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Dennis G Maki
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March 20, 2018: Annals of Internal Medicine
Luz I Valenzuela-García, Víctor M Ayala-García, Ana G Regalado-García, Peter Setlow, Mario Pedraza-Reyes
The absence of base excision repair (BER) proteins involved in processing ROS-promoted genetic insults activates a DNA damage scanning (DisA)-dependent checkpoint event in outgrowing Bacillus subtilis spores. Here, we report that genetic disabling of transcription-coupled repair (TCR) or nucleotide excision repair (NER) pathways severely affected outgrowth of ΔdisA spores, and much more so than the effects of these mutations on log phase growth. This defect delayed the first division of spore's nucleoid suggesting that unrepaired lesions affected transcription and/or replication during outgrowth...
March 13, 2018: MicrobiologyOpen
Jacob J Baker, Robert B Abramovitch
Mycobacterium tuberculosis (Mtb) senses and adapts to acidic environments during the course of infection. Acidic pH-dependent adaptations include the induction of metabolic genes associated with anaplerosis and growth arrest on specific carbon sources. Here we report that deletion of isocitrate lyase or phosphoenolpyruvate carboxykinase results in reduced growth at acidic pH and altered metabolite profiles, supporting that remodeling of anaplerotic metabolism is required for pH-dependent adaptation. Mtb cultured at pH 5...
March 8, 2018: Scientific Reports
Michael Samarkos, Vasiliki Antoniadou, Aristeidis G Vaiopoulos, Mina Psichogiou
We report the case of a 53-year-old healthy man, presenting with confusion. The patient had been clinically diagnosed with cat-scratch disease (CSD) and prescribed a 10-day course of doxycycline orally. Approximately a week after he had completed the treatment, he was admitted to our department with confusion. Neurological examination revealed expressive dysphasia with no motor or sensory deficits. Cerebrospinal fluid (CSF) examination showed only increased content. Imaging with CT and MRI of the brain did not reveal any abnormalities, and funduscopy was normal...
March 5, 2018: BMJ Case Reports
Yu Zhang, Mingqin Zhu, Lifang Wang, Miao Shi, Hui Deng
RATIONALE: Longitudinally extensive transverse myelitis (LETM) is characterized by contiguous inflammatory lesions of spinal cord extending to ≥3 vertebral segments. The etiology of LETM is complicated, including various infection, autoimmune disease, and so on. Neuromyelitis optic spectrum disorder (NMOSD) is the most common cause of LETM. Several case reports have suggested the associations between NMOSD and pulmonary tuberculosis (PTB). PATIENT CONCERNS: Patient 1, a 20-year-old woman who had a past history of PTB, presented with weakness, numbness, and pain in the limbs...
January 2018: Medicine (Baltimore)
Hooman Hennessey, Elna Luckham, Ahmed Kayssi, Mark David Wheatcroft, Elisa Greco, Mohammed Al-Omran, John Harlock, Mohammad Qadura
OBJECTIVE: In the treatment of an infected aorta, open repair and replacement with a rifampin-impregnated Dacron vascular graft decrease the risk of prosthetic graft infections, with several protocols available in the literature. We hypothesize that the same holds true for endovascular aneurysm repair, and after studying and optimizing rifampin solution concentration and incubation period to maximize the coating process of rifampin on Dacron endovascular stent grafts (ESGs), we propose a rapid real-time perioperative protocol...
March 1, 2018: Journal of Vascular Surgery
Salia Farrokh, Edina Avdic
PURPOSE: Optimization of antifungal therapy with voriconazole can be challenging due to inter- and intrapatient variability in voriconazole pharmacokinetics (PK). In this case, we introduce challenges in voriconazole therapy due to drug-drug interactions, autoinduction, and saturable metabolism. SUMMARY: A 32-year-old male on chronic prednisone developed central nervous system (CNS) aspergillosis. He was started on high-dose intravenous (IV) voriconazole 8.5 mg/kg every 12 hours due to concerns for lasting induction effects of recent rifampin therapy...
January 1, 2018: Journal of Pharmacy Practice
Jennifer S Guimbellot, Edward P Acosta, Steven M Rowe
The CFTR potentiator ivacaftor is responsible for significant clinical improvements among a subset of patients with cystic fibrosis. Because it is a substrate of the cytochrome P450 system, specifically CYP3A4/5, ivacaftor is subject to significant drug-drug interactions, including due to commonly used antimicrobials such as rifampin. While the interaction of rifampin and ivacaftor has been examined in vitro, severe adverse events resulting from this interaction have not been reported in the literature. In this report, we describe the termination of steady, long-term improvement in a patient taking ivacaftor, resulting from the use of rifampin and precipitating a significant pulmonary exacerbation...
February 28, 2018: Pediatric Pulmonology
M Naveed Shaik, Brian Hee, Hua Wei, Robert R LaBadie
AIMS: This study aimed to evaluate the effect of a strong CYP3A inducer, rifampin, on glasdegib pharmacokinetics in healthy volunteers. METHODS: In an open-label, fixed-sequence, two-period Phase 1 study, subjects received a single 100-mg oral dose glasdegib alone or following once-daily pre-treatment with 600 mg rifampin administered once daily. Glasdegib pharmacokinetics were calculated using a noncompartmental analysis. RESULTS: Twelve healthy male volunteers (3 whites, 5 blacks and 4 others) were enrolled in the study...
February 28, 2018: British Journal of Clinical Pharmacology
Kanchan Ajbani, Mubin Kazi, Jeffrey Tornheim, Swapna Naik, Rajeev Soman, Anjali Shetty, Camilla Rodrigues
Delayed diagnosis of drug resistance has been a major obstacle to proper management and control of drug-resistant tuberculosis (TB). Expanded access to rapid molecular diagnostics such as Xpert MTB/RIF has been helpful, but has generated confusion about how to interpret genotype-phenotype discordance. Optimal management is not clearly defined for patients with rifampin resistance by Xpert MTB/RIF but rifampin susceptibility by phenotypic testing. To resolve this discrepancy, we performed pyrosequencing of discordant isolates identified at a reference laboratory over a 6-month period...
March 2018: Lung India: Official Organ of Indian Chest Society
Azar Dokht Khosravi, Hossein Meghdadi, Ata A Ghadiri, Ameneh Alami, Amir Hossein Sina, Mehdi Mirsaeidi
The aim of this study was to analyze mutations occurring in the rpoB gene of Mycobacterium tuberculosis (MTB) isolates from clinical samples of extrapulmonary tuberculosis (EPTB). Seventy formalin-fixed, paraffin-embedded samples and fresh tissue samples from confirmed EPTB cases were analyzed. Nested PCR based on the rpoB gene was performed on the extracted DNAs, combined with cloning and subsequent sequencing. Sixty-seven (95.7%) samples were positive for nester PCR. Sequence analysis of the 81 bp region of the rpoB gene demonstrated mutations in 41 (61...
March 2018: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Zahra Farshadzadeh, Behrouz Taheri, Sara Rahimi, Saeed Shoja, Maryam Pourhajibagher, Mohammad A Haghighi, Abbas Bahador
Two different mechanisms of resistance to colistin in Acinetobacter baumannii have been described. The first involves the total loss of lipopolysaccharide (LPS) due to mutations in the lpxACD operon, which is involved in the lipid A biosynthesis pathway. The second entails the addition of ethanolamine to the lipid A of the LPS resulting from mutations in the PmrAB two-component system. To evaluate the impact of colistin resistance-associated mutations on antimicrobial resistance and virulence properties, four pairs of clinical and laboratory-evolved colistin-susceptible/colistin-resistant (ColS /ColR ) A...
2018: Frontiers in Microbiology
Suman Sharma, Bhawna Dahiya, Vishnubhatla Sreenivas, Netrapal Singh, Ankush Raj, Abhishek Sheoran, Aparna Yadav, Krishna B Gupta, Promod K Mehta
AIM: Diagnosis of pleural TB poses serious challenges due to paucibacillary nature of specimens and there is an urgent need to devise a reliable diagnostic test. METHODS: We compared GeneXpert Mycobacterium tuberculosis/rifampin assay and the multiplex PCR (M-PCR) targeting mpb64 (Rv1980c) and IS6110 in pleural fluids (n = 78) of pleural TB patients and non-TB controls. RESULTS: The sensitivities of 89.6 and 33.3%, and specificities of 96...
February 21, 2018: Future Microbiology
Yun Sung Kim, Dong-Min Kim, Na-Ra Yoon, Mi-Sun Jang, Choon-Mee Kim
Background: Doxycycline is currently the most frequently used treatment in patients with scrub typhus, but doxycycline-resistant strains have been found, necessitating the development of a new treatment. Rifampin is known to be effective even for such strains. Thus, this study aimed to compare the effects of rifampin and doxycycline treatment in patients with scrub typhus in areas in which resistance to doxycycline has not been reported. Methods: Patients admitted to Chosun University Hospital and regional network hospitals between 2007 and 2009 with a body temperature of 37...
February 15, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Miranda G Loutet, Jennifer A Davidson, Tim Brown, Martin Dedicoat, H Lucy Thomas, Maeve K Lalor
Among tuberculosis (TB) patients, acquired resistance to anti-TB drugs represents a failure in the treatment pathway. To improve diagnosis and care for patients with drug-resistant TB, we examined the epidemiology and risk factors associated with acquired drug resistance during 2000-2015 among TB patients in England, Wales, and Northern Ireland. We found acquired resistance in 0.2% (158/67,710) of patients with culture-confirmed TB. Using multivariate logistic regression, we identified the following factors associated with acquired drug resistance: having pulmonary disease; initial resistance to isoniazid, rifampin, or both; a previous TB episode; and being born in China or South Africa...
March 2018: Emerging Infectious Diseases
Ahmed H Qavi, Tasnim F Imran, Zachariah Hasan, Fariha Ilyas
Tuberculous meningitis (TBM) is an infection of the central nervous system (CNS) meninges that carries high morbidity and mortality. It is important to recognize, as patients may present with atypical symptoms. We describe the case of a 31-year-old man with a history of diabetes who presented with a sub-acute onset of right-sided facial weakness and right gaze difficulty with diplopia. History revealed low-grade fever, right-sided headache, fatigue and moderate weight loss for the past several weeks. The patient did not report neck stiffness, rigidity, fever, chills or cough...
December 7, 2017: Curēus
Yang-Hui Jin, Shi-Yuan Shi, Qi Zheng, Jian Shen, Xiao-Zhang Ying, Yi-Fan Wang
OBJECTIVE: To investigate the application value of Xpert MTB/RIF in diagnosis of spinal tuberculosis and detection of rifampin resistance. METHODS: The 109 pus specimens were obtained from patients who were primaryly diagnosed as spinal tuberculosis. All of the pus specimens were detected by acid-fast stain, liquid fast culturing by BACTEC MGIT 960 and Xpert MTB/RIF assay to definite the differences in sensitivity and specificity of mycobacterium tuberculosis among detecting methods...
September 25, 2017: Zhongguo Gu Shang, China Journal of Orthopaedics and Traumatology
Jamie E Moscovitz, Amit S Kalgutkar, Kelly Nulick, Nathaniel Johnson, Zhiwu Lin, Theunis C Goosen, Yan Weng
The potential for drug-drug interactions (DDIs) arising from transcriptional regulation of drug disposition genes via activation of nuclear receptors (NRs) such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), and/or aryl hydrocarbon receptor (AhR) remains largely unexplored, as highlighted in a recent guidance document from the European Medicines Agency. The goal of this research was to establish PXR/CAR/AhR-specific drug metabolizing enzyme (DME) and transporter gene expression signatures in sandwich-cultured cryopreserved human hepatocytes using selective activators of PXR (rifampin), CAR (CITCO) and AhR (omeprazole)...
February 12, 2018: Journal of Pharmacology and Experimental Therapeutics
James C Johnston, Mia L van der Kop, Kirsten Smillie, Gina Ogilvie, Fawziah Marra, Mohsen Sadatsafavi, Kamila Romanowski, Matthew A Budd, Jan Hajek, Victoria Cook, Richard T Lester
There is limited high-quality evidence available to inform the use of text messaging to improve latent tuberculosis infection (LTBI) treatment adherence.We performed a parallel, randomised controlled trial at two sites to assess the effect of a two-way short message service on LTBI adherence. We enrolled adults initiating LTBI therapy from June 2012 to September 2015 in British Columbia, Canada. Participants were randomised in a 1:1 ratio to standard LTBI treatment (control) or standard LTBI treatment plus two-way weekly text messaging (intervention)...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Isabella W Martin, Kim Dionne, Sharon M Deml, Nancy L Wengenack, Nicole M Parrish
We examined categorical agreement between automated mycobacterial susceptibility testing methods (Mycobacterial Growth Indicator Tube [MGIT] 960 System and the VersaTREK Mycobacteria Detection and Susceptibility System) which are based on single critical concentration (CC) "breakpoints" and a commercial microbroth dilution method (Sensititre Mycobacterium tuberculosis MIC Plate [MYCOTB]) which provides an MIC value. Mycobacterium tuberculosis isolates (n=355) were tested against three first-line antimycobacterial agents (ethambutol [EMB], isoniazid [INH], rifampin [RIF]) using the MYCOTB plate and either the MGIT 960 (site 1, n=142) or VersaTREK (site 2, n=213) systems...
January 6, 2018: Diagnostic Microbiology and Infectious Disease
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