NDLI: Clinically and Microbiologically Derived Azithromycin Susceptibility Breakpoints for Salmonella enterica Serovars Typhi and Paratyphi A

Content Provider	PubMed Central
Author	Parry, Christopher M. Thieu, Nga Tran Vu Dolecek, Christiane Karkey, Abhilasha Gupta, Ruchi Turner, Paul Dance, David Maude, Rapeephan R. Vinh, Ha Tran, Chinh Nguyen Thi, Phuong Le Van, Be Bay Pham Phi, La Tran Thi Ngoc, Rang Nguyen Ghose, Aniruddha Sabina, Dongol Campbell, James I. Thanh, Duy Pham Thanh, Tuyen Ha Moore, Catrin E. Sona, Soeng Rajni, Gaind Deb, Monorama Anh, Ho Van Van, Sach Nguyen Tran, Tinh Hien Day, Nicholas P. J. Dondorp, Arjen Thwaites, Guy Faiz, Mohamed Abul Phetsouvanh, Rattanaphone Newton, Paul Basnyat, Buddha Farrar, Jeremy J. Baker, Stephen
Copyright Year	2015
Abstract	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.
Related Links	http://dx.doi.org/10.1128/aac.04729-14
Ending Page	2764
Page Count	9
Starting Page	2756
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	5
Volume Number	59
Language	English
Publisher	American Society for Microbiology
Publisher Date	2015-05-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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