Minireview
MinireviewAchromobacter Infections and Treatment OptionsAchromobacter is a genus of nonfermenting Gram-negative bacteria under order Burkholderiales. Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse...
Mechanisms of Action: Physiological Effects
Mechanisms of Action: Physiological EffectsRifabutin Is Bactericidal against Intracellular and Extracellular Forms of Mycobacterium abscessusMycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic...
Mechanisms of Action: Physiological EffectsWeakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding CommunityWith the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, in which multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for the treatment of bacterial infections due to difficulties in selecting the correct combinations and dosages. An additional...
Mechanisms of Resistance
Mechanisms of ResistanceEmergence of Carbapenem-Resistant Providencia rettgeri and Providencia stuartii Producing IMP-Type Metallo-β-Lactamase in JapanFour Providencia rettgeri isolates and one Providencia stuartii isolate were obtained from urine samples of five patients in 2018 in Japan. All of the isolates were resistant to imipenem and meropenem, and three were highly resistant to both carbapenems, with MICs of 512 μg/ml. The three highly...
Mechanisms of ResistanceIn Vivo Evolution of CTX-M-215, a Novel Narrow-Spectrum β-Lactamase in an Escherichia coli Clinical Isolate Conferring Resistance to MecillinamHere, we report a novel narrow-spectrum β-lactamase CTX-M-215 identified in an Escherichia coli clinical isolate in China and conferring high-level resistance to mecillinam but not to cefotaxime. CTX-M-215 differed from CTX-M-125, a CTX-M extended-spectrum β-lactamase (ESBL), by an N132D substitution, which decreased hydrolytic activities toward penicillins and...
Mechanisms of ResistanceRibosome-Mediated Attenuation of vga(A) Expression Is Shaped by the Antibiotic Resistance Specificity of Vga(A) Protein VariantsVga(A) protein variants confer different levels of resistance to lincosamides, streptogramin A, and pleuromutilins (LSAP) by displacing antibiotics from the ribosome. Here, we show that expression of vga(A) variants from Staphylococcus haemolyticus is regulated by cis-regulatory RNA in response to the LSAP antibiotics by the...
Editor's Pick Mechanisms of ResistanceVancomycin Heteroresistance and Clinical Outcomes in Bloodstream Infections Caused by Coagulase-Negative StaphylococciCoagulase-negative staphylococci (CoNS) are a common etiology of serious and recurrent infections in immunocompromised patients. Although most isolates appear susceptible to vancomycin, a single strain might have a subpopulation of resistant bacteria. This phenomenon is termed heteroresistance and may adversely affect the response to treatment. A retrospective cohort study was performed of pediatric patients with leukemia treated at St...
Mechanisms of ResistanceCefiderocol Resistance in Acinetobacter baumannii: Roles of β-Lactamases, Siderophore Receptors, and Penicillin Binding Protein 3Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 μg/ml. Cefiderocol resistance could not be explained by β-lactamase activity. Cefiderocol resistance was associated with reduced...
Mechanisms of ResistanceIn Vitro Activity of the Ultra-Broad-Spectrum Beta-Lactamase Inhibitor QPX7728 in Combination with Meropenem against Clinical Isolates of Carbapenem-Resistant Acinetobacter baumanniiQPX7728 is a recently discovered ultra-broad-spectrum beta-lactamase inhibitor (BLI) with potent inhibition of key serine and metallo-beta-lactamases. QPX7728 enhances the potency of many beta-lactams, including carbapenems, in beta-lactamase-producing Gram-negative bacteria, including Acinetobacter spp. The potency of meropenem alone and in combination with QPX7728 (1 to 16 μg/ml) was tested against 275 clinical isolates of...
Mechanisms of ResistanceR93P Substitution in the PmrB HAMP Domain Contributes to Colistin Heteroresistance in Escherichia coli Isolates from SwineHere, the mechanisms of colistin heteroresistance (CHR) were assessed in 12 Escherichia coli isolates from swine in China. CHR was investigated by population analysis profile tests. CHR stability was studied by culturing isolates for five overnight incubation periods in colistin-free medium. Subsequently, the mcr-1 gene and mutations in PmrAB, PhoPQ, and MgrB...
Susceptibility
SusceptibilityAntifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans IsolatesLomentospora prolificans is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the in vitro susceptibility of 8 drugs against 42 clinical L. prolificans isolates. All isolates showed high MICs to voriconazole (MIC90>16 μg/ml...
SusceptibilityNatural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-Naive PatientsMutations in the genes of the F420 signaling pathway of Mycobacterium tuberculosis complex, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, can lead to delamanid resistance. We searched for such mutations among 129 M. tuberculosis...
SusceptibilityEvaluation of Two Commercial Broth Microdilution Methods Using Different Interpretive Criteria for the Detection of Molecular Mechanisms of Acquired Azole and Echinocandin Resistance in Four Common Candida SpeciesThe abilities of the new Vitek 2 AST-YS08 (YS08) and Sensititre YeastOne (SYO) systems to detect the resistances of Candida isolates to azoles and echinocandins were evaluated. In total, 292 isolates, including 28 Candida albicans (6 Erg11 and 2 Fks mutants), 57 Candida parapsilosis (26...
SusceptibilityIn Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York OutbreakAn ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several...
SusceptibilityComparative In Vitro Activities of Ceftaroline and Tedizolid against Clinical Strains of Staphylococcus aureus and Enterococcus: Results from the China Antimicrobial Surveillance Network (CHINET) in 2018The in vitro activities of ceftaroline and tedizolid were compared against Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium clinical isolates collected from the China Antimicrobial Surveillance...
SusceptibilityLongitudinal Surveillance and Combination Antimicrobial Susceptibility Testing of Multidrug-Resistant Achromobacter Species from Cystic Fibrosis PatientsAchromobacter spp. are recognized as emerging pathogens in patients with cystic fibrosis (CF). Though recent works have established species-level identification using nrdA sequencing, there is a dearth in knowledge relating to species-level antimicrobial susceptibility patterns and antimicrobial combinations, which hampers the use of optimal antimicrobial combinations for the treatment of chronic infections. The aims...
Antiviral Agents
Antiviral AgentsPopulation Pharmacokinetic and Pharmacodynamic Analysis To Evaluate a Switch to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in People Living with HIV-1Doravirine is a non-nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus type 1 (HIV-1) infection. A population pharmacokinetic (PK) model for treatment-naive participants in doravirine clinical studies was updated with data from switch participants in the DRIVE-SHIFT trial and used to estimate individual post hoc PK parameter values and evaluate the efficacy exposure-response relationship....
Antiviral AgentsFilociclovir Is a Potent In Vitro and In Vivo Inhibitor of Human AdenovirusesHuman adenovirus (HAdV) infection is common in the general population and can cause a range of clinical manifestations, among which pneumonia and keratoconjunctivitis are the most common. Although HAdV infections are mostly self-limiting, infections in immunocompromised individuals can be severe. No antiviral drug has been approved for treating adenoviruses. Filociclovir (FCV) is a nucleoside analogue which has successfully completed...
Antiviral AgentsA Five-in-One First-in-Human Study To Assess Safety, Tolerability, and Pharmacokinetics of RO7049389, an Inhibitor of Hepatitis B Virus Capsid Assembly, after Single and Multiple Ascending Doses in Healthy ParticipantsRO7049389, an inhibitor of hepatitis B virus (HBV) capsid assembly, is being developed for the treatment of patients with chronic HBV infection. The objectives of this first-in-human study are to assess the safety, tolerability, pharmacokinetics (PK), food effect, inhibitory effect on CYP3A, and effect on QT of RO7049389 in healthy participants. Five components, single-ascending-dose (SAD) cohorts, multiple-ascending-dose (MAD) cohorts...
Antiviral AgentsPreclinical Profile and Characterization of the Hepatitis B Virus Core Protein Inhibitor ABI-H0731ABI-H0731, a first-generation hepatitis B virus (HBV) core protein inhibitor, has demonstrated effective antiviral activity in chronic hepatitis B (CHB) patients in a phase 1b clinical trial and is currently being further evaluated in phase 2 clinical trials. Here, we report the preclinical profile of ABI-H0731. In in vitro cell culture systems (HepG2-derived cell lines HepAD38 and HepG2-NTCP and primary human hepatocytes [PHHs...
Antiviral AgentsRemoval of Remdesivir’s Metabolite GS-441524 by Hemodialysis in a Double Lung Transplant Recipient with COVID-19Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo. Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining...
Epidemiology and Surveillance
Epidemiology and SurveillanceChromosomal and Plasmid-Borne Tigecycline Resistance Genes tet(X3) and tet(X4) in Dairy Cows on a Chinese FarmWe isolated 47 Acinetobacter strains carrying tet(X3) and 4 ST767 E. coli strains carrying tet(X4) from 296 rectal swab samples from dairy cows on a Chinese farm. tet(X3) was located on chromosomes or diverse plasmids, and tet(X4) was located on IncFIBκ/FIA(HI1)/...
Epidemiology and SurveillanceIdentification of a Novel Plasmid-Borne Gentamicin Resistance Gene in Nontyphoidal Salmonella Isolated from Retail TurkeyThe spread of antibiotic-resistant bacteria presents a global health challenge. Efficient surveillance of bacteria harboring antibiotic resistance genes (ARGs) is a critical aspect to controlling the spread. Increased access to microbial genomic data from many diverse populations informs this surveillance but only when functional ARGs are identifiable within the data set. Current, homology-based approaches are effective at identifying...
Epidemiology and SurveillanceAntimicrobial Resistance of Neisseria gonorrhoeae Isolates from High-Risk Men in Johannesburg, South AfricaNeisseria gonorrhoeae antimicrobial drug resistance has emerged worldwide; however, the situation in sub-Saharan Africa is not well documented. We investigated the molecular epidemiology and occurrence of antimicrobial resistance in Neisseria gonorrhoeae infections in two core transmission groups of...
Epidemiology and SurveillancePrevalence of Plasmodium falciparum Kelch 13 (PfK13) and Ubiquitin-Specific Protease 1 (pfubp1) Gene Polymorphisms in Returning Travelers from Africa Reported in Eastern ChinaDelayed clearance of Plasmodium falciparum by artemisinin-based combination therapies (ACTs) has already been observed for African isolates. Here, we aimed to investigate the prevalence, among travelers returning from African countries, of polymorphisms in two genes correlated with delayed parasite clearance (encoding...
Epidemiology and SurveillanceEpidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel AnalysisEnteric fever, caused by Salmonella enterica serovar Typhi (S. Typhi) and S. enterica serovar Paratyphi (S. Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of...
Epidemiology and SurveillanceIn Vitro Activity and Potency of the Novel Oxazolidinone Contezolid (MRX-I) Tested against Gram-Positive Clinical Isolates from the United States and EuropeContezolid, a new oxazolidinone antibacterial agent currently in development for the treatment of skin and skin structure infections, was susceptibility tested against Gram-positive clinical isolates (n = 1,211). Contezolid demonstrated potent activity against Staphylococcus aureus (MIC50/90, 0.5/1 mg/liter), coagulase-negative Staphylococcus...
Epidemiology and SurveillanceAntimicrobial Activity of Aztreonam-Avibactam and Comparator Agents When Tested against a Large Collection of Contemporary Stenotrophomonas maltophilia Isolates from Medical Centers WorldwideAztreonam-avibactam was tested against 1,839 Stenotrophomonas maltophilia isolates collected worldwide and demonstrated potent activity against isolates from all geographic regions and infection types (overall MIC50/90, 4/4 mg/liter; 97.8% inhibited at ≤8 mg/liter). Trimethoprim-sulfamethoxazole (TMP-SMX) (MIC50/90, ≤0.5/1 mg/liter; 95.4%...
Experimental Therapeutics
Experimental TherapeuticsIdentification of Small-Molecule Inhibitors Targeting Porphyromonas gingivalis Interspecies Adherence and Determination of Their In Vitro and In Vivo EfficaciesPorphyromonas gingivalis is one of the primary causative agents of periodontal disease and initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of a minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (AgI/II). Our...
Experimental TherapeuticsAssessing the Safety, Tolerability, Pharmacokinetics, and Biodistribution of Novel Oral Formulations of Amphotericin B following Single- and Multiple-Dose Administration to Beagle DogsThe purpose of this study was to assess the safety, tolerability, pharmacokinetics (PK), and biodistribution of novel oral amphotericin B (AmpB) formulations following single- and multiple-oral-dose administration to healthy beagle dogs. The liquid formulation of AmpB was administered to three male dogs, and the capsule formulations of AmpB were administered to each of two groups of six male dogs. Blood was collected for pharmacokinetic...
Experimental TherapeuticsTargeting CARD9 with Small-Molecule Therapeutics Inhibits Innate Immune Signaling and Inflammatory Response to Pneumocystis carinii β-GlucansPneumocystis jirovecii, the opportunistic fungus that causes Pneumocystis pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the profound deleterious inflammatory effects of the major β-glucan cell wall carbohydrate constituents of Pneumocystis through Dectin-1 engagement and...
Experimental TherapeuticsTherapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni InfectionPraziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma. Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against...
Experimental TherapeuticsPharmacodynamic Evaluation of MRX-8, a Novel Polymyxin, in the Neutropenic Mouse Thigh and Lung Infection Models against Gram-Negative PathogensMRX-8 is a novel polymyxin analogue in development for the treatment of infections caused by Gram-negative pathogens, including those resistant to other antibiotic classes. In the present study, we examined the pharmacodynamic activity of MRX-8 against a variety of common Gram-negative pathogens in the neutropenic mouse thigh and lung models. Additionally, we examined polymyxin B (PMB) as a comparator. Plasma pharmacokinetics of MRX-8...
Experimental TherapeuticsBuilding Optimal Three-Drug Combination Chemotherapy RegimensMultidrug therapy is often required. Examples include antiviral therapy, nosocomial infections, and, most commonly, anti-Mycobacterium tuberculosis therapy. Our laboratory previously identified a mathematical approach to identify 2-drug regimens with a synergistic or additive interaction using a full factorial study design. Our objective here was to generate a method...
Experimental TherapeuticsEvaluation of the Combination of Azithromycin and Naphthoquine in Animal Malaria ModelsCombination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only a few other combinations are now available. Increasing concern regarding the emergence and spread of artemisinin resistance in Plasmodium falciparum has led to a need for the...
Clinical Therapeutics
Clinical TherapeuticsAntibiotic Consumption and Stewardship at a Hospital outside of an Early Coronavirus Disease 2019 EpicenterThere are scant data on the impact of coronavirus disease 2019 (COVID-19) on hospital antibiotic consumption, and no data from outside epicenters. At our nonepicenter hospital, antibiotic days of therapy (DOT) and bed days of care (BDOC) were reduced by 151.5/month and 285/month, respectively, for March to June 2020 compared to 2018–2019 (P = 0.001 and P < 0.001). DOT per 1,000 BDOC was increased (8.1/month; P...
Clinical TherapeuticsPharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open-Label Phase 1 Multiple Ascending Dose and Food Effect StudyNeurocysticercosis and trichuriasis are difficult-to-treat parasitic infections that affect more than 1.5 billion people worldwide. Oxfendazole, a potent broad-spectrum benzimidazole anthelmintic approved for use in veterinary medicine, has shown substantial antiparasitic activity against neurocysticercosis and intestinal helminths in preclinical studies. As part of a program to transition oxfendazole from veterinary medicine to human...
Clinical TherapeuticsAdjuvant β-Lactam Therapy Combined with Vancomycin or Daptomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: a Systematic Review and Meta-analysisInfections due to methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) seriously threaten public health due to poor outcomes and high mortality. The objective of this study is to perform a systematic review and meta-analysis of the current evidence on adjuvant β-lactam (BL) therapy combined with vancomycin (VAN) or daptomycin (DAP) for MRSAB. PubMed, Embase...
Editor's Pick Clinical TherapeuticsFluoroquinolone versus Beta-Lactam Oral Step-Down Therapy for Uncomplicated Streptococcal Bloodstream InfectionsFluoroquinolones (FQs) are often preferred as oral step-down therapy for bloodstream infections (BSIs) due to favorable pharmacokinetic parameters; however, they are also associated with serious adverse events. The objective of this study was to compare clinical outcomes for patients who received an oral FQ versus an oral beta-lactam (BL) as step-down therapy for uncomplicated streptococcal BSIs. This multicenter, retrospective cohort...
Clinical TherapeuticsNovel Antibiotics May Be Noninferior but Are They Becoming Less Effective?: a Systematic ReviewNovel antibiotics approved by noninferiority trials may become less effective over time in two scenarios: (i) the treatment effect in studies of novel antibiotics may be consistently worse than studies of older antibiotics; (ii) when a decreasingly effective control arm is used in a series of noninferiority trials. Our systematic review of 175 noninferiority antibiotic trials found these scenarios to be rare.
Pharmacology
PharmacologyPopulation Pharmacokinetics of Caspofungin among Extracorporeal Membrane Oxygenation Patients during the Postoperative Period of Lung TransplantationLittle is known about the influence of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of caspofungin. The aim of this study was to describe population PK of caspofungin in patients with and without ECMO during the postoperative period of lung transplantation (LTx) and to investigate covariates influencing caspofungin PK. We compared ECMO patients with non-ECMO patients, and patients before and after ECMO weaning...
PharmacologyCharacteristics of Dolutegravir and Bictegravir Plasma Protein Binding: a First Approach for the Study of Pharmacologic SanctuariesThis study aimed to characterize in vitro dolutegravir (DTG) and bictegravir (BIC) binding. They had a preferential binding to human serum albumin (HSA) with two classes of albumin sites. Human alpha-1-acid glycoprotein (HAAG) binding of DTG and BIC showed an atypical nonlinear binding. The low-affinity site on HSA, the main plasma binding protein, suggests that the high protein binding rate should not impair passive diffusion...
PharmacologyPharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing EnterobacteriaceaeEnterobacteriaceae that produce metallo-β-lactamases (MBLs) are an emerging threat to public health. The metallo-β-lactamase inhibitor (MBLi) ANT2681 inhibits the enzymatic activity of MBLs through interaction with the dinuclear zinc ion cluster present in the active site that is common to these enzymes. ANT2681 is being codeveloped, with meropenem as the partner β-lactam, as a novel combination therapy for infections caused by...
PharmacologyActivities of Cefiderocol with Simulated Human Plasma Concentrations against Carbapenem-Resistant Gram-Negative Bacilli in an In Vitro Chemostat ModelActivities of cefiderocol under simulated human plasma concentrations at the recommended dosing regimen of 2 g every 8 h with a 3-h infusion were evaluated using an in vitro chemostat model. Against a total of 6 meropenem-resistant Gram-negative strains with cefiderocol MICs of 0.5 to 4 μg/ml, including metallo-β-lactamase producers and carbapenem-resistant ...
PharmacologyApplicability of Outpatient Quality Indicators for Appropriate Antibiotic Use in a Primary Health Care Area: a Point Prevalence SurveyThe ability to measure the quality of antibiotic prescriptions is a critical element in all antimicrobial stewardship programs. The aims of the present study were to evaluate the clinimetric properties of 32 recently developed outpatient quality indicators (OQIs) and to identify potential room for improvement in antibiotic use in a primary health care (PHC) area. The study was performed in a PHC area in Barcelona, Spain with 260,657...
PharmacologyIn Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniaeResistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant...
PharmacologyPopulation Pharmacokinetics of Cycloserine and Pharmacokinetic/Pharmacodynamic Target Attainment in Multidrug-Resistant Tuberculosis Patients Dosed with TerizidoneCycloserine is a WHO group B drug for the treatment of multidrug-resistant tuberculosis (TB). Pharmacokinetic/pharmacodynamic data for cycloserine when dosed as terizidone are sparse. The aim of this analysis was to describe the population pharmacokinetics of cycloserine when administered as terizidone and predict the doses of terizidone attaining cycloserine exposures associated with efficacy. The plasma cycloserine level was measured...
PharmacologyOptimal Dosing of Ceftriaxone in Infants Based on a Developmental Population Pharmacokinetic-Pharmacodynamic AnalysisCeftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis...
PharmacologyAn Open-Label Study of the Impact of Hepatic Impairment on the Pharmacokinetics and Safety of Single Oral and Intravenous Doses of OmadacyclineOmadacycline is a once-daily oral or intravenous (i.v.) aminomethylcycline antibiotic approved in the United States for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. Omadacycline pharmacokinetics were characterized in 18 patients with hepatic impairment and 12 matched healthy subjects. Patients with hepatic impairment received i.v. omadacycline...
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