Antibiotic Treatment vs. Placebo for Adenitis from Cat Scratch Disease

ABSTRACT & COMMENTARY

Synopsis: Five days of oral azithromycin was more effective than placebo in reducing the size of adenitis associated with cat scratch disease in this well-designed study with a small number of patients. The difference was most significant at 30 days post-treatment.

Source: Bass JW, et al. Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of Cat-Scratch Disease. Pediatr Infect Dis J 1998;17:447-452.

The article by bass and colleagues describes a prospective, randomized, double-blind, placebo controlled clinical trial that compares azithromycin to placebo in treating adenitis secondary to Bartonella henselae infection or cat-scratch disease.

Patients aged 6-65 years old were enrolled when suspected of having a B. henselae infection if there was: 1) regional lymphadenopathy and a cat-scratch, bite, or papule in the area of the involved node; 2) regional lymphadenopathy and no skin lesion but a history of intimate cat exposure; and 3) a positive immunol fluorescent antibody (IFA) test of 1:64 or more. The number of days until an 80% reduction of the initial lymph node volume was noted using three-dimensional ultrasonography. The dose of azithromycin used was 500 mg initially then 250 mg for a total of five days in patients more than 45.5 kg, and 10 mg/kg on the first day and 5 mg/kg for the subsequent four days in children.

Seven of 14 patients in the azithromycin group and one of 15 in the placebo group had an 80% reduction of node size during the first 30 days following treatment. After 30 days, there was no difference between groups. At 30 days after treatment, the greatest statistical significance was noted (P = 0.02), with an odds ratio of approximately 17 but a wide 95% confidence interval (1.5-196).

Comment by Louis M. Bell, MD, FAAP

Although cat-scratch disease (CSD) was described more than 45 years ago, only recently has a gram-negative coccobacillus, B. henselae (formerly the genus Rochalimaea) been isolated from the lymph node tissue of patients with adenitis. In addition, CSD can be associated with fever of unknown origin, seizures, encephalitis, micro abscesses in the liver or spleen, and aseptic meningitis.

Diagnosis of B. henselae infection by culture is difficult, requiring extended incubation (up to 1 month) on solid agar. PRCR amplification of Bartonella specific nucleic acid sequence is a research tool not routinely available.

Fortunately, an indirect fluorescent antibody (IFA) test is available. A positive result at titers of 1:64 or more occurs in 84-88% of patients with suspected CSD. Patients with adenitis and cat contact, especially in cats younger than 1 year of age, or actual cat scratch are more likely to be seropositive.

Unfortunately, therapy with antibiotics for cat scratch adenitis have not resulted in dramatic clinical improvement. In 1992, Margileth in an uncontrolled retrospective study, attempted to determine the effectiveness of antibiotic therapy. The results were not conclusive and, in immunocompetent patients with uncomplicated CSD adenitis conservative, symptomatic treatment was recommended. The infection is self limited, gradually resolving in 2-3 months.

The current study by Bass et al is well designed with a small number of enrolled subjects comparing treatment with azithromycin and placebo. Ultrasonography was performed at mean intervals of 9.7 (± 4.7) days in the azithromycin group and 8.7 (± 3.7) in the placebo group with no significant difference between the groups at these interval evaluations. However, at one month after treatment, the treatment group was 17 times more likely to have an 80% reduction in the size of the adenitis as compared to the placebo group. However, the 95% confidence interval reveals that the effect of treatment could be as low as 1.5 times that of placebo.

This is a good first step in determining the choice and duration of antibiotic therapy for CSD, but it remains to be seen whether patients with mild-to-moderate CSD adenitis will gain significant clinical benefit from antibiotic therapy.

References

1. Margileth AM. Antibiotic therapy for cat-scratch disease: Clinical study of therapeutic outcome in 268 patients and a review of the literature. Pediatr Infect Dis J 1992;11:474-478.

2. Dalton MJ, et al. Use of Bartonella antigens for serologic diagnosis of cat-scratch disease at a National Referral Center. Arch Intern Med 1995;155:1670-1676.

3. Adal KA, et al. Cat-scratch disease, bacillary angiomatosis, and other infections due to rochalimaea. N Engl J Med 1994;330:1509-1515.

4. Demers DM, et al. Cat-scratch disease in Hawaii: Etiology and Seroepidemiology. J Pediatr 1995;127:23-26.