Plasma concentration of azithromycin and correlation with clinical outcomes in patients with enteric fever.

Abstract

Background: Azithromycin is the only oral option available for XDR enteric fever. Studies correlating azithromycin levels with treatment success are rare.

Methods: Serum azithromycin levels after administration of a once-daily 20 mg/kg dose for 7 days were measured in a single-centre prospective cohort of 25 consecutive adults with blood culture-positive enteric fever. Five blood samples were collected on Day 2 after starting azithromycin, i.e. 30 min before dosing (trough), and 2, 5, 12 and 24 h after dosing. The MIC was determined for all isolates and azithromycin plasma concentration was determined using LC-MS. Clinical and microbiological outcomes were documented.

Results: Salmonella enterica serovar Typhi accounted for 92% (n = 23) and Salmonella enterica serovar Paratyphi 8% (n = 2). Ten (40%) patients received IV azithromycin, and the rest received oral therapy. The median (IQR, range) MIC for azithromycin was 4 (4-6, 3-12) mg/L. Mean azithromycin plasma concentration ranges were: trough, 0.24 ± 0.19 mg/L; 2 h, 1.24 ± 0.98 mg/L; 5 h, 0.64 ± 0.51 mg/L; 12 h, 0.31 ± 0.16 mg/L; and 24 h, 0.37 ± 0.30 mg/L. The C _max/MIC and AUC/MIC for azithromycin were 0.29 ± 0.22 and 2.64 ± 1.64, respectively. The median (IQR, range) fever clearance time was 3 (2-3, 2-5) days and the length of hospital stay was 7 (5.5-12, 4-16) days. There was no clinical or microbiological failure, relapse or mortality.

Conclusions: Azithromycin was effective in treatment of enteric fever, despite low extracellular azithromycin plasma levels.