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

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

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.

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.

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