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Title: Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A
Authors: Christopher M. Parry
Nga Tran Vu Thieu
Christiane Dolecek
Abhilasha Karkey
Ruchi Gupta
Paul Turner
David Dance
Rapeephan R. Maude
Vinh Ha
Chinh Nguyen Tran
Phuong Le Thi
Bay Pham Van Be
La Tran Thi Phi
Rang Nguyen Ngoc
Aniruddha Ghose
Sabina Dongol
James I. Campbell
Duy Pham Thanh
Tuyen Ha Thanh
Catrin E. Moore
Soeng Sona
Rajni Gaind
Monorama Deb
Ho Van Anh
Sach Nguyen Van
Hien Tran Tinh
Nicholas P.J. Day
Arjen Dondorp
Guy Thwaites
Mohamed Abul Faiz
Rattanaphone Phetsouvanh
Paul Newton
Buddha Basnyat
Jeremy J. Farrar
Stephen Bakera
University of Oxford
Liverpool School of Tropical Medicine
Oxford University Clinical Research Unit
Vardhman Mahavir Medical College & Safdarjung Hospital
Angkor Hospital for Children
Shoklo Malaria Research Unit
Mahosot Hospital
Mahidol University
Dong Thap Provincial Hospital
An Giang Provincial Hospital
Chittagong Medical College Hospital
Centre for Specialized Care and Research
London School of Hygiene & Tropical Medicine
Nagasaki University
Keywords: Medicine
Issue Date: 1-May-2015
Citation: Antimicrobial Agents and Chemotherapy. Vol.59, No.5 (2015), 2756-2764
Abstract: Copyright © 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.
ISSN: 10986596
Appears in Collections:Scopus 2011-2015

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