Streptococcus agalactiae in relapsing cellulitis.

To the Editor—We read with interest the report by Del Giudice et al. [1] about a case of relapsing erysipelas caused by Streptococcus agalactiae. Molecular analyses of the strains, which were isolated from skin and vaginal specimens during 2 episodes, revealed identical restriction patterns, leading the authors to suggest that vaginal carriage of S. agalactiae served as a reservoir for relapsing skin infection. Nevertheless, the detailed pathogenesis of relapsing cellulitis/erysipelas has not been fully elucidated. We report a case of fasciitis that was followed by 4 episodes of cellulitis, and we discuss an additional mechanism of recurrence. A 38-year-old, previously healthy woman presented with fever, chills, and severe pain in the left leg. Clinical examination of the extremity revealed edematous erythema with pronounced tenderness. MRI delineated a fluid collection between the subcutaneous tissue and the fascia. Wide debridement was performed immediately, and intravenous antimicrobial treatment (amoxicillinclavulanate, 2.2 g 3 times per day, plus clindamycin, 600 mg 3 times per day) was administered. Gram-positive cocci in chains were abundant throughout the tissue specimens, but they failed to grow on culture. Broad-spectrum PCR and blood culture results remained negative. The patient’s subsequent clinical course was favorable, but lymphedema persisted at the infection site. During the subsequent 2 years, cellulitis occurred in the same area 4 times (7, 15, 17, and 24 months after the occurrence of fasciitis). S. agalactiae grew in blood cultures during the first and fourth episodes of cellulitis and from a vaginal swab culture during the third episode of cellulitis. Extensive investigations, including echocardiography, gynecological, and immunological examinations, revealed neither the source of bacteremia nor evidence of primary or secondary immunosuppression. The infections resolved after 8–14 days of intravenous penicillin (plus aminoglycosides during 2 episodes). After the third episode, a 5-month prophylactic course of amoxicillin (750 mg 3 times per day) was initiated. Two months after completion of the amoxicillin regimen, the cellulitis relapsed. SmaI digestion of the strains isolated from the vagina (third episode) and blood (fourth episode), followed by PFGE, revealed identical restriction patterns. The patient is currently being treated with a second course of long-term oral prophylaxis. Our case and the reported cases of relapsing cellulitis/erysipelas due to S. agalactiae involved a skin region affected by chronic lymphedema [1–3], which is strongly associated with recurrent streptococcal infection [4]. Lymphatic tissue alterations may lead to locally impaired immune responses and insufficient bacterial clearance. Therefore, spread from vaginal colonization may not be the only explanation for multiple relapses. In situ persistence of microorganisms in nonprofessional phagocytes can cause relapsing infection, as shown with Staphylococcus aureus [5, 6]. Furthermore, analyses of biopsy specimens obtained from persons with severe soft-tissue infection have revealed significant amounts of viable Streptococcus pyogenes, despite the administration of antibiotics, up to 14 days after disease onset [7]. Group B streptococci can interact with extracellular matrix components of eukaryotic cells and may invade fibroblasts and epithelial and endothelial cells [8]—findings that could support our hypothesis of in situ persistence. This does not conflict with the results of the study by Del Giudice et al. [1], but it might contribute an additional possible mechanism in recurrent cellulitis/erysipelas. Intracellular persistence of viable group A streptococci in erysipelas is currently being analyzed at our center [9].