P2.L230: Invasive Pneumococcal Meningitis Susceptible but Not Responsive to Ceftriaxone

Introduction: The prevalence of invasive pneumococcal disease (IPD) has significantly decreased since the introduction of pneumococcal conjugate vaccines (PCVs). While the benefits of PCVs in preventing IPD are remarkable, higher incidences of antibiotic resistant Streptococcus pneumoniae have been seen in pediatric patients. The increased virulence seen in some S. pneumonia serotypes has occasionally presented as atypical IPD. The following case highlights a patient with S. pneumoniae meningitis known to be susceptible to ceftriaxone; however, the patient clinically improved only after receiving ceftaroline.

Case Description: 3-year-old vaccinated female presented with lethargy, fever (Tmax 103F), vomiting, and inability to walk worsening over 3 days. Her blood culture grew Streptococcus pneumoniae susceptible to ceftriaxone and vancomycin. Subsequently, clinical findings and MRI brain and spine were consistent with meningoencephalitis. There was leptomeningeal enhancement of the cauda equina nerve roots and prominent enhancement of the surface of the cervical and thoracic spinal cord. Additionally, the patient’s course was notable for urinary retention resulting in bilateral grade 3 hydronephrosis on renal ultrasound. After 7 days on meningitic dose ceftriaxone, she continued to have fevers and inability to walk so rifampin and vancomycin were added. Despite several dose increases and 9 days of vancomycin therapy, the vancomycin trough only reached 11 (goal 15-20 for meningitis).

Initially, the patient’s leukocytosis and CRP normalized. However, the patient continued to have daily fevers (Tmax 104.9F). After 19 days of meningitic dose ceftriaxone and completing a 9 and 5 day course of vancomycin and rifampin respectively, the patient was started on ceftaroline. She had a repeat MRI of the brain and spine which demonstrated no abscess and resolving meningoencephalitis and leptomeningitis. 4 days after ceftaroline was started, the patient’s fevers resolved, she was able to walk, and her leukocytosis and inflammatory markers normalized again.

Discussion: The frequency of IPD has decreased since the introduction of PCVs, but there has been an increase in antibiotic resistant and virulent serotypes of S. pneumoniae. While S. pneumoniae typically responds to ceftriaxone and vancomycin and our patient’s strain was susceptible to both, our patient did not have sustained clinical improvement until starting ceftaroline which does not further enhance coverage of S. pneumoniae serotypes. Most likely, the ceftriaxone and vancomycin did not reach therapeutic concentrations for penetrance across the blood brain barrier resulting in an inadequate response necessitating the use of ceftaroline.

Conclusion: Ceftaroline should be considered for antibiotic coverage for IPD if a patient is unresponsive to typical antibiotic regimens in spite of culture and susceptibility data.