Christopher M. ParryNga Tran Vu ThieuChristiane DolecekAbhilasha KarkeyRuchi GuptaPaul TurnerDavid DanceRapeephan R. MaudeVinh HaChinh Nguyen TranPhuong Le ThiBay Pham Van BeLa Tran Thi PhiRang Nguyen NgocAniruddha GhoseSabina DongolJames I. CampbellDuy Pham ThanhTuyen Ha ThanhCatrin E. MooreSoeng SonaRajni GaindMonorama DebHo Van AnhSach Nguyen VanHien Tran TinhNicholas P.J. DayArjen DondorpGuy ThwaitesMohamed Abul FaizRattanaphone PhetsouvanhPaul NewtonBuddha BasnyatJeremy J. FarrarStephen BakeraUCLUniversity of OxfordLiverpool School of Tropical MedicineOxford University Clinical Research UnitVardhman Mahavir Medical College &amp; Safdarjung HospitalAngkor Hospital for ChildrenShoklo Malaria Research UnitMahosot HospitalMahidol UniversityDong Thap Provincial HospitalAn Giang Provincial HospitalChittagong Medical College HospitalCentre for Specialized Care and ResearchLondon School of Hygiene &amp; Tropical MedicineNagasaki University2018-11-232018-11-232015-05-01Antimicrobial Agents and Chemotherapy. Vol.59, No.5 (2015), 2756-276410986596006648042-s2.0-84931272449https://repository.li.mahidol.ac.th/handle/123456789/36461Copyright © 2015, Parry et al. Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤16 μg/ml or disk inhibition zone size of ≥13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A.Mahidol UniversityMedicineArticleSCOPUS10.1128/AAC.04729-14