32,196 results match your criteria Antimicrobial Agents And Chemotherapy[Journal]


GSK2556286 Is a Novel Antitubercular Drug Candidate Effective with the Potential To Shorten Tuberculosis Treatment.

Antimicrob Agents Chemother 2022 May 24:e0013222. Epub 2022 May 24.

Diseases of the Developing World, GlaxoSmithKline R+D Limited, Tres Cantos, Madrid, Spain.

As a result of a high-throughput compound screening campaign using Mycobacterium tuberculosis-infected macrophages, a new drug candidate for the treatment of tuberculosis has been identified. GSK2556286 inhibits growth within human macrophages (50% inhibitory concentration [IC] = 0.07 μM), is active against extracellular bacteria in cholesterol-containing culture medium, and exhibits no cross-resistance with known antitubercular drugs. Read More

View Article and Full-Text PDF

Characterization of Glucokinases from Pathogenic Free-Living Amoebae.

Antimicrob Agents Chemother 2022 May 23:e0237321. Epub 2022 May 23.

Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson Universitygrid.26090.3d, Clemson, South Carolina, USA.

Infection with pathogenic free-living amoebae, including Naegleria fowleri, spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Read More

View Article and Full-Text PDF

Novel Neplanocin A Derivatives as Selective Inhibitors of Hepatitis B Virus with a Unique Mechanism of Action.

Antimicrob Agents Chemother 2022 May 23:e0207321. Epub 2022 May 23.

Division of Antiviral Chemotherapy, Joint Research Center for Human Retrovirus Infection, Kagoshima Universitygrid.258333.c, Kagoshima, Japan.

Novel neplanocin A derivatives have been identified as potent and selective inhibitors of hepatitis B virus (HBV) replication . These include (1S,2R,5R)-5-(5-bromo-4-methyl-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol (AR-II-04-26) and (1S,2R,5R)-5-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-3-(hydroxylmethyl)cyclopent-3-ene-1,2-diol (MK-III-02-03). The 50% effective concentrations of AR-II-04-26 and MK-III-02-03 were 0. Read More

View Article and Full-Text PDF

Population Pharmacokinetic Model and Alternative Dosing Regimens for Dolutegravir Coadministered with Rifampicin.

Antimicrob Agents Chemother 2022 May 23:e0021522. Epub 2022 May 23.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Towngrid.7836.a, Cape Town, South Africa.

Dolutegravir-based regimens are recommended as first-line therapy for HIV in low- and middle-income countries where tuberculosis is the most common opportunistic infection. Concurrent HIV/tuberculosis treatment is challenging because of drug-drug interactions. Our analysis aimed to characterize dolutegravir's population pharmacokinetics when coadministered with rifampicin and assess alternative dolutegravir dosing regimens. Read More

View Article and Full-Text PDF

Comparative Analysis of the Mechanism of Resistance to Silver Nanoparticles and the Biocide 2,2-Dibromo-3-Nitrilopropionamide.

Antimicrob Agents Chemother 2022 May 23:e0203121. Epub 2022 May 23.

Department of Biological Sciences, Michigan Technological University, Houghton, Michigan, USA.

Antimicrobials such as nanoparticles and biocides are used to control microbial growth. We used Escherichia coli to study the process of acquired resistance to silver nanoparticles (Ag-NP) and the industrial biocide DBNPA when grown in sub-MICs. We determined the MICs of these two antimicrobials against E. Read More

View Article and Full-Text PDF

Determining Susceptibility in Vaginal Isolates.

Antimicrob Agents Chemother 2022 May 23:e0236621. Epub 2022 May 23.

Department of Biochemistry, Microbiology, and Immunology, Wayne State Universitygrid.254444.7, Detroit, Michigan, USA.

Antifungal drug susceptibility tests (AST) for Candida albicans are increasingly demanded for women with refractory or recurrent vaginitis due to fluconazole resistance. Given reduced activity of azole drugs at pH levels found in women with vaginitis, it is proposed that AST be performed at pH 4.5, since testing at only the recommended pH 7. Read More

View Article and Full-Text PDF

Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation.

Antimicrob Agents Chemother 2022 May 23:e0009922. Epub 2022 May 23.

Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Differences in pharmacokinetics/pharmacodynamics (PK/PD) target attainment are rarely considered when antifungals are switched in critically ill patients. This study intends to explore whether the antifungal de-escalation treatment strategy and the new intermittent dosing strategy of echinocandins in critically ill patients are able to achieve the corresponding PK/PD targets. The published population PK models of antifungals in critically ill patients and a public data set from the MIMIC-III database ( = 662) were employed to evaluate PK/PD target attainment of different dosing regimens of antifungals. Read More

View Article and Full-Text PDF

High-Dosage Fosfomycin Results in Adequate Plasma and Target-Site Exposure in Morbidly Obese and Nonobese Nonhyperfiltration Patients.

Antimicrob Agents Chemother 2022 May 23:e0230221. Epub 2022 May 23.

Freie Universitaet Berlin, Institute of Pharmacy, Department of Clinical Pharmacy and Biochemistry, Berlin, Germany.

The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. After characterization of plasma and microdialysis-derived target site pharmacokinetics via population analysis, short-term infusions of fosfomycin 3 to 4 times daily were simulated. Read More

View Article and Full-Text PDF

The Effect of Rifampicin on Darunavir, Ritonavir, and Dolutegravir Exposure within Peripheral Blood Mononuclear Cells: a Dose Escalation Study.

Antimicrob Agents Chemother 2022 May 18:e0013622. Epub 2022 May 18.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Towngrid.7836.a, Cape Town, South Africa.

Ritonavir-boosted darunavir (DRV/r) and dolutegravir (DTG) are affected by induction of metabolizing enzymes and efflux transporters caused by rifampicin (RIF). This complicates the treatment of people living with HIV (PLWH) diagnosed with tuberculosis. Recent data showed that doubling DRV/r dose did not compensate for this effect, and hepatic safety was unsatisfactory. Read More

View Article and Full-Text PDF

Inhibitory Activity of Antibacterial Mouthwashes and Antiseptic Substances against Neisseria gonorrhoeae.

Antimicrob Agents Chemother 2022 May 17:e0004222. Epub 2022 May 17.

Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute, Melbourne, Victoria, Australia.

Improved treatment and prevention strategies, such as antimicrobial mouthwashes, may be important for addressing the public health threat of antimicrobial-resistant Neisseria gonorrhoeae. Here, we describe the activity of seven common antibacterial mouthwashes and antiseptics against N. gonorrhoeae isolates, incorporating the use of a human saliva test matrix. Read More

View Article and Full-Text PDF

Clinical Pharmacology and Utility of Contezolid in Chinese Patients with Complicated Skin and Soft-Tissue Infections.

Antimicrob Agents Chemother 2022 May 16:e0243021. Epub 2022 May 16.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

This study aimed to build a population pharmacokinetic (PopPK) model for contezolid tablet (MRX-I) in healthy subjects and adults with complicated skin and soft-tissue infections (cSSTIs) to further evaluate the efficacy and safety of contezolid and recommend the optimal dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. PopPK analysis was performed using a nonlinear mixed-effects model (NONMEM) to examine the effects of age, body weight, sex, liver and renal functions, albumin, food, dosage strength, and subject type on the PK parameters of contezolid. PK/PD analysis was combined with the MIC of contezolid, clinical/microbiological efficacy, and nonclinical study data. Read More

View Article and Full-Text PDF

Multicenter Population Pharmacokinetic Study of Unbound Ceftriaxone in Critically Ill Patients.

Antimicrob Agents Chemother 2022 May 16:e0218921. Epub 2022 May 16.

University of Queenslandgrid.1003.2 Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, Queensland, Australia.

The objective of this study was to describe the total and unbound population pharmacokinetics of ceftriaxone in critically ill adult patients and to define optimized dosing regimens. Total and unbound ceftriaxone concentrations were obtained from two pharmacokinetic studies and from a therapeutic drug monitoring (TDM) program at a tertiary hospital intensive care unit. Population pharmacokinetic analysis and Monte Carlo simulations were used to assess the probability of achieving a free trough concentration/MIC ratio of ≥1 using Pmetrics for R. Read More

View Article and Full-Text PDF

The NaHCO-Responsive Phenotype in Methicillin-Resistant Staphylococcus aureus (MRSA) Is Influenced by Genotype.

Antimicrob Agents Chemother 2022 May 16:e0025222. Epub 2022 May 16.

Department of Microbiology & Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.

Methicillin-resistant Staphylococcus aureus (MRSA) strains are a leading cause of many invasive clinical syndromes, and pose treatment difficulties due to their resistance to most β-lactams on standard laboratory testing. A novel phenotype frequently identified in MRSA strains, termed 'NaHCO-responsiveness', is a property whereby strains are susceptible to many β-lactams in the presence of NaHCO. Specific genotypes, repression of /PBP2a expression and perturbed maturation of PBP2a by NaHCO have all been associated with this phenotype. Read More

View Article and Full-Text PDF

Coexistence of and on a Novel Plasmid of GR59 from an Acinetobacter towneri Isolate.

Antimicrob Agents Chemother 2022 May 12:e0020622. Epub 2022 May 12.

The School of Basic Medical Science and Public Center of Experimental Technology, Southwest Medical University, Luzhou, Sichuan, China.

View Article and Full-Text PDF

Gene Amplification of : a New Mechanism of Resistance to Azole Compounds in Trichophyton indotineae.

Antimicrob Agents Chemother 2022 May 12:e0005922. Epub 2022 May 12.

Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Trichophyton indotineae causes dermatophytosis that is resistant to terbinafine and azole compounds. The aim of this study was to determine the mechanisms of resistance to itraconazole (ITC) and voriconazole (VRC) in strains of . Two azole-sensitive strains (ITC MIC < 0. Read More

View Article and Full-Text PDF

Islatravir Has a High Barrier to Resistance and Exhibits a Differentiated Resistance Profile from Approved Nucleoside Reverse Transcriptase Inhibitors (NRTIs).

Antimicrob Agents Chemother 2022 May 12:e0013322. Epub 2022 May 12.

Merck & Co., Inc., Infectious Disease and Vaccines, Kenilworth, New Jersey, USA.

Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that inhibits human immunodeficiency virus (HIV) reverse transcription by blocking reverse transcriptase (RT) translocation on the primer:template. ISL is being developed for the treatment of HIV-1 infection. To expand our knowledge of viral variants that may confer reduced susceptibility to ISL, resistance selection studies were conducted with wild-type (WT) subtype A, B, and C viruses. Read More

View Article and Full-Text PDF

Evolution of Enterococcus faecium in Response to a Combination of Daptomycin and Fosfomycin Reveals Distinct and Diverse Adaptive Strategies.

Antimicrob Agents Chemother 2022 May 11:e0233321. Epub 2022 May 11.

Department of Biosciences, Rice Universitygrid.21940.3e, Houston, Texas, USA.

Infections caused by vancomycin-resistant Enterococcus faecium (VREfm) are an important public health threat. VREfm isolates have become increasingly resistant to the front-line antibiotic daptomycin (DAP). As such, the use of DAP combination therapies with other antibiotics like fosfomycin (FOS) has received increased attention. Read More

View Article and Full-Text PDF

Why Bother? Lab Monitoring in Beta-Lactam Outpatient Parenteral Antimicrobial Therapy.

Antimicrob Agents Chemother 2022 May 11:e0057922. Epub 2022 May 11.

University of Utah Health, Division of Infectious Diseases, Salt Lake City, Utah, USA.

View Article and Full-Text PDF

Activity of Nitroxoline in Antifungal-Resistant Species Isolated from the Urinary Tract.

Antimicrob Agents Chemother 2022 May 11:e0226521. Epub 2022 May 11.

Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical faculty and University Hospital of Cologne, Cologne, Germany.

Infections by drug-resistant fungi are increasingly reported worldwide; however, only few novel antifungals are being developed. The old antimicrobial nitroxoline is currently repurposed for oral treatment of bacterial urinary tract infections (UTI). Previously, antifungal activity has been demonstrated and in contrast to many antifungals nitroxoline reaches high urinary concentrations. Read More

View Article and Full-Text PDF

Antiplatelet Therapy in Staphylococcus aureus Bacteremia: No Time Like the Past?

Antimicrob Agents Chemother 2022 May 10:e0036522. Epub 2022 May 10.

Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA.

In this invited commentary, we reflect on the accompanying study by A. R. Caffrey, H. Read More

View Article and Full-Text PDF

Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants.

Antimicrob Agents Chemother 2022 May 9:e0022222. Epub 2022 May 9.

Gilead Sciences, Inc., Foster City, California, USA.

Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern/variants of interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV [VEKLURY]) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Read More

View Article and Full-Text PDF

Distribution of Common and Rare Genetic Markers of Second-Line-Injectable-Drug Resistance in Mycobacterium tuberculosis Revealed by a Genome-Wide Association Study.

Antimicrob Agents Chemother 2022 May 9:e0207521. Epub 2022 May 9.

Laboratory for Pathogenesis of Clinical Drug Resistance and Persistence (LPCDRP), Biomedical Informatics Research Center, Division of Epidemiology, School of Public Health, San Diego State Universitygrid.263081.e, San Diego, California, USA.

Point mutations in the gene and the promoter are known to confer resistance to the second-line injectable drugs (SLIDs) amikacin (AMK), capreomycin (CAP), and kanamycin (KAN). While mutations in these canonical genes confer the majority of SLID resistance, alternative mechanisms of resistance are not uncommon and threaten effective treatment decisions when using conventional molecular diagnostics. In total, 1,184 clinical Mycobacterium tuberculosis isolates from 7 countries were studied for genomic markers associated with phenotypic resistance. Read More

View Article and Full-Text PDF

Pharmacokinetics and Dose Optimization Strategies of Para-Aminosalicylic Acid in Children with Rifampicin-Resistant Tuberculosis.

Antimicrob Agents Chemother 2022 May 4:e0226421. Epub 2022 May 4.

Desmond Tutu TB Center, Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch Universitygrid.11956.3a, Cape Town, South Africa.

Treatment options for children with Rifampicin-resistant tuberculosis (RR-TB) remain limited, and para-aminosalicylic acid (PAS) is still a relevant component of treatment regimens. Prevention of resistance to companion drugs by PAS is dose related, and at higher concentrations, PAS may exhibit significant bactericidal activity in addition to its bacteriostatic properties. The optimal dosing of PAS in children is uncertain, specifically for delayed-release granule preparations, which are the most used. Read More

View Article and Full-Text PDF

Safety of Inhaled Amphotericin B Lipid Complex as Antifungal Prophylaxis in Lung Transplant Recipients.

Antimicrob Agents Chemother 2022 May 4:e0028322. Epub 2022 May 4.

Department of Medicine, Duke Universitygrid.26009.3d Medical Center, Durham, North Carolina, USA.

Inhaled formulations of amphotericin B are the most widely used antifungal prophylactic agents in lung transplant recipients, yet there are limited data on their safety. We performed a single-center retrospective cohort study of 603 consecutive patients who underwent lung transplantation between 2012 and 2017 and received antifungal prophylaxis with inhaled amphotericin B lipid complex (iABLC) from the day of transplantation until hospital discharge. Of 603 patients, 600 (99. Read More

View Article and Full-Text PDF

A Tribute to George A. Jacoby.

Antimicrob Agents Chemother 2022 May 4:e0049822. Epub 2022 May 4.

Warren Alpert Medical School of Brown Universitygrid.40263.33, Providence, Rhode Island, USA.

View Article and Full-Text PDF

Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1.

Antimicrob Agents Chemother 2022 May 3:e0175121. Epub 2022 May 3.

ViiV Healthcare, Branford, Connecticut, USA.

In the phase 3 BRIGHTE study in heavily treatment-experienced adults with multidrug-resistant HIV-1, fostemsavir plus optimized background therapy (OBT) resulted in sustained rates of virologic suppression through 96 weeks. HIV-1 RNA <40 copies/mL was achieved in 163/272 (60%) Randomized Cohort (RC) participants (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants (with 0 fully active antiretrovirals). Here we report genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC participants who met protocol-defined virologic failure (PDVF) criteria through Week 96. Read More

View Article and Full-Text PDF

Evaluation of Experimental and Clinical Efficacy on Surgical Debridement and Systemic Antibiotics Treatment for Early Knee Infection after Anterior Cruciate Ligament Reconstruction.

Antimicrob Agents Chemother 2022 May 2:e0011222. Epub 2022 May 2.

Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan Universitygrid.413247.7, Wuhan, China.

Deep knee infection (DKI) after anterior cruciate ligament reconstruction (ACLR) is rare and challenging. The optimal treatment strategy for infection after ACLR remains controversial. This study aimed to investigate the optimal treatment for early infection after ACLR surgery. Read More

View Article and Full-Text PDF

Evaluation of Tebipenem Hydrolysis by β-Lactamases Prevalent in Complicated Urinary Tract Infections.

Antimicrob Agents Chemother 2022 May 2;66(5):e0239621. Epub 2022 May 2.

Department of Pharmacology and Chemical Biology, Baylor College of Medicinegrid.39382.33, Houston, Texas, USA.

Tebipenem pivoxil is the first orally available carbapenem antibiotic and has been approved in Japan for treating ear, nose, and throat and respiratory infections in pediatric patients. Its active moiety, tebipenem, has shown potent antimicrobial activity against clinical isolates of species from patients with urinary tract infections (UTIs), including those producing extended-spectrum β-lactamases (ESBLs) and/or AmpC β-lactamase. In the present study, tebipenem was tested for stability to hydrolysis by a set of clinically relevant β-lactamases, including TEM-1, AmpC, CTX-M, OXA-48, KPC, and NDM-1 enzymes. Read More

View Article and Full-Text PDF

Activity of Ceftolozane-Tazobactam, Imipenem-Relebactam, Ceftazidime-Avibactam, and Comparators against Pseudomonas aeruginosa Isolates Collected in United States Hospitals According to Results from the SMART Surveillance Program, 2018 to 2020.

Antimicrob Agents Chemother 2022 May 2;66(5):e0018922. Epub 2022 May 2.

IHMA, Schaumburg, Illinois, USA.

Ceftolozane-tazobactam (C/T), imipenem-relebactam (IMR), and ceftazidime-avibactam (CZA) were tested against 2,531 P. aeruginosa strains isolated from patients in the United States from 2018 to 2020 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance program. MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 (2021) breakpoints. Read More

View Article and Full-Text PDF

Activity of Ertapenem against Neisseria gonorrhoeae Clinical Isolates with Decreased Susceptibility or Resistance to Extended-Spectrum Cephalosporins in Nanjing, China (2013 to 2019).

Antimicrob Agents Chemother 2022 May 2;66(5):e0010922. Epub 2022 May 2.

Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.

Neisseria gonorrhoeae isolates collected in Nanjing, China, that possessed decreased susceptibility (or resistance) to extended-spectrum cephalosporins (ESCs) were examined for susceptibility to ertapenem, and their sequence types were determined. Ceftriaxone and cefixime MICs of ≥0.125 mg/L and ≥0. Read More

View Article and Full-Text PDF