Minireviews
MinireviewA Pharmacology Perspective on Simultaneous Tuberculosis and Hepatitis C TreatmentTuberculosis (TB) and hepatitis C virus (HCV) infections are both major public health problems. Despite high rates of coinfection, there is scarce literature addressing the convergence of the two diseases. One particularly unexplored area is the potential for simultaneous treatment of TB and HCV which would allow for leveraging an extensive global TB treatment infrastructure to help scale up HCV treatment.
Editor's Pick MinireviewAntimicrobial Resistance in Methicillin-Resistant Staphylococcus aureus to Newer Antimicrobial AgentsInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) result in significant morbidity and mortality for patients in both community and health care settings. This is primarily due to the difficulty in treating MRSA, which is often resistant to multiple classes of antibiotics.
Mechanisms of Action: Physiological Effects
Mechanisms of Action: Physiological EffectsRexAB Is Essential for the Mutagenic Repair of Staphylococcus aureus DNA Damage Caused by Co-trimoxazoleCo-trimoxazole (SXT) is a combination therapeutic that consists of sulfamethoxazole and trimethoprim that is increasingly used to treat skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, the use of SXT is limited to the treatment of low-burden, superficial...
Mechanisms of Action: Physiological EffectsAutophagy Induction by a Small Molecule Inhibits Salmonella Survival in Macrophages and MiceSalmonella enterica is a natural bacterial pathogen of humans and animals that causes systemic infection or gastroenteritis. During systemic infection, Salmonella generally resides within professional phagocytes, typically macrophages, whereas gastroenteritis is caused by infection of epithelial cells. We are only beginning to understand which host pathways...
Editor's Pick Mechanisms of Action: Physiological EffectsColistin Resistance-Mediated Bacterial Surface Modification Sensitizes Phage InfectionColistin is a drug of last resort for the treatment of many multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKP). However, bacteria readily acquire resistance to this antibiotic via lipopolysaccharide modifications caused by spontaneous mutations or from enzymes acquired by lateral gene transfer. The fitness cost...
Mechanisms of Resistance
Mechanisms of ResistancePhenotypic, Biochemical, and Genetic Analysis of KPC-41, a KPC-3 Variant Conferring Resistance to Ceftazidime-Avibactam and Exhibiting Reduced Carbapenemase ActivityA novel KPC variant, KPC-41, was identified in a Klebsiella pneumoniae clinical isolate from Switzerland. This β-lactamase possessed a 3-amino-acid insertion (Pro-Asn-Lys) located between amino acids 269 and 270 compared to the KPC-3 amino acid sequence.
Mechanisms of ResistanceInteraction of ArmZ with the DNA-Binding Domain of MexZ Induces Expression of mexXY Multidrug Efflux Pump Genes and Antimicrobial Resistance in Pseudomonas aeruginosaMultidrug efflux pumps play an important role in antibiotic resistance in bacteria. In Pseudomonas aeruginosa, the MexXY pump provides intrinsic resistance to many antimicrobials, including aminoglycosides. The expression of the mexXY operon is negatively regulated by the MexZ repressor. This repression is alleviated in response to antibiotic-induced ribosome...
Mechanisms of ResistanceSequence-Based Epidemiology of an OXA-48 Plasmid during a Hospital OutbreakA large OXA-48 outbreak in The Netherlands involved the spread of OXA-48-producing Enterobacteriaceae among at least 118 patients, suggesting horizontal transfer of this resistance gene through one or more plasmids. Elucidating transmission dynamics of resistance plasmids is hampered by the low resolution of classic typing methods. This study aimed to investigate the molecular epidemiology of plasmids carrying the OXA-48...
Mechanisms of ResistanceRoles of Lytic Transglycosylases in Biofilm Formation and β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureusStaphylococcus aureus is responsible for numerous community outbreaks and is one of the most frequent causes of nosocomial infections with significant morbidity and mortality. While the function of lytic transglycosylases (LTs) in relation to cell division, biofilm formation, and antibiotic resistance has been determined for several bacteria, their role in...
Mechanisms of ResistanceComprehensive Genome Analysis of Carbapenem-Resistant Strains of Raoultella Species, an Emerging Multidrug-Resistant Bacterium in HospitalsWe report the characterization of six carbapenem-resistant Raoultella spp. (CRRS) in our hospital and a genomic analysis of 58 publicly available isolates. CRRS isolates are sporadically identified around the world, and different transposons carrying carbapenemases were the resistant mechanisms. Mobile genetic elements play an important role in acquiring antibiotic resistance genes from the hospital.
Mechanisms of ResistanceAcquisition of Class C β-Lactamase PAC-1 by Sequence Type 644 Strains of Pseudomonas aeruginosaFour sequence type 664 (ST664) (serotype O:5) strains of Pseudomonas aeruginosa that were highly resistant to antibiotics, including ceftolozane-tazobactam and ceftazidime-avibactam, but were susceptible to colistin were found to harbor the gene encoding the rare class C β-lactamase PAC-1 on a chromosomally located Tn1721-like transposon. The bla...
Mechanisms of ResistanceCold Shock Induces Chromosomal qnr in Vibrio Species and Plasmid-Mediated qnrS1 in Escherichia coliqnr genes are found in aquatic bacteria and were present in the bacterial community before the introduction of synthetic quinolones. Their natural functions are unknown. We evaluated expression of chromosomal qnr in Vibrio species in response to environmental stresses and DNA-damaging agents. Subinhibitory concentrations of quinolones, but not other DNA-damaging agents, increased expression of chromosomal ...
Mechanisms of ResistanceCTX-M-33 Is a CTX-M-15 Derivative Conferring Reduced Susceptibility to CarbapenemsCTX-M-type extended-spectrum β-lactamases (ESBLs) are widespread among Enterobacterales strains worldwide. The most common variant is CTX-M-15, which hydrolyzes ceftazidime at a high rate but spares carbapenems. Here, we identified CTX-M-33, a point mutation derivative of CTX-M-15 (Asp to Ser substitution at Ambler position 109) that exhibited low carbapenemase activity.
Mechanisms of ResistanceA Large-Scale Whole-Genome Comparison Shows that Experimental Evolution in Response to Antibiotics Predicts Changes in Naturally Evolved Clinical Pseudomonas aeruginosaPseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have mutations that make them antibiotic resistant, making treatment difficult. To identify resistance-associated mutations, we experimentally evolved the antibiotic-sensitive strain...
Editor's Pick Mechanisms of ResistanceA 2.5-Year Within-Patient Evolution of Pseudomonas aeruginosa Isolates with In Vivo Acquisition of Ceftolozane-Tazobactam and Ceftazidime-Avibactam Resistance upon TreatmentCeftolozane-tazobactam is considered to be a last-resort treatment for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. Although resistance to this antimicrobial has been described in vitro, the development of resistance in vivo has rarely been reported. Here, we describe the evolution of resistance to ceftolozane-tazobactam of...
Mechanisms of ResistanceDetection of Candida auris Antifungal Drug Resistance Markers Directly from Clinical Skin SwabsAccurate and rapid assessment of Candida auris antifungal drug resistance is crucial for effective infection prevention and control actions, as well as for patient management. Here, performance of a molecular diagnostic platform, enabling rapid identification of FKS1 and ERG11 mutations conferring echinocandin and azole resistance, respectively, was...
Susceptibility
SusceptibilityRegrowth of Mycobacterium tuberculosis Populations Exposed to Antibiotic Combinations Is Due to the Presence of Isoniazid and Not Bacterial Growth RateModulation of the growth rate in Mycobacterium tuberculosis is key to its survival in the host, particularly with regard to its adaptation during chronic infection, when the growth rate is very slow. The resulting physiological changes influence the way in which this pathogen interacts with the host and responds to antibiotics. Therefore, it is important that we...
SusceptibilityAntimicrobial Susceptibility and Molecular Characterization Using Whole-Genome Sequencing of Clostridioides difficile Collected in 82 Hospitals in Japan between 2014 and 2016We studied the antimicrobial susceptibility and molecular characteristics, using draft whole-genome sequencing, of Clostridioides (Clostridium) difficile strains before and after treatment in adults with...
SusceptibilityIn Vitro Antifungal Combination of Flucytosine with Amphotericin B, Voriconazole, or Micafungin against Candida auris Shows No AntagonismCandida auris is an emerging, multidrug-resistant pathogen responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida species drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is, therefore, noteworthy to test possible combinations with flucytosine...
SusceptibilityHigh In Vitro Susceptibility to the First-in-Class Spiropyrimidinetrione Zoliflodacin among Consecutive Clinical Neisseria gonorrhoeae Isolates from Thailand and South AfricaWe evaluated the in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among recent consecutive clinical Neisseria gonorrhoeae isolates cultured in Thailand (n = 99) (in 2018) and South Africa (n = 100) (in 2015 to 2017).
SusceptibilityActivity of a Novel 1,3-Beta-d-Glucan Synthase Inhibitor, Ibrexafungerp (Formerly SCY-078), against Candida glabrataIbrexafungerp (formerly SCY-078), a novel glucan synthase inhibitor with oral availability, was evaluated for activity against Candida glabrata. The susceptibility of clinical strains to ibrexafungerp was determined by microdilution and time-kill assays. The MIC range against wild-type strains was 1 to 2 μg/ml. Ibrexafungerp was also active against the majority of...
SusceptibilityDerepression of the smvA Efflux System Arises in Clinical Isolates of Proteus mirabilis and Reduces Susceptibility to Chlorhexidine and Other BiocidesProteus mirabilis is a common pathogen of the catheterized urinary tract and often described as intrinsically resistant to the biocide chlorhexidine (CHD). Here, we demonstrate that derepression of the smvA efflux system has occurred in clinical isolates of P. mirabilis and reduces...
Antiviral Agents
Antiviral AgentsAzithromycin Protects against Zika Virus Infection by Upregulating Virus-Induced Type I and III Interferon ResponsesAzithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Here, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle.
Antiviral AgentsSafety, Pharmacokinetics, and Antiviral Activity of AT-527, a Novel Purine Nucleotide Prodrug, in Hepatitis C Virus-Infected Subjects with or without CirrhosisAT-527 is a novel modified guanosine nucleotide prodrug inhibitor of the hepatitis C virus (HCV) NS5B polymerase, with increased in vitro antiviral activity compared to sofosbuvir and a highly differentiated favorable preclinical profile compared to other anti-HCV nucleoside/nucleotide analogs.
Antiviral AgentsInterplay of Amino Acid Residues at Positions 28 and 31 in NS5A Defines Resistance Pathways in Hepatitis C Virus Genotype 2Hepatitis C virus (HCV) genotype 2 (GT2) represents approximately 9% of all viral infections globally. While treatment outcomes for GT2-infected patients have improved substantially with direct-acting antiviral agents (DAAs) compared to alpha interferon, the presence of polymorphisms in NS5A can impact the efficacy of NS5A inhibitor-containing regimens. Thus, pathways of NS5A resistance were explored in GT2 subtypes using elbasvir, an...
Antiviral AgentsDoravirine Exposure and HIV-1 Suppression after Switching from an Efavirenz-Based Regimen to Doravirine-Lamivudine-Tenofovir Disoproxil FumarateDoravirine is a nonnucleoside reverse transcriptase inhibitor that has been approved for the treatment of HIV-1. In a phase 1 trial, doravirine exposure was transiently decreased when treatment was started immediately after the cessation of efavirenz treatment.
Antiviral AgentsSynergistic Lethal Mutagenesis of Hepatitis C VirusLethal mutagenesis is an antiviral approach that consists of extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagenic agent, often a nucleotide analogue. One of its advantages is its broad-spectrum nature, which renders the strategy potentially effective against emergent RNA viral infections. Here we describe the synergistic lethal mutagenesis of hepatitis C virus (HCV) by a combination...
Epidemiology and Surveillance
Epidemiology and SurveillanceNo Evidence of Plasmodium falciparum k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive ParasitesAntimalarial drug resistance is a substantial impediment to malaria control. The spread of resistance has been described using genetic markers, which are important epidemiological tools. We carried out a temporal analysis of changes in allele frequencies of 12 drug resistance markers over 2 decades of changing antimalarial drug policy in Kenya.
Experimental Therapeutics
Experimental TherapeuticsGC-072, a Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat PathogensBurkholderia pseudomallei, the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care; in the case of septicemia, left...
Experimental TherapeuticsProphylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29Globally, more people die annually from tuberculosis than from any other single infectious agent. Unfortunately, there is no commercially available vaccine that is sufficiently effective at preventing the acquisition of pulmonary tuberculosis in adults. In this study, preexposure prophylactic pulmonary delivery of active aerosolized antituberculosis bacteriophage D29 was evaluated as an option for protection against...
Experimental TherapeuticsSpore Germination as a Target for Antifungal TherapeuticsSpores are required for long-term survival of many organisms, including most fungi. For the majority of fatal human fungal pathogens, spore germination is the key process required to initiate vegetative growth and ultimately cause disease. Because germination is required for pathogenesis, the process could hold fungus-specific targets for new antifungal drug development.
Experimental TherapeuticsHAMLET, a Protein Complex from Human Milk, Has Bactericidal Activity and Enhances the Activity of Antibiotics against Pathogenic StreptococciHAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex derived from human milk that was first described for its tumoricidal activity. Later studies showed that HAMLET also has direct bactericidal activity against select species of bacteria, with highest...
Experimental TherapeuticsPromethazine Exhibits Antiparasitic Properties In Vitro and Reduces Worm Burden, Egg Production, Hepatomegaly, and Splenomegaly in a Schistosomiasis Animal ModelThe treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed, and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against...
Experimental TherapeuticsRepurposing Salicylamide for Combating Multidrug-Resistant Neisseria gonorrhoeae...The U.S. Centers for Disease Control and Prevention (CDC) lists Neisseria gonorrhoeae as one of the most urgent antibiotic-resistant threats in the United States. This is due to the emergence of clinical isolates that have developed resistance to nearly every antibiotic used to treat gonorrhea and highlights the critical need to find new therapeutics.
Experimental TherapeuticsMonitoring Tuberculosis Drug Activity in Live Animals by Using Near-Infrared Fluorescence ImagingWorldwide, tuberculosis (TB) is the leading cause of death due to infection with a single pathogenic agent, Mycobacterium tuberculosis. In the absence of an effective vaccine, new, more powerful antibiotics are required to halt the growing spread of multidrug-resistant strains and to shorten the duration of TB treatment. However, assessing drug efficacy at the...
Experimental TherapeuticsExploring Aztreonam in Combination with Ceftazidime-Avibactam or Meropenem-Vaborbactam as Potential Treatments for Metallo- and Serine-β-Lactamase-Producing EnterobacteriaceaeMetallo-β-lactamase (MBL)-producing Enterobacteriaceae, particularly those that coharbor serine β-lactamases, are a serious emerging public health threat given their rapid dissemination and the limited number of treatment options. Preclinical and anecdotal clinical data support the use of aztreonam in combination with ceftazidime-avibactam against these pathogens, but other aztreonam-based combinations have not been explored....
Experimental TherapeuticsDemonstration of the Broad-Spectrum In Vitro Activity of Finafloxacin against Pathogens of Biodefense InterestThis study investigated the in vitro activity of finafloxacin against bacterial strain panels of the biodefense pathogens. Broth microdilution assays were performed at neutral and acidic pH to determine the effectiveness of the antibiotics under conditions typical of an intracellular environment. In all instances, finafloxacin demonstrated superior activity at low pH.
Experimental TherapeuticsAmphotericin B Penetrates into the Central Nervous System through Focal Disruption of the Blood-Brain Barrier in Experimental Hematogenous Candida MeningoencephalitisHematogenous Candida meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeation and low cerebrospinal fluid (CSF) concentrations but is effective in the treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized that AmB may achieve focally higher concentrations in infected CNS lesions.
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Experimental TherapeuticsWCK 5222 (Cefepime-Zidebactam) Pharmacodynamic Target Analysis against Metallo-β-Lactamase-Producing Enterobacteriaceae in the Neutropenic Mouse Pneumonia ModelWCK 5222 is a combination of cefepime and the novel β-lactam enhancer (BLE) zidebactam. Zidebactam has a dual mechanism of action involving high-affinity penicillin binding protein 2 (PBP2) binding as well as inhibition of Ambler class A and C enzymes.
Clinical Therapeutics
Clinical TherapeuticsCost-Effectiveness of Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Bacteremia and PneumoniaCeftazidime-avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant Enterobacteriaceae (CRE) infections compared to those with conventional therapies. However, CAZ-AVI’s cost-effectiveness is unknown. We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE...
Clinical TherapeuticsEarly Discontinuation of Ethambutol in Pulmonary Tuberculosis Treatment Based on Results of the GenoType MTBDRplus Assay: a Prospective, Multicenter, Noninferiority Randomized Trial in South KoreaNo studies have investigated whether the discontinuation of ethambutol (EMB) based on susceptibility to isoniazid and rifampin, as determined by the GenoType MTBDRplus assay, would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of the intensive phase of treatment based on the results of the MTBDRplus assay in patients with pulmonary tuberculosis (PTB).
Clinical TherapeuticsPharmacokinetics and Dialytic Clearance of Isavuconazole during In Vitro and In Vivo Continuous Renal Replacement TherapyThe pharmacokinetics (PK) and dialytic clearance of isavuconazole in vitro and in 7 solid-organ transplant patients undergoing continuous renal replacement therapy (CRRT) were evaluated.
Clinical TherapeuticsPopulation Pharmacokinetics of Ganciclovir after Valganciclovir Treatment in Children with Renal TransplantValganciclovir, the ganciclovir prodrug, is an antiviral agent administered orally to prevent or treat cytomegalovirus infection in solid-organ transplant recipients. The valganciclovir dosing regimen in children is still controversial, as the number of patients reaching the area under the concentration-time curve at steady state (AUCss) target (40 to 60 mg·h/liter) remains highly variable.
Clinical TherapeuticsSafety and Pharmacokinetics of a Four Monoclonal Antibody Combination against Botulinum C and D NeurotoxinsBotulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A to G), which differ by 35% to 68% in amino acid sequences, necessitates the development of serotype-specific countermeasures.
Clinical TherapeuticsA Thrice-Weekly Ertapenem Regimen Is Practical for Hemodialysis PatientsA change of ertapenem dosage from 500 mg daily to thrice weekly, after each hemodialysis session, can maintain the plasma concentration above 2 mg/liter and be practical for hemodialysis patients.
Clinical TherapeuticsUsing State Transition Models To Explore How the Prevalence of Subtherapeutic Posaconazole Exposures Impacts the Clinical Utility of Therapeutic Drug Monitoring for Posaconazole Tablets and Oral SuspensionTherapeutic drug monitoring (TDM) has been recommended in guidelines for patients receiving posaconazole oral suspension, but its utility in patients receiving posaconazole tablet, which has an improved bioavailability, remains unclear.
Clinical TherapeuticsSystematic Review and Meta-analysis of the Association of Acute Kidney Injury with the Concomitant Use of Vancomycin and Piperacillin-Tazobactam in ChildrenConcomitant use of vancomycin plus piperacillin-tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Of 1,381 nonduplicate studies, 10 met our inclusion criteria...
Editor's Pick Clinical TherapeuticsEstimating the Size of the U.S. Market for New Antibiotics with Activity against Carbapenem-Resistant EnterobacteriaceaeNew antibiotics with activity against carbapenem-resistant Enterobacteriaceae (CRE) improve outcomes of CRE-infected patients. However, companies developing these drugs have faced financial difficulties. Sales of ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin in the United States totaled $101 million from February 2018 to January 2019. We estimate that...
Pharmacology
PharmacologyModeling and Simulation of Pretomanid Pharmacodynamics in Pulmonary Tuberculosis PatientsPretomanid (PA-824) is a nitroimidazole in clinical testing for the treatment of tuberculosis. A population pharmacodynamic model for pretomanid was developed using a Bayesian analysis of efficacy data from two early bactericidal activity (EBA) studies, PA-824-CL-007 and PA-824-CL-010, conducted in Cape Town, South Africa.
PharmacologyEarly Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children in a Randomized Controlled TrialMethicillin-resistant staphylococcal infections are a global burden. Area under the concentration-time curve to MIC (AUC/MIC) ratio is the pharmacokinetic (PK) parameter that best predicts vancomycin efficacy. Its therapeutic range is narrow, difficult to achieve because of a wide intersubject variability, especially in children, and is not routinely targeted since the AUC is rarely available.
PharmacologyPreclinical Evaluation of Amphihevir, a First-in-Class Clinical Hepatitis C Virus NS4B InhibitorAmphihevir, a benzofuran derivative, is the first reported hepatitis C virus (HCV) nonstructural protein 4B (NS4B) inhibitor that has advanced to clinical trials (currently in phase Ib trial [CTR20170632]). Here, we report the results of a preclinical study of its potency, toxicity, selectivity, drug metabolism and pharmacokinetics (DMPK), and safety profiles.
PharmacologySafety, Tolerability, and Pharmacokinetics of Oral Nafithromycin (WCK 4873) after Single or Multiple Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult SubjectsNafithromycin (WCK 4873), a novel lactone-ketolide, was administered to healthy adult subjects in 2 randomized, double-blind, placebo-controlled, phase 1 studies. In the first-in-human study, single ascending oral doses of nafithromycin (100 to 1,200 mg) were administered to subjects under fasted or fed conditions, with effects of food on bioavailability of nafithromycin studied at the dose levels of 400 and 800 mg.
PharmacologyPopulation Pharmacokinetics of Doxycycline in ChildrenDoxycycline is a tetracycline-class antimicrobial labeled by the U.S. Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline-class antibiotics and tooth staining, although doxycycline may be used off-label under severe conditions.
PharmacologyComparative In Vivo Antibacterial Activity of Human-Simulated Exposures of Cefiderocol and Ceftazidime against Stenotrophomonas maltophilia in the Murine Thigh ModelCefiderocol is a novel siderophore cephalosporin that utilizes bacterial ferric iron transports to cross the outer membrane. Cefiderocol shows high stability against all classes of β-lactamases, rendering it extremely potent against carbapenem- and multidrug-resistant Gram-negative organisms.
PharmacologyObservational, Prospective Single-Center Study of Antibiotic Prophylaxis with High-Dose Cefoxitin in Bariatric SurgeryThe optimal dose of cefoxitin for antibiotic prophylaxis in obese patients remains uncertain. We evaluated the adequacy of a 4-g dosing regimen of cefoxitin against the most common pathogens that infect patients undergoing bariatric surgery. This observational prospective study included obese patients who required bariatric surgery and a 4-g dose of cefoxitin as an antibiotic prophylaxis. Serum concentrations were measured during...
PharmacologyRenal Glycosuria as a Novel Early Sign of Colistin-Induced Kidney Damage in MiceThe polymyxin colistin represents a last-resort antibiotic for multidrug-resistant infections, but its use is limited by the frequent onset of acute drug-induced kidney injury (DIKI). It is essential to closely monitor kidney function prior to and during colistin treatment in order to pinpoint early signs of injury and minimize long-term renal dysfunction. To facilitate this, a mouse model of colistin-induced nephrotoxicity was used to...
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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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