THERAPEUTIC OPTIONS FOR CAT-SCRATCH DISEASE

Abstract

IN REPLY: We thank Dr. Zangwill for his interest in our study. The study fulfills the objectives as stated in the title; that was to evaluate the effectiveness of azithromycin for the treatment of cat-scratch disease (CSD). We stated why we selected this antibiotic as our prime candidate drug for this investigation, and we listed numerous references supporting this choice. These references are detailed in recent comprehensive reviews on Bartonella infections: one by Zangwill which he referenced in his letter; the other by our group which was referenced1 in our paper. In our paper we did not elaborate on these or other reports nor did we speculate with regard to these reports and our findings. Dr. Zangwill questions the possible effect on outcome of prior antibiotic treatment in our study patients. We evaluated this using the method of analysis noted in our report, and we found no effect of prior antibiotic treatment relevant to beta-lactam or non-beta-lactam antibiotics. Contrary to Zangwill's comments we did not overstate the findings of our study or recommend azithromycin for treatment for typical CSD. We stated that the only statistically significant clinical benefit that we could detect in azithromycin- vs. placebo-treated patients was decrease in lymph node volume after 30 days as quantitated by ultrasonography, not an overstatement, only a fact. Dr. Zangwill takes a part of a sentence in the Conclusions in our Abstract out of context with the rest of the sentence "azithromycin affords significant clinical benefit" inferring overall clinical benefit, while the rest of the sentence reads "as measured by decrease lymph node volume within the first month of treatment." He infers that we recommended routine treatment of patients with CSD with this antibiotic. We did not. Nor did we recommend ultrasonography for routine evaluation and follow-up of patients with this disease. Dr. Zangwill states that "apparent post hoc analysis at the 30-day time period is inherently biased." He further states, "that restricting the analysis to this single point may inappropriately maximize treatment effects." The Methods and Results sections detail that the interval for follow-up of study patients was predetermined and the data analysis was predefined. Data analysis was performed at every point along the period of observation (before and after 30 days) for which there were sufficient numbers of patients in the treatment groups for analysis. These observations were continued for each study patient until 80% resolution of their total initial lymph node volume was achieved. This information is provided in the text and displayed in Figure 1. Zangwill questions our methods for follow-up specifically "... a definition of the clinical parameters evaluated, by whom, for how long and according to what standards were these evaluations performed." These evaluations were conducted by pediatricians, internists and radiologists at Tripler Army Medical Center, all experienced in evaluation of patients with CSD, obvious to any reader on perusing the coauthors' affiliations noted on the title page of our report. The time intervals of follow-up are provided in the Results section, and the duration of follow-up is provided in the text and is shown in Figure 1. We used a clinical data collection form that provided for detailed initial and weekly follow-up of fever, clinical signs and symptoms. Radiologists performed clinical evaluations at each ultrasonography examination. Although six patients in each treatment group reported having had fever, all were afebrile at entrance into the study and none reported having fever thereafter. There were no differences in clinical findings except those related to lymph node volumes. We found physical examination of this "parameter" was far less precise than ultrasonography. It is important to reiterate that all study patients had "typical" CSD as defined in our report. This clinical presentation has a predictable limited, although sometimes extended, course in immunocompetent patients. We did not study patients with "atypical" CSD as defined in our report and we did not make speculations regarding the findings of our study and treatment implications of patients with atypical CSD. To our knowledge our study is the only prospective randomized double blind placebo-controlled study evaluating any antimicrobial agent for treatment of patients with CSD. It involved several hundred clinical evaluations and laboratory tests including >200 ultrasonagraphy studies with coordination of the contributions of 12 coinvestigators during a 2-year period. The data obtained were carefully analyzed, presented succinctly and interpreted conservatively. James W. Bass, M.D. Bonnie C. Freitas, M.D. Alexander D. Freitas, M.D. Debora S. Chan, F.A.S.H.P. Judy M. Vincent, M.D. Donald A. Person, M.D. Robert R. Wittler, M.D. Martin E. Weisse, M.D. Tripler Army Medical Center; Honolulu, HI (JWB, BCF, ADF, DSC, JMV, DAP) Department of Pediatrics; University of Kansas; School of Medicine; Wichita, KS (RRW) Department of Pediatrics; West Virginia University School of Medicine; Morgantown, WV (MEW)