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Antimicrobial Agents and Chemotherapy, April 2008, p. 1278-1284, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01509-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Clinical Response and Outcome of Infection with Salmonella enterica Serotype Typhi with Decreased Susceptibility to Fluoroquinolones: a United States FoodNet Multicenter Retrospective Cohort Study{triangledown}

John A. Crump,1,4*,{dagger} Katrina Kretsinger,1,4,{dagger} Kathryn Gay,2 R. Michael Hoekstra,3 Duc J. Vugia,5 Sharon Hurd,6 Susan D. Segler,7 Melanie Megginson,8 L. Jeffrey Luedeman,9 Beletshachew Shiferaw,10 Samir S. Hanna,11 Kevin W. Joyce,2 Eric D. Mintz,1 Frederick J. Angulo,1 and the Emerging Infections Program FoodNet and NARMS Working Groups

Enteric Diseases Epidemiology Branch, National Center for Zoonotic, Vectorborne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 303331,1 Enteric Diseases Laboratory Preparedness Branch, National Center for Zoonotic, Vectorborne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,2 Division of Foodborne, Bacterial, and Mycotic Diseases, National Center for Zoonotic, Vectorborne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,3 Epidemic Intelligence Service, Division of Applied Public Health Training, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,4 California Department of Health Services, Berkeley, California,5 Connecticut Emerging Infections Program, New Haven, Connecticut,6 Georgia Emerging Infections Program, Atlanta, Georgia,7 Maryland Department of Health and Mental Hygiene, Baltimore, Maryland,8 Minnesota Department of Health, Minneapolis, Minnesota,9 Oregon Department of Human Services, Portland, Oregon,10 Tennessee Department of Health, Nashville, Tennessee,11

Received 21 November 2007/ Returned for modification 20 December 2007/ Accepted 15 January 2008

Patients with typhoid fever due to Salmonella enterica serotype Typhi strains for which fluoroquinolones MICs are elevated yet that are classified as susceptible by the current interpretive criteria of the Clinical and Laboratory Standards Institute may not respond adequately to fluoroquinolone therapy. Patients from seven U.S. states with invasive Salmonella serotype Typhi infection between 1999 and 2002 were enrolled in a multicenter retrospective cohort study. Patients infected with Salmonella serotype Typhi isolates with ciprofloxacin MICs of 0.12 to 1 µg/ml (decreased ciprofloxacin susceptibility but not resistant to ciprofloxacin [DCS]) were compared with patients infected with isolates with ciprofloxacin MICs <0.12 µg/ml for fever clearance time and treatment failure. Of 71 patients, 30 (43%) were female and 24 (34%) were infected with Salmonella serotype Typhi with DCS; the median age was 14 years (range, 1 to 51 years). Twenty-one (88%) of 24 isolates with DCS were resistant to nalidixic acid. The median antimicrobial-related fever clearance times in the DCS and non-DCS groups were 92 h (range, 21 to 373 h) and 72 h (range, 19 to 264 h) (P = 0.010), respectively, and the fluoroquinolone-related fever clearance times in the DCS and non-DCS groups were 90 h (range, 9 to 373 h) and 64 h (range, 34 to 204 h) (P = 0.153), respectively. Four (17%) of 24 patients in the DCS group and 2 (4%) of 46 patients in the non-DCS group (relative risk, 2.5; 95% confidence interval, 1.2 to 5.1) experienced treatment failure. Associations persisted after adjustment for potential confounders. We demonstrate that patients infected with Salmonella serotype Typhi isolates with DCS show evidence of a longer time to fever clearance and more frequent treatment failure. Nalidixic acid screening does not detect all isolates with DCS.

* Corresponding author. Mailing address: Enteric Diseases Epidemiology Branch, Division of Foodborne, Bacterial, and Mycotic Diseases, National Center for Zoonotic, Vectorborne, and Enteric Diseases, MS A-38, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333. Phone: (404) 639-2206. Fax: (404) 639-2205. E-mail: jcrump{at}cdc.gov

{triangledown} Published ahead of print on 22 January 2008.

{dagger} John A. Crump and Katrina Kretsinger contributed equally to this work.

Antimicrobial Agents and Chemotherapy, April 2008, p. 1278-1284, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01509-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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