Pharmacokinetics of Intravenous Delafloxacin in Patients With End-Stage Renal Disease.

This was an open-label, parallel-group, crossover study that examined the pharmacokinetics and safety of delafloxacin, an anionic fluoroquinolone, after a single intravenous infusion in subjects with end-stage renal disease (ESRD; creatinine clearance <15 mL/min) undergoing hemodialysis compared with healthy subjects. Subjects received 300 mg delafloxacin containing sulfobutylether-ß-cyclodextrin in 2 periods separated by ≥14-day washouts. Blood and urine samples were collected, and pharmacokinetic parameters were calculated using noncompartmental methods. The mean total exposure (area under the curve) of delafloxacin was about 2.1 and 2.6 higher for subjects with ESRD compared to healthy subjects when dosed 1 hour before or 1 hour after hemodialysis, respectively. Compared to subjects with normal renal function, the maximum exposure to delafloxacin was 13% and 33% higher for ESRD subjects given delafloxacin 1 hour before and 1 hour after hemodialysis, respectively. The mean clearance was 13.7 L/h for healthy subjects and was lower for subjects with ESRD when given before (7.39 L/h) or after (5.69 L/h) hemodialysis. The clearance of delafloxacin in dialysate was 4.74 L/h with about 19.2% of the delafloxacin dose recovered after a 4-hour dialysis session. Delafloxacin was well tolerated in both healthy and ESRD subjects, with diarrhea being the most reported treatment-emergent adverse event.

Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia.

OBJECTIVE: To assess the effect of baseline variables, including treatment, on outcome in patients with nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: Retrospective analysis of data from two prospective, randomized, double-blind studies. SETTING: Multinational study with 134 sites. PATIENTS: A total of 1,019 patients with suspected Gram-positive nosocomial pneumonia, including 339 patients with documented S aureus pneumonia (S aureus subset) and 160 patients with documented MRSA pneumonia (MRSA subset). INTERVENTIONS: Linezolid, 600 mg, or vancomycin, 1 g, q12h for 7 to 21 days, each with aztreonam. MEASUREMENTS AND RESULTS: Outcome was measured by survival and clinical cure rates (assessed 12 to 28 days after the end of therapy). Logistic regression analysis was used to determine the effect of treatment and other baseline variables on outcome. Kaplan-Meier survival rates for linezolid vs vancomycin were 80.0% (60 of 75 patients) vs 63.5% (54 of 85 patients) for the MRSA subset (p = 0.03). Logistic regression analysis confirmed that the survival difference favoring linezolid remained significant after adjusting for baseline variables (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0 to 4.8; p = 0.05). Other baseline variables associated with significantly higher survival rates in MRSA pneumonia were serum creatinine levels less than or equal to two times the upper limit of normal and absence of cardiac comorbidities. Clinical cure rates for linezolid vs vancomycin (excluding indeterminate or missing outcomes) were 59.0% (36 of 61 patients) vs 35.5% (22 of 62 patients) for the MRSA subset (p < 0.01). Logistic regression analysis confirmed that the difference favoring linezolid remained significant after adjusting for baseline variables (OR, 3.3; 95% CI, 1.3 to 8.3; p = 0.01). Other baseline variables associated with significantly higher clinical cure rates in MRSA pneumonia were single-lobe pneumonia, absence of ventilator-associated pneumonia, and absence of oncologic and renal comorbidities. CONCLUSIONS: In this retrospective analysis, initial therapy with linezolid was associated with significantly better survival and clinical cure rates than was vancomycin in patients with nosocomial pneumonia due to MRSA.

A severity score for complicated skin and soft tissue infections derived from phase III studies of linezolid.

BACKGROUND: Severity scoring systems are useful for assessing patient risk and predicting prognosis. METHODS: We developed a scoring system using data from a phase III study comparing antibiotics in hospitalized patients with complicated skin and soft tissue infections (study A), and used logistic regression analysis to identify factors contributing to treatment failure. We tested this system using data from a similar study (study B). RESULTS: In study A (n = 682), cure rates were lower in patients with at least 1 comorbid condition (P <0.05) and in the highest risk class (P = 0.05); elevated blood urea nitrogen, hyponatremia, anemia, lesion size, and surgical wound infection were independent predictors of failure (P <0.05). In study B (n = 166), findings were similar and significant for risk class (P <0.05). In the combined analysis (n = 848), cure rates were higher for linezolid than for the comparator in all patients (85% versus 77%; P <0.01) and in subanalyses by comorbid conditions, median score, and risk class (P <0.05). CONCLUSIONS: We developed and validated a scoring system in which baseline variables predicted outcome. Patients with higher severity scores generally had poorer outcomes regardless of treatment group. Our finding that linezolid was an independent predictor of cure merits further evaluation.