Meningitis with Group B Streptococcus bacteremia
Endocarditis involving the aortic valve
Diabetic ketoacidosis
This patient, with long-standing non-insulin dependent diabetes mellitus complicated by retinopathy and previous skin infections, developed diabetic ketoacidosis. While in the emergency room of the Ben Taub General Hospital, she abruptly developed agitation, fluctuating and focal neurological signs, followed by a depressed level of consciousness. Initially she was afebrile, with no meningeal signs and an unremarkable CT of the head. She was admitted to the Medical ICU, intubated as she became unable to protect her airway, and prepared for lumbar puncture. CSF was grossly purulent on direct examination, and the patient was empirically treated with ceftriaxone and vancomycin while awaiting the results of CSF and blood cultures. During this time, she developed fever (to 105 F), and meningeal signs. CSF analysis showed a white blood cell count of 7850/mL with a differential count of 92% neutrophils, with elevated protein (290 mg/dL), and a glucose of 68 mg/dL at a time when systemic glucose was greater than 200 mg/dL, suggestive of a bacterial meningitis. An electroencephalogram (EEG) showed generalized slowing with no focal findings and no epileptiform activity. Gram staining of the cerebrospinal fluid was negative, and cultures of CSF also remained negative. However, blood cultures grew Gram-positive cocci in chains, later identified as Group B beta-hemolytic Streptococcus. After two days, the patient began to clinically improve, with resolution of her focal neurological signs.
At this time, the cause of the patient's CNS infection remained unknown. Chest X-rays showed no infiltrates to suggest pneumonia, and there was no evidence of urinary tract infection or active skin infection. MRI of the spine did not reveal evidence of a paraspinal abscess. MRI of the brain likewise showed no abscess, and no significant abnormality in the paranasal sinuses, but did show thickened, enhancing dura in the right frontal region, and diffusely increased CSF signal intensity on FLAIR sequences. Diffusion-weighted images showed abnormal signal in the right parafalcine frontal lobe, located mainly at the gray-white junction beneath the region of thickened dura. It was felt that these findings could be consistent with a bacterial meningitis; however, the question of a source of infection remained open.
A screening transthoracic echocardiogram (TTE) was unremarkable. Due to high clinical suspicion, a transesophageal echocardiogram (TEE) was performed on the following day; this study revealed small, 0.4 cm echodensities on the ventricular side of the aortic valve, consistent with vegetations. Based on these findings, the patient was treated with a long-term course of antibiotics. At no time during the patient's hospital admission, or on follow-up visits, did she develop an audible murmur.
It is possible, although unproven, that the patient's recent skin infections had seeded her heart valves, providing a substrate for either hematogenous seeding or septic embolization to her central nervous system.
The differential diagnoses of altered mental status and acute, focal neurologic signs or symptoms are extensive and can involve dysfunction of virtually any organ system in the body. Although hyperglycemic states including diabetic ketoacidosis and the hyperglycemic-hyperosmolar state (HHS) can cause deterioration of consciousness and focal signs (7), other causes, including vascular occlusion, seizures, CNS infection, and subarachnoid hemorrhage should be considered with high suspicion. The patient was hemodynamically stable, with no serious systemic abnormalities other than diabetic ketoacidosis. We did not believe that seizures accounted for her deterioration, based on absence of suspicious motor activity, lack of improvement with benzodiazepines, and no detectable epileptiform activity on EEG. We entertained the possibility of an evolving vascular occlusion in this patient, although the tempo of her evolving neurologic condition was sufficiently uncertain to cast doubt on this diagnosis. Given the patient's unexplained deterioration of mental status, lumbar puncture was indicated to rule out infection or subarachnoid hemorrhage, even in the absence of fever or signs of meningeal irritation. It is well known that patients with conditions producing immune suppression, including diabetes mellitus, may exhibit blunted clinical responses to infection or inflammatory conditions (4). Furthermore, development of new ketoacidosis in an adult-onset, non-insulin dependent diabetic should occasion a search for a systemic stressor, usually infection.
Infection with Group B beta-hemolytic Streptococcus (GBS) in nonpregnant adults is relatively rare. Comprehensive studies on the presentation and treatment do not exist since large numbers of patients with such infection rarely present to a single institution. Jackson et al. published a population-based surveillance study with appropriate hospital-matched controls, finding that 92% of patients with documented GBS infection had GBS isolated from blood. Risk factors for infection with GBS included cirrhosis, diabetes mellitus, stroke, breast cancer, decubitus ulcer, and neurogenic bladder. Bacteremia without evidence for focal infection was the most common source identified, followed by skin and soft tissue infections. Endocarditis and meningitis represented a relatively small percentage of presentations, 6% and 4% respectively (3, 6), in this series of patients with GBS infection. When infective endocarditis as a result of GBS was identified, diabetes remained the most common comorbid medical condition, regardless of whether the infection was community-acquired or nosocomial; and GBS was isolated from blood cultures in all patients with GBS endocarditis (1).
The incidence of Group B Streptococcus meningitis in nonpregnant adults has been estimated at 4.1 to 7.2 cases per 100,000. As with other modes of GBS infection, diabetes remains a significant comorbid medical condition. GBS meningitis usually presents abruptly. Bacteremia is present in 80% of cases, and a distant focus of infection (i.e., endocarditis) is identified in a significant percentage (2). Although overall mortality from GBS infection has decreased (5), the mortality from identified GBS endocarditis (12.9%, ref. 1) or GBS meningitis (27-34%) remains substantial. Up to 7% of survivors of GBS meningitis may have permanent hearing loss (2).
Early identification of infection with GBS is essential to prevent serious morbidity and significant mortality. Vancomycin, chloramphenicol, cephalosporins, or ampicillin with an aminoglycoside are effective in most cases. If the infection is uncomplicated, treatment for 2 weeks is sufficient. In cases of endocarditis, treatment for at least 4 weeks is recommended (2), with close clinical follow-up.
By the time of hospital discharge, the patient's neurologic function had returned to nearly normal. She will require continued monitoring for development of valvular disease as a result of the endocarditis, as well as monitoring for relapse of infection.
This presentation is an excellent reminder of the need to vigorously search for causes of CNS infection, especially when the presumed causative organism is unusual. In the setting of appropriate clinical suspicion, transesophageal echocardiographic probes usually offer superior imaging of the posteriorly located valves, and improved resolution to detect small lesions (< 0.5 cm). We thank Dr. R.G. Smith, of the Baylor College of Medicine Department of Neurology, and the Ben Taub General Hospital Neurology Service, for assistance with this case.
-- Dennis R. Mosier, M.D., Ph.D.
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