Inappropriate Use of Aztreonam.

BACKGROUND: Aztreonam is not a preferred empiric antibiotic because of variable susceptibilities compared with alternative agents. In addition, it has no Gram-positive activity, necessitating coadministration with vancomycin when used empirically, and is more costly when compared with other Gram-negative active agents. Aztreonam is often given to patients with a reported penicillin allergy without further investigation into the reaction or other relevant allergy information. STUDY QUESTION: How frequently is aztreonam being used inappropriately? STUDY DESIGN: We conducted a retrospective chart review at an academic medical center to assess the appropriateness of our aztreonam use. MEASURES AND OUTCOMES: Our primary outcome was frequency of appropriate aztreonam use, based on a true IgE-mediated allergy reported for each patient. We evaluated whether the patients had tolerated a beta-lactam in the past, and what the reported allergic reaction was. RESULTS: We included 165 patients and found that 46.7% of our aztreonam use was inappropriate, based on previous use of a beta-lactam, or no documentation of an IgE-mediated response. Of the patients with a documented beta-lactam allergy, 63 (38.2%) patients had no allergy manifestation listed, and 37 (22.4%) patients had a non-IgE-mediated allergy manifestation. Of the total population, 61 (37%) patients had tolerated a beta-lactam in the past. CONCLUSIONS: Aztreonam should be avoided, except in the case of a true IgE-mediated allergic reaction. Our goal was to reduce the inappropriate use of aztreonam at our institution by one or more of the following: educating providers, reviewing aztreonam orders, requiring answering of order questions, or requiring an indication for use. Penicillin skin testing and desensitization are options as well.

Plasma-Etched Pattern Transfer of Sub-10 nm Structures Using a Metal-Organic Resist and Helium Ion Beam Lithography.

Field-emission devices are promising candidates to replace silicon fin field-effect transistors as next-generation nanoelectronic components. For these devices to be adopted, nanoscale field emitters with nanoscale gaps between them need to be fabricated, requiring the transfer of, for example, sub-10 nm patterns with a sub-20 nm pitch to substrates like silicon and tungsten. New resist materials must therefore be developed that exhibit the properties of sub-10 nm resolution and high dry etch resistance. A negative tone, metal-organic resist is presented here. It can be patterned to produce sub-10 nm features when exposed to helium ion beam lithography at line doses on the order of tens of picocoulombs per centimeter. The resist was used to create 5 nm wide, continuous, discrete lines spaced on a 16 nm pitch in silicon and 6 nm wide lines on an 18 nm pitch in tungsten, with line edge roughness of 3 nm. After the lithographic exposure, the resist demonstrates high resistance to silicon and tungsten dry etch conditions (SF6 and C4F8 plasma), allowing the pattern to be transferred to the underlying substrates. The resist's etch selectivity for silicon and tungsten was measured to be 6.2:1 and 5.6:1, respectively; this allowed 3 to 4 nm thick resist films to yield structures that were 21 and 19 nm tall, respectively, while both maintained a sub-10 nm width on a sub-20 nm pitch.

Sofosbuvir: A Nucleotide NS5B Inhibitor for the Treatment of Chronic Hepatitis C Infection.

OBJECTIVE: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. DATA SYNTHESIS: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. CONCLUSION: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..

Effects of aggregate and individual antibiotic exposure on vancomycin MICs for Staphylococcus aureus isolates recovered from pediatric patients.

We evaluated the evolution of vancomycin MICs for Staphylococcus aureus and their relationship with vancomycin use among hospitalized children. S. aureus isolates recovered from sterile sites were prospectively tested for vancomycin susceptibility using the Etest between 1 April 2000 and 31 March 2008. Vancomycin MICs were grouped into three categories: ≤ 1, 1.5, and 2 µg/ml. The association between vancomycin MICs and aggregate vancomycin use and individual patient vancomycin exposure 6 months prior to the documented infection was assessed. The geometric mean values for vancomycin MICs for S. aureus fluctuated over time without a significant trend (P = 0.146). Of the 436 patients included in the study, 363 (83%) had methicillin-susceptible S. aureus (MSSA) and 73 (17%) had methicillin-resistant S. aureus (MRSA) infections. The rate of isolates with a vancomycin MIC of 2 µg/ml increased from 4% (2 of 46) in 2000 to 2001 to 24% (11 of 46) in 2007 to 2008, despite a decrease in vancomycin use (r = -0.11; P = 0.825). The percentage of isolates with a vancomycin MIC of 2 µg/ml was higher for MRSA (15%; 11 of 73) than for MSSA strains (5.2%; 19 of 363) (χ(2) = 9.2; P = 0.01). Individual patient vancomycin exposure was not associated with a higher vancomycin MIC. In the unadjusted model, in which we compared patients with S. aureus infections with MICs of ≤ 1 µg/ml, the odds ratios of exposure rates for patients with isolates with MICs of 1.5 µg/ml and 2 µg/ml were 1.02 (P = 0.929) and 1.13 (P = 0.767), respectively. In our experience, the geometric means of vancomycin MICs from S. aureus isolates recovered from hospitalized children oscillated over time and were not associated with previous individual patient vancomycin exposure or aggregate vancomycin use.

Clinical outcomes with ertapenem as a first-line treatment option of infections caused by extended-spectrum ß-lactamase producing gram-negative bacteria.

BACKGROUND: Infections caused by extended-spectrum ß-lactamase (ESBL)-producing gram-negative organisms are a growing concern in hospitalized patients. Traditionally, these infections can be effectively treated by the carbapenem class of drugs. In 2005, our institution initiated a protocol for use of ertapenem, a carbapenem, as the first-line treatment option for these infections. It is unknown whether ertapenem is associated with similar clinical response and microbiologic cure rates as those achieved with group 2 carbapenems (imipenem, meropenem, doripenem). OBJECTIVE: To describe clinical response and microbiologic cure rates associated with ertapenem as first-line treatment of infections caused by ESBL-producing organisms. METHODS: This case series included patients who received ertapenem for more than 48 hours to treat a documented infection with a positive culture for an ESBL-producing organism. Efficacy was determined by the clinical response and microbiologic cure rates achieved with ertapenem. RESULTS: Seventy-three patients received ertapenem for a mean (SD) of 10.7 (5.9) days. The most common (59%) infection site was urine. The most common causative organisms were ESBL-producing Klebsiella pneumoniae (47%) and Escherichia coli (48%). Clinical response was observed in 78% of patients. Microbiologic cure was achieved in 92% of the evaluable population (n = 50). There were no significant differences in clinical or microbiologic cure rates across important subgroups. CONCLUSIONS: Patients treated with ertapenem achieved favorable clinical response and microbiologic cure rates. Our data suggest that ertapenem can be used as an alternative to group 2 carbapenems for the treatment of infections caused by ESBL-producing gram-negative organisms.

Successful prolonged treatment of a carbapenem-resistant Acinetobacter baumannii hip infection with cefiderocol: A case report.

We report a 50-year-old Caucasian male with a complicated past medical history who developed extensive polymicrobial osteomyelitis, including a carbapenem-resistant Acinetobacter baumannii (CRAB). In order to streamline therapy, the patient received compassionate use cefiderocol for 6 weeks which was well tolerated. In addition, the patient's infection was considered cured at end of treatment. Few cases on the use of prolonged cefiderocol for treatment of osteomyelitis due to CRAB have been published. Our patient did not report adverse reactions, nor did he develop laboratory abnormalities which were assessed throughout and at the end of the 6-week course.

Medical Management of Endocarditis Caused by Stenotrophomonas maltophilia: A Case Report.

A 44-year-old female was found to be systemically ill at dialysis and admitted to the hospital. Days into the hospitalization, her blood cultures from dialysis were positive with Stenotrophomonas maltophilia bacteremia with a levofloxacin minimum inhibitory concentration (MIC) of 1. She was discharged on ciprofloxacin 500 mg orally (PO) daily on hospital day 2 to complete a 14-day course. Weeks later, she was again found to be bacteremic at dialysis and sent back to the hospital. She was started on empiric antibiotics upon admission until further identification. Blood cultures again revealed S. maltophilia with a levofloxacin MIC of 32. Antibiotics were tailored to trimethoprim/sulfamethoxazole (TMP-SMX) until susceptibilities for additional agents were available. Further workup revealed mitral valve endocarditis. She was subsequently discharged on both minocycline 100 mg PO every 12 hours and TMP-SMX 1 DS PO daily with a planned duration of 6 weeks. Due to ongoing readmissions for hyperkalemia, TMP-SMX was discontinued and her regimen was modified to ceftazidime 1 g intravenously (IV) after HD plus minocycline 100 mg PO every 12 hours. She was deemed clinically and microbiologically cleared based on follow-up assessments. To our knowledge, this is the first case of S. maltophilia endocarditis treated with oral minocycline in combination with another antibiotic.

Trends of fluoroquinolone-resistant Escherichia coli amongst urinary isolates in children: a 10 year surveillance study.

We evaluated 3122 children with E. coli urinary isolates over a 10 year period in order to assess the emergence of fluoroquinolone resistance. Susceptibilities remained stable; however, hospitalized children had a statistically higher risk of developing fluoroquinolone-resistant isolates when compared with outpatients. Stewardship monitoring of fluoroquinolone use amongst hospitalized children is warranted.

The quest for the best metric of antibiotic use and its correlation with the emergence of fluoroquinolone resistance in children.

We evaluated the correlation between fluoroquinolone use, measured by doses administered and days of therapy, with the emergence of ciprofloxacin and levofloxacin resistance among Gram-negative bacilli infections in children hospitalized at one pediatric center between April 2001 and March 2009. Both metrics and drug resistance were highly correlated.

AtGRP2, a cold-induced nucleo-cytoplasmic RNA-binding protein, has a role in flower and seed development.

The glycine-rich protein AtGRP2 is one of the four members of the cold-shock domain (CSD) protein family in Arabidopsis. It is characterized by the presence of a nucleic acid-binding CSD domain, two glycine-rich domains and two CCHC zinc-fingers present in nucleic acid-binding proteins. In an attempt to further understand the role of CSD/GRP proteins in plants, we have proceeded to the functional characterization of the AtGRP2 gene. Here, we demonstrate that AtGRP2 is a nucleo-cytoplasmic protein involved in Arabidopsis development with a possible function in cold-response. Expression analysis revealed that the AtGRP2 gene is active in meristematic tissues, being modulated during flower development. Down-regulation of AtGRP2 gene, using gene-silencing techniques resulted in early flowering, altered stamen number and affected seed development. A possible role of AtGRP2 as an RNA chaperone is discussed.

Sugarcane expressed sequences tags (ESTs) encoding enzymes involved in lignin biosynthesis pathways

Ligninas säo compostos fenólicos encontrados nas paredes secundárias do sistema vascular vegetal e desempenham importantes papéis biológicos, reduzindo a permeabilidade da parede celular em relaçäo à água, estando também envolvidas em mecanismos de defesa contra patógenos. A via metabólica da lignina e as enzimas envolvidas na sua síntese vem sendo caracterizadas nos últimos anos. Uma série de genes que codificam diferentes enzimas envolvidas na biossíntese da lignina foram identificados em diferentes espécies de plantas. A biossíntese de lignina está acoplada ao metabolismo dos fenilpropanóides, apresentando enzimas compartilhadas com outros processos metabólicos tais como fenilalanina amônio liase (PAL), cinnamato 4-hidroxilase (C4H) and ácido caféico O-metiltransferase (COMT) assim como enzimas específicas como cinamoil-CoA redutase (CCR) e cinamil álcool dehidrogenase (CAD). Em certos tipos de mutantes de milho e sorgo, um aumento na digestibilidade foi associado a uma reduçäo no teor de lignina. Uma reduçäo na atividade de CAD e COMT, importantes enzimas envolvidas na biossíntese de lignina vem sendo demonstrada. Estas observações tem motivado diferentes grupos de pesquisa e alterarem o conteúdo ou a composiçäo da lignina em plantas modelo, assim como culturas de interesse econômico, através de engenharia genética. O principal objetivo prático destes projetos é uma otimizaçäo da utilizaçäo destas plantas levando a uma maior produçäo de papel e digestibilidade da raçäo animal. No presente trabalho foi realizado um inventário das seqüências de ESTs, que codificam enzimas envolvidas no metabolismo de lignina, presentes no Projeto Genoma de Cana-de-açúcar (SUCEST). A análise foi realizada com as enzimas chaves ferulato-5-hidroxilase (F5H), ácido caféico O-metiltransferase (COMT), cafeoil CoA O-metiltransferase (CCoAOMT), hidroxicinamato CoA ligase (4CL), cinamoil-CoA redutase (CCR) and cinamil álcool dehidrogenase (CAD). A análise comparativa destes genes com os descritos em outras espécies poderá servir para a identificaçäo de marcadores moleculares em programas de melhoramento genético, assim como em projetos que visem a manipulaçäo do metabolismo de lignina em cana-de-açúcar.