cThis study evaluated the pulmonary disposition of eravacycline in 20 healthy adult volunteers receiving 1.0 mg of eravacycline/kg intravenously every 12 h for a total of seven doses over 4 days. Plasma samples were collected at 0, 1, 2, 4, 6, and 12 h on day 4, with each subject randomized to undergo a single bronchoalveolar lavage (BAL) at 2, 4, 6, or 12 h. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry, and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations. Pharmacokinetic parameters were estimated by noncompartmental methods. Penetration for ELF and AM was calculated by using a ratio of the area under the concentration time curve (AUC 0 -12 ) for each respective parameter against free drug AUC (fAUC 0 -12 ) in plasma. The total AUC 0 -12 in plasma was 4.56 ؎ 0.94 g·h/ml with a mean fAUC 0 -12 of 0.77 ؎ 0.14 g·h/ml. T he world today is facing an emerging crisis of bacterial resistance in both community-and hospital-acquired pathogens. Extensive use of antibiotics, along with increased industrialization and international transit have all contributed to the rise in antimicrobial resistance, morbidity, and mortality (1-8). According to ATS/IDSA guidelines, the second most common nosocomial infection in the United States is hospital-acquired pneumonia representing 25% of all intensive care unit infections, an excess cost of $40,000 per patient, and an average increase in hospital stay of 7 to 9 days (8).Eravacycline (TP-434) is a novel fluorocycline antibiotic being developed as an intravenous (i.v.) and oral medication for the treatment of serious infections caused by antibiotic-resistant bacteria (9). In vitro microbiological studies of eravacycline have demonstrated potent, broad-spectrum Gram-positive and Gramnegative antibacterial effect exhibiting activity against S. aureus isolates expressing methicillin resistance, as well as Enterobacteriaceae isolates expressing resistance genes from multiple classes of extended-spectrum ␤-lactamase (ESBLs) (9). When tested against clinical isolates of A. baumannii, eravacycline displayed 2-fold greater susceptibility than tigecycline (9), whereas additional testing on Gram-positive isolates of Enterococcus displayed no difference in potency with or without the presence of vancomycin resistance (9). The results from a prospective, randomized, double-blind, phase II study evaluating the safety and efficacy of eravacycline dosed once or twice daily versus ertapenem given once daily in complicated intra-abdominal infections (cIAI) demonstrated Ͼ92% clinical cure rates at the test of cure visit, with 100% cure rates in the twice-daily dosing group with infections caused by ESBL-producing, levofloxacin-and ertapenem-resistant organisms (10).Although preclinical and clinical data offer insight into the use of eravacycline to treat bacterial infections, overall success is dependent upon optimizing drug exposures at the site of infection. We sou...

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