Cervical Lymphadenitis With Mycobacterium stomatepiae: Diagnostic and Management Challenges

To the Editors: A 19-month-old male presented to an infectious disease clinic with an enlarged mass in the right submandibular region that had been present for 8 weeks before the visit. The patient was pretreated with amoxicillin-clavulanate and oral clindamycin over a 2-week course, with no improvement. There was no associated pain, fever, or weight loss, and the rest of his review of the systems was unremarkable. Intermittent discoloration of the skin overlying the mass is observed. There was no recent travel, known sick contact, or animal exposure. He frequently swam in a lake. The patient was fully vaccinated and was otherwise healthy. On the first visit to the clinic, his vital signs were within normal limits. Physical examination at the initial presentation revealed a firm, nontender mass with overlying red and purple skin discoloration. No drainage was noted, and no other masses or lymphadenopathy were palpated. The remaining examination results were within the normal limits. No antibiotics were prescribed during the initial visit. An ultrasound of the area revealed an approximately 3.1 × 2.2 × 2.5 cm heterogeneous hypoechoic fluid collection with internal echogenic debris and slightly increased peripheral vascularity within the right submandibular region. His initial laboratory workup results were unremarkable. His complete blood count revealed a white cell count of 4.6 × 103/μL (normal range: 5.98–13.51 × 10*3/uL), hemoglobin 11.4 g/dL (normal range: 10.1–12.5 g/dL), hematocrit 35.5% (normal range: 30.8%–37.9 %) and C-reactive protein 4.8 mg/L (normal range: <8.0 mg/L). His chemistry, uric acid and lactate dehydrogenase levels were within normal limits. Quantiferon gold, cytomegalovirus and Epstein-barr virus serologies were also negative. Based on the patient’s history and clinical examination, nontuberculous mycobacteria were suspected. Otolaryngology was consulted, and excision could not be performed because of the size of the mass and potential complications. The patient underwent interventional radiology-guided fine needle aspiration of the mass. The aerobic, anaerobic, fungal, and mycobacterial cultures were negative. Histopathologic examination revealed necrotic granulomatous inflammation with negative acid-fast bacilli and bacterial and fungal staining. He was started on azithromycin 10 mg/kg daily and rifampin 10 mg/kg once daily while awaiting bacterial and mycobacterial polymerase chain reaction (PCR) testing of the tissue sample. Three weeks after aspiration, the mycobacterial PCR returned to Mycobacterium stomatepiae. Mycobacterial cultures were negative. Despite compliance with antibiotics, the lymphadenitis worsened. Ethambutol (10 mg/kg once daily) and levofloxacin (10 mg/kg twice daily) were added to his regimen. At the 4-week follow-up visit on quadruple therapy, he had a significant decrease in the size of the lymph node and tolerated all antibiotics with no side effects. Repeat ultrasound revealed at the end of 12-week treatment revealed reduction in the size of the lymph node to 1.9 × 1.2 × 1.7 cm (previously 3.1 × 2.2 × 2.5 cm). He completed a 4-month course of quadruple therapy, with almost complete resolution of the lesion. This report describes a pediatric patient with cervical lymphadenitis caused by M. stomatepiae, a rare non-tuberculous mycobacterium (NTM). M. stomatepiae, also a slow-growing NTM, belongs to the Mycobacterium simiae complex and is primarily found in aquatic environments, particularly in association with fishes.1 In pediatric populations, NTM-related cervical lymphadenitis is most caused by Mycobacterium avium complex, while M. stomatepiae has only been sporadically reported.2 Given the slow growth and specific culture requirements of this organism, its isolation from clinical specimens can be challenging. Unlike most other Mycobacteria, M. stomatepiae does not grow at 37 °C and requires incubation at 30 °C. In this case, the mycobacterial culture was not incubated at 30 °C, resulting in a negative result. PCR amplification of the 16S rRNA gene, along with primer sets targeting the hsp65 and rpoB genes, identified M. stomatepiae. This case highlights the utility of molecular techniques that are particularly valuable for identifying rare NTM infections that may otherwise remain undetected using conventional culture methods.2 The management of M. stomatepiae infections has not been well established because of the paucity of reported cases. The 2020 consensus guidelines from the American Thoracic Society and Infectious Diseases Society of America recommend treating M. simiae, a related species within the same complex, with a multidrug regimen including a macrolide (azithromycin or clarithromycin), moxifloxacin, trimethoprim-sulfamethoxazole (TMP-SMX), and parenteral amikacin or clofazimine.3 These guidelines are based largely on studies in adults with M. simiae pulmonary disease. In a study of 102 patients with M. simiae, 37% were asymptomatic and did not meet diagnostic criteria for NTM pulmonary disease. Among those requiring treatment, a regimen of macrolide, ethambutol, and rifampin for a minimum of 12 months resulted in a full recovery. However, antimicrobial resistance among M. simiae isolates has been reported, with a study from Iran demonstrating 100% resistance to rifampin as well and increased resistance to ethambutol (64%) and linezolid (76%).4 By contrast, the highest susceptibility rates were observed for amikacin (100%) and clarithromycin (85%). In vitro studies have shown M. simiae retains susceptibility to macrolides, TMP-SMX, and clofazimine, whereas resistance patterns for quinolones, aminoglycosides, and cycloserine vary. Clinical cases of M. simiae infection occur primarily in immunosuppressed patients, particularly those with HIV/AIDS and CD4 counts <50 cells/μL. Pediatric cases of M. simiae infection are exceedingly rare, with only one documented case of a 19-month-old immunocompetent child who presented with submandibular lymphadenitis.5 The child underwent partial lymph node excision and achieved clinical resolution without antimicrobial therapy. Given the paucity of data on both M. triplex and M. stomatepiae in children, our treatment approach was extrapolated from the adult NTM guidelines.6 Drug susceptibility testing could not be performed because mycobacterial cultures were negative. We initiated a four-drug regimen consisting of azithromycin, rifampin, levofloxacin, and ethambutol. The treatment duration was determined based on clinical and radiographic improvements. This case highlights the importance of M. stomatepiae in pediatric cervical lymphadenitis, particularly in the context of environmental exposure, such as lake water. Given its potential for multidrug resistance, a combination regimen including macrolides, rifampin, fluoroquinolones, and either ethambutol or TMP-SMX should be considered. For more invasive infections or immunocompromised hosts, treatment with amikacin or clofazimine may be warranted. Our findings highlight the critical role of a high index of clinical suspicion and mycobacterial PCR amplification of the 16S rRNA gene in diagnosing slow-growing NTM infections because reliance on culture alone may lead to delayed diagnosis and treatment initiation.