Stephen J.LurieMD, PhD, Senior Editor
To The Editor: We are concerned that the study of Ikeda et al1 disproportionately influenced the results of the meta-analysis by Dr Safdar and colleagues.2 Specifically, Ikeda et al concluded that use of fosfomycin in the first 2 days of illness, but not later, was associated with decreased risk of HUS. Designating the first day of illness as that on which any sign or symptom first occurred (including fever and abdominal pain and not only diarrhea) is problematic and not clinically useful because of the subjectivity and poor specificity of these assessments. Even if this definition could measure accurately the interval between illness onset and treatment, the benefit accruing to patients starting fosfomycin on day 2 (the only group chosen for analysis by Safdar et al) is no more than subgroup analysis. Moreover, benefit when administered during the second day of symptoms, but not when administered on other days, is microbiologically implausible. Ikeda et al adjusted only for parental report of fever but not for white blood cell count, a repeatedly demonstrated risk factor for HUS. Also, because few patients received no antibiotics, nontreatment with antimicrobials was not assessed.
Tarr PI, Watkins SL, Neill MA. Risk of Hemolytic Uremic Syndrome From Antibiotic Treatment of Escherichia coli O157:H7 Colitis. JAMA. 2002;288(24):3111. doi:10.1001/jama.288.24.3111-JLT1225-2-3