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Linezolid and MM

Rafael Baptista, David M Fazakerley, Manfred Beckmann, Les Baillie, Luis A J Mur
Pretomanid is a promising anti-tubercular drug currently at clinical phase III, but its mechanisms of action are currently unclear. This study aimed to: (i) reveal the metabolome of Mycobacterium smegmatis under pretomanid treatment; (ii) compare major sources of metabolite variation in bacteria treated with pretomanid treatment and other antibiotics; and (iii) to target metabolites responsible for the killing activity of pretomanid in mycobacteria. Untargeted high-resolution metabolite profiling was carried out using flow infusion electrospray ion high resolution mass spectrometry (FIE-HRMS) to identify and quantify metabolites...
March 23, 2018: Scientific Reports
Vincenzo Ferrone, Roberto Cotellese, Maura Carlucci, Lorenzo Di Marco, Giuseppe Carlucci
An ultra high-performance liquid chromatographic (UHPLC) method with PDA detection was developed and validated for the simultaneous quantification of metronidazole, meropenem, ciprofloxacin, linezolid and piperacillin in human plasma and applied to patients suffering from hospital acquired pneumonia (HAP). The method uses an air assisted dispersive liquid-liquid microextraction for sample preparation. All parameters in the extraction step, including selection of extractant, amount of extractant, ionic strength, pH, and extraction cycles, were investigated and optimized...
March 20, 2018: Journal of Pharmaceutical and Biomedical Analysis
Carisa De Anda, Steven Anuskiewicz, Philippe Prokocimer, Jose Vazquez
BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI) are a frequent cause of hospital admissions in the United States. Safe and effective outpatient treatments may lower ABSSSI-associated health care costs by reducing unnecessary hospital admissions. Using data from 2 phase 3 trials (ESTABLISH-1, NCT01170221; ESTABLISH-2, NCT01421511), this post-hoc analysis explored the efficacy and safety of tedizolid in an outpatient setting. METHODS: Subgroup analysis was performed on US outpatients (defined as patients who were not in hospital at the time of treatment initiation) with ABSSSI caused by presumed or proven gram-positive pathogens...
December 2017: Medicine (Baltimore)
Vincenzo Ferrone, Maura Carlucci, Roberto Cotellese, Paolo Raimondi, Annadomenica Cichella, Lorenzo Di Marco, Salvatore Genovese, Giuseppe Carlucci
This study developed a high performance liquid chromatography (HPLC) method involving dried blood spotting (DBS) as a sampling method for the therapeutic drug monitoring of antimicrobial combination therapy with linezolid and ciprofloxacin. DBS for standards, quality control samples, and patient samples was excised and then extracted using a mixture of methanol/water/formic acid 80:20:0.1 (v/v/v), respectively. Linezolid (LZD) and ciprofloxacin (CPR) were measured by HPLC using a Kinetex EVO C18 (100 × 4...
October 2017: Drug Testing and Analysis
Susmita Bhattacharya, Kuhu Pal, Sonia Jain, Shiv Sekhar Chatterjee, Jayashree Konar
INTRODUCTION: Surgical Site Infection (SSI) is the most common healthcare associated infection that could be averted by antibiotics prophylaxis against the probable offending organisms. As Staphylococcus aureus has been playing a substantial role in the aetiology of SSIs, Methicillin Resistant Staphylococcus aureus (MRSA) happens to be a problem while dealing with the postoperative wound infection. AIM: To determine the prevalence of SSI caused by MRSA and the antibiotic sensitivity pattern of MRSA...
September 2016: Journal of Clinical and Diagnostic Research: JCDR
Sonia Jain, Manideepa Sengupta, Soma Sarkar, Sougata Ghosh, Anita Nandi Mitra, Anuradha Sinha, Sriparna Chakravorty
INTRODUCTION: In the present era we are left behind with limited options for the treatment of serious infections caused by multidrug resistant S.aureus, most remarkably nosocomially acquired Methicillin resistant S.aureus (MRSA). The problem increases more when these strains easily become multidrug resistant (MDR) due to biofilm formation. Those staphylococcal species that are vancomycin and linezolid resistant are also resistant to other antistaphylococcal agents which call for an urgent intervention to develop newer antimicrobial agents...
February 2016: Journal of Clinical and Diagnostic Research: JCDR
Vanaporn Wuthiekanun, Premjit Amornchai, Sayan Langla, Nicholas J White, Nicholas P J Day, Direk Limmathurotsakul, Sharon J Peacock
Leptospira Vanaporn Wuthiekanun (LVW) agar was used to develop a disk diffusion assay for Leptospira spp. Ten pathogenic Leptospira isolates were tested, all of which were susceptible to 17 antimicrobial agents (amoxicillin/clavulanic acid, amoxicillin, azithromycin, cefoxitin, ceftazidime, ceftriaxone, chloramphenicol, ciprofloxacin, clindamycin, doripenem, doxycycline, gentamicin, linezolid, nitrofurantoin, penicillin, piperacillin/tazobactam, and tetracycline). All 10 isolates had no zone of growth inhibition for four antimicrobials (fosfomycin, nalidixic acid, rifampicin, and trimethoprim/sulfamethoxazole)...
August 2015: American Journal of Tropical Medicine and Hygiene
Nidhi S Patel, Falguni B Tandel, Yogita D Patel, Kartavya B Thakkar
A stability-indicating reverse phase high performance liquid chromatography method was developed and validated for cefixime and linezolid. The wavelength selected for quantitation was 276 nm. The method has been validated for linearity, accuracy, precision, robustness, limit of detection and limit of quantitation. Linearity was observed in the concentration range of 2-12 μg/ml for cefixime and 6-36 μg/ml for linezolid. For RP-HPLC, the separation was achieved by Phenomenex Luna C18 (250×4.6 mm) 5 μm column using phosphate buffer (pH 7):methanol (60:40 v/v) as mobile phase with flow rate 1 ml/min...
November 2014: Indian Journal of Pharmaceutical Sciences
Andrew F Shorr, Thomas P Lodise, G Ralph Corey, Carisa De Anda, Edward Fang, Anita F Das, Philippe Prokocimer
Tedizolid, a novel oxazolidinone with activity against a wide range of Gram-positive pathogens, was evaluated in two noninferiority phase 3 acute bacterial skin and skin structure infection trials. The data from individual trials showed its noninferior efficacy compared to that of linezolid and a favorable tolerability profile. To evaluate potential differences, the pooled data were analyzed. The patients received 200 mg of tedizolid once daily for 6 days or 600 mg of linezolid twice daily for 10 days. Efficacy was evaluated at 48 to 72 h (primary endpoint), on days 11 to 13 (end of therapy [EOT]), and 7 to 14 days after the EOT (posttherapy evaluation)...
February 2015: Antimicrobial Agents and Chemotherapy
Chaitanya Iragavarapu, Tanush Gupta, Savneek S Chugh, Wilbert S Aronow, William H Frishman
Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide...
July 2016: American Journal of Therapeutics
Thomas P Lodise, Edward Fang, Sonia L Minassian, Philippe G Prokocimer
Tedizolid, the active moiety of tedizolid phosphate, is a recently approved oxazolidinone antibacterial with activity against a wide range of Gram-positive pathogens, including resistant strains such as methicillin-resistant Staphylococcus aureus. To date, 6 days of 200 mg tedizolid once daily has been shown to be noninferior to 10 days of 600 mg linezolid twice daily in two randomized, double-blind phase 3 trials (ESTABLISH-1 and ESTABLISH-2) for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs)...
December 2014: Antimicrobial Agents and Chemotherapy
Takashi Niwa, Tamayo Watanabe, Akio Suzuki, Tomofumi Ohmori, Mayumi Tsuchiya, Tomoyuki Suzuki, Hirotoshi Ohta, Nobuo Murakami, Yoshinori Itoh
The aim of the present study was to evaluate the efficacy of dose modification based on the risk factor for linezolid-induced thrombocytopenia. A multivariate logistic regression analysis performed in the observational study showed that low body weight of <55 kg (odds ratio [OR]: 33.2, 95% confidence interval [CI]: 2.16-510.1, P = 0.012) and the baseline platelet count of <200 × 10(3)/mm(3) (OR: 24.9, 95% CI: 1.53-404.7, P = 0.024) were found to be risk factors for linezolid-induced thrombocytopenia...
May 2014: Diagnostic Microbiology and Infectious Disease
Sally A Helmy
BACKGROUND: Linezolid may be administered in combination with norfloxacin, gatifloxacin, levofloxacin, moxifloxacin, and tinidazole for the treatment of various infections, such as urinary and respiratory tract infections, to improve the efficacy of the treatment or to reduce the duration of therapy. Knowledge of the antibiotic plasma concentrations combined with bacterial susceptibility evaluated in terms of minimum inhibitory concentration would optimize treatment efficacy while limiting the risk of dose-related adverse effects and avoiding suboptimal concentrations...
December 2013: Therapeutic Drug Monitoring
Jagmohan S Saini, Nadine Homeyer, Simone Fulle, Holger Gohlke
Oxazolidinone antibiotics bind to the highly conserved peptidyl transferase center in the ribosome. For developing selective antibiotics, a profound understanding of the selectivity determinants is required. We have performed for the first time technically challenging molecular dynamics simulations in combination with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculations of the oxazolidinones linezolid and radezolid bound to the large ribosomal subunits of the eubacterium Deinococcus radiodurans and the archaeon Haloarcula marismortui...
November 2013: Biological Chemistry
Agnieszka Cios, Kamil Kuś, Joanna Szymura-Oleksiak
A high-performance liquid chromatographic (HPLC) method with UV and DAD detection for the quantitative determination of linezolid in human serum was developed in present work. Chromatography was carried out by reversed-phase technique on a RP-18 column with a mobile phase composed of 50 mM phosphate buffer and acetonitrile (76 : 26, v/v), adjusted to pH 3.5 with orthophosphoric acid. Serum samples were deproteinized with methanol centrifuged and then, the supernatant was analyzed using HPLC procedure. No interference was observed at the retention times of linezolid from blank serum or ten commonly used antibiotics...
July 2013: Acta Poloniae Pharmaceutica
Xianqin Wang, Mengchun Chen, Congcong Wen, Qingwei Zhang, Jianshe Ma
A sensitive and selective liquid chromatography mass spectrometry method for determination of chidamide in rat plasma was developed. After addition of linezolid as internal standard, protein precipitation by acetonitrile-methanol (9:1, v/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 µm) column with acetonitrile-0.1% formic acid as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification using target fragment ions m/z 391...
December 2013: Biomedical Chromatography: BMC
Serena Fortuna, Gennaro De Pascale, Enzo Ragazzoni, Massimo Antonelli, Pierluigi Navarra
A rapid and selective HPLC-UV method was developed for the quantification of linezolid (LNZ) in human plasma and bronchoalveolar lavage (BAL) at the concentrations associated with therapy. Plasma samples were extracted by solid-phase extraction followed by evaporation to dryness and reconstitution in mobile phase solution. The chromatographic separation was carried out on a C18 column with an isocratic mobile phase consisting of dihydrogen phosphate buffer 50 mm (pH 3.5) and acetonitrile (60:40 v/v). The detection was performed using a photodiode array...
November 2013: Biomedical Chromatography: BMC
Kari B Anderson, Sarah Y Lockwood, R Scott Martin, Dana M Spence
Fluidic devices fabricated using conventional soft lithography are well suited as prototyping methods. Three-dimensional (3D) printing, commonly used for producing design prototypes in industry, allows for one step production of devices. 3D printers build a device layer by layer based on 3D computer models. Here, a reusable, high throughput, 3D printed fluidic device was created that enables flow and incorporates a membrane above a channel in order to study drug transport and affect cells. The device contains 8 parallel channels, 3 mm wide by 1...
June 18, 2013: Analytical Chemistry
Jin-rong Liu, Bao-ping Xu, Hui-min Li, Ji-hang Sun, Bao-lin Tian, Shun-ying Zhao, Zai-fang Jiang
OBJECTIVE: Streptococcus pneumoniae necrotizing pneumonia (SPNP) was reported elsewhere but not in China yet. Inappropriate treatment due to poor recognition of this disease could influence its prognosis. This paper presents the clinical characteristics, diagnosis and treatment of SPNP hoping to elevate pediatrician's recognition level for this disease. METHOD: Clinical manifestations, radiological findings, treatment and prognosis of 20 patients (9 boys, 11 girls) who had been hospitalized with SPNP in Beijing Children's Hospital from 2004-2011 were retrospectively analyzed...
June 2012: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Mara N Poulakos, Yasmin Grace, Christina Coakley
PURPOSE: A probable case of linezolid-induced thrombocytopenia is reported. SUMMARY: A 74-year-old Caucasian male with renal dysfunction was diagnosed with diverticulosis. Patient was prescribed linezolid 600 mg orally twice daily for vancomycin-resistant enterococci abdominal infection that developed secondary to colon resection. Upon initiation of linezolid, platelet count dropped from 248 000 cells/mm(3) on day 1 to 97 000 cells/mm(3) on day 5 of treatment. Linezolid was discontinued and platelet counts improved to pretreatment levels...
December 2012: Journal of Pharmacy Practice
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