translates into at least a trend towards reduced length of hospital stay compared with vancomycin, which may offset its several-fold higher acquisition cost. Modelled analyses from the US, despite some limitations, indicate that, compared with vancomycin, linezolid is associated with lower total hospitalisation costs for the treatment of patients with cellulitis and has a favourable incremental cost-effectiveness ratio of approximately US30,000 dollars per QALY gained (2001 value) for patients with ventilator-associated pneumonia. Broadly similar results have also been reported in modelled analyses from other countries. In conclusion, for patients with serious Gram-positive infections, including those caused by suspected or proven multidrug-resistant pathogens such as MRSA, linezolid is an effective and generally well tolerated therapeutic option. Linezolid is currently the only antibacterial agent with good activity against MRSA that can be administered orally (as well as intravenously). It may be particularly useful as an alternative to vancomycin in patients who have impaired renal function, poor or no intravenous access, require outpatient therapy, or who have been unable to tolerate glycopeptides. Healthcare resource use studies and pharmacoeconomic analyses generally support the use of linezolid in some subgroups of patients, although results should be interpreted with due consideration of the study limitations.

Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in Mumbai, India

PubMed Central

Mehta, Salil; Das, Mrinalini; Laxmeshwar, Chinmay; Jonckheere, Sylvie; Thi, Sein Sein; Isaakidis, Petros

2016-01-01

Background Patients on linezolid-containing drug-resistant TB (DR-TB) regimen often develop adverse-events, particularly peripheral and optic neuropathy. Programmatic data and experiences of linezolid-associated optic neuropathy from high DR-TB burden settings are lacking. The study aimed to determine the frequency of and risk-factors associated with linezolid-associated optic neuropathy and document the experiences related to treatment/care of DR-TB patients on linezolid-containing regimens. Methods This was a retrospective cohort study using routine clinical and laboratory data in Médecins Sans Frontières (MSF) HIV/DR-TB clinic in collaboration with Lilavati Hospital & Research Center, Mumbai, India. All DR-TB patients on linezolid-containing treatment regimens were included in the study and underwent routine evaluations for systemic and/or ocular complaints. Ophthalmological evaluation by a consultant ophthalmologist included visual-acuity screening, slit-lamp examination and dilated fundus examination. Results During January 2013-April 2016, 86 of 136 patients (with/without HIV co-infection) initiated linezolid-containing DR-TB treatment. The median age of these 86 patients was 25 (20–35) years and 47% were males. 20 percent of them had HIV co-infection. Of 86, 24 (27.9%) had at least one episode of ocular complaints (the majority blurred-vision) and among them, five (5.8%) had optic neuropathy. Patients received appropriate treatment and improvements were observed. None of the demographic/clinical factors were associated with optic neuropathy in Poissons or multivariate binary logistic-regression models. Discussion This is the first report focusing on optic neuropathy in a cohort of complex DR-TB patients, including patients co-infected with HIV, receiving linezolid-containing regimens. In our study, one out of four patients on linezolid had at least one episode of ocular complaints; therefore, systematic monitoring of patients by primary physicians/nurses, and access to specialized diagnostic-services by specialists are needed. As linezolid will be increasingly added to treatment regimens of DR-TB patients, programmes should allocate adequate resources for early diagnosis, prevention and management of this disabling adverse event. PMID:27611434

Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid.

PubMed

Toh, Seok-Ming; Xiong, Liqun; Arias, Cesar A; Villegas, Maria V; Lolans, Karen; Quinn, John; Mankin, Alexander S

2007-06-01

Linezolid, which targets the ribosome, is a new synthetic antibiotic that is used for treatment of infections caused by Gram-positive pathogens. Clinical resistance to linezolid, so far, has been developing only slowly and has involved exclusively target site mutations. We have discovered that linezolid resistance in a methicillin-resistant Staphylococcus aureus hospital strain from Colombia is determined by the presence of the cfr gene whose product, Cfr methyltransferase, modifies adenosine at position 2503 in 23S rRNA in the large ribosomal subunit. The molecular model of the linezolid-ribosome complex reveals localization of A2503 within the drug binding site. The natural function of cfr likely involves protection against natural antibiotics whose site of action overlaps that of linezolid. In the chromosome of the clinical strain, cfr is linked to ermB, a gene responsible for dimethylation of A2058 in 23S rRNA. Coexpression of these two genes confers resistance to all the clinically relevant antibiotics that target the large ribosomal subunit. The association of the ermB/cfr operon with transposon and plasmid genetic elements indicates its possible mobile nature. This is the first example of clinical resistance to the synthetic drug linezolid which involves a natural resistance gene with the capability of disseminating among Gram-positive pathogenic strains.

Nonadherence to oral linezolid after hospitalization: a retrospective claims analysis of the incidence and consequence of claim reversals.

PubMed

Ball, Amy T; Xu, Yihua; Sanchez, Robert J; Shelbaya, Ahmed; Deminski, Michael C; Nau, David P

2010-12-01

Linezolid is available in an oral as well as an intravenous formulation. It is an oxazolidinone antibiotic and is effective in treating resistant gram-positive organisms such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Streptococcus pneumoniae. The goals of this study were to identify the incidence of claim reversals for oral linezolid in members who were recently discharged from a hospital and to study the subsequent pattern of health care utilization to quantify the consequences for members who have a reversed linezolid claim. This study was a retrospective claims analysis of Humana Medicare Advantage Prescription Drug patients who had a claim for oral linezolid after an inpatient discharge between April 1, 2006, and June 30, 2008. The incidence of reversed claims among those with a linezolid prescription was measured as a proxy for medication adherence. Propensity scores were calculated to account for differences in patients' propensity to have a reversed claim. The association of the claim reversal with subsequent expenditures was assessed through 3 multivariate regression models wherein the dependent variables were drug, medical, and total costs for the 60-day period after discharge. The key independent variable was the occurrence of a reversed linezolid claim, and control variables included the propensity score quartiles and other clinical and demographic characteristics. All costs were provided in US dollars and from the year in which they occurred. Of 1046 patients identified (mean [SD] age, 69 [12] years; 51% male), 252 patients (24.1%) had a claim reversal for linezolid. Among these, 125 patients (49.6%) received linezolid within 10 days of the initial reversal, 39 patients (15.5%) received other antibiotics, and 88 patients (34.9%) did not receive any antibiotics. The unadjusted, mean outpatient drug costs were $696 and $2265 for patients with and without a reversal, respectively, whereas mean medical costs were $13,567 and $9355. Multivariable analyses revealed that members who did not receive linezolid after the claim reversal had significantly higher medical expenditures (Wald χ(2), 8.370; P = 0.004) and lower drug expenditures (Wald χ(2), 122.630; P < 0.01). The total costs did not differ significantly between the 2 groups (Wald χ(2), 1.540; P = 0.215), however, as the medical savings were partially negated by the higher drug costs. These patients with a reversed outpatient claim for linezolid had lower outpatient drug costs and higher medical costs in the 60-day period after the reversal. Copyright © 2010 Elsevier HS Journals, Inc. Published by EM Inc USA.. All rights reserved.

Case Report: Linezolid Optic Neuropathy and Proposed Evidenced-based Screening Recommendation.

PubMed

Dempsey, Sean P; Sickman, Amy; Slagle, William Scott

2018-05-01

This case illustrates a novel screening protocol for linezolid-induced toxic optic neuropathy. To present a case report and analysis of linezolid-induced optic neuropathies in adult patients to develop screening recommendations. A case report of optic neuropathy from extended use of linezolid illustrates its potential effects on vision. We conduct a retrospective analysis of 39 reported cases to derive a recommended screening protocol for linezolid-induced toxic optic neuropathy in adult patients. Of 39 reported adult cases, 32 presented with optic neuropathy within 90 to 365 days of treatment. Within this subset, the duration of linezolid dosage to first symptoms is 235 ± 71 days. Seven outliers either experienced optic neuropathy within the first 28 days or between 600 and 1125 days. Of the 33 cases that quantified visual recovery, 30 reported final binocular visual acuity equivalent to 20/40 or better when the medication was discontinued from 0 to 268 days after symptom onset. Recovery potential was reported over a period of 2 weeks to approximately 6 months after cessation. To evaluate the effect of cumulative dose, the data were separated into patients taking 600 mg twice daily and those at 600 mg once daily. At the higher dosage, a mean of 180 ± 96 days with a mean cumulative dosage of 216 ± 115 g was noted at first symptom, whereas at lower dosage, a mean of 201 ± 102 days was noted with a mean cumulative dose of 138 ± 69 g. We recommend screening adult patients within 1 month after initiating linezolid, followed by a subsequent evaluation every 30 to 60 days beginning 3 months from initiation. Substantial visual recovery is reported when linezolid is discontinued. Toxicity appears to be correlated to duration of treatment, rather than cumulative dose.

Effectiveness and safety of imipenem/clavulanate and linezolid to treat multidrug and extensively drug-resistant tuberculosis at a referral hospital in Brazil.

PubMed

Arbex, M A; Bonini, E H; Kawakame Pirolla, G; D'Ambrosio, L; Centis, R; Migliori, G B

Evidence on effectiveness, safety, and tolerability of imipenem/clavulanate (IC) and linezolid containing regimens to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is scarce. The aim of this observational study is to evaluate the therapeutic contribution of IC and linezolid to manage MDR/XDR-TB cases at the reference centre of São Paulo state, Brazil. Twelve patients (9 males, 1 HIV positive in antiretroviral treatment, 4 MDR, 8 XDR) were treated with IC, 11 of them within linezolid-containing regimens. They all were previously treated with treatment failure, for a median (IQR, interquartile range) of 4.5 (2-6.5) times, having a severe resistance pattern (median number of resistances: 7 (5-8)) and being sputum smear and culture positive. IC and linezolid were prescribed at the dose of 1000mg/day and 600mg/day, respectively. The overall exposure was (median (IQR)) 419 (375.5-658) days for IC and 678 (392-720) days for linezolid. All of them converted their sputum (time to sputum conversion; 60 (37.5-90) days) and culture (75 (60-135) days), and 7 were cured while 5 are still on treatment with a gradually improving clinical picture. While no adverse events were reported for IC, 2 minor side effects, only, were attributed to linezolid (17%); in both cases the drug was re-started without further problems. Our study suggests that IC and linezolid-containing regimens can be used safely and with satisfactory outcomes in reference centres to treat MDR/XDR-TB patients. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Induction therapy with linezolid/clarithromycin combination for Mycobacterium chelonae skin infections in immunocompromised hosts.

PubMed

Parize, P; Hamelin, A; Veziris, N; Morand, P C; Guillemain, R; Lortholary, O; Dupin, N

2016-01-01

The optimal management of Mycobacterium chelonae disease in immunocompromised patients remains unclear. A combination of antimicrobial agents is recommended as monotherapy with clarithromycin has been associated with clinical failures due to acquired resistance. We aim to report the efficacy and tolerability of linezolid in association with clarithromycin for the treatment of M. chelonae infections in immunocompromised patients. We describe four immunocompromised patients treated by linezolid and clarithromycin for cutaneous M. chelonae disease. This combination was associated with rapid clinical efficacy in all patients with no relapse observed after a median follow-up of 2.25 years (1.4 years). However, this treatment was responsible for frequent adverse events including thrombocytopaenia, myalgia and mitochondrial toxicity. All adverse effects were reversible after linezolid discontinuation. We therefore suggest linezolid/clarithromycin combination as the initial therapeutic strategy for M. chelonae skin infections in immunocompromised patients. © 2015 European Academy of Dermatology and Venereology.

Linezolid-induced serotonin syndrome

PubMed Central

Gupta, Vishal; Karnik, Niteen D; Deshpande, Rushikesh; Patil, Meenakshi Amit

2013-01-01

A young drug abuser was admitted to our intensive care unit for organophosphorus poisoning. He required mechanical ventilation and was started empirically on linezolid for suspected nosocomial infection. The patient developed high-grade fever with altered sensorium and clonus. Serotonin syndrome was suspected and the patient was started on cyproheptadine. He recovered within 3 days of withdrawing linezolide and administering cyproheptadine. PMID:23513014

Tedizolid susceptibility in linezolid- and vancomycin-resistant Enterococcus faecium isolates.

PubMed

Klupp, E-M; Both, A; Belmar Campos, C; Büttner, H; König, C; Christopeit, M; Christner, M; Aepfelbacher, M; Rohde, H

2016-12-01

Vancomycin-resistant enterococci (VRE) are of ever-increasing importance, most notably in high-risk patient populations. Therapy options are often limited for these isolates, and apart from tigecycline and daptomycin, oxazolidinone linezolid is frequently administered. The broad usage of linezolid, however, has driven the emergence of linezolid-resistant VRE strains (LR-VRE), further shortening therapeutic options. Second-generation oxazolidinone tedizolid has the advantage of being active against a specific subset of LR-VRE, i.e. isolates expressing the plasmid-encoded chloramphenicol-florfenicol resistance (cfr) gene. Here we tested tedizolid activity in a collection of 30 LR Enterococcus faecium VRE (MIC range 32-256 mg/l) isolated between 2012 and 2015 from clinical and screening specimens. By pulsed field gel electrophoresis (PFGE) isolates were assigned to 16 clonal lineages. In three cases, linezolid-susceptible progenitor isolates of LR-VRE were isolated, thus demonstrating the de-novo emergence of the linezolid-resistant phenotype. PCR did not detect cfr, cfr(B) or novel oxazolidinone resistance gene optrA in LR-VRE. All isolates, however, carried mutations within the 23S rDNA. Compared to linezolid, tedizolid MICs were lower in all isolates (MIC range 2-32 mg/l), but remained above the FDA tedizolid breakpoint for E. faecalis at 0.5 mg/l. Thus, related to the predominant resistance mechanism, tedizolid is of limited value for treatment of most LR-VRE and represents a therapeutic option only for a limited subset of isolates.

Lactic Acidosis Induced by Linezolid Mimics Symptoms of an Acute Intracranial Bleed: A Case Report and Literature Review.

PubMed

Zuccarini, Nichole Suzzanne; Yousuf, Tariq; Wozniczka, Daniel; Rauf, Anis Abdul

2016-10-01

Lactic acidosis is common and most often associated with disturbed acid-base balance. Rarely, it can be a life-threatening medication side effect. Hence, determining the etiology of lactic acidosis early in patients is paramount in choosing the correct therapeutic intervention. Although lactic acidosis as an adverse drug reaction of linezolid is a well-recognized and documented clinical entity, the occurrence of such mimicking an acute intracranial bleed has not been reported to our knowledge. The following case is presented as an example of such an occurrence. A 67-year-old woman presented to the emergency department for lethargy, nausea and syncope. The head CT did not demonstrate any bleeding or mass effect, but lab results were significant for elevated lactic acid. The patient recently underwent left total hip replacement surgery, which was complicated by a methicillin-resistant Staphylococcus aureus (MRSA) infection. She received 6 weeks of oral linezolid therapy. And upon learning that key part of her history, the linezolid was discontinued. Her lactic acid rapidly normalized and she was discharged home. Several publications demonstrate that linezolid induces lactic acidosis by disrupting crucial mitochondrial functions. It is essential that clinicians are aware that linezolid can cause lactic acidosis. And, the important reminder is that adverse drug reactions can often mimic common diseases. If it is not recognized early, ominous clinical consequences may occur. In conclusion, linezolid should be suspected and included in the differential diagnosis if lactic acidosis exists with an uncommon clinical picture.

Two cases of serious rhabdomyolysis during linezolid treatment.

PubMed

Lechner, Arno M; Past, Eva; Porsche, Ulla; Kern, Jan M; Hoppe, Uta; Pretsch, Ingrid

2017-08-01

Linezolid is an oxazolidinone antibiotic with activity against gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA). To the best of our knowledge, there are only two case reports on rhabdomyolysis in patients treated with linezolid. Here, we describe two cases of serious rhabdomyolysis: one in a patient with septic community-acquired (CA)-MRSA pneumonia and a second case in a patient with suspected catheter-related blood stream infection.

Changes in Whole-Body Oxygen Consumption and Skeletal Muscle Mitochondria During Linezolid-Induced Lactic Acidosis.

PubMed

Protti, Alessandro; Ronchi, Dario; Bassi, Gabriele; Fortunato, Francesco; Bordoni, Andreina; Rizzuti, Tommaso; Fumagalli, Roberto

2016-07-01

To better clarify the pathogenesis of linezolid-induced lactic acidosis. Case report. ICU. A 64-year-old man who died with linezolid-induced lactic acidosis. Skeletal muscle was sampled at autopsy to study mitochondrial function. Lactic acidosis developed during continuous infusion of linezolid while oxygen consumption and oxygen extraction were diminishing from 172 to 52 mL/min/m and from 0.27 to 0.10, respectively. Activities of skeletal muscle respiratory chain complexes I, III, and IV, encoded by nuclear and mitochondrial DNA, were abnormally low, whereas activity of complex II, entirely encoded by nuclear DNA, was not. Protein studies confirmed stoichiometric imbalance between mitochondrial (cytochrome c oxidase subunits 1 and 2) and nuclear (succinate dehydrogenase A) DNA-encoded respiratory chain subunits. These findings were not explained by defects in mitochondrial DNA or transcription. There were no compensatory mitochondrial biogenesis (no induction of nuclear respiratory factor 1 and mitochondrial transcript factor A) or adaptive unfolded protein response (reduced concentration of heat shock proteins 60 and 70). Linezolid-induced lactic acidosis is associated with diminished global oxygen consumption and extraction. These changes reflect selective inhibition of mitochondrial protein synthesis (probably translation) with secondary mitonuclear imbalance. One novel aspect of linezolid toxicity that needs to be confirmed is blunting of reactive mitochondrial biogenesis and unfolded protein response.

Aqueous and vitreous penetration of linezolid and levofloxacin after oral administration.

PubMed

George, Jomy M; Fiscella, Richard; Blair, Michael; Rodvold, Keith; Ulanski, Lawrence; Stokes, John; Blair, Norman; Pontiggia, Laura

2010-12-01

To evaluate the time course of drug concentrations achieved in aqueous (AQ), vitreous (V), and serum (S) compartments after oral administration of linezolid and levofloxacin. Randomized, clinical trial. Clinical practice. Sixteen patients (16 eyes) undergoing vitrectomy who had not had a prior pars plana vitrectomy in the study eye were randomly assigned to one of 4 groups. AQ, V, and S samples were obtained from all subjects after single concomitant doses of linezolid 600 mg and levofloxacin 750 mg between 1 and 12 h before the procedure: group A = 1-3 h; group B = 3-6 h; group C = 6-9 h; group D = 9-12 h. AQ, V, and S concentrations of linezolid and levofloxacin. Overall mean concentrations ± standard deviation (μg/mL) achieved by linezolid in AQ, V, and S compartments were 3.32 ± 2.06, 2.98 ± 1.87, and 7.91 ± 3.94, respectively. Overall mean concentrations ±standard deviation (μg/mL) achieved by levofloxacin in AQ, V, and S compartments were 2.19 ± 1.92, 1.95 ± 1.27, and 7.38 ± 3.47, respectively. Single concomitant doses of linezolid and levofloxacin achieved AQ and V concentrations above the minimum inhibitory concentration for 90% of common ocular gram-positive and gram-negative pathogens up to 12 h after administration. The combination of linezolid and levofloxacin represents a viable option for the prophylaxis and management of endophthalmitis.

Antistaphylococcal activity of DX-619 alone and in combination with vancomycin, teicoplanin, and linezolid assessed by time-kill synergy testing.

PubMed

Credito, Kim; Lin, Genrong; Appelbaum, Peter C

2007-04-01

Time-kill synergy studies testing in vitro activity of DX-619 alone and with added vancomycin, teicoplanin, or linezolid against 101 Staphylococcus aureus strains showed synergy between DX-619 and teicoplanin at 12 to 24 h in 72 strains and between DX-619 and vancomycin in 28 strains. No synergy was found with linezolid, and no antagonism was observed with any combination.

Peripheral neuropathy in a diabetic child treated with linezolid for multidrug-resistant tuberculosis: a case report and review of the literature.

PubMed

Swaminathan, Aravind; du Cros, Philipp; Seddon, James A; Mirgayosieva, Shamsiya; Asladdin, Rajabov; Dusmatova, Zulfiya

2017-06-12

Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy. The global burden of DM is increasing, and DM has been associated with a three-fold increased risk of developing TB disease. TB and DM can be a challenging combination to treat. DM can inhibit the host immune response to tuberculosis infection; and TB and some anti-TB drugs can worsen glycaemic control. A child experiencing neuropathy that is a possible complication of both DM and linezolid used to treat TB has not been reported previously. We report peripheral neuropathy in a 15-year-old boy with type 1 DM, diagnosed with MDR-TB and additional resistance to injectable TB medications. The boy was treated with a linezolid-based regimen, but after 8 months developed peripheral neuropathy. It was unclear whether the neuropathy was caused by the DM or the linezolid therapy. He had clinical improvement following cessation of linezolid and was declared cured following 21 months of treatment. Following completion of treatment, nerve conduction studies demonstrated significant improvement in neuropathy. To the best of our knowledge, this is the first case of peripheral neuropathy reported in a diabetic child on long-term linezolid therapy for tuberculosis. This case study underlines the importance of stringent follow-up for side effects of linezolid, especially when associated with co-morbidity such as DM that increases the chances of adverse effects. The presence of both DM and TB should alert a physician to strive for optimal glycaemic control to minimize the risk of complications as well as optimizing the chances of recovery from TB. Our case report shows the need for close and frequent monitoring for neuropathy to enable early intervention and thereby a favourable outcome in children who may otherwise suffer a long-lasting, debilitating, and painful neuropathy.

Nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus treated with linezolid or vancomycin: A secondary economic analysis of resource use from a Spanish perspective.

PubMed

Rello, J; Nieto, M; Solé-Violán, J; Wan, Y; Gao, X; Solem, C T; De Salas-Cansado, M; Mesa, F; Charbonneau, C; Chastre, J

2016-11-01

Adopting a unique Spanish perspective, this study aims to assess healthcare resource utilization (HCRU) and the costs of treating nosocomial pneumonia (NP) produced by methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized adults using linezolid or vancomycin. An evaluation is also made of the renal failure rate and related economic outcomes between study groups. An economic post hoc evaluation of a randomized, double-blind, multicenter phase 4 study was carried out. Nosocomial pneumonia due to MRSA in hospitalized adults. The modified intent to treat (mITT) population comprised 224 linezolid- and 224 vancomycin-treated patients. Costs and HCRU were evaluated between patients administered either linezolid or vancomycin, and between patients who developed renal failure and those who did not. Analysis of HCRU outcomes and costs. Total costs were similar between the linezolid- (€17,782±€9,615) and vancomycin-treated patients (€17,423±€9,460) (P=.69). The renal failure rate was significantly lower in the linezolid-treated patients (4% vs. 15%; P<.001). The total costs tended to be higher in patients who developed renal failure (€19,626±€10,840 vs. €17,388±€9,369; P=.14). Among the patients who developed renal failure, HCRU (days on mechanical ventilation: 13.2±10.7 vs. 7.6±3.6 days; P=.21; ICU stay: 14.4±10.5 vs. 9.9±6.6 days; P=.30; hospital stay: 19.5±9.5 vs. 16.1±11.0 days; P=.26) and cost (€17,219±€8,792 vs. €20,263±€11,350; P=.51) tended to be lower in the linezolid- vs. vancomycin-treated patients. There were no statistically significant differences in costs per patient-day between cohorts after correcting for mortality (€1000 vs. €1,010; P=.98). From a Spanish perspective, there were no statistically significant differences in total costs between the linezolid and vancomycin pneumonia cohorts. The drug cost corresponding to linezolid was partially offset by fewer renal failure adverse events. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Linezolid

MedlinePlus

... that the oral suspension contains aspartame that forms phenylalanine. ... Linezolid may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: diarrhea headache nausea vomiting ...

Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections

PubMed Central

Weigelt, John; Itani, Kamal; Stevens, Dennis; Lau, William; Dryden, Matthew; Knirsch, Charles

2005-01-01

Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P = 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P < 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA. PMID:15917519

Antistaphylococcal Activity of DX-619 Alone and in Combination with Vancomycin, Teicoplanin, and Linezolid Assessed by Time-Kill Synergy Testing▿ †

PubMed Central

Credito, Kim; Lin, Genrong; Appelbaum, Peter C.

2007-01-01

Time-kill synergy studies testing in vitro activity of DX-619 alone and with added vancomycin, teicoplanin, or linezolid against 101 Staphylococcus aureus strains showed synergy between DX-619 and teicoplanin at 12 to 24 h in 72 strains and between DX-619 and vancomycin in 28 strains. No synergy was found with linezolid, and no antagonism was observed with any combination. PMID:17261625

Linezolid Injection

MedlinePlus

... vein. It is usually given as an intravenous infusion over 30 minutes to two hours twice a ... more often than prescribed by your doctor.Linezolid infusions are usually given by a doctor or nurse. ...

Linezolid resistant Staphylococcus haemolyticus: first case report from India.

PubMed

Gupta, Varsha; Garg, Shivani; Jain, Ruby; Garg, Sudhir; Chander, Jagdish

2012-10-01

Linezolid is being increasingly used in the treatment of infections with gram-positive organisms especially methicillin resistant Staphylococcal isolates. Though resistance to this antimicrobial is emerging but it is extremely rare. Here we document first case of linezolid resistant Staphylococcus haemolyticus (S.haemolyticus) from India. This organism was isolated from pus oozing from a postsurgical site in 61 year old male hailing from an adjoining state of Haryana. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

First outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium in an Irish hospital, February to September 2014.

PubMed

O'Driscoll, C; Murphy, V; Doyle, O; Wrenn, C; Flynn, A; O'Flaherty, N; Fenelon, L E; Schaffer, K; FitzGerald, S F

2015-12-01

An outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium (LRVREfm) occurred in the hepatology ward of a tertiary referral hospital in Ireland between February and September 2014. LRVREfm was isolated from 15 patients; pulsed-field gel electrophoresis confirmed spread of a single clone. This is the first report of an outbreak of linezolid-resistant vancomycin-resistant enterococcus in Ireland. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Efficacy, safety and pharmacokinetics of tedizolid versus linezolid in patients with skin and soft tissue infections in Japan - Results of a randomised, multicentre phase 3 study.

PubMed

Mikamo, Hiroshige; Takesue, Yoshio; Iwamoto, Yuji; Tanigawa, Takahiko; Kato, Masaharu; Tanimura, Yoko; Kohno, Shigeru

2018-06-01

The objective of this open-label, randomised (i.e. 2:1 ratio), Phase 3 study was to compare the efficacy and safety of tedizolid phosphate 200 mg, once-daily treatment with that of linezolid 600 mg, twice-daily treatment for 7-14 days in Japanese adult patients (N = 125) with skin and soft tissue infections (SSTIs) and/or for 7-21 days for those with SSTI-related bacteraemia, caused by confirmed or highly suspected methicillin-resistant Staphylococcus aureus (MRSA). Primary outcome was clinical cure rate at test-of-cure (TOC, in SSTI: 7-14 days, in bacteraemia: 4-6 weeks after end-of-therapy [EOT]) time point in the microbiologically evaluable MRSA (ME-MRSA) population (N = 39). Secondary endpoints were clinical and microbiological response rates at EOT. Safety parameters were evaluated in the safety analysis population up to follow up. Data analysis was descriptive in nature. Baseline characteristics of patients were similar between treatment groups. At TOC in the ME-MRSA population, clinical cure rate was similar in tedizolid phosphate (92.6%) and linezolid (88.9%) groups. At EOT, clinical cure (tedizolid phosphate: 93.1%, linezolid: 90.0%) and microbiological success (tedizolid phosphate: 93.1%, linezolid: 100.0%) rates were similar in the ME-MRSA population. Both treatments were well tolerated; overall treatment-emergent adverse events (TEAEs) in tedizolid phosphate (79.5%) and linezolid (75.6%) treatment groups were similar. Drug-related TEAEs were numerically lower with tedizolid phosphate versus linezolid (30.1%; 39.0%, respectively), as well as gastrointestinal (21.7%; 26.8%) and myelosuppression-related (2.4%; 22.0%) TEAEs. One death occurred in the linezolid group. Tedizolid phosphate may be an appropriate antibiotic for the treatment of SSTIs in Japanese adult patients. International clinical trial registration number: NCT01967225. Japanese clinical trial registration number: JapicCTI-132308. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[Characterization of methicillin- and linezolid-resistant Staphylococcus epidermidis and S. haemolyticus strains in a Spanish hospital].

PubMed

Lozano, Carmen; Aspiroz, Carmen; Gómez-Sanz, Elena; Tirado, Gabriel; Fortuño, Blanca; Zarazaga, Myriam; Torres, Carmen

2013-03-01

Linezolid resistance is mainly due to mutations in the 23S rRNA target. The aim of this study was to characterize linezolid and methicillin resistant Staphylococcus epidermidis (SE-LM(R)) and S. haemolyticus (SH-LM(R)) strains detected in a Spanish hospital. SE-LM(R) and SH-LM(R) strains obtained in the period June 2009-August 2011 in a second level hospital were recorded along with the epidemiological characteristics of the patients. These strains were typed, and their resistance, phenotype, genotype and the factors determining their virulence were analysed. Linezolid resistance was explained by the presence of G2603T mutation (23S rRNA) and aminoacid changes in L3 and L4 ribosomal proteins. The 25 SE-LM(R) strains belonged to sequence type ST2, presented SCCmec typeIII, and two different PFGE patterns. The two SH-LM(R) strains showed non-typeable SCCmec. SE-LM(R) strains harboured the resistance genes aac(6')-aph(2"), and dfrS1. SH-LM(R) strains contained these genes and the gene erm(C). No lincomycin resistance mechanism was identified in SE-LM(R) strains regardless of showing lincomycin resistance and diminished susceptibility to clindamycin. Linezolid resistance is of concern in hospitals, and requires continued vigilance. Several linezolid resistance mechanisms (mutation in 23S RNAr and amino acid changes in L3 and L4) were identified in this study. Copyright © 2012 Elsevier España, S.L. All rights reserved.

The activity of several newer antimicrobials against logarithmically multiplying M. leprae in mice.

PubMed

Burgos, Jasmin; de la Cruz, Eduardo; Paredes, Rose; Andaya, Cora Revelyn; Gelber, Robert H

2011-09-01

Moxifloxacin, rifampicin, rifapentine, linezolid, and PA 824, alone and in combination, have been previously administered, as single doses and five times daily doses, to M. leprae infected mice during lag phase multiplication and were each found to have some bactericidal activity. The fluroquinolones, ofloxacin, moxifloxacin and gatifloxacin, (50 mg/kg, 150 mg/kg and 300 mg/kg) and the rifamycins (5 mg/kg, 10 mg/kg, and 20 mg/kg), rifampicin and rifapentine, were evaluated alone and in combination for bactericidal activity against M. leprae using the mouse footpad model during logarithmic multiplication. Linezolid and PA 824 were similarly evaluated alone and linezolid in combination with rifampicin, minocycline and ofloxacin. The three fluroquinolones and rifamycins were found alone and in combination to be bactericidal at all dosage schedules. PA 824 had no activity against M. leprae, while linezolid at a dose of 25 mg/kg was bacteriostatic, and progressively more bactericidal at doses of 50 mg/kg and 100 mg/kg. No antagonisms were detected between any of these drugs when used in combinations. Moxifloxacin, gatifloxacin, rifapentine and linezolid were found bactericidal against rapidly multiplying M. leprae.

Optimal Clinical Doses of Faropenem, Linezolid, and Moxifloxacin in Children With Disseminated Tuberculosis: Goldilocks

PubMed Central

Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

2016-01-01

Background. When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC0–24) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC0–24/MIC ratios when treated with the same dose. Methods. We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis. The linezolid and moxifloxacin exposure targets were AUC0–24/MIC ratios of 62 and 122, and a faropenem percentage of time above MIC >60%, in combination therapy. A linezolid AUC0–24 of 93.4 mg × hour/L was target for toxicity. Population pharmacokinetic parameters of each drug and between-child variability, as well as MIC distribution, were used, and the cumulative fraction of response (CFR) was calculated. We also considered drug penetration indices into meninges, bone, and peritoneum. Results. The linezolid dose of 15 mg/kg in full-term neonates and infants aged up to 3 months and 10 mg/kg in toddlers, administered once daily, achieved CFR ≥ 90%, with <10% achieving linezolid AUC0–24 associated with toxicity. The moxifloxacin dose of 25 mg/kg/day achieved a CFR > 90% in infants, but the optimal dose was 20 mg/kg/day in older children. The faropenem medoxomil optimal dosage was 30 mg/kg 3–4 times daily. Conclusions. The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. PMID:27742641

A validated UPLC-MS/MS method for the analysis of linezolid and a novel oxazolidinone derivative (PH027) in plasma and its application to tissue distribution study in rabbits.

PubMed

Hedaya, Mohsen A; Thomas, Vidhya; Abdel-Hamid, Mohamed E; Kehinde, Elijah O; Phillips, Oludotun A

2017-01-01

Linezolid is the first approved oxazolidinone antibacterial agent, whereas PH027 is a novel compound of the same class that exhibits good in vitro antibacterial activity. The objective of this study was to develop an UPLC-MS/MS assay for the analysis of linezolid and PH027 in plasma and to apply the method for comparative pharmacokinetic and tissue distribution studies of both compounds. Plasma samples and calibrators were extracted with diethyl ether after addition of the internal standard solution. After evaporation of the ether layer, the residue was reconstituted in mobile phase and injected into UPLC-MS/MS. The mobile phase consisted of 2mM ammonium acetate buffer solution and acetonitrile (70:30) at a flow rate of 0.2ml/min. Separation was achieved using UPLC BEH C 18 column, and quantitative determination of the analytes was performed using multiple-reaction monitoring (MRM) scanning mode. The method was validated by analyzing quality control tissue homogenate samples, and was applied to analyze tissue homogenate samples obtained following IV injections of linezolid and PH027 in rabbits. The developed UPLC-MS/MS method was linear in the concentration range of 50-5000ng/ml. Validation of the method proved that the method's precision, selectivity and stability were all within the acceptable limits. Linezolid and PH027 concentrations were accurately determined in the quality control tissue homogenate samples, and analysis of samples obtained following IV administration of the two compounds showed that the tissue to plasma concentration ratio of PH027 was higher than that of linezolid probably due to its higher lipophilicity. The developed UPLC-MS/MS method for the analysis of linezolid and PH027 in rabbit's plasma can accurately determine the concentrations of these compounds in different tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective.

PubMed

von Dach, E; Morel, C M; Murthy, A; Pagani, L; Macedo-Vinas, M; Olearo, F; Harbarth, S

2017-09-01

Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection. We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity. Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin. Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Absolute Bioavailability and Pharmacokinetics of Linezolid in Hospitalized Patients Given Enteral Feedings

PubMed Central

Beringer, Paul; Nguyen, Megan; Hoem, Nils; Louie, Stan; Gill, Mark; Gurevitch, Michael; Wong-Beringer, Annie

2005-01-01

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens which are common causes of infections in hospitalized patients. Many such patients rely on the intravenous or enteral route for nutrition and drug administration. Therefore, the bioavailability of linezolid administered enterally in the presence of enteral feedings in hospitalized patients was examined. Eighteen subjects were assessed in a randomized single-dose crossover study; 12 received continuous enteral feedings, while 6 did not (controls). Both groups received linezolid 600 mg intravenously and orally (control) or enterally, with the alternate route of administration separated by a 24-h washout period. Pharmacokinetic parameters derived from noncompartmental and compartmental analysis incorporating linear and nonlinear elimination pathways were compared between groups: F, Ka, Vs, K23, K32, Vmax, Km, and K20 (bioavailability, absorption rate constant, volume of central compartment normalized to body weight, intercompartmental rate constants, maximum velocity, Michaelis-Menten constant, and elimination rate constant, respectively). Pharmacokinetic (PK) data were available from 17 patients. The linezolid oral suspension was rapidly and completely absorbed by either the oral or enteral route of administration. Bioavailability was unaltered in the presence of enteral feedings. PK estimates remain similar regardless of the model applied. At the therapeutic dose used, only slight nonlinearity in elimination was observed. A linezolid oral suspension may be administered via the enteral route to hospitalized patients without compromise in its excellent bioavailability and rapid rate of absorption. Compartmental pharmacokinetic analysis offers a more flexible study application, since bioavailability (F) can be estimated directly with intermixed intravenous/oral doses without a need for a washout period. PMID:16127039

A validated stability-indicating LC method for the separation of enantiomer and potential impurities of Linezolid using polar organic mode.

PubMed

Satyanarayana Raju, T; Vishweshwari Kutty, O; Ganesh, V; Yadagiri Swamy, P

2012-08-01

Although a number of methods are available for evaluating Linezolid and its possible impurities, a common method for separation if its potential impurities, degradants and enantiomer in a single method with good efficiency remain unavailable. With the objective of developing an advanced method with shorter runtimes, a simple, precise, accurate stability-indicating LC method was developed for the determination of purity of Linezolid drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. This method is capable of separating all the related substances of Linezolid along with the chiral impurity. This method can also be used for the estimation of assay of Linezolid in drug substance as well as in drug product. The method was developed using Chiralpak IA (250 mm×4.6 mm, 5 μm) column. A mixture of acetonitrile, ethanol, n-butyl amine and trifluoro acetic acid in 96:4:0.10:0.16 (v/v/v/v) ratio was used as a mobile phase. The eluted compounds were monitored at 254 nm. Linezolid was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness and system suitability.

Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy.

PubMed

Cunha, B A

2005-07-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a common skin coloniser and less commonly causes infection. MRSA colonisation should be contained by infection control measures and not treated. MRSA infections cause the same spectrum of infection as MSSA infections, i.e., skin/soft tissue infections, bone/joint infections, central IV line infections, and acute bacterial endocarditis (native valve/prosthetic valve). There is a discrepancy between in-vitro sensitivity and in-vivo effectiveness with MRSA. To treat MRSA infections, clinicians should select an MRSA drug with proven in-vivo effectiveness, i.e., daptomycin. Linezolid, quinupristin/dalfopristin, minocycline, or vancomycin, and not rely on in-vitro susceptibility data. For MRSA, doxycycline cannot be substituted for minocycline. Linezolid and minocycline are available for oral administration and both are also effective in treating MRSA CNS infections. Vancomycin is being used less due to side effects, (increasing MICs/resistance, VISA/VRSA), and increased VRE prevalence. The most potent anti-MRSA drug at the present time is daptomycin. Daptomycin is useful when rapid/effective therapy of MRSA bacteraemia/endocarditis is necessary. Daptomycin is also useful to treat persistent MRSA bacteraemias/MRSA treatment failures with other drugs, i.e., vancomycin. There is no difference in virulence between MSSA and MRSA infections if treatment is started early and with an agent that has in-vivo effectiveness.

Systematic Therapeutic Drug Monitoring for Linezolid: Variability and Clinical Impact

PubMed Central

Valerio, Maricela; Muñoz, Patricia; Alcalá, Luis; García-González, Xandra; Burillo, Almudena; Sanjurjo, María; Grau, Santiago

2017-01-01

ABSTRACT Linezolid serum trough (Cmin) and peak (Cmax) levels were determined prospectively in 90 patients. Adequate exposure was defined as a Cmin of 2 to 8 mg/liter. Therapy was empirical (73.3%) or targeted (26.7%). Wide interindividual variability in linezolid Cmin levels was recorded (0.1 to 25.2 μg/ml). Overall, 65.5% of the patients had out-of-range, 41.1% had subtherapeutic, and 24.4% had supratherapeutic trough levels. We did not find a correlation between abnormal levels and adverse events, in-hospital mortality, or overall poor outcome. PMID:28739788

In vitro activity of cadazolid against clinically relevant Clostridium difficile isolates and in an in vitro gut model of C. difficile infection.

PubMed

Chilton, C H; Crowther, G S; Baines, S D; Todhunter, S L; Freeman, J; Locher, H H; Athanasiou, A; Wilcox, M H

2014-03-01

We investigated the in vitro activity of cadazolid against 100 Clostridium difficile isolates and its efficacy in a simulated human gut model of C. difficile infection (CDI). MICs of cadazolid, metronidazole, vancomycin, moxifloxacin and linezolid were determined using agar incorporation for 100 C. difficile isolates, including 30 epidemic strains (ribotypes 027, 106 and 001) with reduced metronidazole susceptibility, 2 linezolid-resistant isolates and 2 moxifloxacin-resistant isolates. We evaluated the efficacy of two cadazolid dosing regimens (250 versus 750 mg/L twice daily for 7 days) to treat simulated CDI. Microflora populations, C. difficile total viable counts and spores, cytotoxin titres, possible emergence of cadazolid, linezolid or quinolone resistance, and antimicrobial concentrations were monitored throughout. Cadazolid was active against all (including linezolid- and moxifloxacin-resistant) C. difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The cadazolid geometric mean MIC was 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduced C. difficile viable counts and cytotoxin with no evidence of recurrence. Cadazolid levels persisted at 50-100-fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut microflora was limited, with the exception of bifidobacteria; Bacteroides fragilis group and Lactobacillus spp. counts were unaffected. There was no evidence for selection of strains resistant to cadazolid, quinolones or linezolid. Cadazolid activity was greater than other tested antimicrobials against 100 C. difficile strains. Cadazolid effectively treated simulated CDI in a gut model, with limited impact on the enumerated gut microflora and no signs of recurrence or emergence of resistance within the experimental timeframe.

A Faropenem, Linezolid, and Moxifloxacin Regimen for Both Drug-Susceptible and Multidrug-Resistant Tuberculosis in Children: FLAME Path on the Milky Way

PubMed Central

Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G.; Swaminathan, Soumya; Gumbo, Tawanda

2016-01-01

Background. The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination. Methods. We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic. First, we varied the percentage of time that faropenem persisted above minimum inhibitory concentration (TMIC) on the moxifloxacin-linezolid regimen. After choosing the best faropenem exposure, we performed experiments in which we varied the moxifloxacin and linezolid doses in the triple regimen. Finally, we performed longer-duration therapy validation experiments. Bacterial burden was quantified using both colony-forming units per milliliter (CFU/mL) and time to positivity (TTP). Kill slopes were modeled using exponential regression. Results. TTP was a more sensitive measure of bacterial burden than CFU/mL. A faropenem TMIC > 62% was associated with steepest microbial kill slope. Regimens of standard linezolid and moxifloxacin plus faropenem TMIC > 60%, as well as higher-dose moxifloxacin, achieved slopes equivalent to those of the standard regimen based by both TTP and CFU/mL over 28 days of treatment. Conclusions. We have developed an oral faropenem-linezolid-moxifloxacin (FLAME) regimen that is free of first-line drugs. The regimen could be effective against both multidrug-resistant and drug-susceptible tuberculosis in children. PMID:27742640

An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany.

PubMed

Patel, Dipen A; Michel, Andre; Stephens, Jennifer; Weber, Bertram; Petrik, Christian; Charbonneau, Claudie

2014-01-01

Across Europe, methicillin-resistant Staphylococcus aureus (MRSA) is considered to be the primary cause of nosocomial pneumonia (NP). In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system. A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros) was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival), failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days) or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10). The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with marginally lower costs (by €123) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP). Approximately 85%-87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). Sensitivity analysis yielded similar results. The model results show that linezolid is a cost-effective alternative to vancomycin for MRSA-confirmed NP, largely attributable to the higher clinical response rate of patients treated with linezolid.

Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo.

PubMed

Ni, Shuaishuai; Wei, Hanwen; Li, Baoli; Chen, Feifei; Liu, Yifu; Chen, Wenhua; Xu, Yixiang; Qiu, Xiaoxia; Li, Xiaokang; Lu, Yanli; Liu, Wenwen; Hu, Linhao; Lin, Dazheng; Wang, Manjiong; Zheng, Xinyu; Mao, Fei; Zhu, Jin; Lan, Lefu; Li, Jian

2017-10-12

Our previous work ( Wang et al. J. Med. Chem. 2016 , 59 , 4831 - 4848 ) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial.

PubMed

Lee, Ji Yeon; Kim, Deog Kyeom; Lee, Jung-Kyu; Yoon, Ho Il; Jeong, Ina; Heo, Eunyoung; Park, Young Sik; Lee, Jae Ho; Park, Sung Soo; Lee, Sang-Min; Lee, Chang-Hoon; Lee, Jinwoo; Choi, Sun Mi; Park, Jong Sun; Joh, Joon-Sung; Cho, Young-Jae; Lee, Yeon Joo; Kim, Se Joong; Hwang, Young Ran; Kim, Hyeonjeong; Ki, Jongeun; Choi, Hyungsook; Han, Jiyeon; Ahn, Heejung; Hahn, Seokyung; Yim, Jae-Joon

2017-02-13

Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis. This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total). This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future. ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection.

PubMed

Harbarth, S; von Dach, E; Pagani, L; Macedo-Vinas, M; Huttner, B; Olearo, F; Emonet, S; Uçkay, I

2015-01-01

The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection. We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1:1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854). Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI -9.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI -6.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/sulfamethoxazole and rifampicin group. Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

First Report of cfr-Carrying Plasmids in the Pandemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Staphylococcal Cassette Chromosome mec Type IV Clone

PubMed Central

Shore, Anna C.; Lazaris, Alexandros; Kinnevey, Peter M.; Brennan, Orla M.; Brennan, Gráinne I.; O'Connell, Brian; Feßler, Andrea T.; Schwarz, Stefan

2016-01-01

Linezolid is often the drug of last resort for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Linezolid resistance is mediated by mutations in 23S rRNA and genes for ribosomal proteins; cfr, encoding phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPSA) resistance; its homologue cfr(B); or optrA, conferring oxazolidinone and phenicol resistance. Linezolid resistance is rare in S. aureus, and cfr is even rarer. This study investigated the clonality and linezolid resistance mechanisms of two MRSA isolates from patients in separate Irish hospitals. Isolates were subjected to cfr PCR, PhLOPSA susceptibility testing, 23S rRNA PCR and sequencing, DNA microarray profiling, spa typing, pulsed-field gel electrophoresis (PFGE), plasmid curing, and conjugative transfer. Whole-genome sequencing was used for single-nucleotide variant (SNV) analysis, multilocus sequence typing, L protein mutation identification, cfr plasmid sequence analysis, and optrA and cfr(B) detection. Isolates M12/0145 and M13/0401 exhibited linezolid MICs of 64 and 16 mg/liter, respectively, and harbored identical 23S rRNA and L22 mutations, but M12/0145 exhibited the mutation in 2/6 23S rRNA alleles, compared to 1/5 in M13/0401. Both isolates were sequence type 22 MRSA staphylococcal cassette chromosome mec type IV (ST22-MRSA-IV)/spa type t032 isolates, harbored cfr, exhibited the PhLOPSA phenotype, and lacked optrA and cfr(B). They differed by five PFGE bands and 603 SNVs. Isolate M12/0145 harbored cfr and fexA on a 41-kb conjugative pSCFS3-type plasmid, whereas M13/0401 harbored cfr and lsa(B) on a novel 27-kb plasmid. This is the first report of cfr in the pandemic ST22-MRSA-IV clone. Different cfr plasmids and mutations associated with linezolid resistance in genotypically distinct ST22-MRSA-IV isolates highlight that prudent management of linezolid use is essential. PMID:26953212

Antipneumococcal activity of ceftobiprole, a novel broad-spectrum cephalosporin.

PubMed

Kosowska, Klaudia; Hoellman, Dianne B; Lin, Gengrong; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bozdogan, Bülent; Shapiro, Stuart; Appelbaum, Peter C

2005-05-01

Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant Staphylococcus aureus cephalosporin, was very highly active against a panel of 299 drug-susceptible and -resistant pneumococci, with MIC(50) and MIC(90) values (microg/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem, and ertapenem had lower MICs against all pneumococcal strains than amoxicillin, cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did not correlate with penicillin or macrolide susceptibility or resistance. All strains were susceptible to linezolid, quinupristin-dalfopristin, daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that at 1x and 2x the MIC, ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively. Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal against 10 to 12 strains at 2x the MIC. Azithromycin and clarithromycin were slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains at 2x the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin-dalfopristin and daptomycin showed marked killing at early time periods. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to yield mutants with high MICs towards this cephalosporin, and single-passage selection showed very low frequencies of spontaneous mutants with breakthrough MICs towards ceftobiprole.

Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin

PubMed Central

Kosowska, Klaudia; Hoellman, Dianne B.; Lin, Gengrong; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bozdogan, Bülent; Shapiro, Stuart; Appelbaum, Peter C.

2005-01-01

Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant Staphylococcus aureus cephalosporin, was very highly active against a panel of 299 drug-susceptible and -resistant pneumococci, with MIC50 and MIC90 values (μg/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem, and ertapenem had lower MICs against all pneumococcal strains than amoxicillin, cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did not correlate with penicillin or macrolide susceptibility or resistance. All strains were susceptible to linezolid, quinupristin-dalfopristin, daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that at 1× and 2× the MIC, ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively. Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal against 10 to 12 strains at 2× the MIC. Azithromycin and clarithromycin were slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains at 2× the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin-dalfopristin and daptomycin showed marked killing at early time periods. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to yield mutants with high MICs towards this cephalosporin, and single-passage selection showed very low frequencies of spontaneous mutants with breakthrough MICs towards ceftobiprole. PMID:15855516

Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation

PubMed Central

Pertinez, Henry; Bonnett, Laura; Hodel, Eva Maria; Dartois, Véronique; Johnson, John L; Caws, Maxine; Bolhuis, Mathieu; Alffenaar, Jan-Willem C; Davies, Geraint; Sloan, Derek J

2018-01-01

Abstract Objectives The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap. Methods We defined linezolid PK/PD targets for efficacy (fAUC0–24:MIC >119 mg/L/h) and safety (fCmin <1.38 mg/L). We extracted individual-level linezolid PK data from existing studies on TB patients and performed meta-analysis, producing summary estimates of fAUC0–24 and fCmin for published doses. Combining these with a published MIC distribution, we performed Monte Carlo simulations of target attainment. Results The efficacy target was attained in all simulated individuals at 300 mg q12h and 600 mg q12h, but only 20.7% missed the safety target at 300 mg q12h versus 98.5% at 600 mg q12h. Although suggesting 300 mg q12h should be used preferentially, these data were reliant on a single centre. Efficacy and safety targets were missed by 41.0% and 24.2%, respectively, at 300 mg q24h and by 44.6% and 27.5%, respectively, at 600 mg q24h. However, the confounding effect of between-study heterogeneity on target attainment for q24h regimens was considerable. Conclusions Linezolid dosing at 300 mg q12h may retain the efficacy of the 600 mg q12h licensed dosing with improved safety. Data to evaluate commonly used 300 mg q24h and 600 mg q24h doses are limited. Comprehensive, prospectively obtained PK/PD data for linezolid doses in drug-resistant TB treatment are required. PMID:29584861

Detection of a cfr(B) Variant in German Enterococcus faecium Clinical Isolates and the Impact on Linezolid Resistance in Enterococcus spp.

PubMed

Bender, Jennifer K; Fleige, Carola; Klare, Ingo; Fiedler, Stefan; Mischnik, Alexander; Mutters, Nico T; Dingle, Kate E; Werner, Guido

2016-01-01

The National Reference Centre for Staphylococci and Enterococci in Germany has received an increasing number of clinical linezolid-resistant E. faecium isolates in recent years. Five isolates harbored a cfr(B) variant gene locus the product of which is capable of conferring linezolid resistance. The cfr(B)-like methyltransferase gene was also detected in Clostridium difficile. Antimicrobial susceptibility was determined for cfr(B)-positive and linezolid-resistant E. faecium isolates and two isogenic C. difficile strains. All strains were subjected to whole genome sequencing and analyzed with respect to mutations in the 23S rDNA, rplC, rplD and rplV genes and integration sites of the cfr(B) variant locus. To evaluate methyltransferase function, the cfr(B) variant of Enterococcus and Clostridium was expressed in both E. coli and Enterococcus spp. Ribosomal target site mutations were detected in E. faecium strains but absent in clostridia. Sequencing revealed 99.9% identity between cfr(B) of Enterococcus and cfr of Clostridium. The methyltransferase gene is encoded by transposon Tn6218 which was present in C. difficile Ox3196, truncated in some E. faecium and absent in C. difficile Ox3206. The latter finding explains the lack of linezolid and chloramphenicol resistance in C. difficile Ox3206 and demonstrates for the first time a direct correlation of elevated linezolid MICs in C. difficile upon cfr acquisition. Tn6218 insertion sites revealed novel target loci for integration, both within the bacterial chromosome and as an integral part of plasmids. Importantly, the very first plasmid-association of a cfr(B) variant was observed. Although we failed to measure cfr(B)-mediated resistance in transformed laboratory strains the occurrence of the multidrug resistance gene cfr on putatively highly mobile and/or extrachromosomal DNA in clinical isolates is worrisome with respect to dissemination of antibiotic resistances.

Detection of a cfr(B) Variant in German Enterococcus faecium Clinical Isolates and the Impact on Linezolid Resistance in Enterococcus spp.

PubMed Central

Fleige, Carola; Klare, Ingo; Fiedler, Stefan; Mischnik, Alexander; Mutters, Nico T.; Dingle, Kate E.; Werner, Guido

2016-01-01

The National Reference Centre for Staphylococci and Enterococci in Germany has received an increasing number of clinical linezolid-resistant E. faecium isolates in recent years. Five isolates harbored a cfr(B) variant gene locus the product of which is capable of conferring linezolid resistance. The cfr(B)-like methyltransferase gene was also detected in Clostridium difficile. Antimicrobial susceptibility was determined for cfr(B)-positive and linezolid-resistant E. faecium isolates and two isogenic C. difficile strains. All strains were subjected to whole genome sequencing and analyzed with respect to mutations in the 23S rDNA, rplC, rplD and rplV genes and integration sites of the cfr(B) variant locus. To evaluate methyltransferase function, the cfr(B) variant of Enterococcus and Clostridium was expressed in both E. coli and Enterococcus spp. Ribosomal target site mutations were detected in E. faecium strains but absent in clostridia. Sequencing revealed 99.9% identity between cfr(B) of Enterococcus and cfr of Clostridium. The methyltransferase gene is encoded by transposon Tn6218 which was present in C. difficile Ox3196, truncated in some E. faecium and absent in C. difficile Ox3206. The latter finding explains the lack of linezolid and chloramphenicol resistance in C. difficile Ox3206 and demonstrates for the first time a direct correlation of elevated linezolid MICs in C. difficile upon cfr acquisition. Tn6218 insertion sites revealed novel target loci for integration, both within the bacterial chromosome and as an integral part of plasmids. Importantly, the very first plasmid-association of a cfr(B) variant was observed. Although we failed to measure cfr(B)-mediated resistance in transformed laboratory strains the occurrence of the multidrug resistance gene cfr on putatively highly mobile and/or extrachromosomal DNA in clinical isolates is worrisome with respect to dissemination of antibiotic resistances. PMID:27893790

Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

PubMed

Töpper, Christoph; Steinbach, Cathérine L; Dorn, Christoph; Kratzer, Alexander; Wicha, Sebastian G; Schleibinger, Michael; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

2016-10-01

Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration-time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200-400 mg*h/L, Cmin 2-10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted. Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48-618 mg*h/L, calculated Cmin 2.92, 0.0062-18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin <0.4 mg/L). The median unbound fraction in all 20 patients was 90.9%. Drug exposure after standard doses of linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.

In vitro activities of DA-7867, a novel oxazolidinone, against recent clinical isolates of aerobic and anaerobic bacteria.

PubMed

Yong, Dongeun; Yum, Jong Hwa; Lee, Kyungwon; Chong, Yunsop; Choi, Sung Hak; Rhee, Jae Keol

2004-01-01

In vitro activities of DA-7867, a novel oxazolidinone, were compared to those of linezolid and commonly used antimicrobials. DA-7867 had the lowest MIC for 90% of the aerobic gram-positive bacterial strains tested,

ANTI-ADHESIVE AND ANTI-BIOFILM ACTIVITIES IN VITRO OF LINEZOLID, VANCOMYCIN, TIGECYCLINE AND DAPTOMYCIN AGAINST STAPHYLOCOCCUS HAEMOLYTICUS.

PubMed

Juda, Marek; Helon, Pawel; Malm, Anna

2016-11-01

Biofilm may be formed on wide variety of surfaces, including indwelling medical devices, leading to several infectious diseases, e.g., bacteremia and sepsis. The most,important pathogens related with infections associated with medical devices are coagulase-negative staphylococci, including Staphylococcus haeinolyticus - bacterial species which express quite often the multidrug resistance. The four clinical multiresistant and methicillin-resistant S. haenzolyticus were included in the present study. The evaluation of drug susceptibility was performed by using disc-diffusion method and broth microdilution method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The biofilm formation on the Nelaton catheter and the effect of linezolid, vancomycin, tigecycline and daptomycin on the biofilm formation and disruption of mature structure was based on the method with TTC (2,3,5-triphenyltetrazolium chloride). The adhesion process of S. haenzolyticus to the Nelaton catheter was inhibited by antibiotics, as follows: line-zolid at concentration 0.25-0.5 x MIC, vancomycin - concentration 0.5 x MIC, tigecycline - concentration 0.25-4 x MIC and daptomycin - concentration 0.06-1 x MIC, depending on the isolate. Linezolid inhibited the biofilm formation at concentration between 0.5-1 x MIC, vancomycin - 1-2 x MIC, tigecycline - 0.5-4 x MIC and daptomycin - 0.06-2 x MIC. The concentration of linezolid eradicating the mature biofilm was found to be 1-2 x MIC, vancomycin - 2-8 x MIC, tigecycline - 2-4 x MIC and daptomycin - 0.06-2 x MIC. The most active antibiotic against S. haentolyticus biofilm formation and disruption of mature structure seems to be daptomycin.

In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA) Mediated Orthopaedic Device Related Infections

PubMed Central

Kaur, Sandeep; Harjai, Kusum; Chhibber, Sanjay

2016-01-01

Staphylococcus comprises up to two-thirds of all pathogens in orthopaedic implant infections with two species respectively Staphylococcus aureus and Staphylococcus epidermidis, being the predominate etiological agents isolated. Further, with the emergence of methicillin-resistant S. aureus (MRSA), treatment of S. aureus implant infections has become more difficult, thus representing a devastating complication. Use of local delivery system consisting of S.aureus specific phage along with linezolid (incorporated in biopolymer) allowing gradual release of the two agents at the implant site represents a new, still unexplored treatment option (against orthopaedic implant infections) that has been studied in an animal model of prosthetic joint infection. Naked wire, hydroxypropyl methylcellulose (HPMC) coated wire and phage and /or linezolid coated K-wire were surgically implanted into the intra-medullary canal of mouse femur bone of respective groups followed by inoculation of S.aureus ATCC 43300(MRSA). Mice implanted with K-wire coated with both the agents i.e phage as well as linezolid (dual coated wires) showed maximum reduction in bacterial adherence, associated inflammation of the joint as well as faster resumption of locomotion and motor function of the limb. Also, all the coating treatments showed no emergence of resistant mutants. Use of dual coated implants incorporating lytic phage (capable of self-multiplication) as well as linezolid presents an attractive and aggressive early approach in preventing as well as treating implant associated infections caused by methicillin resistant S. aureus strains as assessed in a murine model of experimental joint infection. PMID:27333300

Development and validation of a fast micro-extraction by packed sorbent UHPLC-PDA method for the simultaneous determination of linezolid and ciprofloxacin in human plasma from patients with hospital-acquired pneumonia.

PubMed

Ferrone, Vincenzo; Carlucci, Maura; Cotellese, Roberto; Raimondi, Paolo; Cichella, Annadomenica; Marco, Lorenzo Di; Carlucci, Giuseppe

2017-03-01

An ultra high-performance liquid chromatographic (UHPLC) method with PDA detection was developed and validated for the simultaneous quantification of linezolid and ciprofloxacin in human plasma and applied in hospital acquired pneumonia patients (HAP). The method uses a semi-automated microextraction by packed sorbent for sample preparation. All parameters in the extraction step (pH, sample volume, sample dilution and number of aspiration - ejection cycles) and in the desorption step (percentage of acetonitrile in the solvent of elution and number of aspirations of elution solvent through the device) were statistically significant when the recovery was used as response. The method showed good linearity with correlation coefficients, r 2 >0.9995 for the two drugs, as well as high precision (RSD%<9.77% in each case), accuracy ranged from -6.2% to +8.2. The limit of quantification of the two drugs was established at 0.01 and 0.02μg/mL for ciprofloxacin and linezolid, respectively. Linezolid, ciprofloxacin and internal standard were extracted from human plasma with a mean recovery ranging from 92.4% to 97.4%. During validation, the concentrations of linezolid and ciprofloxacin were found to be stable after 3 freeze-thaw cycles and for at least 24h after extraction. This method will subsequently be used to quantify the drugs dosage in patients with HAP to establish if the dosage regimen given is sufficient to eradicate the infection at the target site. Copyright © 2016 Elsevier B.V. All rights reserved.

In vitro activities of CG400549, a novel FabI inhibitor, against recently isolated clinical staphylococcal strains in Korea.

PubMed

Yum, Jong Hwa; Kim, Chang Ki; Yong, Dongeun; Lee, Kyungwon; Chong, Yunsop; Kim, Cheol Min; Kim, Jeong Mi; Ro, Seonggu; Cho, Joong Myung

2007-07-01

The in vitro activities of CG400549, a novel FabI inhibitor, were compared to those of linezolid and commonly used antimicrobials against recent bacterial isolates. CG400549 had an MIC(90) of 0.5 microg/ml for Staphylococcus aureus strains and was more potent than either linezolid or vancomycin.

Scleritis Caused by In Vitro Linezolid-Resistant Nocardia asteroides

PubMed Central

Tuli, Sonal

2014-01-01

Purpose. To describe a case of postoperative scleritis caused by a novel strain of Nocardia resistant to linezolid and trimethoprim-sulfamethoxazole (TMP-SMX). Methods. Case report of a patient with microbiologically proven scleritis due to Nocardia asteroides. Results. The patient presented with pain, redness, and nodules on the sclera three months following pterygium excision with mitomycin C and amniotic membrane placement. As no response was noted with empiric treatment for bacterial scleritis, debridement was performed. The cytopathology report showed gram positive filamentous bacteria. A presumptive diagnosis of Nocardia scleritis was made and therapy was initiated based on a literature review on treatments for Nocardia infections. Cultures returned growing Nocardia asteroides. Antibiotic sensitivity testing revealed resistance to linezolid and TMP-SMX which are the traditional drugs of choice for Nocardia. The patient was treated with amikacin and imipenem as well as extensive debridement with pedicle grafts. The patient's scleritis resolved with a good visual outcome. Conclusions. Cultures should be obtained in all cases of necrotizing scleritis in patients with a recent history of conjunctival surgery to rule out unusual organisms such as Nocardia. Although literature states that resistance to linezolid and TMP-SMX is rare in Nocardia, sensitivity testing can be useful in unresponsive cases. PMID:25400961

Scleritis Caused by In Vitro Linezolid-Resistant Nocardia asteroides.

PubMed

Gonzalez, Andres; Fakhar, Kaihan; Gubernick, David; Tuli, Sonal

2014-01-01

Purpose. To describe a case of postoperative scleritis caused by a novel strain of Nocardia resistant to linezolid and trimethoprim-sulfamethoxazole (TMP-SMX). Methods. Case report of a patient with microbiologically proven scleritis due to Nocardia asteroides. Results. The patient presented with pain, redness, and nodules on the sclera three months following pterygium excision with mitomycin C and amniotic membrane placement. As no response was noted with empiric treatment for bacterial scleritis, debridement was performed. The cytopathology report showed gram positive filamentous bacteria. A presumptive diagnosis of Nocardia scleritis was made and therapy was initiated based on a literature review on treatments for Nocardia infections. Cultures returned growing Nocardia asteroides. Antibiotic sensitivity testing revealed resistance to linezolid and TMP-SMX which are the traditional drugs of choice for Nocardia. The patient was treated with amikacin and imipenem as well as extensive debridement with pedicle grafts. The patient's scleritis resolved with a good visual outcome. Conclusions. Cultures should be obtained in all cases of necrotizing scleritis in patients with a recent history of conjunctival surgery to rule out unusual organisms such as Nocardia. Although literature states that resistance to linezolid and TMP-SMX is rare in Nocardia, sensitivity testing can be useful in unresponsive cases.

Cost-effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug-resistant tuberculosis in Germany.

PubMed

Wirth, Daniel; Dass, Ramesh; Hettle, Robert

2017-03-08

Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective. A cohort-based Markov model was developed to simulate the incremental cost-effectiveness ratio of bedaquiline plus BR, delamanid plus BR, or linezolid plus BR versus BR alone in the treatment of MDR-TB, over a 10-year time horizon. Effectiveness of treatment was evaluated in Quality-Adjusted Life-Years (QALYs) and Life-Years Gained (LYG), using inputs from clinical trials for bedaquiline and delamanid and from a German observational study for linezolid. Cost data were obtained from German Drug Directory costs (€/2015), published literature, and expert opinion. A 3% yearly discount rate was applied. Probabilistic and deterministic sensitivity analyses were conducted. The total discounted costs per-patient were €85,575 for bedaquiline plus BR, €81,079 for delamanid plus BR, and €80,460 for linezolid plus BR, compared with a cost of €60,962 for BR alone. The total discounted QALYs per-patient were 5.95 for bedaquiline plus BR, 5.36 for delamanid plus BR, and 3.91 for linezolid plus BR, compared with 3.68 for BR alone. All interventions were therefore associated with higher QALYs and higher costs than BR alone, with incremental costs per QALY gained of €22,238 for bedaquiline, €38,703 for delamanid, and €87,484 for linezolid, versus BR alone. In a fully incremental analysis, bedaquiline plus BR was the most cost-effective treatment option at thresholds greater than €22,000 per QALY gained. In probabilistic analyses, the probability that bedaquiline plus BR was the most cost-effective treatment strategy at a willingness-to-pay threshold of €30,000 was 54.5%, compared with 22.9% for BR alone, 18.2% for delamanid plus BR, and 4.4% for linezolid. In Germany, the addition of bedaquiline, delamanid, or linezolid to a BR would result in QALY gains over BR alone. Based on this analysis, bedaquiline is likely to be the most cost-effective intervention for the treatment of MDR-TB, when added to a BR regimen at thresholds greater than €22,000 per QALY.

Successful long-term treatment of cerebral nocardiosis with unexpectedly low doses of linezolid in an immunocompromised patient receiving complex polytherapy.

PubMed

Pea, Federico; Cojutti, Piergiorgio; Pagotto, Alberto; Cristini, Francesco; Furlanut, Mario; Viale, Pierluigi

2012-06-01

Cerebral nocardiosis is a severe infection that carries the highest mortality rate among all bacterial cerebral abscesses. We report on a case in an immunocompromised patient which was successfully treated with unexpectedly low doses of linezolid. Therapeutic drug monitoring was very helpful in highlighting issues of poor compliance and of drug-drug interactions.

In Vitro Activities of CG400549, a Novel FabI Inhibitor, against Recently Isolated Clinical Staphylococcal Strains in Korea▿

PubMed Central

Yum, Jong Hwa; Kim, Chang Ki; Yong, Dongeun; Lee, Kyungwon; Chong, Yunsop; Kim, Cheol Min; Kim, Jeong Mi; Ro, Seonggu; Cho, Joong Myung

2007-01-01

The in vitro activities of CG400549, a novel FabI inhibitor, were compared to those of linezolid and commonly used antimicrobials against recent bacterial isolates. CG400549 had an MIC90 of 0.5 μg/ml for Staphylococcus aureus strains and was more potent than either linezolid or vancomycin. PMID:17420210

The potential role of newer gram-positive antibiotics in the setting of osteomyelitis of adults.

PubMed

Moenster, Ryan P; Linneman, Travis W; Call, William B; Kay, Chad L; McEvoy, Theresa A; Sanders, Jamie L

2013-04-01

To summarize available literature regarding the potential role of linezolid, daptomycin, telavancin, tigecycline and ceftaroline for the treatment of osteomyelitis caused by resistant gram-positive organisms. Literature was obtained through PubMed searches from January 1980 to October 2011 using the terms osteomyelitis, bone, linezolid, daptomycin, telavancin, tigecycline and ceftaroline. Results were limited to those published in English. All articles identified from the PubMed searches were evaluated. Any published data related to bone penetration (animal or human) or clinical outcomes in adult osteomyelitis of these agents were included in the review. Animal models report bone concentrations of 2·3 mcg/dL (vertebral) for linezolid, 0·45 mcg/mL (tibiae) for daptomycin, 0·78 mcg/mL (tibiae) for tigecycline and 0·27 mcg/mL (tibiae) for telavancin; no data are available for ceftaroline. Human studies demonstrate bone concentrations of 4·6, 17·0 and 3·9 mcg/mL (sternal, metatarsal and cancellous bone respectively) for linezolid, 4·7 mcg/mL (metatarsal) for daptomycin and 0·078 mcg/mL (unspecified) for tigecycline; no data are available for telavancin and ceftaroline. Retrospective cohort data, and prospective/retrospective case series support the use of linezolid in this setting; however, side-effects may limit use. Retrospective and prospective cohort data support daptomycin use. A retrospective case series is available supporting the use of telavancin. No data are available supporting clinical effectiveness for ceftaroline or tigecycline in the setting of osteomyelitis. Limited data are available evaluating the safety and efficacy of these agents in osteomyelitis in adults. Daptomycin and telavancin may be potential alternatives or second-line agents to vancomycin in selected patients. Linezolid, because of an increase in clinically important ADRs with prolonged use, should be reserved as a second- or third-line agent. Due to a lack of clinical data and poor bone penetration, along with concerns regarding outcomes in severe infections, tigecycline's potential is limited. Little data exist regarding ceftaroline use in osteomyelitis. © 2013 Blackwell Publishing Ltd.

Nocardia asteroides peritoneal dialysis-related peritonitis: First case in pediatrics, treated with protracted linezolid.

PubMed

El-Naggari, Mohamed; El Nour, Ibtisam; Al-Nabhani, Dana; Al Muharrmi, Zakaria; Gaafar, Heba; Abdelmogheth, Anas A W

2016-01-01

Nocardia asteroides is a rare pathogen in peritoneal dialysis-related peritonitis. We report on a 13-year-old female with Nocardia asteroides peritonitis complicated by an intra-abdominal abscess. Linezolid was administered intravenously for 3 months and followed by oral therapy for an additional 5 months with close monitoring for adverse effects. The patient was discharged after 3 months of hospitalization on hemodialysis. The diagnosis and management of such cases can be problematic due to the slow growth and difficulty of identifying Nocardia species. The optimal duration of treatment for Nocardia peritonitis is not known. Linezolid can be used for prolonged periods in cases of trimethoprim/sulfamethoxazole-resistant cases with close monitoring for adverse effects. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Linezolid-resistant Staphylococcus haemolyticus and Staphylococcus hominis: single and double mutations at the domain V of 23S rRNA among isolates from a Rio de Janeiro hospital.

PubMed

Chamon, Raiane Cardoso; Iorio, Natalia Lopes Pontes; Cavalcante, Fernanda Sampaio; Teodoro, Cristiane R S; de Oliveira, Ana Paula Chaves; Maia, Fernanda; dos Santos, Kátia Regina Netto

2014-12-01

In this work, the molecular and phenotypic antimicrobial resistance and clonal diversity of 10 linezolid-resistant Staphylococcus spp. isolates were investigated. The 7 Staphylococcus haemolyticus isolates presented Staphylococcal cassete chromosome mec (SCCmec) V and belonged to the same pulsed-field gel electrophoresis pulsotype. Their MICs for oxacillin, vancomycin, and linezolid were ≥ 256 μg/mL, 1-4 μg/mL, and 8-16 μg/mL, respectively. The 3 S. hominis presented MIC values 32 to >256 μg/mL, 2-4 μg/mL, and 12-24 μg/mL, and all carried the nontypeable SCCmec (ccr1 + mecA class) and belonged to 2 different genotypes. The cfr gene was not found, but the mutation G2603T was detected in S. haemolyticus and C2190T and G2603T in Staphylococcus hominis in 23S rRNA. This study demonstrates the spread of a linezolid-resistant S. haemolyticus genotype and, for the first time, describes the mutation C2190T among S. hominis isolates with a double mutation in Brazil. Copyright © 2014 Elsevier Inc. All rights reserved.

Adsorption of various antimicrobial agents to endotoxin removal polymyxin-B immobilized fiber (Toraymyxin®). Part 2: Adsorption of two drugs to Toraymyxin PMX-20R cartridges.

PubMed

Shimokawa, Ken-ichi; Takakuwa, Ryotaro; Wada, Yuko; Yamazaki, Noriko; Ishii, Fumiyoshi

2013-01-01

In our previous study, the degree of adsorption of 9 representative antimicrobial agents to Toraymyxin(®) PMX-F sheets was quantitatively evaluated. As a result, the adsorption rate was 22.1% for Linezolid in the presence of serum. Therefore, we investigated whether two types of antimicrobial agents (Ciprofroxacin and Linezolid) can be better adsorbed on PMX-F sheets. When the number of PMX-F sheets was increased in a step wise manner, specifically 2, 4, 6, 8 and 12, the adsorption rate increased linearly. In addition, the adsorption to polymyxin-B immobilized fiber (Toraymyxin(®) PMX-20R) cartridges, widely used to remove endotoxins from circulating blood in the treatment of sepsis, was quantitatively evaluated. As a result, in the presence of serum, Linezolid showed adsorption to PMX-20R, and the adsorption rate after 2h was 54.5%, and that after 4h was 65.8%. The results of this study suggest the necessity of monitoring blood antimicrobial concentration during treatment for sepsis with Linezolid, which showed adsorption to PMX-20R in an environment close to a clinical environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Pasteurella multocida infected total knee arthroplasty: a case report and review of the literature

PubMed Central

Ferguson, KB; Bharadwaj, R; MacDonald, A; Syme, B

2014-01-01

Pasteurella multocida is a rare cause of prosthetic joint infection. This infection generally follows significant animal contact, usually licks and scratches. We report a case of P multocida infection that was treated with linezolid with salvage of the implant. Linezolid is generally active against Gram-positive organisms only with the exception of Pasteurella, which is Gram-negative. We extensively review the previous reported cases of implant infection with P multocida. PMID:24780653

Cellular pharmacodynamics of the novel biaryloxazolidinone radezolid: studies with infected phagocytic and nonphagocytic cells, using Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, and Legionella pneumophila.

PubMed

Lemaire, Sandrine; Kosowska-Shick, Klaudia; Appelbaum, Peter C; Verween, Gunther; Tulkens, Paul M; Van Bambeke, Françoise

2010-06-01

Radezolid is a novel biaryloxazolidinone in clinical development which shows improved activity, including against linezolid-resistant strains. In a companion paper (29), we showed that radezolid accumulates about 11-fold in phagocytic cells, with approximately 60% of the drug localized in the cytosol and approximately 40% in the lysosomes of the cells. The present study examines its activity against (i) bacteria infecting human THP-1 macrophages and located in different subcellular compartments (Listeria monocytogenes, cytosol; Legionella pneumophila, vacuoles; Staphylococcus aureus and Staphylococcus epidermidis, mainly phagolysosomal), (ii) strains of S. aureus with clinically relevant mechanisms of resistance, and (iii) isogenic linezolid-susceptible and -resistant S. aureus strains infecting a series of phagocytic and nonphagocytic cells. Radezolid accumulated to similar levels ( approximately 10-fold) in all cell types (human keratinocytes, endothelial cells, bronchial epithelial cells, osteoblasts, macrophages, and rat embryo fibroblasts). At equivalent weight concentrations, radezolid proved consistently 10-fold more potent than linezolid in all these models, irrespective of the bacterial species and resistance phenotype or of the cell type infected. This results from its higher intrinsic activity and higher cellular accumulation. Time kill curves showed that radezolid's activity was more rapid than that of linezolid both in broth and in infected macrophages. These data suggest the potential interest of radezolid for recurrent or persistent infections where intracellular foci play a determinant role.

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin

PubMed Central

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care. PMID:29670380

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin.

PubMed

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.

Treatment of methicillin-resistant Staphylococcus aureus: vancomycin and beyond.

PubMed

Holmes, Natasha E; Tong, Steven Y C; Davis, Joshua S; van Hal, Sebastiaan J

2015-02-01

There has been a welcome increase in the number of agents available for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target. Numerous practicalities, however, would need to be resolved before implementation. Lipoglycopeptides as a class show excellent in vitro potency. Their long half-lives and complex PKs may preclude these agents being used in critically ill patients. Anti-MRSA cephalosporins provide great promise in the treatment of MRSA. These agents, despite broad-spectrum activity, should be reserved for patients with MRSA infections as it is likely that usage will be associated with increased rates of resistance. Daptomycin is currently the only antibiotic to have shown noninferiority to vancomycin in the treatment of MRSA bacteremia. The results of an open-labeled trial to address the superiority of daptomycin compared with vancomycin in reduced vancomycin susceptibility infections are eagerly anticipated. No drug to date has shown superiority to vancomycin in the treatment of MRSA infections with the possible exception of linezolid in hospital-acquired pneumonia (HAP), making linezolid an important option in the treatment of MRSA-proven HAP. Whether these strengths and features are agent or class specific are unclear but will likely be answered with the marketing of tedizolid. There are insufficient data to recommend either quinupristin/dalfopristin or tigecycline, as first line in the treatment of severe MRSA infections. These agents however remain options in patients with no other alternatives. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Linezolid Is Associated with Serotonin Syndrome in a Patient Receiving Amitriptyline, and Fentanyl: A Case Report and Review of the Literature

PubMed Central

Savvari, Paraskevi; Kontogiannis, Sofoklis

2013-01-01

We report a unique case of an adverse interaction between the oxazolidinone antibiotic linezolid, the tricyclic antidepressant amitriptyline and the opioid analgesic fentanyl in a 68-year-old woman with advanced ischemic peripheral arterial disease and sepsis, under empirical antibiotic treatment. We also summarize the current relevant literature as identified via PubMed, EMBASE, and PsycINFO as well as reference sections of selected articles. PMID:23533900

Determination of Residual Solvents in Linezolid by Static Headspace GC

PubMed Central

Feng, Xiao-Zhen; Han, Guo-Cheng; Qin, Jianhe; Yin, Shi-min; Chen, Zhencheng

2016-01-01

A headspace gas chromatographic method was developed for the determination of residual solvents in linezolid active substances. The solvents include petroleum ether (60–90°C), acetone, tetrahydrofuran, ethyl acetate, methanol, dichloromethane (DCM) and pyridine. The method showed the possibility to detect the tested solvents with a linear determination correlation coefficient (r) greater than 0.9995 except for petroleum ether (0.9980). The limits of detection ranged between 0.12 μg/mL (petroleum ether) and 3.56 μg/mL (DCM), and the limits of quantity ranged between 0.41 μg/mL (petroleum ether) and 11.86 μg/mL (DCM). The method achieved good accuracy (recoveries ranging from 92.8 to 102.5%) and precision for both run-to-run and day-to-day assay (relative standard deviation ranging from 0.4 to 1.3%) for all seven solvents concerned, which were applied in the quality control of three batches of linezolid successfully. PMID:26657409

Diabetic foot infections: microbiological aspects, current and future antibiotic therapy focusing on methicillin-resistant Staphylococcus aureus.

PubMed

Ambrosch, Andreas; Haefner, Simone; Jude, Edward; Lobmann, Ralf

2011-12-01

Diabetic patients are at increased risk of complicated skin, skin structure and bone infections including infections of diabetic foot ulcerations (DFU). Analyses of epidemiology and microbial pathogenicity show that staphylococci seem to be predestined to induce such infections. In addition, multidrug resistance particularly due to an increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) seems to be the challenge for effective antibiotic therapy. With regard to infections with MRSA, classical agents like vancomycin, linezolid, fosfomycin or trimethroprim-sulphametoxazol might be agents of choice in DFU. New-generation drugs including broad-spectrum tetracyclines like tigecycline, first and second generation of cyclic lipopeptides, anti-MRSA β-lactams including ceftobiprole and anti-MRSA antibodies are developed or in progress and the hope for the future. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Efficacy of tigecycline alone and in combination with gentamicin in the treatment of experimental endocarditis due to linezolid-resistant Enterococcus faecium.

PubMed

Pontikis, Konstantinos; Pefanis, Angelos; Tsaganos, Thomas; Tzepi, Ira-Maria; Carrer, Dionyssia-Pinelopi; Giamarellou, Helen

2013-07-01

We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log10-CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment groups.

Efficacy of Tigecycline Alone and in Combination with Gentamicin in the Treatment of Experimental Endocarditis Due to Linezolid-Resistant Enterococcus faecium

PubMed Central

Pefanis, Angelos; Tsaganos, Thomas; Tzepi, Ira-Maria; Carrer, Dionyssia-Pinelopi; Giamarellou, Helen

2013-01-01

We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log10-CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment groups. PMID:23587961

Recommendations to address the difficulties encountered when determining linezolid resistance from whole genome sequencing data.

PubMed

Beukers, Alicia G; Hasman, Henrik; Hegstad, Kristin; van Hal, Sebastiaan J

2018-05-29

Mutations associated with linezolid resistance within the V domain of 23S rRNA are annotated using an Escherichia coli numbering system. The 23S rRNA gene varies in length, nucleotide sequence and copy number between bacterial species. Consequently, this numbering system is not intuitive and can lead to confusion when locating mutation sites using whole genome sequencing data. Using the mutation G2576T as an example, we demonstrate the difficulties associated with using the E. coli numbering system. © Crown copyright 2018.

Mutations in Ribosomal Protein L3 Are Associated with Oxazolidinone Resistance in Staphylococci of Clinical Origin▿

PubMed Central

Locke, Jeffrey B.; Hilgers, Mark; Shaw, Karen Joy

2009-01-01

Following recent reports of ribosomal protein L3 mutations in laboratory-derived linezolid-resistant (LZDr) Staphylococcus aureus, we investigated whether similar mutations were present in LZDr staphylococci of clinical origin. Sequence analysis of a variety of LZDr isolates revealed two L3 mutations, ΔSer145 (S. aureus NRS127) and Ala157Arg (Staphylococcus epidermidis 1653059), both occurring proximal to the oxazolidinone binding site in the peptidyl transferase center. The oxazolidinone torezolid maintained a ≥8-fold potency advantage over linezolid for both strains. PMID:19805557

Simultaneous determination and stability studies of linezolid, meropenem and vancomycin in bacterial growth medium by high-performance liquid chromatography.

PubMed

Wicha, Sebastian G; Kloft, Charlotte

2016-08-15

For pharmacokinetic/pharmacodynamic (PK/PD) assessment of antibiotics combinations in in vitro infection models, accurate and precise quantification of drug concentrations in bacterial growth medium is crucial for derivation of valid PK/PD relationships. We aimed to (i) develop a high-performance liquid chromatography (HPLC) assay to simultaneously quantify linezolid (LZD), vancomycin (VAN) and meropenem (MER), as typical components of broad-spectrum antibiotic combination therapy, in bacterial growth medium cation-adjusted Mueller-Hinton broth (CaMHB) and (ii) determine the stability profiles of LZD, VAN and MER under conditions in in vitro infection models. To separate sample matrix components, the final method comprised the pretreatment of 100μL sample with 400μL methanol, the evaporation of supernatant and its reconstitution in water. A low sample volume of 2μL processed sample was injected onto an Accucore C-18 column (2.6μm, 100×2.1mm) coupled to a Dionex Ultimate 3000 HPLC+ system. UV detection at 251, 240 and 302nm allowed quantification limits of 0.5, 2 and 0.5μg/mL for LZD, VAN and MER, respectively. The assay was successfully validated according to the relevant EMA guideline. The rapid method (14min) was successfully applied to quantify significant degradation of LZD, VAN and MER in in vitro infection models: LZD was stable, VAN degraded to 90.6% and MER to 62.9% within 24h compared to t=0 in CaMHB at 37°C, which should be considered when deriving PK/PD relationships in in vitro infection models. Inclusion of further antibiotics into the flexible gradient-based HPLC assay seems promising. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia

PubMed Central

Lee, Hao-Yuan; Chen, Chyi-Liang; Liu, Shu-Ying; Yan, Yu-Shan; Chang, Chee-Jen; Chiu, Cheng-Hsun

2015-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial. Methods A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed. Results Most MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759). Conclusions Giving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality. PMID:26295150

Delafloxacin for the treatment of respiratory and skin infections.

PubMed

Bassetti, Matteo; Della Siega, Paola; Pecori, Davide; Scarparo, Claudio; Righi, Elda

2015-03-01

There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infections including complicated skin and skin structure infections and respiratory tract infections. In this review, the authors report the microbiological spectrum of activity of delafloxacin as well as its pharmacokinetic characteristics. They also report the results of recent studies investigating its safety and efficacy. The profile of delafloxacin offers several advantages. Delafloxacin presents a broad spectrum of activity against pathogens involved in respiratory infections and complicated skin and skin structure infections (SSSIs), including methicillin-resistant Staphylococcus aureus. It has also shown activity against Gram-negative pathogens, such as quinolone-susceptible and -resistant strains of Escherichia coli and Klebsiella pneumoniae and quinolone-susceptible Pseudomonas aeruginosa. The availability of an oral formulation supports its use in sequential therapy. The efficacy and tolerability of delafloxacin have been demonstrated in Phase II clinical trials in comparison with moxifloxacin for respiratory infections and linezolid and vancomycin in SSSIs. Compared with other quinolones such as moxifloxacin, delafloxacin showed comparable efficacy and a lower rate of adverse effects. The results of new Phase III studies are awaited to confirm delafloxacin's future applications in the treatment of SSSIs.

[New antibiotics - standstill or progress].

PubMed

Rademacher, J; Welte, T

2017-04-01

The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA. The fluoroketolide solithromycin should help against macrolide-resistant pathogens and has been shown to be noninferior to the fluorochinolones. The oxazolidinone tedizolid is effective against linezolid-resistant MRSA. The two cephalosporins ceftolozane/tazobactam and ceftazidime/avibactam are not only effective against gram-negative pathogens, but they have a very broad spectrum. Due to the efficacy against extended-spectrum β‑lactamases, they can relieve the selection pressure of the carbapenems. We benefit from all new antibiotics which can take the selection pressure from other often used antibiotics. The increasing number of resistant gram-negative pathogens worldwide is alarming. Thus, focusing on the development of new drugs is extremely important.

Analysis of the spectrum and antibiotic resistance of uropathogens in outpatients at a tertiary hospital.

PubMed

Yang, Bo; Yang, Fujia; Wang, Shanmei; Wang, Qian; Liu, Zhirui; Feng, Wei; Sun, Fengjun; Xia, Peiyuan

2018-05-01

The objective of this study was to analyse the distribution and antimicrobial resistance of bacterial uropathogens isolated from outpatients at Henan Provincial People's Hospital. A total of 1419 samples from 823 newly diagnosed and 596 recurrent UTI outpatients culture positive. Escherichia coli was the most common uropathogen. Compared with the recurrent group, the newly diagnosed group had a higher isolation rate of E. coli and Enterobacter cloacae but a lower isolation rate of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Except for P. aeruginosa, the resistance of Gram-negative bacteria to most antibiotics was less than 30%. All Enterococcus and Staphylococcus spp. were sensitive to linezolid, vancomycin and teicoplanin. Both Gram-negative and -positive bacteria exhibited high susceptibility to fosfomycin. Uropathogens isolated from recurrent outpatients had higher resistance rates than did those isolated from newly diagnosed outpatients. Our study indicated that fosfomycin might be an excellent treatment option for outpatients with UTIs.

[Spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome complicated by urinary tract infection: an analysis of 97 cases].

PubMed

Song, Shao-Na; Zhang, Bi-Li; Wang, Wen-Hong; Zhang, Xuan

2012-09-01

To investigate the spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome (NS) complicated by urinary tract infection (UTI). A retrospective analysis was performed on the spectrum and drug sensitivity of pathogenic bacteria in 97 children with NS complicated by UTI, who hospitalized from January to December, 2011. The incidence of UTI in children with NS was 36.5%. It was significantly more common in children with recurrent NS than in those with primary NS (44.0% vs 31.9%; P<0.05). These cases mainly presented with asymptomatic bacteriuria. Enterococcus was the most common pathogenic bacteria (50.5%), including Enterococcus faecium (29.4%) and Enterococcus faecalis (21.1%), followed by Gram-negative bacteria, such as Escherichia coli (15.6%) and Klebsiella pneumoniae (14.7%). Enterococcus was highly sensitive to nitrofurantoin, vacomycin and linezolid, but was highly resistant to tetracycline and moxifloxacin. More multi-resistant strains were detected in Enterococcus faecium than in Enterococcus faecalis (72% vs 17%; P<0.05). Escherichia coli and Klebsiella pneumoniae were highly sensitive to amikacin, imipenem and piperacillin/tazobactam. Of the Gram-negative bacteria, 25% produced extended spectrum β-lactamases (ESBLs). ESBLs-producing bacteria had 100% sensitivity to imipenem, amikacin and piperacillin/tazobactam but were highly resistant to ampicillin, cefazolin and ceftriaxone. Children with recurrent NS are more susceptible to UTI than those with primary NS. Enterococcus is becoming major pathogenic bacteria for UTI in children with NS and has relatively high drug resistance, and most strains of Enterococcus faecium are multi-resistant.

Impact of spores on the comparative efficacies of five antibiotics for treatment of Bacillus anthracis in an in vitro hollow fiber pharmacodynamic model.

PubMed

Louie, Arnold; VanScoy, Brian D; Brown, David L; Kulawy, Robert W; Heine, Henry S; Drusano, George L

2012-03-01

Bacillus anthracis, the bacterium that causes anthrax, is an agent of bioterrorism. The most effective antimicrobial therapy for B. anthracis infections is unknown. An in vitro pharmacodynamic model of B. anthracis was used to compare the efficacies of simulated clinically prescribed regimens of moxifloxacin, linezolid, and meropenem with the "gold standards," doxycycline and ciprofloxacin. Treatment outcomes for isogenic spore-forming and non-spore-forming strains of B. anthracis were compared. Against spore-forming B. anthracis, ciprofloxacin, moxifloxacin, linezolid, and meropenem reduced the B. anthracis population by 4 log(10) CFU/ml over 10 days. Doxycycline reduced the population of this B. anthracis strain by 5 log(10) CFU/ml (analysis of variance [ANOVA] P = 0.01 versus other drugs). Against an isogenic non-spore-forming strain, meropenem killed the vegetative B. anthracis the fastest, followed by moxifloxacin and ciprofloxacin and then doxycycline. Linezolid offered the lowest bacterial kill rate. Heat shock studies using the spore-producing B. anthracis strain showed that with moxifloxacin, ciprofloxacin, and meropenem therapies the total population was mostly spores, while the population was primarily vegetative bacteria with linezolid and doxycycline therapies. Spores have a profound impact on the rate and extent of killing of B. anthracis. Against spore-forming B. anthracis, the five antibiotics killed the total (spore and vegetative) bacterial population at similar rates (within 1 log(10) CFU/ml of each other). However, bactericidal antibiotics killed vegetative B. anthracis faster than bacteriostatic drugs. Since only vegetative-phase B. anthracis produces the toxins that may kill the infected host, the rate and mechanism of killing of an antibiotic may determine its overall in vivo efficacy. Further studies are needed to examine this important observation.

Impact of Spores on the Comparative Efficacies of Five Antibiotics for Treatment of Bacillus anthracis in an In Vitro Hollow Fiber Pharmacodynamic Model

PubMed Central

VanScoy, Brian D.; Brown, David L.; Kulawy, Robert W.; Heine, Henry S.; Drusano, George L.

2012-01-01

Bacillus anthracis, the bacterium that causes anthrax, is an agent of bioterrorism. The most effective antimicrobial therapy for B. anthracis infections is unknown. An in vitro pharmacodynamic model of B. anthracis was used to compare the efficacies of simulated clinically prescribed regimens of moxifloxacin, linezolid, and meropenem with the “gold standards,” doxycycline and ciprofloxacin. Treatment outcomes for isogenic spore-forming and non-spore-forming strains of B. anthracis were compared. Against spore-forming B. anthracis, ciprofloxacin, moxifloxacin, linezolid, and meropenem reduced the B. anthracis population by 4 log10 CFU/ml over 10 days. Doxycycline reduced the population of this B. anthracis strain by 5 log10 CFU/ml (analysis of variance [ANOVA] P = 0.01 versus other drugs). Against an isogenic non-spore-forming strain, meropenem killed the vegetative B. anthracis the fastest, followed by moxifloxacin and ciprofloxacin and then doxycycline. Linezolid offered the lowest bacterial kill rate. Heat shock studies using the spore-producing B. anthracis strain showed that with moxifloxacin, ciprofloxacin, and meropenem therapies the total population was mostly spores, while the population was primarily vegetative bacteria with linezolid and doxycycline therapies. Spores have a profound impact on the rate and extent of killing of B. anthracis. Against spore-forming B. anthracis, the five antibiotics killed the total (spore and vegetative) bacterial population at similar rates (within 1 log10 CFU/ml of each other). However, bactericidal antibiotics killed vegetative B. anthracis faster than bacteriostatic drugs. Since only vegetative-phase B. anthracis produces the toxins that may kill the infected host, the rate and mechanism of killing of an antibiotic may determine its overall in vivo efficacy. Further studies are needed to examine this important observation. PMID:22155821

Passive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus.

PubMed

Karau, Melissa J; Tilahun, Mulualem E; Krogman, Ashton; Osborne, Barbara A; Goldsby, Richard A; David, Chella S; Mandrekar, Jayawant N; Patel, Robin; Rajagopalan, Govindarajan

2017-10-03

Drugs such as linezolid that inhibit bacterial protein synthesis may be beneficial in treating infections caused by toxigenic Staphylococcus aureus. As protein synthesis inhibitors have no effect on preformed toxins, neutralization of pathogenic exotoxins with anti-toxin antibodies may be beneficial in conjunction with antibacterial therapy. Herein, we evaluated the efficacy of human-mouse chimeric high-affinity neutralizing anti-staphylococcal enterotoxin B (SEB) antibodies in the treatment of experimental pneumonia caused by SEB-producing S. aureus. Since HLA class II transgenic mice mount a stronger systemic immune response following challenge with SEB and are more susceptible to SEB-induced lethal toxic shock than conventional mice strains, HLA-DR3 transgenic mice were used. Lethal pneumonia caused by SEB-producing S. aureus in HLA-DR3 transgenic mice was characterized by robust T cell activation and elevated systemic levels of several pro-inflammatory cytokines and chemokines. Prophylactic administration of a single dose of linezolid 30 min prior to the onset of infection attenuated the systemic inflammatory response and protected from mortality whereas linezolid administered 60 min after the onset of infection failed to confer significant protection. Human-mouse chimeric high-affinity neutralizing anti-SEB antibodies alone, but not polyclonal human IgG, mitigated this response and protected from death when administered immediately after initiation of infection. Further, anti-SEB antibodies as well as intact polyclonal human IgG, but not its Fab or Fc fragments, protected from lethal pneumonia when followed with linezolid therapy 60 min later. In conclusion, neutralization of superantigens with high-affinity antibodies may have beneficial effects in pneumonia.

Development, Optimization, and Validation of a Microplate Bioassay for Relative Potency Determination of Linezolid Using a Design Space Concept, and its Measurement Uncertainty.

PubMed

Saviano, Alessandro Morais; Francisco, Fabiane Lacerda; Ostronoff, Celina Silva; Lourenço, Felipe Rebello

2015-01-01

The aim of this study was to develop, optimize, and validate a microplate bioassay for relative potency determination of linezolid in pharmaceutical samples using quality-by-design and design space approaches. In addition, a procedure is described for estimating relative potency uncertainty based on microbiological response variability. The influence of culture media composition was studied using a factorial design and a central composite design was adopted to study the influence of inoculum proportion and triphenyltetrazolium chloride in microbial growth. The microplate bioassay was optimized regarding the responses of low, medium, and high doses of linezolid, negative and positive controls, and the slope, intercept, and correlation coefficient of dose-response curves. According to optimization results, design space ranges were established using: (a) low (1.0 μg/mL), medium (2.0 μg/mL), and high (4.0 μg/mL) doses of pharmaceutical samples and linezolid chemical reference substance; (b) Staphylococcus aureus ATCC 653 in an inoculum proportion of 10%; (c) antibiotic No. 3 culture medium pH 7.0±0.1; (d) 6 h incubation at 37.0±0.1ºC; and (e) addition of 50 μL of 0.5% (w/v) triphenyltetrazolium chloride solution. The microplate bioassay was linear (r2=0.992), specific, precise (repeatability RSD=2.3% and intermediate precision RSD=4.3%), accurate (mean recovery=101.4%), and robust. The overall measurement uncertainty was reasonable considering the increased variability inherent in microbiological response. Final uncertainty was comparable with those obtained with other microbiological assays, as well as chemical methods.

Two Novel Point Mutations in Clinical Staphylococcus aureus Reduce Linezolid Susceptibility and Switch on the Stringent Response to Promote Persistent Infection

PubMed Central

Gao, Wei; Chua, Kyra; Davies, John K.; Newton, Hayley J.; Seemann, Torsten; Harrison, Paul F.; Holmes, Natasha E.; Rhee, Hyun-Woo; Hong, Jong-In; Hartland, Elizabeth L.; Stinear, Timothy P.; Howden, Benjamin P.

2010-01-01

Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure of antibiotic therapy to eradicate infection is frequently described; in some cases associated with altered S. aureus antimicrobial resistance or the small colony variant (SCV) phenotype. Newer antimicrobials, such as linezolid, remain the last available therapy for some patients with multi-resistant S. aureus infections. Using comparative and functional genomics we investigated the molecular determinants of resistance and SCV formation in sequential S. aureus isolates from a patient who had a persistent and recurrent S. aureus infection, after failed therapy with multiple antimicrobials, including linezolid. Two point mutations in key staphylococcal genes dramatically affected clinical behaviour of the bacterium, altering virulence and antimicrobial resistance. Most strikingly, a single nucleotide substitution in relA (SACOL1689) reduced RelA hydrolase activity and caused accumulation of the intracellular signalling molecule guanosine 3′, 5′-bis(diphosphate) (ppGpp) and permanent activation of the stringent response, which has not previously been reported in S. aureus. Using the clinical isolate and a defined mutant with an identical relA mutation, we demonstrate for the first time the impact of an active stringent response in S. aureus, which was associated with reduced growth, and attenuated virulence in the Galleria mellonella model. In addition, a mutation in rlmN (SACOL1230), encoding a ribosomal methyltransferase that methylates 23S rRNA at position A2503, caused a reduction in linezolid susceptibility. These results reinforce the exquisite adaptability of S. aureus and show how subtle molecular changes cause major alterations in bacterial behaviour, as well as highlighting potential weaknesses of current antibiotic treatment regimens. PMID:20548948

Development of an integrated semi-automated system for in vitro pharmacodynamic modelling.

PubMed

Wang, Liangsu; Wismer, Michael K; Racine, Fred; Conway, Donald; Giacobbe, Robert A; Berejnaia, Olga; Kath, Gary S

2008-11-01

The aim of this study was to develop an integrated system for in vitro pharmacodynamic modelling of antimicrobials with greater flexibility, easier control and better accuracy than existing in vitro models. Custom-made bottle caps, fittings, valve controllers and a modified bench-top shaking incubator were used. A temperature-controlled automated sample collector was built. Computer software was developed to manage experiments and to control the entire system including solenoid pinch valves, peristaltic pumps and the sample collector. The system was validated by pharmacokinetic simulations of linezolid 600 mg infusion. The antibacterial effect of linezolid against multiple Staphylococcus aureus strains was also studied in this system. An integrated semi-automated bench-top system was built and validated. The temperature-controlled automated sample collector allowed unattended collection and temporary storage of samples. The system software reduced the labour necessary for many tasks and also improved the timing accuracy for performing simultaneous actions in multiple parallel experiments. The system was able to simulate human pharmacokinetics of linezolid 600 mg intravenous infusion accurately. A pharmacodynamic study of linezolid against multiple S. aureus strains with a range of MICs showed that the required 24 h free drug AUC/MIC ratio was approximately 30 in order to keep the organism counts at the same level as their initial inoculum and was about > or = 68 in order to achieve > 2 log(10) cfu/mL reduction in the in vitro model. The integrated semi-automated bench-top system provided the ability to overcome many of the drawbacks of existing in vitro models. It can be used for various simple or complicated pharmacokinetic/pharmacodynamic studies efficiently and conveniently.

Carrier-free nanoassemblies of a novel oxazolidinone compound FYL-67 display antimicrobial activity on methicillin-resistant Staphylococcus aureus

NASA Astrophysics Data System (ADS)

Gong, Changyang; Yang, Tao; Yang, Xiaoyan; Liu, Yuanyuan; Ang, Wei; Tang, Jianying; Pi, Weiyi; Xiong, Li; Chang, Ying; Ye, Weiwei; Wang, Zhenling; Luo, Youfu; Zhao, Xia; Wei, Yuquan

2012-12-01

In this work, a novel oxazolidinone compound FYL-67 was synthesized, and the obtained FYL-67 could form nanoassemblies in aqueous solution by a self-assembly method without using any carrier, organic solvent, or surfactant. The prepared FYL-67 nanoassemblies had a particle size of 264.6 +/- 4.3 nm. The FYL-67 nanoassemblies can be lyophilized into a powder form without any cryoprotector or excipient, and the re-dissolved FYL-67 nanoassemblies are stable and homogeneous. The in vitro release profile showed a significant difference between rapid release of free FYL-67 and much slower and sustained release of FYL-67 nanoassemblies. In vitro susceptibility tests were conducted in three strains of methicillin-susceptible Staphylococcus aureus (MSSA) and three strains of methicillin-resistant Staphylococcus aureus (MRSA), using linezolid as a positive control. FYL-67 nanoassemblies exhibited excellent in vitro activity, with a minimum inhibitory concentration (MIC) value of 0.5 μg mL-1 against MRSA. In the in vitro post-antibiotic effect (PAE) evaluation, FYL-67 nanoassemblies showed a more powerful effect than linezolid. Besides, in vitro cytotoxicity tests indicated that FYL-67 nanoassemblies had a very low cytotoxicity on HEK293 cells and L02 cells. Furthermore, in both MSSA and MRSA systemic infection mouse models, FYL-67 nanoassemblies showed a lower ED50 than linezolid. In a murine model of MRSA systemic infection, FYL-67 nanoassemblies displayed an ED50 of less than 4.0 mg kg-1, which is 2.3-fold better than that of linezolid. Our findings suggested that the FYL-67 nanoassemblies may be a potential drug candidate in MRSA therapy.

Treatment of infections due to resistant Staphylococcus aureus.

PubMed

Anstead, Gregory M; Cadena, Jose; Javeri, Heta

2014-01-01

This chapter reviews data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review covers findings reported in the English language medical literature up to January of 2013. Despite the emergence of resistant and multidrug-resistant S. aureus, we have seven effective drugs in clinical use for which little resistance has been observed: vancomycin, quinupristin-dalfopristin, linezolid, tigecycline, telavancin, ceftaroline, and daptomycin. However, vancomycin is less effective for infections with MRSA isolates that have a higher MIC within the susceptible range. Linezolid is probably the drug of choice for the treatment of complicated MRSA skin and soft tissue infections (SSTIs); whether it is drug of choice in pneumonia remains debatable. Daptomycin has shown to be non-inferior to either vancomycin or β-lactams in the treatment of staphylococcal SSTIs, bacteremia, and right-sided endocarditis. Tigecycline was also non-inferior to comparator drugs in the treatment of SSTIs, but there is controversy about whether it is less effective than other therapeutic options in the treatment of more serious infections. Telavancin has been shown to be non-inferior to vancomycin in the treatment of SSTIs and pneumonia, but has greater nephrotoxicity. Ceftaroline is a broad-spectrum cephalosporin with activity against MRSA; it is non-inferior to vancomycin in the treatment of SSTIs. Clindamycin, trimethoprim-sulfamethoxazole, doxycycline, rifampin, moxifloxacin, and minocycline are oral anti-staphylococcal agents that may have utility in the treatment of SSTIs and osteomyelitis, but the clinical data for their efficacy is limited. There are also several drugs with broad-spectrum activity against Gm-positive organisms that have reached the phase II and III stages of clinical testing that will hopefully be approved for clinical use in the upcoming years: oritavancin, dalbavancin, omadacycline, tedizolid, delafloxacin, and JNJ-Q2. Thus, there are currently many effective drugs to treat resistant S. aureus infections and many promising agents in the pipeline. Nevertheless, S. aureus remains a formidable adversary, and despite our deep bullpen of potential therapies, there are still frequent treatment failures and unfortunate clinical outcomes. The following discussion summarizes the clinical challenges presented by MRSA, the clinical experience with our current anti-MRSA antibiotics, and the gaps in our knowledge on how to use these agents to most effectively combat MRSA infections.

Molecular epidemiology of vancomycin-resistant enterococcal bacteraemia: results from the Canadian Nosocomial Infection Surveillance Program, 1999-2009.

PubMed

McCracken, M; Wong, A; Mitchell, R; Gravel, D; Conly, J; Embil, J; Johnston, L; Matlow, A; Ormiston, D; Simor, A E; Smith, S; Du, T; Hizon, R; Mulvey, M R

2013-07-01

Vancomycin-resistant enterococci (VRE) can be associated with serious bacteraemia. The focus of this study was to characterize the molecular epidemiology of VRE from bacteraemia cases that were isolated from 1999 to 2009 as part of Canadian Nosocomial Infection Surveillance Program (CNISP) surveillance activities. From 1999 to 2009, enterococci were collected from across Canada in accordance with the CNISP VRE surveillance protocol. MICs were determined using broth microdilution. PCR was used to identify vanA, B, C, D, E, G and L genes. Genetic relatedness was examined using multilocus sequence typing (MLST). A total of 128 cases of bacteraemia were reported to CNISP from 1999 to 2009. In 2007, a significant increase in bacteraemia rates was observed in western and central Canada. Eighty-one of the 128 bacteraemia isolates were received for further characterization and were identified as Enterococcus faecium. The majority of isolates were from western Canada (60.5%), followed by central (37.0%) and eastern (2.5%) Canada. Susceptibilities were as follows: daptomycin, linezolid, tigecycline and chloramphenicol, 100%; quinupristin/dalfopristin, 96.3%; high-level gentamicin, 71.6%; tetracycline, 50.6%; high-level streptomycin, 44.4%; rifampicin, 21.0%; nitrofurantoin, 11.1%; clindamycin, 8.6%; ciprofloxacin, levofloxacin and moxifloxacin, 1.2%; and ampicillin, 0.0%. vanA contributed to vancomycin resistance in 90.1% of isolates and vanB in 9.9%. A total of 17 sequence types (STs) were observed. Beginning in 2006 there was a shift in ST from ST16, ST17, ST154 and ST80 to ST18, ST412, ST203 and ST584. The increase in bacteraemia observed since 2007 in western and central Canada appears to coincide with the shift of MLST STs. All VRE isolates remained susceptible to daptomycin, linezolid, chloramphenicol and tigecycline.

An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants.

PubMed

Phetsang, Wanida; Blaskovich, Mark A T; Butler, Mark S; Huang, Johnny X; Zuegg, Johannes; Mamidyala, Sreeman K; Ramu, Soumya; Kavanagh, Angela M; Cooper, Matthew A

2014-08-15

An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Successful treatment of MRSA native valve endocarditis with oral linezolid therapy: a case report.

PubMed

Nathani, N; Iles, P; Elliott, T S J

2005-11-01

Staphylococcal endocarditis is potentially fatal and is now the most common cause of infective endocarditis with a mortality rate of 25-47% [Hecht SR, Berger M. Right-sided endocarditis in intravenous drug users: prognostic features in 102 episodes. Ann Intern Med 1992;117:560-6]. Its treatment requires maintenance of bactericidal level of antibiotics for prolonged periods to attain a culture-negative state. Although intravenous vancomycin is currently the drug of choice for methicillin resistant Staphylococcus aureus (MRSA) endocarditis, we present a case treated successfully with oral linezolid for 4 weeks due to a lack of venous access.

Streptococcus sanguinis isolate displaying a phenotype with cross-resistance to several rRNA-targeting agents.

PubMed

Mendes, Rodrigo E; Deshpande, Lalitagauri M; Kim, Jihye; Myers, Debra S; Ross, James E; Jones, Ronald N

2013-08-01

This study describes a clinical case of a 71-year-old male with a history of ischemic cardiomyopathy after left ventricular assist device (LVAD) endocarditis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and a rare linezolid-resistant Streptococcus sanguinis strain (MIC, 32 μg/ml). The patient received courses of several antimicrobial agents, including linezolid for 79 days. The S. sanguinis strain had mutations in the 23S rRNA (T2211C, T2406C, G2576T, C2610T) and an amino acid substitution (N56D) in L22 and exhibited cross-resistance to ribosome-targeting agents.

Streptococcus sanguinis Isolate Displaying a Phenotype with Cross-Resistance to Several rRNA-Targeting Agents

PubMed Central

Deshpande, Lalitagauri M.; Kim, Jihye; Myers, Debra S.; Ross, James E.; Jones, Ronald N.

2013-01-01

This study describes a clinical case of a 71-year-old male with a history of ischemic cardiomyopathy after left ventricular assist device (LVAD) endocarditis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and a rare linezolid-resistant Streptococcus sanguinis strain (MIC, 32 μg/ml). The patient received courses of several antimicrobial agents, including linezolid for 79 days. The S. sanguinis strain had mutations in the 23S rRNA (T2211C, T2406C, G2576T, C2610T) and an amino acid substitution (N56D) in L22 and exhibited cross-resistance to ribosome-targeting agents. PMID:23698536

Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates.

PubMed

Jones, Ronald N; Moet, Gary J; Sader, Helio S; Fritsche, Thomas R

2004-05-01

To evaluate the potency of a novel peptide deformylase inhibitor, NVP PDF-713, against Gram-positive organisms having resistances to linezolid or quinupristin/dalfopristin. A total of 45 strains from three genera (six species groups) were tested by reference broth microdilution methods. The mechanism of resistance to the oxazolidinone was determined by sequencing of the gene encoding the ribosomal target. NVP PDF-713 retained activity against linezolid-resistant staphylococci (MIC range 0.25-2 mg/L), Streptococcus oralis (MIC 0.5 mg/L), Enterococcus faecalis (MIC range 2-4 mg/L) and Enterococcus faecium (MIC range 0.5-4 mg/L). Quinupristin/dalfopristin-resistant E. faecium (MIC range 1-2 mg/L) and staphylococci (MIC range 0.12-2 mg/L) were also inhibited by NVP PDF-713. Many (10 of 13 strains) of the linezolid-resistant enterococci were resistant to vancomycin and these clinical strains had a G2576U ribosomal target mutation. NVP PDF-713 appears to be a promising clinical candidate among the peptide deformylase inhibitors for the treatment of infections caused by Gram-positive organisms that possess resistances to oxazolidinones or streptogramin combinations.

Improved outcome of ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus in a trauma population.

PubMed

Gonzalez, Richard P; Rostas, Jack; Simmons, Jon D; Allen, John; Frotan, Mohammad A; Brevard, Sidney B

2013-03-01

The treatment of ventilator-associated pneumonia (VAP) secondary to methicillin-resistant Staphylococcus aureus (MRSA) remains controversial. We performed a review of all blunt trauma patients diagnosed with MRSA VAP from June 2005 to June 2011. VAP for the first 3 years was diagnosed by sputum aspiration and treated with vancomycin. For the last 3 years of the study period, VAP was diagnosed with bronchoalveolar lavage and treated with linezolid. MRSA VAP patients treated with vancomycin had an average hospital length of stay (LOS) of 49 days (range 9-99 days), an average intensive care unit (ICU) LOS of 43 days (range 6-98 days), and average ventilator days of 34.4 (range 3-76 days). Seventeen MRSA VAP patients treated with linezolid had an average hospital LOS of 27 days (range 11-61), an average ICU LOS of 22 days (range 10-42) days, and average ventilator days of 16.6 (range 2-42). Trauma patients who develop MRSA VAP appear to have fewer ventilator days and shorter ICU and hospital LOS when treated with linezolid. Copyright © 2013 Elsevier Inc. All rights reserved.

Activity of Ceftaroline and Epidemiologic Trends in Staphylococcus aureus Isolates Collected from 43 Medical Centers in the United States in 2009▿

PubMed Central

Richter, Sandra S.; Heilmann, Kristopher P.; Dohrn, Cassie L.; Riahi, Fathollah; Costello, Andrew J.; Kroeger, Jennifer S.; Biek, Donald; Critchley, Ian A.; Diekema, Daniel J.; Doern, Gary V.

2011-01-01

A Staphylococcus aureus surveillance program was initiated in the United States to examine the in vitro activity of ceftaroline and epidemiologic trends. Susceptibility testing by Clinical and Laboratory Standards Institute broth microdilution was performed on 4,210 clinically significant isolates collected in 2009 from 43 medical centers. All isolates were screened for mecA by PCR and evaluated by pulsed-field gel electrophoresis. Methicillin-resistant S. aureus (MRSA) were analyzed for Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosome mec (SCCmec) type. All isolates had ceftaroline MICs of ≤2 μg/ml with an MIC50 of 0.5 and an MIC90 of 1 μg/ml. The overall resistance rates, expressed as the percentages of isolates that were intermediate and resistant (or nonsusceptible), were as follows: ceftaroline, 1.0%; clindamycin, 30.2% (17.4% MIC ≥ 4 μg/ml; 12.8% inducible); daptomycin, 0.2%; erythromycin, 65.5%; levofloxacin, 39.9%; linezolid, 0.02%; oxacillin, 53.4%; tetracycline, 4.4%; tigecycline, 0%; trimethoprim-sulfamethoxazole, 1.6%; vancomycin, 0%; and high-level mupirocin, 2.2%. The mecA PCR was positive for 53.4% of the isolates. The ceftaroline MIC90s were 0.25 μg/ml for methicillin-susceptible S. aureus and 1 μg/ml for MRSA. Among the 2,247 MRSA isolates, 51% were USA300 (96.9% PVL positive, 99.7% SCCmec type IV) and 17% were USA100 (93.4% SCCmec type II). The resistance rates for the 1,137 USA300 MRSA isolates were as follows: erythromycin, 90.9%; levofloxacin, 49.1%; clindamycin, 7.6% (6.2% MIC ≥ 4 μg/ml; 1.4% inducible); tetracycline, 3.3%; trimethoprim-sulfamethoxazole, 0.8%; high-level mupirocin, 2.7%; daptomycin, 0.4%; and ceftaroline and linezolid, 0%. USA300 is the dominant clone causing MRSA infections in the United States. Ceftaroline demonstrated potent in vitro activity against recent S. aureus clinical isolates, including MRSA, daptomycin-nonsusceptible, and linezolid-resistant strains. PMID:21709080

Oxazolidinone antimicrobials: a patent review (2012-2015).

PubMed

Phillips, Oludotun A; Sharaf, Leyla H

2016-05-01

Antimicrobial resistance in Gram-positive bacteria is a major health care issue. This review summarizes patent publications from 2012 to 2015 that divulged novel oxazolidinones as antibacterial agents. A total of 25 patents obtained from Espacenet, WIPO Patentscope and FreePatentsOnline, and AcclaimIP search engines were reviewed. The patents were scrutinized based on the novelty of the compounds, their antibacterial activity (MIC, µg/mL), and the process of preparation. The oxazolidinones with promising antibacterial activity were classified according to the following structural diversities, as biaryl heterocyclic, fused heteroaryl rings containing oxazolidinones, and others. The biaryl heterocyclic, fused heteroaryl, benzoxazine, and the 1H-pyrazol-1-yl containing oxazolidinone derivatives demonstrated potent antibacterial activities superior to linezolid against Gram-positive bacteria. Some derivatives were effective against standard strains of Gram-negative bacteria, namely Moraxella catarrhalis ATCC A894, and Escherichia coli ATCC 25922. In addition, a patent disclosed a structural isomer of linezolid with marginal activity against the aerobic Gram-negative bacteria MDR Stenotrophomonas (Xanthomonas) maltophilia, while linezolid and vancomycin did not inhibit growth. Finally, some derivatives showed activity against respiratory infectious diseases' causative agents, such as B. anthracis, B. mallei, Y. pestis, and M. pneumoniae. Overall, there is limited in vivo data to support the potential clinical advancement of the currently reported novel derivatives.

Susceptibility Profile of Staphylococcus epidermidis and Staphylococcus haemolyticus Isolated from Blood Cultures to Vancomycin and Novel Antimicrobial Drugs over a Period of 12 Years.

PubMed

Pinheiro, Luiza; Brito, Carla Ivo; Pereira, Valéria Cataneli; Oliveira, Adilson; Bartolomeu, Ariane Rocha; Camargo, Carlos Henrique; Cunha, Maria Lourdes Ribeiro Souza

2016-06-01

The aim of this study was to evaluate the antimicrobial susceptibility profile of 85 Staphylococcus epidermidis and 84 Staphylococcus haemolyticus strains isolated from blood cultures to oxacillin, vancomycin, tigecycline, linezolid, daptomycin, and quinupristin/dalfopristin over a period of 12 years. S. epidermidis and S. haemolyticus isolated from blood cultures of inpatients, attended at a teaching hospital, were analyzed for the presence of the mecA gene and by SCCmec typing. The minimum inhibitory concentration (MIC) values of tigecycline, linezolid, daptomycin, quinupristin/dalfopristin, and vancomycin were determined. Isolates exhibiting vancomycin MICs of ≥2 μg/ml were typed by pulsed-field gel electrophoresis (PFGE). The rate of mecA positivity was 92.9% and 100% in S. epidermidis and S. haemolyticus, respectively. The most frequent SCCmec types were type III (53.2%) in S. epidermidis and type I (32.1%) in S. haemolyticus. All isolates were susceptible to linezolid and daptomycin, but 7.1% of S. haemolyticus and 2.3% of S. epidermidis isolates were resistant to tigecycline, and 1.2% each of S. haemolyticus and S. epidermidis were resistant and intermediately resistant to quinupristin/dalfopristin, respectively. S. epidermidis exhibited higher vancomycin MICs (40% with MIC of ≥2 μg/ml). Clonal typing of strains with vancomycin MIC of ≥2 μg/ml revealed the presence of different PFGE types of S. epidermidis and S. haemolyticus over a period of up to 4 years (2002-2004, 2005-2008, 2006-2009, 2010-2011). Despite the observation of a high prevalence of mecA, the clinical strains were fully susceptible to vancomycin and to the new drugs linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. The PFGE types with vancomycin MIC of ≥2 μg/ml exhibited a great diversity of SCCmec cassettes, demonstrating that S. epidermidis and S. haemolyticus may easily acquire these resistance-conferring genetic elements.

Molecular epidemiology of coagulase-negative bloodstream isolates: detection of Staphylococcus epidermidis ST2, ST7 and linezolid-resistant ST23.

PubMed

Martínez-Meléndez, Adrián; Morfín-Otero, Rayo; Villarreal-Treviño, Licet; Camacho-Ortíz, Adrián; González-González, Gloria; Llaca-Díaz, Jorge; Rodríguez-Noriega, Eduardo; Garza-González, Elvira

2016-01-01

The mechanisms contributing to persistence of coagulase-negative staphylococci are diverse; to better understanding of their dynamics, the characterization of nosocomial isolates is needed. Our aim was to characterize phenotypic and molecular characteristics of Staphylococcus epidermidis and Staphylococcus haemolyticus human blood isolates from two tertiary care hospitals in Mexico, the Hospital Universitario in Monterrey and the Hospital Civil in Guadalajara. Antimicrobial susceptibility was determined. Biofilm formation was assessed by crystal violet staining. Detection of the ica operon and Staphylococcal Cassette Chromosome mec typing were performed by PCR. Clonal relatedness was determined by Pulsed-fiel gel electrophoresis and Multi locus sequence typing. Methicillin-resistance was 85.5% and 93.2% for S. epidermidis and S. haemolyticus, respectively. Both species showed resistance >70% to norfloxacin, clindamycin, levofloxacin, trimethoprim/sulfamethoxazole, and erythromycin. Three S. epidermidis and two S. haemolyticus isolates were linezolid-resistant (one isolate of each species was cfr+). Most isolates of both species were strong biofilm producers (92.8% of S. epidermidis and 72.9% of S. haemolyticus). The ica operon was amplified in 36 (43.4%) S. epidermidis isolates. SCCmec type IV was found in 47.2% of the S. epidermidis isolates and SCCmec type V in 14.5% of S. haemolyticus isolates. No clonal relatedness was found in either species. Resistance to clindamycin, levofloxacin, erythromycin, oxacillin, and cefoxitin was associated with biofilm production for both species (p<0.05). A G2576T mutation in 23S rRNA gene was detected in an S. haemolyticus linezolid-resistant isolate. All linezolid-resistant S. epidermidis isolates belonged to ST23; isolate with SCCmec type IV belonged to ST7, and isolate with SCCmec type III belonged to ST2. This is the first report of ST7 in Mexico. There was a high genetic diversity in both species, though both species shared characteristics that may contibute to virulence. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Estimated generic prices for novel treatments for drug-resistant tuberculosis.

PubMed

Gotham, Dzintars; Fortunak, Joseph; Pozniak, Anton; Khoo, Saye; Cooke, Graham; Nytko, Frederick E; Hill, Andrew

2017-04-01

The estimated worldwide annual incidence of MDR-TB is 480 000, representing 5% of TB incidence, but 20% of mortality. Multiple drugs have recently been developed or repurposed for the treatment of MDR-TB. Currently, treatment for MDR-TB costs thousands of dollars per course. To estimate generic prices for novel TB drugs that would be achievable given large-scale competitive manufacture. Prices for linezolid, moxifloxacin and clofazimine were estimated based on per-kilogram prices of the active pharmaceutical ingredient (API). Other costs were added, including formulation, packaging and a profit margin. The projected costs for sutezolid were estimated to be equivalent to those for linezolid, based on chemical similarity. Generic prices for bedaquiline, delamanid and pretomanid were estimated by assessing routes of synthesis, costs/kg of chemical reagents, routes of synthesis and per-step yields. Costing algorithms reflected variable regulatory requirements and efficiency of scale based on demand, and were validated by testing predictive ability against widely available TB medicines. Estimated generic prices were US$8-$17/month for bedaquiline, $5-$16/month for delamanid, $11-$34/month for pretomanid, $4-$9/month for linezolid, $4-$9/month for sutezolid, $4-$11/month for clofazimine and $4-$8/month for moxifloxacin. The estimated generic prices were 87%-94% lower than the current lowest available prices for bedaquiline, 95%-98% for delamanid and 94%-97% for linezolid. Estimated generic prices were $168-$395 per course for the STREAM trial modified Bangladesh regimens (current costs $734-$1799), $53-$276 for pretomanid-based three-drug regimens and $238-$507 for a delamanid-based four-drug regimen. Competitive large-scale generic manufacture could allow supplies of treatment for 5-10 times more MDR-TB cases within current procurement budgets. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Linezolid Compared with Eperezolid, Vancomycin, and Gentamicin in an In Vitro Model of Antimicrobial Lock Therapy for Staphylococcus epidermidis Central Venous Catheter-Related Biofilm Infections

PubMed Central

Curtin, John; Cormican, Martin; Fleming, Gerard; Keelehan, John; Colleran, Emer

2003-01-01

Central venous catheter (CVC)-related infection (CVC-RI) is a common complication of CVC use. The most common etiological agents of CVC-RI are gram-positive organisms, in particular, staphylococci. An in vitro model for the formation of biofilms by Staphylococcus epidermidis ATCC 35984 on polyurethane coupons in a modified Robbins device was established. Biofilm formation was confirmed by electron microscopy and was quantified by determination of viable counts. Mueller-Hinton broth was replaced with sterile physiological saline (control) or a solution of vancomycin (10 mg/ml), gentamicin (10 mg/ml), linezolid (2 mg/ml), or eperezolid (4 mg/ml). Viable counts were performed with the coupons after exposure to antimicrobials for periods of 24, 72, 168, and 240 h. The mean viable count per coupon following establishment of the biofilm was 4.6 × 108 CFU/coupon, and that after 14 days of exposure to physiological saline was 2.5 × 107 CFU/coupon. On exposure to vancomycin (10 mg/ml), the mean counts were 2.5 × 107 CFU/coupon at 24 h, 4.3 × 106 CFU/coupon at 72 h, 1.4 × 105 CFU/coupon at 168 h, and undetectable at 240 h. With gentamicin (10 mg/ml) the mean counts were 2.7 × 107 CFU/coupon at 24 h, 3.7 × 106 CFU/coupon at 72 h, 8.4 × 106 CFU/coupon at 168 h, and 6.5 × 106 CFU/coupon at 240 h. With linezolid at 2 mg/ml the mean counts were 7.1 × 105 CFU/coupon at 24 h and not detectable at 72, 168, and 240 h. With eperezolid (4 mg/ml) no viable cells were recovered after 168 h. These data suggest that linezolid (2 mg/ml) and eperezolid (4 mg/ml) achieve eradication of S. epidermidis biofilms more rapidly than vancomycin (10 mg/ml) and gentamicin (10 mg/ml). PMID:14506022

Efficacy of high doses of levofloxacin in experimental foreign-body infection by methicillin-susceptible Staphylococcus aureus.

PubMed

Murillo, O; Doménech, A; Garcia, A; Tubau, F; Cabellos, C; Gudiol, F; Ariza, J

2006-12-01

Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at doses of 50 mg/kg/day and 100 mg/kg/day (mimicking the usual and high human doses of 500 mg/day and 750 to 1,000 mg/day, respectively) and compared it to that of to linezolid, cloxacillin, vancomycin, and rifampin in a rat tissue cage model of experimental foreign-body infection by Staphylococcus aureus. The antimicrobial efficacy in vitro (by MIC, minimum bactericidal concentration, and kill curves) for logarithmic- and stationary-phase bacteria was compared with the in vivo efficacy. In vitro bactericidal activity at clinically relevant concentrations was reached by all drugs except rifampin and linezolid in the log-phase studies but only by levofloxacin in the stationary-phase studies. The bacterial count decreases from in vivo tissue cage fluids (means) for levofloxacin at 50 and 100 mg/kg/day, rifampin, cloxacillin, vancomycin, linezolid, and controls, respectively, were: -1.24, -2.26, -2.1, -1.56, -1.47, -1.15, and 0.33 (all groups versus controls, P < 0.05). Levofloxacin at 100 mg/kg/day (area under the concentration-time curve/MIC ratio, 234) was the most active therapy (P = 0.03 versus linezolid). Overall, in vivo efficacy was better predicted by stationary-phase studies, in which it reached a high correlation coefficient even if the rifampin group was excluded (r = 0.96; P < 0.05). Our results, including in vitro studies with nongrowing bacteria, pharmacodynamic parameters, and antimicrobial efficacy in experimental infection, provide good evidence to support the use of levofloxacin at high doses (750 to 1,000 mg/day), as recently recommended for treating patients with orthopedic prosthesis infections.

Comparative activity of ceftobiprole against Gram-positive and Gram-negative isolates from Europe and the Middle East: the CLASS study.

PubMed

Rossolini, Gian M; Dryden, Matthew S; Kozlov, Roman S; Quintana, Alvaro; Flamm, Robert K; Läuffer, Jörg M; Lee, Emma; Morrissey, Ian; CLASS Study Group

2011-01-01

to assess the in vitro activity of ceftobiprole and comparators against a recent collection of Gram-positive and Gram-negative pathogens, in order to detect potential changes in susceptibility patterns, and to evaluate the Etest assay for ceftobiprole susceptibility testing. contemporary Gram-positive and Gram-negative isolates (excluding extended-spectrum β-lactamase-producing isolates) from across Europe and the Middle East were collected, and their susceptibility to ceftobiprole, vancomycin, teicoplanin, linezolid, ceftazidime and cefepime was assessed using the Etest method. Quality testing [using Etest and broth microdilution (BMD)] was conducted at a central reference laboratory. some 5041 Gram-positive and 4026 Gram-negative isolates were included. Against Gram-positive isolates overall, ceftobiprole had the lowest MIC50 (0.5 mg/L), compared with 1 mg/L for its comparators (vancomycin, teicoplanin and linezolid). Against methicillin-resistant Staphylococcus aureus, all four agents had a similar MIC90 (2 mg/L), but ceftobiprole had a 4-fold better MIC90 (0.5 mg/L) against methicillin-susceptible strains. Only 38 Gram-positive isolates were confirmed as ceftobiprole resistant. Among Gram-negative strains, 86.9%, 91.7% and 95.2% were susceptible to ceftobiprole, ceftazidime and cefepime, respectively. Pseudomonas aeruginosa was less susceptible to all three antimicrobials than any other Gram-negative pathogen. There was generally good agreement between local Etest results and those obtained at the reference laboratory (for ceftobiprole: 86.8% with Gram-negatives; and 94.7% with Gram-positives), as well as between results obtained by BMD and Etest methods (for ceftobiprole: 98.2% with Gram-negatives; and 98.4% with Gram-positives). ceftobiprole exhibits in vitro activity against a wide range of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. No changes in its known susceptibility profile were identified.

Oxycodone

MedlinePlus

... this type of medication for at least one week. Oxycodone is in a class of medications called ... have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), ...

Hydromorphone

MedlinePlus

... this type of medication for at least one week and should not be used to treat mild ... have stopped taking them within the past 2 weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), ...

Fosfomycin synergy in vitro with amoxicillin, daptomycin, and linezolid against vancomycin-resistant Enterococcus faecium from renal transplant patients with infected urinary stents.

PubMed

Descourouez, Jillian L; Jorgenson, Margaret R; Wergin, Justine E; Rose, Warren E

2013-03-01

Fosfomycin is a potential option for vancomycin-resistant enterococcus (VRE) infections despite limited in vitro and clinical data. In this study, 32 VRE isolates from renal transplant patients with urinary stent infections were susceptible to fosfomycin, daptomycin, and linezolid and resistant to amoxicillin, minocycline, and nitrofurantoin based on their MIC(50)s and MIC(90)s. Fosfomycin was bacteriostatic at 0.5 to 16× the MIC (32 to 2,048 μg/ml); synergy occurred when fosfomycin was combined with daptomycin (2.8 to 3.9 log(10) CFU/ml kill; P < 0.001) or amoxicillin (2.6 to 3.4; P < 0.05). These combinations may be potent options to treat VRE urinary infections pending investigation of clinical efficacy.

What is the best therapeutic approach to methicillin-resistant Staphylococcus aureus pneumonia?

PubMed

Peyrani, Paula; Ramirez, Julio

2015-04-01

The purpose of this review is to define what the best therapeutic approach is for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Although two meta-analyses reported conflicting findings, recent retrospective studies reported higher success rates in patients with MRSA pneumonia treated with linezolid when compared to vancomycin. Only registration trials are available for some anti-MRSA antibiotics, such as telavancin, ceftaroline, and ceftobiprole. Scarce information is available regarding the best therapeutic approach for MRSA community-acquired pneumonia. Linezolid seems to be a better choice than vancomycin for the treatment of MRSA ventilator-associated pneumonia. It is still unclear whether this affirmation holds for other forms of MRSA pneumonia. Further research is needed to define whether newer antibiotics are better alternatives than currently recommended agents.

Comparative efficacy and safety of antibiotics used to treat acute bacterial skin and skin structure infections: Results of a network meta-analysis.

PubMed

Guest, Julian F; Esteban, Jaime; Manganelli, Anton G; Novelli, Andrea; Rizzardini, Giuliano; Serra, Miquel

2017-01-01

This NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (≥18 years of age) with ABSSSI. Comparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality. Study interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline. Dalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes.

Comparative efficacy and safety of antibiotics used to treat acute bacterial skin and skin structure infections: Results of a network meta-analysis

PubMed Central

Esteban, Jaime; Manganelli, Anton G.; Novelli, Andrea; Rizzardini, Giuliano; Serra, Miquel

2017-01-01

Objective This NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (≥18 years of age) with ABSSSI. Methods Comparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality. Results Study interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline. Conclusion Dalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes. PMID:29136035

Ethambutol/Linezolid Toxic Optic Neuropathy.

PubMed

Libershteyn, Yevgeniya

2016-02-01

To report a rare toxic optic neuropathy after long-term use of two medications: ethambutol and linezolid. A 65-year-old man presented to the Miami Veterans Affairs Medical Center in December 2014 for evaluation of progressive vision decrease in both eyes. The patient presented with best-corrected visual acuities of 20/400 in the right eye and counting fingers at 5 feet in the left eye. Color vision was significantly reduced in both eyes. Visual fields revealed a cecocentral defect in both eyes. His fundus and optic nerve examination was unremarkable. Because vision continued to decline after discontinuation of ethambutol, linezolid was also discontinued, after which vision, color vision, and visual fields improved. Because of these findings, the final diagnosis was toxic optic neuropathy. Final visual outcome was 20/30 in the right eye and 20/40 in the left eye. Drug-associated toxic optic neuropathy is a rare but vision-threatening condition. Diagnosis is made based on an extensive case history and careful clinical examination. The examination findings include varying decrease in vision, normal pupils and extraocular muscles, and unremarkable fundoscopy, with the possibility of swollen optic discs in the acute stage of the optic neuropathy. Other important findings descriptive of toxic optic neuropathy include decreased color vision and cecocentral visual field defects. This case illustrates the importance of knowledge of all medications and/or substances a patient consumes that may cause a toxic reaction and discontinuing them immediately if the visual functions are worsening or not improving.

The human clone ST22 SCCmec IV methicillin-resistant Staphylococcus aureus isolated from swine herds and wild primates in Nepal: is man the common source?

PubMed

Roberts, Marilyn C; Joshi, Prabhu Raj; Greninger, Alexander L; Melendez, Daira; Paudel, Saroj; Acharya, Mahesh; Bimali, Nabin Kishor; Koju, Narayan P; No, David; Chalise, Mukesh; Kyes, Randall C

2018-05-01

Swine nasal samples [n = 282] were collected from 12 randomly selected farms around Kathmandu, Nepal, from healthy animals. In addition, wild monkey (Macaca mulatta) saliva samples [n = 59] were collected near temples areas in Kathmandu using a non-invasive sampling technique. All samples were processed for MRSA using standardized selective media and conventional biochemical tests. MRSA verification was done and isolates characterized by SCCmec, multilocus sequence typing, whole genome sequencing [WGS] and antibiotic susceptibilities. Six (2.1%) swine MRSA were isolated from five of the different swine herds tested, five were ST22 type IV and one ST88 type V. Four (6.8%) macaques MRSA were isolated, with three ST22 SCCmec type IV and one ST239 type III. WGS sequencing showed that the eight ciprofloxacin resistant ST22 isolates carried gyrA mutation [S84L]. Six isolates carried the erm(C) genes, five isolates carried aacC-aphD genes and four isolates carried blaZ genes. The swine linezolid resistant ST22 did not carry any known acquired linezolid resistance genes but had a mutation in ribosomal protein L22 [A29V] and an insertion in L4 [68KG69], both previously associated with linezolid resistance. Multiple virulence factors were also identified. This is the first time MRSA ST22 SCCmec IV has been isolated from livestock or primates.

Synergistic Interaction of Methanol Extract from Canarium odontophyllum Miq. Leaf in Combination with Oxacillin against Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC 33591

PubMed Central

Sandra, Vimashiinee

2016-01-01

Canarium odontophyllum (CO) Miq. has been considered as one of the most sought-after plant species in Sarawak, Malaysia, due to its nutritional and pharmacological benefits. This study aimed to evaluate the pharmacodynamic interaction of crude methanol and acetone extracts from CO leaves in combination with oxacillin, vancomycin, and linezolid, respectively, against MRSA ATCC 33591 as preliminary study has reported its potential antistaphylococcal activity. The broth microdilution assay revealed that both methanol and acetone extracts were bactericidal with Minimum Inhibitory Concentration (MIC) of 312.5 μg/mL and 156.25 μg/mL and Minimum Bactericidal Concentration (MBC) of 625 μg/mL and 312.5 μg/mL, respectively. Fractional Inhibitory Concentration (FIC) indices were obtained via the chequerboard dilution assay where methanol extract-oxacillin, acetone extract-oxacillin, methanol extract-linezolid, and acetone extract-linezolid combinations exhibited synergism (FIC index ≤ 0.5). The synergistic action of the methanol extract-oxacillin combination was verified by time-kill analysis where bactericidal effect was observed at concentration of 1/8 × MIC of both compounds at 9.6 h compared to oxacillin alone. As such, these findings postulated that both extracts exert their anti-MRSA mechanism of action similar to that of vancomycin and provide evidence that the leaves of C. odontophyllum have the potential to be developed into antistaphylococcal agents. PMID:27006659

Synergistic Interaction of Methanol Extract from Canarium odontophyllum Miq. Leaf in Combination with Oxacillin against Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC 33591.

PubMed

Basri, Dayang Fredalina; Sandra, Vimashiinee

2016-01-01

Canarium odontophyllum (CO) Miq. has been considered as one of the most sought-after plant species in Sarawak, Malaysia, due to its nutritional and pharmacological benefits. This study aimed to evaluate the pharmacodynamic interaction of crude methanol and acetone extracts from CO leaves in combination with oxacillin, vancomycin, and linezolid, respectively, against MRSA ATCC 33591 as preliminary study has reported its potential antistaphylococcal activity. The broth microdilution assay revealed that both methanol and acetone extracts were bactericidal with Minimum Inhibitory Concentration (MIC) of 312.5 μg/mL and 156.25 μg/mL and Minimum Bactericidal Concentration (MBC) of 625 μg/mL and 312.5 μg/mL, respectively. Fractional Inhibitory Concentration (FIC) indices were obtained via the chequerboard dilution assay where methanol extract-oxacillin, acetone extract-oxacillin, methanol extract-linezolid, and acetone extract-linezolid combinations exhibited synergism (FIC index ≤ 0.5). The synergistic action of the methanol extract-oxacillin combination was verified by time-kill analysis where bactericidal effect was observed at concentration of 1/8 × MIC of both compounds at 9.6 h compared to oxacillin alone. As such, these findings postulated that both extracts exert their anti-MRSA mechanism of action similar to that of vancomycin and provide evidence that the leaves of C. odontophyllum have the potential to be developed into antistaphylococcal agents.

The bactericidal effects of anti-MRSA agents with rifampicin and sulfamethoxazole-trimethoprim against intracellular phagocytized MRSA.

PubMed

Yamaoka, Toshimori

2007-06-01

We experienced therapeutic failure with vancomycin in patients with serious methicillin-resistant Staphylococcus aureus (MRSA) infections, in some of whom the bacteria were found to be alive in the leukocytes. We therefore evaluated the antimicrobial activity of several anti-MRSA agents (vancomycin, linezolid, quinupristin/dalfopristin, arbekacin) and co-administered agents (rifampicin, sulfamethoxazole-trimethoprim) against clinically isolated MRSA in phagocytized human polymorphonuclear leukocytes. After allowing the leukocytes to phagocytize the bacteria, the mixture was separated into leukocytes and supernatant, to which MRSA agents were added, and incubated for 24 h. After incubation, the leukocytes were crushed and the intracellular MRSA was cultured quantitatively. Vancomycin resulted in a less than 1% survival ratio of extracellular MRSA, but it was one of the highest ratios of intracellular MRSA with 33.8% compared with other agents. The survival ratios of intracellular MRSA with vancomycin plus rifampicin and with vancomycin plus rifampicin plus sulfamethoxazole-trimethoprim were 0.78% and 1.02%, respectively, which is significantly lower than that of vancomycin. For linezolid, quinupristin/dalfopristin, and arbekacin, there were no significant differences in the survival ratios between monotherapy and combination therapy against either extracellular or intracellular MRSA. The results suggest that the concomitant use of rifampicin or rifampicin plus sulfamethoxazole/trimethoprim with vancomycin is effective for MRSA phagocytized in leukocytes when vancomycin monotherapy is not sufficiently effective. Combination therapy showed no difference in efficacy in the case of linezolid, quinupristin/dalfopristin, and arbekacin.

In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria.

PubMed

Citron, D M; Merriam, C V; Tyrrell, K L; Warren, Y A; Fernandez, H; Goldstein, E J C

2003-07-01

By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at or=256 microg/ml. Ramoplanin displays excellent activity against C. difficile and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.

Heterogeneity of Genetic Pathways toward Daptomycin Nonsusceptibility in Staphylococcus aureus Determined by Adjunctive Antibiotics

PubMed Central

Berti, Andrew D.; Baines, Sarah L.; Howden, Benjamin P.; Sakoulas, George; Nizet, Victor; Proctor, Richard A.

2015-01-01

Daptomycin is increasingly used in combination with other antibiotics to enhance antimicrobial efficacy and/or to mitigate the emergence of daptomycin nonsusceptibility (DNS). This study used a clinical methicillin-resistant Staphylococcus aureus (MRSA) strain in which DNS emerged upon therapy to examine the influence of antibiotic combinations on the development of mutations in specific genes (mprF, rpoBC, dltA, cls2, and yycFG) previously associated with DNS. Whole genomes of bacteria obtained following 28 days of in vitro exposure to daptomycin with or without adjunctive clarithromycin, linezolid, oxacillin, or trimethoprim-sulfamethoxazole were sequenced, and the sequences were compared to that of the progenitor isolate. The addition of oxacillin to medium containing daptomycin prevented the emergence of mprF mutation but did not prevent rpoBC mutation (P < 0.01). These isolates maintained susceptibility to daptomycin during the combined exposure (median MIC, 1 mg/liter). Daptomycin plus clarithromycin or linezolid resulted in low-level (1.5 to 8 mg/liter) and high-level (12 to 96 mg/liter) DNS, respectively, and did not prevent mprF mutation. However, these same combinations prevented rpoBC mutation. Daptomycin alone or combined with linezolid or trimethoprim-sulfamethoxazole resulted in high-level DNS and mutations in mprF plus rpoBC, cls2, and yycFG. Combining daptomycin with different antimicrobials alters the mutational space available for DNS development, thereby favoring the development of predictable collateral susceptibilities. PMID:25733508

Heterogeneity of genetic pathways toward daptomycin nonsusceptibility in Staphylococcus aureus determined by adjunctive antibiotics.

PubMed

Berti, Andrew D; Baines, Sarah L; Howden, Benjamin P; Sakoulas, George; Nizet, Victor; Proctor, Richard A; Rose, Warren E

2015-05-01

Daptomycin is increasingly used in combination with other antibiotics to enhance antimicrobial efficacy and/or to mitigate the emergence of daptomycin nonsusceptibility (DNS). This study used a clinical methicillin-resistant Staphylococcus aureus (MRSA) strain in which DNS emerged upon therapy to examine the influence of antibiotic combinations on the development of mutations in specific genes (mprF, rpoBC, dltA, cls2, and yycFG) previously associated with DNS. Whole genomes of bacteria obtained following 28 days of in vitro exposure to daptomycin with or without adjunctive clarithromycin, linezolid, oxacillin, or trimethoprim-sulfamethoxazole were sequenced, and the sequences were compared to that of the progenitor isolate. The addition of oxacillin to medium containing daptomycin prevented the emergence of mprF mutation but did not prevent rpoBC mutation (P < 0.01). These isolates maintained susceptibility to daptomycin during the combined exposure (median MIC, 1 mg/liter). Daptomycin plus clarithromycin or linezolid resulted in low-level (1.5 to 8 mg/liter) and high-level (12 to 96 mg/liter) DNS, respectively, and did not prevent mprF mutation. However, these same combinations prevented rpoBC mutation. Daptomycin alone or combined with linezolid or trimethoprim-sulfamethoxazole resulted in high-level DNS and mutations in mprF plus rpoBC, cls2, and yycFG. Combining daptomycin with different antimicrobials alters the mutational space available for DNS development, thereby favoring the development of predictable collateral susceptibilities. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Quantitative proteomic view associated with resistance to clinically important antibiotics in Gram-positive bacteria: a systematic review

PubMed Central

Lee, Chang-Ro; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

2015-01-01

The increase of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) poses a worldwide and serious health threat. Although new antibiotics, such as daptomycin and linezolid, have been developed for the treatment of infections of Gram-positive pathogens, the emergence of daptomycin-resistant and linezolid-resistant strains during therapy has now increased clinical treatment failures. In the past few years, studies using quantitative proteomic methods have provided a considerable progress in understanding antibiotic resistance mechanisms. In this review, to understand the resistance mechanisms to four clinically important antibiotics (methicillin, vancomycin, linezolid, and daptomycin) used in the treatment of Gram-positive pathogens, we summarize recent advances in studies on resistance mechanisms using quantitative proteomic methods, and also examine proteins playing an important role in the bacterial mechanisms of resistance to the four antibiotics. Proteomic researches can identify proteins whose expression levels are changed in the resistance mechanism to only one antibiotic, such as LiaH in daptomycin resistance and PrsA in vancomycin resistance, and many proteins simultaneously involved in resistance mechanisms to various antibiotics. Most of resistance-related proteins, which are simultaneously associated with resistance mechanisms to several antibiotics, play important roles in regulating bacterial envelope biogenesis, or compensating for the fitness cost of antibiotic resistance. Therefore, proteomic data confirm that antibiotic resistance requires the fitness cost and the bacterial envelope is an important factor in antibiotic resistance. PMID:26322035

Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus.

PubMed

Eissa, Ibrahim H; Mohammad, Haroon; Qassem, Omar A; Younis, Waleed; Abdelghany, Tamer M; Elshafeey, Ahmed; Abd Rabo Moustafa, Mahmoud M; Seleem, Mohamed N; Mayhoub, Abdelrahman S

2017-04-21

A new class of diphenylurea was identified as a novel antibacterial scaffold with an antibacterial spectrum that includes highly resistant staphylococcal isolates, namely methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA & VRSA). Starting with a lead compound 3 that carries an aminoguanidine functionality from one side and a n-butyl moiety on the other ring, several analogues were prepared. Considering the pharmacokinetic parameters as a key factor in structural optimization, the structure-activity-relationships (SARs) at the lipophilic side chain were rigorously examined leading to the discovery of the cycloheptyloxyl analogue 21n as a potential drug-candidate. This compound has several notable advantages over vancomycin and linezolid including rapid killing kinetics against MRSA and the ability to target and reduce the burden of MRSA harboring inside immune cells (macrophages). Furthermore, the potent anti-MRSA activity of 21n was confirmed in vivo using a Caenorhabditis elegans animal model. The present study provides a foundation for further development of diphenylurea compounds as potential therapeutic agents to address the burgeoning challenge of bacterial resistance to antibiotics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative Staphylococcus strains in vitro.

PubMed

Wojtyczka, Robert D; Dziedzic, Arkadiusz; Kępa, Małgorzata; Kubina, Robert; Kabała-Dzik, Agata; Mularz, Tomasz; Idzik, Danuta

2014-05-22

Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

Bacterial lung sepsis in patients with febrile neutropenia.

PubMed

Lanoix, Jean-Philippe; Schmit, Jean-Luc; Douadi, Youcef

2012-05-01

This review provides an update on microbiological and therapeutic data in febrile neutropenic patients in general and those with bacterial lung sepsis in particular. Although the Infectious Diseases Society of America updated its guidelines on febrile neutropenia in 2010, changing epidemiological factors and the spread of new drug resistance constitutes challenges for initial treatment of this condition. Lung sepsis stands out because of the frequent absence of microbiological identification. We review the use of newly available, novel, broad-spectrum antibiotics (linezolid, tigecycline, daptomycin, etc.) in this indication. Although the incidence of Gram-negative infections in neutropenic fever is leveling off, there is a worrying increase in resistance. New drugs are available but not well studied in febrile neutropenia; daptomycin and tigecycline should not be used in suspected lung sepsis in these patients. New diagnostic tools (such as the procalcitonin assay and the LightCycler SeptiFast assay, Roche Molecular Systems) appear to be unhelpful in febrile neutropenia, although more data on fungal sepsis are required. There are no specific features of the treatment of pneumonia or septic shock in neutropenic fever, but both conditions increase the mortality rate.

In vivo bioluminescence imaging to evaluate systemic and topical antibiotics against community-acquired methicillin-resistant Staphylococcus aureus-infected skin wounds in mice.

PubMed

Guo, Yi; Ramos, Romela Irene; Cho, John S; Donegan, Niles P; Cheung, Ambrose L; Miller, Lloyd S

2013-02-01

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents.

In Vitro Activities of Ramoplanin, Teicoplanin, Vancomycin, Linezolid, Bacitracin, and Four Other Antimicrobials against Intestinal Anaerobic Bacteria

PubMed Central

Citron, D. M.; Merriam, C. V.; Tyrrell, K. L.; Warren, Y. A.; Fernandez, H.; Goldstein, E. J. C.

2003-01-01

By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at ≤2 μg/ml against 287 of 300 (95.7%) gram-positive organisms, including 18 strains of Clostridium difficile for which MICs of ramoplanin were 0.25 to 0.5 μg/ml; for 3 of these, linezolid MICs were 8 to 16 μg/ml. Nineteen Clostridium innocuum strains for which the vancomycin MIC at which 90% of strains were inhibited was 16 μg/ml were susceptible to ramoplanin at 0.06 to 0.25 μg/ml and to teicoplanin at 0.125 to 1.0 μg/ml. All strains of Eubacterium, Actinomyces, Propionibacterium, and Peptostreptococcus spp. were inhibited by ≤0.25 μg of ramoplanin per ml and ≤1 μg of vancomycin per ml. Ramoplanin was also active at ≤4 μg/ml against 15 of 22 of the Prevotella and Porphyromonas strains tested, but ramoplanin MICs for all 31 strains of the Bacteroides fragilis group, the Fusobacterium mortiferum-Fusobacterium varium group, and Veillonella spp. were ≥256 μg/ml. Ramoplanin displays excellent activity against C. difficile and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora. PMID:12821492

Linezolid-Resistant Staphylococcus aureus Strain 1128105, the First Known Clinical Isolate Possessing the cfr Multidrug Resistance Gene

PubMed Central

Zuill, Douglas E.; Scharn, Caitlyn R.; Deane, Jennifer; Sahm, Daniel F.; Denys, Gerald A.; Goering, Richard V.; Shaw, Karen J.

2014-01-01

The Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribosomal subunit, including some oxazolidinones, such as linezolid (LZD). The mobile cfr gene was identified in European veterinary isolates from the late 1990s, although the earliest report of a clinical cfr-positive strain was the 2005 Colombian methicillin-resistant Staphylococcus aureus (MRSA) isolate CM05. Here, through retrospective analysis of LZDr clinical strains from a U.S. surveillance program, we identified a cfr-positive MRSA isolate, 1128105, from January 2005, predating CM05 by 5 months. Molecular typing of 1128105 revealed a unique pulsed-field gel electrophoresis (PFGE) profile most similar to that of USA100, spa type t002, and multilocus sequence type 5 (ST5). In addition to cfr, LZD resistance in 1128105 is partially attributed to the presence of a single copy of the 23S rRNA gene mutation T2500A. Transformation of the ∼37-kb conjugative p1128105 cfr-bearing plasmid from 1128105 into S. aureus ATCC 29213 background strains was successful in recapitulating the Cfr antibiogram, as well as resistance to aminoglycosides and trimethoprim. A 7-kb cfr-containing region of p1128105 possessed sequence nearly identical to that found in the Chinese veterinary Proteus vulgaris isolate PV-01 and in U.S. clinical S. aureus isolate 1900, although the presence of IS431-like sequences is unique to p1128105. The cfr gene environment in this early clinical cfr-positive isolate has now been identified in Gram-positive and Gram-negative strains of clinical and veterinary origin and has been associated with multiple mobile elements, highlighting the versatility of this multidrug resistance gene and its potential for further dissemination. PMID:25155597

First report of Nocardia asiatica olecranon bursitis in an immunocompetent traveler returning to Austria.

PubMed

Leitner, Eva; Valentin, Thomas; Hoenigl, Martin; Lanz, Philipp; Flick, Holger; Zollner-Schwetz, Ines; Grisold, Andrea J; Feierl, Gebhard; Krause, Robert

2013-07-01

Nocardia spp. are rarely isolated in extrapulmonary clinical specimens. We describe the first case of olecranon bursitis caused by Nocardia asiatica. The patient, a traveler returning from Thailand, was successfully treated with linezolid.

First Report of Nocardia asiatica Olecranon Bursitis in an Immunocompetent Traveler Returning to Austria

PubMed Central

Leitner, Eva; Valentin, Thomas; Lanz, Philipp; Flick, Holger; Zollner-Schwetz, Ines; Grisold, Andrea J.; Feierl, Gebhard; Krause, Robert

2013-01-01

Nocardia spp. are rarely isolated in extrapulmonary clinical specimens. We describe the first case of olecranon bursitis caused by Nocardia asiatica. The patient, a traveler returning from Thailand, was successfully treated with linezolid. PMID:23637291

In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

PubMed Central

Guo, Yi; Ramos, Romela Irene; Cho, John S.; Donegan, Niles P.; Cheung, Ambrose L.

2013-01-01

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents. PMID:23208713

Rapid MRSA PCR on respiratory specimens from ventilated patients with suspected pneumonia: a tool to facilitate antimicrobial stewardship.

PubMed

Trevino, S E; Pence, M A; Marschall, J; Kollef, M H; Babcock, H M; Burnham, C-A D

2017-05-01

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in ventilated patients. Our objective was to evaluate the GeneXpert MRSA/SA SSTI Assay (Xpert MRSA/SA) (Cepheid, Sunnyvale, CA) for use in lower respiratory tract (LRT) specimens for rapid MRSA detection and to determine the potentially saved antibiotic-days if a culture-based identification method was replaced by this assay. Remnant LRT samples from ventilated patients submitted to the microbiology laboratory for routine culture were tested using conventional culture and Xpert MRSA/SA. One hundred of 310 LRT specimens met the inclusion criteria. Ten samples were positive for MRSA by Xpert MRSA/SA, while six were positive by routine culture methods. Xpert MRSA/SA correctly identified 5/6 positive and 89/94 negative MRSA specimens, for a sensitivity of 83.3%, specificity of 94.7%, positive predictive value of 45.6%, and negative predictive value of 98.9%. The assay also correctly detected 3/3 positive and 90/97 negative methicillin-susceptible S. aureus (MSSA) specimens, for a sensitivity of 100%, specificity of 92.8%, positive predictive value of 30%, and negative predictive value of 100%. A total of 748 vancomycin and 305 linezolid antibiotic-days were associated with the enrolled specimens. Vancomycin and linezolid utilization could decrease by 68.4% and 83%, respectively, if discontinued 1 day after negative polymerase chain reaction (PCR) results. The Xpert MRSA/SA SSTI rapid MRSA PCR assay performed well in respiratory samples from ventilated patients with suspected pneumonia and has the potential to facilitate stewardship efforts such as reducing empiric vancomycin and linezolid therapy.

MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a Staphylococcus aureus Immunocompromised Pneumonia Model

PubMed Central

Hua, L.; Cohen, T. S.; Shi, Y.; Datta, V.; Hilliard, J. J.; Tkaczyk, C.; Suzich, J.; Stover, C. K.

2015-01-01

Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. aureus pneumonia; however, the effects of the MAb in immunocompromised mice have not been reported. In this study, passive immunization with MEDI4893* increased survival rates and reduced bacterial numbers in the lungs in an immunocompromised murine S. aureus pneumonia model. Lungs from infected mice exhibited alveolar epithelial damage, protein leakage, and bacterial overgrowth, whereas lungs from mice passively immunized with MEDI4893* retained a healthy architecture, with an intact epithelial barrier. Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined with subtherapeutic doses of vancomycin or linezolid improved survival rates, compared with the monotherapies. Furthermore, coadministration of MEDI4893* with vancomycin or linezolid extended the antibiotic treatment window. These data suggest that MAb-mediated neutralization of AT holds promise in strategies for prevention and adjunctive therapy among immunocompromised patients. PMID:25987629

Deposition and transport of linezolid mediated by a synthetic surfactant Synsurf® within a pressurized metered dose inhaler: a Calu-3 model

PubMed Central

van Rensburg, Lyné; van Zyl, Johann M; Smith, Johan

2018-01-01

Background Previous studies in our laboratory demonstrated that a synthetic peptide containing lung surfactant enhances the permeability of chemical compounds through bronchial epithelium. The purpose of this study was to test two formulations of Synsurf® combined with linezolid as respirable compounds using a pressurized metered dose inhaler (pMDI). Methods Aerosolization efficiency of the surfactant-drug microparticles onto Calu-3 monolayers as an air interface culture was analyzed using a Next Generation Impactor™. Results The delivered particles and drug dose showed a high dependency from the preparation that was aerosolized. Scanning electron microscopy imaging allowed for visualization of the deposited particles, establishing them as liposomal-type structures (diameter 500 nm to 2 μm) with filamentous features. Conclusion The different surfactant drug combinations allow for an evaluation of the significance of the experimental model system, as well as assessment of the formulations providing a possible noninvasive, site-specific, delivery model via pMDI. PMID:29765201

NOS2-deficient mice with hypoxic necrotizing lung lesions predict outcomes of tuberculosis chemotherapy in humans.

PubMed

Gengenbacher, Martin; Duque-Correa, Maria A; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Zedler, Ulrike; Reece, Stephen T; Nayyar, Amit; Cole, Stewart T; Makarov, Vadim; Barry Iii, Clifton E; Dartois, Véronique; Kaufmann, Stefan H E

2017-08-18

During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2 -/- mice incapable of NO-production in immune cells as microbial defence uniformly develop hypoxic necrotizing lung lesions, widely observed in human TB. To study the impact of hypoxic necrosis on the efficacy of antimycobacterials and drug candidates, we subjected Nos2 -/- mice with TB to monotherapy before or after establishment of human-like pathology. Isoniazid induced a drug-tolerant persister population only when necrotic lesions were present. Rifapentine was more potent than rifampin prior to development of human-like pathology and equally potent thereafter, in agreement with recent clinical trials. Pretomanid, delamanid and the pre-clinical candidate BTZ043 were bactericidal independent of pulmonary pathology. Linezolid was bacteriostatic in TB-infected Nos2 -/- mice but significantly improved lung pathology. Hypoxic necrotizing lesions rendered moxifloxacin less active. In conclusion, Nos2 -/- mice are a predictive TB drug development tool owing to their consistent development of human-like pathology.

[Pathogens in expressed prostatic secretion and their correlation with serum prostate specific antigen: analysis of 320 cases].

PubMed

Wang, Shu-Xia; Zhang, Jia-Ming; Wu, Kai; Chen, Juan; Shi, Jian-Feng

2014-08-01

To investigate the pathogenic infection and its drug resistance in expressed prostatic secretion (EPS) and its correlation with serum PSA, and provide some evidence for the systematic and normalized diagnosis and treatment of prostatitis. Three EPS swabs were collected from each of the 320 prostatis patients following measurement of the serum PSA level, 1 for bacterial culture and identification, 1 for detection of Mycoplasma and drug sensitivity, and the other for examination of Chlamydia trachomatis antigen by colloidal gold immunoblot. Totally 244 strains were isolated from the 320 EPS samples, including 188 bacterial strains (dominated by Staphylococcus and sensitive to vancomycin or linezolid) and 44 Mycoplasma and Chlamydia strains (mainly Ureaplasma urealyticum and susceptible to josamycin or doxycycline). The serum PSA level was significantly higher in the pathogen-positive than in the pathogen-negative group ([6.98 +/- 0.56] microg/L vs [2.32 +/- 0.12] microg/L, P < 0.05). Prostatitis may lead to the elevation of the serum PSA level and the pathogens involved vary in their resistance to different antibacterial spectrums. Therefore, appropriate and individualized antibiotic therapy should be selected according to etiological diagnosis and the results of drug sensitivity test.

Impact of a computer-generated alert system prompting review of antibiotic use in hospitals.

PubMed

Lesprit, Philippe; Duong, Trung; Girou, Emmanuelle; Hemery, François; Brun-Buisson, Christian

2009-05-01

The aim of this study was to measure the impact on antibiotic use of a computer-generated alert prompting post-prescription review and direct counselling in hospital wards. A computer-generated alert on new prescriptions of 15 antibiotics was reviewed weekly by an infectious disease physician for 41 weeks. During the first 6 months of the study, criteria selected for potential intervention were: (i) a planned duration of treatment of > or =10 days; (ii) discordance between the spectrum of the prescribed antibiotic and available microbiological results; or (iii) prescriptions of broad-spectrum beta-lactams, fluoroquinolones, glycopeptides or linezolid. During the following 5 months, the alert was restricted to any prescription of the 15 antibiotics in the 9 wards where overall antibiotic use had not decreased in the past year. We analysed 2385 prescriptions, 932 (39%) of which generated an alert for potential intervention. Among the latter, 482 (51.7%) prescriptions prompted direct counselling, mainly for shortening the planned duration of therapy (18.9%), withdrawing antibiotics (16.2%) or streamlining therapy (15.5%). The attending physicians' compliance with the recommendations was 80%. The overall median (interquartile range) days of therapy prescribed by the attending physicians was reduced from an initial duration of 8 (7-14) to 7 (6-11) days (P < 0.0001), resulting in 26.5% less antibiotic days prescribed. The time required for the intervention was 6 h per week. This computer-prompted post-prescription review led physicians to modify one half of the antibiotic courses initially prescribed and was well accepted by the majority, although they had not requested counselling.

[Saccharomyces cerevisiae fungemia in an elderly patient following probiotic treatment].

PubMed

Eren, Zehra; Gurol, Yeşim; Sonmezoglu, Meral; Eren, Hatice Seyma; Celik, Gülden; Kantarci, Gülçin

2014-04-01

Saccharomyces cerevisiae, known as baker's yeast, is also used as a probiotic agent to treat gastroenteritis by modulating the endogenous flora and immune system. However, since there have been increasing reports of fungemia due to S.cerevisiae and its subspecies S.boulardii, it is recommended that probiotics should be cautiously used in immunosuppressed patients, people with underlying diseases and low-birth weight babies. To emphasize this phenomenon, in this report, a case of S.cerevisiae fungemia developed in a patient given probiotic treatment for antibiotic-associated diarrhea, was presented. An 88-year-old female patient was admitted to our hospital with left hip pain, hypotension, and confusion. Her medical history included hypertension, chronic renal failure, left knee replacement surgery, and recurrent urinary tract infections due to neurogenic bladder. She was transferred to the intensive care unit with the diagnosis of urosepsis. After obtaining blood and urine samples for culture, empirical meropenem (2 x 500 mg) and linezolid (1 x 600 mg) treatment were administered. A central venous catheter (CVC) was inserted and after one day of inotropic support, her hemodynamic parameters were stabilized. The urine culture obtained on admission yielded extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Urine culture was repeated after three days and no bacteria were isolated. On the 4th day of admission she developed diarrhea. Toxin A/B tests for Clostridium difficile were negative. To relieve diarrhea, S.boulardii (Reflor 250 mg capsules, Sanofi Aventis, Turkey) was administered twice a day, without opening capsules. Two days later, her C-reactive protein (CRP) level increased from 23.2 mg/L to 100 mg/L without fever. Her blood culture taken from the CVC yielded S.cerevisiae. Linezolid and meropenem therapies were stopped on the 13th and 14th days, respectively, while prophylactic fluconazole therapy was replaced with caspofungin 1 x 50 mg on the fifth day. After seven days of therapy CRP and serum creatinine levels decreased to 9.1 mg/L and 1.2 mg/dl, respectively; and she was discharged from the hospital with improvement. The probiotic capsules were used unopen, thus, it was proposed that S.cerevisiae fungemia originated from translocation from the intestinal mucosa. Since it was not possible to investigate the molecular genetics of the strain isolated from the blood culture and the strain present in the probiotic, a definite conclusion about the origin of the strain could not be reached. It was thought that old age and underlying disease of the patient were the related predisposing factors for S.cerevisiae fungemia. This case emphasized that clinicians should be cautious in case of probiotic application even though in encapsulated form, even in immunocompetent patients with a history of long-term hospital stay and use of broad-spectrum antimicrobials since there may be a risk of S.cerevisiae fungemia development.

Susceptibility rates in Latin American nations: report from a regional resistance surveillance program (2011).

PubMed

Jones, Ronald N; Guzman-Blanco, Manuel; Gales, Ana C; Gallegos, Belisario; Castro, Aura Lucia Leal; Martino, Marines Dalla Valle; Vega, Silvio; Zurita, Jeannete; Cepparulo, Mario; Castanheira, Mariana

2013-01-01

To establish a resistance (R) surveillance program monitoring antimicrobial susceptibility patterns in Latin America (LATAM; Argentina [ARG], Brazil [BRA], Chile, Colombia [CBA], Costa Rica, Ecuador [ECU], Guatemala [GUA], Mexico [MEX], Panama [PAN], Peru, and Venezuela [VEN]). In 2011, 4979 organisms were collected from 11 nations (20 laboratories) for susceptibility testing in a central laboratory design. Antimicrobials were tested by CLSI methods and results interpreted by CLSI and EUCAST breakpoints. Most common Gram-positive (Staphylococcus aureus [SA, 921], other staphylococci [CoNS; 299], enterococci [218], Streptococcus pneumoniae [SPN; 182], β-haemolytic streptococci [115]) and Gram-negative (E. coli [EC; 644], Klebsiella spp. [KSP; 517], Enterobacters [272], Pseudomonas aeruginosa [PSA; 586], Acinetobacters [ACB; 494]) pathogens were analyzed against linezolid (LZD), vancomycin (VAN), tigecycline (TIG), colistin (COL), cefoperazone/sulbactam (C/S), and amikacin (AMK). MRSA rates varied from 29% (CBA, BRA) to 79% (Peru); but LZD (MIC90, 2mg/L), TIG (MIC90, 0.12mg/L) and VAN (MIC90, 1mg/L) covered all strains. Enterococci showed a 14% VRE rate, highest in BRA and MEX; all inhibited by TIG and daptomycin, but not LZD (three non-susceptible with G2576T mutations or cfr). Penicillin-R among SPN and viridans streptococci was 51.6 and 41.1%, respectively. LZD overall R against Gram-positives was 0.3%. High ESBL rates were observed in EC (54-71%) and KSP (≥50%) from GUA, MEX and Peru, and six nations, respectively. Carbapenem-R in KSP was 9%, highest rates associated with KPC in BRA, CBA, ECU, PAN and VEN; also a NDM-1 in KSP from CBA. AMK, TIG, C/S and carbapenems were the broadest-spectrum agents tested against Enterobacteriaceae. Only COL inhibited >90% of PSA; COL and TIG (≤2mg/L) covered ≥85% of ACB. LATAM nations demonstrated variable levels of antimicrobial R especially among Enterobacteriaceae (β-lactamase-mediated), PSA and ACB. MRSA (48%), VRE (14%) and multidrug-R SPN were also regional therapeutic challenges. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

77 FR 18793 - Spectrum Sharing Innovation Test-Bed Pilot Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

.... 120322212-2212-01] Spectrum Sharing Innovation Test-Bed Pilot Program AGENCY: National Telecommunications... Innovation Test-Bed pilot program to assess whether devices employing Dynamic Spectrum Access techniques can... Spectrum Sharing Innovation Test-Bed (Test-Bed) pilot program to examine the feasibility of increased...

Non Diphtheritic Corynebacteria: An Emerging Nosocomial Pathogen in Skin and Soft Tissue Infection.

PubMed

Rudresh, Shoorashetty Manohar; Ravi, G S; Alex, Ann Mary; Mamatha, K R; Sunitha, L; Ramya, K Thangam

2015-12-01

Non-diphtheritic corynebacteria are normal inhabitants of skin and mucous membrane. When isolated from clinical specimens they are often considered as contaminants. Recent reports suggest their role as emerging nosocomial pathogens. To speciate non-diphtheritic corynebacteria isolated from wound specimens, to correlate their clinical significance and to determine their invitro antimicrobial susceptibilities to 9 antimicrobial agents. Twenty five non-diphtheritic corynebacteria from skin and soft tissue infections were selected for study. Isolates were identified by battery of tests and minimum inhibitory concentration (MIC) was detected by Clinical & Laboratory Standards Institute (CLSI) described broth microdilution method. MIC was interpreted according CLSI and British Society for Antimicrobial Chemotherapy (BSAC) guidelines. C. amycolatum was the predominant species (20%) followed by C. striatum (16%). Penicillin was least effective invitro followed by clindamycin and ciprofloxacin. Excellent activities were shown by vancomycin, linezolid and imipenem. Multidrug resistance was found in all the species. Non-diphtheritic corynebacteria are potential nosocomial pathogens among acute/chronic complicated skin and soft tissue infection. Vancomycin or linezolid can be used empirically to treat such infections until the invitro susceptibility results are available.

MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a Staphylococcus aureus Immunocompromised Pneumonia Model.

PubMed

Hua, L; Cohen, T S; Shi, Y; Datta, V; Hilliard, J J; Tkaczyk, C; Suzich, J; Stover, C K; Sellman, B R

2015-08-01

Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. aureus pneumonia; however, the effects of the MAb in immunocompromised mice have not been reported. In this study, passive immunization with MEDI4893* increased survival rates and reduced bacterial numbers in the lungs in an immunocompromised murine S. aureus pneumonia model. Lungs from infected mice exhibited alveolar epithelial damage, protein leakage, and bacterial overgrowth, whereas lungs from mice passively immunized with MEDI4893* retained a healthy architecture, with an intact epithelial barrier. Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined with subtherapeutic doses of vancomycin or linezolid improved survival rates, compared with the monotherapies. Furthermore, coadministration of MEDI4893* with vancomycin or linezolid extended the antibiotic treatment window. These data suggest that MAb-mediated neutralization of AT holds promise in strategies for prevention and adjunctive therapy among immunocompromised patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

UPLC-MS/MS method for therapeutic drug monitoring of 10 antibiotics used in intensive care units.

PubMed

El-Najjar, Nahed; Hösl, Julian; Holzmann, Thomas; Jantsch, Jonathan; Gessner, André

2018-03-01

A large variation in the levels of different ß-lactams and other antibiotics used in critically ill patients has been documented. The aim of this study is to establish and validate a fast, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous analysis of ten antibiotics (Meropenem, Cefepime, Ceftazidime, Piperacillin, Benzylpenicillin, Ampicillin, Flucloxacillin, Linezolid, and Sulfamethoxazole/Trimethoprim) in human plasma according to European Medicines Agency (EMA) guidelines. Protein precipitation with ice-cold methanol containing 9 isotopically labeled internal standards was used for sample clean up. Antibiotics were detected, following a 4-minute gradient separation, in multiple reactions monitoring (MRM) using API 4000 instrument equipped with electrospray source operating in positive ion mode. The lower limit of quantification was 0.1 mg/L for Meropenem, Ceftazidime, Piperacillin, Ampicillin, Flucloxacillin, and Sulfamethoxazole; 0.05 mg/L for Cefepime, Benzylpenicillin, and Trimethoprim; and 0.02 mg/L for Linezolid. The method proved to be precise and accurate and applicable for therapeutic drug monitoring and other pharmacokinetic studies. Copyright © 2017 John Wiley & Sons, Ltd.

Mechanisms of antibiotic resistance in Staphylococcus aureus.

PubMed

Pantosti, Annalisa; Sanchini, Andrea; Monaco, Monica

2007-06-01

Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus.

A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin.

PubMed

Kingsley, Jeff; Mehra, Purvi; Lawrence, Laura E; Henry, Eugenia; Duffy, Erin; Cammarata, Sue K; Pullman, John

2016-03-01

Delafloxacin is an investigational anionic fluoroquinolone being developed to treat infections caused by Gram-positive and -negative organisms. This clinical trial evaluated the efficacy and safety of delafloxacin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs). In a double-blind, Phase 2 trial, 256 patients were randomized (1 : 1 : 1) to 300 mg of delafloxacin, 600 mg of linezolid or 15 mg/kg vancomycin (actual body weight), each administered intravenously twice daily for 5-14 days. Randomization was stratified by infection category. The primary endpoint was the investigator's assessment of cure, defined as complete resolution of baseline signs and symptoms at follow-up. Secondary endpoints included reductions in the total areas of erythema and induration and assessments of bacterial eradication. This trial has been registered at ClinicalTrials.gov under registration number NCT01283581. Cure rates were significantly greater with delafloxacin versus vancomycin (mean difference: -16.3%; 95% CI, -30.3% to -2.3%; P = 0.031); differences were significant for obese patients (BMI ≥30 kg/m(2); mean difference: -30.0%; 95% CI, -50.7% to -9.3%; P = 0.009), but not for non-obese patients. Cure rates with delafloxacin and linezolid were similar. Using digital measurement, the percentage decrease in total erythema area was significantly greater with delafloxacin versus vancomycin at follow-up (-96.4% versus -84.5%; P = 0.028). There were no differences in bacterial eradication among the treatment groups. The most frequently reported treatment-emergent adverse events were nausea, diarrhoea and vomiting. These data show that delafloxacin is effective in the treatment of ABSSSIs and is well tolerated. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin

PubMed Central

Kingsley, Jeff; Mehra, Purvi; Lawrence, Laura E.; Henry, Eugenia; Duffy, Erin; Cammarata, Sue K.; Pullman, John

2016-01-01

Objectives Delafloxacin is an investigational anionic fluoroquinolone being developed to treat infections caused by Gram-positive and -negative organisms. This clinical trial evaluated the efficacy and safety of delafloxacin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Methods In a double-blind, Phase 2 trial, 256 patients were randomized (1 : 1 : 1) to 300 mg of delafloxacin, 600 mg of linezolid or 15 mg/kg vancomycin (actual body weight), each administered intravenously twice daily for 5–14 days. Randomization was stratified by infection category. The primary endpoint was the investigator's assessment of cure, defined as complete resolution of baseline signs and symptoms at follow-up. Secondary endpoints included reductions in the total areas of erythema and induration and assessments of bacterial eradication. This trial has been registered at ClinicalTrials.gov under registration number NCT01283581. Results Cure rates were significantly greater with delafloxacin versus vancomycin (mean difference: −16.3%; 95% CI, −30.3% to −2.3%; P = 0.031); differences were significant for obese patients (BMI ≥30 kg/m2; mean difference: −30.0%; 95% CI, −50.7% to −9.3%; P = 0.009), but not for non-obese patients. Cure rates with delafloxacin and linezolid were similar. Using digital measurement, the percentage decrease in total erythema area was significantly greater with delafloxacin versus vancomycin at follow-up (−96.4% versus −84.5%; P = 0.028). There were no differences in bacterial eradication among the treatment groups. The most frequently reported treatment-emergent adverse events were nausea, diarrhoea and vomiting. Conclusions These data show that delafloxacin is effective in the treatment of ABSSSIs and is well tolerated. PMID:26679243

Nasal Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Testing Reduces the Duration of MRSA-Targeted Therapy in Patients with Suspected MRSA Pneumonia.

PubMed

Baby, Nidhu; Faust, Andrew C; Smith, Terri; Sheperd, Lyndsay A; Knoll, Laura; Goodman, Edward L

2017-04-01

The objective of this study was to evaluate the impact of pharmacist-ordered methicillin-resistant Staphylococcus aureus (MRSA) PCR testing on the duration of empirical MRSA-targeted antibiotic therapy in patients with suspected pneumonia. This is a retrospective analysis of patients who received vancomycin or linezolid for suspected pneumonia before and after the implementation of a pharmacist-driven protocol for nasal MRSA PCR testing. Patients were included if they were adults of >18 years of age and initiated on vancomycin or linezolid for suspected MRSA pneumonia. The primary endpoint was the duration of vancomycin or linezolid therapy. After screening 368 patients, 57 patients met inclusion criteria (27 pre-PCR and 30 post-PCR). Baseline characteristics were similar between the two groups, with the majority of patients classified as having health care-associated pneumonia (68.4%). The use of the nasal MRSA PCR test reduced the mean duration of MRSA-targeted therapy by 46.6 h (74.0 ± 48.9 h versus 27.4 ± 18.7 h; 95% confidence interval [CI], 27.3 to 65.8 h; P < 0.0001). Fewer patients in the post-PCR group required vancomycin serum levels and dose adjustment (48.1% versus 16.7%; P = 0.02). There were no significant differences between the pre- and post-PCR groups regarding days to clinical improvement (1.78 ± 2.52 versus 2.27 ± 3.34; P = 0.54), length of hospital stay (11.04 ± 9.5 versus 8.2 ± 7.8; P = 0.22), or hospital mortality (14.8% versus 6.7%; P = 0.41). The use of nasal MRSA PCR testing in patients with suspected MRSA pneumonia reduced the duration of empirical MRSA-targeted therapy by approximately 2 days without increasing adverse clinical outcomes. Copyright © 2017 American Society for Microbiology.

[Evaluation of antibiotic susceptibilities and VISA-VRSA rates among MRSA strains isolated from hospitalized patients in intensive care units of hospitals in seven provinces of Turkey].

PubMed

Cesur, Salih; Irmak, Hasan; Simşek, Hüsniye; Cöplü, Nilay; Kılıç, Hasan; Arslan, Uğur; Bayramoğlu, Gülçin; Baysan, Betil Ozhak; Gülay, Zeynep; Hoşoğlu, Salih; Berktaş, Mustafa; Gencer, Serap; Demiröz, Ali Pekcan; Esen, Berrin; Karabiber, Nihal; Aydın, Faruk; Yalçın, Ata Nevzat

2012-07-01

The aim of this study was to determine whether vancomycin resistant Staphylococcus aureus (VRSA) and vancomycin intermediate susceptible S.aureus (VISA) strains were present among methicillin-resistant S.aureus (MRSA) strains isolated from patients hospitalised at intensive care units (ICU) of hospitals located at different regions of Turkey and to determine the minimum inhibitory concentration (MIC) values of teicoplanin, linezolid, tigecycline, quinupristin-dalfopristin and daptomycin, which are alternative drugs for the treatment of MRSA infections. A total of 260 MRSA clinical strains (isolated from 113 lower respiratory tract, 90 blood, 24 wound, 17 catheter, 13 nasal swabs, two urine and one CSF sample) were collected from nine health-care centers in eight provinces [Ankara (n= 52), Konya (n= 49), Antalya (n= 40), Istanbul (n= 7), Izmir (37), Diyarbakir (n= 15), Van (n= 12), Trabzon (n= 48)] selected as representatives of the seven different geographical regions of Turkey. Methicillin resistance was determined by cefoxitin disk diffusion in the hospitals where the strains were isolated and confirmed by oxacillin salt agar screening at the Refik Saydam National Public Health Agency. Screening for VISA and VRSA was conducted using the agar screening test and E-test. Susceptibility of the MRSA strains to other antibiotics was also determined by E-test method. None of the 260 MRSA strains were determined to be VRSA or VISA. All were susceptible to teicoplanin and linezolid, and susceptibility rates to daptomycin, tigecycline and quinupristin-dalfopristin were 99.6%, 96.9%, and 95%, respectively. Absence of VISA and VRSA among the MRSA strains surveyed currently seemed hopeful, however, continuous surveillance is necessary. In order to prevent the development of VISA and VRSA strains the use of linezolid, tigecycline, quinupristin-dalfopristin and daptomycin should be encouraged as alternative agents of treatment of MRSA infections.

In Vitro, In Vivo, and Clinical Studies of Tedizolid To Assess the Potential for Peripheral or Central Monoamine Oxidase Interactions

PubMed Central

Bartizal, K.; Minassian, S. L.; Fang, E.; Prokocimer, P.

2013-01-01

Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS). PMID:23612197

In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

PubMed

Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

2013-07-01

Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

Assessment by Time-Kill Methodology of the Synergistic Effects of Oritavancin in Combination with Other Antimicrobial Agents against Staphylococcus aureus▿

PubMed Central

Belley, Adam; Neesham-Grenon, Eve; Arhin, Francis F.; McKay, Geoffrey A.; Parr, Thomas R.; Moeck, Gregory

2008-01-01

Oritavancin is a semisynthetic lipoglycopeptide in clinical development for serious gram-positive infections. This study describes the synergistic activity of oritavancin in combination with gentamicin, linezolid, moxifloxacin, or rifampin in time-kill studies against methicillin-susceptible, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus. PMID:18644953

Reducing the Bottleneck in Discovery of Novel Antibiotics.

PubMed

Jones, Marcus B; Nierman, William C; Shan, Yue; Frank, Bryan C; Spoering, Amy; Ling, Losee; Peoples, Aaron; Zullo, Ashley; Lewis, Kim; Nelson, Karen E

2017-04-01

Most antibiotics were discovered by screening soil actinomycetes, but the efficiency of the discovery platform collapsed in the 1960s. By now, more than 3000 antibiotics have been described and most of the current discovery effort is focused on the rediscovery of known compounds, making the approach impractical. The last marketed broad-spectrum antibiotics discovered were daptomycin, linezolid, and fidaxomicin. The current state of the art in the development of new anti-infectives is a non-existent pipeline in the absence of a discovery platform. This is particularly troubling given the emergence of pan-resistant pathogens. The current practice in dealing with the problem of the background of known compounds is to use chemical dereplication of extracts to assess the relative novelty of a compound it contains. Dereplication typically requires scale-up, extraction, and often fractionation before an accurate mass and structure can be produced by MS analysis in combination with 2D NMR. Here, we describe a transcriptome analysis approach using RNA sequencing (RNASeq) to identify promising novel antimicrobial compounds from microbial extracts. Our pipeline permits identification of antimicrobial compounds that produce distinct transcription profiles using unfractionated cell extracts. This efficient pipeline will eliminate the requirement for purification and structure determination of compounds from extracts and will facilitate high-throughput screen of cell extracts for identification of novel compounds.

Registered and investigational drugs for the treatment of methicillin-resistant Staphylococcus aureus infection.

PubMed

Pan, Angelo; Lorenzotti, Silvia; Zoncada, Alessia

2008-01-01

First isolated in the 1960s methicillin-resistant Staphylococcus aureus (MRSA) has become a leading hospital acquired (HA) pathogen, although community acquired isolates (CA-MRSA) are on the rise, particularly in the USA. Treatment of serious MRSA infections has been based for many years upon the use of glycopeptides, i.e. vancomycin and teicoplanin. Other drugs indicated in particular clinical settings, such as prosthetic valve endocarditis or osteomyelitis, are rifampin, gentamycin, fusidic acid, minocycline, co-trimoxazole, clindamycin. Quinolones and doxycycline may be active on some MRSA isolates, and add some this important clinical setting. In the last few years new anti-MRSA drugs have been registered and patented, expanding therapeutic opportunities, i.e. linezolid, the first oxazolidinone, available both as oral and parenteral formulation in being the most widely used new anti-MRSA agent, quinupristin-dalfopristin, daptomycin, a novel lipopeptide, active on germs both in the replicating and in the resting phase, and tigecycline, the first approved glycylcycline. Other drugs from different classes are in the pipeline and will further enhance in the next few years our therapeutic armamentarium: three glycopeptides, i.e. dalbavancin, telavancin, and oritavancin, two broad spectrum cephalosporins, ceftobiprole and ceftaroline, iclaprim, a diaminopyrimidine, as well as a carbapenem, CS-023/RO-4908463, and adjuvant therapies such as the monoclonal antibody tefibazumab.

Vancomycin-Resistance Enterococci Infections in the Department of the Defense: Annual Report 2014

DTIC Science & Technology

2015-07-22

change in 2014 as VRE continues to predominately affect elderly females and manifest as urinary tract infections ( UTIs ). In addition, antibiotic...urinary tract infections ( UTIs ). In addition, antibiotic susceptibility patterns did not substantially change in 2014. Daptomycin, linezolid and...the infection continues to predominately affect elderly females and manifest as UTIs . In addition, antibiotic susceptibility patterns did not

Non Diphtheritic Corynebacteria: An Emerging Nosocomial Pathogen in Skin and Soft Tissue Infection

PubMed Central

Ravi, GS; Alex, Ann Mary; Mamatha, KR; Sunitha, L; Ramya, K Thangam

2015-01-01

Introduction Non-diphtheritic corynebacteria are normal inhabitants of skin and mucous membrane. When isolated from clinical specimens they are often considered as contaminants. Recent reports suggest their role as emerging nosocomial pathogens. Aim To speciate non-diphtheritic corynebacteria isolated from wound specimens, to correlate their clinical significance and to determine their invitro antimicrobial susceptibilities to 9 antimicrobial agents. Materials and Methods Twenty five non-diphtheritic corynebacteria from skin and soft tissue infections were selected for study. Isolates were identified by battery of tests and minimum inhibitory concentration (MIC) was detected by Clinical & Laboratory Standards Institute (CLSI) described broth microdilution method. MIC was interpreted according CLSI and British Society for Antimicrobial Chemotherapy (BSAC) guidelines. Results C. amycolatum was the predominant species (20%) followed by C. striatum (16%). Penicillin was least effective invitro followed by clindamycin and ciprofloxacin. Excellent activities were shown by vancomycin, linezolid and imipenem. Multidrug resistance was found in all the species. Conclusion Non-diphtheritic corynebacteria are potential nosocomial pathogens among acute/chronic complicated skin and soft tissue infection. Vancomycin or linezolid can be used empirically to treat such infections until the invitro susceptibility results are available. PMID:26816891

Evaluation of reporting quality for observational studies using routinely collected health data in pharmacovigilance.

PubMed

Nie, Xiaolu; Zhang, Ying; Wu, Zehao; Jia, Lulu; Wang, Xiaoling; Langan, Sinéad M; Benchimol, Eric I; Peng, Xiaoxia

2018-06-01

To appraise the reporting quality of studies which concerned linezolid related thrombocytopenia referring to REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. Medline, Embase, Cochrane library and clinicaltrial.gov were searched for observational studies concerning linezolid related thrombocytopenia using routinely collected health data from 2000 to 2017. Two reviewers screened potential eligible articles and extracted data independently. Finally, reporting quality assessment was performed by two senior researchers using RECORD statement. Of 25 included studies, 11 (44.0%) mentioned the type of data in the title and/or abstract. In 38 items derived from RECORD statement, the median number of items reported in the included studies was 22 (interquartile range (IQR) 18 to 27). Inadequate reporting issues were discovered in the following aspects: validation studies of the codes or algorithms, study size estimation, quantitative variables, subgroup statistical methods, missing data, follow-up/matching or sampling strategy, sensitivity analysis and cleaning methods, funding and role of funders and accessibility of protocol, raw data. This study provides the evidence that the reporting quality of post-marketing safety evaluation studies conducted using routinely collected health data was often insufficient. Future stakeholders are encouraged to endorse the RECORD guidelines in pharmacovigilance.

Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections.

PubMed

Wei, Hanwen; Mao, Fei; Ni, Shuaishuai; Chen, Feifei; Li, Baoli; Qiu, Xiaoxia; Hu, Linghao; Wang, Manjiong; Zheng, Xinyu; Zhu, Jin; Lan, Lefu; Li, Jian

2018-02-10

Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H 2 O 2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Fast Fourier Transform Spectral Analysis Program

NASA Technical Reports Server (NTRS)

Daniel, J. A., Jr.; Graves, M. L.; Hovey, N. M.

1969-01-01

Fast Fourier Transform Spectral Analysis Program is used in frequency spectrum analysis of postflight, space vehicle telemetered trajectory data. This computer program with a digital algorithm can calculate power spectrum rms amplitudes and cross spectrum of sampled parameters at even time increments.

In vitro activities of the new semisynthetic glycopeptide telavancin (TD-6424), vancomycin, daptomycin, linezolid, and four comparator agents against anaerobic gram-positive species and Corynebacterium spp.

PubMed

Goldstein, Ellie J C; Citron, Diane M; Merriam, C Vreni; Warren, Yumi A; Tyrrell, Kerin L; Fernandez, Helen T

2004-06-01

Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca(2+) to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC(90)s) for telavancin and vancomycin were as follows: Actinomyces spp. (n = 45), 0.25 and 1 microg/ml, respectively; Clostridium difficile (n = 14), 0.25 and 1 microg/ml, respectively; Clostridium ramosum (n = 16), 1 and 4 microg/ml, respectively; Clostridium innocuum (n = 15), 4 and 16 microg/ml, respectively; Clostridium clostridioforme (n = 15), 8 and 1 microg/ml, respectively; Eubacterium group (n = 33), 0.25 and 2 microg/ml, respectively; Lactobacillus spp. (n = 26), 0.5 and 4 microg/ml, respectively; Propionibacterium spp. (n = 34), 0.125 and 0.5 microg/ml, respectively; Peptostreptococcus spp. (n = 52), 0.125 and 0.5 microg/ml, respectively; and Corynebacterium spp. (n = 31), 0.03 and 0.5 microg/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three- to fivefold more active. Daptomycin had decreased activity (MIC > 4 microg/ml) against 14 strains of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 microg/ml) against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus spp. Imipenem and piperacillin-tazobactam were active against >98% of strains. The MICs of ampicillin for eight Clostridium spp. and three strains of L. casei were >1 microg/ml. The MIC(90) of TD-6424 for all strains tested was

Activity of OPT-80, a novel macrocycle, compared with those of eight other agents against selected anaerobic species.

PubMed

Credito, Kim L; Appelbaum, Peter C

2004-11-01

Agar dilution MIC was used to compare activities of OPT-80, linezolid, vancomycin, teicoplanin, quinupristin/dalfopristin, amoxicillin/clavulanate, imipenem, clindamycin, and metronidazole against 350 gram-positive and -negative anaerobes. OPT-80 was active against gram-positive strains only, especially Clostridium spp. (85 strains tested, including 21 strains of C. difficile), with MICs ranging between

Design, synthesis and antibacterial evaluation of honokiol derivatives.

PubMed

Wu, Bo; Fu, Su-Hong; Tang, Huan; Chen, Kai; Zhang, Qiang; Peng, Ai-Hua; Ye, Hao-Yu; Cheng, Xing-Jun; Lian, Mao; Wang, Zhen-Ling; Chen, Li-Juan

2018-02-15

Staphylococcus aureus is a major and dangerous human pathogen that causes a range of clinical manifestations of varying severity, and is the most commonly isolated pathogen in the setting of skin and soft tissue infections, pneumonia, suppurative arthritis, endovascular infections, foreign-body associated infections, septicemia, osteomyelitis, and toxic shocksyndrome. Honokiol, a pharmacologically active natural compound derived from the bark of Magnolia officinalis, has antibacterial activity against Staphylococcus aureus which provides a great inspiration for the discovery of potential antibacterial agents. Herein, honokiol derivatives were designed, synthesized and evaluated for their antibacterial activity by determining the minimum inhibitory concentration (MIC) against S. aureus ATCC25923 and Escherichia coli ATCC25922 in vitro. 7c exhibited better antibacterial activity than other derivatives and honokiol. The structure-activity relationships indicated piperidine ring with amino group is helpful to improve antibacterial activity. Further more, 7c showed broad spectrum antibacterial efficiency against various bacterial strains including eleven gram-positive and seven gram-negative species. Time-kill kinetics against S. aureus ATCC25923 in vitro revealed that 7c displayed a concentration-dependent effect and more rapid bactericidal kinetics better than linezolid and vancomycin with the same concentration. Gram staining assays of S. aureus ATCC25923 suggested that 7c could destroy the cell walls of bacteria at 1×MIC and 4×MIC. Copyright © 2017. Published by Elsevier Ltd.

The MUT056399 Inhibitor of FabI Is a New Antistaphylococcal Compound▿

PubMed Central

Escaich, S.; Prouvensier, L.; Saccomani, M.; Durant, L.; Oxoby, M.; Gerusz, V.; Moreau, F.; Vongsouthi, V.; Maher, Kirsty; Morrissey, Ian; Soulama-Mouze, C.

2011-01-01

MUT056399 is a highly potent new inhibitor of the FabI enzyme of both Staphylococcus aureus and Escherichia coli. In vitro, MUT056399 was very active against S. aureus strains, including methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), linezolid-resistant, and multidrug-resistant strains, with MIC90s between 0.03 and 0.12 μg/ml. MUT056399 was also active against coagulase-negative staphylococci, with MIC90s between 0.12 and 4 μg/ml. The antibacterial spectrum is consistent with specific FabI inhibition with no activity against bacteria using FabK but activity against FabI-containing Gram-negative bacilli. In vitro, resistant clones of S. aureus were obtained at a low frequency. All of the resistant clones analyzed were found to contain mutations in the fabI gene. In vivo, MUT056399, administered subcutaneously, protected mice from a lethal systemic infection induced by MSSA, MRSA, and vancomycin-intermediate S. aureus strains (50% effective doses ranging from 19.3 mg/kg/day to 49.6 mg/kg/day). In the nonneutropenic murine thigh infection model, the same treatment with MUT056399 reduced the bacterial multiplication of MSSA and MRSA in the thighs of immunocompetent mice. These properties support MUT056399 as a very promising candidate for a novel drug to treat severe staphylococcal infections. PMID:21825292

The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus.

PubMed

Hodille, Elisabeth; Rose, Warren; Diep, Binh An; Goutelle, Sylvain; Lina, Gerard; Dumitrescu, Oana

2017-10-01

Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease. Copyright © 2017 American Society for Microbiology.

Drug Susceptibility Testing of 31 Antimicrobial Agents on Rapidly Growing Mycobacteria Isolates from China.

PubMed

Pang, Hui; Li, Guilian; Zhao, Xiuqin; Liu, Haican; Wan, Kanglin; Yu, Ping

2015-01-01

Several species of rapidly growing mycobacteria (RGM) are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Clinical isolates (73) were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. M. abscessus (75.34%) and M. fortuitum (15.07%), the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians.

Drug Susceptibility Testing of 31 Antimicrobial Agents on Rapidly Growing Mycobacteria Isolates from China

PubMed Central

Pang, Hui; Li, Guilian; Zhao, Xiuqin; Liu, Haican; Wan, Kanglin; Yu, Ping

2015-01-01

Objectives. Several species of rapidly growing mycobacteria (RGM) are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Methods. Clinical isolates (73) were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. Results. M. abscessus (75.34%) and M. fortuitum (15.07%), the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Conclusions. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians. PMID:26351633

Rhabdomyolysis secondary to interaction between atorvastatin and fusidic acid

PubMed Central

Saeed, Nabeel Tahir Muhammad; Azam, Mohammad

2009-01-01

A 48-year-old ill-looking man presented with nausea and vomiting. He had been on fusidic acid 500 mg three times a day and linezolid 600 mg twice a day for 2 weeks for right knee methicillin-resistant Staphylococcus aureus infection post right knee arthroscopy performed a month previously. He had been on atorvastatin 40 mg daily and Aspirin 75 mg once a day for a year. His investigations showed elevated creatine phosphokinase (CPK) (759 IU/litre) and transaminases (aspartate transaminase (AST) 58 IU/litre and alanine transaminase (ALT) 123 IU/litre). Atorvastatin was discontinued and the patient was treated with intravenous fluids, a proton pump inhibitor, antiemetics and discharged with follow-up in 2 days for repeat blood results. The patient presented 5 days later with rhabdomyolysis and acute hepatitis. His antibiotics (fusidic acid and linezolid) were stopped. The patient was managed conservatively with intravenous fluids and was transferred for possible dialysis but did not need it. After 3 weeks investigations showed normal urea, creatinine, electrolytes, CPK and liver function tests suggesting earlier rise in transaminases secondary to muscle damage rather than liver. The patient had intensive physiotherapy and his mobility improved, and he was discharged home. The case was reported to pharmacovigilance services. PMID:21918658

Dalbavancin for the treatment of acute bacterial skin and skin structure infections

PubMed Central

Ramdeen, Sheena; Boucher, Helen W

2015-01-01

Introduction Acute bacterial skin and skin structure infections (ABSSSI) have increased in incidence and severity. The involvement of resistant organisms, particularly methicillin-resistant Staphylococcus aureus, presents additional challenges. The lipoglycopeptide dalbavancin has a prolonged half-life, high protein binding, and excellent tissue levels which led to its development as a once-weekly treatment for ABSSSI. In the pivotal DISCOVER 1 and DISCOVER 2 trials, dalbavancin proved non-inferior to vancomycin followed by linezolid when used sequentially for ABSSSI, forming the basis for its recent approval in the US and Europe for ABSSSI. Areas covered A literature search of published pharmacologic and clinical data was conducted to review the chemistry, pharmacodynamics, and pharmacokinetics of dalbavancin. We also discuss its development process, highlighting efficacy and safety data from pertinent clinical trials and the role it could play in the current clinical landscape. Expert opinion DISCOVER 1 and DISCOVER 2 demonstrated dalbavancin’s non-inferiority to vancomycin followed by linezolid for ABSSSI and confirmed its safety and tolerability. They were among the first trials to use new, early primary efficacy endpoints, and dalbavancin was among the first agents designated a Qualified Infectious Disease Product for expedited review. Dalbavancin may prove to be a valuable option for ABSSSI patients in whom conventional therapy is limited. PMID:26239321

Mechanism Underlying Linezolid-induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model

PubMed Central

Nishijo, Nao; Tsuji, Yasuhiro; Matsunaga, Kazuhisa; Kutsukake, Masahiko; Okazaki, Fumiyasu; Fukumori, Shiro; Kasai, Hidefumi; Hiraki, Yoichi; Sakamaki, Ippei; Yamamoto, Yoshihiro; Karube, Yoshiharu; To, Hideto

2017-01-01

Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression. PMID:28405130

Pharmacokinetics of linezolid during continuous hemodiafiltration: A case report.

PubMed

Yamashina, Takuya; Tsuruyama, Moeko; Odawara, Miki; Tsuruta, Minako; Miyata, Hirochika; Kozono, Aki; Tsuji, Yasuhiro; Miyoshi, Takanori; Kawamata, Yosei; Hiraki, Yoichi

2017-10-01

The pharmacokinetics of linezolid clearance (CL LZD ) during continuous hemodiafiltration (CHDF) has not been comprehensively analyzed. Here, we examined CL LZD by CHDF in a patient with septic shock and disseminated intravascular coagulation due to methicillin-resistant Staphylococcus aureus. The extraction ratio of LZD by CHDF was 22.6%, and the protein-binding rate was 17.9% ± 7.7%. In addition, it was determined that the calculated total body clearance of LZD was 30.2 mL/min, plasma elimination half-life was 8.66 h, and the CL LZD by the dialyzer used for CHDF was 23.0 mL/min. From the obtained pharmacokinetics, the CL LZD of patients continuing CHDF was estimated to be approximately half of the reported CL LZD for healthy subjects. In addition, the LZD concentration of the sepsis patient who underwent CHDF remained higher than the minimum inhibitory concentration and was similar to the LZD concentrations reported in normal renal function patients. Although further studies are warranted, when LZD is administered to patients treated with CHDF, the present findings suggest that dose regulation is not required. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

ACOUSTIC LINERS FOR TURBOFAN ENGINES

NASA Technical Reports Server (NTRS)

Minner, G. L.

1994-01-01

This program was developed to design acoustic liners for turbofan engines. This program combines results from theoretical models of wave alternation in acoustically treated passages with experimental data from full-scale fan noise suppressors. By including experimentally obtained information, the program accounts for real effects such as wall boundary layers, duct terminations, and sound modal structure. The program has its greatest use in generating a number of design specifications to be used for evaluation of trade-offs. The program combines theoretical and empirical data in designing annular acoustic liners. First an estimate of the noise output of the fan is made based on basic fan aerodynamic design variables. Then, using a target noise spectrum after alternation and the estimated fan noise spectrum, a design spectrum is calculated as their difference. Next, the design spectrum is combined with knowledge of acoustic liner performance and the liner design variables to specify the acoustic design. Details of the liner design are calculated by combining the required acoustic impedance with a mathematical model relating acoustic impedance to the physical structure of the liner. Input to the noise prediction part of the program consists of basic fan operating parameters, distance that the target spectrum is to be measured and the target spectrum. The liner design portion of the program requires the required alternation spectrum, desired values of length to height and several option selection parameters. Output from the noise prediction portion is a noise spectrum consisting of discrete tones and broadband noise. This may be used as input to the liner design portion of the program. The liner design portion of the program produces backing depths, open area ratios, and face plate thicknesses. This program is written in FORTRAN V and has been implemented in batch mode on a UNIVAC 1100 series computer with a central memory requirement of 12K (decimal) of 36 bit words.

Activity of OPT-80, a Novel Macrocycle, Compared with Those of Eight Other Agents against Selected Anaerobic Species

PubMed Central

Credito, Kim L.; Appelbaum, Peter C.

2004-01-01

Agar dilution MIC was used to compare activities of OPT-80, linezolid, vancomycin, teicoplanin, quinupristin/dalfopristin, amoxicillin/clavulanate, imipenem, clindamycin, and metronidazole against 350 gram-positive and -negative anaerobes. OPT-80 was active against gram-positive strains only, especially Clostridium spp. (85 strains tested, including 21 strains of C. difficile), with MICs ranging between ≤0.016 and 0.25 μg/ml. PMID:15504874

Antistaphylococcal activity of LBM415, a new peptide deformylase inhibitor, compared with those of other agents.

PubMed

Credito, Kim; Lin, Gengrong; Ednie, Lois M; Appelbaum, Peter C

2004-10-01

The MICs of LBM415, a new peptide diformylase inhibitor, were

Antistaphylococcal activity of dalbavancin, an experimental glycopeptide.

PubMed

Lin, Gengrong; Credito, Kim; Ednie, Lois M; Appelbaum, Peter C

2005-02-01

Dalbavancin, tested against 146 staphylococci, was more potent than other drugs tested, with an MIC at which 50% of staphylococci were inhibited of 0.03 microg/ml and an MIC at which 90% of staphylococci were inhibited of 0.06 microg/ml by microdilution. For all strains, MICs of vancomycin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin were

Bacterial epidemiology of osteoarticular infections in a referent center: 10-year study.

PubMed

Titécat, M; Senneville, E; Wallet, F; Dezèque, H; Migaud, H; Courcol, R-J; Loïez, C

2013-10-01

Management of osteoarticular infections combines surgical treatment with antibiotic therapy. For some teams the immediate postoperative regimen requires at least partly wide-spectrum probabilistic treatment while waiting for the microbiological results. This protocol exposes the patient to the selection of resistant bacteria and the hospital unit to a modification of its bacterial ecology. The objective of this study was to retrospectively describe the microbial epidemiology of the Traumatology and Orthopaedics Department of the Lille University Hospital over 10 years (2002-2011). The bacterial species isolated in culture of osteoarticular samples were listed, after removing any duplicates. The antibiotics retained for follow-up were those used in treatment of these infections as well as those recognized as markers of resistance. For Gram-positive species, the antibiotics considered were methicillin, rifampicin, fluoroquinolones, glycopeptides, and linezolid; for the Gram-negative species, cefotaxime, cefepime, imipenem, and fluoroquinolones were considered. Of the 5006 strains isolated between 2002 and 2011, Gram-positive cocci accounted for more than 71%; Staphylococcus aureus 27%, and coagulase-negative staphylococci (CoNS) 54%. Contrary to S. aureus, resistance to methicillin, fluoroquinolones, and teicoplanin significantly increased in CoNS, reaching 44%, 34%, and 22%, respectively, of the strains in 2011. The proportion of streptococcal and enterococcal infections remained stable, a mean 7.4% and 5.3%, respectively, per year. Enterobacteria (12.5% of the isolates) were producers of extended-spectrum beta-lactamase in 7.8% of the cases. Pseudomonas aeruginosa was involved in 3.6% of the infections, and 12% of the strains remained resistant to ceftazidime. Propionibacterium acnes accounted for 5.8% of the bacteria isolated and showed few antibiotic resistance problems. Stability in the distribution and the susceptibility of different bacterial species was noted over this 10-year period. Although the evolution of S. aureus resistance was favourable, the resistance of CoNS specially to methicillin and glycopeptides increased. Level IV. Retrospective cohort study. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Strength-Based Educational Programming for Students with Autism Spectrum Disorders: A Case for Video Self-Modeling

ERIC Educational Resources Information Center

Bellini, Scott; McConnell, Luke L.

2010-01-01

Video-self modeling (VSM) is an effective but underused instructional strategy for youth on the autism spectrum. The authors present VSM in the context of strength-based educational programming for youth on the autism spectrum. The authors summarize research studies investigating VSM with youth on the autism spectrum in school settings and discuss…

Clinical and economic outcomes from a community hospital's antimicrobial stewardship program.

PubMed

Malani, Anurag N; Richards, Patrick G; Kapila, Shikha; Otto, Michael H; Czerwinski, Jennifer; Singal, Bonita

2013-02-01

Data from community antimicrobial stewardship programs (ASPs) are limited. We describe clinical and economic outcomes from the first year of our hospital's ASP. The ASP team comprised 2 infectious disease physicians and 3 intensive care unit pharmacists. The team prospectively audited the new starts and weekly use of 8 target antimicrobials: aztreonam, caspofungin, daptomycin, ertapenem, linezolid, meropenem, tigecycline, and voriconazole. Using administrative data, outcomes from the first year of the program, including death within 30 days of hospitalization, readmission within 30 days of discharge, and development of Clostridium difficile infection (CDI), were compared with outcomes from a similar period before institution of the program. A total of 510 antimicrobial orders were reviewed, of which 323 (63%) were appropriate, 94 (18%) prompted deescalation, 61 (12%) were denied, and 27 (5%) led to formal consultation with an infectious disease physician. On multivariate analysis, implementation of the ASP was associated with an approximate 50% reduction in the odds of developing CDI (odds ratio, 0.46; 95% confidence interval, 0.25-0.82). The ASP was not associated with decreased mortality at 30 days after discharge or readmission rate. The antimicrobial cost per patient-day decreased by 13.3%, from $10.16 to $8.81. The antimicrobial budget decreased by 15.2%, resulting in a total savings of $228,911. There was a 25.4% decrease in defined daily doses of the target antimicrobials. Implementation of the ASP was associated with significant reductions in CDI rate, antimicrobial use, and pharmacy costs. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

SLAM, a Mathematica interface for SUSY spectrum generators

NASA Astrophysics Data System (ADS)

Marquard, Peter; Zerf, Nikolai

2014-03-01

We present and publish a Mathematica package, which can be used to automatically obtain any numerical MSSM input parameter from SUSY spectrum generators, which follow the SLHA standard, like SPheno, SOFTSUSY, SuSeFLAV or Suspect. The package enables a very comfortable way of numerical evaluations within the MSSM using Mathematica. It implements easy to use predefined high scale and low scale scenarios like mSUGRA or mhmax and if needed enables the user to directly specify the input required by the spectrum generators. In addition it supports an automatic saving and loading of SUSY spectra to and from a SQL data base, avoiding the rerun of a spectrum generator for a known spectrum. Catalogue identifier: AERX_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AERX_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 4387 No. of bytes in distributed program, including test data, etc.: 37748 Distribution format: tar.gz Programming language: Mathematica. Computer: Any computer where Mathematica version 6 or higher is running providing bash and sed. Operating system: Linux. Classification: 11.1. External routines: A SUSY spectrum generator such as SPheno, SOFTSUSY, SuSeFLAV or SUSPECT Nature of problem: Interfacing published spectrum generators for automated creation, saving and loading of SUSY particle spectra. Solution method: SLAM automatically writes/reads SLHA spectrum generator input/output and is able to save/load generated data in/from a data base. Restrictions: No general restrictions, specific restrictions are given in the manuscript. Running time: A single spectrum calculation takes much less than one second on a modern PC.

Antistaphylococcal Activity of LBM415, a New Peptide Deformylase Inhibitor, Compared with Those of Other Agents

PubMed Central

Credito, Kim; Lin, Gengrong; Ednie, Lois M.; Appelbaum, Peter C.

2004-01-01

The MICs of LBM415, a new peptide diformylase inhibitor, were ≤0.06 to 4.0 μg/ml for 258 isolates of Staphylococcus aureus and coagulase-negative staphylococci. LBM415 MICs were similar irrespective of whether the strains were methicillin susceptible or resistant. All strains were also susceptible to vancomycin, linezolid, ranbezolid, daptomycin, oritavancin, and quinupristin-dalfopristin. LBM415 at the MIC was bacteriostatic after 24 h. PMID:15388473

Umbilical Sepsis Caused by Multidrug Resistant Strain of Kocuria kristinae in a New Born: A Case Report

PubMed Central

Subramanian, Pramodhini; Ramakrishnan, Kalaivani; Seetha, K.S

2016-01-01

Kocuria species were placed previously under the genus Micrococcus, are skin and oropharynx commensals in mammals, including man. A rare bacteria, Kocuria kristinae isolated from a new born with umbilical sepsis. Identification and antibiotic susceptibility was done by Vitek 2 compact system (Biomerieux). The isolate was sensitive to higher antibiotics like vancomycin, teicoplanin and linezolid. As this new pathogen resembles coagulase negative staphylococcus, it should not be misidentified. PMID:27190805

Umbilical Sepsis Caused by Multidrug Resistant Strain of Kocuria kristinae in a New Born: A Case Report.

PubMed

Sivaraman, Umadevi; Subramanian, Pramodhini; Ramakrishnan, Kalaivani; Seetha, K S

2016-04-01

Kocuria species were placed previously under the genus Micrococcus, are skin and oropharynx commensals in mammals, including man. A rare bacteria, Kocuria kristinae isolated from a new born with umbilical sepsis. Identification and antibiotic susceptibility was done by Vitek 2 compact system (Biomerieux). The isolate was sensitive to higher antibiotics like vancomycin, teicoplanin and linezolid. As this new pathogen resembles coagulase negative staphylococcus, it should not be misidentified.

Real-time monitoring of bacterial infection in vivo: development of bioluminescent staphylococcal foreign-body and deep-thigh-wound mouse infection models.

PubMed

Kuklin, Nelly A; Pancari, Gregory D; Tobery, Timothy W; Cope, Leslie; Jackson, Jesse; Gill, Charles; Overbye, Karen; Francis, Kevin P; Yu, Jun; Montgomery, Donna; Anderson, Annaliesa S; McClements, William; Jansen, Kathrin U

2003-09-01

Staphylococcal infections associated with catheter and prosthetic implants are difficult to eradicate and often lead to chronic infections. Development of novel antibacterial therapies requires simple, reliable, and relevant models for infection. Using bioluminescent Staphylococcus aureus, we have adapted the existing foreign-body and deep-wound mouse models of staphylococcal infection to allow real-time monitoring of the bacterial colonization of catheters or tissues. This approach also enables kinetic measurements of bacterial growth and clearance in each infected animal. Persistence of infection was observed throughout the course of the study until termination of the experiment at day 16 in a deep-wound model and day 21 in the foreign-body model, providing sufficient time to test the effects of antibacterial compounds. The usefulness of both animal models was assessed by using linezolid as a test compound and comparing bioluminescent measurements to bacterial counts. In the foreign-body model, a three-dose antibiotic regimen (2, 5, and 24 h after infection) resulted in a decrease in both luminescence and bacterial counts recovered from the implant compared to those of the mock-treated infected mice. In addition, linezolid treatment prevented the formation of subcutaneous abscesses, although it did not completely resolve the infection. In the thigh model, the same treatment regimen resulted in complete resolution of the luminescent signal, which correlated with clearance of the bacteria from the thighs.

Rapidly growing mycobacteria in Singapore, 2006-2011.

PubMed

Tang, S S; Lye, D C; Jureen, R; Sng, L-H; Hsu, L Y

2015-03-01

Nontuberculous mycobacteria infection is a growing global concern, but data from Asia are limited. This study aimed to describe the distribution and antibiotic susceptibility profiles of rapidly growing mycobacterium (RGM) isolates in Singapore. Clinical RGM isolates with antibiotic susceptibility tests performed between 2006 and 2011 were identified using microbiology laboratory databases and minimum inhibitory concentrations of amikacin, cefoxitin, clarithromycin, ciprofloxacin, doxycycline, imipenem, linezolid, moxifloxacin, sulfamethoxazole or trimethoprim-sulfamethoxazole, tigecycline and tobramycin were recorded. Regression analysis was performed to detect changes in antibiotic susceptibility patterns over time. A total of 427 isolates were included. Of these, 277 (65%) were from respiratory specimens, 42 (10%) were related to skin and soft tissue infections and 36 (8%) were recovered from blood specimens. The two most common species identified were Mycobacterium abscessus (73%) and Mycobacterium fortuitum group (22%), with amikacin and clarithromycin being most active against the former, and quinolones and trimethoprim-sulfamethoxazole against the latter. Decreases in susceptibility of M. abscessus to linezolid by 8.8% per year (p 0.001), M. fortuitum group to imipenem by 9.5% per year (p 0.023) and clarithromycin by 4.7% per year (p 0.033) were observed. M. abscessus in respiratory specimens is the most common RGM identified in Singapore. Antibiotic options for treatment of RGM infections are increasingly limited. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Smart Methods for Linezolid Determination in the Presence of Alkaline and Oxidative Degradation Products Utilizing Their Overlapped Spectral Bands

NASA Astrophysics Data System (ADS)

Abd El-Monem Hegazy, M.; Shaaban Eissa, M.; Abd El-Sattar, O. I.; Abd El-Kawy, M. M.

2014-09-01

Linezolid (LIN) is considered the first available oxazolidinone antibacterial agent. It is susceptible to hydrolysis and oxidation. Five simple, accurate, sensitive and validated UV spectrophotometric methods were developed for LIN determination in the presence of its alkaline (ALK) and oxidative (OXD) degradation products in bulk powder and pharmaceutical formulation. Method A is a second derivative one (D2) in which LIN is determined at 240.9 nm. Method B is a pH-induced differential derivative one where LIN is determined using the fourth derivative (D4) of the difference spectra (ΔA) at 285.3 nm. Methods C, D, and E are manipulating ratio spectra, where C is the double divisor-ratio difference spectrophotometric one (DD-RD) in which LIN was determined by calculating the amplitude difference at 243.7 and 267.6 nm of the ratio spectra. Method D is the double divisor-first derivative of ratio spectra (DD-DD1) in which LIN was determined at 270.2 nm. Method E is a mean centering of ratio spectra one (MCR) in which LIN was determined at 318.0 nm. The developed methods have been validated according to ICH guidelines. The results were statistically compared to that of a reported HPLC method and there was no significant difference regarding both accuracy and precision.

Empiric therapy directed against MRSA in patients admitted to the intensive care unit does not improve outcomes in community-acquired pneumonia.

PubMed

Griffin, A T; Peyrani, P; Wiemken, T L; Ramirez, J A; Arnold, F W

2013-04-01

The Infectious Diseases Society of America has recommended empiric therapy active against methicillin-resistant Staphylococcus aureus (MRSA) for all community-acquired pneumonia (CAP) patients admitted to the intensive care unit (ICU). However, there is sparse data to support this recommendation. The objective of our study was to ascertain if such a practice improves outcomes. This study was a secondary, retrospective analysis of the Community-Acquired Pneumonia Organization (CAPO) international database on CAP. Outcomes in patients admitted to the ICU were compared according to empiric initiation of anti-MRSA therapy (vancomycin or linezolid) with standard ICU CAP therapy (MRSA therapy group) or standard therapy alone for ICU CAP (standard therapy group). A total of 621 patients were identified with ICU pneumonia, of whom 57 patients had been initiated empirically on vancomycin or linezolid (MRSA therapy group). Patients of the MRSA therapy group had more comorbidities and were more severely ill than those of the standard therapy group. However, there were no statistical differences between the MRSA therapy group and standard therapy group for the primary outcomes of in-hospital and 28-day mortality, length of stay and time to clinical stability. These findings suggest that empiric MRSA therapy in all ICU CAP patients may not improve outcomes and argue for clinician review of local epidemiologic trends on MRSA prevalence to ascertain the need for empiric MRSA coverage.

Volunteer Evaluations of the Transitions Program for Young Adults with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Evans, Lacey

2018-01-01

This study examined the effects of participation of peer volunteers in the Transitions Program for young adults with Autism Spectrum Disorder (ASD), a program that facilitates social skills and social interactions. Participants in this study were peer volunteers in the Transitions Program. Each peer volunteer completed a questionnaire, following…

A Comprehensive Inclusion Program for Kindergarten Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Sainato, Diane M.; Morrison, Rebecca S.; Jung, Sunhwa; Axe, Judah; Nixon, Patricia A.

2015-01-01

To date, reports of empirically validated comprehensive intervention programs for children with autism spectrum disorder (ASD) have been limited to preschool-age children. We examined the effects of a model inclusive kindergarten program for children with ASD. Forty-one children received instruction in an inclusive kindergarten program with their…

Improving Psychosexual Knowledge in Adolescents with Autism Spectrum Disorder: Pilot of the Tackling Teenage Training Program

ERIC Educational Resources Information Center

Dekker, Linda P.; van der Vegt, Esther J.; Visser, Kirsten; Tick, Nouchka; Boudesteijn, Frieda; Verhulst, Frank C.; Maras, Athanasios; Greaves-Lord, Kirstin

2015-01-01

Previous studies have shown that psychosexual functioning in adolescents with autism spectrum disorder (ASD) is hampered and emphasize the need for a specialized training program tailored to their needs. Therefore, an individual training program was developed; the Tackling Teenage Training (TTT) program. The current pilot study systematically…

Two Feathers Endowment Scholarship Program: Program Evaluation

ERIC Educational Resources Information Center

Pierce, Alexandra

2004-01-01

The Saint Paul Foundation contracted with the Wilder Research Center to conduct an evaluation of their Two Feathers Scholarship Program. The Two Feathers Scholarship Program is funded through the Two Feathers Endowment, which is one part of the Foundation's SpectrumTrust. SpectrumTrust is a unique partnership between communities of color and The…

Computer program to simulate Raman scattering

NASA Technical Reports Server (NTRS)

Zilles, B.; Carter, R.

1977-01-01

A computer program is described for simulating the vibration-rotation and pure rotational spectrum of a combustion system consisting of various diatomic molecules and CO2 as a function of temperature and number density. Two kinds of spectra are generated: a pure rotational spectrum for any mixture of diatomic and linear triatomic molecules, and a vibrational spectrum for diatomic molecules. The program is designed to accept independent rotational and vibrational temperatures for each molecule, as well as number densities.

[Identification and drug susceptibility testing of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis].

PubMed

Li, W B; Ji, L Y; Xu, D L; Liu, H C; Zhao, X Q; Wu, Y M; Wan, K L

2018-05-10

Objective: To understand the etiological characteristics and drug susceptibility of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis and provide evidence for the prevention and control of infectious mastitis in cows. Methods: The milk sample was collected from a cow with mastitis, which was pretreated with 4 % NaOH and inoculated with L-J medium for Mycobacterium isolation. The positive cultures were initially identified by acid-fast staining and multi-loci PCR, then Mycobacterium species was identified by the multiple loci sequence analysis (MLSA) with 16S rRNA , hsp65 , ITS and SodA genes. The drug sensitivity of the isolates to 27 antibiotics was tested by alamar blue assay. Results: Two anti-acid stain positive strains were isolated from the milk of a cow with mastitis, which were identified as non- tuberculosis mycobacterium by multi-loci PCR, and multi-loci nucleic acid sequence analysis indicated that one strain was Mycobacterium thermoresistibile and another one was Mycobacterium elephantis . The results of the drug susceptibility test showed that the two strains were resistant to most antibiotics, including rifampicin and isoniazid, but they were sensitive to amikacin, moxifloxacin, levofloxacin, ethambutol, streptomycin, tobramycin, ciprofloxacin and linezolid. Conclusions: Mycobacterium thermoresistibile and Mycobacterium elephantis were isolated in a cow with mastitis and the drug susceptibility spectrum of the pathogens were unique. The results of the study can be used as reference for the prevention and control the infection in cows.

Antistaphylococcal Activity of Dalbavancin, an Experimental Glycopeptide

PubMed Central

Lin, Gengrong; Credito, Kim; Ednie, Lois M.; Appelbaum, Peter C.

2005-01-01

Dalbavancin, tested against 146 staphylococci, was more potent than other drugs tested, with an MIC at which 50% of staphylococci were inhibited of 0.03 μg/ml and an MIC at which 90% of staphylococci were inhibited of 0.06 μg/ml by microdilution. For all strains, MICs of vancomycin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin were ≤4.0 μg/ml. Dalbavancin was bactericidal at four times the MIC against all six strains tested. PMID:15673763

Feasibility of an Empirically Based Program for Parents of Preschoolers with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Dababnah, Sarah; Parish, Susan L.

2016-01-01

This article reports on the feasibility of implementing an existing empirically based program, "The Incredible Years," tailored to parents of young children with autism spectrum disorder. Parents raising preschool-aged children (aged 3-6?years) with autism spectrum disorder (N?=?17) participated in a 15-week pilot trial of the…

What Youths with Autism Spectrum Disorder and Their Parents Want from Social Competence Programs

ERIC Educational Resources Information Center

MacCormack, Jeffrey W. H.

2017-01-01

Program designers develop a wide range of intervention programs to address the social challenges faced by children and youth with autism spectrum disorder (ASD) but it is not clear how those programs are perceived by families of youth with ASD and the extent to which those programs are accessed. To explore the perceptions of families of youth with…

Implementing a Communication Coaching Program for Students with Autism Spectrum Disorders in Postsecondary Education

ERIC Educational Resources Information Center

Weiss, Amy L.; Rohland, Pamela

2015-01-01

This article describes the operation of a Communication Coaching Program, which was designed to provide supports for students with autism spectrum disorders (ASDs) attending the University of Rhode Island. To succeed in college programs, many students with ASDs need access to specialized programming and personnel who are able to foster their…

Spectrum/Orbit-Utilization Program

NASA Technical Reports Server (NTRS)

Miller, Edward F.; Sawitz, Paul; Zusman, Fred

1988-01-01

Interferences among geostationary satellites determine allocations. Spectrum/Orbit Utilization Program (SOUP) is analytical computer program for determining mutual interferences among geostationary-satellite communication systems operating in given scenario. Major computed outputs are carrier-to-interference ratios at receivers at specified stations on Earth. Information enables determination of acceptability of planned communication systems. Written in FORTRAN.

An Evolution of Virtual Reality Training Designs for Children with Autism and Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Strickland, Dorothy C.; McAllister, David; Coles, Claire D.; Osborne, Susan

2007-01-01

This article describes an evolution of training programs to use first-person interaction in virtual reality (VR) situations to teach safety skills to children with autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD). Multiple VR programs for children aged 2 to 9 were built and tested between 1992 and 2007. Based on these…

A Randomized Controlled Trial to Improve Social Skills in Young Adults with Autism Spectrum Disorder: The UCLA PEERS® Program

ERIC Educational Resources Information Center

Laugeson, Elizabeth A.; Gantman, Alexander; Kapp, Steven K.; Orenski, Kaely; Ellingsen, Ruth

2015-01-01

Research suggests that impaired social skills are often the most significant challenge for those with autism spectrum disorder (ASD), yet few evidence-based social skills interventions exist for adults on the spectrum. This replication trial tested the effectiveness of PEERS, a caregiver-assisted social skills program for high-functioning young…

Brief Report: The Feasibility and Effectiveness of an Advocacy Program for Latino Families of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Burke, Meghan M.; Magaña, Sandra; Garcia, Marlene; Mello, Maria P.

2016-01-01

Latino, Spanish-speaking families of children with autism spectrum disorder (ASD) face unique barriers in special education advocacy. Although advocacy programs are becoming more common in the United States, none of these programs target Latino families. This is a pilot study to examine the feasibility and effectiveness of an advocacy program for…

Microbiologic profile of Staphylococci isolated from osteoarticular infections: evolution over ten years.

PubMed

Titécat, Marie; Senneville, Eric; Wallet, Frédéric; Dezèque, Hervé; Migaud, Henri; Courcol, René J; Loïez, Caroline

2015-02-01

Staphylococci, especially coagulase-negative staphylococci (CoNS) represent the most frequent micro-organism associated with osteoarticular infections (OAIs), especially those involving orthopedic devices. The antibiotic susceptibility profile of the bacteria mostly responsible for OAIs is therefore crucial information for choosing the appropriate antibiotic regimen administered during the removal procedure until the first results of the conventional culture. The antibiotic susceptibility profile of staphylococci isolated from OAIs in a referent center for osteoarticular infection was studied over a 10-y period to adapt antibiotic protocols to the ecology. From 2002 to 2011, the resistance of Staphylococcus aureus to methicillin and rifampicin decreased (27.9% versus 20.6% and 13% versus 1%, respectively); the resistance to fluoroquinolones (FQ) was stable (24% on average), and all the isolates were susceptible to glycopeptides. For CoNS, the resistance to methicillin, rifampicin, and FQ increased (30.4% versus 43.9%, 13% versus 18.5%, and 20.3% versus 34.1%, respectively) over the same period. Resistance of the CoNS to vancomycin was observed in 2011 for the first time (2.3%), and 3.8% were resistant to teicoplanin in 2002 compared with 22% in 2011, with 3.5% resistant to linezolid in 2011. The sensibility of bacteria over 10 y remained stable, except for CoNS. The increase of the resistances for CoNS led us to exclude teicoplanin from the first-line empiric antibiotic treatment, to avoid linezolid, and to prefer vancomycin or daptomycin.

In vitro activity of daptomycin and comparator agents against Staphylococcus aureus isolates from intravenous drug users with right endocarditis.

PubMed

Sanchez-Porto, Antonio; Casanova-Roman, Manuel; Casas-Ciria, Javier; Santaella, Maria Jose; Sanchez-Morenilla, Immaculada; Eiros-Bouza, Jose Maria

2010-06-01

There is an increasing need for alternative agents in endocarditis, especially with the increasing incidence of vancomycin-intermediate Staphylococcus aureus (VISA). We evaluated the in vitro activity of daptomycin and several comparator agents against 33 non-duplicate clinical Staphylococcus aureus isolates from intravenous drug users with right endocarditis. Wider microdilution panels were used for all the comparator agents and daptomycin. Daptomycin was also tested using E-test strips. E-test strips were used to confirm the vancomycin MICs. Methicillin-resistant Staphylococcus aureus (MRSA isolates with vancomycin MICs ≥ 2 g/mL were screened using the E-test GRD. In all, 30 isolates were methicillin-susceptible (MSSA) and 3 MRSA. The three MRSA isolates exhibited a false vancomycin MIC >2 g/mL determined by Wider microdilution panels. They were screened using the E-test GRD and they were GRD negative. Their final MIC was 2 g/mL. Three MSSA and three MRSA isolates had a vancomycin MIC of 2 g/mL. Four MSSA isolates had a vancomycin MIC of 1.5 g/mL, daptomycin MIC90 0.25 g/mL, linezolid MIC90 2 g/mL. As regards daptomycin, wider microdilution panels and E-test strips yielded the same results. Our findings suggest that daptomycin and linezolid are a viable alternative for treating right endocarditis and bacteraemia caused by MSSA, MRSA and hVISA.

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits.

PubMed

Weiss, Shay; Altboum, Zeev; Glinert, Itai; Schlomovitz, Josef; Sittner, Assa; Bar-David, Elad; Kobiler, David; Levy, Haim

2015-12-01

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Community-Based Early Intervention Program for Toddlers with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rollins, Pamela Rosenthal; Campbell, Michelle; Hoffman, Renee Thibodeau; Self, Kayli

2016-01-01

This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used.…

A mixed-method evaluation of the feasibility and acceptability of a telehealth-based parent-mediated intervention for children with autism spectrum disorder.

PubMed

Pickard, Katherine E; Wainer, Allison L; Bailey, Kathryn M; Ingersoll, Brooke R

2016-10-01

Research within the autism spectrum disorder field has called for the use of service delivery models that are able to more efficiently disseminate evidence-based practices into community settings. This study employed telehealth methods in order to deliver an Internet-based, parent training intervention for autism spectrum disorder, ImPACT Online. This study used mixed-methods analysis to create a more thorough understanding of parent experiences likely to influence the adoption and implementation of the program in community settings. Specific research questions included (1) What are parents' perceptions of the online program? (2) How does ImPACT Online compare to other services that parents are accessing for their children? And (3) Do parents' experience in, and perceptions of, the program differ based on whether they received a therapist-assisted version of the program? Results from 28 parents of a child with autism spectrum disorder indicate that parents saw improvements in their child's social communication skills and their own competence during the course of the program, regardless of whether they received therapist assistance. However, qualitative interviews indicate that parents who received therapist assistance were more likely endorse the acceptability and observability of the program. These findings support the potential for Internet-based service delivery to more efficiently disseminate evidence-based parent training interventions for autism spectrum disorder. © The Author(s) 2016.

Randomized, Controlled Trial of a Comprehensive Program for Young Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Young, Helen E.; Falco, Ruth A.; Hanita, Makoto

2016-01-01

This randomized, controlled trial, comparing the Comprehensive Autism Program (CAP) and business as usual programs, studied outcomes for 3-5 year old students with autism spectrum disorder (ASD). Participants included 84 teachers and 302 students with ASD and their parents. CAP utilized specialized curricula and training components to implement…

A Meta-Analytic Review of the Effectiveness of Behavioural Early Intervention Programs for Children with Autistic Spectrum Disorders

ERIC Educational Resources Information Center

Makrygianni, Maria K.; Reed, Phil

2010-01-01

The effectiveness of behavioural intervention programs for children with Autistic Spectrum Disorders was addressed by a meta-analysis, which reviewed 14 studies. The findings suggest that the behavioural programs are effective in improving several developmental aspects in the children, in terms of their treatment gains, and also relative to…

Development of a College Transition and Support Program for Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

White, Susan W.; Elias, Rebecca; Capriola-Hall, Nicole N.; Smith, Isaac C.; Conner, Caitlin M.; Asselin, Susan B.; Howlin, Patricia; Getzel, Elizabeth E.; Mazefsky, Carla A.

2017-01-01

Empirically based, consumer-informed programming to support students with Autism Spectrum Disorder (ASD) transitioning to college is needed. Informed by theory and research, the Stepped Transition in Education Program for Students with ASD (STEPS) was developed to address this need. The first level (Step 1) supports high school students and the…

Physical Activity into Socialization: A Movement-Based Social Skills Program for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Lee, Jihyun; Vargo, Kristina K.

2017-01-01

Children with autism spectrum disorder (ASD) often exhibit deficits in social-communicative behaviors. Given the increased prevalence of children with ASD, programs designed to teach social-communicative behaviors are necessary. This article introduces a movement-based program that embeds social-skill components to improve the motor skills and…

SoundScape: An Interdisciplinary Music Intervention for Adolescents and Young Adults on the Autism Spectrum

ERIC Educational Resources Information Center

Greher, Gena R.; Hillier, Ashleigh; Dougherty, Margaret; Poto, Nataliya

2010-01-01

Service provision for adolescents and young adults with autism spectrum disorders (ASD) is lacking, particularly post high school. We report on a music intervention program, outline our program model, and report some initial pilot data evaluating the program outcomes. We also discuss implications for undergraduate and graduate students who were…

The Experience of Parents of Toddlers Diagnosed with Autism Spectrum Disorder in the More than Words Parent Education Program

ERIC Educational Resources Information Center

Patterson, Stephanie Y.; Smith, Veronica

2011-01-01

A variety of parent-mediated communication intervention programs are available to families of young children with autism spectrum disorder including Hanen's "More Than Words" (MTW). Although the program is widely used, researchers understand little about parents' grasp of the information presented. Through a multiple case study, the unique…

The Impact of a Year-Long, Same School Social Skills Instruction Program on Students' with Verified Behavioral Disorders, Autism Spectrum Disorders, and Attention Deficit Hyperactivity Disorders Perceptions of Program Effectiveness

ERIC Educational Resources Information Center

Gaden, Gregory G.

2012-01-01

The purpose of this study was to determine the impact of a year-long, same school classroom social skills instruction program on students' with verified Emotional Behavior Disorders, Autism Spectrum Disorders, and Attention Deficit Hyperactivity Disorders perceptions of program effectiveness. This study indicated that youth can demonstrate…

The Organizational Communication Consulting Spectrum.

ERIC Educational Resources Information Center

Tubbs, Stewart L.

Surveys of businesses and business managers indicate that developing communication skills within organizations is a priority. Communication consulting exists over a wide spectrum of activities that include guest speaking, conducting workshops, and conducting management training programs. These three processes can include a "canned program" that…

An IEP for Me: Program Improvement for Rural Teachers of Students with Moderate to Severe Disability and Autism Spectrum Disorder

ERIC Educational Resources Information Center

Pennington, Robert C.

2017-01-01

Developing high-quality programming for students with moderate to severe disability (MSD) and/or autism spectrum disorder (ASD) can be challenging for teachers across the range of experience and training including those in rural contexts. This article outlines a process for the iterative refinement of teaching programs comprised of an evaluation…

A Formative Program Evaluation of a Postsecondary Support Program for Students with High Functioning Autism Spectrum Disorder

ERIC Educational Resources Information Center

Wise, Kelly L.

2015-01-01

Adults with a diagnosis of High Functioning Autism Spectrum Disorder (HF ASD) are becoming a significant presence on college campuses across the United States. A number of colleges have created programs to provide services to support accommodations for these students under the Americans with Disabilities Act (ADA); the first was created in 2002.…

VACTIV: A graphical dialog based program for an automatic processing of line and band spectra

NASA Astrophysics Data System (ADS)

Zlokazov, V. B.

2013-05-01

The program VACTIV-Visual ACTIV-has been developed for an automatic analysis of spectrum-like distributions, in particular gamma-ray spectra or alpha-spectra and is a standard graphical dialog based Windows XX application, driven by a menu, mouse and keyboard. On the one hand, it was a conversion of an existing Fortran program ACTIV [1] to the DELPHI language; on the other hand, it is a transformation of the sequential syntax of Fortran programming to a new object-oriented style, based on the organization of event interactions. New features implemented in the algorithms of both the versions consisted in the following as peak model both an analytical function and a graphical curve could be used; the peak search algorithm was able to recognize not only Gauss peaks but also peaks with an irregular form; both narrow peaks (2-4 channels) and broad ones (50-100 channels); the regularization technique in the fitting guaranteed a stable solution in the most complicated cases of strongly overlapping or weak peaks. The graphical dialog interface of VACTIV is much more convenient than the batch mode of ACTIV. [1] V.B. Zlokazov, Computer Physics Communications, 28 (1982) 27-37. NEW VERSION PROGRAM SUMMARYProgram Title: VACTIV Catalogue identifier: ABAC_v2_0 Licensing provisions: no Programming language: DELPHI 5-7 Pascal. Computer: IBM PC series. Operating system: Windows XX. RAM: 1 MB Keywords: Nuclear physics, spectrum decomposition, least squares analysis, graphical dialog, object-oriented programming. Classification: 17.6. Catalogue identifier of previous version: ABAC_v1_0 Journal reference of previous version: Comput. Phys. Commun. 28 (1982) 27 Does the new version supersede the previous version?: Yes. Nature of problem: Program VACTIV is intended for precise analysis of arbitrary spectrum-like distributions, e.g. gamma-ray and X-ray spectra and allows the user to carry out the full cycle of automatic processing of such spectra, i.e. calibration, automatic peak search and estimation of parameters of interest. VACTIV can run on any standard modern laptop. Reasons for the new version: At the time of its creation (1999) VACTIV was seemingly the first attempt to apply the newest programming languages and styles to systems of spectrum analysis. Its goal was to both get a convenient and efficient technique for data processing, and to elaborate the formalism of spectrum analysis in terms of classes, their properties, their methods and events of an object-oriented programming language. Summary of revisions: Compared with ACTIV, VACTIV preserves all the mathematical algorithms, but provides the user with all the benefits of an interface, based on a graphical dialog. It allows him to make a quick intervention in the work of the program; in particular, to carry out the on-line control of the fitting process: depending on the intermediate results and using the visual form of data representation, to change the conditions for the fitting and so achieve the optimum performance, selecting the optimum strategy. To find the best conditions for the fitting one can compress the spectrum, delete the blunders from it, smooth it using a high-frequency spline filter and build the background using a low-frequency spline filter; use not only automatic methods for the blunder deletion, the peak search, the peak model forming and the calibration, but also use manual mouse clicking on the spectrum graph. Restrictions: To enhance the reliability and portability of the program the majority of the most important arrays have a static allocation; all the arrays are allocated with a surplus, and the total pool of the program is restricted only by the size of the computer virtual memory. A spectrum has the static size of 32 K real words. The maximum size of the least-square matrix is 314 (the maximum number of fitted parameters per one analyzed spectrum interval, not for the whole spectrum), from which it follows that the maximum number of peaks in one spectrum interval is 154. The maximum total number of peaks in the spectrum is not restricted. Running time: The calculation time is negligibly small compared with the time for the dialog; using ini-files the program can be partly used in a semi-dialog mode.

Antibiotic Prescriptions in Critically-Ill Patients: A Latin American Experience

PubMed Central

Curcio, D

2013-01-01

Background: It is widely acknowledged that the presence of infection is an important outcome determinant for intensive care unit (ICU) patients. In fact, antibiotics are one of the most common therapies administered in the ICU settings. Aim: To evaluate the current usage of antibiotics in Latin American ICUs. Subjects and Methods: A one-day p-oint prevalence study to investigate the patterns of antibiotic was undertaken in 72 Latin American (LA) ICUs. Data was analyzed using the Statistix 8 statistical software, version 2.0 (USA). Results were expressed as proportions. When applicable, two tailed hypothesis testing for difference in proportions was used (Proportion Test); a P value of <0.05 was considered significant. Results: Of 704 patients admitted, 359 received antibiotic treatment on the day of the study (51%), of which 167/359 cases (46.5%) were due to hospital-acquired infections. The most frequent infection reorted was nosocomial pneumonia (74/359, 21%). Only in 264/359 patients (73.5%), cultures before starting antibiotic treatment were performed. Thirty-eight percent of the isolated microorganisms were Enterobacteriaceae extended-spectrum β-lactamase-producing, 11% methicillin-resistant Staphylococcus aureus and 10% carbapenems-resistant non-fermentative Gram-negatives. The antibiotics most frequently prescribed were carbapenems (125/359, 35%), alone or in combination with vancomycin or other antibiotic. There were no significant differences in the “restricted” antibiotic prescription (carbapenems, vancomycin, piperacillin–tazobactam, broad-spectrum cephalosporins, fluoroquinolones, tigecycline and linezolid) between patients with APACHE II score at the beginning of the antibiotic treatment <15 [83/114 (72.5%)] and ≥15 [179/245 (73%)] (P = 0.96). Only 29% of the antibiotic treatments were cultured directed (104/359). Conclusion: Carbapenems (alone or in combination) were the most frequently prescribed antibiotics in LA ICUs. However, the problem of carbapenem resistance in LA requires that physicians improve the use of this class of antibiotics. Our findings show that our web-based method for collection of one-day point prevalence was implemented successfully. However, based on the limitations of the model used, the results of this study must be taken with caution. PMID:23919194

Update of contemporary antimicrobial resistance rates across China: reference testing results for 12 medical centers (2011).

PubMed

Jones, Ronald N; Castanheira, Mariana; Hu, Bijie; Ni, Yuxing; Lin, Stephen S F; Mendes, Rodrigo E; Wang, Yao

2013-11-01

Antimicrobial resistance (R) surveillance across Asia and especially in China has documented unique patterns and mechanisms. This 2011 study reports results for 2278 isolates from 12 hospitals in China (94-216 strains/site); most from bacteremia (20.4%), pneumonias (29.1%), or skin and skin structure infections (20.9%). Samples were tested by reference broth microdilution methods, interpreted by published susceptibility (S) breakpoints. The most common species were Staphylococcus aureus (343, 45.8% MRSA), Escherichia coli (EC; 288), Pseudomonas aeruginosa (PSA; 221), Klebsiella spp. (KSP; 208), acinetobacters (ACB; 178), enterobacters (155), Streptococcus pneumoniae (SPN; 154, 46.8% penicillin-S), and enterococci (ENT; 137). Among 849 Gram-positive (GP) cocci, linezolid, tigecycline (TIG), daptomycin, and vancomycin provided best antimicrobial coverage (≥99.7% S). Resistance patterns of concern were 0.3% VISA, 15.4% teicoplanin non-S coagulase-negative staphylococci, 1.5% vancomycin-R ENT (all Enterococcus faecium), 1.9% levofloxacin-R β-haemolytic streptococci, and 35.1 and 12.7% ceftriaxone-non-S rates for SPN and viridans group streptococci, respectively. For Gram-negative bacilli, R among Enterobacteriaceae was highest against β-lactams (extended spectrum β-lactamase-phenotype strains at 73.6 and 42.8% in EC and KSP, respectively; carbapenem-R was only 2.1-4.3% with KPC and IMP type enzymes detected in KSP). The widest spectrum agents were cefoperazone/sulbactam (79.5-86.1%), piperacillin/tazobactam (88.9-92.0%), TIG (98.6-100%), amikacin (AMK; 91.8-93.7%), and meropenem (95.7-97.1% S). PSA was most inhibited by AMK (90.5% S) and colistin (COL; 99.5%), with cefepime (67.9%) best among the tested β-lactams. Only COL (100% S) and TIG (MIC90, 2 μg/mL) showed significant potencies against ACB. In conclusion, R among pathogens from 12 Chinese hospitals illustrates several agents active against GP pathogens, but more serious R problems were noted among Enterobacteriaceae, PSA, and ACB. Combination treatment for the latter multidrug-R strains appears necessary, guided by local antibiograms and national surveillance results applying reference methods. © 2013.

Supporting Dynamic Spectrum Access in Heterogeneous LTE+ Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luiz A. DaSilva; Ryan E. Irwin; Mike Benonis

As early as 2014, mobile network operators’ spectral capac- ity is expected to be overwhelmed by the demand brought on by new devices and applications. With Long Term Evo- lution Advanced (LTE+) networks likely as the future one world 4G standard, network operators may need to deploy a Dynamic Spectrum Access (DSA) overlay in Heterogeneous Networks (HetNets) to extend coverage, increase spectrum efficiency, and increase the capacity of these networks. In this paper, we propose three new management frameworks for DSA in an LTE+ HetNet: Spectrum Accountability Client, Cell Spectrum Management, and Domain Spectrum Man- agement. For these spectrum managementmore » frameworks, we define protocol interfaces and operational signaling scenar- ios to support cooperative sensing, spectrum lease manage- ment, and alarm scenarios for rule adjustment. We also quan- tify, through integer programs, the benefits of using DSA in an LTE+ HetNet, that can opportunistically reuse vacant TV and GSM spectrum. Using integer programs, we consider a topology using Geographic Information System data from the Blacksburg, VA metro area to assess the realistic benefits of DSA in an LTE+ HetNet.« less

A Summary of the Naval Postgraduate School Research Program and Recent Publications

DTIC Science & Technology

1990-09-01

principles to divide the spectrum of MATLAB computer program on a 386-type a wide-band spread-spectrum signal into sub- computer. Because of the high rf...original in time and a large data sample was required. An signal. Effects due the fiber optic pickup array extended version of MATLAB that allows and...application, such as orbital mechanics and weather prediction. Professor Gragg has also developed numerous MATLAB programs for linear programming problems

The Feasibility and Effects of a Parent-Facilitated Social Skills Training Program on Social Engagement of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Radley, Keith C.; Jenson, William R.; Clark, Elaine; O'Neill, Robert E.

2014-01-01

Due to impairments in social interactions and communication, children with autism spectrum disorders (ASD) have a need for effective social skills training programs. However, many programs fail due to a lack of acquisition, maintenance, and generalization of target skills. The primary purpose of this study was to evaluate the feasibility and…

Predicting Treatment Success in Social Skills Training for Adolescents with Autism Spectrum Disorders: The UCLA Program for the Education and Enrichment of Relational Skills

ERIC Educational Resources Information Center

Chang, Ya-Chih; Laugeson, Elizabeth A.; Gantman, Alexander; Ellingsen, Ruth; Frankel, Fred; Dillon, Ashley R.

2014-01-01

This study seeks to examine the predictors of positive social skills outcomes from the University of California, Los Angeles Program for the Education and Enrichment of Relational Skills, an evidence-based parent-assisted social skills program for high-functioning middle school and high school adolescents with autism spectrum disorders. The…

A Preliminary Evaluation of a School Support Program for Children with Autism Spectrum Disorders: Educator and School Level Outcomes and Program Processes

ERIC Educational Resources Information Center

McDougall, Janette; Servais, Michelle; Meyer, Katherine; Case, Sheila; Dannenhold, Kara; Johnson, Sue; Riggin, Colleen

2009-01-01

This is a preliminary evaluation of a program aimed at providing training, consultation, and resource materials to educators in public schools in order to build the capacity of those educators and schools to meet the needs of students with autism spectrum disorders. Educator and school level outcomes were evaluated and information about program…

Social and Clinical Effects of a Leisure Program on Adults with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Garcia-Villamisar, Domingo; Dattilo, John

2011-01-01

Using a pre-test, post-test experimental design, effects of a 1-year group leisure program were examined on 31 participants (20 male and 11 female), ages 27-38 (M = 32.05 at start of program), with an autism spectrum disorder (ASD) diagnosis randomly assigned to the experimental condition and a group of 20 adults with ASD randomly assigned to the…

[Pharmacoeconomic assessment of daptomycin as first-line therapy for bacteraemia and complicated skin and skin structure infections caused by gram-positive pathogens in Spain].

PubMed

Grau, S; Rebollo, P; Cuervo, J; Gil-Parrado, S

2011-09-01

To assess the efficiency of daptomycin as firstline therapy (D) versus daptomycin as salvage therapy after vancomycin (V→D ) or linezolid (L→D) failure in gram-positive bacteraemia and complicated skin and skin-structure infections (cSSTIs). Cost-effectiveness analysis of 161 bacteraemia and 84 cSSTIs patients comparing the above mentioned therapeutic alternatives was performed using the data from 27 Spanish hospitals involved in the EUCORE study. Direct medical costs were considered. Patients were observed from the first antibiotic dose for infection until either the end of daptomycin therapy or exitus. A multivariate Monte Carlo probabilistic sensitivity analysis was applied for costs (lognormal distribution) and effectiveness (normal distribution). In terms of effectiveness there were no statistical differences between groups but referring total costs per patient, there were significant differences. Sensitivity analysis confirmed that D dominates over L→D between 44.2%-62.1% of simulations in bacteraemia and between 48.2%-67.5% in cSSTIs. In comparison to V→D, D dominance was detected in 29.2%-33.2% of simulations in bacteraemia and between 48.2%-59.3% in cSSTIs. Daptomycin as first-line therapy dominates over daptomycin as salvage therapy after linezolid failure both in bacteraemia and cSSTIs. Comparing daptomycin as first-line therapy with its use after vancomycin failure, in cSSTIs the former is dominant. In bacteremia daptomycin as first line therapy is as effective as daptomycin as salvage therapy after vancomycin failure and implies lower costs.

In vitro activity of Tedizolid phosphate against multidrug-resistant Streptococcus pneumoniae isolates from Asian countries.

PubMed

Baek, Jin Yang; Kang, Cheol-In; Kim, So Hyun; Ko, Kwan Soo; Chung, Doo Ryeon; Peck, Kyong Ran; Hsueh, Po-Ren; Thamlikitkul, Visanu; So, Thomas Man-Kit; Lee, Nam Yong; Song, Jae-Hoon

2016-06-01

Tedizolid phosphate is a second-generation oxazolidinone prodrug that is potential activity against a wide range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, penicillin-resistant streptococci, and vancomycin-resistant enterococci. The in vitro activity of tedizolid and other comparator agents against multidrug-resistant (MDR) pneumococci from various Asian countries were evaluated. Of the S. pneumoniae clinical pneumonia isolates collected during 2008 and 2009 from 8 Asian countries (Korea, Taiwan, Thailand, Hong Kong, Vietnam, Malaysia, Philippines, and Sri Lanka), 104 isolates of MDR pneumococci were included in this study. Antimicrobial susceptibility testing for 18 antimicrobial agents was performed by broth microdilution method. Tedizolid was highly active against pneumococci. All isolates tested were inhibited at a tedizolid minimum inhibitory concentration (MIC) value of ≤0.25μg/ml (ranged from ≤0.03μg/ml to 0.25μg/ml). The MIC50 and MIC90 of tedizolid against MDR pneumococci were both 0.12μg/ml, while MIC50 and MIC90 of linezolid were 0.5μg/ml and 1μg/ml, respectively. In addition, tedizolid maintained the activity against S. pneumoniae regardless of the extensively drug-resistant (XDR) phenotype of the isolates. The activity of tedizolid was excellent against all types of MDR pneumococci, exhibiting and maintaining at least 4-fold-greater potency compared to linezolid, regardless of resistance phenotypes to other commonly utilized agents. Tedizolid has the potential to be an agent to treat infections caused by MDR pneumococci in the Asia. Copyright © 2016 Elsevier Inc. All rights reserved.

Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline.

PubMed

Hamad, Tarza; Hellmark, Bengt; Nilsdotter-Augustinsson, Åsa; Söderquist, Bo

2015-12-01

In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S. epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S. epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Dissecting the Mechanisms of Linezolid Resistance in a Drosophila melanogaster Infection Model of Staphylococcus aureus

PubMed Central

Diaz, Lorena; Kontoyiannis, Dimitrios P.; Panesso, Diana; Albert, Nathaniel D.; Singh, Kavindra V.; Tran, Truc T.; Munita, Jose M.; Murray, Barbara E.; Arias, Cesar A.

2013-01-01

Background. Mini-host models are simple experimental systems to study host-pathogen interactions. We adapted a Drosophila melanogaster infection model to evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance in Staphylococcus aureus. Methods. Fly survival was evaluated after infection with LNZ-resistant S. aureus strains NRS119 (which has mutations in 23S ribosomal RNA [rRNA]), CM-05 and 004-737X (which carry cfr), LNZ-susceptible derivatives of CM-05 and 004-737X (which lack cfr), and ATCC 29213 (an LNZ-susceptible control). Flies were then fed food mixed with LNZ (concentration, 15–500 µg/mL). Results were compared to those in mouse peritonitis, using LNZ via oral gavage at 80 and 120 mg/kg every 12 hours. Results. LNZ at 500 µg/mL in fly food protected against all strains, while concentrations of 15–250 µg/mL failed to protect against NRS119 (survival, 1.6%–20%). An in vivo effect of cfr was only detected at concentrations of 30 and 15 µg/mL. In the mouse peritonitis model, LNZ (at doses that mimic human pharmacokinetics) protected mice from challenge with the cfr+ 004-737X strain but was ineffective against the NRS119 strain, which carried 23S rRNA mutations. Conclusions. The fly model offers promising advantages to dissect the in vivo effect of LNZ resistance in S. aureus, and findings from this model appear to be concordant with those from the mouse peritonitis model. PMID:23547139

Repurposing Clinical Molecule Ebselen to Combat Drug Resistant Pathogens.

PubMed

Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N

2015-01-01

Without a doubt, our current antimicrobials are losing the battle in the fight against newly-emerged multidrug-resistant pathogens. There is a pressing, unmet need for novel antimicrobials and novel approaches to develop them; however, it is becoming increasingly difficult and costly to develop new antimicrobials. One strategy to reduce the time and cost associated with antimicrobial innovation is drug repurposing, which is to find new applications outside the scope of the original medical indication of the drug. Ebselen, an organoselenium clinical molecule, possesses potent antimicrobial activity against clinical multidrug-resistant Gram-positive pathogens, including Staphylococcus, Streptococcus, and Enterococcus, but not against Gram-negative pathogens. Moreover, the activity of ebselen against Gram-positive pathogens exceeded those activities determined for vancomycin and linezolid, drugs of choice for treatment of Enterococcus and Staphylococcus infections. The minimum inhibitory concentrations of ebselen at which 90% of clinical isolates of Enterococcus and Staphylococcus were inhibited (MIC90) were found to be 0.5 and 0.25 mg/L, respectively. Ebselen showed significant clearance of intracellular methicillin-resistant S. aureus (MRSA) in comparison to vancomycin and linezolid. We demonstrated that ebselen inhibits the bacterial translation process without affecting mitochondrial biogenesis. Additionally, ebselen was found to exhibit excellent activity in vivo in a Caenorhabditis elegans MRSA-infected whole animal model. Finally, ebselen showed synergistic activities with conventional antimicrobials against MRSA. Taken together, our results demonstrate that ebselen, with its potent antimicrobial activity and safety profiles, can be potentially used to treat multidrug resistant Gram-positive bacterial infections alone or in combination with other antibiotics and should be further clinically evaluated.

Antimicrobial susceptibility of clinical isolates of Actinomyces and related genera reveals an unusual clindamycin resistance among Actinomyces urogenitalis strains.

PubMed

Barberis, Claudia; Budia, Mabel; Palombarani, Susana; Rodriguez, Carlos Hernán; Ramírez, María Soledad; Arias, Barbara; Bonofiglio, Laura; Famiglietti, Angela; Mollerach, Marta; Almuzara, Marisa; Vay, Carlos

2017-03-01

Patterns of antimicrobial susceptibility in Actinomyces and related genera are very limited in the literature. Data of predominant susceptibility profiles could contribute to the establishment of an accurate empirical treatment. A total of 113 isolates from clinical samples were included in this study. Each isolate was identified using phenotypic methods and MALDI-TOF/MS. When discrepancies were observed, 16S rRNA gene sequencing was performed. The minimum inhibitory concentrations (MICs) of nine antimicrobial agents (penicillin, ceftriaxone, linezolid, tetracycline, clindamycin, erythromycin, ciprofloxacin, levofloxacin and vancomycin) were tested against the species Actinotignum schaalii (n=23), Actinomyces turicensis (n=18), Actinomyces europaeus (n=13), Actinomyces naeslundii/Actinomyces viscosus group (n=12), Actinomyces urogenitalis (n=11), Actinomyces radingae (n=11), Actinomyces neuii (n=9), Actinomyces odontolyticus (n=8), Bifidobacterium scardovii (n=3), Actinomyces graevenitzii (n=2), Alloscardovia omnicolens (n=2) and Varibaculum cambriense (n=1). All of the isolates were susceptible to penicillin, ceftriaxone, vancomycin and linezolid. Almost all of the A. urogenitalis isolates (8/11) were resistant to clindamycin and showed susceptibility to erythromycin, suggesting an L-phenotype, however no determinants of clindamycin resistance (lnu and lsa genes) were detected by PCR. High MIC values to quinolones were observed in 54/113 isolates (47.8%). All of the A. urogenitalis isolates were highly resistant to ciprofloxacin and levofloxacin. These data highlight the importance of ongoing surveillance to provide relevant information for empirical management of infections caused by these organisms. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium-intracellulare complex.

PubMed

Maurer, Florian P; Pohle, Philipp; Kernbach, Margrit; Sievert, Daniela; Hillemann, Doris; Rupp, Jan; Hombach, Michael; Kranzer, Katharina

2018-06-12

To determine MIC distributions for Mycobacterium chimaera, Mycobacterium intracellulare, Mycobacterium colombiense and Mycobacterium avium, and to derive tentative epidemiological cutoff (ECOFF) values. 683 bacterial isolates (M. chimaera, n = 203; M. intracellulare; n = 77; M. colombiense, n = 68; M. avium, n = 335) from 627 patients were tested by broth microdilution according to CLSI protocol M24-A2 on Sensititre RAPMYCOI plates. MICs were interpreted based on CLSI breakpoints for clarithromycin, and tentative breakpoints for amikacin, moxifloxacin and linezolid. Tentative ECOFFs were determined by visual approximation and the ECOFFinder algorithm. Modal MIC, MIC 50 and MIC 90 values were within ± one dilution step from the respective aggregated dataset for 47 / 48 (97.9 %), 48 / 48 (100 %), and 48 / 48 (100 %) species-drug combinations. Clarithromycin wild-type populations were mostly classified as susceptible (MIC 90 = 4 to 8 mg / l; S ≤ 8 mg/l). Rifabutin MICs were lower than those of rifampicin. Tentative moxifloxacin, linezolid and amikacin breakpoints split wild-type populations. No ECOFFs could be set for rifampicin, ethambutol, ciprofloxacin, isoniazid, trimethoprim/sulfamethoxazole and doxycycline due to truncation of MIC distributions. Agreement between the visually determined and the modelled 97.5 % ECOFFs was 90.9 %. All 99.0 % ECOFFs were one titer step higher than by visual approximation. Drug susceptibility patterns of M. chimaera are comparable to those of closely related species. Except for clarithromycin, breakpoints for MAIC should be reevaluated. Statistical determination of the 99.0 % ECOFF may be superior to visual approximation. Copyright © 2018. Published by Elsevier Ltd.

Linezolid Induced Twice Pure Red Cell Aplasia in a Patient with Central Nervous System Infection after Allogeneic Stem Cell Transplantation.

PubMed

Hu, Wenqing; Shi, Bing; Liu, Lihui; He, Shengke; Ye, Liping; Tian, DengMei; Zhang, Yongqing

2016-01-01

Linezolid (LZD), severed as the first oxazolidinone antibiotic, was active against multidrug-resistant gram-positive strains. LZD can induce thrombocytopenia, anemia and leukocytopenia. Currently, reports on pure red cell aplasia (PRCA) cases induced by LZD are relatively rare (4-7). In this paper, we reported a patient with PRCA twice induced by LZD. A 37-year-old man was diagnosed with myelodysplatic syndrome (MDS) and underwent allo-HSCT from an unrelated donor with ABO blood type and leukocyte antigen (HLA)-matching. After HSCT for 2 years, the patient suffered from refractory fever and headache. He was first treated with empirical antifungal agent and antibiotics for central nervous system (CNS) infection, but then changed to LZD therapy for little effect. Twenty-eight days after LZD treatment, the symptom improved significantly but the hemoglobin declined to 70 g/L and the reticulocyte level was only 0.23%. The LZD therapy was stopped and the fever and headache symptoms reoccurred 1 week latter. Then, erythropoietin (EPO) and halved dosage of LZD were used for treatment. The CNS infection and the anemia symptom relieved gradually and the level of hemoglobin and reticulocyte declined again. After blood transfusion, the half dose of LZD was sustained without anaemia recovery. In summary, patients with anemia, myelosuppressants history or potential abnormal proliferation of T cells may suffer PRCA with long term LZD treatment. The monitoring of complete blood count and reticulocyte count were necessary during LZD therapy. If the clinical condition permits, LZD dosage reduction and blood transfusion should be considered.

Antibiotic susceptibility patterns and prevalence of group B Streptococcus isolated from pregnant women in Misiones, Argentina

PubMed Central

Quiroga, M.; Pegels, E.; Oviedo, P.; Pereyra, E.; Vergara, M.

2008-01-01

This study was performed to determine the susceptibility patterns and the colonization rate of Group B Streptococcus (GBS) in a population of pregnant women. From January 2004 to December 2006, vaginal-rectal swabs were obtained from 1105 women attending Dr. Ramón Madariaga Hospital, in Posadas, Misiones, Argentina. The carriage rate of GBS among pregnant women was 7.6%. A total of 62 GBS strains were randomly selected for in vitro susceptibility testing to penicillin G, ampicillin, tetracycline, levofloxacin, gatifloxacin, ciprofloxacin, quinupristin-dalfopristin, linezolid, vancomycin, rifampicin, trimethoprim- sulfametoxazol, nitrofurantoin, gentamicin, clindamycin and erythromycin, and determination of resistance phenotypes. No resistance to penicillin, ampicillin, quinupristin-dalfopristin, linezolid, and vancomycin was found. Of the isolates examined 96.8%, 98.3%, 46.8%, and 29.0% were susceptible to rifampicin, nitrofurantoin, trimethoprim-sulfametoxazol and tetracycline, respectively. Rank order of susceptibility for the quinolones was: gatifloxacin (98.4%) > levofloxacin (93.5%) > ciprofloxacin (64.5%). The rate of resistance to erythromycin (9.7%) was higher than that of other reports from Argentina. High-level resistance to gentamicin was not detected in any of the isolates. Based on our finding of 50% of GBS isolates with MIC to gentamicin equal o lower than 8 μg/ml, a concentration used in one of the selective media recommended for GBS isolation, we suggested, at least in our population, the use of nalidixic acid and colistin in selective media with the aim to improve the sensitivity of screening cultures for GBS carriage in women. PMID:24031210

Methicillin-resistant Staphylococcus aureus intracranial abscess: An analytical series and review on molecular, surgical and medical aspects.

PubMed

Bahubali, Veena Kumari Haradara; Vijayan, Priya; Bhandari, Vasundhra; Siddaiah, Nagarathna; Srinivas, Dwarakanath

2018-01-01

Intracranial abscess caused by methicillin-resistant Staphylococcus aureus (MRSA) is rare and unexplored. The aim of the present study is to examine the prevalence, clinical and molecular characteristics, treatment options and outcome of MRSA intracranial abscess over a period of 6 years. A total of 21 patients were included in this retrospective study. The demographic and clinical details of all the patients were collected. Molecular typing including staphylococcal cassette chromosome mec typing, spa typing and polymerase chain reaction of Panton-Valentine leucocidin toxin (PVL) gene for the latter 6 isolates was performed. The paediatric population was the most affected group (33.3%). The primary route of infection was post-operative/trauma in 7 (33.3%) cases. All the patients were treated surgically either by aspiration or excision. Fifteen (71%) patients received anti-MRSA treatment with vancomycin or linezolid, where linezolid-treated patients showed better prognosis. Of the 11 patients who were on follow-up, unfavourable outcome was observed in 3 (27.3%) cases and 8 (72.7%) cases improved. The molecular typing of six isolates revealed four community-associated (CA) MRSA, one each of livestock-associated (LA) and healthcare-associated MRSA with PVL gene noted in all. We propose that timely diagnosis, surgical intervention and appropriate anti-MRSA treatment would contribute to better outcome. The occurrence of CA-MRSA and LA-MRSA infection in the central nervous system signifies the threat from the community and livestock reservoir, thus drawing attention towards surveillance and tracking to understand the epidemiology and implement infection control measures.

Breast Implant-Associated Infections: The Role of the National Surgical Quality Improvement Program and the Local Microbiome.

PubMed

Cohen, Justin B; Carroll, Cathy; Tenenbaum, Marissa M; Myckatyn, Terence M

2015-11-01

The most common cause of surgical readmission after breast implant surgery remains infection. Six causative organisms are principally involved: Staphylococcus epidermidis and S. aureus, Escherichia, Pseudomonas, Propionibacterium, and Corynebacterium. The authors investigated the infection patterns and antibiotic sensitivities to characterize their local microbiome and determine ideal antibiotic selection. A retrospective review of 2285 consecutive implant-based breast procedures was performed. Included surgical procedures were immediate and delayed breast reconstruction, tissue expander exchange, and cosmetic augmentation. Patient demographics, chemotherapy and/or irradiation status, implant characteristics, explantation reason, time to infection, microbiological data, and antibiotic sensitivities were reviewed. Forty-seven patients (2.1 percent) required inpatient admission for antibiotics, operative explantation, or drainage by interventional radiology. The infection rate varied depending on surgical procedure, with the highest rate seen in mastectomy and immediate tissue expander reconstruction (6.1 percent). The mean time to explantation was 41 days. Only 50 percent of infections occurred within 30 days of the indexed National Surgical Quality Improvement Program operation. The most commonly isolated organisms were coagulase-negative Staphylococcus (27 percent), methicillin-sensitive S. aureus (25 percent), methicillin-resistant S. aureus (7 percent), Pseudomonas (7 percent), and Peptostreptococcus (7 percent). All Gram-positive organisms were sensitive to vancomycin, linezolid, tetracycline, and doxycycline; all Gram-negative organisms were sensitive to gentamicin and cefepime. Empiric antibiotics should be vancomycin (with the possible inclusion of gentamicin) based on their broad effectiveness against the authors' unique microbiome. Minor infections should be treated with tetracycline or doxycycline as a second-line agent. National Surgical Quality Improvement Program data are adequate for monitoring and comparing breast infections but certainly not comprehensive. Therapeutic, IV.

Individualized Education Programs for Youth with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Wilczynski, Susan M.; Menousek, Kathryn; Hunter, Melissa; Mudgal, Dipti

2007-01-01

Children with Autism Spectrum Disorders (ASD) present with a broad array of deficits and excesses that require educational intervention. The Individualized Education Program (IEP) serves as the blueprint for educational intervention but it can sometimes be difficult to identify which goals and objectives should be addressed with this population.…

A computer program for estimating the power-density spectrum of advanced continuous simulation language generated time histories

NASA Technical Reports Server (NTRS)

Dunn, H. J.

1981-01-01

A computer program for performing frequency analysis of time history data is presented. The program uses circular convolution and the fast Fourier transform to calculate power density spectrum (PDS) of time history data. The program interfaces with the advanced continuous simulation language (ACSL) so that a frequency analysis may be performed on ACSL generated simulation variables. An example of the calculation of the PDS of a Van de Pol oscillator is presented.

Geosynchronous platform definition study. Volume 3: Geosynchronous mission characteristics

NASA Technical Reports Server (NTRS)

1973-01-01

The objectives of the study were to examine the nature of currently planned and new evolutionary geosynchronous programs, to analyze alternative ways of conducting missions, to establish concepts for new systems to support geosynchronous programs in an effective and economical manner, and to define the logistic support to carry out these programs. In order to meet these objectives, it was necessary to define and examine general geosynchronous mission characteristics and the potentially applicable electromagnetic spectrum characteristics. An organized compilation of these data is given with emphasis on the development and use of the data. Fundamental geosynchronous orbit time histories, mission profile characteristics, and delivery system characteristics are presented. In addition, electromagnetic spectrum utilization is discussed in terms of the usable frequency spectrum, the spectrum potentially available considering established frequency allocations, and the technology status as it affects the ability to operate within specific frequency bands.

The spectral positioning algorithm of new spectrum vehicle based on convex programming in wireless sensor network

NASA Astrophysics Data System (ADS)

Zhang, Yongjun; Lu, Zhixin

2017-10-01

Spectrum resources are very precious, so it is increasingly important to locate interference signals rapidly. Convex programming algorithms in wireless sensor networks are often used as localization algorithms. But in view of the traditional convex programming algorithm is too much overlap of wireless sensor nodes that bring low positioning accuracy, the paper proposed a new algorithm. Which is mainly based on the traditional convex programming algorithm, the spectrum car sends unmanned aerial vehicles (uses) that can be used to record data periodically along different trajectories. According to the probability density distribution, the positioning area is segmented to further reduce the location area. Because the algorithm only increases the communication process of the power value of the unknown node and the sensor node, the advantages of the convex programming algorithm are basically preserved to realize the simple and real-time performance. The experimental results show that the improved algorithm has a better positioning accuracy than the original convex programming algorithm.

Current and novel antibiotics against resistant Gram-positive bacteria.

PubMed

Perez, Federico; Salata, Robert A; Bonomo, Robert A

2008-01-01

The challenge posed by resistance among Gram-positive bacteria, epitomized by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and vancomycin-intermediate and -resistant S. aureus (VISA and VRSA) is being met by a new generation of antimicrobials. This review focuses on the new β-lactams with activity against MRSA (ceftobiprole and ceftaroline) and on the new glycopeptides (oritavancin, dalbavancin, and telavancin). It will also consider the role of vancomycin in an era of existing alternatives such as linezolid, daptomycin and tigecycline. Finally, compounds in early development are described, such as iclaprim, friulimicin, and retapamulin, among others.

The Challenge of Students with Autism Spectrum Disorder (ASD) in Honors Programs

ERIC Educational Resources Information Center

Yager, Susan

2016-01-01

Students with autism are increasingly present on college campuses, and because many young adults with autism are cognitively gifted, it follows that honors programs and colleges are obliged to be aware of this "invisible" disability and be ready to accommodate, and educate, honors students on the autism spectrum. Susan Yager describes…

Comprehensive Special Education Programming for Students with Autism Spectrum Disorder in the United States

ERIC Educational Resources Information Center

Morse, Timothy E.

2010-01-01

As the identification of students with autism spectrum disorder (ASD) continues to increase unabated, there exists a need to provide school personnel with information they can use for the purpose of designing and implementing appropriate comprehensive programs for these students. Accordingly, this article identifies and discusses comprehensive…

Effects of Peer Networks on the Social Interactions of High School Students with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Gardner, Karen F.; Carter, Erik W.; Gustafson, Jenny R.; Hochman, Julia M.; Harvey, Michelle N.; Mullins, Teagan S.; Fan, Hannah

2014-01-01

Supporting social interactions and positive peer relationships is an important element of comprehensive secondary education and transition programming. For many adolescents with autism spectrum disorders (ASDs), such social connections may be fairly limited apart from intentional programming. We examined the efficacy and social validity of peer…

Cognitive Behavioral Therapy for Anxiety in Children with Autism Spectrum Disorders: A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Wood, Jeffrey J.; Drahota, Amy; Sze, Karen; Har, Kim; Chiu, Angela; Langer, David A.

2009-01-01

Background: Children with autism spectrum disorders often present with comorbid anxiety disorders that cause significant functional impairment. This study tested a modular cognitive behavioral therapy (CBT) program for children with this profile. A standard CBT program was augmented with multiple treatment components designed to accommodate or…

Effects of a Decoding Program on a Child with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Infantino, Josephine; Hempenstall, Kerry

2006-01-01

This case study examined the effects of a parent-presented Direct Instruction decoding program on the reading and language skills of a child with high functioning Autism Spectrum Disorder. Following the 23 hour intervention, reading comprehension, listening comprehension and fluency skills improved to grade level, whilst statistically significant…

Evidence-Based Practices in Public School Programs for Young Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Herzog, Tania

2011-01-01

This study surveyed 77 special education teachers currently instructing elementary aged students diagnosed with Autism Spectrum Disorders to determine the extent of evidence-based practices utilized within public school programs. In addition, the survey examined the pre-service and on-going training these teachers receive to prepare them to…

JobTIPS: A Transition to Employment Program for Individuals with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Strickland, Dorothy C.; Coles, Claire D.; Southern, Louise B.

2013-01-01

This study evaluated the effectiveness of an internet accessed training program that included Theory of Mind-based guidance, video models, visual supports, and virtual reality practice sessions in teaching appropriate job interview skills to individuals with high functioning Autism Spectrum Disorders. In a randomized study, twenty-two youth, ages…

School-based social skills training for preschool-age children with autism spectrum disorder.

PubMed

Radley, Keith C; Hanglein, Jeanine; Arak, Marisa

2016-11-01

Individuals with autism spectrum disorder display impairments in social interactions and communication that appear at early ages and result in short- and long-term negative outcomes. As such, there is a need for effective social skills training programs for young children with autism spectrum disorder-particularly interventions capable of being delivered in educational settings. The study evaluated the effects of the Superheroes Social Skills program on accurate demonstration of social skills in young children with autism spectrum disorder. Two preschool-age children with autism spectrum disorder participated in a weekly social skills intervention. A multiple probe design across skills was used to determine the effects of the intervention. Both participants demonstrated substantial improvements in skill accuracy. Social skills checklists also indicated improvements in social functioning over baseline levels. © The Author(s) 2016.

Implementing the Learner-Designed Individual Program Style in Physical Education

ERIC Educational Resources Information Center

Chatoupis, Constantine

2018-01-01

The purpose of this article is to guide the teacher in implementing the learner-designed individual program style (LDIP) in physical education settings. The LDIP style is one of the 11 spectrum teaching styles that promote self-directed learning. The spectrum of teaching styles is a conceptual framework that helps describe and organize the…

A Randomized Controlled Trial to Examine the Effects of the Tackling Teenage Psychosexual Training Program for Adolescents with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka T.; Verhulst, Frank C.; Maras, Athanasios; van der Vegt, Esther J. M.

2017-01-01

Background: Previous research underscores the importance of psychosexual guidance for adolescents with autism spectrum disorder (ASD). Such guidance is provided in the Tackling Teenage Training (TTT) program, in which adolescents with ASD receive psycho-education and practice communicative skills regarding topics related to puberty, sexuality, and…

An Exploration of a Community-Based LEGO® Social-Skills Program for Youth with Autism Spectrum Disorder

ERIC Educational Resources Information Center

MacCormack, Jeffrey W. H.; Matheson, Ian A.; Hutchinson, Nancy L.

2015-01-01

Clinical interventions have been effective at increasing social skills of youth with autism spectrum disorder (ASD). However, generalization of those skills to non-clinical environments is often low. To reduce this generalization gap, community-based programs have been designed to help youth develop social skills in naturalistic settings. This…

A Qualitative Study of the Perceived Health Benefits of a Therapeutic Riding Program for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Stickney, Margaret Ann

2010-01-01

Therapeutic horseback riding can be recommended as a useful health promotion intervention for individuals with disabilities who face challenges to optimal health and wellness. This qualitative study examined the perceived benefits of a therapeutic riding program for children with autism spectrum disorders (ASD), with particular focus on aspects…

Teaching Students with Fetal Alcohol Spectrum Disorder: Building Strengths, Creating Hope. Programming for Students with Special Needs. Book 10

ERIC Educational Resources Information Center

Clarren, Sandra G. Bernstein

2004-01-01

"Teaching Students with Fetal Alcohol Spectrum Disorder: Building Strengths, Creating Hope" is Book 10 in the Programming for Students with Special Needs series; a revision and expansion of the 1997 Alberta Learning teacher resource, "Teaching Students with Fetal Alcohol Syndrome and Possible Prenatal Alcohol-Related Effects."…

Psychotropic Medication Trends among Children and Adolescents with Autism Spectrum Disorder in the Medicaid Program

ERIC Educational Resources Information Center

Schubart, Jane R.; Camacho, Fabian; Leslie, Douglas

2014-01-01

This study characterized psychotropic medication use among Medicaid-enrolled children and adolescents with autism spectrum disorders by examining trends over time, including length of treatment and polypharmacy using 4 years of administrative claims data from 41 state Medicaid programs (2000-2003). The data set included nearly 3 million children…

Effects of Psychomotor Intervention Program on Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

ElGarhy, Sayed; Liu, Ting

2016-01-01

The purpose of this study was to examine the effects of a psychomotor intervention program (PIP) on body awareness and psychomotor concepts for students with autism spectrum disorder (ASD). Twenty-eight students (23 boys and 5 girls) with ASD participated in this study. Fourteen students with ASD were randomly assigned to the experimental group…

The Effect of an Education Program for Mothers of Children with Autism Spectrum Disorder in Jordan

ERIC Educational Resources Information Center

Al-Khalaf, Amany; Dempsey, Ian; Dally, Kerry

2014-01-01

There are few support services for parents of children with a disability in Jordan. The present exploratory study investigated whether the provision of an education program in Jordan for mothers of children with Autism Spectrum Disorder increased mothers' understanding of their child's behaviour, improved the mothers' coping skills, and reduced…

Effects of a Summer Camp Program on Enhancing the Academic Achievement Skills of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Davenport, Teresa L.

2011-01-01

The purpose of this study was to determine if a summer camp utilizing academic and behavioral remediation programming could increase the academic achievement of children with autism spectrum disorders. Academic achievement was measured using the Wide Range Achievement Test-Fourth Edition (WRAT4; Wilkinson & Robertson, 2006) and an Informal…

MICROBIAL PROFILE AND ANTIBIOTIC SUSCEPTIBILITY PATTERNS OF PATHOGENS CAUSING VENTILATOR- ASSOCIATED PNEUMONIA AT INTENSIVE CARE UNIT, SESTRE MILOSRDNICE UNIVERSITY HOSPITAL CENTER, ZAGREB, CROATIA.

PubMed

Turković, Tihana Magdić; Grginić, Ana Gverić; Cucujić, Branka Đuras; Gašpar, Božena; Širanović, Mladen; Perić, Mladen

2015-06-01

Ventilator-associated pneumonia (VAP) is very common in many intensive care Units, but there are still many uncertainties about VAP, especially about the choice of initial empiric antibiotics. The incidence of specific pathogens with different susceptibility patterns causing VAP varies from hospital to hospital. This is the reason why empiric initial antibiotic treatment for VAP should be based not only on general guidelines (that recommend therapy according to the presence of risk factors for multidrug-resistant bacteria), but also on up-to-date information on local epidemiology. The aim of this study was to determine the microbial profile of pathogens causing VAP and their antibiotic susceptibility patterns. The study was conducted in the 15-bed surgical and neurosurgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Sestre milosrdnice University Hospital Center, Zagreb, Croatia. Retrospective data were collected from September 2009 to March 2013. All patients that developed VAP during the study period were eligible for the study. According to study results, the incidence of VAP was 29.4%. The most commonly isolated bacterium was Staphylococcus aureus (21.1%), followed by Pseudomonas aeruginosa (19.0%) and Acinetobacter species (13.6%). All Staphylococcus aureus isolates were susceptible to vancomycin and linezolid. Pseudomonas aeruginosa showed 100% susceptibility to cefepime and very high susceptibility to pip'eracillin-tazobactam (96%), ceftazidime (93%) and ciprofloxacin (89%). Ampicillin-sulbactam was highly effective for Acinetobacter species, showing resistance in only 8% of isolates. In conclusion, according to study data, appropriate empiric antibiotic therapy for patients with VAP without risk factors for multidrug-resistant bacteria is ceftriaxone and for patients with risk factors for multidrug-resistant bacteria ampicillin-sulbactam plus cefepime plus vancomycin or linezolid.

A holistic approach to MRSA eradication in critically ill patients with MRSA pneumonia.

PubMed

Wenisch, C; Laferl, H; Szell, M; Smolle, K H; Grisold, A; Bertha, G; Krause, R

2006-06-01

The number of Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia cases is increasing in many European countries. In this observational study in one medical and three surgical ICUs multiple interventions for the treatment and eradication of nosocomial MRSA-pneumonia were used. Twenty-one critically ill patients (age: 59 +/- 14 years, 15 males/6 females, 18 ventilator-associated, 3 nosocomial, clinical pulmonary infection score > 6 in all patients, APACHE II 18 +/- 5) were enrolled. The patients were treated with a 7-day course of iv linezolid (600 mg bid) plus rifampicin (600 mg bid), endotracheal vancomycin 100 mg qid, thrice daily mouth and throat washing with chlorhexidine 1% fluid and nasal mupirocin ointment, twice daily skin and hair washings with chlorhexidine gluconate 4% and tracheostomy (n = 8) wound care with povidone-iodine spray. Control samples (endotracheal secretions, nose, wound, and pharyngeal swabs) were taken 2, 3, 4, 7 days and 2 months thereafter. Multilobular pneumonia was seen in 16, pleural effusion in 12, and MRSA bacteremia in 4 patients. One patient died during the follow-up period due to cerebral bleeding. In the remaining 20 patients, pneumonia was clinically cured in all patients and all patients were free of MRSA after eradication. Six patients died due to myocardial infarction (n = 3), gram-negative septic shock (n = 2), herpes encephalitis (n = 1) > 7 days after eradication. No MRSA reinfection occurred during the control period. We conclude that in patients with MRSA pneumonia an approach using a 7-day course of intravenous linezolid plus rifampicin, intratracheal vancomycin, nasal mupirocin, cutaneous and oropharyngeal chlorhexidin plus povidone-iodine cures pneumonia and is effective for MRSA eradication.

Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case-control studies of incidence and associated risk factors.

PubMed

Mori, Nobuaki; Kamimura, Yoshio; Kimura, Yuki; Hirose, Shoko; Aoki, Yasuko; Bito, Seiji

2018-04-01

Lactic acidosis is a rare complication of linezolid (LZD) therapy, and its incidence and risk factors remain unknown. This study aimed to compare the incidence of LZD-associated lactic acidosis (LALA) and vancomycin (VAN)-associated lactic acidosis (VALA) and investigate the risk factors for LALA. We performed a retrospective cohort study using propensity score-matched analyses comparing the incidence of lactic acidosis between LZD and VAN therapy. We included adult patients administered LZD or VAN between April 2014 and March 2016 and extracted patient baseline data. In a case-control study, we identified the risk factors of lactic acidosis in patients treated with LZD. We identified 94 and 313 patients who were administered LZD and VAN, respectively. The incidence of lactic acidosis after LZD and VAN therapy was 10.6 and 0.3%, respectively. After propensity score-matched analyses, the incidence of lactic acidosis with LZD therapy was significantly higher than that with VAN therapy [10.0% (8/80) vs. 0% (0/80), respectively; risk difference, 0.1; 95% confidence interval (CI), 0.03-0.17; p = 0.004]. In a case-control study, 10 patients with LALA were matched to 20 non-lactic acidosis patients by age and sex. Patients with LALA were more likely to have renal insufficiency than non-lactic acidosis patients that were in the univariate analysis (odds ratio, 7.4; 95% CI, 1.0-84.4; p = 0.02). This study indicates that LALA occurs more frequently than VALA does and is associated with renal insufficiency. Therefore, close monitoring of kidney function and serum lactate is recommended during LZD therapy.

Random Mutagenesis of the Multidrug Transporter AcrB from Escherichia coli for Identification of Putative Target Residues of Efflux Pump Inhibitors

PubMed Central

Kohler, Samay; Buck, Annika; Dambacher, Christine; König, Armin; Bohnert, Jürgen A.; Kern, Winfried V.

2014-01-01

Efflux is an important mechanism of bacterial multidrug resistance (MDR), and the inhibition of MDR pumps by efflux pump inhibitors (EPIs) could be a promising strategy to overcome MDR. 1-(1-Naphthylmethyl)-piperazine (NMP) and phenylalanine-arginine-β-naphthylamide (PAβN) are model EPIs with activity in various Gram-negative bacteria expressing AcrB, the major efflux pump of Escherichia coli, or similar homologous pumps of the resistance-nodulation-cell division class. The aim of the present study was to generate E. coli AcrB mutants resistant to the inhibitory action of the two model EPIs and to identify putative EPI target residues in order to better understand mechanisms of pump inhibition. Using an in vitro random mutagenesis approach focusing on the periplasmic domain of AcrB, we identified the double mutation G141D N282Y, which substantially compromised the synergistic activity of NMP with linezolid, was associated with similar intracellular linezolid concentrations in the presence and absence of NMP, and did not impair the intrinsic MICs of various pump substrates and dye accumulation. We propose that these mutations near the outer face of the distal substrate binding pocket reduce NMP trapping. Other residues found to be relevant for efflux inhibition by NMP were G288 and A279, but mutations at these sites also changed the susceptibility to several pump substrates. Unlike with NMP, we were unable to generate AcrB periplasmic domain mutants with resistance or partial resistance to the EPI activity of PAβN, which is consistent with the modes of action of PAβN differing from those of NMP. PMID:25182653

Cellular Pharmacokinetics and Intracellular Activity of Gepotidacin against Staphylococcus aureus Isolates with Different Resistance Phenotypes in Models of Cultured Phagocytic Cells

PubMed Central

Peyrusson, Frédéric

2018-01-01

ABSTRACT Gepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase inhibitor, is currently in clinical development for the treatment of bacterial infections. This study examined in vitro its activity against intracellular Staphylococcus aureus (involved in the persistent character of skin and skin structure infections) by use of a pharmacodynamic model and in relation to cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin, linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more potent intracellularly (the apparent bacteriostatic concentration [Cs] was reached at an extracellular concentration about 0.7× its MIC and was not affected by mechanisms of resistance to the comparators) and (ii) caused a maximal reduction of the intracellular burden (maximum effect) of about −1.6 log10 CFU (which was better than that caused by linezolid, macrolides, and daptomycin and similar to that caused by moxifloxacin). After 24 h of incubation of infected cells with antibiotics at 100× their MIC, the intracellular persisting fraction was <0.1% with moxifloxacin, 0.5% with gepotidacin, and >1% with the other drugs. The accumulation and efflux of gepotidacin in phagocytes were very fast (kin and kout, ∼0.3 min−1; the plateau was reached within 15 min) but modest (intracellular concentration-to-extracellular concentration ratio, ∼1.6). In cell fractionation studies, about 40 to 60% of the drug was recovered in the soluble fraction and ∼40% was associated with lysosomes in uninfected cells. In infected cells, about 20% of cell-associated gepotidacin was recovered in a sedimentable fraction that also contained bacteria. This study highlights the potential for further study of gepotidacin to fight infections where intracellular niches may play a determining role in bacterial persistence and relapses. PMID:29358297

Susceptibility Testing of Extensively Drug-Resistant and Pre-Extensively Drug-Resistant Mycobacterium tuberculosis against Levofloxacin, Linezolid, and Amoxicillin-Clavulanate

PubMed Central

Ahmed, Imran; Jabeen, Kauser; Inayat, Raunaq

2013-01-01

Pakistan is a high-burden country for tuberculosis (TB). The emergence and increasing incidence of extensively drug-resistant (XDR) TB has been reported in Pakistan. Similarly, the prevalence of multidrug-resistant TB infections with fluoroquinolone resistance (pre-XDR) is also increasing. To treat these infections, local drug susceptibility patterns of alternate antituberculosis agents, including levofloxacin (LVX), linezolid (LZD), and amoxicillin-clavulanate (AMC), is urgently needed. The aim of this study was to determine the susceptibility frequencies of drug-resistant (DR) Mycobacterium tuberculosis against LVX, LZD, and AMC. All susceptibilities were determined on Middlebrook 7H10 agar. A critical concentration was used for LVX (1 μg/ml), whereas MICs were determined for LZD and AMC. M. tuberculosis H37Rv was used as a control strain. A total of 102 M. tuberculosis isolates (XDR, n = 59; pre-XDR, n = 43) were tested. Resistance to LVX was observed in 91.2% (93/102). Using an MIC value of 0.5 μg/ml as a cutoff, resistance to LZD (MIC ≥ 1 μg/ml) was noted in 5.9% (6/102). Although the sensitivity breakpoints are not established for AMC, the MIC values were high (>16 μg/ml) in 97.1% (99/102). Our results demonstrate that LZD may be effective for the treatment of XDR and pre-XDR cases from Pakistan. High resistance rates against LVX in our study suggest the use of this drug with caution for DR-TB cases from this area. Drug susceptibility testing against LVX and AMC may be helpful in complicated and difficult-to-manage cases. PMID:23507286

Susceptibility testing of extensively drug-resistant and pre-extensively drug-resistant Mycobacterium tuberculosis against levofloxacin, linezolid, and amoxicillin-clavulanate.

PubMed

Ahmed, Imran; Jabeen, Kauser; Inayat, Raunaq; Hasan, Rumina

2013-06-01

Pakistan is a high-burden country for tuberculosis (TB). The emergence and increasing incidence of extensively drug-resistant (XDR) TB has been reported in Pakistan. Similarly, the prevalence of multidrug-resistant TB infections with fluoroquinolone resistance (pre-XDR) is also increasing. To treat these infections, local drug susceptibility patterns of alternate antituberculosis agents, including levofloxacin (LVX), linezolid (LZD), and amoxicillin-clavulanate (AMC), is urgently needed. The aim of this study was to determine the susceptibility frequencies of drug-resistant (DR) Mycobacterium tuberculosis against LVX, LZD, and AMC. All susceptibilities were determined on Middlebrook 7H10 agar. A critical concentration was used for LVX (1 μg/ml), whereas MICs were determined for LZD and AMC. M. tuberculosis H37Rv was used as a control strain. A total of 102 M. tuberculosis isolates (XDR, n = 59; pre-XDR, n = 43) were tested. Resistance to LVX was observed in 91.2% (93/102). Using an MIC value of 0.5 μg/ml as a cutoff, resistance to LZD (MIC ≥ 1 μg/ml) was noted in 5.9% (6/102). Although the sensitivity breakpoints are not established for AMC, the MIC values were high (>16 μg/ml) in 97.1% (99/102). Our results demonstrate that LZD may be effective for the treatment of XDR and pre-XDR cases from Pakistan. High resistance rates against LVX in our study suggest the use of this drug with caution for DR-TB cases from this area. Drug susceptibility testing against LVX and AMC may be helpful in complicated and difficult-to-manage cases.

Virulence-suppressing effects of linezolid on methicillin-resistant Staphylococcus aureus: possible contribution to early defervescence.

PubMed

Yoshizawa, Sadako; Tateda, Kazuhiro; Saga, Tomoo; Ishii, Yoshikazu; Yamaguchi, Keizo

2012-04-01

In the present study, immunomodulatory effects of linezolid (LZD) on methicillin-resistance Staphylococcus aureus (MRSA) infections were evaluated. We have retrospectively reviewed treatment effects of LZD on 52 patients with severe MRSA infections. Sixty-four percent of the febrile patients demonstrated significant defervescence within 3 days, despite the presence of positive culture results. We speculated that this finding might be due to early anti-inflammatory effects of LZD, and to investigate this further we initiated in vivo experiments using mice MRSA pneumonia models. Mice were treated with either LZD or vancomycin (VCM) immediately after intranasal administration of MRSA. Bacterial numbers and levels of inflammatory cytokines in the lungs were determined. Although the bacterial burden in the lungs was not apparently different between the two groups, LZD but not VCM treatment significantly reduced induction of inflammatory cytokines in the lungs (P < 0.05). To evaluate whether this anti-inflammatory response was due to suppression of virulence factor expression, filter-sterilized supernatants of MRSA incubated in broth overnight with sub-MICs of LZD were subcutaneously administered to mice. To clarify whether LZD possesses direct host-modulating activity, cytokine responses to the supernatants were examined in mice pretreated with LZD. Interestingly, MRSA solutions prepared in the presence of sub-MICs of LZD revealed significant suppression of interleukin 6 (IL-6) in a dose-dependent manner (P < 0.05), but pretreatment of mice with LZD revealed no changes in cytokines. These findings suggest that sub-MICs of LZD might suppress virulence factors of MRSA, which may be associated with a reduction in endogenous pyrogens. These data may explain at least in part early defervescence observed in LZD-treated individuals.

Antibiotic susceptibilities and prevalence of Methicillin resistant Staphylococcus aureus (MRSA) isolated from bovine milk in Pakistan.

PubMed

Aqib, Amjad Islam; Ijaz, Muhammad; Anjum, Aftab Ahmad; Malik, Muhammad Abdul Rauf; Mehmood, Khalid; Farooqi, Shahid Hussain; Hussain, Kashif

2017-12-01

The study was designed to investigate bovine milk for prevalence of an emerging zoonotic pathogen Methicillin resistant Staphylococcus aureus (MRSA), and in-vitro therapeutic response of various antibiotics against MRSA. Nine hundred (900) milk samples were collected (half from cattle and half from buffalo) from private and public farms located in various tehsils of district Faisalabad, using the convenient sampling method. Milk samples were put to biochemical identification of Staphylococcus aureus and later oxacilline disk sensitivity testing for confirmation of MRSA. The MRSA isolates were confirmed by PCR targeting mecA gene in Staphylococcus aureus. The study found 34% prevalence of MRSA in overall bovine milk from district Faisalabad with 30% and 38% prevalence in cattle and buffalo, respectively. Tehsil Samundari presented comparatively higher MRSA prevalence followed by tehsil Jaranwala and tehsil Faisalabad. However, there was non-significant difference of MRSA prevalence between cattle and buffalo, and among different tehsils. All assumed risk factors except specie were significantly associated with mastitis spread. The in-vitro drug trial against MRSA from buffalo milk presented 100% efficacy of Ciprofloxcin, Moxifloxacin, Linezolid, and Trimethoprim plus Sulphamethoxazole combination, followed by Gentamicin and Levofloxacin presenting 90%, and Amikacin becoming 80% efficacious against MRSA from buffalo milk. The MRSA isolates of cattle milk presented similar pattern with some variations of higher susceptibility against Oxytetracycline, and Fusidic acid. The conclusion of the study states uniform prevalence of MRSA in cattle and buffalo milk in study area having assumed risk factors positively associated with disease spread, while Ciprofloxcin, Moxifloxacin, Linezolid, and Trimethoprim plus Sulphamethoxazole drugs showed the highest efficacy to combat this pathogen. Copyright © 2017 Elsevier B.V. All rights reserved.

Sub-inhibitory tigecycline concentrations induce extracellular matrix binding protein Embp dependent Staphylococcus epidermidis biofilm formation and immune evasion.

PubMed

Weiser, Julian; Henke, Hanae A; Hector, Nina; Both, Anna; Christner, Martin; Büttner, Henning; Kaplan, Jeffery B; Rohde, Holger

2016-09-01

Biofilm-associated Staphylococcus epidermidis implant infections are notoriously reluctant to antibiotic treatment. Here we studied the effect of sub-inhibitory concentrations of penicillin, oxacillin, vancomycin, daptomycin, linezolid and tigecycline on S. epidermidis 1585 biofilm formation, expression of extracellular matrix binding protein (Embp) and potential implications for S. epidermidis - macrophage interactions. Penicillin, vancomycin, daptomycin, and linezolid had no biofilm augmenting effect at any of the concentrations tested. In contrast, at sub-inhibitory concentrations tigecycline and oxacillin exhibited significant biofilm inducing activity. In S. epidermidis 1585, SarA is a negative regulator of giant 1 MDa Embp, and down regulation of sarA induces Embp-dependent assembly of a multi-layered biofilm architecture. Dot blot immune assays, confocal laser scanning microscopy, and qPCR showed that under biofilm inducing conditions, tigecycline augmented embp expression compared to the control grown without antibiotics. Conversely, expression of regulator sarA was suppressed, suggesting that tigecycline exerts its effects on embp expression through SarA. Tigecycline failed to induce biofilm formation in embp transposon mutant 1585-M135, proving that under these conditions Embp up-regulation is necessary for biofilm accumulation. As a functional consequence, tigecycline induced biofilm formation significantly impaired the up-take of S. epidermidis by mouse macrophage-like cell line J774A.1. Our data provide novel evidence for the molecular basis of antibiotic induced biofilm formation, a phenotype associated with inherently increased antimicrobial tolerance. While this could explain failure of antimicrobial therapies, persistence of S. epidermidis infections in the presence of sub-inhibitory antimicrobials is additionally propelled by biofilm-related impairment of macrophage-mediated pathogen eradication. Copyright © 2016 Elsevier GmbH. All rights reserved.

Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains.

PubMed

Shahzad, Shakeel; Ashraf, M Adnan; Sajid, M; Shahzad, Aqeel; Rafique, Azhar; Mahmood, M Shahid

2018-02-02

Multiple drug resistant super bugs of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) are becoming challenge for healthcare professionals. In this study, vitamins were evaluated for synergistic activity with the antibiotics. Synergistic effect between antibiotic and stock solutions of vitamins is evaluated by using Kirby-Bauer disc diffusion assay. Distilled water and propylene glycol were used as solvent for water soluble vitamins and fat-soluble vitamins respectively. The final concentration of 10mg/ml of each water-soluble vitamin B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine) B12 (Methylcobalamin), C (Ascorbic acid) and 0.1mg/ml of each fat soluble vitamin A (retinol), D (cholecalciferol) E (αTocopherol) K (Menadione) were used with the antibiotics. The results depicted that vitamin K and E have better synergistic activity with piperacillin-tazobactam, imipenem and doripenem antibiotics against A. baumannii. While vitamin B1, B2 and B12 showed remarkable synergistic activity with linezolid against MRSA. Vitamin B1 was further tested to have better synergism with antibiotics oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K were good in synergism against Gram negative A. baumannii while water soluble vitamins as B1, B2 and B12 were effective against MRSA but not against A. baumannii. This synergistic action of vitamins with the antibiotics can be used as a tool to treat multiple drug resistant super bugs with further evaluation at molecular level. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Current antibiotic management of prosthetic joint infections in Italy: the 'Udine strategy'.

PubMed

Bassetti, Matteo; Cadeo, Barbara; Villa, Giovanni; Sartor, Assunta; Cainero, Vanni; Causero, Araldo

2014-09-01

The rate of prosthetic joint infections followed and cured at our institution is constantly increasing, in line with epidemiological data from the recent literature. This is probably related to the greater number of knee and hip prostheses implanted every year. For intermediate and late infections, only the two-stage approach is applied, as this demonstrates the best outcome in our experience. Particular attention is paid to microbiological isolation of the pathogen: multiple samples of tissue are collected during the interventions, and kept in culture for a longer period of time than usual. Sonication of prosthetic devices is used to enhance the sensitivity and specificity of the microbiological cultures. Histological examination influences surgical choices either towards implantation of a new prosthesis or replacement of the spacer. An empirical antibiotic backbone of a glycopeptide/lipopeptide and rifampicin is chosen, due to the leading role of Gram-positive bacteria in this setting and the high incidence of methicillin resistance in our centre (>30%), followed by an antibiotic regimen containing linezolid. If specific risk factors are present, an anti-Gram-negative drug is added to the regimen. Duration of therapy depends upon the approach that is chosen, usually being 6 weeks when the prosthesis is removed. Despite at the moment being limited by its small sample size, data from our experience confirms that our empirical approach may represent a valid choice during the early phase of treatment, by keeping linezolid for a step-down therapy of shorter duration (4 weeks). © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antibiotics and sweeteners in the aquatic environment: biodegradability, formation of phototransformation products, and in vitro toxicity.

PubMed

Bergheim, Marlies; Gminski, Richard; Spangenberg, Bernd; Debiak, Malgorzata; Bürkle, Alexander; Mersch-Sundermann, Volker; Kümmerer, Klaus; Gieré, Reto

2015-11-01

In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, marbofloxacin, and sarafloxacin) and of their phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and consequently may help to reduce antimicrobial resistance in wastewaters. Nevertheless, the study also highlights that some PTPs may exhibit a higher ecotoxicity than the respective parent compounds. Consequently, UV treatment does not transform all micropollutants into harmless compounds and may not be a large-scale effluent treatment option.

Efficacies of Ceftobiprole Medocaril and Comparators in a Rabbit Model of Osteomyelitis Due to Methicillin-Resistant Staphylococcus aureus▿

PubMed Central

Yin, Li-Yan; Calhoun, Jason H.; Thomas, Jacob K.; Shapiro, Stuart; Schmitt-Hoffmann, Anne

2008-01-01

The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand White rabbits were determined after subcutaneous administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum concentration of the drug in serum, trough concentration, area under the concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose proportional, and there was no accumulation of ceftobiprole following repeated (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial matrix and marrow were 3.2 ± 1.3 μg/g and 11.2 ± 6.5 μg/g, respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and 13.4 ± 7.3 μg/g and 66.3 ± 43.2 μg/g, respectively, in uninfected animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole titers were observed between right and left tibiae for either bone matrix or marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c. q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis. After treatment with ceftobiprole, the bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; the mean titers of ceftobiprole were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model. PMID:18332175

Efficacies of ceftobiprole medocaril and comparators in a rabbit model of osteomyelitis due to methicillin-resistant Staphylococcus aureus.

PubMed

Yin, Li-Yan; Calhoun, Jason H; Thomas, Jacob K; Shapiro, Stuart; Schmitt-Hoffmann, Anne

2008-05-01

The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand White rabbits were determined after subcutaneous administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum concentration of the drug in serum, trough concentration, area under the concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose proportional, and there was no accumulation of ceftobiprole following repeated (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial matrix and marrow were 3.2 +/- 1.3 microg/g and 11.2 +/- 6.5 microg/g, respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and 13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/g, respectively, in uninfected animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole titers were observed between right and left tibiae for either bone matrix or marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c. q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis. After treatment with ceftobiprole, the bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; the mean titers of ceftobiprole were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model.

Leap forward in the treatment of Pythium insidiosum keratitis.

PubMed

Bagga, Bhupesh; Sharma, Savitri; Madhuri Guda, Sai Jeevan; Nagpal, Ritu; Joseph, Joveeta; Manjulatha, Kodiganti; Mohamed, Ashik; Garg, Prashant

2018-03-15

Pythium insidiosum is a parafungus that causes keratitis resembling fungal keratitis. This study compares outcome in a large cohort of patients with P insidiosum keratitis treated with antifungal drugs, to a pilot group treated with antibacterial antibiotics. Between January 2014 and December 2016, 114 patients with culture positive P insidiosum keratitis were included in the study. A subset of culture isolates was tested in vitro for response to nine antibacterial antibiotics by disc diffusion and E test. Patients were treated with topical natamycin in 2014, 2015 and up until mid 2016. Thereafter, the patients received a combination of topical linezolid and topical and oral azithromycin. Therapeutic penetrating keratoplasty (TPK) was done for patients not responding to medical therapy. In vitro disc diffusion assay showed linezolid to be most effective. The rate of TPK was significantly higher in 2015 compared with 2016 (43/45, 95.6% vs 22/32, 68.8%; p=0.002). Eighteen patients were treated with antibacterial and 14 were treated with antifungal antibiotic in 2016. One patient was lost to follow-up in each group. The rate of TPK was higher and proportion of healed ulcers was lower (p=0.21, Fisher's exact test) in the group on antifungal therapy (TPK-11/13, 84.6%; Healed-2/13, 15.3%) compared with the group on antibacterial therapy (TPK-11/17, 64.7%; Healed-6/17, 35.2%). We report favourable but not statistically significant response of P insidiosum keratitis to antibacterial agents in a pilot series of patients. Further evaluation of this strategy in larger number of patients is recommended. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Antibiotic modulation of the plasminogen binding ability of viridans group streptococci.

PubMed

Teles, Cristina; Smith, Andrew; Lang, Sue

2012-01-01

The ability of viridans group streptococci to bind human plasminogen and its subsequent activation into plasmin may contribute to the pathogenesis of infective endocarditis (IE) by leading to a decreased stability of the streptococcal vegetation and facilitating dehiscence of emboli. At levels greater than or equal to their MICs, penicillin, vancomycin, and linezolid are efficacious in the treatment of streptococcal endocarditis. However, at sub-MICs, antibiotics can modulate the expression of bacterial genes, including virulence-associated genes, which can have counterproductive effects on the treatment of endocarditis. The effects of 1/8× and 1/4× MICs of penicillin, vancomycin, and linezolid on the plasminogen binding ability of IE isolates Streptococcus mitis 881/956, Streptococcus oralis 12601, and Streptococcus sanguinis 12403 were assessed phenotypically and the expression of plasminogen receptors α-enolase and glyceraldehyde 3-phosphate dehydrogenase of S. oralis 12601 when exposed to 1/4× MIC of penicillin, was analyzed through quantitative reverse transcription (qRT)-PCR. The plasminogen binding ability of S. mitis 881/956 and S. sanguinis 12403 remained unaffected by exposure to sub-MICs of all of the antibiotics tested, while that of S. oralis 12601 was significantly enhanced by all of the antibiotics tested at sub-MICs. qRT-PCR analysis of S. oralis 12601 demonstrated an upregulation of the eno and gapdh genes, indicating an overexpression of plasminogen receptors. These findings suggest that for some endocarditis isolates, the effect of antibiotic sub-MICs, in addition to a reduced antibacterial effect, may influence the clinical response to nonsurgical therapy. It remains difficult to accurately predict isolate responses to sub-MIC antimicrobials since there appears to be interspecies variation.

Molecular Epidemiology of Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium Isolated from Clinical Specimens in the Northwest of Iran.

PubMed

Jahansepas, Ali; Ahangarzadeh Rezaee, Mohammad; Hasani, Alka; Sharifi, Yaeghob; Rahnamaye Farzami, Marjan; Dolatyar, Alireza; Aghazadeh, Mohammad

2018-04-30

This study was conducted to investigate the phenotypic and genotypic characteristics of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. Antibiotic resistance and virulence genes in the aforementioned resistant isolates were studied using the epsilometer (E)-test and polymerase chain reaction (PCR). These isolates were subjected to typing by pulsed-field gel electrophoresis (PFGE). Thirty vancomycin-resistant enterococci (VRE; 18.75%) were isolated from a total of 160 various clinical specimens cultured for any bacterial growth. Of these, 11 (36.7%) isolates were identified as E. faecalis and 19 (63.3%) as E. faecium. Minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, and three alternative therapeutic options (linezolid, daptomycin, and quinupristin/dalfopristin) were determined using the E-test. Multiplex PCR was done for confirming species, identification of the resistant genotypes, and the detection of the virulence genes. Finally, the clonal relationship of all VRE strains was studied by PFGE. All VRE strains showed vancomycin MIC ≥256 μg/mL, and 27 (90%) isolates carried the vanA gene, whereas none of the isolates carried vanB. The most common resistance antibiotic pattern observed was toward rifampicin (n = 30 [100%]). Among all virulence genes studied, gelE (n = 28 [93.33%]) was found as the most prevalent virulent gene. VRE isolates exhibited 90%, 46.67%, 100%, and 66.67% resistance to teicoplanin, linezolid, quinupristin/dalfopristin, and daptomycin, respectively. Molecular typing demonstrated 16 PFGE types of VRE isolates (A-P). Although vanA was carried by most of the isolates, PFGE displayed small clonal dissemination among VR E. faecium and VR E. faecalis species.

Antimicrobial Susceptibility Patterns of Clostridium difficile Isolates from Family Dairy Farms.

PubMed

Bandelj, P; Golob, M; Ocepek, M; Zdovc, I; Vengust, M

2017-05-01

A significant risk factor for developing Clostridium difficile infection (CDI) in humans and animals is associated with the antimicrobial use. It has often been hypothesized that farm animals could be the source for human infection with Clostridium difficile (CD). In the European Union, family-run dairy farms are the predominant farming model, which are more interlinked within the community compared to large-scale intensive dairy or beef farms. Therefore, it is important to investigate antimicrobial susceptibility patterns of CD in such environment. A total of 159 CD isolates from 20 family dairy farms were tested with a customized broth microdilution plate for their antimicrobial resistance. Seventeen antimicrobials were selected (amoxicillin, ceftriaxone, clindamycin, daptomycin, erythromycin, fusidic acid, imipenem, levofloxacin, linezolid, metronidazole, moxifloxacin, oxacillin, rifampicin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole and vancomycin), which are commonly used for treatment of CDI in veterinary and human medicine, or were previously applied in CD epidemiological studies. Antimicrobials, which are used for treatment of CDI in humans (metronidazole, vancomycin, fusidic acid, tigecycline, linezolid) inhibited CD growth in vitro. Most CD isolates were resistant to erythromycin (93.1%), daptomycin (69.2%) and clindamycin (46.5%). High multiple-resistance was found in CD ribotype 012 (n = 5, 100%), some CD SLO 060 (n = 4, 25%) and one CD 033 (n = 1, 1.1%). High multiple-resistance in this study was linked with CD ribotypes and not with the origin of CD. The low prevalence of these ribotypes (6.3%; 10/159) indicates that family-run dairy farms are an unlikely source of CD with multiple-resistance to antimicrobials. © 2016 Blackwell Verlag GmbH.

Vancomycin resistant enterococci in urine cultures: Antibiotic susceptibility trends over a decade at a tertiary hospital in the United Kingdom.

PubMed

Toner, Liam; Papa, Nathan; Aliyu, Sani H; Dev, Harveer; Lawrentschuk, Nathan; Al-Hayek, Samih

2016-03-01

Enterococci are a common cause of urinary tract infection and vancomycin-resistant strains are more difficult to treat. The purpose of this surveillance program was to assess the prevalence of and determine the risk factors for vancomycin resistance in adults among urinary isolates of Enterococcus sp. and to detail the antibiotic susceptibility profile, which can be used to guide empirical treatment. From 2005 to 2014 we retrospectively reviewed 5,528 positive Enterococcus sp. urine cultures recorded in a computerized laboratory results database at a tertiary teaching hospital in Cambridge, United Kingdom. Of these cultures, 542 (9.8%) were vancomycin resistant. No longitudinal trend was observed in the proportion of vancomycin-resistant strains over the course of the study. We observed emerging resistance to nitrofurantoin with rates climbing from near zero to 40%. Ampicillin resistance fluctuated between 50% and 90%. Low resistance was observed for linezolid and quinupristin/dalfopristin. Female sex and inpatient status were identified as risk factors for vancomycin resistance. The incidence of vancomycin resistance among urinary isolates was stable over the last decade. Although resistance to nitrofurantoin has increased, it still serves as an appropriate first choice in uncomplicated urinary tract infection caused by vancomycin-resistant Enterococcus sp.

Evaluation of free or anchored antimicrobial peptides as candidates for the prevention of orthopaedic device-related infections.

PubMed

D'Este, Francesca; Oro, Debora; Boix-Lemonche, Gerard; Tossi, Alessandro; Skerlavaj, Barbara

2017-10-01

The prevention of implant-associated infection, one the most feared complications in orthopaedic surgery, remains a major clinical challenge and urges development of effective methods to prevent bacterial colonization of implanted devices. Alpha-helical antimicrobial peptides (AMPs) may be promising candidates in this respect due to their potent and broad-spectrum antimicrobial activity, their low tendency to elicit resistance and possible retention of efficacy in the immobilized state. The aim of this study was to evaluate the potential of five different helical AMPs, the cathelicidins BMAP-27 and BMAP-28, their (1-18) fragments and the rationally designed, artificial P19(9/G7) peptide, for the prevention of orthopaedic implant infections. Peptides were effective at micromolar concentrations against 22 Staphylococcus and Streptococcus isolates from orthopaedic infections, while only BMAP-28 and to a lesser extent BMAP-27 were active against Enterococcus faecalis. Peptides in solution showed activities comparable to those of cefazolin and linezolid, on a molar basis, and also a variable capacity to neutralize bacterial lipopolysaccharide, while devoid of adverse effects on MG-63 osteoblast cells at concentrations corresponding to the MIC. The (1-18) BMAP fragments and P19(9/G7) were selected for further examination, based on better selectivity indices, and showed effectiveness in the presence of hyaluronic acid and in synovial fluid, while human serum affected their activity to variable extents, with BMAP-27(1-18) best retaining activity. This peptide was immobilized on streptavidin-resin beads and retained activity against reference Staphylococcus epidermidis and Staphylococcus aureus strains, with negligible toxicity towards osteoblasts, underlining its potential for the development of infection-resistant biomaterials for orthopaedic application. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Antibiotic resistance and virulence traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates.

PubMed

Rathnayake, I U; Hargreaves, M; Huygens, F

2012-07-01

This study compared virulence and antibiotic resistance traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates. E. faecalis isolates harboured a broader spectrum of virulence determinants compared to E. faecium isolates. The virulence traits Cyl-A, Cyl-B, Cyl-M, gel-E, esp and acm were tested and environmental isolates predominantly harboured gel-E (80% of E. faecalis and 31.9% of E. faecium) whereas esp was more prevalent in clinical isolates (67.8% of E. faecalis and 70.4% of E. faecium). E. faecalis and E. faecium isolated from water had different antibiotic resistance patterns compared to those isolated from clinical samples. Linezolid resistance was not observed in any isolates tested and vancomycin resistance was observed only in clinical isolates. Resistance to other antibiotics (tetracycline, gentamicin, ciprofloxacin and ampicillin) was detected in both clinical and water isolates. Clinical isolates were more resistant to all the antibiotics tested compared to water isolates. Multi-drug resistance was more prevalent in clinical isolates (71.2% of E. faecalis and 70.3% of E. faecium) compared to water isolates (only 5.7% E. faecium). tet L and tet M genes were predominantly identified in tetracycline-resistant isolates. All water and clinical isolates resistant to ciprofloxacin and ampicillin contained mutations in the gyrA, parC and pbp5 genes. A significant correlation was found between the presence of virulence determinants and antibiotic resistance in all the isolates tested in this study (p<0.05). The presence of antibiotic resistant enterococci, together with associated virulence traits, in surface recreational water could be a public health risk. Copyright © 2012 Elsevier GmbH. All rights reserved.

Evaluation of a Web-Based Professional Development Program (Project ACE) for Teachers of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rakap, Salih; Jones, Hazel A.; Emery, Alice Kaye

2015-01-01

This article describes the development, implementation, and second-year evaluation of Project Autism Competencies for Endorsement (ACE), a web-based professional development (PD) program that is designed to train teachers currently working in the field to meet the unique and diverse needs of children with autism spectrum disorders (ASDs). A…

Effects of a Multimedia Social Skills Program in Increasing Social Responses and Initiations of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Block, Heidi M.; Radley, Keith C.; Jenson, William R.; Clark, Elaine; O'Neill, Robert E.

2015-01-01

The current study evaluated the effectiveness of Superheroes Social Skills, a multimedia social skills package, in improving social responsiveness and social initiation behaviors of four elementary school children with an autism spectrum disorder (ASD). The program was implemented in a public school setting in the southwestern United States for…

Can "Special" Programs for Children with Autism Spectrum Disorders Be Inclusive?

ERIC Educational Resources Information Center

Marks, Susan Unok

2007-01-01

With the increased public attention to a rapidly growing number of children being diagnosed with autism spectrum disorder (ASD), it seems as if there is an equally rapid growth of new specialized programs catering to this group of children. The question to be considered is, if there are indeed promising models based on inclusive settings, why does…

Evaluating the Effectiveness of Two Commonly Used Discrete Trial Procedures for Teaching Receptive Discrimination to Young Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Gutierrez, Anibal, Jr.; Hale, Melissa N.; O'Brien, Heather A.; Fischer, Aaron J.; Durocher, Jennifer S.; Alessandri, Michael

2009-01-01

Discrete trial teaching procedures have been demonstrated to be effective in teaching a variety of important skills for children with autism spectrum disorders (ASD). Although all discrete trial programs are based in the principles of applied behavior analysis, some variability exists between programs with regards to the precise teaching…

Quality of Educational Support for Children with Autism Spectrum Disorder in Bosnia and Herzegovina--Perception of Parents and Professionals

ERIC Educational Resources Information Center

Mujkanovic, Elvira; Mujkanovic, Edin; Pasalic, Arnela; Biscevic, Inga; Memisevic, Haris

2017-01-01

Children with autism spectrum disorder (ASD) attend regular education schools and special education schools in Bosnia and Herzegovina. Regardless of the setting, it is important to provide early, high quality, programs to children with ASD. High quality educational support must encompass evidence-based programs for these children. The goal of the…

Teaching Advanced Operation of an iPod-Based Speech-Generating Device to Two Students with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Achmadi, Donna; Kagohara, Debora M.; van der Meer, Larah; O'Reilly, Mark F.; Lancioni, Giulio E.; Sutherland, Dean; Lang, Russell; Marschik, Peter B.; Green, Vanessa A.; Sigafoos, Jeff

2012-01-01

We evaluated a program for teaching two adolescents with autism spectrum disorders (ASD) to perform more advanced operations on an iPod-based speech-generating device (SGD). The effects of the teaching program were evaluated in a multiprobe multiple baseline across participants design that included two intervention phases. The first intervention…

Process Evaluation of the Boost-A™ Transition Planning Program for Adolescents on the Autism Spectrum: A Strengths-Based Approach

ERIC Educational Resources Information Center

Hatfield, Megan; Falkmer, Marita; Falkmer, Torbjörn; Ciccarelli, Marina

2018-01-01

A process evaluation was conducted to determine the effectiveness, usability, and barriers and facilitators related to the Better OutcOmes & Successful Transitions for Autism (BOOST-A™), an online transition planning program. Adolescents on the autism spectrum (n = 33) and their parents (n = 39) provided feedback via an online questionnaire.…

Program Experiences of Adults with Autism, Their Families, and Providers: Findings from a Focus Group Study

ERIC Educational Resources Information Center

Koffer Miller, Kaitlin H.; Mathew, Mary; Nonnemacher, Stacy L.; Shea, Lindsay L.

2018-01-01

A growing number of individuals with autism spectrum disorder are aging into adulthood. In the United States, Medicaid is the primary payer for services for adults with autism spectrum disorder, yet there are few funded programs that provide dedicated supports to this population. This study examined the experiences of adults with autism spectrum…

Verbal Behavior in Young Children with Autism Spectrum Disorders at the Onset of an Early Behavioral Intervention Program

ERIC Educational Resources Information Center

Rivard, Melina; Forget, Jacques

2012-01-01

The scope of this study was direct observation of verbal behaviors of 14 children with autism spectrum disorders at the onset of an early behavioral intervention (EBI) program delivered in a public services agency. Objectives were to (1) describe frequencies of vocal, verbal, and listener behaviors; (2) evaluate the relationship between the…

In Vitro Activities of the Everninomicin SCH 27899 and Other Newer Antimicrobial Agents against Borrelia burgdorferi

PubMed Central

Dever, Lisa L.; Torigian, Christine V.; Barbour, Alan G.

1999-01-01

The in vitro activity of the everninomicin antibiotic SCH 27899 against 17 isolates of Borrelia spp. was investigated. MICs ranged from 0.06 to 0.5 μg/ml. Time-kill studies with the B31 strain of B. burgdorferi demonstrated ≥3-log10-unit killing after 72 h with concentrations representing four times the MIC. The in vitro activity of four other newer antimicrobial agents, meropenem, cefepime, quinupristin-dalfopristin, and linezolid, was also tested against the B31 strain. Meropenem was the most potent of the latter agents, with an MIC of 0.125 μg/ml. PMID:10390242

Alternatives to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.

PubMed

Micek, Scott T

2007-09-15

Vancomycin remains the reference standard for the treatment of systemic infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, as a result of limited tissue distribution, as well as the emergence of isolates with reduced susceptibility and in vitro resistance to vancomycin, the need for alternative therapies that target MRSA has become apparent. New treatment options for invasive MRSA infections include linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. Additionally, a number of new anti-MRSA compounds are in development, including novel glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. The present article will review clinical issues surrounding the newly marketed and investigational agents with activity against MRSA.

The Effectiveness of Aquatic Group Therapy for Improving Water Safety and Social Interactions in Children with Autism Spectrum Disorder: A Pilot Program

ERIC Educational Resources Information Center

Alaniz, Michele L.; Rosenberg, Sheila S.; Beard, Nicole R.; Rosario, Emily R.

2017-01-01

Drowning is the number one cause of accidental death in children with Autism Spectrum Disorder (ASD). Few studies have examined the effectiveness of swim instruction for improving water safety skills in children with moderate to severe ASD. This study examines the feasibility and effectiveness of an aquatic therapy program on water safety and…

The Secret Agent Society Social Skills Program for Children with High-Functioning Autism Spectrum Disorders: A Comparison of Two School Variants

ERIC Educational Resources Information Center

Beaumont, Renae; Rotolone, Cassie; Sofronoff, Kate

2015-01-01

School is often considered an ideal setting for child social skills training due to the opportunities it provides for skills teaching, modeling, and practice. The current study evaluated the effectiveness of two variants of the Secret Agent Society social skills program for children with high-functioning autism spectrum disorders (HFASD) in a…

A Parent Education Program for Parents of Chinese American Children with Autism Spectrum Disorders (ASDs): A Pilot Study

ERIC Educational Resources Information Center

Chiang, Hsu-Min

2014-01-01

This study was conducted to examine the effectiveness of a parent education program on decreasing parenting stress and increasing parental confidence and quality of life in parents of Chinese American children with autism spectrum disorders (ASDs). A pre-, posttest group design was used in this study. A total of nine families of Chinese American…

A Retrospective Chart Review of Dietary Diversity and Feeding Behavior of Children with Autism Spectrum Disorder before and after Admission to a Day-Treatment Program

ERIC Educational Resources Information Center

Sharp, William G.; Jaquess, David L.; Morton, Jane F.; Miles, Aida G.

2011-01-01

The nutritional status and mealtime performance among a group of children with autism spectrum disorders (ASD) were examined before and after admission to an intensive feeding day-treatment program. Treatment involved escape extinction, reinforcement, and stimulus fading procedures. Outcomes focused on dietary diversity and mealtime performance,…

Social Tools and Rules for Teens (The START Program): Program Description and Preliminary Outcomes of an Experiential Socialization Intervention for Adolescents with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Vernon, Ty W.; Miller, Amber R.; Ko, Jordan A.; Wu, Victoria L.

2016-01-01

Experiential learning is an essential process in the development of core social competencies. Unfortunately, adolescents with autism spectrum disorders often do not possess the prerequisite skillset and motivation to sustain the level of social immersion needed to benefit from this learning process. These persisting social vulnerabilities can…

The Effects of a Social Skills Training Package on Social Engagement of Children with Autism Spectrum Disorders in a Generalized Recess Setting

ERIC Educational Resources Information Center

Radley, Keith C.; Ford, W. Blake; Battaglia, Allison A.; McHugh, Melissa B.

2014-01-01

The present study provides a preliminary evaluation of the effects of the Superheroes Social Skills program, a practice-ready, multimedia social skills program, on social engagements of elementary-age children with autism spectrum disorders (ASD). Four children with ASD between the ages of 8 and 10 with current placements in inclusive public…

School-Based Social Skills Training for Preschool-Age Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Radley, Keith C.; Hanglein, Jeanine; Arak, Marisa

2016-01-01

Individuals with autism spectrum disorder display impairments in social interactions and communication that appear at early ages and result in short- and long-term negative outcomes. As such, there is a need for effective social skills training programs for young children with autism spectrum disorder--particularly interventions capable of being…

Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders

DTIC Science & Technology

2015-09-01

2 AWARD NUMBER: W81XWH-14-1-0261 TITLE: Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders PRINCIPAL...Treatment Response in Autism Spectrum Disorders 5b. GRANT NUMBER W81XWH-14-1-0261 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...for Autism Spectrum Disorder (ASD), but almost half of the children do not make significant gains. Implicit learning skills are integral to

Predicting treatment success in social skills training for adolescents with autism spectrum disorders: the UCLA Program for the Education and Enrichment of Relational Skills.

PubMed

Chang, Ya-Chih; Laugeson, Elizabeth A; Gantman, Alexander; Ellingsen, Ruth; Frankel, Fred; Dillon, Ashley R

2014-05-01

This study seeks to examine the predictors of positive social skills outcomes from the University of California, Los Angeles Program for the Education and Enrichment of Relational Skills, an evidence-based parent-assisted social skills program for high-functioning middle school and high school adolescents with autism spectrum disorders. The results revealed that adolescents with higher parent-reported baseline social skills and lower self-reported perceived social functioning demonstrated greater improvement in social skills following the intervention.

State of the Art and Challenges of Radio Spectrum Monitoring in China

NASA Astrophysics Data System (ADS)

Lu, Q. N.; Yang, J. J.; Jin, Z. Y.; Chen, D. Z.; Huang, M.

2017-10-01

This paper provides an overview of radio spectrum monitoring in China. First, research background, the motivation is described and then train of thought, the prototype system, and the accomplishments are presented. Current radio spectrum monitoring systems are man-machine communication systems, which are unable to detect and process the radio interference automatically. In order to realize intelligent radio monitoring and spectrum management, we proposed an Internet of Things-based spectrum sensing approach using information system architecture and implemented a pilot program; then some very interesting results were obtained.

National Center for Advancing Translational Sciences

MedlinePlus

... Models Core Technologies Clinical Innovation Clinical and Translational Science Awards Program Rare Diseases Clinical Research Network Patient ... to our monthly e-newsletter. About Translation Translational Science Spectrum Explore the full spectrum of translational science, ...

The Coping Cat Program for Children with Anxiety and Autism Spectrum Disorder: A Pilot Randomized Controlled Trial

ERIC Educational Resources Information Center

McNally Keehn, Rebecca H.; Lincoln, Alan J.; Brown, Milton Z.; Chavira, Denise A.

2013-01-01

The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder (ASD). Twenty-two children (ages 8-14; IQ greater than or equal to 70) with ASD and clinically significant anxiety were randomly assigned to 16 sessions of the Coping…

A Pilot Randomized Controlled Trial of the ACCESS Program: A Group Intervention to Improve Social, Adaptive Functioning, Stress Coping, and Self-Determination Outcomes in Young Adults with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Oswald, Tasha M.; Winder-Patel, Breanna; Ruder, Steven; Xing, Guibo; Stahmer, Aubyn; Solomon, Marjorie

2018-01-01

The purpose of this pilot randomized controlled trial was to investigate the acceptability and efficacy of the Acquiring Career, Coping, Executive control, Social Skills (ACCESS) Program, a group intervention tailored for young adults with autism spectrum disorder (ASD) to enhance critical skills and beliefs that promote adult functioning,…

Effects of Water Exercise Swimming Program on Aquatic Skills and Social Behaviors in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Pan, Chien-Yu

2010-01-01

The purpose of this study was to determine the effectiveness of a 10 week water exercise swimming program (WESP) on the aquatic skills and social behaviors of 16 boys with autism spectrum disorders (ASDs). In the first 10 week phase (phase I), eight children (group A) received the WESP while eight children (group B) did not. A second 10 week phase…

Outcome-Based Evaluation of a Social Skills Program Using Art Therapy and Group Therapy for Children on the Autism Spectrum

ERIC Educational Resources Information Center

Epp, Kathleen Marie

2008-01-01

There is a paucity of literature on social skills therapy for students on the autism spectrum, revealing an urgent need for additional research. Past research has focused on the use of small groups or single-case study designs. The present study examines the effectiveness of a social skills therapy program for school-age children ages 11 through…

Feasibility of Training Early Childhood Educators in a Community Child Care Setting Using a Caregiver-Mediated Intervention for Toddlers with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Brian, Jessica; Bernardi, Kate; Dowds, Erin; Easterbrook, Rachel; MacWilliam, Stacey; Bryson, Susan

2017-01-01

Parent-mediated intervention programs have demonstrated benefits for toddlers with autism spectrum disorder (ASD). Interest is emerging in other community-level models, such as those that can be integrated into child care settings. These programs have the potential to reach a wide range of high-risk toddlers who spend the majority of their day in…

Interactive spectral analyzer and comparator (ISAAC)

NASA Astrophysics Data System (ADS)

Latković, O.; Cséki, A.; Vince, I.

2003-10-01

We are developing an application for graphical comparison of observed and synthetic spectra (ISAAC). Synthetic spectrum calculation is performed by SPECTRUM, Stellar Spectral Synthesis Program by Richard O. Gray that we use with his kind permission. This program computes line profiles under LTE conditions in the given wavelength interval using a stellar (solar) atmosphere model, a spectral line data list (wavelength, energy levels, oscillator strengths, and damping constants), a file containing data for atoms and molecules, as well as a data file for hydrogen line profiles calculation. ISAAC offers a simple interface for viewing and changing any atomic parameter SPECTRUM uses for line profile calculation, enabling quick comparison of the new synthetic line profile with the observed one. In this way parameters like relative abundances, oscillator strengths and van der Waals damping constants can be improved, achieving a better agreement with the observed spectrum.

Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Intervention.

PubMed

Stenehjem, Edward; Hersh, Adam L; Buckel, Whitney R; Jones, Peter; Sheng, Xiaoming; Evans, R Scott; Burke, John P; Lopansri, Bert K; Srivastava, Rajendu; Greene, Tom; Pavia, Andrew T

2018-02-23

Studies on the implementation of antibiotic stewardship programs (ASPs) in small hospitals are limited. Accreditation organizations now require all hospitals to have ASPs. The objective of this cluster-randomized intervention was to assess the effectiveness of implementing ASPs in Intermountain Healthcare's 15 small hospitals. Each hospital was randomized to 1 of 3 ASPs of escalating intensity. Program 1 hospitals were provided basic antibiotic stewardship education and tools, access to an infectious disease hotline, and antibiotic utilization data. Program 2 hospitals received those interventions plus advanced education, audit and feedback for select antibiotics, and locally controlled antibiotic restrictions. Program 3 hospitals received program 2 interventions plus audit and feedback on the majority of antibiotics, and an infectious diseases-trained clinician approved restricted antibiotics and reviewed microbiology results. Changes in total and broad-spectrum antibiotic use within programs (intervention versus baseline) and the difference between programs in the magnitude of change in antibiotic use (eg, program 3 vs 1) were evaluated with mixed models. Program 3 hospitals showed reductions in total (rate ratio, 0.89; confidence interval, .80-.99) and broad-spectrum (0.76; .63-.91) antibiotic use when the intervention period was compared with the baseline period. Program 1 and 2 hospitals did not experience a reduction in antibiotic use. Comparison of the magnitude of effects between programs showed a similar trend favoring program 3, but this was not statistically significant. Only the most intensive ASP intervention was associated with reduction in total and broad-spectrum antibiotic use when compared with baseline. NCT03245879.

Characterizing psychiatric comorbidity in children with autism spectrum disorder receiving publicly funded mental health services.

PubMed

Brookman-Frazee, Lauren; Stadnick, Nicole; Chlebowski, Colby; Baker-Ericzén, Mary; Ganger, William

2017-09-01

Publicly funded mental health programs play a significant role in serving children with autism spectrum disorder. Understanding patterns of psychiatric comorbidity for this population within mental health settings is important to implement appropriately tailored interventions. This study (1) describes patterns of psychiatric comorbidity in children with autism spectrum disorder who present to mental health services with challenging behaviors and (2) identifies child characteristics associated with comorbid conditions. Data are drawn from baseline assessments from 201 children with autism spectrum disorder who participated in a community effectiveness trial across 29 publicly funded mental health programs. Non-autism spectrum disorder diagnoses were assessed using an adapted Mini-International Neuropsychiatric Interview, parent version. Approximately 92% of children met criteria for at least one non-autism spectrum disorder diagnosis (78% attention deficit hyperactivity disorder, 58% oppositional defiant disorder, 56% anxiety, 30% mood). Logistic regression indicated that child gender and clinical characteristics were differentially associated with meeting criteria for attention deficit hyperactivity disorder, oppositional defiant disorder, an anxiety, or a mood disorder. Exploratory analyses supported a link between challenging behaviors and mood disorder symptoms and revealed high prevalence of these symptoms in this autism spectrum disorder population. Findings provide direction for tailoring intervention to address a broad range of clinical issues for youth with autism spectrum disorder served in mental health settings.

Office of Positioning, Navigation and Timing (PNT) and Spectrum Management Program Overview.

DOT National Transportation Integrated Search

2017-01-01

Civil Global Positioning System (GPS)/PNT Leadership : Coordinate the development of departmental positions on PNT and : spectrum policy and protection from harmful radio frequency : interference and operational degradation of capabilities : ...

AN OPTIMIZED 64X64 POINT TWO-DIMENSIONAL FAST FOURIER TRANSFORM

NASA Technical Reports Server (NTRS)

Miko, J.

1994-01-01

Scientists at Goddard have developed an efficient and powerful program-- An Optimized 64x64 Point Two-Dimensional Fast Fourier Transform-- which combines the performance of real and complex valued one-dimensional Fast Fourier Transforms (FFT's) to execute a two-dimensional FFT and its power spectrum coefficients. These coefficients can be used in many applications, including spectrum analysis, convolution, digital filtering, image processing, and data compression. The program's efficiency results from its technique of expanding all arithmetic operations within one 64-point FFT; its high processing rate results from its operation on a high-speed digital signal processor. For non-real-time analysis, the program requires as input an ASCII data file of 64x64 (4096) real valued data points. As output, this analysis produces an ASCII data file of 64x64 power spectrum coefficients. To generate these coefficients, the program employs a row-column decomposition technique. First, it performs a radix-4 one-dimensional FFT on each row of input, producing complex valued results. Then, it performs a one-dimensional FFT on each column of these results to produce complex valued two-dimensional FFT results. Finally, the program sums the squares of the real and imaginary values to generate the power spectrum coefficients. The program requires a Banshee accelerator board with 128K bytes of memory from Atlanta Signal Processors (404/892-7265) installed on an IBM PC/AT compatible computer (DOS ver. 3.0 or higher) with at least one 16-bit expansion slot. For real-time operation, an ASPI daughter board is also needed. The real-time configuration reads 16-bit integer input data directly into the accelerator board, operating on 64x64 point frames of data. The program's memory management also allows accumulation of the coefficient results. The real-time processing rate to calculate and accumulate the 64x64 power spectrum output coefficients is less than 17.0 mSec. Documentation is included in the price of the program. Source code is written in C, 8086 Assembly, and Texas Instruments TMS320C30 Assembly Languages. This program is available on a 5.25 inch 360K MS-DOS format diskette. IBM and IBM PC are registered trademarks of International Business Machines. MS-DOS is a registered trademark of Microsoft Corporation.

The Efficacy of an Aquatic Program on Physical Fitness and Aquatic Skills in Children with and without Autism Spectrum Disorders

ERIC Educational Resources Information Center

Pan, Chien-Yu

2011-01-01

This study evaluated the efficacy of a 14-week aquatic program on physical fitness and aquatic skills for children with autism spectrum disorders (ASD) and their siblings without a disability. Children with ASD (n = 15) and their siblings (n = 15), between 7 and 12 years (8.55 [plus or minus] 2.19 years) participated. In the first 14-week phase,…

Multicontext Diversity: The critical dimension of diversity that can attract students and help them thrive

NASA Astrophysics Data System (ADS)

Weissmann, G. S.; Ibarra, R.; Howland-Davis, M.

2017-12-01

Diversity programs on college campuses have expanded over the past several decades, bringing a broad range of students to academia; however, these programs have not resulted in diversification of faculty or PhD students. Current diversity programs generally focus on two dimensions of diversity: (1) structural diversity, which aims to bring in students from underrepresented groups to college campuses through scholarships, admissions policies, and targeted marketing; and (2) multicultural diversity, which uses programs designed to give students from underrepresented groups homes on campus and programs designed to study cultural aspects of different groups. Though these programs are important, something else must be controlling the lack of minority participation in STEM at advanced levels. We posit that a third dimension of diversity, context diversity, is lacking in university education, especially in STEM fields, and without accessing this form of diversity, programs will never benefit from the broader diversity of society. Context diversity results through application of Multicontext theory, which both explains and predicts the inclusion of exclusion of people within an institutional culture. It describes how different cultures approach understanding the world around them. This "cultural ways of knowing and doing" has been described using a binary system, consisting of "Low Context" and "High Context" cultures. Ibarra (2001) described how a spectrum exists between these end members, and thus individuals brought up in different cultures will understand the world from somewhere along this context diversity spectrum. Academic culture tends to fall on the low context side of the spectrum. Thus, students (and faculty) who come from cultures that tend toward the high context side of the spectrum often feel excluded from the academic setting, especially in STEM fields which tend to be strongly low context in nature. A high percentage of students from underrepresented groups and women tend to fall on toward the high context side of the spectrum, thus this disproportionately affects women and minorities. Multicontextuality can be readily applied in classroom and research settings, thus leading to helping all students thrive in the academic setting.

Development of the Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills Program for Adults on the Autism Spectrum: Results of Initial Study

ERIC Educational Resources Information Center

Baker-Ericzén, Mary J.; Fitch, Meghan A.; Kinnear, Mikaela; Jenkins, Melissa M.; Twamley, Elizabeth W.; Smith, Linda; Montano, Gabriel; Feder, Joshua; Crooke, Pamela J.; Winner, Michelle G.; Leon, Juan

2018-01-01

The population of adults on the autism spectrum continues to increase, and vocational outcomes are particularly poor. Longitudinal studies of adults with autism spectrum and without intellectual disability have shown consistent and persistent deficits across cognitive, social, and vocational domains, indicating a need for effective treatments of…

An application of artificial intelligence to the interpretation of mass spectra.

NASA Technical Reports Server (NTRS)

Buchanan, B. G.; Duffield, A. M.; Robertson, A. V.

1971-01-01

Description of the DENDRAL (Dendritic Algorithm) project, the objectives of which were to base the computer program on an alogorithm that generates an exhaustive, nonredundant list of all the structural isomers of a given chemical composition, and to devise a computer program that would perform an organic structure determination, given a molecular formula and a mass spectrum. This program is called 'Heuristic DENDRAL' and it operates by using the known structure/spectrum correlations to constrain the DENDRAL isomer generator to produce a single isomer for that composition. The collaboration of chemists and computer scientists has produced a tool of some practical utility from the chemical viewpoint, and an interesting program from the viewpoint of artificial intelligence.

Efficacy of the Direct Instruction Language for Learning (DI-LL) Program to Promote Expressive and Receptive Language in Children with Autism Spectrum Disorder

DTIC Science & Technology

2016-07-01

Receptive Language in Children with Autism Spectrum Disorder PRINCIPAL INVESTIGATOR: Lawrence Scahill, MSN, PhD CONTRACTING ORGANIZATION: Emory...REPORT TYPE Annual 3. DATES COVERED 15Jun2015 - 14Jun2016 4. TITLE AND SUBTITLE Receptive Language in Children with Autism Spectrum Disorder 5a...indicates that as many as 75% of children with autism spectrum disorder (ASD) have language delay ranging from mild to severe. Many interventions have

Medicaid Waivers Targeting Children With Autism Spectrum Disorder Reduce The Need For Parents To Stop Working.

PubMed

Leslie, Douglas L; Iskandarani, Khaled; Velott, Diana L; Stein, Bradley D; Mandell, David S; Agbese, Edeanya; Dick, Andrew W

2017-02-01

Several states have passed Medicaid home and community-based services waivers that expand eligibility criteria and available services for children with autism spectrum disorder. Although previous research has shown considerable variation in these waivers, little is known about the programs' impact on parents' workforce participation. We used nationally representative survey data combined with detailed information on state Medicaid waiver programs to determine the effects of waivers on whether parents of children with autism spectrum disorder had to stop working because of the child's condition. Increases in the Medicaid home and community-based services waiver cost limit and enrollment limit significantly reduced the likelihood that a parent had to stop working, although the results varied considerably by household income level. These findings suggest that the Medicaid waivers are effective policies to address the care-related needs of children with autism spectrum disorder. Project HOPE—The People-to-People Health Foundation, Inc.

Susceptibilities of Legionella spp. to Newer Antimicrobials In Vitro

PubMed Central

Schülin, T.; Wennersten, C. B.; Ferraro, M. J.; Moellering, R. C.; Eliopoulos, G. M.

1998-01-01

The in vitro activities of 13 antimicrobial agents against 30 strains of Legionella spp. were determined. Rifapentine, rifampin, and clarithromycin were the most potent agents (MICs at which 90% of isolates are inhibited [MIC90s], ≤0.008 μg/ml). The ketolide HMR 3647 and the fluoroquinolones levofloxacin and BAY 12-8039 (MIC90s, 0.03 to 0.06 μg/ml) were more active than erythromycin A or roxithromycin. The MIC90s of dalfopristin-quinupristin and linezolid were 0.5 and 8 μg/ml, respectively. Based on class characteristics and in vitro activities, several of these agents may have potential roles in the treatment of Legionella infections. PMID:9624509

Comparative in vitro activities of dalbavancin and seven comparator agents against 41 Staphylococcus species cultured from osteomyelitis infections and 18 VISA and hVISA strains.

PubMed

Citron, Diane M; Tyrrell, Kerin L; Goldstein, Ellie J C

2014-08-01

Due to a high rate of relapse, osteomyelitis remains difficult to treat, requiring prolonged parenteral therapy. MICs for 41 consecutive Staphylococcus species recovered from patients with osteomyelitis were determined for dalbavancin, daptomycin, doxycycline, levofloxacin, linezolid, vancomycin, trimethoprim-sulfamethoxazole, rifampin, and vancomycin. Strains of vancomycin-intermediate Staphylococcus aureus (VISA) and heteroresistant VISA were included for additional comparison. Except for rifampin, dalbavancin was the most active agent tested. Dalbavancin is given once a week, making treatment of infections such as osteomyelitis potentially more convenient and thus could help reduce the rate of hospitalizations and outpatient costs. Copyright © 2014 Elsevier Inc. All rights reserved.

Antistaphylococcal activity of CG400549, a new experimental FabI inhibitor, compared with that of other agents.

PubMed

Bogdanovich, Tatiana; Clark, Catherine; Kosowska-Shick, Klaudia; Dewasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C

2007-11-01

Among 203 strains of Staphylococcus aureus, the MICs of CG400549 were 0.06 to 1.0 microg/ml, with MIC(50) and MIC(90) values of 0.25 microg/ml each. All strains were susceptible to linezolid and quinupristin-dalfopristin (MICs, 0.25 to 2.0 microg/ml). The daptomycin MICs were 0.25 to 2.0 microg/ml for methicillin-susceptible and 0.25 to 4.0 microg/ml against methicillin-resistant strains (including vancomycin-intermediate strains). Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested.

Comparative in vitro activities of XRP 2868, pristinamycin, quinupristin-dalfopristin, vancomycin, daptomycin, linezolid, clarithromycin, telithromycin, clindamycin, and ampicillin against anaerobic gram-positive species, actinomycetes, and lactobacilli.

PubMed

Goldstein, Ellie J C; Citron, Diane M; Merriam, C Vreni; Warren, Yumi A; Tyrrell, Kerin L; Fernandez, Helen T; Bryskier, Andre

2005-01-01

A comparative study of the in vitro activities of XRP 2868, a new oral streptogramin, against 266 anaerobic gram-positive clinical isolates using the agar dilution method showed that the XRP 2868 MICs for 95% (254 of 266) of isolates were < or =0.5 microg/ml. XRP 2868 MICs for only two strains, one being Clostridium clostridioforme (MIC, 16 microg/ml) and the other being Clostridium difficile (MIC, 32 microg/ml), were >2 microg/ml. Depending on its pharmacokinetics and pharmacodynamics, XRP 2868 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.

Clinico-Microbiological Investigation of Catheter Associated Urinary Tract Infection by Enterococcus faecalis: vanA Genotype

PubMed Central

Padmavathy, Kesavaram; Madhavan, Radha; Krithika, Nagarajan; Kiruthiga, Alexander

2015-01-01

Prolonged hospitalization and exposure to third generation cephalosporins are reported to facilitate the acquisition and colonization of Vancomycin Resistant Enterococci (VRE). Though VRE is not uncommon in India, urinary tract infection with a vanA genotype is a cause of serious concern as VRE co-exhibit resistance to aminoglycosides. In India, majority of the VRE isolates recovered from hospitalized patients include Enterococcus faecium. We report a case of catheter associated urinary tract infection by an endogenous, multidrug resistant E. faecalis of vanA genotype following prolonged hospitalization, ICU stay, catheterisation and exposure to 3G cephalosporin and metronidazole. The patient responded to linezolid therapy. PMID:26435949

3 CFR - Expanding America's Leadership in Wireless Innovation

Code of Federal Regulations, 2014 CFR

2014-01-01

... results from the Networking and Information Technology Research and Development Program, shall publish an... in research, development, testing, and evaluation of technologies to enhance spectrum sharing and... templates governing the following: research, development, testing, and evaluation of spectrum sharing...

Great SEP events and space weather: 2. Automatic determination of the solar energetic particle spectrum

NASA Astrophysics Data System (ADS)

Applbaum, David; Dorman, Lev; Pustil'Nik, Lev; Sternlieb, Abraham; Zagnetko, Alexander; Zukerman, Igor

In Applbaum et al. (2010) it was described how the "SEP-Search" program works automat-ically, determining on the basis of on-line one-minute NM data the beginning of a great SEP event. The "SEP-Search" next uses one-minute data in order to check whether or not the observed increase reflects the beginning of a real great SEP event. If yes, the program "SEP-Research/Spectrum" automatically starts to work on line. We consider two variants: 1) quiet period (no change in cut-off rigidity), 2) disturbed period (characterized with possible changing of cut-off rigidity). We describe the method of determining the spectrum of SEP in the 1st vari-ant (for this we need data for at least two components with different coupling functions). For the 2nd variant we need data for at least three components with different coupling functions. We show that for these purposes one can use data of the total intensity and some different mul-tiplicities, but that it is better to use data from two or three NM with different cut-off rigidities. We describe in detail the algorithms of the program "SEP-Research/Spectrum." We show how this program worked on examples of some historical great SEP events. The work of NM on Mt. Hermon is supported by Israel (Tel Aviv University and ISA) -Italian (UNIRoma-Tre and IFSI-CNR) collaboration.

The ABC's of Teaching Social Skills to Adolescents with Autism Spectrum Disorder in the Classroom: The UCLA "PEERS®" Program

ERIC Educational Resources Information Center

Laugeson, Elizabeth A.; Ellingsen, Ruth; Sanderson, Jennifer; Tucci, Lara; Bates, Shannon

2014-01-01

Social skills training is a common treatment method for adolescents with autism spectrum disorder (ASD), yet very few evidence-based interventions exist to improve social skills for high-functioning adolescents on the spectrum, and even fewer studies have examined the effectiveness of teaching social skills in the classroom. This study examines…

Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0057 TITLE: Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation...Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation 5b. GRANT NUMBER W81XWH-13-2-0057 5c. PROGRAM ELEMENT...Finally in Aim 8 we will develop standardization of protocols and clinical monitoring and treatment for VCA targeting vascular health. hand and face

Autistic Spectrum Disorder: Intervention Guidance for Service Providers and Families of Young Children with Autistic Spectrum Disorder. Service Guideline 1. Revised.

ERIC Educational Resources Information Center

Connecticut Birth to Three System, Hartford.

This guide for parents and service providers contains information on autistic spectrum disorder (ASD) in young children and is the product of a review of research-based programs and models and requirements of the Individuals with Disabilities Education Act. The document begins with discussion of the definition of ASD, possible causes of ASD, and…

A Pilot Randomised Controlled Trial of a School-Based Resilience Intervention to Prevent Depressive Symptoms for Young Adolescents with Autism Spectrum Disorder: A Mixed Methods Analysis

ERIC Educational Resources Information Center

Mackay, Bethany A.; Shochet, Ian M.; Orr, Jayne A.

2017-01-01

Despite increased depression in adolescents with Autism Spectrum Disorder (ASD), effective prevention approaches for this population are limited. A mixed methods pilot randomised controlled trial (N = 29) of the evidence-based Resourceful Adolescent Program-Autism Spectrum Disorder (RAP-A-ASD) designed to prevent depression was conducted in…

Improving psychosexual knowledge in adolescents with autism spectrum disorder: pilot of the tackling teenage training program.

PubMed

Dekker, Linda P; van der Vegt, Esther J M; Visser, Kirsten; Tick, Nouchka; Boudesteijn, Frieda; Verhulst, Frank C; Maras, Athanasios; Greaves-Lord, Kirstin

2015-06-01

Previous studies have shown that psychosexual functioning in adolescents with autism spectrum disorder (ASD) is hampered and emphasize the need for a specialized training program tailored to their needs. Therefore, an individual training program was developed; the Tackling Teenage Training (TTT) program. The current pilot study systematically evaluated whether psychosexual knowledge increased after taking part in the TTT program, using a pre- and post-training design in 30 adolescents with ASD (77 % male, mean age = 14.80 years, mean intelligence = 96.96). Psychosexual knowledge increased significantly (pre-training total score: M = 25.74, SD = 6.20; post-training total score: M = 33.52 (SD = 2.78); F(1,29) = 65.20, p < .001). The TTT program may be useful to improve psychosexual knowledge and functioning in adolescents with ASD, yet these findings are preliminary, and a more elaborate controlled trial is needed.

The Spectrum Orbit Utilization Program (SOUP) used for DBS plan analysis at RARC '83

NASA Technical Reports Server (NTRS)

Davidson, J.; Ottey, H. R.; Sawitz, P.; Zusman, F. S.

1985-01-01

This paper describes the history, functions, and usage of the program that was used to analyze the plans for direct broadcast satellite service developed in the course of the 1983 Regional Administrative Radio Conference for ITU Region 2. Given the requirements for direct broadcast service by the administrations, the conference delegates (1) developed the appropriate technical parameters; (2) made tentative assignments to the orbit locations, frequencies, and polarizations of space stations, (3) calculated the interferences and margins of such assignments through the use of the Spectrum Orbit Utilization Program (SOUP); and (4) iterated this procedure until an acceptable plan was found.

A terrain based simulation system to predict the interference caused by networks of spread spectrum systems

NASA Astrophysics Data System (ADS)

Hagen, William E.; Holtzman, Julian C.

The Army Terrain Integrated Interference Prediction System (ATIIPS), a CAD terrain based simulation tool for determining the degradation effects on a network on nonspread spectrum radios caused by a network of spread spectrum radios is presented. A brief overview of the program is given, with typical graphics displays shown. Typical results for both a link simulation of interference and for a network simulation, using a slow hopped FM/FSK spread spectrum interfering radio network on a narrow band FM/FSK fixed frequency digital radio are presented.

Spectral and cross-spectral analysis of uneven time series with the smoothed Lomb-Scargle periodogram and Monte Carlo evaluation of statistical significance

NASA Astrophysics Data System (ADS)

Pardo-Igúzquiza, Eulogio; Rodríguez-Tovar, Francisco J.

2012-12-01

Many spectral analysis techniques have been designed assuming sequences taken with a constant sampling interval. However, there are empirical time series in the geosciences (sediment cores, fossil abundance data, isotope analysis, …) that do not follow regular sampling because of missing data, gapped data, random sampling or incomplete sequences, among other reasons. In general, interpolating an uneven series in order to obtain a succession with a constant sampling interval alters the spectral content of the series. In such cases it is preferable to follow an approach that works with the uneven data directly, avoiding the need for an explicit interpolation step. The Lomb-Scargle periodogram is a popular choice in such circumstances, as there are programs available in the public domain for its computation. One new computer program for spectral analysis improves the standard Lomb-Scargle periodogram approach in two ways: (1) It explicitly adjusts the statistical significance to any bias introduced by variance reduction smoothing, and (2) it uses a permutation test to evaluate confidence levels, which is better suited than parametric methods when neighbouring frequencies are highly correlated. Another novel program for cross-spectral analysis offers the advantage of estimating the Lomb-Scargle cross-periodogram of two uneven time series defined on the same interval, and it evaluates the confidence levels of the estimated cross-spectra by a non-parametric computer intensive permutation test. Thus, the cross-spectrum, the squared coherence spectrum, the phase spectrum, and the Monte Carlo statistical significance of the cross-spectrum and the squared-coherence spectrum can be obtained. Both of the programs are written in ANSI Fortran 77, in view of its simplicity and compatibility. The program code is of public domain, provided on the website of the journal (http://www.iamg.org/index.php/publisher/articleview/frmArticleID/112/). Different examples (with simulated and real data) are described in this paper to corroborate the methodology and the implementation of these two new programs.

Family Studies of Sensorimotor and Neurocognitive Heterogeneity in Autism Spectrum Disorders (ASD)

DTIC Science & Technology

2013-09-01

Autism Spectrum Disorders (ASD) PRINCIPAL INVESTIGATOR: John Sweeney, Ph.D. CONTRACTING ORGANIZATION: University of Texas...in Autism Spectrum Disorders (ASD) 5b. GRANT NUMBER W81XWH-11-1-0738 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) John A. Sweeney, Ph.D.; Matthew W...Southwestern Medical Center Center for Autism and Developmental Disabilities 5323 Harry Hinds Boulevard, MC9086 Dallas, Texas 75390-9086

In vitro activity of novel anti-MRSA cephalosporins and comparator antimicrobial agents against staphylococci involved in prosthetic joint infections.

PubMed

Isnard, Christophe; Dhalluin, Anne; Malandain, Damasie; Bruey, Quentin; Auzou, Michel; Michon, Jocelyn; Giard, Jean-Christophe; Guérin, François; Cattoir, Vincent

2018-02-05

Ceftaroline and ceftobiprole are new parenteral cephalosporins with potent activity against methicillin-resistant (MR) staphylococci, which are the leading cause of prosthetic joint infections (PJIs). The aim of this study was to determine and compare the in vitro activities of both molecules against staphylococcal isolates recovered from clinically documented PJIs. A collection of 200 non-duplicate clinical isolates [100 Staphylococcus aureus and 100 coagulase-negative staphylococci (CoNS), including 19 and 27 MR isolates, respectively] was studied. Minimum inhibitory concentrations (MICs) of oxacillin, ceftaroline, ceftobiprole, vancomycin, teicoplanin, clindamycin, levofloxacin, linezolid and daptomycin were determined by the broth microdilution method. Bactericidal activity (at 4× MIC) of ceftaroline, ceftobiprole, vancomycin, teicoplanin, linezolid and daptomycin was assessed by time-kill assay. Among the S. aureus isolates, 100% were susceptible to ceftaroline (MIC 50/90 , 0.25/0.5μg/mL) and 98% were susceptible to ceftobiprole (MIC 50/90 , 0.5/1μg/mL), regardless of their methicillin resistance. The two ceftobiprole-non-susceptible strains (including one MRSA) showed MICs at 4mg/L. Against CoNS isolates, ceftaroline and ceftobiprole exhibited in vitro potency with MIC 50/90 values at 0.06/0.25μg/mL and 0.25/1μg/mL, respectively. At 4× MIC, ceftaroline and ceftobiprole showed rapid and marked bactericidal activity against both S. aureus and CoNS (after 24/12h and 12/6h of incubation, respectively), whilst none of the other molecules tested had a bactericidal effect by 24h. This study showed that ceftaroline and ceftobiprole have excellent in vitro activity against clinical isolates of staphylococci involved in PJIs. These molecules may therefore represent promising alternatives for the treatment of such infections. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Identification of non-tuberculous mycobacteria isolated from clinical specimens at a tertiary care hospital: a cross-sectional study

PubMed Central

2013-01-01

Background Non-tuberculous mycobacteria (NTM) are opportunistic pathogens in immuno-compromised patients. They are also increasingly recognized as pathogens in immuno-competent individuals. Globally, an increase in NTM isolation is being reported with a varied geographic prevalence of different species around the world. There is lack of data on species distribution of these organisms from Pakistan. Treatment options differ according to the species isolated and its susceptibility profile. Knowledge of local species variation would help targeted therapy. This study was performed to determine frequencies of different NTM species isolated from various clinical specimens submitted at a tertiary care hospital laboratory. Methods NTM isolated from 25955 clinical specimens over a period of two years (2010 to 2011) were included. All NTM were identified using conventional tests. Drug susceptibility testing (DST) was performed by broth microdilution and interpreted according to Clinical and Laboratory Standards Institute’s document M24-A2. Results A total of 104 NTM were included in the study. Of these, 76% (54/71) rapidly growing mycobacteria (RGM) and 57.6% (19/33) slow growing mycobacteria (SGM) could be further identified. Mycobacterium fortuitum (21/54) was the commonest NTM identified among RGM followed by M. mucogenicum (12/54) and M. smegmatis (11/54). Among SGM, M. avium complex (MAC) was the most frequent (14/19). Clinical significance could be assessed in a limited number (52/104) of NTM isolates and MAC appeared to be the commonest significant NTM. Three extra-pulmonary cases were found to be healthcare associated infections. DST results for RGM showed susceptibility to amikacin (100%), clarithromycin (100%, except M. fortuitum where it is not reportable), linezolid (90%) and moxifloxacin (75%). Whereas SGM were susceptible to clarithromycin (100%), linezolid (58.8%) and moxifloxacin (64.7%). Conclusion This is the first study reporting NTM species and their clinical significance isolated from clinical specimens from Pakistan. Isolation of NTM from clinical specimens should prompt to evaluate their clinical significance. PMID:24148198

Identification of non-tuberculous mycobacteria isolated from clinical specimens at a tertiary care hospital: a cross-sectional study.

PubMed

Ahmed, Imran; Jabeen, Kauser; Hasan, Rumina

2013-10-22

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens in immuno-compromised patients. They are also increasingly recognized as pathogens in immuno-competent individuals. Globally, an increase in NTM isolation is being reported with a varied geographic prevalence of different species around the world. There is lack of data on species distribution of these organisms from Pakistan. Treatment options differ according to the species isolated and its susceptibility profile. Knowledge of local species variation would help targeted therapy. This study was performed to determine frequencies of different NTM species isolated from various clinical specimens submitted at a tertiary care hospital laboratory. NTM isolated from 25955 clinical specimens over a period of two years (2010 to 2011) were included. All NTM were identified using conventional tests. Drug susceptibility testing (DST) was performed by broth microdilution and interpreted according to Clinical and Laboratory Standards Institute's document M24-A2. A total of 104 NTM were included in the study. Of these, 76% (54/71) rapidly growing mycobacteria (RGM) and 57.6% (19/33) slow growing mycobacteria (SGM) could be further identified. Mycobacterium fortuitum (21/54) was the commonest NTM identified among RGM followed by M. mucogenicum (12/54) and M. smegmatis (11/54). Among SGM, M. avium complex (MAC) was the most frequent (14/19). Clinical significance could be assessed in a limited number (52/104) of NTM isolates and MAC appeared to be the commonest significant NTM. Three extra-pulmonary cases were found to be healthcare associated infections. DST results for RGM showed susceptibility to amikacin (100%), clarithromycin (100%, except M. fortuitum where it is not reportable), linezolid (90%) and moxifloxacin (75%). Whereas SGM were susceptible to clarithromycin (100%), linezolid (58.8%) and moxifloxacin (64.7%). This is the first study reporting NTM species and their clinical significance isolated from clinical specimens from Pakistan. Isolation of NTM from clinical specimens should prompt to evaluate their clinical significance.

Culture methods impact recovery of antibiotic-resistant Enterococci including Enterococcus cecorum from pre- and postharvest chicken.

PubMed

Suyemoto, M M; Barnes, H J; Borst, L B

2017-03-01

Pathogenic strains of Enterococcus cecorum (EC) expressing multidrug resistance have emerged. In National Antimicrobial Resistance Monitoring System (NARMS) data, EC is rarely recovered from chickens. Two NARMS methodologies (FDA and USDA) were compared with standard culture (SC) techniques for recovery of EC. NARMS methods failed to detect EC in 58 caecal samples, 20 chicken breast or six whole broiler samples. EC was recovered from 1 of 38 (2·6%) and 2 of 38 (5·2%) preharvest spinal lesions (USDA and FDA method, respectively). In contrast, using the SC method, EC was recovered from 44 of 53 (83%) caecal samples, all 38 (100%) spinal lesions, 14 of 20 (70%) chicken breast samples, and all three spinal lesions identified in whole carcasses. Compared with other Enterococcus spp., EC isolates had a higher prevalence of resistance to macrolides. The NARMS methods significantly affected recovery of enterococcal species other than EC. When the postharvest FDA method was applied to preharvest caecal samples, isolates of Enterococcus faecium were preferentially recovered. All 11 E. faecium isolates were multidrug resistant, including resistance to penicillin, daptomycin and linezolid. These findings confirm that current methodologies may not accurately identify the amount and range of antimicrobial resistance of enterococci from chicken sources. Enterococci are an important reservoir for antimicrobial resistance. This study demonstrates how current culture methods underreport resistance to macrolides in enterococci by selecting against strains of Enterococcus cecorum in pre- and postharvest chicken. Further, the application of postharvest surveillance methods to preharvest samples resulted in selective recovery of Enterococcus faecium over Enterococcus faecalis. Isolates of E. faecium recovered exhibited multidrug resistance including penicillin, daptomycin and linezolid resistance. These findings suggest that culture methodology significantly impacts the range and amount of antimicrobial resistance detected in enterococci isolated from chicken. © 2016 The Society for Applied Microbiology.

Novel Piperazine Arylideneimidazolones Inhibit the AcrAB-TolC Pump in Escherichia coli and Simultaneously Act as Fluorescent Membrane Probes in a Combined Real-Time Influx and Efflux Assay.

PubMed

Bohnert, Jürgen A; Schuster, Sabine; Kern, Winfried V; Karcz, Tadeusz; Olejarz, Agnieszka; Kaczor, Aneta; Handzlik, Jadwiga; Kieć-Kononowicz, Katarzyna

2016-04-01

In this study, we tested five compounds belonging to a novel series of piperazine arylideneimidazolones for the ability to inhibit the AcrAB-TolC efflux pump. The biphenylmethylene derivative (BM-19) and the fluorenylmethylene derivative (BM-38) were found to possess the strongest efflux pump inhibitor (EPI) activities in the AcrAB-TolC-overproducingEscherichia colistrain 3-AG100, whereas BM-9, BM-27, and BM-36 had no activity at concentrations of up to 50 μM in a Nile red efflux assay. MIC microdilution assays demonstrated that BM-19 at 1/4 MIC (intrinsic MIC, 200 μM) was able to reduce the MICs of levofloxacin, oxacillin, linezolid, and clarithromycin 8-fold. BM-38 at 1/4 MIC (intrinsic MIC, 100 μM) was able to reduce only the MICs of oxacillin and linezolid (2-fold). Both compounds markedly reduced the MIC of rifampin (BM-19, 32-fold; and BM-38, 4-fold), which is suggestive of permeabilization of the outer membrane as an additional mechanism of action. Nitrocefin hydrolysis assays demonstrated that in addition to their EPI activity, both compounds were in fact weak permeabilizers of the outer membrane. Moreover, it was found that BM-19, BM-27, BM-36, and BM-38 acted as near-infrared-emitting fluorescent membrane probes, which allowed for their use in a combined influx and efflux assay and thus for tracking of the transport of an EPI across the outer membrane by an efflux pump in real time. The EPIs BM-38 and BM-19 displayed the most rapid influx of all compounds, whereas BM-27, which did not act as an EPI, showed the slowest influx. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Evaluation of linezolid or trimethoprim/sulfamethoxazole in combination with rifampicin as alternative oral treatments based on an in vitro pharmacodynamic model of staphylococcal biofilm.

PubMed

El Haj, Cristina; Murillo, Oscar; Ribera, Alba; Lloberas, Nuria; Gómez-Junyent, Joan; Tubau, Fe; Fontova, Pere; Cabellos, Carme; Ariza, Javier

2018-06-01

Combinations of linezolid (LZD) or trimethoprim/sulfamethoxazole (SXT) plus rifampicin (RIF) are alternative oral treatments for staphylococcal prosthetic joint infections (PJIs) when fluoroquinolones are not possible to use, but there is limited evidence regarding their activity. This study evaluated the efficacy of LZD and SXT, alone and in combination with RIF, against Staphylococcus aureus in an in vitro pharmacokinetic/pharmacodynamic biofilm model. Using the CDC Biofilm Reactor ® system, simulated regimens of LZD (600 mg every 12 h), SXT (160/800 mg every 8 h) and levofloxacin (LVX) (750 mg/day), alone and in combination with RIF (600 mg/day), were evaluated against one methicillin-susceptible S. aureus (MSSA) and one methicillin-resistant S. aureus (MRSA) strain. Antibiotic efficacy was evaluated by the decrease in planktonic bacterial counts from medium and biofilm-embedded bacteria from coupons over 56 h. Resistant strains were screened. In both strains, SXT alone was ineffective and LZD presented low activity, but no resistance emerged. Combinations with RIF significantly increased the antibiofilm efficacy against MSSA (Δlog CFU/mL 56h-0h: SXT + RIF, -2.9 and LZD + RIF, -3.1), but RIF-resistant strains appeared with SXT + RIF. Against MRSA, LZD + RIF (-3.1) protected against the emergence of resistance and was more effective than SXT + RIF (-0.6; P <0.05), in which RIF-resistant strains were again detected. LVX + RIF confirmed its high efficacy against biofilm-embedded bacteria, this being the most effective therapy (-5.1 against MSSA). The emergence of RIF-resistant strains with SXT + RIF poses serious concerns for its use in clinical practice. Interestingly, LZD + RIF appears to be an appropriate alternative for PJI caused by LVX-resistant S. aureus. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin.

PubMed

Wang, Yang; Lv, Yuan; Cai, Jiachang; Schwarz, Stefan; Cui, Lanqing; Hu, Zhidong; Zhang, Rong; Li, Jun; Zhao, Qin; He, Tao; Wang, Dacheng; Wang, Zheng; Shen, Yingbo; Li, Yun; Feßler, Andrea T; Wu, Congming; Yu, Hao; Deng, Xuming; Xia, Xi; Shen, Jianzhong

2015-08-01

The oxazolidinone-resistant Enterococcus faecalis E349 from a human patient tested negative for the cfr gene and 23S rRNA mutations. Here we report the identification of a novel oxazolidinone resistance gene, optrA, and a first investigation of the extent to which this gene was present in E. faecalis and Enterococcus faecium from humans and food-producing animals. The resistance gene optrA was identified by whole-plasmid sequencing and subsequent cloning and expression in a susceptible Enterococcus host. Transformation and conjugation assays served to investigate the transferability of optrA. All optrA-positive E. faecalis and E. faecium isolates of human and animal origin were analysed for their MICs and their genotype, as well as the location of optrA. The novel plasmid-borne ABC transporter gene optrA from E. faecalis E349 conferred combined resistance or elevated MICs (when no clinical breakpoints were available) to oxazolidinones (linezolid and tedizolid) and phenicols (chloramphenicol and florfenicol). The corresponding conjugative plasmid pE349, on which optrA was located, had a size of 36 331 bp and also carried the phenicol exporter gene fexA. The optrA gene was functionally expressed in E. faecalis, E. faecium and Staphylococcus aureus. It was detected more frequently in E. faecalis and E. faecium from food-producing animals (20.3% and 5.7%, respectively) than from humans (4.2% and 0.6%, respectively). Enterococci with elevated MICs of linezolid and tedizolid should be tested not only for 23S rRNA mutations and the gene cfr, but also for the novel resistance gene optrA. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels.

PubMed

Guerra, Alberto Daniel; Rose, Warren E; Hematti, Peiman; Kao, W John

2017-03-15

Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels. Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial bioburden on the hydrogel. This combinatorial approach to biomaterial development has the potential to impact wound healing for contaminated full thickness cutaneous wounds. Copyright © 2017. Published by Elsevier Ltd.

Early-switch/early-discharge opportunities for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections: proof of concept in the United Arab Emirates.

PubMed

El Houfi, Ashraf; Javed, Nadeem; Solem, Caitlyn T; Macahilig, Cynthia; Stephens, Jennifer M; Raghubir, Nirvana; Chambers, Richard; Li, Jim Z; Haider, Seema

2015-01-01

To describe real-world treatment patterns and health care resource use and to estimate opportunities for early-switch (ES) from intravenous (IV) to oral (PO) antibiotics and early-discharge (ED) for patients hospitalized in the United Arab Emirates (UAE) with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections. This retrospective observational medical chart review study enrolled physicians from four UAE sites to collect data for 24 patients with documented MRSA complicated skin and soft tissue infections, hospitalized between July 2010 and June 2011, and discharged alive by July 2011. Data include clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and PO antibiotic use, and ES and ED eligibility using literature-based and expert-validated criteria. Five included patients (20.8%) were switched from IV to PO antibiotics while being inpatients. Actual length of MRSA-active treatment was 10.8±7.0 days, with 9.8±6.6 days of IV therapy. Patients were hospitalized for a mean 13.9±9.3 days. The most frequent initial MRSA-active therapies used were vancomycin (37.5%), linezolid (16.7%), and clindamycin (16.7%). Eight patients were discharged with MRSA-active antibiotics, with linezolid prescribed most frequently (n=3; 37.5%). Fifteen patients (62.5%) met ES criteria and potentially could have discontinued IV therapy 8.3±6.0 days sooner, and eight (33.3%) met ED criteria and potentially could have been discharged 10.9±5.8 days earlier. While approximately one-fifth of patients were switched from IV to PO antibiotics in the UAE, there were clear opportunities for further optimization of health care resource use. Over half of UAE patients hospitalized for MRSA complicated skin and soft tissue infections could be eligible for ES, with one-third eligible for ED opportunities, resulting in substantial potential for reductions in IV days and bed days.

Quantum Entanglement Molecular Absorption Spectrum Simulator

NASA Technical Reports Server (NTRS)

Nguyen, Quang-Viet; Kojima, Jun

2006-01-01

Quantum Entanglement Molecular Absorption Spectrum Simulator (QE-MASS) is a computer program for simulating two photon molecular-absorption spectroscopy using quantum-entangled photons. More specifically, QE-MASS simulates the molecular absorption of two quantum-entangled photons generated by the spontaneous parametric down-conversion (SPDC) of a fixed-frequency photon from a laser. The two-photon absorption process is modeled via a combination of rovibrational and electronic single-photon transitions, using a wave-function formalism. A two-photon absorption cross section as a function of the entanglement delay time between the two photons is computed, then subjected to a fast Fourier transform to produce an energy spectrum. The program then detects peaks in the Fourier spectrum and displays the energy levels of very short-lived intermediate quantum states (or virtual states) of the molecule. Such virtual states were only previously accessible using ultra-fast (femtosecond) laser systems. However, with the use of a single-frequency continuous wave laser to produce SPDC photons, and QEMASS program, these short-lived molecular states can now be studied using much simpler laser systems. QE-MASS can also show the dependence of the Fourier spectrum on the tuning range of the entanglement time of any externally introduced optical-path delay time. QE-MASS can be extended to any molecule for which an appropriate spectroscopic database is available. It is a means of performing an a priori parametric analysis of entangled photon spectroscopy for development and implementation of emerging quantum-spectroscopic sensing techniques. QE-MASS is currently implemented using the Mathcad software package.

Iowa's High School Super Senior School-to-Work Transition Program

ERIC Educational Resources Information Center

Nietupski, John; Warth, Judy; Winslow, Amy; Johnson, Russ; Douglas, Beverly; Johnson, Maggie; Cilek, Judy

2006-01-01

This article describes an innovative school-to-work transition program incorporating identified best practices. Iowa's Super Senior program serves students in the "middle range" of the disability severity spectrum during the student's senior and 5th, or "Super Senior" year. The article describes the program elements, presents…

Reduction of Broad-Spectrum Antimicrobial Use in a Tertiary Children's Hospital Post Antimicrobial Stewardship Program Guideline Implementation.

PubMed

Lee, Kelley R; Bagga, Bindiya; Arnold, Sandra R

2016-03-01

The core strategies recommended for antimicrobial stewardship programs, formulary restriction with preauthorization and prospective audit and feedback, can be difficult to implement with limited resources; therefore, we took an approach of guideline development and education with the goal of reducing overall antibiotic use and unwarranted use of broad-spectrum antimicrobials. Retrospective chart review before and after intervention. Le Bonheur Children's Hospital pediatric, neonatal, and cardiac ICUs. All patients in our pediatric, neonatal, and cardiac ICUs within the time frame of the study. Baseline review in our ICUs revealed excessive use of broad-spectrum antibiotics and inconsistency in managing common pediatric infections. Guidelines were developed and implemented using cycles of education, retrospective review, and feedback. Purchasing and antibiotic use data were obtained to assess changes before and after guideline implementation. Unit-specific days of therapy were measured using periodic chart audit. Segmented regression analysis was used to assess changes in purchasing and broad-spectrum antibiotic days of therapy. The change in median monthly purchases was assessed using 2-tail Student t test. Hospital-wide targeted broad-spectrum antibiotic days of therapy/1,000 patient-days during the preimplementation year averaged 105 per month and decreased 33% to 70 per month during the postimplementation year. The overall antibiotic days of therapy decreased 41%, 21%, and 18%, and targeted broad-spectrum antibiotic days of therapy decreased by 99%, 75%, and 61% in the cardiac, pediatric, and neonatal ICUs, respectively, after guideline implementation. Yearly purchases of our most common broad-spectrum antibiotics decreased 62% from $230,059 to $86,887 after guideline implementation. Median monthly purchases of these drugs before implementation were $19,389 and $11,043 after implementation (p < 0.001). Guideline implementation was successful in reducing targeted broad-spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible.

Impact of malaria interventions on child mortality in endemic African settings: comparison and alignment between LiST and Spectrum-Malaria model.

PubMed

Korenromp, Eline; Hamilton, Matthew; Sanders, Rachel; Mahiané, Guy; Briët, Olivier J T; Smith, Thomas; Winfrey, William; Walker, Neff; Stover, John

2017-11-07

In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity. The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults. Spectrum-Malaria uses statistical models fitted to simulations of the dynamic effects of increasing intervention coverage on these burdens as a function of baseline malaria endemicity, seasonality in transmission and malaria intervention coverage levels (estimated for years 2000 to 2015 by the World Health Organization and Malaria Atlas Project). Spectrum-Malaria projections of proportional reductions in under-five malaria mortality were compared with those of the Lives Saved Tool (LiST) for the Democratic Republic of the Congo and Zambia, for given (standardized) scenarios of ITN and/or CMU scale-up over 2016-2030. Proportional mortality reductions over the first two years following scale-up of ITNs from near-zero baselines to moderately higher coverages align well between LiST and Spectrum-Malaria -as expected since both models were fitted to cluster-randomized ITN trials in moderate-to-high-endemic settings with 2-year durations. For further scale-up from moderately high ITN coverage to near-universal coverage (as currently relevant for strategic planning for many countries), Spectrum-Malaria predicts smaller additional ITN impacts than LiST, reflecting progressive saturation. For CMU, especially in the longer term (over 2022-2030) and for lower-endemic settings (like Zambia), Spectrum-Malaria projects larger proportional impacts, reflecting onward dynamic effects not fully captured by LiST. Spectrum-Malaria complements LiST by extending the scope of malaria interventions, program packages and health outcomes that can be evaluated for policy making and strategic planning within and beyond the perspective of child survival.

Supporting university students with autism spectrum disorder.

PubMed

Hillier, Ashleigh; Goldstein, Jody; Murphy, Deirdra; Trietsch, Rhoda; Keeves, Jacqueline; Mendes, Eva; Queenan, Alexa

2018-01-01

Increasing numbers of students with autism spectrum disorder are entering higher education. Their success can be jeopardized by organizational, social/emotional, and academic challenges if appropriate supports are not in place. Our objective was to evaluate the effectiveness of a support group model for university students with autism spectrum disorder in improving psychological and functional outcomes. A curriculum guided the weekly discussions and consisted of topics such as time and stress management, managing group work, and social communication. Efficacy was assessed through pre- and post self-report measures focused on self-esteem, loneliness, anxiety, and depression. Functional changes in academic and social skills were examined through qualitative analysis of focus groups. Findings from the self-report measures indicated significant reductions in feelings of loneliness and general anxiety, and a significant increase in self-esteem at the end of the program compared to the beginning. Five prominent themes were identified in the focus-group analysis and reflected how the program had positively impacted participants' skills and coping: executive functioning; goal setting; academics and resources; stress and anxiety; and social. Given the cost effectiveness of "in-house" interventions and the potential for improving academic outcomes and retention of students with autism spectrum disorder, further research examining similar program models is warranted.

Noise produced by turbulent flow into a rotor: Theory manual for noise calculation

NASA Technical Reports Server (NTRS)

Amiet, R. K.

1989-01-01

An analysis is presented for the calculation of noise produced by turbulent flow into a helicopter rotor. The method is based on the analysis of Amiet for the sound produced by an airfoil moving in rectilinear motion through a turbulent flow field. The rectilinear motion results are used in a quasi-steady manner to calculate the instantaneous spectrum of the rotor noise at any given rotor position; the overall spectrum is then found by averaging the instantaneous spectrum over all rotor azimuth angles. Account is taken of the fact that the rotor spends different amounts of retarded time at different rotor positions. Blade to blade correlation is included in the analysis, leading to harmonics of blade passing frequency. The spectrum of the turbulence entering the rotor is calculated by applying rapid distortion theory to an isotropic turbulence spectrum, assuming that the turbulence is stretched as it is pulled into the rotor. The inputs to the program are obtained from the atmospheric turbulence model and mean flow distortion calculation, described in another volume of this set of reports. The analytical basis is provided for a module which was incorporated in NASA's ROTONET helicopter noise prediction program.

Signal processing in SETI.

PubMed

Cullers, D K; Linscott, I R; Oliver, B M

1985-11-01

The development of a multi-channel spectrum analyzer (MCSA) for the SETI program is described. The spectrum analyzer is designed for both all-sky surveys and targeted searches. The mechanisms of the MCSA are explained and a diagram is provided. Detection of continuous wave signals, pulses, and patterns is examined.

The prevention and management of infections due to multidrug resistant organisms in haematology patients

PubMed Central

Trubiano, Jason A; Worth, Leon J; Thursky, Karin A; Slavin, Monica A

2015-01-01

Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens. PMID:24341410

Antistaphylococcal Activity of CG400549, a New Experimental FabI Inhibitor, Compared with That of Other Agents▿

PubMed Central

Bogdanovich, Tatiana; Clark, Catherine; Kosowska-Shick, Klaudia; Dewasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C.

2007-01-01

Among 203 strains of Staphylococcus aureus, the MICs of CG400549 were 0.06 to 1.0 μg/ml, with MIC50 and MIC90 values of 0.25 μg/ml each. All strains were susceptible to linezolid and quinupristin-dalfopristin (MICs, 0.25 to 2.0 μg/ml). The daptomycin MICs were 0.25 to 2.0 μg/ml for methicillin-susceptible and 0.25 to 4.0 μg/ml against methicillin-resistant strains (including vancomycin-intermediate strains). Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested. PMID:17875997

Comparative In Vitro Activities of XRP 2868, Pristinamycin, Quinupristin-Dalfopristin, Vancomycin, Daptomycin, Linezolid, Clarithromycin, Telithromycin, Clindamycin, and Ampicillin against Anaerobic Gram-Positive Species, Actinomycetes, and Lactobacilli

PubMed Central

Goldstein, Ellie J. C.; Citron, Diane M.; Merriam, C. Vreni; Warren, Yumi A.; Tyrrell, Kerin L.; Fernandez, Helen T.; Bryskier, Andre

2005-01-01

A comparative study of the in vitro activities of XRP 2868, a new oral streptogramin, against 266 anaerobic gram-positive clinical isolates using the agar dilution method showed that the XRP 2868 MICs for 95% (254 of 266) of isolates were ≤0.5 μg/ml. XRP 2868 MICs for only two strains, one being Clostridium clostridioforme (MIC, 16 μg/ml) and the other being Clostridium difficile (MIC, 32 μg/ml), were >2 μg/ml. Depending on its pharmacokinetics and pharmacodynamics, XRP 2868 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation. PMID:15616322

Molecular characterization of vancomycin-resistant Enterococcus faecium isolates from Bermuda

PubMed Central

Akpaka, Patrick Eberechi; Kissoon, Shivnarine; Wilson, Clyde; Jayaratne, Padman; Smith, Ashley; Golding, George R.

2017-01-01

Molecular characteristics of vancomycin resistant enterococci isolates from Bermuda Island is currently unknown. This study was conducted to investigate phenotypic and genotypic characteristics of VRE isolates from Bermuda Island using the chromogenic agar, E-tests, polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Eighteen E. faecium isolates were completely analyzed and were all resistant to vancomycin, susceptible to linezolid and quinupristin/dalfopristin, positive for vanA and esp genes. The MLST analysis confirmed most isolates were of the sequence types linked to clonal complex 17 (CC17) that is widely associated with outbreaks in hospitals. Infection control measures, antibiotic stewardship, and surveillance activities will continue to be a priority in hospital on the Island. PMID:28267763

Molecular characterization of vancomycin-resistant Enterococcus faecium isolates from Bermuda.

PubMed

Akpaka, Patrick Eberechi; Kissoon, Shivnarine; Wilson, Clyde; Jayaratne, Padman; Smith, Ashley; Golding, George R

2017-01-01

Molecular characteristics of vancomycin resistant enterococci isolates from Bermuda Island is currently unknown. This study was conducted to investigate phenotypic and genotypic characteristics of VRE isolates from Bermuda Island using the chromogenic agar, E-tests, polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Eighteen E. faecium isolates were completely analyzed and were all resistant to vancomycin, susceptible to linezolid and quinupristin/dalfopristin, positive for vanA and esp genes. The MLST analysis confirmed most isolates were of the sequence types linked to clonal complex 17 (CC17) that is widely associated with outbreaks in hospitals. Infection control measures, antibiotic stewardship, and surveillance activities will continue to be a priority in hospital on the Island.

An astrophysics data program investigation of a synoptic study of quasar continua

NASA Technical Reports Server (NTRS)

Elvis, Martin

1991-01-01

A summary of the program is presented. The major product of the program, an atlas of quasar energy distributions, is presented in the appendices along with papers written as a result of this research. The topics covered in the papers include: (1) accurate galactic N(sub h) values toward quasars and active galactic nuclei (AGN); (2) weak bump quasars; (3) millimeter measurements of hard x ray selected active galaxies- implications for the nature of the continuous spectrum; (3) persistence and change in the soft x ray spectrum of the quasar PG1211+143; (4) the soft x ray excess in einstein quasar spectra; and (5) EXOSAT x ray spectra of quasars.

Assessing Quality of Program Environments for Children and Youth with Autism: Autism Program Environment Rating Scale (APERS)

ERIC Educational Resources Information Center

Odom, Samuel L.; Cox, Ann; Sideris, John; Hume, Kara A.; Hedges, Susan; Kucharczyk, Suzanne; Shaw, Evelyn; Boyd, Brian A.; Reszka, Stephanie; Neitzel, Jennifer

2018-01-01

The purpose of this study was to examine the psychometric properties of the "Autism Program Environment Rating Scale" ("APERS"), an instrument designed to assess quality of program environments for students with autism spectrum disorder. Data sets from two samples of public school programs that provided services to children and…

A Simulation Program for Dynamic Infrared (IR) Spectra

ERIC Educational Resources Information Center

Zoerb, Matthew C.; Harris, Charles B.

2013-01-01

A free program for the simulation of dynamic infrared (IR) spectra is presented. The program simulates the spectrum of two exchanging IR peaks based on simple input parameters. Larger systems can be simulated with minor modifications. The program is available as an executable program for PCs or can be run in MATLAB on any operating system. Source…

The Role of the New mTOR Complex, mTORC2, in Autism Spectrum Disorders

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-1-0380 TITLE: "The Role of the New mTOR Complex, mTORC2, in Autism Spectrum Disorders " PRINCIPAL INVESTIGATOR: Mauro...34The Role of the New mTOR Complex, mTORC2, in Autism Spectrum Disorders " 5a. CONTRACT NUMBER W81XWH-13-1-0380 5b. GRANT NUMBER 5c. PROGRAM...Pten. These insights hold the promise for new mTORC2-based treatment of ASD. 15. SUBJECT TERMS Autism Spectrum Disorder (ASD), mTORC2, mTORC1

Power Spectrum Analysis of BNL Decay-Rate Data

DTIC Science & Technology

2010-01-01

1/31 Power Spectrum Analysis of BNL Decay-Rate Data P.A. Sturrocka,*, J.B. Buncherb, E. Fischbachb, J.T. Gruenwaldb, D. Javorsek...Power Spectrum Analysis of BNL Decay-Rate Data 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...spectra in the rotational search band formed from BNL data and from ACRIM total solar irradiance data. Since rotation rate estimates derived from

Development of the Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills program for adults on the autism spectrum: Results of initial study.

PubMed

Baker-Ericzén, Mary J; Fitch, Meghan A; Kinnear, Mikaela; Jenkins, Melissa M; Twamley, Elizabeth W; Smith, Linda; Montano, Gabriel; Feder, Joshua; Crooke, Pamela J; Winner, Michelle G; Leon, Juan

2018-01-01

The population of adults on the autism spectrum continues to increase, and vocational outcomes are particularly poor. Longitudinal studies of adults with autism spectrum and without intellectual disability have shown consistent and persistent deficits across cognitive, social, and vocational domains, indicating a need for effective treatments of functional disabilities as each impact employment. This initial pilot study is an open trial investigation of the feasibility, acceptability, and initial estimates of outcomes for the newly developed Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills intervention, a manualized "soft skills" curriculum, to enhance both cognitive and social development in adults with autism spectrum. A total of eight adults with autism spectrum, without intellectual disability (78% males), participated in the study. Results support the original hypothesis that adults with autism spectrum can improve both cognitive (i.e. executive functioning) and social cognitive (i.e. social thinking and social communication) abilities. Further Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills was found to be feasible, acceptable, and highly satisfactory for participants and parents. Employment rates more than doubled post-intervention, with an increase from 22% to 56% of participants employed. Conclusion is that Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills has promise as an intervention that can be easily embedded into exiting supported employment vocational training programs to improve cognitive, social, and vocational outcomes.

Development of the Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills program for adults on the autism spectrum: Results of initial study

PubMed Central

Baker-Ericzén, Mary J; Fitch, Meghan A; Kinnear, Mikaela; Jenkins, Melissa M; Twamley, Elizabeth W; Smith, Linda; Montano, Gabriel; Feder, Joshua; Crooke, Pamela J; Winner, Michelle G; Leon, Juan

2018-01-01

The population of adults on the autism spectrum continues to increase, and vocational outcomes are particularly poor. Longitudinal studies of adults with autism spectrum and without intellectual disability have shown consistent and persistent deficits across cognitive, social, and vocational domains, indicating a need for effective treatments of functional disabilities as each impact employment. This initial pilot study is an open trial investigation of the feasibility, acceptability, and initial estimates of outcomes for the newly developed Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills intervention, a manualized “soft skills” curriculum, to enhance both cognitive and social development in adults with autism spectrum. A total of eight adults with autism spectrum, without intellectual disability (78% males), participated in the study. Results support the original hypothesis that adults with autism spectrum can improve both cognitive (i.e. executive functioning) and social cognitive (i.e. social thinking and social communication) abilities. Further Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills was found to be feasible, acceptable, and highly satisfactory for participants and parents. Employment rates more than doubled post-intervention, with an increase from 22% to 56% of participants employed. Conclusion is that Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills has promise as an intervention that can be easily embedded into exiting supported employment vocational training programs to improve cognitive, social, and vocational outcomes. PMID:29034696

Adaptation of the Children's Friendship Training Program for Children with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Laugeson, Elizabeth A.; Paley, Blair; Schonfeld, Amy M.; Carpenter, Erika M.; Frankel, Fred; O'Connor, Mary J.

2007-01-01

Previous research attests to the marked impairments in social functioning exhibited by children with Fetal Alcohol Spectrum Disorders (FASD), suggesting that such children are in need of social skills intervention. Recently, an existing evidence-based manualized behavioral treatment for improving children's friendships was implemented and…

Beyond [lambda][subscript max] Part 2: Predicting Molecular Color

ERIC Educational Resources Information Center

Williams, Darren L.; Flaherty, Thomas J.; Alnasleh, Bassam K.

2009-01-01

A concise roadmap for using computational chemistry programs (i.e., Gaussian 03W) to predict the color of a molecular species is presented. A color-predicting spreadsheet is available with the online material that uses transition wavelengths and peak-shape parameters to predict the visible absorbance spectrum, transmittance spectrum, chromaticity…

Autism Spectrum Disorder in Popular Media: Storied Reflections of Societal Views

ERIC Educational Resources Information Center

Belcher, Christina; Maich, Kimberly

2014-01-01

This article explores how storied representations of characters with Autism Spectrum Disorder (ASD) are typified in a world that is increasingly influenced by popular media. Twenty commercially published children's picture books, popular novels, mainstream television programs, and popular movies from 2006-2012 were selected using purposive,…

Brief Report: Theatre as Therapy for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Corbett, Blythe A.; Gunther, Joan R.; Comins, Dan; Price, Jenifer; Ryan, Niles; Simon, David; Schupp, Clayton W.; Rios, Taylor

2011-01-01

The pilot investigation evaluated a theatrical intervention program, Social Emotional NeuroScience Endocrinology (SENSE) Theatre, designed to improve socioemotional functioning and reduce stress in children with autism spectrum disorder (ASD). Eight children with ASD were paired with typically developing peers that served as expert models.…

76 FR 18476 - Improving Communications Services for Native Nations by Promoting Greater Utilization of Spectrum...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... CONTACT: Wireless Telecommunications Bureau, Auctions and Spectrum Access Division: Stephen Johnson... 25 employees. I. Synopsis 1. While competitive market forces have spurred robust wireless.... Although the Commission has adopted a range of programs intended to promote access to wireless radio and...

Advanced composite stabilizer for Boeing 737 aircraft

NASA Technical Reports Server (NTRS)

1978-01-01

Activities related to development of an advanced composites stabilizer for the Boeing 737 commercial transport are reported. Activities include discussion of criteria and objectives, design loads, the fatigue spectrum definition to be used for all spectrum fatigue testing, fatigue analysis, manufacturing producibility studies, the ancillary test program, quality assurance, and manufacturing development.

Evaluation of spray droplet spectrum of sprayers used for vector control

USDA-ARS?s Scientific Manuscript database

Droplet spectra data were collected from spray equipment intended for use in vector control by the US Department of Defense pest management programs to determine if they produce droplets in the ultra-low volume (ULV) spectrum. Droplets generated by 26 sprayers utilizing water + non-ionic surfactant...

NASA's Commercial Communication Technology Program

NASA Technical Reports Server (NTRS)

Bagwell, James W.

1998-01-01

Various issues associated with "NASA's Commercial Communication Technology Program" are presented in viewgraph form. Specific topics include: 1) Coordination/Integration of government program; 2) Achievement of seamless interoperable satellite and terrestrial networks; 3) Establishment of program to enhance Satcom professional and technical workforce; 4) Precompetitive technology development; and 5) Effective utilization of spectrum and orbit assets.

Global Rural Autism Asperger Information Network: A Distance Learning Inservice Training Program.

ERIC Educational Resources Information Center

Bock, Marjorie A.; Swinney, Lori; Smart, Kathy

The University of North Dakota's Global Rural Autism Asperger Information Network (GRAAIN) provides a special graduate certificate program in Autistic Spectrum Disorder (ASD) consisting of six online courses. The program started over 4 years ago as a pilot program to provide specialized ASD training to educators and personnel serving children with…

Social Tools And Rules for Teens (The START Program): Program Description and Preliminary Outcomes of an Experiential Socialization Intervention for Adolescents with Autism Spectrum Disorder.

PubMed

Vernon, Ty W; Miller, Amber R; Ko, Jordan A; Wu, Victoria L

2016-05-01

Experiential learning is an essential process in the development of core social competencies. Unfortunately, adolescents with autism spectrum disorders often do not possess the prerequisite skillset and motivation to sustain the level of social immersion needed to benefit from this learning process. These persisting social vulnerabilities can limit their long-term relational success and associated quality of life, creating a need for comprehensive social programming. This paper describes a multi-component socialization intervention that simultaneously targets motivational, conceptual, and skill deficits using a hybrid experiential/didactic treatment approach. Evidence of social competence improvements was noted in survey and live conversational measures, indicating that the START program may hold promise as a method for improving the social success of participating adolescents with ASD.

Antibiotic resistance, virulence determinants and production of biogenic amines among enterococci from ovine, feline, canine, porcine and human milk

PubMed Central

2013-01-01

Background Recent studies have shown that mammalian milk represents a continuous supply of commensal bacteria, including enterococci. The objectives of this study were to evaluate the presence of enterococci in milk of different species and to screen them for several genetic and phenotypic traits of clinical significance among enterococci. Results Samples were obtained from, at least, nine porcine, canine, ovine, feline and human healthy hosts. Enterococci could be isolated, at a concentration of 1.00 × 102 -1.16 × 103 CFU/ml, from all the porcine samples and, also from 85, 50, 25 and 25% of the human, canine, feline and ovine ones, respectively. They were identified as Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Enterococcus casseliflavus and Enterococcus durans. Among the 120 initial enterococcal isolates, 36 were selected on the basis of their different PFGE profiles and further characterized. MLST analysis revealed a wide diversity of STs among the E. faecalis and E. faecium strains, including some frequently associated to hospital infections and novel STs. All the E. faecalis strains possessed some of the potential virulence determinants (cad, ccf, cob, cpd, efaAfs, agg2, gelE, cylA, espfs) assayed while the E. faecium ones only harboured the efaAfm gene. All the tested strains were susceptible to tigecycline, linezolid and vancomycin, and produced tyramine. Their susceptibility to the rest of the antimicrobials and their ability to produce other biogenic amines varied depending on the strain. Enterococci strains isolated from porcine samples showed the widest spectrum of antibiotic resistance. Conclusions Enterococci isolated from milk of different mammals showed a great genetic diversity. The wide distribution of virulence genes and/or antibiotic resistance among the E. faecalis and E. faecium isolates indicates that they can constitute a reservoir of such traits and a risk to animal and human health. PMID:24325647

A Randomized Controlled Trial to Improve Social Skills in Young Adults with Autism Spectrum Disorder: The UCLA PEERS(®) Program.

PubMed

Laugeson, Elizabeth A; Gantman, Alexander; Kapp, Steven K; Orenski, Kaely; Ellingsen, Ruth

2015-12-01

Research suggests that impaired social skills are often the most significant challenge for those with autism spectrum disorder (ASD), yet few evidence-based social skills interventions exist for adults on the spectrum. This replication trial tested the effectiveness of PEERS, a caregiver-assisted social skills program for high-functioning young adults with ASD. Using a randomized controlled design, 22 young adults 18-24 years of age were randomly assigned to a treatment (n = 12) or delayed treatment control (n = 10) group. Results revealed that the treatment group improved significantly in overall social skills, frequency of social engagement, and social skills knowledge, and significantly reduced ASD symptoms related to social responsiveness following PEERS. Most treatment gains were maintained at a 16-week follow-up assessment with new improvements observed.

Improvements in Spectrum's fit to program data tool.

PubMed

Mahiane, Severin G; Marsh, Kimberly; Grantham, Kelsey; Crichlow, Shawna; Caceres, Karen; Stover, John

2017-04-01

The Joint United Nations Program on HIV/AIDS-supported Spectrum software package (Glastonbury, Connecticut, USA) is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with program and vital registration data, such as historical trends in the number of newly diagnosed infections or people living with HIV and AIDS related deaths. This article describes development and application of the fit to program data (FPD) tool in Joint United Nations Program on HIV/AIDS' 2016 estimates round. In the FPD tool, HIV incidence trends are described as a simple or double logistic function. Function parameters are estimated from historical program data on newly reported HIV cases, people living with HIV or AIDS-related deaths. Inputs can be adjusted for proportions undiagnosed or misclassified deaths. Maximum likelihood estimation or minimum chi-squared distance methods are used to identify the best fitting curve. Asymptotic properties of the estimators from these fits are used to estimate uncertainty. The FPD tool was used to fit incidence for 62 countries in 2016. Maximum likelihood and minimum chi-squared distance methods gave similar results. A double logistic curve adequately described observed trends in all but four countries where a simple logistic curve performed better. Robust HIV-related program and vital registration data are routinely available in many middle-income and high-income countries, whereas HIV seroprevalence surveillance and survey data may be scarce. In these countries, the FPD tool offers a simpler, improved approach to estimating HIV incidence trends.

Development of a College Transition and Support Program for Students with Autism Spectrum Disorder.

PubMed

White, Susan W; Elias, Rebecca; Capriola-Hall, Nicole N; Smith, Isaac C; Conner, Caitlin M; Asselin, Susan B; Howlin, Patricia; Getzel, Elizabeth E; Mazefsky, Carla A

2017-10-01

Empirically based, consumer-informed programming to support students with Autism Spectrum Disorder (ASD) transitioning to college is needed. Informed by theory and research, the Stepped Transition in Education Program for Students with ASD (STEPS) was developed to address this need. The first level (Step 1) supports high school students and the second level (Step 2) is for postsecondary students with ASD. Herein, we review the extant research on transition supports for emerging adults with ASD and describe the development of STEPS, including its theoretical basis and how it was informed by consumer input. The impact of STEPS on promotion of successful transition into college and positive outcomes for students during higher education is currently being evaluated in a randomized controlled trial.

Development of program package for investigation and modeling of carbon nanostructures in diamond like carbon films with the help of Raman scattering and infrared absorption spectra line resolving

NASA Astrophysics Data System (ADS)

Hayrapetyan, David B.; Hovhannisyan, Levon; Mantashyan, Paytsar A.

2013-04-01

The analysis of complex spectra is an actual problem for modern science. The work is devoted to the creation of a software package, which analyzes spectrum in the different formats, possesses by dynamic knowledge database and self-study mechanism, performs automated analysis of the spectra compound based on knowledge database by application of certain algorithms. In the software package as searching systems, hyper-spherical random search algorithms, gradient algorithms and genetic searching algorithms were used. The analysis of Raman and IR spectrum of diamond-like carbon (DLC) samples were performed by elaborated program. After processing the data, the program immediately displays all the calculated parameters of DLC.

Spectrum Orbit Utilization Program documentation: SOUP5 version 3.8 user's manual, volume 1, chapters 1 through 5

NASA Technical Reports Server (NTRS)

Davidson, J.; Ottey, H. R.; Sawitz, P.; Zusman, F. S.

1985-01-01

The underlying engineering and mathematical models as well as the computational methods used by the Spectrum Orbit Utilization Program 5 (SOUP5) analysis programs are described. Included are the algorithms used to calculate the technical parameters, and references to the technical literature. The organization, capabilities, processing sequences, and processing and data options of the SOUP5 system are described. The details of the geometric calculations are given. Also discussed are the various antenna gain algorithms; rain attenuation and depolarization calculations; calculations of transmitter power and received power flux density; channelization options, interference categories, and protection ratio calculation; generation of aggregrate interference and margins; equivalent gain calculations; and how to enter a protection ratio template.

A "Sampler" of Environmental Education Activities and Programs in the United States of America.

ERIC Educational Resources Information Center

Federal Interagency Committee on Education, Washington, DC.

Seventy-four environmental education programs/projects, identified by program/project title and state, are described. The programs were selected for inclusion on the bases of geographic representation, across a spectrum of target audiences and funding sources. Although the descriptions differ in format, they include one or more of the following:…

The Collaborative Autism Support Program at Brooklyn College: A Formative Program Evaluation

ERIC Educational Resources Information Center

Coombs, Natalie

2017-01-01

In the last decade, postsecondary institutions have seen a tremendous increase in the enrollment of students with autism spectrum disorder (ASD). As a result, in 2012, Brooklyn College (BC), a large public college in an urban setting serving 17,000 students, created the Collaborative Autism Support Program (CASP). The program has a structured…

Impact of a Rural Community-Based Event for Families of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Doody, Kathy Ralabate; Patti, Angela L.

2017-01-01

Children with autism spectrum disorders (ASDs) often have difficulty demonstrating appropriate communication, social skills, behavior, and sensory responses; thus, it can be challenging for families, particularly those in rural areas, to find suitable community-based opportunities. The Au-some Evenings program was developed at a local children's…

Establishing the Basis for a CIS (Computer Information Systems) Undergraduate Program: On Seeking the Body of Knowledge

ERIC Educational Resources Information Center

Longenecker, Herbert E., Jr.; Babb, Jeffry; Waguespack, Leslie J.; Janicki, Thomas N.; Feinstein, David

2015-01-01

The evolution of computing education spans a spectrum from "computer science" ("CS") grounded in the theory of computing, to "information systems" ("IS"), grounded in the organizational application of data processing. This paper reports on a project focusing on a particular slice of that spectrum commonly…

Experiences of Parents Who Homeschool Their Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Hurlbutt, Karen S.

2011-01-01

Teachers may be inadequately prepared for the increasing number of students being identified with autism spectrum disorders (ASD), as students with ASD may not respond to traditional methods of instruction. Some parents of children with ASD are concerned with educational programming available through public school systems and are turning to…

Explaining Differences in Age at Autism Spectrum Disorder Diagnosis: A Critical Review

ERIC Educational Resources Information Center

Daniels, Amy M.; Mandell, David S.

2014-01-01

The diagnosis of autism is often delayed, which translates into a missed opportunity to provide treatment during a critical developmental period. This study reviews studies that assessed factors associated with age at autism spectrum disorder diagnosis and provides recommendations on future research, programs, and policies to improve early…

Teaching Students with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Online Submission, 2003

2003-01-01

This resource is Book 9 in the Programming for Students with Special Needs series. The information in each book in the series is interrelated and can be used to provide instruction to all students. Chapters one and two cover the prevalence, causes, diagnoses, and characteristics of autism spectrum disorders. Chapters three and four cover…

Mediating Access to Headsprout® Early Reading for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Plavnick, Joshua B.; Thompson, Julie L.; Englert, Carol Sue; Mariage, Troy; Johnson, Katie

2016-01-01

Many children with autism spectrum disorder (ASD) require instructional programs that simultaneously address academic content, interfering behavior, and potential gaps in prerequisite skills for a given curriculum. This study examined the impact of an intervention package consisting of contingent reinforcement and match-to-sample training on the…

A Review of Parent Education Programs for Parents of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Schultz, Tia R.; Schmidt, Carla T.; Stichter, Janine P.

2011-01-01

Benefits of parent education have been demonstrated for decades. However, there exists a lack of formative evaluation of parent education for parents of children with autism spectrum disorders (ASD), limiting the interpretation of ongoing and future research. To understand the current status, key characteristics, and evaluation methods of parent…

Note-Taking Instruction for College Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Reed, Deborah K.; Hallett, Abigail; Rimel, Hillary

2016-01-01

Using a multiple baseline across participants design, this study examines the functional relationship between instruction in note-taking skills and the ability of young adults with autism spectrum disorder to take notes on college lectures. The three participants were enrolled in a program aligned with the Higher Education Opportunity Act (Public…

The Diagnosis of Autism in Community Pediatric Settings: Does Advanced Training Facilitate Practice Change?

ERIC Educational Resources Information Center

Swanson, Amy R.; Warren, Zachary E.; Stone, Wendy L.; Vehorn, Alison C.; Dohrmann, Elizabeth; Humberd, Quentin

2014-01-01

The increased prevalence of autism spectrum disorder and documented benefits of early intensive intervention have created a need for flexible systems for determining eligibility for autism-specific services. This study evaluated the effectiveness of a training program designed to enhance autism spectrum disorder identification and assessment…

Sibling Involvement in Interventions for Individuals with Autism Spectrum Disorders: A Systematic Review

ERIC Educational Resources Information Center

Shivers, Carolyn M.; Plavnick, Joshua B.

2015-01-01

Many researchers have studied various interventions for individuals with autism spectrum disorder (ASD). Occasionally, siblings will be included in intervention studies, participating in programs designed to address a number of challenges faced by individuals with ASD. Although sibling involvement in such interventions is not a new phenomenon,…

Group Social Skills Instruction for Adolescents with High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

White, Susan W.; Koenig, Kathleen; Scahill, Lawrence

2010-01-01

Given the increased recognition of autism spectrum disorders (ASD) and the chronic and pervasive nature of associated deficits, there is a pressing need for effective treatments. The feasibility and preliminary efficacy of a structured, group social skills training program for high-functioning youth with ASD was examined in this study. Fifteen…

Innovative Technology-Based Interventions for Autism Spectrum Disorders: A Meta-Analysis

ERIC Educational Resources Information Center

Grynszpan, Ouriel; Weiss, Patrice L.; Perez-Diaz, Fernando; Gal, Eynat

2014-01-01

This article reports the results of a meta-analysis of technology-based intervention studies for children with autism spectrum disorders. We conducted a systematic review of research that used a pre-post design to assess innovative technology interventions, including computer programs, virtual reality, and robotics. The selected studies provided…

What Do Parents of Children with Autism Spectrum Disorders Think?

ERIC Educational Resources Information Center

Thompson, Catherine Creighton

2014-01-01

The purpose of this mixed methods study was to better understand the perspectives of parents with children who are diagnosed with autism spectrum disorders regarding the Individualized Education Program (IEP) process, and interventions implemented to help their child meet IEP goals. The web-based survey included both closed and open-ended items.…

Designing Studies to Evaluate Parent-Mediated Interventions for Toddlers with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Siller, Michael; Morgan, Lindee; Turner-Brown, Lauren; Baggett, Kathleen M.; Baranek, Grace T.; Brian, Jessica; Bryson, Susan E.; Carter, Alice S.; Crais, Elizabeth R.; Estes, Annette; Kasari, Connie; Landa, Rebecca J.; Lord, Catherine; Messinger, Daniel S.; Mundy, Peter; Odom, Samuel L.; Reznick, J. Steven; Roberts, Wendy; Rogers, Sally J.; Schertz, Hannah H.; Smith, Isabel M.; Stone, Wendy L.; Watson, Linda R.; Wetherby, Amy M.; Yoder, Paul J.; Zwaigenbaum, Lonnie

2013-01-01

Given recent advances in science, policy, and practice of early identification in autism spectrum disorder (ASD), questions about the effectiveness of early intervention have far-reaching service and policy implications. However, rigorous research evaluating the efficacy and effectiveness of intervention programs for toddlers with ASD faces a…

Preliminary Efficacy of a Cognitive-Behavioral Treatment Program for Anxious Youth with Autism Spectrum Disorders

ERIC Educational Resources Information Center

White, Susan W.; Ollendick, Thomas; Scahill, Lawrence; Oswald, Donald; Albano, Anne Marie

2009-01-01

Anxiety is a commonly occurring psychiatric concern in adolescents with autism spectrum disorders (ASD). This pilot study examined the preliminary efficacy of a manual-based intervention targeting anxiety and social competence in four adolescents with high-functioning ASD. Anxiety and social functioning were assessed at baseline, midpoint,…

Online Communication Training for Parents of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Douglas, Sarah N.; Kammes, Rebecca; Nordquist, Erica

2018-01-01

Parent training is an essential part of quality programming for children with autism spectrum disorder (ASD). However, limited research exists exploring online training approaches to support parents of children with both ASD and complex communication needs (CCN; e.g., limited verbal ability), despite the many benefits that online training might…

Using Robot Animation to Promote Gestural Skills in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

So, W.-C.; Wong, M. K.-Y.; Cabibihan, J.-J.; Lam, C. K.-Y.; Chan, R. Y.-Y.; Qian, H.-H.

2016-01-01

School-aged children with autism spectrum disorders (ASDs) have delayed gestural development, in comparison with age-matched typically developing children. In this study, an intervention program taught children with low-functioning ASD gestural comprehension and production using video modelling (VM) by a computer-generated robot animation. Six to…

School-Based Social Skills Training for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Radley, Keith C.; McHugh, Melissa B.; Taber, Traci; Battaglia, Allison A.; Ford, W. Blake

2017-01-01

The present study evaluated the effects of the Superheroes Social Skills program, a social skills curriculum for children with autism spectrum disorders (ASD). Previous research has found the curriculum to improve social engagements of children with ASD during unstructured recess periods but has been limited in research design and lack of…

Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Mann, Joshua R.; McDermott, Suzanne; Bao, Haikun; Hardin, James; Gregg, Anthony

2010-01-01

Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important. In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly inversely associated with the odds of ASD (OR = 0.78, p = 0.001 for each additional…

A Systematic Review of Training Programs for Parents of Children with Autism Spectrum Disorders: Single Subject Contributions

ERIC Educational Resources Information Center

Patterson, Stephanie Y.; Smith, Veronica; Mirenda, Pat

2012-01-01

Aim: The purpose of this systematic review was to examine research utilizing single subject research designs (SSRD) to explore the effectiveness of interventions designed to increase parents' ability to support communication and social development in children with autism spectrum disorders (ASDs). Method: Included studies were systematically…

Gender dysphoria and the controversy over the Safe Schools program.

PubMed

Parkinson, Patrick

2017-10-01

The Safe Schools program has attracted great controversy. On one end of the spectrum, it is defended as an anti-bullying program for young people who identify themselves as gay or lesbian, or have issues concerning their gender identity. On the other end of the spectrum, it is regarded as social engineering. This article seeks to promote a discussion of the way in which gender identity issues are addressed in the Safe Schools program. It is argued that the information in this program to Principals, teachers and young people is inaccurate and misleading. The program, as presently designed, may actually cause harm to children and young people who experience gender identity issues because it promotes gender transitioning without expert medical advice. The Safe Schools materials do not acknowledge that the great majority of children resolve gender dysphoria issues around the time of puberty. It may be much more difficult for a child to accept his or her gender at puberty if he or she has already changed name and gender identity in primary school. These deficits need to be addressed if the program is to continue.

Misidentification of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals in Tripoli, Libya

PubMed Central

Ahmed, Mohamed O.; Abuzweda, Abdulbaset R.; Alghazali, Mohamed H.; Elramalli, Asma K.; Amri, Samira G.; Aghila, Ezzeddin Sh.; Abouzeed, Yousef M.

2010-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial (hospital-acquired) pathogen of exceptional concern. It is responsible for life-threatening infections in both the hospital and the community. Aims To determine the frequency of MRSA misidentification in hospitals in Tripoli, Libya using current testing methods. Methods One hundred and seventy S. aureus isolates previously identified as MRSA were obtained from three hospitals in Tripoli. All isolates were reidentified by culturing on mannitol salt agar, API 20 Staph System and retested for resistance to methicillin using the cefoxitin disk diffusion susceptibility test and PBP2a. D-tests and vancomycin E-tests (Van-E-tests) were also performed for vancomycin-resistant isolates. Results Of the 170 isolates examined, 86 (51%) were confirmed as MRSA (i.e. 49% were misidentified as MRSA). Fifteen (17%) of the confirmed MRSA strains exhibited inducible clindamycin resistance. Of the 86 confirmed MRSA isolates, 13 (15%) were resistant to mupirocin, 53 (62%) were resistant to ciprofloxacin, 41 (48%) were resistant to trimethoprim-sulfamethoxazole, and none were resistant to linezolid. Although disc-diffusion testing indicated that 23 (27%) of the isolates were resistant to vancomycin, none of the isolates were vancomycin-resistant by Van-E-test. Conclusions Misidentification of nosocomial S. aureus as MRSA is a serious problem in Libyan hospitals. There is an urgent need for the proper training of microbiology laboratory technicians in standard antimicrobial susceptibility procedures and the implementation of quality control programs in microbiology laboratories of Libyan hospitals. PMID:21483574

Economics in Detention

ERIC Educational Resources Information Center

Elonge, Michael

2013-01-01

Economics in Detention is a University of Maryland Extension program that teaches inmates essential principles of economics as a foundation to a spectrum of decision making. Also, the program includes an emphasis on starting a small business after incarceration. The idea of this program emanates from an invitation by the Baltimore City Detention…

Examination of a Museum Program for Children with Autism

ERIC Educational Resources Information Center

Mulligan, Shelley; Rais, Paula; Steele-Driscoll, Jacqueline; Townsend, Samantha

2013-01-01

This study examined the effectiveness of a children's museum program designed to support young children with autism spectrum disorders (ASD) and their families. The program offers specialized materials, financial incentives, an exclusive time, and trained volunteers to increase the comfort level, enjoyment, and learning opportunities of attendees.…

Exposure to Hazardous Chemical Substances--A Major Campus Environmental Health & Safety Concern.

ERIC Educational Resources Information Center

Robinson, Donald A.; Sorensen, Alfred J.

1980-01-01

A broad spectrum of potentially hazardous chemicals offers serious exposure risks to members of college and university communities. A formal program is needed to minimize exposure to these substances and maintain a prevention oriented protective program. The University of Massachusetts has developed such a program. (JN)

A Parent-Focused Early Intervention Program for Autism: Who Gets Access?

ERIC Educational Resources Information Center

Birkin, Christina; Anderson, Angelika; Seymour, Fred; Moore, Dennis W.

2008-01-01

Background: The EarlyBird program is a psycho-educational early intervention program for parents of children with autistic spectrum disorder (ASD). It aims to provide parents with skills to increase their child's communication and manage challenging behaviour using behavioural techniques. Method: Two interlinked studies examined access to the…

Pilot Study of a School-Based Parent Training Program for Preschoolers with ASD

ERIC Educational Resources Information Center

Ingersoll, Brooke R; Wainer, Allison L

2013-01-01

This study investigated the feasibility and preliminary effectiveness of a parenting training program designed for early intervention and early childhood special education (EI/ESCE) programs serving students with autistic spectrum disorders. Thirteen teachers representing three intermediate school districts implemented the intervention with 27…

A New Spectrum.

ERIC Educational Resources Information Center

Hamilton, Kendra

2000-01-01

Examination of Black Studies programs notes there are currently fewer programs than in the 1960s and 1970s, but that existing programs are healthier and offer a greater diversity of approaches. Tables list total minority associate and baccalaureate degrees awarded in area/ethnic/cultural studies. Notes the influence of celebrity professors,…

A Fortran 90 Hartree-Fock program for one-dimensional periodic π-conjugated systems using Pariser-Parr-Pople model

NASA Astrophysics Data System (ADS)

Kondayya, Gundra; Shukla, Alok

2012-03-01

Pariser-Parr-Pople (P-P-P) model Hamiltonian is employed frequently to study the electronic structure and optical properties of π-conjugated systems. In this paper we describe a Fortran 90 computer program which uses the P-P-P model Hamiltonian to solve the Hartree-Fock (HF) equation for infinitely long, one-dimensional, periodic, π-electron systems. The code is capable of computing the band structure, as also the linear optical absorption spectrum, by using the tight-binding and the HF methods. Furthermore, using our program the user can solve the HF equation in the presence of a finite external electric field, thereby, allowing the simulation of gated systems. We apply our code to compute various properties of polymers such as trans-polyacetylene, poly- para-phenylene, and armchair and zigzag graphene nanoribbons, in the infinite length limit. Program summaryProgram title: ppp_bulk.x Catalogue identifier: AEKW_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKW_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 87 464 No. of bytes in distributed program, including test data, etc.: 2 046 933 Distribution format: tar.gz Programming language: Fortran 90 Computer: PCs and workstations Operating system: Linux, Code was developed and tested on various recent versions of 64-bit Fedora including Fedora 14 (kernel version 2.6.35.12-90). Classification: 7.3 External routines: This program needs to link with LAPACK/BLAS libraries compiled with the same compiler as the program. For the Intel Fortran Compiler we used the ACML library version 4.4.0, while for the gfortran compiler we used the libraries supplied with the Fedora distribution. Nature of problem: The electronic structure of one-dimensional periodic π-conjugated systems is an intense area of research at present because of the tremendous interest in the physics of conjugated polymers and graphene nanoribbons. The computer program described in this paper provides an efficient way of solving the Hartree-Fock equations for such systems within the P-P-P model. In addition to the Bloch orbitals, band structure, and the density of states, the program can also compute quantities such as the linear absorption spectrum, and the electro-absorption spectrum of these systems. Solution method: For a one-dimensional periodic π-conjugated system lying in the xy-plane, the single-particle Bloch orbitals are expressed as linear combinations of p-orbitals of individual atoms. Then using various parameters defining the P-P-P Hamiltonian, the Hartree-Fock equations are set up as a matrix eigenvalue problem in the k-space. Thereby, its solutions are obtained in a self-consistent manner, using the iterative diagonalizing technique at several k points. The band structure and the corresponding Bloch orbitals thus obtained are used to perform a variety of calculations such as the density of states, linear optical absorption spectrum, electro-absorption spectrum, etc. Running time: Most of the examples provided take only a few seconds to run. For a large system, however, depending on the system size, the run time may be a few minutes to a few hours.

The effects of scripted peer tutoring and programming common stimuli on social interactions of a student with autism spectrum disorder.

PubMed

Petursdottir, Anna-Lind; McComas, Jennifer; McMaster, Kristen; Horner, Kathy

2007-01-01

This study examined the effects of scripted peer-tutoring reading activities, with and without programmed common play-related stimuli, on social interactions between a kindergartner with autism spectrum disorder and his typically developing peer-tutoring partners during free play. A withdrawal design with multiple baselines across peers showed no effects of peer tutoring on social interactions. A withdrawal design with 1 peer and continuing baselines across the other 2 peers showed that adding play-related common stimuli to the peer-tutoring activity increased social interactions during free play.

The Effects of Scripted Peer Tutoring and Programming Common Stimuli on Social Interactions of a Student with Autism Spectrum Disorder

PubMed Central

Petursdottir, Anna-Lind; McComas, Jennifer; McMaster, Kristen; Horner, Kathy

2007-01-01

This study examined the effects of scripted peer-tutoring reading activities, with and without programmed common play-related stimuli, on social interactions between a kindergartner with autism spectrum disorder and his typically developing peer-tutoring partners during free play. A withdrawal design with multiple baselines across peers showed no effects of peer tutoring on social interactions. A withdrawal design with 1 peer and continuing baselines across the other 2 peers showed that adding play-related common stimuli to the peer-tutoring activity increased social interactions during free play. PMID:17624077

Determination of $sup 241$Am in soil using an automated nuclear radiation measurement laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engstrom, D.E.; White, M.G.; Dunaway, P.B.

The recent completion of REECo's Automated Laboratory and associated software systems has provided a significant increase in capability while reducing manpower requirements. The system is designed to perform gamma spectrum analyses on the large numbers of samples required by the current Nevada Applied Ecology Group (NAEG) and Plutonium Distribution Inventory Program (PDIP) soil sampling programs while maintaining sufficient sensitivities as defined by earlier investigations of the same type. The hardware and systems are generally described in this paper, with emphasis being placed on spectrum reduction and the calibration procedures used for soil samples. (auth)

Training of child and adolescent psychiatry fellows in autism and intellectual disability.

PubMed

Marrus, Natasha; Veenstra-Vanderweele, Jeremy; Hellings, Jessica A; Stigler, Kimberly A; Szymanski, Ludwik; King, Bryan H; Carlisle, L Lee; Cook, Edwin H; Pruett, John R

2014-05-01

Patients with autism spectrum disorders and intellectual disability can be clinically complex and often have limited access to psychiatric care. Because little is known about post-graduate clinical education in autism spectrum disorder and intellectual disability, we surveyed training directors of child and adolescent psychiatry fellowship programs. On average, child and adolescent psychiatry directors reported lectures of 3 and 4 h per year in autism spectrum disorder and intellectual disability, respectively. Training directors commonly reported that trainees see 1-5 patients with autism spectrum disorder or intellectual disability per year for outpatient pharmacological management and inpatient treatment. Overall, 43% of directors endorsed the need for additional resources for training in autism spectrum disorder and intellectual disability, which, coupled with low didactic and clinical exposure, suggests that current training is inadequate.

Spectrum and power allocation in cognitive multi-beam satellite communications with flexible satellite payloads

NASA Astrophysics Data System (ADS)

Liu, Zhihui; Wang, Haitao; Dong, Tao; Yin, Jie; Zhang, Tingting; Guo, Hui; Li, Dequan

2018-02-01

In this paper, the cognitive multi-beam satellite system, i.e., two satellite networks coexist through underlay spectrum sharing, is studied, and the power and spectrum allocation method is employed for interference control and throughput maximization. Specifically, the multi-beam satellite with flexible payload reuses the authorized spectrum of the primary satellite, adjusting its transmission band as well as power for each beam to limit its interference on the primary satellite below the prescribed threshold and maximize its own achievable rate. This power and spectrum allocation problem is formulated as a mixed nonconvex programming. For effective solving, we first introduce the concept of signal to leakage plus noise ratio (SLNR) to decouple multiple transmit power variables in the both objective and constraint, and then propose a heuristic algorithm to assign spectrum sub-bands. After that, a stepwise plus slice-wise algorithm is proposed to implement the discrete power allocation. Finally, simulation results show that adopting cognitive technology can improve spectrum efficiency of the satellite communication.

Training adults and children with an autism spectrum disorder to be compliant with a clinical dental assessment using a TEACCH-based approach.

PubMed

Orellana, Lorena M; Martínez-Sanchis, Sonia; Silvestre, Francisco J

2014-04-01

The specific neuropsychological and sensory profile found in persons with autism spectrum disorders complicate dental procedures and as a result of this, most are treated under general anesthesia or unnecessary sedation. The main goal of the present study was to evaluate the effectiveness of a short treatment and education of autistic and related communication-handicapped children-based intervention program (five sessions) to facilitate a 10-component oral assessment in children (n = 38, aged 4-9 years) and adults (n = 34, aged 19-41) with autism spectrum disorder (with or without associated intellectual disability). The assessment ranges from entering into the examination room to the evaluation of the dental occlusion. There were statistically significant differences in the number of components reached and in compliance before and after the training program.

Efficacy of the Get Ready to Learn yoga program among children with autism spectrum disorders: a pretest-posttest control group design.

PubMed

Koenig, Kristie Patten; Buckley-Reen, Anne; Garg, Satvika

2012-01-01

Occupational therapists use school-based yoga programs, but these interventions typically lack manualization and evidence from well-designed studies. Using an experimental pretest-posttest control group design, we examined the effectiveness of the Get Ready to Learn (GRTL) classroom yoga program among children with autism spectrum disorders (ASD). The intervention group received the manualized yoga program daily for 16 wk, and the control group engaged in their standard morning routine. We assessed challenging behaviors with standardized measures and behavior coding before and after intervention. We completed a between-groups analysis of variance to assess differences in gain scores on the dependent variables. Students in the GRTL program showed significant decreases (p < .05) in teacher ratings of maladaptive behavior, as measured with the Aberrant Behavior Checklist, compared with the control participants. This study demonstrates that use of daily classroomwide yoga interventions has a significant impact on key classroom behaviors among children with ASD. Copyright © 2012 by the American Occupational Therapy Association, Inc.

Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus

PubMed Central

Eyal, Zohar; Matzov, Donna; Krupkin, Miri; Wekselman, Itai; Paukner, Susanne; Zimmerman, Ella; Rozenberg, Haim; Bashan, Anat; Yonath, Ada

2015-01-01

The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid and telithromycin, as well as with a new, highly potent pleuromutilin derivative, BC-3205. These crystal structures shed light on specific structural motifs of the S. aureus ribosome and the binding modes of the aforementioned antibiotics. Moreover, by analyzing the ribosome structure and comparing it with those of nonpathogenic bacterial models, we identified some unique internal and peripheral structural motifs that may be potential candidates for improving known antibiotics and for use in the design of selective antibiotic drugs against S. aureus. PMID:26464510

Overlapping of Serotonin Syndrome with Neuroleptic Malignant Syndrome due to Linezolid-Fluoxetine and Olanzapine-Metoclopramide Interactions: A Case Report of Two Serious Adverse Drug Effects Caused by Medication Reconciliation Failure on Hospital Admission.

PubMed

Mazhar, Faizan; Akram, Shahzad; Haider, Nafis; Ahmed, Rafeeque

2016-01-01

Antipsychotic and antidepressant are often used in combination for the treatment of neuropsychiatric disorders. The concomitant use of antipsychotic and/or antidepressant with drugs that may interact can lead to rare, life-threatening conditions such as serotonin syndrome and neuroleptic malignant syndrome. We describe a patient who has a history of taking two offending drugs that interact with drugs given during the course of hospital treatment which leads to the development of serotonin syndrome overlapped with neuroleptic malignant syndrome. The physician should be aware that both NMS and SS can appear as overlapping syndrome especially when patients use a combination of both antidepressants and antipsychotics.

A review of the current place of glycopeptides in turkish medical practice

PubMed Central

Erdem, Hakan; Oncul, Oral

2007-01-01

Background: Glycopeptide antibiotics are considered by many investigators to be the last resort in the treatment of gram-positive bacterial infections. Objective: The aim of this review was to assess the place of glycopeptides in the treatment of common gram-positive bacteria in accordance with the current epidemiologic data in Turkey. Methods: A search of both the English- and Turkish-language literature indexed on MEDLINE, Ulakbim (Turkey), and Pleksus (Turkey) was performed using the terms: vancomycin, teicoplanin, and glycopeptides, or their Turkish-language counterparts. The complete texts of the articles found in these databases were obtained from the electronic library of Gulhane Medical Academy, Ankara, Turkey. Articles from regional journals, without the support of an electronic format, were obtained by direct communication. Articles of interest were those based on studies occurring in Turkish populations, with special consideration given to publications in press after 2002. Results: Staphylococci were the most frequent gram-positive pathogens encountered in Turkish hospitals. Studies have found that ∼74% of strains were Staphylococcus aureus and the remaining strains were coagulase-negative staphylococci (CoNS). Overall methicillin resistance in staphylococci was reported as ∼60%. In Turkey, S aureus was one of the most common infectious agents found inside hospitals and is deemed a growing threat in the community. While the rate of methicillin resistance in community-acquired isolates is ∼4%, the data from hospitals suggest that reduced resistance comprises most of the isolates. In the studies reviewed, older quinolones like ciprofloxacin and ofloxacin seem to be ineffective in nearly half of the S aureus isolates. Alternatives like rifampicin, gentamicin, tetracycline, trimethoprim/sulfamethoxazole (TMP/SMX), clindamycin, and erythromycin have had substantial resistance profiles in >50% of the strains. In recent Turkish studies, in vitro profiles of linezolid, quinupristin/dalfopristin (QD), and daptomycin have had positive results. As in the S aureus isolates, resistance trends have been observed in the CoNS group of pathogens. The possible use of β-lactams seems restricted, and alternative approaches have become necessary. Quinolones, gentamicin, tetracycline, TMP/SMX, clindamycin, and erythromycin have resistance profiles of >50%. Although glycopeptide resistance was not detected, the frequency of heterogenous vancomycin-intermediate S aureus, a precursor to future resistance, was 13% in 1 study. Current studies in Turkey have found that Enterococcus faecalis comprises three quarters of enterococci while the rest are comprised of Enterococcus faecium. Initial studies performed with linezolid, QD, and daptomycin suggest that these drugs might be effective alternatives for future enterococcal infections that may have high glycopeptide resistance. Approximately 8% of the Streptococcus pneumoniae strains had high-level resistance in Turkey. However, 10 million units of crystallized penicillin or 3 g of oral amoxicillin maintains the optimum treatment of pneumococcal infections outside the central nervous system (CNS). Resistance profiles in third-generation cephalosporins in Turkey range between 2% and 2.5%. Conclusions: In Turkey, a review of the existing literature found that the current use of glycopeptides in pneumococcal infections is restricted to CNS infections facing therapeutic failure in due course. However, the belief that these drugs are the last resort, either in staphylococcal or enterococcal infections, is no longer valid. If a patient has a critical status due to probable gram-positive microorganisms, clinicians should consider the empiric use of glycopeptides. However, new molecules such as linezolid, QD, and daptomycin, offered for use in the treatment of gram-positive bacterial diseases, should be reserved for the future, when glycopeptides eventually become obsolete. PMID:24678118

Evaluation of Interactive Computerized Training to Teach Parents to Implement Photographic Activity Schedules with Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Gerencser, Kristina R.; Higbee, Thomas S.; Akers, Jessica S.; Contreras, Bethany P.

2017-01-01

Training parents of children with autism spectrum disorder can be a challenge due to limited resources, time, and money. Interactive computerized training (ICT)--a self-paced program that incorporates instructions, videos, and interactive questions--is one method professionals can use to disseminate trainings to broader populations. This study…

Effects of a School-Based Social Skills Training Program for Adolescents with Autism Spectrum Disorder and Intellectual Disability

ERIC Educational Resources Information Center

Plavnick, Joshua B.; Kaid, Tiffany; MacFarland, Mari C.

2015-01-01

Social deficits are a core characteristic of individuals with autism spectrum disorders and co-occurring intellectual disabilities (ASD-ID). Despite persistence of these deficits into adolescence, few social skills interventions have been empirically evaluated for older individuals with ASD-ID. The present investigation adapted an efficacious…

Cost-Effectiveness Analysis Comparing Pre-Diagnosis Autism Spectrum Disorder (ASD)-Targeted Intervention with Ontario's Autism Intervention Program

ERIC Educational Resources Information Center

Penner, Melanie; Rayar, Meera; Bashir, Naazish; Roberts, S. Wendy; Hancock-Howard, Rebecca L.; Coyte, Peter C.

2015-01-01

Novel management strategies for autism spectrum disorder (ASD) propose providing interventions before diagnosis. We performed a cost-effectiveness analysis comparing the costs and dependency-free life years (DFLYs) generated by pre-diagnosis intensive Early Start Denver Model (ESDM-I); pre-diagnosis parent-delivered ESDM (ESDM-PD); and the Ontario…

Services Received and Parental Perception of Quality of Life for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Cholewicki, Judith Marie

2015-01-01

With the rapid increase in the rate of children diagnosed with Autism Spectrum Disorder (ASD), there has been a surge in treatment interventions and outcome measures. Treatment interventions consist of evidence-based practices and programs that lack scientific validation. Parents' selection of a treatment or multiple treatments is often based on…

Determinants of Stress in Parents of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rivard, Mélina; Terroux, Amélie; Parent-Boursier, Claudel; Mercier, Céline

2014-01-01

Parents of children with autism spectrum disorder are known to experience more stress than parents of children with any other conditions. The current study describes the parental stress of 118 fathers and 118 mothers at the onset of their children's Early Intensive Behavioral Intervention program. The objectives of the study were to compare…

Health Care Expenditures for Children with Autism Spectrum Disorders in Medicaid

ERIC Educational Resources Information Center

Wang, Li; Leslie, Douglas L.

2010-01-01

Objective: To study trends in health care expenditures associated with autism spectrum disorders (ASDs) in state Medicaid programs. Method: Using Medicaid data from 42 states from 2000 to 2003, patients aged 17 years and under who were continuously enrolled in fee-for-service Medicaid were studied. Patients with claims related to autistic disorder…

Social Competence and Social Skills Training and Intervention for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Cotugno, Albert J.

2009-01-01

This study examined the effectiveness of a 30 week social competence and social skills group intervention program with children, ages 7-11, diagnosed with Autism Spectrum Disorders (ASD). Eighteen children with ASD were assessed with pretreatment and posttreatment measures on the Walker-McConnell Scale (WMS) and the MGH YouthCare Social Competence…

Professional Development Needs for Educators Working with Children with Autism Spectrum Disorders in Inclusive School Environments

ERIC Educational Resources Information Center

Corkum, Penny; Bryson, Susan E.; Smith, Isabel M.; Giffen, Cynthia; Hume, Kym; Power, Ann

2014-01-01

The primary objective of this mixed methods study was to identify educators' professional development needs to determine how best to support them in providing quality programming for children with Autism Spectrum Disorders (ASD) within an inclusive educational system. Information was collected through focus groups with key school board informants…

Impact of a High School Career and Technical Education Program on Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Gogan, Bradley E.

2017-01-01

Autism spectrum disorder rates are climbing in the United States. Because this population is growing, research is needed to understand how to assist these individuals in pursuit of postsecondary educational and employment opportunities. The purpose of this qualitative study, as reflected in the central research question, was to investigate how a…

Effectiveness of a Standardized Equine-Assisted Therapy Program for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Borgi, Marta; Loliva, Dafne; Cerino, Stefania; Chiarotti, Flavia; Venerosi, Aldina; Bramini, Maria; Nonnis, Enrico; Marcelli, Marco; Vinti, Claudia; De Santis, Chiara; Bisacco, Francesca; Fagerlie, Monica; Frascarelli, Massimo; Cirulli, Francesca

2016-01-01

In this study the effectiveness of an equine-assisted therapy (EAT) in improving adaptive and executive functioning in children with autism spectrum disorder (ASD) was examined (children attending EAT, n = 15, control group n = 13; inclusion criteria: IQ > 70). Therapeutic sessions consisted in structured activities involving horses and…

Computing the Power-Density Spectrum for an Engineering Model

NASA Technical Reports Server (NTRS)

Dunn, H. J.

1982-01-01

Computer program for calculating of power-density spectrum (PDS) from data base generated by Advanced Continuous Simulation Language (ACSL) uses algorithm that employs fast Fourier transform (FFT) to calculate PDS of variable. Accomplished by first estimating autocovariance function of variable and then taking FFT of smoothed autocovariance function to obtain PDS. Fast-Fourier-transform technique conserves computer resources.

Brief Report: Problem Solving Therapy in College Students with Autism Spectrum Disorders: Feasibility and Preliminary Efficacy

ERIC Educational Resources Information Center

Pugliese, Cara E.; White, Susan W.

2014-01-01

Students with autism spectrum disorder (ASD), though academically capable, can have difficulty succeeding in college. Evidence-based intervention to promote effective problem solving may improve quality of life, as well as success and satisfaction in college. This study adapted and piloted a group-based cognitive-behavioral intervention program,…

The Effectiveness of Art Therapy for Teaching Social Skills to Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

D'Amico, Miranda; Lalonde, Corinne

2017-01-01

The purpose of this quasi-experimental research study was to evaluate the effectiveness of art therapy for teaching social skills to children with autism spectrum disorder (ASD). The program we tested was structured to provide a therapeutic setting for children to discuss difficulties they experience in their social interactions, and give them…

Infusing a Peer-to-Peer Support Program with Adventure Therapy for Adolescent Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Karoff, Maggie; Tucker, Anita R.; Alvarez, Tony; Kovacs, Patricia

2017-01-01

Background: Key findings from the literature on treatment interventions with youth with Autism Spectrum Disorder (ASD) indicate that the most successful approaches allow frequent opportunities for uncontrived social interactions and are customizable to the needs of individuals and the group. Adventure therapy meets these criteria while providing…

Using Family Leisure Activities to Support Families Living with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Lock, Robin H.; Hendricks, C. Bret; Bradley, Loretta J.; Layton, Carol A.

2010-01-01

Support for families of children with autism spectrum disorders continues to be important, but formal support groups may not ft every need. The authors describe Family Fun Days, a program that paired leisure activities with opportunities for support. There was an increase in the number of participants over traditional support meetings,…

Brief Report of Preliminary Outcomes of an Emotion Regulation Intervention for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Thomson, Kendra; Burnham Riosa, Priscilla; Weiss, Jonathan A.

2015-01-01

Children with autism spectrum disorder (ASD) often present with comorbid psychopathology including problems with emotion regulation. The goal of the present research was to investigate the feasibility of a multicomponent manualized cognitive behavior therapy treatment program for improving emotion regulation in youth with ASD 8-12 years of age.…

Effects of ABRACADBRA Instruction on Spelling in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Bailey, Benjamin; Arciuli, Joanne; Stancliffe, Roger J.

2017-01-01

This study explored the effects of an evidence-based literacy program, ABRACADABRA, on the spelling abilities of children with autism spectrum disorder (ASD). Twenty children with ASD aged 5-11 years were assigned to matched instruction and waitlist control groups. Children in the instruction group received 26 hrs of individualized, home-based…

Efficacy of Caregiver-Mediated Joint Engagement Intervention for Young Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Chiang, Chung-Hsin; Chu, Ching-Lin; Lee, Tsung-Chin

2016-01-01

Joint attention intervention for children with autism spectrum disorders was focused on improving joint engagement and joint attention skills. The purpose of this study was to develop a caregiver-mediated joint engagement intervention program combined with body movement play to investigate the effects of joint engagement/joint attention skills in…

Early Intervention Outcomes for Toddlers with Autism Spectrum Disorder and Their Families

ERIC Educational Resources Information Center

Noyes-Grosser, Donna M.; Elbaum, Batya; Wu, Yan; Siegenthaler, Kirsten M.; Cavalari, Rachel S.; Gillis, Jennifer M.; Romanczyk, Raymond G.

2018-01-01

Autism spectrum disorder (ASD) can be diagnosed as early as 18 months of age. State Early Intervention (EI) programs under Part C of the Individuals with Disabilities Education Act (IDEA) are serving increasing numbers of children with ASD; however, little is known about outcomes of these services. This study evaluated the impact of EI for…

Avoiding the "Brick Wall of Awkward": Perspectives of Youth with Autism Spectrum Disorder on Social-Focused Intervention Practices

ERIC Educational Resources Information Center

Bottema-Beutel, Kristen; Mullins, Teagan S.; Harvey, Michelle N.; Gustafson, Jenny R.; Carter, Erik W.

2016-01-01

Many youth with autism spectrum disorder participate in school-based, peer-mediated intervention programs designed to improve their social experiences. However, there is little research discerning how these youth view intervention practices currently represented in the literature, information which could improve the social validity of intervention…

Assessment, Intervention, and Training Needs of Service Providers for Children with Intellectual Disabilities or Autism Spectrum Disorders and Concurrent Problem Behaviours

ERIC Educational Resources Information Center

Rivard, Mélina; Morin, Diane; Dionne, Carmen; Mello, Catherine; Gagnon, Marc-André

2015-01-01

This study documented the perceived needs of therapists, specialists, and managers who work with children with intellectual disabilities (ID) and/or autism spectrum disorders (ASD) and concurrent problem behaviours (PBs). Seventy-five respondents from specialized PB and early childhood programs within eight public rehabilitation centres were…

Teaching Reading Comprehension and Language Skills to Students with Autism Spectrum Disorders and Developmental Disabilities Using Direct Instruction

ERIC Educational Resources Information Center

Flores, Margaret M.; Nelson, Cynthia; Hinton, Vanessa; Franklin, Toni M.; Strozier, Shaunita D.; Terry, LaTonya; Franklin, Susan

2013-01-01

There is limited research demonstrating Direct Instruction (DI) as an effective reading comprehension intervention for students with autism spectrum disorders (ASD) and developmental disabilities (DD). Previous research has shown that DI, when portions of the program were implemented, resulted in increased skills (Flores & Ganz, 2007; Flores…

Evidence-Based Practices in Interventions for Children and Youth with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Odom, Samuel L.; Collet-Klingenberg, Lana; Rogers, Sally J.; Hatton, Deborah D.

2010-01-01

Evidence-based practices (EBPs) are the basis on which teachers and other service providers are required to design educational programs for learners with autism spectrum disorders (ASD). As part of their work with the National Professional Development Center (NPDC) on ASD, researchers developed a process for reviewing the research literature and…

Evaluation of Two Instruction Methods to Increase Employment Options for Young Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Burke, Raymond V.; Andersen, Melissa N.; Bowen, Scott L.; Howard, Monica R.; Allen, Keith D.

2010-01-01

We evaluated the efficacy of a vocational training program including behavioral skills training, and a "performance cue system" (i.e., a proprietary iPhone application adapted for the study) to teach targeted social-vocational skills to six young adults with an Autism Spectrum Disorder. In two separate studies, participants were employed…

Considering Homeschooling Your Child on the Autism Spectrum? Some Helpful Hints and Suggestions for Parents

ERIC Educational Resources Information Center

Hurlbutt, Karen

2010-01-01

With the increase in the numbers of diagnosed children on the autism spectrum, schools are being challenged to provide proper educational services for these children. In Educating Children with Autism, the National Research Council recommended that educational programs for students with autism include three basic components. These are direct…

Instructional Design, Autism Spectrum Disorders, and Online Learning: What's Being Done?

ERIC Educational Resources Information Center

Pearson, Laurie A.

2014-01-01

It is now estimated that 1 in 88 children have autism. As children diagnosed with this disorder continues to increase, so does the demand for appropriate educational programs that meet the diverse needs of the students on the autism spectrum. Results of this basic qualitative study, which included 15 instructional designers who create online…

Use of Superheroes Social Skills with Middle School-Age Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Murphy, Ashley N.; Radley, Keith C.; Helbig, Kate A.

2018-01-01

The current study evaluated use of the Superheroes Social Skills program as a means of increasing social skill accuracy in adolescents with autism spectrum disorder. Participants included four Caucasian male students that were eligible for special education services within the autism category. Social skills training was presented twice weekly for…

Autism Spectrum Disorder and Youth Sports: The Role of the Sports Manager and Coach

ERIC Educational Resources Information Center

Ohrberg, N. Jonas

2013-01-01

The number of children diagnosed with autism spectrum disorder (ASD) is rapidly increasing throughout the United States. This increase also has an impact on participation in local community programs such as youth sports and recreational activities. The administrators of these agencies and departments will be required to develop and implement…

Indicators of Intellectual Disabilities in Young Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rivard, Mélina; Terroux, Amélie; Mercier, Céline; Parent-Boursier, Claudel

2015-01-01

No agreement has been reached yet on the co-occurrence of Intellectual Disability (ID) and Autism Spectrum Disorders (ASD) in young children. This study describes the clinical profiles of 253 children with ASD between 30 and 65 months old, on IQ and adaptive behaviors, prior to their entry in an early behavioral intervention program. Results…

Medicaid 1915(c) Home- and Community-Based Services Waivers for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Velott, Diana L.; Agbese, Edeanya; Mandell, David; Stein, Bradley D.; Dick, Andrew W.; Yu, Hao; Leslie, Douglas L.

2016-01-01

This research aims to describe the characteristics of 1915(c) Home- and Community-Based Services waivers for children with autism spectrum disorder across states and over time. While increasingly popular, little is known about these Medicaid waivers. Understanding the characteristics of these programs is important to clinicians and policymakers in…

Effects of a Social Skills Intervention on Children with Autism Spectrum Disorder and Peers with Shared Deficits

ERIC Educational Resources Information Center

Radley, Keith C.; O'Handley, Roderick D.; Battaglia, Allison A.; Lum, John D. K.; Dadakhodjaeva, Komila; Ford, William B.; McHugh, Melissa B.

2017-01-01

The current study evaluated the effects of the "Superheroes Social Skills" program (Jenson et al. 2011) in promoting accurate demonstration of target social skills in training and generalization conditions in young children with autism spectrum disorder (ASD) and peers with shared social deficits. Three preschool-age children with ASD…

The Heavy Burden of Psychiatric Comorbidity in Youth with Autism Spectrum Disorders: A Large Comparative Study of a Psychiatrically Referred Population

ERIC Educational Resources Information Center

Joshi, Gagan; Petty, Carter; Wozniak, Janet; Henin, Aude; Fried, Ronna; Galdo, Maribel; Kotarski, Meghan; Walls, Sarah; Biederman, Joseph

2010-01-01

The objective of the study was to systematically examine patterns of psychiatric comorbidity in referred youth with autism spectrum disorders (ASD) including autistic disorder and pervasive developmental disorder not otherwise specified. Consecutively referred children and adolescents to a pediatric psychopharmacology program were assessed with…

Brief Report: Treating Stuttering in an Adult with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Brundage, Shelley B.; Whelan, Cory J.; Burgess, Cathleen M.

2013-01-01

Stuttering and autism can co-occur and when they do it presents a significant communication challenge. This study examined the effectiveness of a modified version of the fluency rules program (FRP; Runyan and Runyan, Stuttering and related disorders of fluency, in 2007) to reduce stuttering frequency in a man with autism spectrum disorder (ASD).…

The orbifolder: A tool to study the low-energy effective theory of heterotic orbifolds

NASA Astrophysics Data System (ADS)

Nilles, H. P.; Ramos-Sánchez, S.; Vaudrevange, P. K. S.; Wingerter, A.

2012-06-01

The orbifolder is a program developed in C++ that computes and analyzes the low-energy effective theory of heterotic orbifold compactifications. The program includes routines to compute the massless spectrum, to identify the allowed couplings in the superpotential, to automatically generate large sets of orbifold models, to identify phenomenologically interesting models (e.g. MSSM-like models) and to analyze their vacuum configurations. Program summaryProgram title: orbifolder Catalogue identifier: AELR_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AELR_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 3 No. of lines in distributed program, including test data, etc.: 145 572 No. of bytes in distributed program, including test data, etc.: 930 517 Distribution format: tar.gz Programming language:C++ Computer: Personal computer Operating system: Tested on Linux (Fedora 15, Ubuntu 11, SuSE 11) Word size: 32 bits or 64 bits Classification: 11.1 External routines: Boost (http://www.boost.org/), GSL (http://www.gnu.org/software/gsl/) Nature of problem: Calculating the low-energy spectrum of heterotic orbifold compactifications. Solution method: Quadratic equations on a lattice; representation theory; polynomial algebra. Running time: Less than a second per model.

Effectiveness of a Standardized Equine-Assisted Therapy Program for Children with Autism Spectrum Disorder.

PubMed

Borgi, Marta; Loliva, Dafne; Cerino, Stefania; Chiarotti, Flavia; Venerosi, Aldina; Bramini, Maria; Nonnis, Enrico; Marcelli, Marco; Vinti, Claudia; De Santis, Chiara; Bisacco, Francesca; Fagerlie, Monica; Frascarelli, Massimo; Cirulli, Francesca

2016-01-01

In this study the effectiveness of an equine-assisted therapy (EAT) in improving adaptive and executive functioning in children with autism spectrum disorder (ASD) was examined (children attending EAT, n = 15, control group n = 13; inclusion criteria: IQ > 70). Therapeutic sessions consisted in structured activities involving horses and included both work on the ground and riding. Results indicate an improvement in social functioning in the group attending EAT (compared to the control group) and a milder effect on motor abilities. Improved executive functioning was also observed (i.e. reduced planning time in a problem-solving task) at the end of the EAT program. Our findings provide further support for the use of animal-assisted intervention programs as complementary intervention strategies for children with ASD.

NASA Langley/CNU Distance Learning Programs.

ERIC Educational Resources Information Center

Caton, Randall; Pinelli, Thomas E.

NASA Langley Research Center and Christopher Newport University (CNU) provide, free to the public, distance learning programs that focus on math, science, and/or technology over a spectrum of education levels from K-adult. The effort started in 1997, and currently there are a suite of five distance-learning programs. This paper presents the major…

Exploring Perspectives on Child Care with Families of Children with Autism

ERIC Educational Resources Information Center

Mereoiu, Mariana; Bland, Carol; Dobbins, Nicole; Niemeyer, Judith A.

2015-01-01

Early childhood programs serve increasing numbers of children with autism spectrum disorders (ASD) and their families. While many programs have made significant progress in providing educational services responsive to the needs of children with ASD, concerns persist about whether early education programs can meet the educational needs of such…

The Early Intervention Readiness Program (EIRP): A Post-ASD Diagnosis Family Support Program

ERIC Educational Resources Information Center

Tolmie, Rhiannon S.; Bruck, Susan; Kerslake, Rachel

2017-01-01

A child's diagnosis with autism spectrum disorder (ASD) can be an extremely stressful time for families. Researchers suggest that the period immediately following ASD diagnosis is a key time for professionals to guide families by providing appropriate information about support options. This article describes a family support program, developed by…

Family Literacy Programs: Where Have They Come from and Where Are They Going?

ERIC Educational Resources Information Center

Doyle, Antoinette

2012-01-01

Family literacy programs in North America and the United Kingdom have enjoyed widespread public and political support. Thousands of initiatives following a variety of models currently operate under the spectrum of family literacy programs. In this paper, the influence of learning theories, the research on children's early literacy development, and…

The Role of the New mTOR Complex, MTORC2, in Autism Spectrum Disorders

DTIC Science & Technology

2014-10-01

AWARD NUMBER: W81XWH-13-1-0380 TITLE: “The Role of the New mTOR complex, MTORC2, in Autism Spectrum Disorders” PRINCIPAL INVESTIGATOR: Mauro...THE NEW MTOR COMPLEX, MTORC2, IN AUTISM SPECTRUM DISORDERS” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0380 5c. PROGRAM ELEMENT NUMBER 6...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goal of my DOD-supported research is determine the role of the new mTOR complex (mTORC2) in

78 FR 50399 - Spectrum Monitoring Pilot Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... National Telecommunications and Information Administration (NTIA) to design and conduct a pilot program to... to Congress for fiscal year (FY) 2014 seeks an initial $7.5 million research and development... design, features, deployment options, operational parameters, expected utility, potential benefits, and...

Pilot Study of a Parent Training Program for Young Children with Autism: The PLAY Project Home Consultation Program

ERIC Educational Resources Information Center

Solomon, Richard; Necheles, Jonathan; Ferch, Courtney; Bruckman, David

2007-01-01

The PLAY Project Home Consultation (PPHC) program trains parents of children with autistic spectrum disorders using the DIR/Floortime model of Stanley Greenspan MD. Sixty-eight children completed the 8-12 month program. Parents were encouraged to deliver 15 hours per week of 1:1 interaction. Pre/post ratings of videotapes by blind raters using the…

Optimization techniques applied to spectrum management for communications satellites

NASA Astrophysics Data System (ADS)

Ottey, H. R.; Sullivan, T. M.; Zusman, F. S.

This paper describes user requirements, algorithms and software design features for the application of optimization techniques to the management of the geostationary orbit/spectrum resource. Relevant problems include parameter sensitivity analyses, frequency and orbit position assignment coordination, and orbit position allotment planning. It is shown how integer and nonlinear programming as well as heuristic search techniques can be used to solve these problems. Formalized mathematical objective functions that define the problems are presented. Constraint functions that impart the necessary solution bounds are described. A versatile program structure is outlined, which would allow problems to be solved in stages while varying the problem space, solution resolution, objective function and constraints.

Inoculum Effects of Ceftobiprole, Daptomycin, Linezolid, and Vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at Inocula of 105 and 107 CFU Injected into Opposite Thighs of Neutropenic Mice

PubMed Central

Lee, Dong-Gun; Murakami, Yoichi; Andes, David R.

2013-01-01

Reduced bactericidal efficacy at a high inoculum is known as the inoculum effect (IE). We used neutropenic mice to compare the IEs of ceftobiprole (CFB), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6 to 9 strains of Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in opposite thighs of the same mice. Neutropenic mice had 104.5 to 105.7 CFU/thigh (low inoculum [LI]) in one thigh and 106.4 to 107.2 CFU/thigh (high inoculum [HI]) in the opposite thigh when treated for 24 h with subcutaneous (s.c.) doses every 12 h of DAP at 0.024 to 100 mg/kg of body weight and LZD at 0.313 to 320 mg/kg and s.c. doses every 6 h of CFB at 0.003 to 160 mg/kg and VAN at 0.049 to 800 mg/kg. Dose-response data were analyzed by a maximum effect (Emax) model using nonlinear regression. Static doses for each drug and at each inoculum were calculated, and the difference between HI and LI (IE index) gave the magnitude of IE for each drug-organism combination. Mean (range) IE indexes of S. aureus were 2.9 (1.7 to 4.6) for CFB, 4.1 (2.6 to 9.3) for DAP, 4.6 (1.7 to 7.1) for LZD, and 10.1 (6.3 to 20.3) for VAN. In S. pneumoniae, the IE indexes were 2.5 (1.3 to 3.3) for CFB, 2.0 (1.6 to 2.8) for DAP, 1.9 (1.7 to 2.2) for LZD, and 1.5 (0.8 to 3.2) for VAN; these values were similar for all drugs. In S. aureus, the IE was much larger with VAN than with CFB, DAM, and LZD (P < 0.05). An in vivo time course of vancomycin activity showed initiation of killing at 4- to 16-fold-higher doses at HI than at LI despite similar initial growth of controls. PMID:23295932

[Vocational Training and Job Placement for People with Autism Spectrum Disorders in the Business Sector].

PubMed

Suzuki, Keita

2015-01-01

Kaien was founded in 2009 in order to help people with autism spectrum disorders work by leveraging their unique capabilities. Our four offices are all located in the Tokyo Metropolitan Area. Our services include job training and placement for adults, career awareness programs for college students, and career experience programs for teens with autism spectrum disorders. Currently, we help over 100 people on a daily basis. We believe that two factors play important roles when we provide job training programs for people. Firstly, they usually find it difficult to identify their occupational "fit" by themselves due to their weakness regarding imagination. It is not a good idea to convince them only through counseling. Rather, when we take their weaknesses into consideration, multiple trial sessions in the work environment are key because even people without imagination can understand their occupational "fit" once they try. The other aspect is to articulate communication as much as possible. In this case, it is also true that words are not enough to help people fully develop the communication skills necessary in an office. Thus, our trainers intervene very frequently in the job programs in order for trainees to get feedback at the right time on the spot. In other words, our five-year experience at Kaien has revealed that our "Here and Now" approach in the quasi-work environment is the most effective way. Most of our trainers do not have medical or social welfare backgrounds. This fact has revealed huge possibilities when it comes to helping people with autism spectrum disorders to get a job. That is, in many cases, autism experts may not be mandatory, and supervisors or colleagues, who work with people with autism every day, can become "job supporters" with a little knowledge and some training. Some estimates indicate that the prevalence rate of autism spectrum disorders is above one in one hundred, and might be as high as five or six percent. This number is daunting because only autism experts with marked experience cannot handle all issues. Therefore, we believe that empowering amateur supporters in the business arena is important, and we are thrilled to think that our findings and programs may be helpful to increase the proficiency of such amateur supporters.

Social Media Use as a Third Place for Community College Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Eckhardt, Scott C.

2017-01-01

In recent years, statistics have displayed a consistent increase in the enrollment in college programs of students with autism spectrum disorder (ASD). The research has explained that ASD college students currently face academic and social barriers as they transition to the college setting. There is reason to believe that the use of online…

Parent and Family Outcomes of PEERS: A Social Skills Intervention for Adolescents with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Karst, Jeffrey S.; Van Hecke, Amy Vaughan; Carson, Audrey M.; Stevens, Sheryl; Schohl, Kirsten; Dolan, Bridget

2015-01-01

Raising a child with an Autism Spectrum Disorder (ASD) is associated with increased family chaos and parent distress. Successful long-term treatment outcomes are dependent on healthy systemic functioning, but the family impact of treatment is rarely evaluated. The Program for the Education and Enrichment of Relational Skills (PEERS) is a social…

Feasibility and Initial Efficacy of a Comprehensive School-Based Intervention for High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Lopata, Christopher; Thomeer, Marcus L.; Volker, Martin A.; Lee, Gloria K.; Smith, Tristram H.; Smith, Rachael A.; Mcdonald, Christin A.; Rodgers, Jonathan D.; Lipinski, Alanna M.; Toomey, Jennifer A.

2012-01-01

This study examined the feasibility and initial efficacy of a comprehensive school-based intervention (CSBI) for 12 children with high-functioning autism spectrum disorders, aged 6 to 9 years. Treatment included a 3-week summer preparation program followed by a 10-month CSBI, comprising social skills groups, therapeutic activities, face and voice…

Project SEARCH for Youth with Autism Spectrum Disorders: Increasing Competitive Employment on Transition from High School

ERIC Educational Resources Information Center

Wehman, Paul; Schall, Carol; McDonough, Jennifer; Molinelli, Alissa; Riehle, Erin; Ham, Whitney; Thiss, Weston R.

2013-01-01

Supporting youth with autism spectrum disorder (ASD) in the transition to adulthood is challenging. This article provides a description of how Project SEARCH, a model transition program for youth with disabilities, was used to help youth with ASD gain competitive employment. This article includes two case studies and a thorough description of the…

Teaching Language Skills to Preschool Students with Developmental Delays and Autism Spectrum Disorder Using Language for Learning

ERIC Educational Resources Information Center

Flores, Margaret M.; Schweck, Kelly B.; Hinton, Vanessa

2016-01-01

Language intervention using Direct Instruction (DI) has shown positive results. There is a growing body of investigation of Language for Learning (LL), a DI program, on the performance of students with autism spectrum disorders (ASD) and students with developmental delays (DD). There is need for replication and extension of research to include…

Applying an Implementation Science Framework for Adoption of a Comprehensive Program for High School Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Odom, Samuel L.; Duda, Michelle A.; Kucharczyk, Suzanne; Cox, Ann W.; Stabel, Aaron

2014-01-01

Post-school outcomes for adolescents and young adults with autism spectrum disorder (ASD) are exceedingly poor. The convergence of adolescence as a development period, the expression of ASD during adolescence, and the complicated logistic nature of high schools create a perfect storm of complexity that may pose challenges and establish barriers to…

Examining the Clinical Correlates of Autism Spectrum Disorder in Youth by Ascertainment Source

ERIC Educational Resources Information Center

Joshi, Gagan; Faraone, Stephen V.; Wozniak, Janet; Petty, Carter; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L.; McDermott, Katie; Epstien, Cecily; Walker, Rosemary; Caron, Ashley; Feinberg, Leah; Biederman, Joseph

2014-01-01

To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. ASD youth referred to a specialized ambulatory program for ASD (N = 143) were compared to ASD youth referred to a general child psychiatry clinic (N = 217). More ASD clinic youth met criteria…

Targeting Heterogeneity and Comorbidity in Children with Autism Spectrum Disorder through the Resilience Builder Group Therapy Program

ERIC Educational Resources Information Center

Habayeb, Serene; Rich, Brendan; Alvord, Mary K.

2017-01-01

Background: Children with autism spectrum disorders (ASD) often carry co-morbid diagnoses and present with impairing heterogeneous symptomatology (Leyfer et al. in "J Autism Dev Disord" 36(7): 849-861, 2006. doi:10.1007/s10803-006-0123-0). However, research from controlled laboratory settings often fails to examine the vast number of…

Metaphor Comprehension in Autistic Spectrum Disorders: Case Studies of Two High-Functioning Children

ERIC Educational Resources Information Center

Melogno, Sergio; D'Ardia, Caterina; Pinto, Maria Antonietta; Levi, Gabriel

2012-01-01

This article presents case studies on metaphor comprehension in two boys with high-functioning autistic spectrum disorder, aged 9;1 (9 years, 1 month) and 8;11. The participants were assessed twice, before and after an intervention program aimed at improving their social skills. The focus of the article is on the specific patterns exhibited by…

Open-Trial Pilot Study of a Comprehensive School-Based Intervention for High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Lopata, Christopher; Thomeer, Marcus L.; Volker, Martin A.; Lee, Gloria K.; Smith, Tristram H.; Rodgers, Jonathan D.; Smith, Rachael A.; Gullo, Gaetano; McDonald, Christin A.; Mirwis, Joshua; Toomey, Jennifer A.

2013-01-01

There is a notable lack of manualized comprehensive school-based interventions (CSBIs) for children with high-functioning autism spectrum disorders (HFASDs). This pilot study examined the feasibility and initial efficacy of a CSBI for 12 children with HFASDs, aged 6 to 9 years. Treatment included a 3-week summer preparation program followed by a…

Effects of a Prototypical Training Program on the Implementation of Systematic Observational Data Collection on IEP Objectives for the Core Deficits of Autism Spectrum Disorders

ERIC Educational Resources Information Center

Harkins, Jessica L.

2013-01-01

Legal mandates and best practice recommendations for the education of students with autism spectrum disorders (ASD) emphasize the importance of systematic, ongoing observational data collection in order to monitor progress and demonstrate accountability. The absence of such documentation in decision-making on instructional objectives indicates a…

Effectiveness of the Picture Exchange Communication System (PECS) on Communication and Speech for Children with Autism Spectrum Disorders: A Meta-Analysis

ERIC Educational Resources Information Center

Flippin, Michelle; Reszka, Stephanie; Watson, Linda R.

2010-01-01

Purpose: The Picture Exchange Communication System (PECS) is a popular communication-training program for young children with autism spectrum disorders (ASD). This meta-analysis reviews the current empirical evidence for PECS in affecting communication and speech outcomes for children with ASD. Method: A systematic review of the literature on PECS…

An Evaluation of a Social Skills Intervention for Adults with Autism Spectrum Disorder and Intellectual Disabilities Preparing for Employment in Ireland: A Pilot Study

ERIC Educational Resources Information Center

Walsh, Edith; Holloway, Jennifer; Lydon, Helena

2018-01-01

Individuals with autism spectrum disorder (ASD) are faced with significant barriers relating to employment opportunities and workplace participation. This study evaluated the effectiveness of the Walker social skills curriculum: the ACCESS program and video modeling to increase social communication skills necessary for workplace inclusion.…

Effects of the Relationship Enhancement® Program on Social Skills, Empathy and Social Support for Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Cunningham, Alexandra

2014-01-01

An important area of research is emerging for adults diagnosed with autism spectrum disorders (ASD) with respect to the challenges they face in their social relationships. Social relationships include those that are romantic in nature such as dating, cohabitation and marriage. Researchers suggest that engaging in a healthy and happy romantic…