Minireview
MinireviewTreatment of Infections by OXA-48-Producing EnterobacteriaceaeCarbapenemase-producing Enterobacteriaceae (CPE) contribute significantly to the global public health threat of antimicrobial resistance. OXA-48 and its variants are unique carbapenemases with low-level hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins.
Mechanisms of Action: Physiological Effects
Mechanisms of Action: Physiological EffectsMechanism of Macrolide-Induced Inhibition of Pneumolysin Release Involves Impairment of Autolysin Release in Macrolide-Resistant Streptococcus pneumoniaeStreptococcus pneumoniae is a leading cause of community-acquired pneumonia. Over the past 2 decades, macrolide resistance among S. pneumoniae organisms has been increasing steadily and has escalated at an alarming rate worldwide.
Mechanisms of Action: Physiological EffectsArgentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by ChemoproteomicsParacoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the Paracoccidioides genus, which is restricted to Latin America.
Mechanisms of Action: Physiological EffectsCandida albicans Zn Cluster Transcription Factors Tac1 and Znc1 Are Activated by Farnesol To Upregulate a Transcriptional Program Including the Multidrug Efflux Pump CDR1Farnesol, a quorum-sensing molecule, inhibits Candida albicans hyphal formation, affects its biofilm formation and dispersal, and impacts its stress response. Several aspects of farnesol's mechanism of action remain incompletely uncharacterized.
Mechanisms of Action: Physiological EffectsCaspofungin Modulates Ryanodine Receptor-Mediated Calcium Release in Human Cardiac MyocytesRecent studies showed that critically ill patients might be at risk for hemodynamic impairment during caspofungin (CAS) therapy. The aim of our present study was to examine the mechanisms behind CAS-induced cardiac alterations.
Mechanisms of Action: Physiological EffectsHeterologous Expression of Full-Length Lanosterol 14α-Demethylases of Prominent Fungal Pathogens Candida albicans and Candida glabrata Provides Tools for Antifungal DiscoveryTargeting lanosterol 14α-demethylase (LDM) with azole drugs provides prophylaxis and treatments for superficial and disseminated fungal infections, but cure rates are modest for immunocompromised patients and individuals with comorbidities. The efficacy of azole drugs has also been reduced due to the emergence of drug-resistant fungal pathogens.
Mechanisms of Action: Physiological EffectsCrystal Structures of Full-Length Lanosterol 14α-Demethylases of Prominent Fungal Pathogens Candida albicans and Candida glabrata Provide Tools for Antifungal DiscoveryTargeting lanosterol 14α-demethylase (LDM) with azole drugs provides prophylaxis and treatments for superficial and disseminated fungal infections, but cure rates are not optimal for immunocompromised patients and individuals with comorbidities. The efficacy of azole drugs has also been reduced due to the emergence of drug-resistant fungal pathogens.
Mechanisms of Action: Physiological EffectsIdentification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosaThe long-term use of antibiotics has led to the emergence of multidrug-resistant bacteria. A promising strategy to combat bacterial infections aims at hampering their adaptability to the host environment without affecting growth.
Mechanisms of Resistance
Mechanisms of ResistanceDysfunction of Prohibitin 2 Results in Reduced Susceptibility to Multiple Antifungal Drugs via Activation of the Oxidative Stress-Responsive Transcription Factor Pap1 in Fission YeastThe fight against resistance to antifungal drugs requires a better understanding of the underlying cellular mechanisms. In order to gain insight into the mechanisms leading to antifungal drug resistance, we performed a genetic screen on a model organism, Schizosaccharomyces pombe, to identify genes whose overexpression caused resistance to antifungal drugs, including...
Mechanisms of ResistanceBifunctional Enzyme SpoT Is Involved in Biofilm Formation of Helicobacter pylori with Multidrug Resistance by Upregulating Efflux Pump Hp1174 (gluP)The drug resistance of Helicobacter pylori is gradually becoming a serious problem. Biofilm formation is an important factor that leads to multidrug resistance (MDR) in bacteria.
Mechanisms of ResistanceMagnitude of Voriconazole Resistance in Clinical and Environmental Isolates of Aspergillus flavus and Investigation into the Role of Multidrug Efflux Pumps...The magnitude of azole resistance in Aspergillus flavus and its underlying mechanism is obscure. We evaluated the frequency of azole resistance in a collection of clinical (n = 121) and environmental isolates (n = 68) of A. flavus by the broth microdilution method.
Mechanisms of ResistanceContributions of yap1 Mutation and Subsequent atrF Upregulation to Voriconazole Resistance in Aspergillus flavusAspergillus flavus is the second most significant pathogenic cause of invasive aspergillosis; however, its emergence risks and mechanisms of voriconazole (VRC) resistance have not yet been elucidated in detail. Here, we demonstrate that repeated exposure of A. flavus to subinhibitory concentrations...
Mechanisms of ResistanceImpacts of L1 Promoter Variation and L2 Clavulanate Susceptibility on Ticarcillin-Clavulanate Susceptibility of Stenotrophomonas maltophiliaInducible expression of L1 and L2 β-lactamases is the principal mechanism responsible for β-lactam resistance in Stenotrophomonas maltophilia. Ticarcillin-clavulanate (TIM) is one of the few effective β-lactams for S. maltophilia treatment.
Mechanisms of ResistanceFirst Report of an OXA-48- and CTX-M-213-Producing Kluyvera Species Clone Recovered from Patients Admitted in a University Hospital in Madrid, SpainEnterobacterales species other than Klebsiella pneumoniae also contribute to OXA-48 carbapenemase endemicity. We studied the emergence of an OXA-48-producing Kluyvera species clone, which expresses the novel CTX-M-213 enzyme,...
Mechanisms of ResistanceBiolog Phenotype Microarray Is a Tool for the Identification of Multidrug Resistance Efflux Pump InducersMultidrug resistance efflux pumps frequently present low levels of basal expression. However, antibiotic-resistant mutants that overexpress these resistance determinants are selected during infection.
Mechanisms of ResistanceCarbapenem Resistance Caused by High-Level Expression of OXA-663 β-Lactamase in an OmpK36-Deficient Klebsiella pneumoniae Clinical IsolateCarbapenem resistance is mainly mediated by carbapenemases or extended-spectrum β-lactamases (ESBL) plus a loss of porins. However, we have identified a Klebsiella pneumoniae clinical isolate that contains neither carbapenemases nor ESBLs.
Mechanisms of ResistanceIn Vitro Activity of PBTZ169 against Multiple Mycobacterium SpeciesIn this study, we demonstrate that PBTZ169 exhibits significant differences in in vitro activity against multiple Mycobacterium species. The amino acid polymorphism at codon 387 of decaprenylphosphoryl-beta-d-ribose oxidase (DprE1) can be used as a surrogate marker for in vitro susceptibility to PBTZ169 in mycobacteria.
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Mechanisms of ResistanceActive-Site Conformational Fluctuations Promote the Enzymatic Activity of NDM-1β-Lactam antibiotics are the mainstay for the treatment of bacterial infections. However, elevated resistance to these antibiotics mediated by metallo-β-lactamases (MBLs) has become a global concern.
Mechanisms of ResistanceExpression of Pseudomonas aeruginosa Antibiotic Resistance Genes Varies Greatly during Infections in Cystic Fibrosis PatientsThe lungs of individuals with cystic fibrosis (CF) become chronically infected with Pseudomonas aeruginosa that is difficult to eradicate by antibiotic treatment. Two key P. aeruginosa antibiotic resistance mechanisms are the AmpC β-lactamase that degrades β-lactam antibiotics and MexXYOprM, a three...
Susceptibility
SusceptibilityOptimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169)The efficacy of the standardized four-drug regimen (comprising isoniazid, rifampin, pyrazinamide, and ethambutol) for the treatment of tuberculosis (TB) is menaced by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. Intensive efforts have been made to develop new antibiotics or to repurpose old...
SusceptibilityChloroquine Analogues as Leads against Pneumocystis Lung PathogensThe impact of Pneumocystis pneumonia (PcP) on morbidity and mortality remains substantial for immunocompromised individuals, including those afflicted by HIV infection, organ transplantation, cancer, autoimmune diseases, or subject to chemotherapy or corticosteroid-based therapies. Previous work from our group has shown that repurposing antimalarial compounds for PcP...
SusceptibilityScreening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P. berghei Identifies Transmission-Blocking CompoundsMalaria remains an important parasitic disease with a large morbidity and mortality burden. Plasmodium transmission-blocking (TB) compounds are essential for achieving malaria elimination efforts.
SusceptibilityIn Vitro Activities of the Benzoquinolizine Fluoroquinolone Levonadifloxacin (WCK 771) and Other Antimicrobial Agents against Mycoplasmas and Ureaplasmas in Humans, Including Isolates with Defined Resistance MechanismsLevonadifloxacin (WCK 771) was evaluated against 68 type strains and clinical isolates of Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma pneumoniae, and ...
SusceptibilityIn Vitro Susceptibility Testing of a Novel Benzimidazole, SPR719, against Nontuberculous MycobacteriaNontuberculous mycobacterium (NTM) infections are increasing globally. The Mycobacterium avium complex (MAC) and Mycobacterium abscessus are the most frequently encountered NTM among clinical laboratories, and treatment options are extremely limited.
Analytical Procedures
Analytical ProceduresInvestigating the Efficacy of Triple Artemisinin-Based Combination Therapies for Treating Plasmodium falciparum Malaria Patients Using Mathematical ModelingThe first line treatment for uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT), which consists of an artemisinin derivative coadministered with a longer-acting partner drug. However, the spread of Plasmodium falciparum resistant to both artemisinin and its partner drugs poses a major global threat to malaria control activities.
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Analytical ProceduresReliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Assay for Quantification of Olorofim (F901318), a Novel Antifungal Drug, in Human Plasma and SerumA fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, olorofim (F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated. Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation.
Antiviral Agents
Antiviral AgentsEvaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating Acute Uncomplicated InfluenzaWe evaluated MEDI8852, a human IgG1 monoclonal antibody that binds a highly conserved influenza A hemagglutinin stalk epitope, in outpatients with uncomplicated influenza A infection. A total of 126 subjects aged 18 to 65 years were enrolled during the 2015 to 2016 Northern and 2016 Southern Hemisphere seasons.
Antiviral AgentsNitazoxanide Inhibits Human Norovirus Replication and Synergizes with Ribavirin by Activation of Cellular Antiviral ResponseNorovirus is the main cause of viral gastroenteritis worldwide. Although norovirus gastroenteritis is self-limiting in immunocompetent individuals, chronic infections with debilitating and life-threatening complications occur in immunocompromised patients.
Antiviral AgentsCan We Improve Stavudine's Safety Profile in Children? Pharmacokinetics of Intracellular Stavudine Triphosphate with Reduced DosingStavudine remains a useful replacement option for treatment for HIV+ children. WHO reduced the adult dose to 30 mg twice daily, which maintains efficacy and lowers mitochondrial toxicity.
Antiviral AgentsCharacterization of Influenza B Virus Variants with Reduced Neuraminidase Inhibitor SusceptibilityTreatment options for influenza B virus infections are limited to neuraminidase inhibitors (NAIs), which block the neuraminidase (NA) glycoprotein on the virion surface. The development of NAI resistance would therefore result in a loss of antiviral treatment options for influenza B virus infections.
Antiviral AgentsThe Small-Compound Inhibitor K22 Displays Broad Antiviral Activity against Different Members of the Family Flaviviridae and Offers Potential as a Panviral InhibitorThe virus family Flaviviridae encompasses several viruses, including (re)emerging viruses which cause widespread morbidity and mortality throughout the world. Members of this virus family are positive-strand RNA viruses and replicate their genome in close association with reorganized intracellular host cell membrane compartments.
Antiviral AgentsIn Vitro Antiviral Profile of Ruzasvir, a Potent and Pangenotype Inhibitor of Hepatitis C Virus NS5AInhibition of NS5A has emerged as an attractive strategy to intervene in hepatitis C virus (HCV) replication. Ruzasvir (formerly MK-8408) was developed as a novel NS5A inhibitor to improve upon the potency and barrier to resistance of early compounds.
Antiviral AgentsSynthetic Ingenols Maximize Protein Kinase C-Induced HIV-1 Latency ReversalAntiretroviral therapy (ART) does not cure HIV-1 infection due to the persistence of proviruses in long-lived resting T cells. Strategies targeting these latently infected cells will be necessary to eradicate HIV-1 in infected individuals.
Antiviral AgentsEffect of Plasma Protein Binding on the Anti-Hepatitis B Virus Activity and Pharmacokinetic Properties of NVR 3-778High plasma protein binding (PPB) levels not only affect drug-target engagement but can also impact exposure of hepatocytes to antivirals and thereby affect antiviral activity. In this study, we assessed the effect of PPB on the antiviral activity of NVR 3-778, a sulfamoylbenzamide capsid assembly modulator (CAM).
Epidemiology and Surveillance
Epidemiology and SurveillanceAbsence of a High Level of Duplication of the Plasmepsin II Gene in AfricaResistance to piperaquine has been associated with the amplification of the plasmepsin II gene in Cambodia. None of the 175 African isolates that we analyzed had plasmepsin II gene amplification (piperaquine 50% inhibitory concentration ranged from 0.94 to 137.5 nM), suggesting there is a low prevalence of piperaquine reduced susceptibility in Africa.
Epidemiology and SurveillanceAttributable Cost and Length of Stay Associated with Nosocomial Gram-Negative Bacterial CulturesFew studies have estimated the excess inpatient costs due to nosocomial cultures of Gram-negative bacteria (GNB), and those that do are often subject to time-dependent bias. Our objective was to generate estimates of the attributable costs of the underlying infections associated with nosocomial cultures by using a unique inpatient cost data set from the U.S.
Epidemiology and SurveillanceShort-Term Peripheral Venous Catheter-Related Bloodstream Infections: Evidence for Increasing Prevalence of Gram-Negative Microorganisms from a 25-Year Prospective Observational StudyThe aim of this study was to describe the etiology and outcome of short-term peripheral venous catheter (PVC)-related bloodstream infections (PVCRBSI) in a 25-year period (1992 to 2016) and to identify predictive factors of Gram-negative PVCRBSI. This was a prospective observational study including all episodes of PVCRBSI.
Epidemiology and SurveillanceGenomic Analysis of Multiresistant Staphylococcus capitis Associated with Neonatal SepsisCoagulase-negative staphylococci (CoNS), such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A)...
Experimental Therapeutics
Experimental TherapeuticsNovel Self-Assembled Micelles Based on Cholesterol-Modified Antimicrobial Peptide (DP7) for Safe and Effective Systemic Administration in Animal Models of Bacterial InfectionOwing to their broad-spectrum antibacterial properties, multitarget effects, and low drug resistance, antimicrobial peptides (AMPs) have played critical roles in the clinical therapy of drug-resistant bacterial infections. However, the potential hazard of hemolysis following systemic administration has greatly limited their application.
Experimental TherapeuticsBiocompatibility and Targeting Efficiency of Encapsulated Quinapyramine Sulfate-Loaded Chitosan-Mannitol Nanoparticles in a Rabbit Model of Surra...Quinapyramine sulfate (QS) produces trypanocidal effects against the parasite Trypanosoma evansi but is often poorly tolerated and causes serious reactions in animals. The encapsulation of QS in chitosan-mannitol to provide sustained release would improve both the therapeutic effect of QS and the quality of life of animals treated with this formulation.
Experimental TherapeuticsTreatment of Pseudomonas aeruginosa Biofilm Present in Endotracheal Tubes by Poly-l-LysineThe endotracheal tube (ETT) is an essential interface between the patient and ventilator in mechanically ventilated patients. However, a microbial biofilm is formed gradually on this tube and is associated with the development of ventilator-associated pneumonia.
Experimental TherapeuticsPopulation Pharmacokinetics of Tafenoquine, a Novel AntimalarialTafenoquine is a novel 8-aminoquinoline antimalarial drug recently approved by the U.S. Food and Drug Administration (FDA) for the radical cure of acute Plasmodium vivax malaria, which is the first new treatment in almost 60 years.
Experimental TherapeuticsCharacterizing the Effects of Glutathione as an Immunoadjuvant in the Treatment of TuberculosisMycobacterium tuberculosis is the etiological agent that is responsible for causing tuberculosis (TB), which continues to affect millions of people worldwide, and the rate of resistance of M. tuberculosis to antibiotics is ever increasing. We tested the synergistic effects of N-acetyl...
Experimental TherapeuticsDisrupting Gram-Negative Bacterial Outer Membrane Biosynthesis through Inhibition of the Lipopolysaccharide Transporter MsbAThere is a critical need for new antibacterial strategies to counter the growing problem of antibiotic resistance. In Gram-negative bacteria, the outer membrane (OM) provides a protective barrier against antibiotics and other environmental insults.
Experimental TherapeuticsAdjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus EndocarditisWe tested the ability of clavulanic acid to restore the efficacy of cefazolin against Staphylococcus aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the coadministration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 ± 0.5 log10 CFU/g) compared to...
Experimental TherapeuticsIdentifying Vancomycin as an Effective Antibiotic for Killing Borrelia burgdorferiBorrelia burgdorferi is the causative agent of Lyme borreliosis. Antibiotic therapy of early acute infection is effective for most patients, but 10 to 20% go on to develop posttreatment Lyme disease syndrome (PTLDS).
Experimental TherapeuticsIn Vivo Efficacy of VT-1129 against Experimental Cryptococcal Meningitis with the Use of a Loading Dose-Maintenance Dose Administration StrategyVT-1129 is a novel fungal enzyme-specific Cyp51 inhibitor with potent cryptococcal activity. Because of its long half-life (>6 days in mice) and our desire to quickly reach potent efficacy, we evaluated a VT-1129 loading dose-maintenance dose strategy against cryptococcal meningitis.
Experimental TherapeuticsEffects of PERK eIF2α Kinase Inhibitor against Toxoplasma gondiiToxoplasma gondii is an obligate intracellular parasite that has infected one-third of the population. Upon infection of warm-blooded vertebrates, the replicating form of the parasite (tachyzoite) converts into a latent form (bradyzoite) present in tissue cysts.
Experimental TherapeuticsIsavuconazole for Treatment of Experimental Fungal Endophthalmitis Caused by Aspergillus fumigatusFungal endophthalmitis remains a significant cause of vision impairment and blindness. Moreover, the prognosis is poor, in part due to delay in diagnosis and to limited availability of effective antifungal agents with good ocular penetration.
Experimental TherapeuticsPharmacodynamic Evaluation of Rezafungin (CD101) against Candida auris in the Neutropenic Mouse Invasive Candidiasis ModelRezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4 Candida auris strains, using the neutropenic mouse invasive candidiasis model.
Clinical Therapeutics
Clinical TherapeuticsProspective Cohort Study of Single-Day Doxycycline Therapy for Mediterranean Spotted FeverThe objective of this study is to evaluate the results of single-day doxycycline therapy for Mediterranean spotted fever (MSF). This is a prospective cohort study of cases with confirmed MSF treated with the single-day doxycycline regimen in a teaching hospital from 1990 to 2015.
Clinical TherapeuticsAlanine Scanning Mutagenesis of the MEDI4893 (Suvratoxumab) Epitope Reduces Alpha Toxin Lytic Activity In Vitro and Staphylococcus aureus Fitness in Infection ModelsAlpha toxin (AT) is a cytolytic pore-forming toxin that plays a key role in Staphylococcus aureus pathogenesis; consequently, extensive research was undertaken to understand the AT mechanism of action and its utility as a target for novel prophylaxis and treatment strategies against S. aureus...
Clinical TherapeuticsSimplified Aztreonam Dosing in Patients with End-Stage Renal Disease: Results of a Monte Carlo SimulationThe manufacturer-recommended aztreonam dosing for patients with creatinine clearance values of <10 ml/min/1.73 m2 is complex. It is not known whether simpler posthemodialysis dosing administered once daily or thrice weekly can reliably achieve pharmacodynamic goals.
Clinical TherapeuticsImpact of Efavirenz-, Ritonavir-Boosted Lopinavir-, and Nevirapine-Based Antiretroviral Regimens on the Pharmacokinetics of Lumefantrine and Safety of Artemether-Lumefantrine in Plasmodium falciparum-Negative HIV-Infected Malawian Adults Stabilized on Antiretroviral TherapyThere is conflicting evidence of the impact of commonly used antiretroviral therapies (ARTs) on the pharmacokinetics of lumefantrine and the safety profile of artemether-lumefantrine. We compared the area under the concentration-time curve from 0 h to 14 days (AUC0–14 days) of lumefantrine and the safety profile of artemether-lumefantrine in malaria-negative human immunodeficiency virus (HIV)-infected adults in two steps....
Clinical TherapeuticsEfficacy and Safety of Low-Dose Liposomal Amphotericin B in Adult Patients Undergoing Unrelated Cord Blood TransplantationLiposomal amphotericin B (L-AMB) is widely used for empirical or preemptive therapy and treatment of invasive fungal infections after cord blood transplantation (CBT). We retrospectively examined the efficacy and safety of low-dose L-AMB in 48 adult patients who underwent CBT between 2006 and 2017 in our institute.
Clinical TherapeuticsImplementation of Rapid Diagnostic Testing without Active Stewardship Team Notification for Gram-Positive Blood Cultures in a Community Teaching HospitalIn community hospitals, antimicrobial stewardship team notification of rapid diagnostic testing (RDT) results may not be feasible. A retrospective quasi-experimental study was conducted evaluating 252 adult inpatients with blood cultures positive for Gram-positive cocci in clusters (pre-RDT, n = 143; post-RDT, n = 109).
Clinical TherapeuticsEffect of Diabetes Mellitus on the Pharmacokinetics and Pharmacodynamics of Tuberculosis TreatmentDiabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-TB drugs remains poorly characterized.
Clinical TherapeuticsCeftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosaClinical susceptibility breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa for the ceftazidime-avibactam dosage regimen of 2,000/500 mg every 8 h (q8h) by 2-h intravenous infusion (adjusted for renal function) have been established by the FDA, CLSI, and EUCAST as susceptible (MIC, ≤8...
Pharmacology
PharmacologyActivity of Aromathecins against African TrypanosomesAfrican sleeping sickness is responsible for thousands of deaths annually, and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African trypanosomes.
PharmacologyAssessment of the In Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) against Carbapenem-Resistant Acinetobacter baumannii in the Neutropenic Murine Lung Infection ModelWe evaluated the in vivo efficacy of human-simulated WCK 5222 (cefepime-zidebactam) against cefepime-resistant Acinetobacter baumannii strains (n = 13) in the neutropenic murine lung infection model. Twelve isolates were meropenem resistant.
PharmacologyPlasma and Intrapulmonary Concentrations of ETX2514 and Sulbactam following Intravenous Administration of ETX2514SUL to Healthy Adult SubjectsETX2514 is a novel β-lactamase inhibitor that broadly inhibits Ambler class A, C, and D β-lactamases. ETX2514 combined with sulbactam (SUL) in vitro restores sulbactam activity against Acinetobacter baumannii.
PharmacologyMeropenem Combined with Ciprofloxacin Combats Hypermutable Pseudomonas aeruginosa from Respiratory Infections of Cystic Fibrosis PatientsHypermutable Pseudomonas aeruginosa organisms are prevalent in chronic respiratory infections and have been associated with reduced lung function in cystic fibrosis (CF); these isolates can become resistant to all antibiotics in monotherapy. This study aimed to evaluate the time course of bacterial killing and resistance of meropenem and ciprofloxacin in combination...
PharmacologyRandomized, Double-Blind, Placebo-Controlled Studies of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of EravacyclineEravacycline is a novel, fully synthetic fluorocycline antibiotic with in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens, including multidrug-resistant (MDR) bacteria. The pharmacokinetics (PK), urinary excretion, and safety/tolerability of intravenous (i.v.) eravacycline were evaluated in single- and multiple-ascending-dose studies.
PharmacologyAntimicrobial Prophylaxis for Patients Undergoing Cardiac Surgery: Intraoperative Cefazolin Concentrations and Sternal Wound InfectionsThis study characterizes the pharmacodynamics of antimicrobial prophylaxis and sternal wound infections following cardiac surgery. Duration of surgery and cefazolin plasma concentration during wound closure were independently associated with surgical site infection at 30 days.
PharmacologyIn Vitro and In Vivo Assessment of FK506 Analogs as Novel Antifungal Drug CandidatesFK506 (tacrolimus) is an FDA-approved immunosuppressant indicated for the prevention of allograft rejections in patients undergoing organ transplants. In mammals, FK506 inhibits the calcineurin-nuclear factor of activated T cells (NFAT) pathway to prevent T-cell proliferation by forming a ternary complex with its binding protein, FKBP12, and calcineurin.
Letters to the Editor
Letter to the EditorImmunosuppressed Adult Zebrafish Model of Mucormycosis
Letter to the EditorGrowing Knowledge about Mycobacterium simiae from Two Recent Studies
Letter to the EditorVitamin C and Mycobacterium tuberculosis Persisters
Letter to the EditorReply to Yew et al., “Vitamin C and Mycobacterium tuberculosis Persisters”
Errata
Author Corrections
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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.
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Dr. Louis B. Rice, Editor in Chief