Linezolid and MM

OBJECTIVE: Anti-tuberculosis (antiTB) drugs are characterized by an important inter-interindividual pharmacokinetic variability poorly predictable from individual patients' characteristics. Therapeutic drug monitoring (TDM) may therefore be beneficial for patients with Mycobacterium tuberculosis infection, especially for the management of multidrug/extensively drug resistant- (MDR/XDR)-TB. Our objective was to develop robust HPLC-MS/MS methods for plasma quantification of 15 antiTB drugs and 2 metabolites, namely rifampicin, isoniazid plus N-acetyl-isoniazid, pyrazinamide, ethambutol (the conventional quadritherapy for susceptible TB) as well as combination of agents against MDR/XDR-TB: bedaquiline, clofazimine, delamanid and its metabolite M1, levofloxacin, linezolid, moxifloxacin, pretomanid, rifabutin, rifapentine, sutezolid, and cycloserine...

Pythium keratitis is a potentially devastating ocular condition. Incidence of Pythium keratitis has been reported in tropical and subtropical areas. In previous reports, there were no effective or standard treatments, and combinations of medication, immunotherapy, and surgery were proposed. Pythium insidiosum antigen immunotherapy (PIAI) showed an acceptable safety profile, but its efficacy is questionable in Pythium keratitis. This retrospective review included 10 eyes from 10 patients. All cases were confirmed diagnosis of P...

Pythium insidiosum (PI) is an oomycete, a protist belonging to the clade Stramenopila. PI causes vision-threatening keratitis closely mimicking fungal keratitis (FK), hence it is also labeled as "parafungus". PI keratitis was initially confined to Thailand, USA, China, and Australia, but with growing clinical awareness and improvement in diagnostic modalities, the last decade saw a massive upsurge in numbers with the majority of reports coming from India. In the early 1990s, pythiosis was classified as vascular, cutaneous, gastrointestinal, systemic, and ocular...

This paper reports the separation of two chiral antibacterial agents namely, linezolid and tedizolid using a validated high-performance liquid chromatographic method. In the current work, glycopeptide-based chiral column, CHIROBIOTIC® V2 (5-μm particle size, L × I.D. 25 cm × 4.6 mm) was employed with a mobile phase containing methanol and 0.15% aq. trifluoracetic acid (75:25%, v/v) in isocratic elution approach at flow rate of 1 ml min-1 . The separation condition was customized (in terms of resolution values and retention times) was carried out by changing the content of the mobile phase, column temperature, flow rate, and so on...

Nowadays, infectious diseases caused by drug-resistant bacteria have become especially important. Linezolid is an antibacterial drug active against clinically important Gram positive strains; however, resistance showed by these bacteria has been reported. Nanotechnology has improved a broad area of science, such as medicine, developing new drug delivery and transport systems. In this work, several covalently bounded conjugated nanomaterials were synthesized from multiwalled carbon nanotubes (MWCNTs), a different length oligoethylene chain ( S n ), and two linezolid precursors (4 and 7), and they were evaluated in antibacterial assays...

Pharmacokinetics/pharmacodynamics is the foundation for guiding the rational application of antibiotics in clinical practice, so it is necessary to establish quantitative methods for accurate drug concentration determination. This study aimed to develop a rapid and simple ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of 14 antibiotics (amikacin, etimicin, ceftazidime, cefepime, cefoperazone, ceftriaxone, daptomycin, latamoxef, linezolid, meropenem, biapenem, ampicillin, norvancomycin, and vancomycin) in human plasma and cerebrospinal fluid...

Appropriate antibiotic dosing in critically ill patients requires concentration monitoring due to the occurrence of pathophysiological changes and frequent extracorporeal therapy that could significantly alter the normal pharmacokinetics of drugs. Herein, we describe an ultra-performance liquid chromatography with photodiode array (UPLC-PDA) for the simultaneous concentration determination of seven frequently used antibiotics (meropenem, cefotaxime, cefoperazone, piperacillin, linezolid, moxifloxacin, and tigecycline) in plasma from critically ill patients...

Few pieces of research have focused on Micrococcus luteus bloodstream infection (BSI) because of its low incidence; hence data is needed to illustrate this uncommon infection. This study aimed to explore the clinical characteristics of patients with M. luteus BSI. From January 2010 to December 2019, inpatients that met the criteria for M. luteus BSI were included in this study. Data was collected by reviewing electronic records. Ninety-seven patients were enrolled in this study. Sixty-three percent of the patients have a higher neutrophil percentage (NEUT%)...

Molecular modeling (MM) results for tedizolid and radezolid with heptakis-(2,3-diacetyl-6-sulfo)-β-cyclodextrin (HDAS-β-CD) are presented and compared with the results previously obtained for linezolid and sutezolid. The mechanism of interaction of chiral oxazolidinone ligands belonging to a new class of antibacterial agents, such as linezolid, tedizolid, radezolid, and sutezolid, with HDAS-β-CD based on capillary electrokinetic chromatography (cEKC), nuclear magnetic resonance (NMR) spectroscopy, and MM methods was described...

The contribution of the metabolites of linezolid to the associated myelosuppression is unknown in patients who are renal impairment. In this research, the purpose of our experiment was to explore and develop a quick and robust ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the determination of linezolid and its metabolite PNU-142300 in human serum simultaneously. The analytes were prepared using a simple and convenient approach with acetonitrile for protein crash, and then separated from the matrix on a Waters Acquity Ultra performance liquid chromatography (UPLC) BEH C18 (2...

Purpose: The aim of this work was to study demography, clinical profile, laboratory diagnosis, and management of Pythium keratitis at a tertiary eye care center in Eastern India. Methods: Eighteen patients with culture-positive Pythium keratitis managed at our center between January 2016 and December 2018 were included in this retrospective study. Clinical features, laboratory investigations, treatment, and outcomes were analysed. Results: Pythium keratitis commonly affects middle-aged males with low socioeconomic profile and history of trauma...

PURPOSE: Pythium insidiosum causes a rare sight-threatening keratitis and is a devastating ocular pathology with a high morbidity. It is frequently mistaken as fungal keratitis. Here we highlight a rare case of pediatric Pythium insidiosum keratitis which was successfully managed using an antibiotic combination of linezolid and azithromycin with cyanoacrylate glue. CASE DESCRIPTION: A 9-year-old young male child presented to our clinic with defective vision, pain, redness in the right eye for 5 days post stick injury...

Tedizolid phosphate (TZP) a prodrug of Tedizolid (TDZ) is a novel oxazolidinone antibiotic, used for the treatment of acute bacterial skin, skin structure infections and other serious gram positive and MRSA infections. In the present study, a sensitive UPLC-MS/MS analytical method was developed and validated for the quantification of TDZ in rabbit's aqueous humor (AqH) by using linezolid as internal standard (IS). Both TDZ and IS were separated on an Acquity™ HILIC column using an isocratic mobile phase comprising of acetonitrile: 20 mM ammonium acetate (85:15, v/v), eluted at 0...

OBJECTIVES: Critically ill patients in intensive care unit (ICU) are susceptible to infectious diseases, thus empirical therapy is recommended. However, the therapeutic effect in ICU patients is difficult to predict due to fluctuation in pharmacokinetics because of various factors. This problem can be solved by developing personalized medicine through therapeutic drug monitoring. However, when different measurement systems are used for various drugs, measurements are complicated and time consuming in clinical practice...

PURPOSE: To describe the clinical features, microbiological profile, and outcome of a series of cases of Pythium keratitis treated with topical and oral linezolid and topical azithromycin eye drops. METHODS: This was a retrospective interventional case series of microbiologically and/or histopathologically proven cases of Pythium keratitis seen between October 2016 and December 2019. All patients received a combination of topical linezolid and/or azithromycin eye drops with oral linezolid...

To obtain a healthy human being with beneficial microflora against different pathogenic infections, classical antibiotics with nanosized biomaterials were used to inhibit the growth of bacterium by their potent synergistic effect. Hence, this study planned to load an oxazolidinone antibiotic named linezolid (LD) onto functionalized chitosan (CN) with 3, 5- dinitrosalyslic acid (DA) via microwave synthesis without harsh condition. The exploring synergistic effect of linezolid (LD) with CN/DA controllable nanostructure was compact efflux-mediated methicillin-resistant Staphylococcus aureus (MRSA) burden and other selected bactericide Gram-positive ( (S...

BACKGROUND: ClpP is important for bacterial growth and plays an indispensable role in cellular protein quality control systems by refolding or degrading damaged proteins, but the physiological significance of ClpP in Enterococcus faecalis remains obscure. A clpP deletion mutant (△clpP) was constructed using the E. faecalis OG1RF strain to clarify the effect of ClpP on E. faecalis. The global abundance of proteins was determined by a mass spectrometer with tandem mass tag labeling. RESULTS: The ΔclpP mutant strain showed impaired growth at 20 °C or 45 °C at 5% NaCl or 2 mM H2 O2 ...

Studies suggest a link between added copper (Cu) and co-selection of antimicrobial resistance (AMR) in Enterococcus spp., but data are inconsistent. This study aimed to assess the impact of added Cu, alone or with a feed-grade antimicrobial, on growth performance, transferable Cu resistance gene (tcrB) prevalence, abundance of tcrB in fecal community DNA, and AMR in fecal enterococci in weaned piglets. A total of 320 barrows (DNA 200 × 400, DNA Genetics) weaned at approximately 21 days of age with 7.4 kg (7...

Linezolid (LZD) is a widely used antimicrobial that is active against a broad range of disease-causing bacteria. Myelosuppression is major treatment-limiting toxicity of LZD that occurs more frequently in patients with renal insufficiency. Quantification of LZD and its two primary metabolites (PNU-142300 and PNU-142586), which undergo significant renal elimination, may support design of improved dosing strategies to mitigate the risk of myelosuppression. In this study, we established the first liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of LZD and its main metabolites in human serum...

Background: The study aimed to assess the prevalence of Enterococcus faecalis infections among patients with hospital-acquired surgical wound sepsis and bacteremia in surgical wards and identify the antimicrobial susceptibility in these pathogens. Genetic role of erythromycin, vancomycin, and cephalosporin resistance in these pathogens was also examined. Methods: Two hundred samples were collected from surgical wound infections and 100 blood cultures from patients with suggested bacteremia to identify E faecalis by phenotypic and genotypic methods...