Clinical improvement despite rising anti-streptococcal antibody titers during adjunctive bacteriophage therapy in refractory PANDAS: a hypothesis-generating case report

Background Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by the abrupt onset of anxiety, obsessive-compulsive symptoms, tics, and other neuropsychiatric manifestations associated with Group A Streptococcus exposure. Although antimicrobial and immunomodulatory therapies are widely employed, many patients experience persistent or relapsing symptoms despite prolonged treatment. Bacteriophage therapy has not previously been reported in PANDAS and represents an experimental, pathogen-directed therapeutic approach. Case presentation We report the case of an 11-year-old girl with severe refractory PANDAS characterized by obsessive-compulsive symptoms, anxiety, motor and vocal tics, emotional dysregulation, insomnia, agitation, and marked functional impairment, including school refusal. The diagnosis was supported by elevated antistreptococcal serology. The patient received several escalating interventions, including intramuscular benzathine penicillin, azithromycin, plasma exchange, intravenous immunoglobulins, psychotherapy, and aripiprazole. A clinical improvement was initially observed after penicillin administration, although the benefit was incomplete and transient. No active streptococcal isolate was available for phage susceptibility testing. On the basis of repeated antibiotic responsiveness, empirical anti-streptococcal bacteriophage therapy was initiated using Pyo Bacteriophages (Eliava biopreparation), administered twice daily for three 15-day cycles as add-on therapy, while antibiotics were maintained. Results Clinical sustained improvement became evident approximately six days after initiation of bacteriophage therapy, mirroring the latency previously observed after penicillin, and was followed by sustained clinical stabilization. No adverse events were reported. Serial serological evaluation demonstrated a paradoxical increase in ASO and anti-DNase titres despite continuous neurological and psychiatric improvement. Conclusions This case suggests that bacteriophage therapy may represent a plausible pathogen-directed strategy in selected patients with refractory PANDAS, particularly when a reproducible clinical response to anti-streptococcal antibiotics suggests persistent microbial involvement. More importantly, the observed dissociation between rising anti-streptococcal antibody titers and sustained clinical improvement raises the possibility that serological kinetics may not accurately reflect disease activity during effective pathogen-directed therapy. One possible explanation is that bacteriophage-induced bacterial lysis increased antigen exposure while simultaneously reducing the bacterial burden responsible for persistent immune activation. However, because bacteriophages were administered as add-on therapy in a single uncontrolled case, causality cannot be established. Prospective studies are required to determine the role of bacteriophage-based interventions in post-infectious neuroimmune disorders.