Utility of multiplex PCR syndromic panel for respiratory infections in the diagnosis of acute bacterial meningitis

A five-year-old girl, up-to-date on vaccinations and with no history of interest, attended the emergency department due to a clinical picture over the previous 24 h of fever (39.2 °C), vomiting, hyporexia, lethargy and headache. She was admitted to paediatrics with progressive worsening at 24 h, left periorbital swelling, tendency to drowsiness and tripod position when attempting to sit. A lumbar puncture and CT were performed, being compatible with acute bacterial meningitis (polymorphonuclear pleocytosis, glucose 4 mg/dl, proteins 106 mg/dl). No microorganisms were visible in gram staining. She was admitted to the ICU, starting empirical antibiotic therapy with cefotaxime (300 mg/kg/day) and vancomycin (60 mg/kg/day), as well as dexamethasone (0.15 mg/kg/day).

A Filmarray® meningitis/encephalitis panel (BioMérieux, France) was conducted and was negative for the microorganisms that usually cause meningitis in our setting. Gram staining of the blood culture revealed clusters of gram-positive cocci. A Filmarray® respiratory panel (RP2plus) was performed, amplifying Streptococcus pyogenes (SPY). The paediatrician was informed, but did not modify the treatment until SPY growth was obtained in cerebrospinal fluid (CSF). A coagulase-negative staphylococcus grew in the blood culture, but was considered a contaminant. Vancomycin was suspended and clindamycin added for nine days as toxic shock was suspected due to hypotension and erythrodermia in the hands and face. On the sixth day after admission, the patient returned to paediatrics, with progressive improvement of her general condition and resolution of the neurological symptoms, with the exception of right peripheral facial paralysis. She was diagnosed with acute otitis media, which gradually resolved after maintaining dexamethasone for four days (0.15 mg/kg/day) and left preseptal cellulitis, for which treatment was initiated with Tobradex® for 10 days.

On the seventh day, she was readmitted to the ICU due to a frontal headache (dexamethasone restarted for 48 h) and hyponatraemia, with findings compatible with cerebral salt wasting syndrome. After eight days of treatment, coinciding with the administration of cefotaxime, she presented an exanthematic pruriginous reaction on the face and trunk, which was alleviated with corticosteroids. Subsequently, she presented a similar reaction with vancomycin, and again with meropenem, likewise alleviated with intravenous corticosteroids. The allergology unit recommended administering vancomycin premedicated with ranitidine and polaramine and avoiding beta-lactams, and 20 days of treatment were completed without skin reactions. At discharge, the physical examination and audiometry were normal, with minimal left ptosis. One year later, she had presented no sequelae.

SPY is a gram-positive bacteria that causes a wide spectrum of diseases, with acute pharyngotonsillitis being the most common.¹ It can be responsible for otitis media, sinusitis, and various invasive and immunological infections. On occasions, it can cause meningitis and other intracranial infections, either through direct extension of a contiguous focus or haematogenous dissemination.^1,2 According to the Centers for Disease Control and Prevention, meningitis due to SPY has a prevalence of 0.06 cases per 100,000 children/year (<0.2% of bacterial meningitis cases)³ with a 43% mortality rate.

Acute bacterial meningitis is a medical emergency, and therefore early diagnosis and treatment are essential in order to avoid a fatal outcome. Given that SPY is a rare cause of pyogenic meningitis in comparison with Streptococcus pneumoniae and Neisseria meningitidis, empirical therapy with a third-generation cephalosporin plus vancomycin is recommended. Once SPY has been isolated in CSF, penicillin is the antibiotic of choice, although in some cases, such as ours, the cephalosporin is maintained, not always with good clinical progression.^4,5

In the last decade, hospitals have incorporated syndromic panels in their diagnostic arsenal, which in the case of acute meningitis detect 14 microorganisms in 70 min. However, when the aetiological agent is not observed in gram staining and is not one of the usual pathogens, it is imperative to resort to other alternatives, such as a syndromic panel intended for the diagnosis of respiratory infections, in a similar manner to the use of the syndromic panel for sepsis to detect S. pneumoniae in pleural fluid⁶ or N. meningitidis in blood cultures and CSF.⁷ The meningoencephalitis panel⁸ has also been used to detect Streptococcus agalactiae in pleural fluid and Listeria monocytogenes in amniotic fluid.

In conclusion, in spite of multiple complications, the patient had a favourable long-term clinical course. Although microbiology used all the tools available to identify the aetiological agent within a few hours without considering the high cost, the early result did not alter the management of the patient. We believe that the barrier of convention needs to be overcome in order to adapt to the new technologies.

Funding

This study received no specific funding from public, private or non-profit organisations.