Minireviews
MinireviewFocusing the Lens on the CAMERA Concepts: Early Combination β-Lactam and Vancomycin Therapy in Methicillin-Resistant Staphylococcus aureus BacteremiaMethicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on health care systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Diseases Society of America currently recommend...
Editor's Pick MinireviewThe Emerging Role of β-Lactams in the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream InfectionsMethicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-...
Chemistry; Biosynthesis
Chemistry; BiosynthesisIn Vitro Evaluation of Radiolabeled Amphotericin B for Molecular Imaging of Mold InfectionsInvasive pulmonary aspergillosis and mucormycosis are life-threatening complications in immunocompromised patients. A rapid diagnosis followed by early antifungal treatment is essential for patient survival. Given the limited spectrum of biomarkers for invasive mold infections, recent studies have proposed the use of radiolabeled siderophores or antibodies as molecular probes to increase the specificity of radiological findings by...
Mechanisms of Action: Physiological Effects
Mechanisms of Action: Physiological EffectsIn Vitro and In Vivo Antibiotic Capacity of Two Host Defense PeptidesTwo nonamidated host defense peptides named Pin2[G] and FA1 were evaluated against three types of pathogenic bacteria: two (Staphylococcus aureus UPD13 and Pseudomonas aeruginosa UPD3) isolated from diabetic foot ulcer patients, and another (...
Mechanisms of Action: Physiological EffectsLeishmanicidal Activity of an In Silico-Screened Novel Inhibitor against Ascorbate Peroxidase of Leishmania donovaniPeroxidases are a heterogeneous family of enzymes that have diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defense system of Leishmania. In view of developing new and novel therapeutics, we performed in silico studies in order to search for a ligand library and identify new drug candidates and their physiological roles...
Mechanisms of Resistance
Mechanisms of ResistanceStructural Basis of Reduced Susceptibility to Ceftazidime-Avibactam and Cefiderocol in Enterobacter cloacae Due to AmpC R2 Loop DeletionCeftazidime-avibactam and cefiderocol are two of the latest generation β-lactam agents that possess expanded activity against highly drug-resistant bacteria, including carbapenem-resistant Enterobacterales. Here, we show that structural changes in AmpC β-lactamases can confer reduced susceptibility to both agents. A multidrug-resistant Enterobacter cloacae...
Mechanisms of ResistanceEmergence of fexA in Mediating Resistance to Florfenicols in CampylobacterFlorfenicol belongs to a class of phenicol antimicrobials widely used as feed additives and for the treatment of respiratory infections. In recent years, increasing resistance to florfenicol has been reported in Campylobacter spp., the leading foodborne enteric pathogens causing diarrheal diseases worldwide. Here, we reported the identification of fexA, a novel mobile florfenicol resistance gene in Campylobacter...
Mechanisms of ResistancePathogenicity Genomic Island-Associated CrpP-Like Fluoroquinolone-Modifying Enzymes among Pseudomonas aeruginosa Clinical Isolates in EuropeMany transferable quinolone resistance mechanisms have been identified in Gram-negative bacteria. The plasmid-encoded 65-amino-acid-long ciprofloxacin-modifying enzyme CrpP was recently identified in Pseudomonas aeruginosa isolates. We analyzed a collection of 100 clonally unrelated and multidrug-resistant...
Mechanisms of ResistanceInfluence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivaxCytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of...
Mechanisms of ResistanceMutation of kvrA Causes OmpK35 and OmpK36 Porin Downregulation and Reduced Meropenem-Vaborbactam Susceptibility in KPC-Producing Klebsiella pneumoniaeMeropenem-vaborbactam resistance in Klebsiella pneumoniae isolates is associated with loss-of-function mutations in the OmpK35 and OmpK36 porins. We identify two previously unknown loss-of-function mutations that confer cefuroxime resistance in K. pneumoniae isolates. The proteins lost were NlpD and...
Mechanisms of ResistanceA Genotype-Phenotype Correlation Study of SHV β-Lactamases Offers New Insight into SHV Resistance ProfilesThe SHV β-lactamases (BLs) have undergone strong allele diversification that has changed their substrate specificities. Based on 147 NCBI entries for SHV alleles, in silico mathematical models predicted 5 positions as relevant for the β-lactamase inhibitor (BLI)-resistant (2br) phenotype, 12 positions as relevant for the extended-spectrum BL (ESBL) (2be) phenotype, and 2 positions as related solely to the narrow-spectrum (2b)...
Mechanisms of ResistanceProbing the Molecular Mechanism of Rifampin Resistance Caused by the Point Mutations S456L and D441V on Mycobacterium tuberculosis RNA Polymerase through Gaussian Accelerated Molecular Dynamics SimulationRifampin is the first-line antituberculosis drug, with Mycobacterium tuberculosis RNA polymerase as the molecular target. Unfortunately, M. tuberculosis strains that are resistant to rifampin have been identified in clinical settings, which limits its therapeutic effects. In clinical isolates, S531L...
Mechanisms of ResistanceExperimentally Engineered Mutations in a Ubiquitin Hydrolase, UBP-1, Modulate In Vivo Susceptibility to Artemisinin and Chloroquine in Plasmodium bergheiAs resistance to artemisinins (current frontline drugs in malaria treatment) emerges in Southeast Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other regions where malaria is endemic. Reduced susceptibility to artemisinin in Southeast...
Susceptibility
SusceptibilityThioridazine Is an Efflux Pump Inhibitor in Mycobacterium avium Complex but of Limited Clinical RelevanceTreatment of Mycobacterium avium complex pulmonary disease (MAC-PD) is challenging partly due to high efflux pump expression. Thioridazine might block these efflux pumps. We explore the efficacy of thioridazine against M. avium isolates using MICs, time-kill combination assays, ex vivo...
SusceptibilityAntimicrobial Susceptibilities of Clostridium difficile Isolates from 12 Asia-Pacific Countries in 2014 and 2015Clostridium (Clostridioides) difficile causes toxin-mediated diarrhea and pseudomembranous colitis, primarily among hospital inpatients. Outbreaks of C. difficile infection (CDI) have been caused by strains with acquired antimicrobial resistance, particularly fluoroquinolone resistance, including...
SusceptibilityManogepix (APX001A) Displays Potent In Vitro Activity against Human Pathogenic Yeast, but with an Unexpected Correlation to Fluconazole MICsManogepix (APX001A) is the active moiety of the novel drug candidate fosmanogepix (APX001). We previously reported the broad-spectrum activity of manogepix but also observed a correlation between increased manogepix and fluconazole MICs. Here, we extended this study and included isolates with acquired fluconazole resistance. Isolates (n = 835) were identified using CHROMagar, matrix-assisted laser desorption ionization–time of...
SusceptibilitySpecies Distribution and Comparison between EUCAST and Gradient Concentration Strips Methods for Antifungal Susceptibility Testing of 112 Aspergillus Section Nigri IsolatesAspergillus niger, the third species responsible for invasive aspergillosis, has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the Aspergillus section Nigri. However, little is yet known among the section Nigri about the species...
SusceptibilityActivity of Epigenetic Inhibitors against Plasmodium falciparum Asexual and Sexual Blood StagesEarlier genetic and inhibitor studies showed that epigenetic regulation of gene expression is critical for malaria parasite survival in multiple life stages and a promising target for new antimalarials. We therefore evaluated the activity of 350 diverse epigenetic inhibitors against multiple stages of Plasmodium falciparum. We observed ≥90% inhibition at 10 μM for 28...
Antiviral Agents
Antiviral AgentsDevelopment of Novel Anti-influenza Thiazolides with Relatively Broad-Spectrum Antiviral PotentialsSeasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug resistance to specific anti-influenza virus drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug, nitazoxanide, with antiviral activity against influenza and a broad range of viruses...
Antiviral AgentsLaninamivir-Interferon Lambda 1 Combination Treatment Promotes Resistance by Influenza A Virus More Rapidly than Laninamivir AloneEach year, 5% to 20% of the population of the United States becomes infected with influenza A virus. Combination therapy with two or more antiviral agents has been considered a potential treatment option for influenza virus infection. However, the clinical results derived from combination treatment with two or more antiviral drugs have been variable. We examined the effectiveness of cotreatment with two distinct classes of anti-...
Antiviral AgentsA Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of MHAA4549A, a Monoclonal Antibody, plus Oseltamivir in Patients Hospitalized with Severe Influenza A Virus InfectionFor patients hospitalized with severe influenza A virus infection, morbidity and mortality remain high. MHAA4549A, a human monoclonal antibody targeting the influenza A virus hemagglutinin stalk, has demonstrated pharmacological activity in animal studies and in a human influenza A challenge study. We evaluated the safety and efficacy of MHAA4549A plus oseltamivir against influenza A virus infection in hospitalized patients. The CRANE...
Antiviral AgentsQuercetin Blocks Ebola Virus Infection by Counteracting the VP24 Interferon-Inhibitory FunctionEbola virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The epidemics from 2013 to 2016 resulted in more than 11,000 deaths, and another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type I...
Antiviral AgentsNovel Class of Chikungunya Virus Small Molecule Inhibitors That Targets the Viral Capping MachineryDespite the worldwide reemergence of the chikungunya virus (CHIKV) and the high morbidity associated with CHIKV infections, there is no approved vaccine or antiviral treatment available. Here, we aimed to identify the target of a novel class of CHIKV inhibitors, i.e., the CHVB series. CHVB compounds inhibit the in vitro replication of CHIKV isolates with 50% effective concentrations in the low-micromolar range. A CHVB-resistant...
Editor's Pick Antiviral AgentsIdentification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved DrugsDrug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in...
Antiviral AgentsInhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025)Cyclophilins play a key role in the life cycle of coronaviruses. Alisporivir (Debio 025) is a nonimmunosuppressive analogue of cyclosporine with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC50) of 0.46 ± 0.04 μM. Alisporivir inhibited a postentry step of the SARS-CoV-2 life cycle. These results justify...
Antiviral AgentsEfficacy of Neuraminidase Inhibitors against H5N6 Highly Pathogenic Avian Influenza Virus in a Nonhuman Primate ModelAttention has been paid to H5N6 highly pathogenic avian influenza virus (HPAIV) because of its heavy burden on the poultry industry and human mortality. Since an influenza A virus carrying N6 neuraminidase (NA) has never spread in humans, the potential for H5N6 HPAIV to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. We used nonhuman primates to elucidate the pathogenesis of...
Epidemiology and Surveillance
Epidemiology and SurveillanceEpidemiological Study on Prevalence, Serovar Diversity, Multidrug Resistance, and CTX-M-Type Extended-Spectrum β-Lactamases of Salmonella spp. from Patients with Diarrhea, Food of Animal Origin, and Pets in Several Provinces of ChinaA total of 2,283 Salmonella isolates were recovered from 18,334 samples, including samples from patients with diarrhea, food of animal origin, and pets, across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Salmonella enterica...
Epidemiology and SurveillanceEmergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular TreatmentA case of Mycobacterium leprae rifampin resistance after irregular antileprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved...
Epidemiology and SurveillanceGenetic Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis in MongoliaGlobally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al. analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA...
Epidemiology and SurveillanceImpact of vanA-Positive Enterococcus faecium Exhibiting Diverse Susceptibility Phenotypes to Glycopeptides on 30-Day Mortality of Patients with a Bloodstream InfectionThis study was performed to evaluate the impacts of vanA positivity of Enterococcus faecium exhibiting diverse susceptibility phenotypes to glycopeptides on clinical outcomes in patients with a bloodstream infection (BSI) through a prospective, multicenter, observational study. A total of 509 patients with...
Epidemiology and SurveillancePrediction of Antibiotic Susceptibility for Urinary Tract Infection in a Hospital SettingEmpiric antibiotic prescribing can be supported by guidelines and/or local antibiograms, but these have limitations. We sought to use data from a comprehensive electronic health record to use statistical learning to develop predictive models for individual antibiotics that incorporate patient- and hospital-specific factors. This paper reports on the development and validation of these models with a large retrospective cohort. This was a...
Epidemiology and SurveillanceComparative Genomic Analysis of Third-Generation-Cephalosporin-Resistant Escherichia coli Harboring the blaCMY-2-Positive IncI1 Group, IncB/O/K/Z, and IncC Plasmids Isolated from Healthy Broilers in JapanThe off-label use of third-generation cephalosporins (3GCs) during in ovo vaccination or vaccination of newly hatched chicks has been a common practice worldwide. CMY-2-producing Escherichia coli strains have been disseminated in broiler chicken production. The objective of this study was to determine the epidemiological linkage of blaCMY-2...
Experimental Therapeutics
Experimental TherapeuticsThe Added Value of Longitudinal Imaging for Preclinical In Vivo Efficacy Testing of Therapeutic Compounds against Cerebral CryptococcosisBrain infections with Cryptococcus neoformans are associated with significant morbidity and mortality. Cryptococcosis typically presents as meningoencephalitis or fungal mass lesions called cryptococcomas. Despite frequent in vitro discoveries of promising novel antifungals, the clinical need for drugs that can more efficiently treat these brain infections...
Editor's Pick Experimental TherapeuticsAntileishmanial Effects of Synthetic EhPIb Analogs Derived from the Entamoeba histolytica LipopeptidephosphoglycanWith an estimated number of new cases annually of approximately 1.4 million, leishmaniasis belongs to the most important parasitic diseases in the world. Nevertheless, existing drugs against leishmaniasis in general have several drawbacks that urgently necessitate new drug development. A glycolipid molecule of the intestinal protozoan parasite Entamoeba histolytica...
Experimental TherapeuticsTherapeutic Efficacy of a Mixed Formulation of Conventional and PEGylated Liposomes Containing Meglumine Antimoniate, Combined with Allopurinol, in Dogs Naturally Infected with Leishmania infantumThe treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome...
Experimental TherapeuticsBacteriophage-Antibiotic Combination Strategy: an Alternative against Methicillin-Resistant Phenotypes of Staphylococcus aureusComparative time-kill experiments with Staphylococcus aureus bacteriophage (phage) Sb-1 alone and phage-antibiotic combinations (PACs) against two methicillin-resistant S. aureus (MRSA) strains have shown synergy with both daptomycin-phage and vancomycin-phage combinations. PACs prevented...
Experimental TherapeuticsRepurposing Fenamic Acid Drugs To Combat Multidrug-Resistant Neisseria gonorrhoeaeThe rise of extensively drug-resistant and multidrug-resistant strains of Neisseria gonorrhoeae has occurred in parallel with the increasing demand for new drugs. However, the current methods of drug discovery are burdened with rigorous assessments and require more time than can be spared until gonococcal infections become difficult to control. To address this urgency...
Clinical Therapeutics
Clinical TherapeuticsCombination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic PhaseChagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are...
Clinical TherapeuticsPopulation Pharmacokinetics and Exposure-Response Relationships of Baloxavir Marboxil in Influenza Patients at High Risk of ComplicationsBaloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11,846 plasma concentration data items from 1,827 subjects, including 2,341 plasma concentration data items from 664 patients at high...
Clinical TherapeuticsConcurrent Local Delivery of Diflunisal Limits Bone Destruction but Fails To Improve Systemic Vancomycin Efficacy during Staphylococcus aureus OsteomyelitisStaphylococcus aureus osteomyelitis is a debilitating infection of bone. Treatment of osteomyelitis is impaired by the propensity of invading bacteria to induce pathological bone remodeling that may limit antibiotic penetration to the infectious focus. The nonsteroidal anti-inflammatory drug diflunisal was previously identified as an osteoprotective adjunctive therapy...
Clinical TherapeuticsPhase 2a Pharmacokinetic, Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in Female Participants with Uncomplicated Urinary Tract Infection (Acute Uncomplicated Cystitis)Gepotidacin, a triazaacenaphthylene bacterial type II topoisomerase inhibitor, is in development for treatment of uncomplicated urinary tract infection (uUTI). This phase 2a study in female participants with uUTI evaluated the pharmacokinetics (primary objective), safety, and exploratory efficacy of gepotidacin. Eligible participants (n = 22) were confined to the clinic at baseline, received oral gepotidacin at 1,500 mg twice...
Clinical TherapeuticsAdvanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs In VitroOne of the reasons for the lengthy tuberculosis (TB) treatment is the difficulty to treat the nonmultiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our preclinical drug development pipeline. In most available dormancy models, it takes a long time to create a dormant state, and it is difficult to identify and quantify this...
Clinical TherapeuticsAmpicillin and Ceftriaxone Solution Stability at Different Temperatures in Outpatient Parenteral Antimicrobial TherapyThe inclusion of ampicillin-containing regimens in outpatient parenteral antimicrobial therapy programs (OPAT) depends upon solution stability under conditions similar to those experienced in these programs. Lack of this information could hinder the inclusion in OPAT of patients suffering from Enterococcus faecalis infective endocarditis treated with ampicillin plus...
Clinical TherapeuticsSafety and Tolerability of More than Six Days of Tedizolid TreatmentTedizolid has demonstrated its efficacy and safety in clinical trials; however, data concerning its tolerability in long-term treatments are scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid. A multicentric retrospective study of patients who received tedizolid for more than 6 days was conducted. Adverse events (AEs) were identified from patients’ medical records and...
Clinical TherapeuticsPooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum MalariaDihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of...
Editor's Pick Clinical TherapeuticsEfficacy of Early Oral Switch with β-Lactams for Low-Risk Staphylococcus aureus BacteremiaThe aim of this study was to assess the safety of early oral switch (EOS) prior to 14 days for low-risk Staphylococcus aureus bacteremia (LR-SAB), which is the primary treatment strategy used at our institution. The usual recommended therapy is 14 days of intravenous (i.v.) antibiotics. All patients with SAB at our hospital were identified between 1 January 2014 and...
Clinical TherapeuticsPopulation Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target AttainmentPharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1). The...
Pharmacology
PharmacologySafety, Pharmacokinetics, and Drug-Drug Interaction Potential of Intravenous Durlobactam, a β-Lactamase Inhibitor, in Healthy SubjectsDurlobactam (DUR; also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem-cilastatin (IMI-CIL)...
PharmacologyAnidulafungin and Micafungin Concentrations in Cerebrospinal Fluid and in Cerebral CortexAnidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01 to 0.66 μg/ml) and micafungin levels (<0.01 to 0.16 μg/ml) were lower than those in plasma concentrations (0.77 to 5.07 and 1.21 to 8.70 μg/ml, respectively) drawn simultaneously. In cerebral cortex, anidulafungin and micafungin levels were 0.21 to 2.34...
PharmacologyDistribution of Linezolid in Tuberculosis Lesions in Patients with Spinal Multidrug-Resistant TuberculosisLinezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study was to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR...
PharmacologyClinically Relevant Epithelial Lining Fluid Concentrations of Meropenem with Ciprofloxacin Provide Synergistic Killing and Resistance Suppression of Hypermutable Pseudomonas aeruginosa in a Dynamic Biofilm ModelTreatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation, and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR...
PharmacologyEffect of the Lysin Exebacase on Cardiac Vegetation Progression in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Endocarditis as Determined by EchocardiographyMethicillin-resistant Staphylococcus aureus (MRSA) poses significant therapeutic challenges related to its frequency in clinical infections, innate virulence properties, and propensity for multiantibiotic resistance. MRSA is among the most common causes of endovascular infections, including infective endocarditis (IE). Our objective was to employ transthoracic...
PharmacologyPopulation Pharmacokinetic Analyses for Omadacycline Using Phase 1 and 3 DataOmadacycline, a novel aminomethylcycline antibiotic with activity against Gram-positive and -negative organisms, including tetracycline-resistant pathogens, received FDA approval in October 2018 for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). A previously developed population pharmacokinetic (PK) model based on phase 1 intravenous and oral...
PharmacologyComparative Plasma Pharmacokinetics of Ceftriaxone and Ertapenem in Normoalbuminemia, Hypoalbuminemia, and Albumin Replacement in a Sheep ModelOptimal concentrations of unbound antimicrobials are essential for a maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare the effects of different albumin states on total and unbound concentrations of...
Letters to the Editor
Author Corrections
Masthead
NEW! Podcast from AAC
Current Issue
About AAC
Antimicrobial Agents and Chemotherapy® (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.
For Authors
AAC Podcast: New Episode
Watch Antimicrobial Agents and Chemotherapy Journal - Past, Present and Future hosted by AAC Editor in Chief, Cesar A. Arias.
Commentary
Staphylococcus aureus bacteremia (SAB) is a complicated, high-risk disease. For selected low-risk SAB, the role of oral antibiotic stepdown therapy is unknown. Bupha-Intr et al. report a retrospective cohort of low-risk SAB patients who did well with a short duration of intravenous antibiotics, followed by an additional ∼10 days of oral antibiotics, primarily using...