30,047 results match your criteria Antimicrobial agents and chemotherapy[Journal]


Natamycin and voriconazole exhibit synergistic interactions with non-antifungal ophthalmic agents against ocular isolates.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Geisel School of Medicine at Dartmouth, Department of Microbiology and Immunology Hanover, NH, United States

The activities of two antifungal drugs in combination with four non-antifungal ophthalmic agents were evaluated using a micro-broth dilution method and a collection of eight ocular isolates that exhibited resistance to both natamycin (MICs: 14-32 μg/mL) and voriconazole (4->128 μg/mL). Synergistic interactions were observed for natamycin with 5-fluorouracil (FICIs: 0.34-0. Read More

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http://dx.doi.org/10.1128/AAC.02505-18DOI Listing

Limited sampling strategies using linear regression and the Bayesian approach for therapeutic drug monitoring of moxifloxacin in tuberculosis patients.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands

Therapeutic drug monitoring (TDM) of moxifloxacin is recommended to improve response to tuberculosis treatment and reduce acquired drug resistance. Limited sampling strategies (LSSs) are able to reduce the burden of TDM by using a small number of appropriately timed samples to estimate the parameter of interest; the area under the concentration time curve. This study aimed to develop LSSs for moxifloxacin alone (MFX) and together with rifampicin (MFX+RIF) in TB patients. Read More

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http://dx.doi.org/10.1128/AAC.00384-19DOI Listing

Comparing Antimicrobial Susceptibilities among Isolated from Pediatric Patients in Japan between Two Recent Epidemic Periods.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Department of Pediatrics, Kawasaki Medical School, Okayama, Japan.

We compared the antimicrobial susceptibility of isolated from pediatric patients in Japan in 2011-2012 and 2015-2016 when epidemics occurred. The antimicrobial activity of macrolides and tetracyclines against tended to be restored in 2015-2016. There was no change in the antimicrobial activity of quinolones against . Read More

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http://dx.doi.org/10.1128/AAC.02517-18DOI Listing

Isoniazid resistance in is a heterogeneous phenotype comprised of overlapping MIC distributions with different underlying resistance mechanisms.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

MIC testing using the BACTEC 960 MGIT system of 70 phylogenetically diverse, isoniazid-resistant clinical strains of revealed a complex pattern of overlapping MIC distributions. Whole-genome sequencing could explain most of the level of resistance observed. The MIC distribution of strains with only promoter mutations was split by the current concentration that is endorsed by the Clinical Laboratory Standards Institute to detect low-level resistance to isoniazid and is, consequently, likely not optimally set. Read More

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http://dx.doi.org/10.1128/AAC.00092-19DOI Listing

Efficacy of aerosolized rifaximin versus tobramycin for the treatment of pneumonia in mice.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Department of Biomedical Sciences, Department of Pediatrics, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV 25755-9320

is a Gram-negative opportunistic bacterial pathogen that can cause chronic lung infections in patients with cystic fibrosis (CF). The current preferred treatment for CF lung infections includes inhaled tobramycin (TOB); however, studies suggest TOB cannot effectively inhibit biofilm formation. Using a NIH small compounds drug library approved for safe use in humans, we identified rifaximin (RFX), a semisynthetic, rifamycin family, non-systemic antibiotic that inhibits alginate production and growth in Inhibition of alginate production was further analyzed using the uronic acid carbazole assay and a promoter reporter assay that measures the transcription of the alginate biosynthetic operon. Read More

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http://dx.doi.org/10.1128/AAC.02341-18DOI Listing

Joint modelling of resistance to six antimicrobials in urinary isolates in Quebec, Canada.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Department of Microbiology, Infectious Diseases & Immunology, Université de Montréal, Montréal, QC, Canada

Empirical treatment of urinary tract infections should be based on susceptibility profiles specific to the locale and patient population. Additionally, these susceptibility profiles should account for correlations between resistance to different types of antimicrobials. We used hierarchical logistic regression models to investigate geographic, temporal, and demographic trends in resistance to six antimicrobials in community-acquired and nosocomial urinary isolates from three communities in the province of Quebec, Canada procured between April 2010 and December 2017. Read More

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http://aac.asm.org/lookup/doi/10.1128/AAC.02531-18
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http://dx.doi.org/10.1128/AAC.02531-18DOI Listing
April 2019
1 Read

VALIDATION AND APPLICATION OF A HPLC-DAD METHOD FOR ROUTINE THERAPEUTIC DRUG MONITORING OF CEFTOBIPROLE.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Laboratory of Pharmacology and Toxicology, department of clinical pharmacology, Amiens University Hospital, Amiens, France.

Ceftobiprole is a fifth-generation cephalosporin approved for the treatment of pneumonia, with a broad antibacterial spectrum including potent activity against methicillin-resistant As for the other cephalosporins, high pharmacokinetic variability and concentration-dependent neurotoxicity are expected. We describe here the first simple and rapid analytical method intended for ceftobiprole serum concentration monitoring. We report the data of 5 patients treated with ceftobiprole, among who 2 developed reversible neurological disorders with high ceftobiprole serum concentration. Read More

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http://dx.doi.org/10.1128/AAC.00515-19DOI Listing

The Microbiology of Bloodstream Infection: 20-Year Trends from the SENTRY Antimicrobial Surveillance Program.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

JMI Laboratories, North Liberty, Iowa, USA.

Bloodstream infection (BSI) organisms were consecutively collected from >200 medical centers in 45 nations between 1997 and 2016. Species identification and susceptibility testing followed Clinical and Laboratory Standards Institute broth microdilution methods at a central laboratory. Clinical data and isolates from 264,901 BSI episodes were collected. Read More

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http://dx.doi.org/10.1128/AAC.00355-19DOI Listing

The combination rifampin-nitazoxanide, but not rifampin-isoniazid-pyrazinamide-ethambutol, kills dormant in hypoxia at neutral pH.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Dipartimento di Malattie Infettive, and Organismo Notificato Unificato,Istituto Superiore di Sanità, Via Regina Elena 299, 00161 Rome, Italy

The activities of rifampin, nitazoxanide, PA-824, sutezolid, were tested against dormant under conditions mimicking caseous granulomas (hypoxia at pH 7.3), in comparison with the combination rifampin-isoniazid-pyrazinamide-ethambutol (R-I-Z-E), used for human therapy. Mycobacterial viability was monitored by CFU and regrowth in MGIT 960 tubes. Read More

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http://dx.doi.org/10.1128/AAC.00273-19DOI Listing

Advancing the therapeutic potential of indoleamides for tuberculosis.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Indole-2-carboxamide derivatives are inhibitors of MmpL3, the cell wall associated mycolic acid transporter of (Mtb). In the present study, we characterized indoleamide effects on bacterial cell morphology and re-evaluated pharmacokinetics and efficacy using an optimized oral formulation. Morphologically, indoleamide-treated Mtb cells demonstrated significantly higher numbers of dimples near the poles or septum, which may serve as the mechanism of cell death for this bactericidal scaffold. Read More

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http://dx.doi.org/10.1128/AAC.00343-19DOI Listing

Biofilm-associated cells have altered antibiotic tolerance and surface glycolipids in Artificial Cystic Fibrosis Sputum Media.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Department of Biology, University of Texas Arlington

() is a biofilm-forming, multi-drug resistant, non-tuberculous mycobacterial (NTM) pathogen increasingly found in Cystic Fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due to 's high intrinsic antibiotic resistance. It is not clear whether antibiotic tolerance caused by biofilm formation also contributes to poor treatment outcomes. Read More

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http://dx.doi.org/10.1128/AAC.02488-18DOI Listing

Isolation of phage lysins that effectively kill in mouse models of lung and skin infection.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.

Multi-drug resistance (MDR) is rapidly increasing in prevalence among isolates of the opportunistic pathogen , leaving few treatment options. Phage lysins are cell wall hydrolases that have a demonstrated therapeutic potential against Gram-positive pathogens, however the outer membrane of Gram-negative bacteria prevents most lysins from reaching the peptidoglycan, making them less effective as therapeutics. Nevertheless, a few lysins from gram-negative phage can penetrate the bacterial outer membrane, aided by an amphipathic tail found in the molecule's termini. Read More

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http://dx.doi.org/10.1128/AAC.00024-19DOI Listing

Bicarbonate Resensitization of Methicillin-Resistant to β-Lactam Antibiotics.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA.

Endovascular infections caused by methicillin-resistant () are a major healthcare concern, especially infective endocarditis (). Standard antimicrobial susceptibility testing () defines most MRSA strains as 'resistant' to β-lactams, often leading to use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. Read More

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http://dx.doi.org/10.1128/AAC.00496-19DOI Listing

Clinical prognoses of patients with a bloodstream infection caused by ampicillin-susceptible but penicillin-resistant : prospective observational study.

Antimicrob Agents Chemother 2019 Apr 22. Epub 2019 Apr 22.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea

To evaluate the clinical impacts of ampicillin-susceptible but penicillin-resistant (ASPR) phenotypes of on clinical outcomes in patients with a bloodstream infection (BSI). A total of 295 patients with an BSI from six sentinel hospitals during a two-year period (from May 2016 to April 2018) were enrolled in this study. Putative risk factors, including host-, treatment-, and pathogen-related variables, were assessed to determine the associations with the 30-day mortality rate of patients with an BSI. Read More

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http://dx.doi.org/10.1128/AAC.00291-19DOI Listing
April 2019
2 Reads

Comparative performance of urinary biomarkers for vancomycin induced kidney injury according to timeline of injury.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA

Urinary biomarkers are superior to serum creatinine for defining onset and extent of kidney injury. This study classifies the temporal predictive ability of biomarkers for vancomycin-induced kidney injury (VIKI) as defined by histopathologic damage.: Male Sprague-Dawley rats (n=125) were randomized to receive 150 to 400 mg/kg/day vancomycin via once or twice daily intraperitoneal injection over 1, 3, or 6 days. Read More

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http://dx.doi.org/10.1128/AAC.00079-19DOI Listing

In vitro activity of cefepime-enmetazobactam against Gram-negative isolates collected from United States and European hospitals during 2014-2015.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Allecra Therapeutics SAS, St-Louis, France

Enmetazobactam, formerly AAI101, is a novel penicillanic acid sulfone extended-spectrum β-lactamase inhibitor. The combination of enmetazobactam with cefepime has entered clinical trials to assess safety and efficacy in patients with complicated urinary tract infections. Here, the in vitro activity of cefepime-enmetazobactam was determined for 1,993 clinical isolates of Enterobacteriaceae and collected in the US and Europe during 2014 and 2015. Read More

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http://dx.doi.org/10.1128/AAC.00514-19DOI Listing

Report on two hypervirulent producing a carbapenemase from a Canadian patient.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Jewish General Hospital, Montreal, Quebec, Canada (Y. Longtin)

This report describes two hypervirulent producing KPC identified from a rectal swab and urine culture upon hospital admission. The patient had recent travel to Greece where he was hospitalized. The isolates were sequence type 86, contained an IncHI1B, IncFIB(K) hypervirulent plasmid and an IncFII(K) plasmid harbouring KPC. Read More

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http://aac.asm.org/lookup/doi/10.1128/AAC.00517-19
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http://dx.doi.org/10.1128/AAC.00517-19DOI Listing
April 2019
1 Read

Synergistic effect of colistin combined with PFK-158 against colistin-resistant Enterobacteriaceae.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

As increasing numbers of colistin-resistant bacteria emerge, new therapies are urgently needed to treat infections caused by these pathogens. The discovery of new combination therapies is one important way to solve such problems. Herein, we report that the antitumor drug PFK-158 and its analogs PFK-015 and 3PO can exert synergistic effects with colistin against colistin-resistant Enterobacteriaceae, including positive or high-level colistin resistant (HLCR) isolates, as shown by a checkerboard assay. Read More

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http://dx.doi.org/10.1128/AAC.00271-19DOI Listing

The application of CRISPR/Cas9-based genome editing in studying the mechanism of pandrug resistance in .

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

School of Physical Science and Technology, Shanghai Tech University, Shanghai 201210, China

In this study, a CRISPR/Cas9-mediated genome editing method was used to study the functions of genes , and in mediating colistin and tigecycline resistance in carbapenem-resistant Inactivation of the , , or genes by CRISPR/Cas9 affected bacterial susceptibility to tigecycline or colistin, respectively. This study proved that the CRISPR/Cas9-based genome editing method could be effectively applied to and should be further utilized for genetic characterization. Read More

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http://dx.doi.org/10.1128/AAC.00113-19DOI Listing

BSA-Based Dosing Regimen of Caspofungin in Children: A Population Pharmacokinetics Confirmatory Study.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France

We evaluated the population pharmacokinetics of caspofungin in children (2-12 years old). The real-world data from 48 children were best fit by a two-compartment model with first-order elimination. Subsequent covariate analysis demonstrated that body surface area had a significant correlation with caspofungin pharmacokinetics compared to body weight. Read More

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http://dx.doi.org/10.1128/AAC.00248-19DOI Listing

Comparable Efficacy and Better Safety of Double β-Lactam Combination Therapy versus β-Lactam plus Aminoglycoside in Gram-negatives: A Meta-analysis of Randomized, Controlled Trials.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Departments of Pharmaceutics and Pharmacotherapy & Translational Research, College of Pharmacy, University of Florida, Orlando, FL

There is a great need for efficacious therapies against Gram-negative bacteria. Double β-lactam combinations (DBL) are relatively safe and preclinical data are promising; however, their clinical role has not been well defined. We conducted a meta-analysis of the clinical and microbiological efficacy of DBL compared to β-lactam plus aminoglycoside combinations (BLAG). Read More

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http://dx.doi.org/10.1128/AAC.00425-19DOI Listing

Efficacy and safety of tedizolid phosphate versus linezolid in a randomized Phase 3 trial in patients with acute bacterial skin and skin structure infection.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Leeds Teaching Hospitals & University of Leeds, Leeds, UK.

Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infection (ABSSSI) caused by Gram-positive bacteria in the USA, Europe, and other countries.In this multicenter, double-blind, Phase 3 study, 598 adult ABSSSI patients in China, Taiwan, the Philippines, and the USA were randomized to receive tedizolid 200 mg, intravenous (IV)/oral (PO), once daily for 6 days or linezolid 600 mg, IV/PO twice daily for 10 days. The primary endpoint was early clinical response rate at 48-72 hours. Read More

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http://dx.doi.org/10.1128/AAC.02252-18DOI Listing

Most domestic livestock possess colistin-resistant commensal harboring in a rural community in Vietnam.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan

Colistin is recognized as the last resort for treatment of life-threatening infections caused by multidrug-resistant bacteria; however, the increasing prevalence of colistin-resistant bacteria harboring the mobile colistin resistance gene () poses a threat to the treatment (1).…. Read More

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http://dx.doi.org/10.1128/AAC.00594-19DOI Listing

A novel, widespread allele results in reduced chlorhexidine susceptibility in .

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Seattle Children's Research Institute, Seattle, WA, USA

Chlorhexidine gluconate (CHG) is a topical antiseptic widely used in healthcare settings. In spp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution. Read More

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http://dx.doi.org/10.1128/AAC.02607-18DOI Listing
April 2019
1 Read

Modified mouse model of infection as a platform for probiotic efficacy studies.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Department of Medicine, Division of Infectious Disease, University of Wisconsin - Madison School of Medicine and Public Health, Madison, Wisconsin, USA.

Probiotics may represent a promising approach for reducing () infections (CDI). A clinical trial conducted by our group demonstrated CDI patients undergoing adjunctive treatment with probiotics had reduction in diarrhea duration and compositional changes in their stool microbiome. Here we modified a CDI mouse model to represent clinical outcomes observed in patients and employ this model to identify evidence for prevention of primary CDI and relapse with the same probiotic. Read More

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http://aac.asm.org/lookup/doi/10.1128/AAC.00111-19
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http://dx.doi.org/10.1128/AAC.00111-19DOI Listing
April 2019
1 Read

Population Pharmacokinetic Modeling of VL-2397, A Novel Systemic Antifungal Agent: Analysis of a Single and Multiple Ascending Dose Study in Healthy Subjects.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

University of Liverpool, Liverpool UK.

VL-2397, a novel, systemic antifungal agent, has potent and fungicidal activity against species. Plasma concentrations from a Phase 1 study were used to construct a population pharmacokinetic (PPK) model for VL-2397.: Healthy subjects aged 18 to 55 years received single doses of VL-2397 ranging from 3 to 1200mg, multiple daily doses of 300, 600, or 1200mg for 7 days, or 300mg three-times/day for 7 days followed by 600mg daily for 21 days. Read More

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http://dx.doi.org/10.1128/AAC.00163-19DOI Listing

Treatment with the glycoside hydrolase PslG combats wound infection by improving antibiotic efficacy and host innate immune activity.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Department of Microbiology, University of Washington, Seattle, Washington, United States of America

is an opportunistic, nosocomial bacterial pathogen that forms persistent infections due to the formation of protective communities, known as biofilms. Once formed, the bacteria embedded within the biofilm are recalcitrant to antimicrobial treatment and host immune defenses. Moreover, the presence of biofilms in wounds is correlated with chronic infection and delayed healing. Read More

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http://dx.doi.org/10.1128/AAC.00234-19DOI Listing

Tissue distribution and penetration of isavuconazole at the site of infection in Experimental Invasive Aspergillosis in Mice with underlying Chronic Granulomatous Disease.

Antimicrob Agents Chemother 2019 Apr 15. Epub 2019 Apr 15.

Public Health Research Institute, Rutgers Biomedical and Health Sciences, Newark, NJ, USA

Isavuconazole, the active moiety of the prodrug, isavuconazonium sulfate, has potent activity against a wide spectrum of fungal pathogens and is approved for the treatment of invasive aspergillosis. Yet, little is known for tissue penetration of isavuconazole at the target sites of infection. Herein, we explored spatial and quantitative distribution of isavuconazole in tissue lesions in experimental pulmonary aspergillosis established in mice with chronic granulomatous disease (CGD) (gp91). Read More

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http://dx.doi.org/10.1128/AAC.00524-19DOI Listing
April 2019
1 Read
4.476 Impact Factor

Revised interpretation of the Hain Lifescience GenoType MTBC to differentiate and members of the complex.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Department of Genetics, University of Cambridge, Cambridge, UK.

Using 894 phylogenetically diverse genomes of the complex (MTBC), we simulated the ability of the Hain Lifescience GenoType MTBC to differentiate the causative agents of tuberculosis. We propose a revised interpretation of this assay to reflect its strengths (e.g. Read More

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http://dx.doi.org/10.1128/AAC.00159-19DOI Listing

Daptomycin Dose-Ranging Evaluation with Single vs. Multi-Dose Ceftriaxone Combinations against in an Simulated Endocarditis Vegetation Model.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI

The viridans group streptococci (VGS) are a heterogeneous group of organisms which are important components of the normal human oral flora. Among the VGS, the subgroup is one of the most common causes of infective endocarditis (IE). Daptomycin (DAP) is a potential alternative therapeutic option for invasive infections, given high rates of β-lactam resistance and vancomycin tolerance in such strains. Read More

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http://dx.doi.org/10.1128/AAC.00386-19DOI Listing
April 2019
4 Reads

Novel MenA inhibitors are bactericidal against and synergize with electron-transport chain inhibitors.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Avenue E, Seattle, WA 98102, USA.

is the leading cause of morbidity and mortality by infectious disease worldwide. The incredible disease burden combined with the long course of drug treatment and increasing incidence of antimicrobial resistance among isolates necessitates a need for both novel drugs and drug targets to treat this deadly pathogen. Recent work has produced several promising clinical candidates targeting components of the electron-transport chain (ETC) of , highlighting this pathway's potential as a viable drug target. Read More

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http://dx.doi.org/10.1128/AAC.02661-18DOI Listing

An OXA-23-producing clone spreads under the radar in the French community.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

UMR6249 CNRS Chrono-Environnement, Université de Bourgogne Franche-Comté, Besançon, France.

Nineteen isolates producing carbapenemase OXA-23 were recovered over a 2-year period in 19 French hospitalized patients, of whom 12 had community-onset infections. The isolates exhibited a slightly reduced susceptibility to carbapenems. Compared to other 149 , whole genome analysis revealed that all 19 isolates formed a cluster. Read More

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http://dx.doi.org/10.1128/AAC.00191-19DOI Listing
April 2019
1 Read

Lysocins: Bioengineered Antimicrobials that Deliver Lysins Across the Outer Membrane of Gram-Negative Bacteria.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY 10065.

The prevalence of multidrug-resistant has stimulated development of alternative therapeutics. Bacteriophage peptidoglycan hydrolases, termed lysins, represent an emerging antimicrobial option for targeting Gram-positive bacteria. However, lysins against Gram-negatives are generally deterred by the outer membrane and their inability to work in serum. Read More

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http://dx.doi.org/10.1128/AAC.00342-19DOI Listing

Escherichia coli harboring in a cluster of liver transplant recipients: detection through active surveillance and whole genome sequencing.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Division of Infectious Diseases, Columbia University Irving Medical Center, New York City, NY, United States

, a plasmid-associated gene for colistin resistance, was first described in China in 2015 but its spread in the United States is unknown. We report detection of carrying ST117 in a cluster of three liver transplant recipients. Read More

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http://dx.doi.org/10.1128/AAC.02680-18DOI Listing

Synergic effect of allopurinol in combination with nitro-heterocyclic compounds against .

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Laboratório de Doenças Parasitárias, Escola de Medicina & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil.

Combination therapy has gained attention as a possible strategy for overcoming the limitations of the present therapeutic arsenal for Chagas disease. The aim of this study was to evaluate the effect of allopurinol in association with nitro-heterocyclic compounds on infection with the Y strain of The effect of allopurinol plus benznidazole or nifurtimox on intracellular amastigotes in H9c2 infected cells was assessed in a 72 h assay. The interactions were classified as synergic for both allopurinol/nifurtimox (sums of fractional inhibitory concentrations - ∑FICs = 0. Read More

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http://dx.doi.org/10.1128/AAC.02264-18DOI Listing
April 2019
1 Read

Halogen bond interactions of novel HIV-1 protease inhibitors (PI)(GRL-001-15 and GRL-003-15) with the flap of protease are critical for their potent activity against wild-type and multi-PI-resistant HIV-1 variants.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Tokyo, Japan

We newly generated two nonpeptidic HIV-1 protease inhibitors (PIs), GRL-001-15 and GRL-003-15, which contain a unique P2-crown-THF (THF) and P2'-cyclopropyl-amino-benzothiazole (Cp-Abt) moieties. GRL-001-15 and GRL-003-15 have --fluorophenyl and --fluorophenyl at the P1 site, exert highly potent activity against wild-type HIV-1 with 50% effective concentrations (ECs) of 57 and 50 pM, and have favorable cytotoxicity profiles with 50% cytotoxic concentrations (CCs) of 38 and 11 μM, respectively. The activity of GRL-001-15 against multi-PI-resistant HIV-1 variants was generally greater than that of GRL-003-15. Read More

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http://dx.doi.org/10.1128/AAC.02635-18DOI Listing
April 2019
1 Read

Ceftolozane/tazobactam population pharmacokinetics and dose selection for further clinical evaluation in pediatric patients with complicated urinary tract or complicated intraabdominal infections.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Merck & Co, Inc., Kenilworth, NJ, USA

Ceftolozane/tazobactam, a combination of the novel anti-pseudomonal cephalosporin ceftolozane and the well-established extended-spectrum β-lactamase inhibitor tazobactam, is approved for treating complicated urinary tract (cUTI) and complicated intra-abdominal infections (cIAI) in adults. To determine doses likely to be safe and efficacious in phase 2 pediatric trials for these same indications, single-dose ceftolozane/tazobactam plasma pharmacokinetic data from a recently completed phase 1 trial in pediatric patients (birth to <18 years old) with proven/suspected gram-negative infections, along with pharmacokinetic data from 12 adult studies, were integrated into a population pharmacokinetic (popPK) analysis. Two-compartment linear models with first-order elimination described the concentration-time profiles of ceftolozane and tazobactam in pediatric patients well. Read More

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http://aac.asm.org/lookup/doi/10.1128/AAC.02578-18
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http://dx.doi.org/10.1128/AAC.02578-18DOI Listing
April 2019
6 Reads

Mind the Coverage Gap: A PK-PD Evaluation of Ertapenem for Patients with Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Institute for Clinical Pharmacodynamics, Inc., Schenectady, NY, USA.

Ertapenem provides activity against many pathogens commonly associated with hospital-acquired and ventilator-associated bacterial pneumoniae (HABP and VABP, respectively), including methicillin-susceptible and numerous Gram-negative pathogens with one major gap in coverage - Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were conducted to evaluate ertapenem against the most prevalent Enterobacteriaceae causing HABP/VABP. The objective of these analyses was to provide dose selection support for and demonstrate the appropriateness of ertapenem to empirically treat patients with HABP/VABP when administered with murepavadin, a novel targeted antimicrobial exhibiting a highly specific spectrum of activity against A previously-developed population pharmacokinetic model, total-drug epithelial lining fluid to free-drug serum penetration ratio, contemporary surveillance data for ertapenem against Enterobacteriaceae, and %T>MIC targets associated with efficacy were used to conduct Monte Carlo simulations for five ertapenem regimens administered over short or prolonged durations of infusion. Overall total-drug ELF percent probabilities of PK-PD target attainment based on a %T>MIC target of 35% among simulated patients with HABP/VABP arising from Enterobacteriaceae based on pathogen prevalence data for nosocomial pneumonia ranged from 89. Read More

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http://aac.asm.org/lookup/doi/10.1128/AAC.00318-19
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http://dx.doi.org/10.1128/AAC.00318-19DOI Listing
April 2019
2 Reads

Co-carriage of distinct and plasmids in a single ST11 carbapenem-resistant isolate.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

The endemic spread of carbapenemase-producing in Taiwan has become problematic (1).…. Read More

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http://aac.asm.org/lookup/doi/10.1128/AAC.02282-18
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http://dx.doi.org/10.1128/AAC.02282-18DOI Listing
April 2019
1 Read
4.476 Impact Factor

Pulmonary Pharmacokinetics of Oseltamivir Carboxylate in Rats after Nebulization or Intravenous Administration of its Prodrug Oseltamivir Phosphate.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

INSERM, U1070, UFR de Médecine Pharmacie, Université de Poitiers, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9, France

The aim of this study was to investigate the pharmacokinetics of oseltamivir phosphate, a prodrug, and its active moiety in plasma and lung after its nebulization and intravenous administration, in rats. Only 2% of prodrug was converted into active moiety pre-systematically, attesting to a low advantage of oseltamivir phosphate nebulization suggesting that oseltamivir phosphate nebulization is not a good option to obtain a high exposure of the active moiety at the infection site within lung. Read More

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http://dx.doi.org/10.1128/AAC.00074-19DOI Listing

The Impact of Timing of Antibiotics on Digestive Colonization with Carbapenemase-Producing in a Murine Model.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Univ. Lille, EA 7366 - Recherche Translationnelle Relations Hôte-Pathogènes, F-59000 Lille, France

While antibiotic use is a risk factor of carbapenemase-producing (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization with NDM-1-producing , a single injection of clindamycin within at most one week before or after CPE exposure induced colonization persisting up to 100-days. Timing of antibiotic administration relative to CPE exposure may be relevant to infection control and antimicrobial stewardship approaches. Read More

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http://dx.doi.org/10.1128/AAC.00360-19DOI Listing

Preclinical development of inhalable D-cycloserine and ethionamide to overcome pharmacokinetic interaction and enhance efficacy against .

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

CSIR-Central Drug Research Institute, Janakipuram Extension, Sutapur Road, Lucknow, UP, 226031, India.

We compared pharmacokinetics and efficacy of a combination of D-cycloserine (DCS) and ethionamide (ETO) via oral and inhalation routes in mice. The plasma t of oral ETO at human-equivalent dose reduced from 4.63±0. Read More

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http://dx.doi.org/10.1128/AAC.00099-19DOI Listing
April 2019
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Population Pharmacokinetics and dosing optimisation of Imipenem in Children with haematological malignancies.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Department of Clinical Pharmacy, School of PharmaceuticalSciences, Shandong University, Jinan, China

Imipenem is widely used for the treatment of children with serious infections. Currently, there is lack of pharmacokinetic studies of imipenem in children with hematological malignancies. Given the significant impact of disease on pharmacokinetics and increased resistance, we aimed to conduct a population based pharmacokinetic study of imipenem and optimize the dosage regimens for this vulnerable population. Read More

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http://dx.doi.org/10.1128/AAC.00006-19DOI Listing
April 2019
3 Reads
4.476 Impact Factor

Emergence of IMP-34 and OXA-58-producing carbapenem-resistant .

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Department of Infection Control and Laboratory Diagnosis, Internal Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan.

spp. are emerging pathogens causing opportunistic and healthcare-associated infections.…. Read More

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http://dx.doi.org/10.1128/AAC.02633-18DOI Listing

and exposure-effect relationship of liposomal amphotericin B against .

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Clinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

pharmacokinetic/pharmacodynamic data of liposomal amphotericin B (L-AMB) were compared with animal data from neutropenic and non-neutropenic models of azole-susceptible and azole-resistant invasive aspergillosis. L-AMB was equally effective. The C/MIC ratio associated with 50% of maximal activity was 0. Read More

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http://aac.asm.org/lookup/doi/10.1128/AAC.02673-18
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http://dx.doi.org/10.1128/AAC.02673-18DOI Listing
April 2019
3 Reads

In Vitro Activity of New Tetracycline Analogs Omadacycline and Eravacycline Against Drug-Resistant Clinical Isolates of .

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Tigecycline is used in multidrug regimens for salvage therapy of infections but is often poorly tolerated and has no oral formulation. Here, we report similar in vitro activity of two newly approved tetracycline analogs, omadacycline and eravacycline, against 28 drug-resistant clinical isolates of complex. Since omadacycline and eravacycline appear better tolerated than tigecycline and omadacycline is also formulated for oral dosing, they may represent new treatment options for infections. Read More

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http://dx.doi.org/10.1128/AAC.00470-19DOI Listing

No Dose Adjustment for Isavuconazole Based on Age or Sex.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Astellas Pharma Inc, Tokyo, Japan.

This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy non-elderly (18-45 years) and elderly (≥65 years) males and females. Overall, 48 subjects were enrolled in the study ( = 12 each, non-elderly male and female and elderly male and female). All subjects received a single oral dose of 372 mg of isavuconazonium sulfate (equivalent to 200 mg isavuconazole). Read More

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http://dx.doi.org/10.1128/AAC.02629-18DOI Listing
April 2019
4.476 Impact Factor

Pharmacokinetics of Caspofungin in Critically Ill Patients in Relation to Liver Dysfunction: Differential Impact of Plasma Albumin and Bilirubin Levels.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Caspofungin has a liver-dependent metabolism. Reduction of the dose is recommended based on Child-Pugh (C-P) score. In critically ill patients drug pharmacokinetics (PK) may be altered. Read More

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http://dx.doi.org/10.1128/AAC.02466-18DOI Listing
April 2019
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A Novel VIM-type Metallo-β-Lactamase Variant, VIM-60, with Increased Fourth-generation Cephalosporin-hydrolyzing Activities in Clinical Isolates in Japan.

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Department of Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

A novel VIM-type metallo-β-lactamase variant, VIM-60, was identified in multidrug-resistant clinical isolates in Japan. Compared with VIM-2, VIM-60 had two amino acid substitutions (Arg228Leu and His252Arg) and higher catalytic activities against fourth-generation cephalosporins. The genetic context for was - on the chromosome. Read More

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http://dx.doi.org/10.1128/AAC.00124-19DOI Listing

Mildred Rebstock: Profile of the Medicinal Chemist who Synthesized Chloramphenicol.

Authors:
David M Aronoff

Antimicrob Agents Chemother 2019 Apr 8. Epub 2019 Apr 8.

Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center

This year marks the 70 anniversary since Parke-Davis and Company announced the synthesis of chloramphenicol, the first naturally-occurring antibiotic to be chemically generated for large-scale production. The effort was led by the chemist Mildred Rebstock, Ph.D. Read More

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http://dx.doi.org/10.1128/AAC.00648-19DOI Listing