Delafloxacin is a new fluoroquinolone antimicrobial approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults using dosage regimens of 300 mg intravenously every 12 hours, 450 mg orally every 12 hours, or switching from intravenous to oral regimens for a 5-to 14-day treatment duration. Dosage adjustments in patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] = 15-29 ml/min/1.73 m 2 ) are not required for oral doses but should be decreased to 200 mg intravenously every 12 hours in patients requiring parenteral therapy. Due to insufficient data, use of delafloxacin is not recommended for patients on hemodialysis or with endstage renal disease (eGFR < 15 ml/min/1.73 m 2 ). Delafloxacin works through inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV, which are essential enzymes for bacterial DNA transcription, replication, repair, and recombination and exhibits bactericidal activity against gram-positive and gram-negative organisms through a concentration-dependent matter. Delafloxacin has a very broad spectrum of activity against atypical, anaerobic, and resistant gram-negative and gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. During phase 3 trials, the most common side effects associated with delafloxacin were gastrointestinal (nausea, diarrhea). Unlike other fluoroquinolones, there does not seem to be a risk of QTc prolongation or phototoxicity with delafloxacin. The availability of both parenteral and oral formulations for delafloxacin distinguishes it from many of the currently available agents approved for ABSSSIs. Phase 3 studies for the treatment of respiratory infections are currently under way, and future results of these studies will further help delineate the role of delafloxacin. KEY WORDS delafloxacin, fluoroquinolone, methicillin-resistant Staphylococcus aureus, skin infection.

bWe report on the pharmacokinetics (PK) and pharmacodynamics (PD) of high-dose (>15 mg/kg of body weight per day) amikacin. A mean (standard deviation [SD]) maximum drug concentration in the serum (C max ) and 24-h area under the concentration-time curve (AUC 24 ) of 101 (49.4) mg/liter and 600 (387) mg · h/liter, respectively, were observed (n ‫؍‬ 73) with 28.0 (8.47) mg/kg/day doses. An initial amikacin dose of 2,500 mg in adults weighing 40 kg to 200 kg with therapeutic drug monitoring to adjust the maintenance dose will optimize its PK and PD.A mikacin is an important component of an initial empirical antimicrobial treatment strategy against major Gram-negative pathogens associated with serious infections. The regulatory approved dose of this aminoglycoside is 15 mg/kg of body weight per day as 2 to 3 divided doses (1). Aminoglycoside dosing has shifted from divided daily dosing to single daily dosing in order to optimize its concentration-dependent pharmacokinetic-pharmacodynamic (PK-PD) profile (2, 3). This dosing paradigm seeks to achieve a maximum concentration of drug in the serum (C max )/ MIC of 8 to 10 and an area under the concentration-time curve (AUC)/MIC of 75 (3-5). As a consequence, currently accepted standard doses of aminoglycosides, such as tobramycin, are now administered 5 to 10 mg/kg once daily in patients with normal kidney function, that is roughly 2-fold higher than the regulatory approved dose of 3 to 5 mg/kg/day in divided doses (5).The typical 4-fold higher MIC 90 (4 to 8 mg/liter) of amikacin against Pseudomonas aeruginosa compared to tobramycin (1 to 2 mg/liter) coupled with the dose proportionality of aminoglycosides led our institution to adopt an initial empirical amikacin dose of 24 mg/kg in noncritically ill patients and 30 to 40 mg/kg in critically ill patients. Two amikacin concentrations are measured, at 1 to 2 h and at 8 to 10 h after the end of infusion of this first dose, to permit dose individualization (6). Recent clinical studies corroborate this approach by suggesting that an initial amikacin dose Ն25 mg/kg is likely needed as empirical therapy of certain Gramnegative infections (7-10). Herein, we report on the amikacin exposure profile observed in our patients with this higher-thanregulatory-approved amikacin treatment strategy (1). We also provide a clear rationale for the consideration of an alternate empirical fixed amikacin dosing strategy in line with the current clinical adult total body weight (TBW) distribution.After institution review board approval, patients Ն21 years of age who received at least one dose of amikacin from 1 January 2012 to 30 June 2014, who had two serial amikacin measurable concentrations, and who had an estimated creatinine clearance (CL CR ) Ͼ30 ml/min based on the Cockcroft-Gault equation were included (11). Information pertaining to patient demographics, laboratory values, amikacin dose, administration and infusion times, amikacin concentration, and sample collection times were collected. Amikacin concentrations were measured by an a...

BACKGROUND Current guidelines from the Infectious Diseases Society of America and the American Society of Health-System Pharmacists recommend vancomycin troughs of 15 mg/L to 20 mg/L for serious methicillin-resistant Staphylococcus aureus infections. The pharmacokinetics of vancomycin are altered in critically ill patients, leading to inadequate serum levels. Rates of initial therapeutic vancomycin troughs have ranged from 17.6% to 33% using intermittent infusions (i.e., 15–20 mg/L) and approximately 60% using continuous infusions (i.e., 15–25 mg/L) in critically ill trauma patients (1–4). We hypothesized that our dosing protocol would achieve higher rates of initial therapeutic troughs compared with previously published reports due to more aggressive loading doses than those seen in previously published reports. METHODS This was a retrospective study of all critically ill trauma patients admitted to a Level I trauma intensive care unit over a 39-month period who had a suspected serious infection, who were treated with empiric vancomycin per the “pharmacy to dose” protocol, and who had an appropriately drawn steady state trough level. The primary outcome was the rate of initial therapeutic troughs, which was defined as 14.5 mg/L to 20.5 mg/L. RESULTS One hundred ninety-seven patients were screened. Seventy patients met inclusion criteria. The study cohort had a median age of 47.5 years and a median Injury Severity Score of 28. Augmented renal clearances were observed, with a median creatinine clearance of 159.1 mL/min and a median Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) score of 7. The median vancomycin loading dose was 24.6 mg/kg with an initial maintenance dose of 17.71 mg/kg. An every eight hour dosing interval was initiated on 47.14% of the patients, and 45.71% of the patients were initially started on an every 12 hour dosing interval. Only 15.71% of the study patients achieved an initial therapeutic trough; 42.86% were less than 10 mg/L, and 8.57% were greater than 20.5 mg/L. Acute kidney injury occurred in 10% based on the Infectious Diseases Society of America/American Society of Health-System Pharmacists vancomycin guidelines and in 11.4% based on the Acute Kidney Injury Network criteria. CONCLUSION Our incidence of initial therapeutic troughs was slightly below previously reported studies. Based on our results, which are consistent with previous literature, it would appear that our guideline-adherent protocol of intermittent vancomycin is insufficient to achieve troughs of 15 mg/L to 20 mg/L. LEVEL OF EVIDENCE Therapeutic, level III.

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