title: Cavitary penetration of levofloxacin among patients with multidrug-resistant tuberculosis.
abstract: A better understanding of second-line drug (SLD) pharmacokinetics, including cavitary penetration, may help optimize SLD dosing. Patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the time of cavitary removal to measure levofloxacin concentrations. After surgery, microdialysis was performed using the ex vivo cavity, and levofloxacin concentrations in the collected dialysate fluid were measured. Noncompartmental analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio was calculated. Twelve patients received levofloxacin for a median of 373 days before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration in serum (Cmax) was 6.5 μg/ml, and it was <2 μg/ml in 3 (25%) patients. Among 11 patients with complete data, the median cavitary concentration of levofloxacin was 4.36 μg/ml (range, 0.46 to 8.82). The median cavitary/serum levofloxacin ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1. There was a significant correlation between serum and cavitary concentrations (r = 0.71; P = 0.01). Levofloxacin had excellent penetration into chronic cavitary TB lesions, and there was a good correlation between serum and cavitary concentrations. Optimizing serum concentrations will help ensure optimal cavitary concentrations of levofloxacin, which may enhance treatment outcomes.
authors.affiliation: Division of Infectious Diseases Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA rkempke@emory.edu.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Kempker
authors.affiliation: University of Florida, College of Pharmacy, Gainesville, Florida, USA.
authors.forename: Aline B
authors.initials: AB
authors.lastname: Barth
authors.affiliation: National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
authors.forename: Sergo
authors.initials: S
authors.lastname: Vashakidze
authors.affiliation: National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
authors.forename: Ketino
authors.initials: K
authors.lastname: Nikolaishvili
authors.affiliation: National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
authors.forename: Irina
authors.initials: I
authors.lastname: Sabulua
authors.affiliation: National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
authors.forename: Nestani
authors.initials: N
authors.lastname: Tukvadze
authors.affiliation: National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
authors.forename: Nino
authors.initials: N
authors.lastname: Bablishvili
authors.affiliation: National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
authors.forename: Shota
authors.initials: S
authors.lastname: Gogishvili
authors.affiliation: University of Florida, College of Pharmacy, Gainesville, Florida, USA.
authors.forename: Ravi Shankar P
authors.initials: RS
authors.lastname: Singh
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Guarner
authors.affiliation: University of Florida, College of Pharmacy, Gainesville, Florida, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.affiliation: University of Florida, College of Pharmacy, Gainesville, Florida, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
authors.affiliation: Division of Infectious Diseases Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA Departments of Epidemiology and Global Health, Emory Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Blumberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D064704:Levofloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D064704:Levofloxacin