pharmacodynamics
PharmacologyPharmacokinetics and Pharmacodynamics of the Nitroimidazole DNDI-0690 in Mouse Models of Cutaneous LeishmaniasisThe nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for the treatment of CL, we investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative...
SusceptibilityAuranofin Activity Exposes Thioredoxin Reductase as a Viable Drug Target in Mycobacterium abscessusNontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended treatment regimens are poor, especially for Mycobacterium abscessus. New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for...
PharmacologyPharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative InfectionsTebipenem pivoxil HBr (TBPM-PI-HBr) is a novel orally bioavailable carbapenem. The active moiety is tebipenem. Tebipenem pivoxil is licensed for use in Japan in children with ear, nose, and throat infections and respiratory infections. The HBr salt was designed to improve drug substance and drug product properties, including stability. TBPM-PI-HBr is now being developed as an agent for the treatment of complicated urinary tract...
MinireviewA Guide to Understanding Antimicrobial Drug Dosing in Critically Ill Patients on Renal Replacement Therapy...A careful management of antimicrobials is essential in the critically ill with acute kidney injury, especially if renal replacement therapy is required. Acute kidney injury may lead per se to clinically significant modifications of drugs’ pharmacokinetic parameters, and the need for renal replacement therapy represents a further variable that should be considered to avoid inappropriate antimicrobial therapy.
Experimental TherapeuticsPharmacodynamics of Ceftazidime plus Avibactam against KPC-2-Bearing Isolates of Klebsiella pneumoniae in a Hollow Fiber Infection ModelCeftazidime-avibactam (CAZ/AVI) combines ceftazidime with a diazabicyclooctane non-β-lactam β-lactamase inhibitor. This has potent inhibitory activity against KPC-type enzymes. We studied activity of clinically relevant regimens of CAZ/AVI against two KPC-2-bearing Klebsiella pneumoniae isolates (sequence type 258 recovered sequentially from the same patient) with and...
Experimental TherapeuticsIn Vivo Pharmacodynamics of Omadacycline against Staphylococcus aureus in the Neutropenic Murine Thigh Infection ModelOmadacycline is a novel aminomethylcycline antibiotic with potent activity against Staphylococcus aureus, including methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). We investigated the...
Editor's Pick PharmacologyIn Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) against Multidrug-Resistant Pseudomonas aeruginosa in the Neutropenic Murine Thigh Infection ModelWe describe the in vivo efficacy of human-simulated WCK 5222 (cefepime-zidebactam) exposure against multidrug-resistant Pseudomonas aeruginosa (meropenem MICs 8 to >256 μg/ml) in a neutropenic murine thigh infection model. WCK 5222 MICs ranged from 4 to 32 μg/ml.
PharmacologyIn Vivo Pharmacodynamic Profile of Ceftibuten-Clavulanate Combination against Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in the Murine Thigh Infection ModelCeftibuten-clavulanate (CTB-CLA) is a novel β-lactam–β-lactamase combination with potential utility for the management of urinary tract infections caused by extended-spectrum-β-lactamase (ESBL)-producing organisms. We examined the pharmacodynamics of the combination against 25 Enterobacteriaceae expressing β-lactamases (CTX-M, TEM, and SHV wild types and SHV-ESBL) in...
PharmacologyUsing Mycobacterium tuberculosis Single-Nucleotide Polymorphisms To Predict Fluoroquinolone Treatment ResponseClinical phenotypic fluoroquinolone susceptibility testing of Mycobacterium tuberculosis is currently based on M. tuberculosis growth at a single critical concentration, which provides limited information for a nuanced clinical response. We propose using specific resistance-conferring...
Clinical TherapeuticsFluoroquinolones in Drug-Resistant Tuberculosis: Culture Conversion and Pharmacokinetic/Pharmacodynamic Target Attainment To Guide Dose SelectionFluoroquinolones are group A drugs in tuberculosis guidelines. We aim to compare the culture conversion between new-generation (levofloxacin and moxifloxacin) and old-generation (ciprofloxacin and ofloxacin) fluoroquinolones, develop pharmacokinetic models, and calculate target attainment for levofloxacin and moxifloxacin. We included three U.S. tuberculosis centers.