Late-onset brain abscess due to group B Streptococcus

Introduction

Group B Streptococcus (GBS) is one of the leading causes of invasive bacterial infections during the first year of life. Ten GBS serotypes are known, with a different distribution between early-onset (EO) disease (from birth to 6 days of age), and late-onset (LO) infection (from 7 days to 3 months), being serotypes I and II predominant in EO disease, and serotype III almost exclusive in LO cases [1]. Clinical manifestations in EO and LO diseases also differ; EO disease usually begins with pneumonia or bacteraemia, while common presentations of LO GBS infection are sepsis and meningitis or sepsis alone, followed by septic arthritis, osteomyelitis, pneumonia and cellulitis [1]. In literature, just one brain abscess due to GBS has been reported [2].

Here we present an infant with a LO sepsis with brain abscess due to GBS type I. Parents signed the informed consent to present the case.

Presentation of the case

The patient was an at-term baby born by vaginal primigravida delivery. GBS recto-vaginal swab at 34 weeks of gestation was negative. The baby was discharged at day of life 3 on breast milk and infant formula.

At 42 days of age, he suddenly became unwell, exhibiting insufficient sucking, vomiting, irritability and fever. He was taken to a local hospital where laboratory investigation showed increased neutrophil count and elevated serum C-reactive protein (CRP) (104.4 mg/dL, normal value <5). A brain computerized tomography (CT) scan revealed bilateral increase of the cerebrospinal fluid (CSF) of the extra-axial brain spaces. Because of the suspicion of meningitis, the infant received empirically a dose of ceftriaxone and was transferred to a Pediatric Infectious Diseases Unit. Here, physical examination revealed hypertonia of arms and legs, brisk reflexes, and positive Babinsky sign. Laboratory investigations showed elevated CRP (196.2 mg/dL) and peripheral white blood cells of 16.2×10³ cells/μL (60.7% neutrophils). His CSF was turbid with 2900 nucleated cells/μL (prevalence of neutrophils). CSF latex antigen test was positive for GBS. GBS isolated from blood was susceptible to ampicillin, penicillin, cephalosporin, vancomycin and teicoplanin.

Subtyping revealed a GBS serotype Ia. Treatment with parenteral antibiotics (ampicillin 300 mg/kg/day and amikacin 15 mg/kg/day) was started. Other diseases (immunodeficiencies, tubercolosis) were ruled out. No other risk factors (as preterm delivery, prolonged rupture of membranes, known genital GBS colonization, intrapartum fever) were identified. A brain magnetic resonance imaging (MRI), performed at the 4^th hospital day, revealed an abscess of 9×6 mm, located in the left anterior parietal lobe that appeared typically hyperintense on exponential apparent diffusion coefficient (eADC) map (Figure 1A). After gadolinium, a strong enhancement of its capsule and a thick enhancement of the leptomeninges were appreciable (Figure 1B). CSF and blood cultures performed at the 4^th hospital day were sterile. Because of a mild increase of serum CRP on the 5^th hospital day, meropemen (60 mg/kg/day) was introduced. Meropemen and ampicillin were administered for a total 4-week course, while amikacin was stopped at the 14^th treatment-day. Intramuscular ceftriaxone was instituted after stopping meropemen and ampicillin and continued until the patient’s discharge (total of 10 days).

Figure 1:

Brain magnetic resonance imaging of the patient.

(A) Axial exponential apparent diffusion coefficient (eADC) map shows the typical hyperintense purulent content of the abscess (white arrow), that was in fact hyperintense on diffusion weighted imaging (DWI) and hypointense on apparent diffusion coefficient (ADC) map. (B) Sagittal spin echo (SE) T1-weighted after endovenous contrast administration shows the thick leptomeningeal enhancement on the left fronto-parietal convexity (black arrow) associated to the enhancement at the periphery of the omolateral parietal abscess (white arrow).

A brain MRI, at 1 month from admission, showed complete resolution of the brain abscess and meningitis. The baby was discharged after 40 days with normal laboratory exams. Now, at 3 years of age, he has no neurological sequelae and a normal global development.

Discussion

Brain abscess due to GBS is very rare and even large series of EO and LO GBS disease do not include this kind of lesion [1]. Furthermore, type I GBS is rarely reported in LO disease [1]. To our knowledge, this is the first case of GBS serotype I involved in causing a LO brain abscess.

A challenging point is the optimal treatment of LO disease and brain abscesses. Predominant pathogens in LO sepsis are staphylococci, followed by Escherichia coli, Klebsiella spp., Enterobacter spp., Pseudomonas spp. and GBS [3]. Empirical antibiotic therapy is usually initiated on suspicion of sepsis, due to the potential negative outcomes associated to delayed treatment. An ideal choice of antibiotic is to cover the most common pathogens. For this reason, a combination of ampicillin and gentamicin represents the recommended first line antimicrobial therapy in neonatal sepsis [3]. Alternatively, ceftriaxone or cefotaxime can be considered in infants aged <2 months because of the possibility of Streptococcus pneumonia as the causative agent [3]. In a series including 104 infants with LO, cephalosporins in association with vancomycin and/or amoxicillin were used [4]. In other series of LO GBS infection, antibiotic treatment is not reported at all [1]. The choice, route and duration of antibiotics in the case of brain abscess are even more controversial and variable. Carbapenems may be considered as a possible choice. They have a their broad spectrum of activity, good CSF penetration and safety profile [5]. Furthermore, while aminoglycoside-, amikacin- and cephalosporins-resistant GBS strains have been reported, meropemen-resistant bacteria are very rarely found [5, 6]. Empiric treatment with carbapenems has been shown to be effective in 90% of cases of pediatric brain abscess [7].

In our case, combined therapy with broad-spectrum β-lactams was a pertinent choice considering the excellent outcome. Furthermore, data on the duration of antimicrobial therapy are lacking. In a recent retrospective study, infants with GBS disease received antibiotics for a mean of 21 days (range 14–44) [8]. In a series of pediatric brain abscesses, the total duration of antibiotic treatment ranged from 5 to 176 days, with the most frequent duration of 6 weeks [7]. In our case, duration of treatment (a 4-week combined therapy) was guided by clinical, laboratory and MRI features.

Finally, LO GBS disease is burdened by a high rate of mortality and, in survivors, by poor neurological outcome [1]. In our patient, we observed a full recovery without sequelae. Our long follow-up (about 3 years) excluded learning disabilities or cognitive impairments that manifest later in life. Little is known on the role of GBS serotype in the prediction of outcomes. If the excellent outcome observed in our patient may be related to the GBS serotype, to the prompt antibiotic treatment or to patient-related factors is unknown.

A higher index of suspicion and close observation are mandatory for the detection of GBS infections, even in absence of maternal colonization. Although mortality and morbidity of pediatric brain abscess is high, a prompt and appropriate treatment may reduce complications, need for surgical drainage, and long-term sequelae. However, a long interval of follow-up is required to exclude late impairment of development.