Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania

Abstract

Background Early detection and correction of low fluoroquinolone exposure may improve treatment of MDR-TB. Objectives To explore a recently developed portable, battery-powered, UV spectrophotometer for measuring levofloxacin in saliva of people treated for MDR-TB. Methods Patients treated with levofloxacin as part of a regimen for MDR-TB in Northern Tanzania had serum and saliva collected concurrently at 1 and 4 h after 2 weeks of observed levofloxacin administration. Saliva levofloxacin concentrations were quantified in the field via spectrophotometry, while serum was analysed at a regional laboratory using HPLC. A Bayesian population pharmacokinetics model was used to estimate the area under the concentration–time curve (AUC0–24). Subtarget exposures of levofloxacin were defined by serum AUC0–24 <80 mg·h/L. The study was registered at Clinicaltrials.gov with clinical trial identifier NCT04124055. Results Among 45 patients, 11 (25.6%) were women and 16 (37.2%) were living with HIV. Median AUC0–24 in serum was 140 (IQR = 102.4–179.09) mg·h/L and median AUC0–24 in saliva was 97.10 (IQR = 74.80–121.10) mg·h/L. A positive linear correlation was observed with serum and saliva AUC0–24, and a receiver operating characteristic curve constructed to detect serum AUC0–24 below 80 mg·h/L demonstrated excellent prediction [AUC 0.80 (95% CI = 0.62–0.94)]. Utilizing a saliva AUC0–24 cut-off of 91.6 mg·h/L, the assay was 88.9% sensitive and 69.4% specific in detecting subtarget serum AUC0–24 values, including identifying eight of nine patients below target. Conclusions Portable UV spectrophotometry as a point-of-care screen for subtarget levofloxacin exposure was feasible. Use for triage to other investigation or personalized dosing strategy should be tested in a randomized study.

Clinical Efficacy and Safety Analysis of Levofloxacin for the Prevention of Infection after Traumatic Osteoarthrosis and Internal Fixation: Systematic Review and Meta-Analysis

“…Over 60 years old in patients receiving levofloxacin there was a higher incidence of adverse reactions to prevent infection treatment mainly includes: the main reasons for elderly patients with viscera function decline, easily complicated by a variety of disease, and levofloxacin by kidney metabolism, effects on kidney burden, clinical applications in the old people should take into consideration the reduction and regular monitoring of kidney function [31]. In addition, from the animal experiments on quinolone antibiotics, it was found that young animals taking quinolone antibiotics would produce cartilage damage to joint tissue, so children, pregnant and lactating women should be forbidden levofloxacin [32][33][34][35]. At the same time, because levofloxacin belongs to quinolones antibiotic effect, from this group of cases cure effect and ADRs of reaction after taking levofloxacin, static drop 1-or 2-times daily fee sand star of left oxygen drugs for prevention of postoperative infection, there was no significant difference, and oxygen cost effect of medication to reduce the incidence of ADR is safer and more effective [36][37][38][39].…”

Population Pharmacokinetics of Levofloxacin and Moxifloxacin, and the Probability of Target Attainment in Ethiopian Patients with Multidrug-Resistant Tuberculosis

“…Lastly, more rigorous PopPK analyses to determine the optimal starting dose, if performed at local or regional levels, may be able to determine a setting-specific dose that could mitigate the routine need for TDM. [55][56][57]…”

Pharmacokinetic-Pharmacodynamic Determinants of Clinical Outcomes for Rifampin-Resistant Tuberculosis: A Multisite Prospective Cohort Study

“…For RR/MDR-TB, drugs of priority should include fluoroquinolones and pyrazinamide where in vitro and clinically identified targets now appear to align. Alternative sample matrices such as saliva [ 21 ] and urine [ 22 ] that use spectrophotometric methods may bring such personalized dosing closer to the point of care.…”