Minireviews
MinireviewGenerating Robust and Informative Nonclinical In Vitro and In Vivo Bacterial Infection Model Efficacy Data To Support Translation to HumansIn June 2017, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens.” The aims were to discuss details of various PK/PD models and identify sound practices for deriving and utilizing PK/PD relationships to design optimal dosage regimens for patients. Workshop...
MinireviewConsiderations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial AgentsIn June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens” to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants...
Chemistry; Biosynthesis
Editor's Pick Chemistry; BiosynthesisSynthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of DiselenidesA novel series of thirty-one N-substituted urea, thiourea, and selenourea derivatives containing diphenyldiselenide entities were synthesized, fully characterized by spectroscopic and analytical methods, and screened for their in vitro leishmanicidal activities. The cytotoxic activity of these derivatives was tested against Leishmania infantum axenic...
Mechanisms of Action: Physiological Effects
Mechanisms of Action: Physiological EffectsIn Vitro and In Vivo Activities of β-Lactams in Combination with the Novel β-Lactam Enhancers Zidebactam and WCK 5153 against Multidrug-Resistant Metallo-β-Lactamase-Producing Klebsiella pneumoniaeZidebactam and WCK 5153 are novel bicyclo-acyl hydrazide (BCH) agents that have previously been shown to act as β-lactam enhancer (BLE) antibiotics in Pseudomonas aeruginosa and Acinetobacter baumannii. The objectives of this work were to identify the molecular targets of these BCHs in...
Mechanisms of Action: Physiological EffectsThe Widely Used Antimicrobial Triclosan Induces High Levels of Antibiotic Tolerance In Vitro and Reduces Antibiotic Efficacy up to 100-Fold In VivoThe antimicrobial triclosan is used in a wide range of consumer products ranging from toothpaste, cleansers, socks, and baby toys. A bacteriostatic inhibitor of fatty acid synthesis, triclosan is extremely stable and accumulates in the environment.
Editor's Pick Mechanisms of Action: Physiological EffectsThe Quinazolinone Allosteric Inhibitor of PBP 2a Synergizes with Piperacillin and Tazobactam against Methicillin-Resistant Staphylococcus aureusThe quinazolinones are a new class of antibacterials with in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA). The quinazolinones target cell wall biosynthesis and have a unique mechanism of action by binding to the allosteric site of penicillin-binding protein 2a (PBP 2a).
Mechanisms of Resistance
Mechanisms of ResistanceNG-Test Carba 5 for Rapid Detection of Carbapenemase-Producing Enterobacterales from Positive Blood CulturesThe immunochromatographic assay, NG-test Carba 5 (NG Biotech), has been evaluated for detection of carbapenemase-producing Enterobacterales (CPE) from spiked blood cultures (n = 205). It detected and discriminated in less than 30 minutes KPC, IMP, VIM, NDM, and OXA-48-like producers with a sensitivity and specificity of 97.7% and 96.1%, respectively.
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Mechanisms of ResistanceIdentification of Antimalarial Compounds That Require CLAG3 for Their Uptake by Plasmodium falciparum-Infected ErythrocytesDuring the intraerythrocytic asexual cycle malaria parasites acquire nutrients and other solutes through a broad selectivity channel localized at the membrane of the infected erythrocyte termed the plasmodial surface anion channel (PSAC). The protein product of the Plasmodium falciparum clonally variant clag3.1 and clag3.2 genes determines PSAC...
Mechanisms of ResistanceA Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida SpeciesThe increasing incidence of and high mortality rates associated with invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. In addition to microbiological resistance to existing antifungal drugs, the large number of unexplained treatment failures is a serious concern.
Mechanisms of ResistanceContribution of Clinically Derived Mutations in the Gene Encoding the Zinc Cluster Transcription Factor Mrr2 to Fluconazole Antifungal Resistance and CDR1 Expression in Candida albicansMutations in genes encoding zinc cluster transcription factors (ZCFs) such as TAC1, MRR1, and UPC2 play a key role in Candida albicans azole antifungal resistance. Artificial activation of the ZCF Mrr2 has shown increased expression of the gene encoding the Cdr1 efflux pump and resistance to fluconazole.
Mechanisms of ResistanceAnalysis of the Pseudomonas aeruginosa Aminoglycoside Differential Resistomes Allows Defining Genes Simultaneously Involved in Intrinsic Antibiotic Resistance and VirulenceHigh-throughput screening of transposon insertion libraries is a useful strategy for unveiling bacterial genes whose inactivation results in an altered susceptibility to antibiotics. A potential drawback of these studies is they are usually based on just one model antibiotic for each structural family, under the assumption that the results can be extrapolated to all members of said family.
Mechanisms of ResistanceResistance and Virulence Mechanisms of Escherichia coli Selected by Enrofloxacin in ChickenThis study aimed to investigate the genetic characteristics, antibiotic resistance patterns, and novel mechanisms involved in fluoroquinolone (FQ) resistance in commensal Escherichia coli isolates. The E. coli isolates were recovered from a previous clinical study and subjected to antimicrobial...
Mechanisms of ResistanceCandida albicans Biofilms Are Generally Devoid of Persister CellsCandida albicans is known for its ability to form biofilms, which are communities of microorganisms embedded in an extracellular matrix developing on different surfaces. Biofilms are highly tolerant to antifungal therapy.
Mechanisms of ResistanceInhibition of Vesicular Transport Influences Fungal Susceptibility to FluconazoleFungal infections pose a substantial threat to the human population. They can cause either mild and relatively harmless infections or invasive and often lethal diseases in patients with a weakened immune system.
Editor's Pick Mechanisms of ResistanceRemodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant Staphylococcus aureusStaphylococcus aureus is a significant human pathogen whose evolution and adaptation have been shaped in part by mobile genetic elements (MGEs), facilitating the global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs, in particular, how changes in the structure of multidrug resistance (MDR)...
Mechanisms of ResistanceGain- and Loss-of-Function Screens Coupled to Next-Generation Sequencing for Antibiotic Mode of Action and Resistance Studies in Streptococcus pneumoniaeTwo whole-genome screening approaches are described for studying the mode of action and the mechanisms of resistance to trimethoprim (TMP) in the Gram-positive Streptococcus pneumoniae. The gain-of-function approach (Int-Seq) relies on a genomic library of DNA fragments integrated into a fucose-inducible cassette.
Mechanisms of ResistanceFalse-Positive Carbapenem-Hydrolyzing Confirmatory Tests Due to ACT-28, a Chromosomally Encoded AmpC with Weak Carbapenemase Activity from Enterobacter kobeiIn Enterobacter cloacae complex (ECC), the overproduction of the chromosome-encoded cephalosporinase (cAmpC) associated with decreased outer membrane permeability may result in carbapenem resistance. In this study, we have characterized ACT-28, a cAmpC with weak carbapenemase activity, from a single ...
Mechanisms of ResistanceComparative Analysis of blaKPC Expression in Tn4401 Transposons and the Tn3-Tn4401 ChimeraTwo basic structures that carry the blaKPC gene, the Tn4401 transposon and the Tn3-Tn4401 chimera, have been identified within and outside China. However, the different blaKPC expression levels and promoter activities of these two structures are not completely understood.
Mechanisms of ResistanceFate of CMY-2-Encoding Plasmids Introduced into the Human Fecal Microbiota by Exogenous Escherichia coliThe gut is a hot spot for transfer of antibiotic resistance genes from ingested exogenous bacteria to the indigenous microbiota. The objective of this study was to determine the fate of two nearly identical blaCMY-2-harboring plasmids introduced into the human fecal microbiota by two Escherichia coli strains isolated from a human and from poultry...
Mechanisms of ResistanceWhole-Genome Sequencing Analysis of Multidrug-Resistant Serotype 15A Streptococcus pneumoniae in Japan and the Emergence of a Highly Resistant Serotype 15A-ST9084 CloneSince the introduction of pneumococcal conjugate vaccines (PCVs), an increase in the incidence of disease attributable to serotype 15A-ST63 (sequence type 63) pneumococci has been observed in many regions worldwide. We conducted a nationwide pediatric pneumococcal infection surveillance study between 2012 and 2014 in Japan.
Mechanisms of ResistanceThe Evolution of Azole Resistance in Candida albicans Sterol 14α-Demethylase (CYP51) through Incremental Amino Acid SubstitutionsRecombinant Candida albicans CYP51 (CaCYP51) proteins containing 23 single and 5 double amino acid substitutions found in clinical strains and the wild-type enzyme were expressed in Escherichia coli and purified by Ni2+-nitrilotriacetic acid agarose chromatography. Catalytic tolerance to...
Mechanisms of ResistanceInterplay among IncA and blaKPC-Carrying Plasmids in Citrobacter freundiiWe report two KPC-producing Citrobacter freundii isolates from unrelated patients. In one case, blaKPC-2 was harbored on a novel variant of a Tn4401 transposon of an IncN plasmid conjugated together with a coresident IncA plasmid, whereas in the other one, blaKPC-3 was on a Tn4401a transposon located on an...
Susceptibility
SusceptibilityAztreonam plus Clavulanate, Tazobactam, or Avibactam for Treatment of Infections Caused by Metallo-β-Lactamase-Producing Gram-Negative BacteriaMetallo-β-lactamase (MBL)-producing Gram-negative bacteria are often extremely resistant, leading to a real therapeutic dead end. Here, we evaluated the in vitro and in vivo efficacy of aztreonam in combination with ceftazidime-avibactam, ceftolozane-tazobactam, or amoxicillin-clavulanate for the treatment of infections caused by MBL-producing ...
SusceptibilityAssessment of the Potential for Inducing Resistance in Multidrug-Resistant Organisms from Exposure to Minocycline, Rifampin, and Chlorhexidine Used To Treat Intravascular DevicesTo assess the potential for the induction of antimicrobial resistance following repeated subinhibitory exposures to the combination minocycline (MIN), rifampin (RIF), and chlorhexidine (CHX), a total of 29 clinical microbial pathogenic isolates were repeatedly exposed to subinhibitory concentrations of MIN, RIF, and CHX for 20 passages. MICs of the MIN, RIF, and CHX combination were assessed at each passage to evaluate the potential for...
SusceptibilityIn Vitro Activity of Combinations of Zinc Chelators with Amphotericin B and Posaconazole against Six Mucorales SpeciesMucormycosis is an emerging disease with high mortality rates. Few antifungal drugs are active against Mucorales.
SusceptibilityDifferences in Clinical Manifestations, Antimicrobial Susceptibility Patterns, and Mutations of Fluoroquinolone Target Genes between Chryseobacterium gleum and Chryseobacterium indologenesChryseobacterium infections are uncommon, and previous studies have revealed that Chryseobacterium gleum is frequently misidentified as Chryseobacterium indologenes. We aimed to explore the differences in clinical manifestations and antimicrobial susceptibility patterns between...
SusceptibilitySynergistic Effect of Ceftazidime-Avibactam with Meropenem against Panresistant, Carbapenemase-Harboring Acinetobacter baumannii and Serratia marcescens Investigated Using Time-Kill and Disk Approximation AssaysSusceptibility of ceftazidime-avibactam and in vitro synergy with meropenem were investigated using disk approximation and time-kill assays against 11 multiresistant Acinetobacter baumannii isolates harboring oxacillinases and 5 Serratia marcescens isolates carrying blaKPC-2...
SusceptibilityIn Vitro Activities of Omadacycline against Rapidly Growing MycobacteriaThe in vitro activity of omadacycline, a new tetracycline derivative, was evaluated against isolates of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum using a broth microtiter dilution assay...
SusceptibilityEvaluation of the Bactericidal Activity of Fosfomycin in Combination with Selected Antimicrobial Comparison Agents Tested against Gram-Negative Bacterial Strains by Using Time-Kill CurvesThe effects of combining fosfomycin with various antimicrobial agents were evaluated in vitro by broth microdilution checkerboard and time-kill kinetic studies. Checkerboard analyses were used to evaluate the following 30 Gram-negative isolates: 5 Pseudomonas aeruginosa, 5 Acinetobacter baumannii...
Analytical Procedures
Analytical ProceduresMeasuring Antimicrobial Efficacy against Biofilms: a Meta-analysisThrough a statistical meta-analysis of published data on antimicrobial efficacy against biofilms formed by two common bacterial species, it was concluded that the particular experimental method used is the most important factor determining the outcome of the test. An expected dose-response relationship (greater killing with higher doses or longer treatment times) was observed for data sets derived from a single method but was not...
Antiviral Agents
Antiviral AgentsComparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 MutantsWe compared the activity of the integrase inhibitor bictegravir against HIV-1 and HIV-2 using a culture-based, single-cycle assay. Values of 50% effective concentrations ranged from 1.2 to 2.5 nM for 9 HIV-1 isolates and 1.4 to 5.6 nM for 15 HIV-2 isolates.
Antiviral AgentsDifferences in the Likelihood of Acyclovir Resistance-Associated Mutations in the Thymidine Kinase Genes of Herpes Simplex Virus 1 and Varicella-Zoster VirusAcyclovir (ACV) resistance-associated mutations in two recombinant herpes simplex virus 1 (HSV-1) clones were compared. Recombinant HSV-1 lacking its thymidine kinase (TK) and expressing varicella-zoster virus (VZV) TK ectopically had no mutations in the VZV TK gene.
Antiviral AgentsDoravirine and the Potential for CYP3A-Mediated Drug-Drug InteractionsIdentifying and understanding potential drug-drug interactions (DDIs) are vital for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This article discusses DDIs between doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), and cytochrome P450 3A (CYP3A) substrates and drugs that modulate CYP3A activity.
Antiviral AgentsInvestigation of Pharmacokinetic Interactions between Doravirine and Elbasvir-Grazoprevir and Ledipasvir-Sofosbuvir...Doravirine is a non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Due to the high prevalence of HIV-1 and hepatitis C virus (HCV) coinfection and coadministration of HIV-1 and HCV treatment, potential drug-drug interactions (DDIs) between doravirine and two HCV treatments were investigated in two phase 1 drug interaction trials in healthy participants.
Antiviral AgentsResistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 WeeksIn clinical studies GS-US-380-1489 (study 1489) and GS-US-380-1490 (study 1490), bictegravir-emtricitabine-tenofovir alafenamide (B-F-TAF), dolutegravir-abacavir-lamivudine (DTG-ABC-3TC), and dolutegravir plus emtricitabine-tenofovir alafenamide (DTG+F-TAF) treatment achieved high rates of virologic suppression in HIV-1 treatment-naive participants through week 48. Preexisting primary drug resistance was present at levels of 1.3%...
Epidemiology and Surveillance
Epidemiology and SurveillanceA Nationwide Screen of Carbapenem-Resistant Klebsiella pneumoniae Reveals an Isolate with Enhanced Virulence and Clinically Undetected Colistin HeteroresistanceThe convergence of hypervirulence and multidrug resistance in Klebsiella pneumoniae is a significant concern. Here, we report the first screen for hypermucoviscosity, a trait associated with increased virulence, using a U.S.
Epidemiology and SurveillanceMutation Profile of pfdhfr and pfdhps in Plasmodium falciparum among Returned Chinese Migrant Workers from AfricaWe evaluated markers of sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum among 254 returned migrant workers in China from Africa from 2013 to 2016. High prevalences of pfdhfr (97.2%) and pfdhps (96.5%) mutations were observed.
Epidemiology and SurveillanceMonitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of BrazilEmerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered...
Epidemiology and SurveillanceExpansion of Vancomycin-Resistant Enterococcus faecium in an Academic Tertiary Hospital in Southwest Germany: a Large-Scale Whole-Genome-Based Outbreak InvestigationVancomycin-resistant Enterococcus faecium (VREfm) is a frequent cause of nosocomial outbreaks. In the second half of 2015, a sharp increase in the incidence of VREfm was observed at our university medical center.
Epidemiology and SurveillanceAn Integrative Database of β-Lactamase Enzymes: Sequences, Structures, Functions, and Phylogenetic Treesβ-Lactamase enzymes have attracted substential medical attention from researchers and clinicians because of their clinical, ecological, and evolutionary interest. Here, we present a comprehensive online database of β-lactamase enzymes.
Epidemiology and SurveillanceMolecular Characterization of Multidrug-Resistant Pseudomonas aeruginosa Isolates in Hospitals in MyanmarThe emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa has become a serious worldwide medical problem. This study was designed to clarify the genetic and epidemiological properties of MDR P. aeruginosa strains isolated from hospitals in Myanmar.
Epidemiology and SurveillanceBaseline Ex Vivo and Molecular Responses of Plasmodium falciparum Isolates to Piperaquine before Implementation of Dihydroartemisinin-Piperaquine in SenegalDihydroartemisinin-piperaquine, which was registered in 2017 in Senegal, is not currently used as the first-line treatment against uncomplicated malaria. A total of 6.6% to 17.1% of P. falciparum isolates collected in Dakar in 2013 to 2015 showed ex vivo-reduced susceptibility to piperaquine.
Experimental Therapeutics
Experimental TherapeuticsContribution of Pretomanid to Novel Regimens Containing Bedaquiline with either Linezolid or Moxifloxacin and Pyrazinamide in Murine Models of TuberculosisNovel regimens combining bedaquiline and pretomanid with either linezolid (BPaL regimen) or moxifloxacin and pyrazinamide (BPaMZ regimen) shorten the treatment duration needed to cure tuberculosis (TB) in BALB/c mice compared to that of the first-line regimen and have yielded promising results in initial clinical trials. However, the independent contribution of the investigational new drug pretomanid to the efficacy of BPaMZ has not...
Experimental TherapeuticsBeyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent β-Lactam−β-Lactamase Inhibitor CombinationImpeding, as well as reducing, the burden of antimicrobial resistance in Gram-negative pathogens is an urgent public health endeavor. Our current antibiotic armamentarium is dwindling, while major resistance determinants (e.g., extended-spectrum β-lactamases [ESBLs]) continue to evolve and disseminate around the world.
Experimental TherapeuticsApotransferrin in Combination with Ciprofloxacin Slows Bacterial Replication, Prevents Resistance Amplification, and Increases Antimicrobial Regimen EffectThere has been renewed interest in combining traditional small-molecule antimicrobial agents with nontraditional therapies to potentiate antimicrobial effects. Apotransferrin, which decreases iron availability to microbes, is one such approach.
Experimental TherapeuticsPep5, a Fragment of Cyclin D2, Shows Antiparasitic Effects in Different Stages of the Trypanosoma cruzi Life Cycle and Blocks Parasite InfectivityPep5 (WELVVLGKL) is a fragment of cyclin D2 that exhibits a 2-fold increase in the S phase of the HeLa cell cycle. When covalently bound to a cell-penetrating peptide (Pep5-cpp), the nonapeptide induces cell death in several tumor cells, including breast cancer and melanoma cells.
Experimental TherapeuticsEffective Treatment of Staphylococcal Enterotoxin B Aerosol Intoxication in Rhesus Macaques by Using Two Parenterally Administered High-Affinity Monoclonal Antibodies
Staphylococcal enterotoxin B (SEB) is a protein exotoxin found on the cell surface of Staphylococcus aureus that is the source for multiple pathologies in humans. When purified and concentrated in aerosol form, SEB can cause an acute and often fatal intoxication and thus is considered a biological threat agent.
Experimental TherapeuticsEfficacy of Aminomethyl Spectinomycins against Complex Upper Respiratory Tract Bacterial InfectionsThe most frequent ailment for which antibiotics are prescribed is otitis media (ear infections), which is most commonly caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Treatment of otitis...
Experimental TherapeuticsImproved Methods for Assessing Therapeutic Potential of Antifungal Agents against Dermatophytes and Their Application in the Development of NP213, a Novel Onychomycosis Therapy CandidateOnychomycosis is a common, difficult-to-treat nail infection that is mainly caused by dermatophytes. Current therapies are not wholly effective and are associated with manifold side effects.
Experimental TherapeuticsIn Vitro and In Vivo Activities of the Riminophenazine TBI-166 against Mycobacterium tuberculosisThe riminophenazine agent clofazimine (CFZ) is repurposed as an important component of the new short-course multidrug-resistant tuberculosis regimen and significantly shortens first-line regimen for drug-susceptible tuberculosis in mice. However, CFZ use is hampered by its unwelcome skin discoloration in patients.
Experimental TherapeuticsEnzymatic and Structural Characterization of the Naegleria fowleri GlucokinaseInfection with the free-living amoeba Naegleria fowleri leads to life-threatening primary amoebic meningoencephalitis. Efficacious treatment options for these infections are limited, and the mortality rate is very high (∼98%).
Experimental TherapeuticsCombination of Cystatins 9 and C Modulates Serum Biomarkers Associated with Inflammation and Provides Prophylactic as Well as Long-Term Protection against Multidrug-Resistant Klebsiella pneumoniaeWe have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae. We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K....
Experimental TherapeuticsControl of Klebsiella pneumoniae Infection in Mice by Using Dissolving Microarray Patches Containing GentamicinUsing a murine model of Klebsiella pneumoniae bacterial infection, we demonstrate that gentamicin dissolving microarray patches, applied to murine ears, could control K. pneumoniae infection. Mice treated with microarray patches had reduced bacterial burden in the nasal-associated lymphoid tissue...
Clinical Therapeutics
Clinical TherapeuticsCycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with TuberculosisLimited pharmacokinetic/pharmacodynamic (PK/PD) data exist on cycloserine in tuberculosis (TB) patients. We pooled several studies into a large PK data set to estimate the population PK parameters for cycloserine in TB patients.
Clinical TherapeuticsPharmacokinetics, Safety, and Clinical Outcomes of Omadacycline in Women with Cystitis: Results from a Phase 1b StudyOmadacycline, an aminomethylcycline antibiotic, is approved as once-daily intravenous (i.v.) and oral (p.o.) monotherapy for acute bacterial skin and skin structure infections and for community-acquired bacterial pneumonia, and it is under development for treatment of urinary tract infection (UTI). This is a phase 1b, randomized, open-label study of omadacycline in women with cystitis (defined as UTI symptoms and a positive urine...
Editor's Pick Clinical TherapeuticsSafety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint InfectionsDalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related...
Clinical TherapeuticsClinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus BacteremiaVancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an...
Editor's Pick Clinical TherapeuticsA Systematic Review and Meta-analysis of Antibiotic Treatment Duration for Bacteremia Due to EnterobacteriaceaeThe duration of antibiotic therapy for bacteremia due to Enterobacteriaceae is not well defined. We sought to evaluate the clinical outcomes with shorter- versus longer-course treatment.
Clinical TherapeuticsPharmacokinetics of Levofloxacin in Children Treated for Exposure to Drug-Resistant TuberculosisLevofloxacin is used to treat and prevent drug-resistant tuberculosis in children. We assessed levofloxacin serum drug concentrations in 24 children aged 2 to 10 years who received levofloxacin-based tuberculosis preventive therapy in Karachi, Pakistan.
Clinical TherapeuticsA Novel 1,3-Beta-d-Glucan Inhibitor, Ibrexafungerp (Formerly SCY-078), Shows Potent Activity in the Lower pH Environment of VulvovaginitisIbrexafungerp (IBX) (formerly SCY-078) is a novel glucan synthase inhibitor whose oral availability is being evaluated for efficacy against vulvovaginal candidiasis (VVC). Bioavailability and in vitro activity are important efficacy indicators, but accepted susceptibility methods do not always accurately predict activity in an acidic environment, such as the vagina.
Pharmacology
PharmacologyRevising Pediatric Vancomycin Dosing Accounting for Nephrotoxicity in a Pharmacokinetic-Pharmacodynamic ModelThis study aimed to suggest an initial pediatric vancomycin dose regimen through population pharmacokinetic-pharmacodynamic modeling. A population pharmacokinetic approach was used to analyze vancomycin concentration-time data from a large pediatric cohort.
PharmacologyHepatotoxicity Induced by Isoniazid-Lipopolysaccharide through Endoplasmic Reticulum Stress, Autophagy, and Apoptosis Pathways in ZebrafishIsoniazid (INH) is a first-line antituberculosis drug. The incidence of adverse reactions accompanied by inflammation in the liver during drug administration to tuberculosis patients is high and severely affects clinical treatment.
PharmacologyEvaluation of Saliva as a Potential Alternative Sampling Matrix for Therapeutic Drug Monitoring of Levofloxacin in Patients with Multidrug-Resistant TuberculosisSaliva may be a useful alternative matrix for monitoring levofloxacin concentrations in multidrug-resistant tuberculosis (MDR-TB) patients. The objectives of this study were (i) to evaluate the correlation between plasma and salivary levofloxacin (Lfx) concentrations in MDR-TB patients and (ii) to gauge the possibility of using saliva as an alternative sampling matrix for therapeutic drug monitoring of Lfx in areas where TB is endemic...
PharmacologyA Novel Small Molecule, ZY354, Inhibits Dental Caries-Associated Oral BiofilmsBiofilm control is a critical approach to the better management of dental caries. Antimicrobial small molecules have shown their potential in the disruption of oral biofilm and control of dental caries.
Editor's Pick PharmacologyFluoroquinolone Efficacy against Tuberculosis Is Driven by Penetration into Lesions and Activity against Resident Bacterial PopulationsFluoroquinolones represent the pillar of multidrug-resistant tuberculosis (MDR-TB) treatment, with moxifloxacin, levofloxacin, or gatifloxacin being prescribed to MDR-TB patients. Recently, several clinical trials of “universal” drug regimens, aiming to treat drug-susceptible and drug-resistant TB, have included a fluoroquinolone.
PharmacologyExternal Evaluation of Population Pharmacokinetic Models of Vancomycin in Large Cohorts of Intensive Care Unit PatientsDosing of vancomycin is often guided by therapeutic drug monitoring and population pharmacokinetic models in the intensive care unit (ICU). The validity of these models is crucial, as ICU patients have marked pharmacokinetic variability.
PharmacologyIncidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam, Cefepime, or MeropenemCritically ill patients are frequently treated with empirical antibiotic therapy, including vancomycin and β-lactams. Recent evidence suggests an increased risk of acute kidney injury (AKI) in patients who received a combination of vancomycin and piperacillin-tazobactam (VPT) compared with patients who received vancomycin alone or vancomycin in combination with cefepime (VC) or meropenem (VM), but most studies were conducted...
Letters to the Editor
Letter to the EditorProteus mirabilis Producing the OXA-58 Carbapenemase in Poland
Letter to the EditorLong-Term Low Rate of Macrolide-Resistant Mycoplasma pneumoniae Strains in Germany
Letter to the EditorSerum Levels of Crushed Posaconazole Delayed-Release Tablets
Erratum
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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