Pharmacokinetic (PK) and pharmacodynamic (PD) analyses were conducted to determine the cumulative fraction of response (CFR) for 100 mg twice-daily (BID) and 200 mg once-daily (QD) delamanid in patients with multidrug-resistant tuberculosis (MDR-TB), using a pharmacodynamic target (PDT) that achieves 80% of maximum efficacy. First, in the mouse model of chronic TB, the PK/PD index for delamanid efficacy was determined to be area under the drug concentration-time curve over 24 h divided by MIC (AUC/MIC), with a PDT of 252. Second, in the hollow-fiber system model of tuberculosis, plasma-equivalent PDTs were identified as an AUC/MIC of 195 in log-phase bacteria and 201 in pH 5.
View Article and Find Full Text PDFBackground: d-cycloserine is used to treat multidrug-resistant tuberculosis. Its efficacy, contribution in combination therapy, and best clinical dose are unclear, also data on the d-cycloserine minimum inhibitory concentration (MIC) distributions is scant.
Methods: We performed a systematic search to identify pharmacokinetic and pharmacodynamic studies performed with d-cycloserine.
J Antimicrob Chemother
September 2017
Objectives: To determine if ceftaroline and ceftazidime combined with avibactam are efficacious against pulmonary Mycobacterium avium complex (MAC) disease.
Methods: First, we performed a concentration-effect study of ceftaroline and ceftaroline/avibactam against extracellular MAC in test tubes. Given the difficulty of obtaining avibactam at the time of experimentation, we used a single concentration of commercial ceftazidime/avibactam, and two sets of non-treated controls, one with ceftazidime/avibactam and the other without.
Introduction. Neonatal septicemia is defined as infection in the first 28 days of life. Early-onset neonatal septicemia and late-onset neonatal septicemia are defined as illnesses appearing from birth to three days and from four to twenty-eight days postnatally, respectively.
View Article and Find Full Text PDFBackground: Multi-drug resistance (MDR) in Gram-negative organisms is an alarming problem in the world. MDR and extensively-drug resistance (XDR) is in increasing trend due to the production of different types of beta (β)-lactamases. Thus the aim of this study was to document the incidence of MDR and XDR in clinical isolates of Escherichia coli and also to find out the enzymatic mechanisms of β-lactam antibiotics resistance.
View Article and Find Full Text PDFIntroduction. Children are among the most vulnerable population groups to contract illnesses. The varying microbiological pattern of septicemia warrants the need for an ongoing review of the causative organisms and their antimicrobial susceptibility pattern.
View Article and Find Full Text PDFBackground: Staphylococcus aureus is the most commonly isolated organism from the different clinical samples in hospital. The emergence and dissemination of methicillin resistant Staphylococcus aureus (MRSA) and growing resistance to non-beta-lactam antibiotics is making treatment of infections due to this organism increasingly difficult.
Methods: This study was conducted to determine the frequency of Staphylococcus aureus isolated from different clinical samples, rates of MRSA and full antibiotic susceptibility profiles.
Immune complexes composed of IgG-opsonized pathogens, particles, or proteins are phagocytosed by macrophages through Fcγ receptors (FcγRs). Macrophages primed with IFNγ or other pro-inflammatory mediators respond to FcγR engagement by secreting high levels of cytokines and nitric oxide (NO). We found that unprimed macrophages produced lower levels of NO, which required efficient calcium (Ca(2+)) flux as demonstrated by using macrophages lacking selenoprotein K, which is required for FcγR-induced Ca(2+) flux.
View Article and Find Full Text PDFIt has been suggested that JC virus (JCV) might travel to the central nervous system in infected B cells. Moreover, recent data suggest the presence of JCV in bone marrow plasma cells. However, the evidence for infection and replication of JCV in B cells is unclear.
View Article and Find Full Text PDFA recent report demonstrated that JC virus (JCV) employs serotonin receptor 2A (5HT(2A)R) to infect the glial cells. To assess the ability of a potent 5HT(2A)R blocker, risperidone, to inhibit JCV infection, the authors treated primary human fetal glial (PHFG) cells in vitro with risperidone for 24 h and inoculated with JCV(Mad1). There was no significant difference in JCV genome copies or mRNA transcripts and protein expression in treatment-naive and risperidone-treated PHFG cells.
View Article and Find Full Text PDFAlthough human polyomavirus JC (JCV) is known to cause progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals, the mechanism by which JCV crosses the blood-brain barrier (BBB) remains unclear. To test our hypothesis that cell-free JCV gains entry into the brain by infecting endothelial cells, we inoculated human brain microvascular endothelial (HBMVE) cells with 50 HAU (1.33+/-0.
View Article and Find Full Text PDFHuman polyomavirus JC (JCV), the etiological agent of the disease progressive multifocal leukoencephalopathy (PML) affects immunocompromised patients particularly patients with AIDS. In vitro studies of JCV infection are hampered by the lack of sensitive JCV quantitation tests. Although the hemagglutination (HA) assay has been routinely employed for in vitro quantitation of JCV, its sensitivity is severely limited.
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