Invasive Streptococcus Gallolyticus Infections in Infants At Texas Children’s Hospital: A 9-Year Retrospective Review

The Streptococcus bovis group has undergone significant taxonomic changes over recent decades.1Streptococcus gallolyticus subsp. pasteurianus (SGP), a nonenterococcal group D streptococcus, was formerly known as Streptococcus bovis biotype II.2. SGP is an uncommon pathogen capable of causing meningitis and bacteremia, including in the newborn period.2,3 Previous reports outline its clinical manifestations, which can be indistinguishable from disease caused by group B Streptococci.3,4 Much of the knowledge of SGP infections in children comes from individual case reports or limited case series.2,4–11 We report a large pediatric case series of S. gallolyticus bacteremia with and without meningitis over the span of 9 years at a single institution.

METHODS Study Design and Population

We conducted a retrospective review of infants with invasive S. gallolyticus disease from July 2012 to June 2021 at Texas Children’s Hospital (TCH). Patients were identified by reviewing the pediatric infectious disease consultation database. Infants less than 90 days were included in this study. Demographic and clinical data were obtained from the electronic medical record system (Epic Systems, Verona, WI) for each patient. When available, this information included the following: age, gestational age, gender, underlying medical conditions, clinical presentation, laboratory, microbiology, radiology data, antibiotic agent(s) used for treatment, treatment duration and outcomes. The TCH Medical Microbiology Laboratory performed organism identification using Vitek 2 (bioMérieux, Inc, Durham, NC) and Vitek MS matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) technology (bioMérieux, Inc). Antimicrobial susceptibility was performed using Etest and Clinical Laboratory Standards Institute guidelines.12 This study was approved by the Baylor College of Medicine Institutional Review Board.

Definitions

Infants born at less than 37 weeks gestational age were considered premature. Neutropenia was defined as an absolute neutrophil count of less than 1500 cells/mm3. Meningitis was defined as cerebrospinal fluid (CSF) pleocytosis (>20 white blood cells/mm3) and/or growth of S. gallolyticus or S. bovis from CSF culture. Bacteremia was defined as isolation of S. gallolyticus or S. bovis from blood culture.

RESULTS Demographics and Patient Characteristics

Fifteen patients with invasive S. gallolyticus disease met inclusion criteria. Eight patients had both meningitis and bacteremia, 4 had bacteremia and 3 patients had meningitis. The median age was 24 days (range, 1–74 days) and 9 patients (60%) were male (Table 1). Eleven of the 15 infants presented after the first week of life. Six infants were born prematurely including a set of twins, born at 32 weeks gestational age.4 No other underlying medical conditions were reported. Fever and irritability were present in 9 patients (60%) and were the most common presenting symptoms. Additional symptoms included difficulty feeding (33%), decreased activity or lethargy (27%), respiratory distress or apnea (27%), seizure-like activity (20%) and emesis or diarrhea (20%). One patient each had cough and congestion, jaundice or pallor. Premature and term infants had similar presenting symptoms. All patients had peripheral white blood cell counts performed and the mean was 9.7 × 103/μL (range, 1.3–21 × 103/μL). Three patients were neutropenic. Seven patients had a C-reactive protein and the mean was 8.1 mg/dL (range, 3.9–15.6 mg/dL). No significant differences were observed in laboratory values among premature versus term infants.

TABLE 1. - Clinical Course and Neurologic Manifestations of Invasive Streptococcus gallolyticus subsp. pasteurianus [Case] Year Sex, Age (d) Underlying
Disease Site(s) of
Isolation Empirical
Treatment Definitive
Therapy Antibiotic
Duration (d) Imaging Findings; Timing* (Modality) Hearing
Screen Outcome [1] 2012 M, 4 None Blood Amp, Gen Amp 21 None; 13 (CT) Passed Lived [2] 2013 M, 24 Prematurity Blood, CSF Van, Gen, COTX Amp 14 Bilateral grade III IVH; 4 (HUS, MRI) Passed Lived [3] 2013 F, 24 Prematurity Blood Amp, Gen Amp 10 None; 13 (HUS) Passed Lived [4] 2013 F, 29 None CSF Amp, Gen, COTX Amp 21 None; 6 (MRI) Passed Lived [5] 2014 F, 64 None Blood, CSF Amp, Van, COTX PCN 14 Ventriculitis and subdural collection; 5 (CT) Passed Lived [6] 2016 M, 20 None Blood Amp, COTX Amp 9 N/A N/A Died† [7] 2016 M, 48 None Blood, CSF Amp, CTX, Van CTX 21 Leptomeningitis and subarachnoid purulent debris; 18 (MRI) Passed Lived [8] 2017 F, 4 None CSF Amp, Gen, Van Amp 14 N/A Passed Lived [9] 2017 F, 14 Prematurity Blood, CSF Amp, Gen, CTZ Amp 14 None; 13 (MRI) Passed Lived [10] 2018 F, 12 Prematurity Blood, CSF, urine Amp, CTZ, Van Amp 14 None; 0 (HUS). Leptomeningitis and subarachnoid purulent debris; 15 (MRI) Passed Lived [11] 2019 M, 4 None CSF Amp, Gen, CTZ PCN 21 Leptomeningitis, ventriculitis and subarachnoid purulent debris; 11 (MRI) Passed Lived [12] 2019 M, 31 None Blood Amp, CTX Amp 9 N/A N/A Lived [13] 2019 M, 38 None Blood Amp, CTX None 1 N/A N/A Lived‡ [14] 2020 M, 1 Prematurity Blood, CSF Amp, Gen Amp§ 21 Leptomeningitis, ventriculitis and subarachnoid purulent debris; 8 (MRI) Passed Lived [15] 2021 M, 74 Prematurity Blood, CSF Van, CTX Amp 28 Leptomeningitis, subarachnoid purulent debris and bilateral subdural effusions; 14 (MRI) Passed Lived

*Days since onset of symptoms.

†This infant presumably died from sepsis.

‡Despite receipt of only 1 day of antibiotic treatment, this patient has had normal reported development through 3 years of age.

§Patient received penicillin for 8 days before transition to ampicillin.

Amp indicates ampicillin; COTX, cefotaxime; CT, computed tomography; CTX, ceftriaxone; CTZ, ceftazidime; F, female; Gen, gentamicin; HUS, head ultrasound; M, male; MRI, magnetic resonance imaging; N/A, not available; PCN, penicillin; Van, vancomycin.


Microbiologic Data

Of 13 positive blood cultures, 5 were reported as S. gallolyticus (39%), 6 were reported as SGP (46%) and 1 was reported as S. bovis (8%). One patient’s isolate from an outside hospital was initially reported as Enterococcus bacillus but later found to be a gamma Streptococcus species; this patient had SGP isolated from their CSF.

Eleven patients had meningitis. Initial and repeat CSF analyses are provided (Table, Supplemental Digital Content 1, https://links.lww.com/INF/E801). Of 10 positive CSF cultures, 5 isolates (50%) were reported as S. gallolyticus, 4 were reported as SGP (40%) and 1 (10%) was reported as S. bovis. Nine patients had a repeat lumbar puncture following their initial positive CSF culture; timing of repeat lumbar puncture ranged from 2 to 19 days later with a median of 4 days. The need for repeat CSF analysis was at the discretion of the treating physicians and rationale was not always documented. All repeat CSF cultures were sterile.

Antimicrobial susceptibility testing was performed on 20 isolates (10 blood and 10 CSF). Isolates from 5 patients were intermediate to penicillin—4 had an minimal inhibitory concentration (MIC) of 0.25 µg/mL and 1 had an MIC of 0.19 µg/mL. All isolates were susceptible to ampicillin (MIC 0.19–0.25 µg/mL), cefotaxime (MIC 0.25–0.5 µg/ml) or ceftriaxone (0.125–0.25 µg/ml) and vancomycin (0.5–1 µg/mL).

Clinical Course, Treatment and Outcomes

Head imaging was performed in 10 of 11 patients with meningitis: MRI (8), computed tomography (2) or head ultrasound (3). Neuroimaging timing and findings on MRI including leptomeningitis, purulent debris in the subarachnoid space, ventriculitis (ependymal enhancement, intraventricular purulent debris), intraventricular hemorrhage (IVH) and/or subdural effusions are described in Table 1. Bilateral grade III IVH was noted in 1 former 32-week gestational age infant. No patients had parenchymal abscess, subdural empyema, hydrocephalus or venous or arterial stroke. No patients required neurosurgical intervention. Two patients with meningitis had seizures and required antiepileptic therapy.

All patients received empiric antibiotic therapy. Treatment duration was a median of 14 days (range, 9–28 days); all courses were parenteral and completed while hospitalized. Six patients received an extended duration of greater than 14 days. Five completed 21 days for ventriculitis or concern for ongoing inflammation and 1 received 28 days. Antibiotic therapy was discontinued in 1 patient because the positive blood culture was thought to be a contaminant. Every patient treated for meningitis passed a hearing screen before discharge. Follow-up information was available for 9 patients through at least 6 months of age. The premature infant with bilateral grade III IVH received speech and occupational therapy and developed profound hearing loss of the right ear. The patient with bilateral subdural effusions was developing appropriately at their 6-month well-child check before being lost to follow-up. One patient with SPG bacteremia died; Escherichia coli was isolated from a postmortem blood culture and was the presumed cause of death.

DISCUSSION

We report 15 cases of invasive S. gallolyticus infections among infants over the course of 9 years at a single institution. We found that half of all cases (8/15, 53%) had concomitant bacteremia and meningitis. Six of 15 cases (40%) involved premature neonates, which is in line with previous report of prematurity as a risk factor for invasive S. gallolyticus disease.11 Notably, S. gallolyticus was isolated from blood and CSF in 5 of 6 premature patients (83%).

In a 12-year national surveillance study from France, Beneteau et al11 described 23 cases of childhood meningitis due to S. bovis group. The subspecies was identified in 10 cases, with 8 cases of SGP. Similarly, in our study, not all isolates were identified to the subspecies level. It is important to pursue identification to the subspecies level to monitor for epidemiologic changes over time. We also found 5 of 15 patients (33%) had isolates that were intermediately resistant to penicillin, while all isolates were susceptible to ampicillin, third-generation cephalosporins and vancomycin. No clear trend was observed to suggest emergence of penicillin resistance over time (isolates were from 2012, 2016, 2017). In a case series of 4 neonates with SGP meningitis, Klatte et al2 also reported 1 neonate with an isolate intermediately resistant to penicillin. By comparison, a retrospective review in South India of 15 cases of SGP bacteremia in adults identified 2 isolates with intermediate resistance to penicillin.13 Given a possible difference in penicillin resistance prevalence in the United States, it is important to not only pursue identification but also antibiotic susceptibility data of each isolate. In our case series, there was no difference between penicillin intermediate and penicillin-susceptible strains with regard to clinical courses and outcomes.

In our study, most infants with meningitis had expected neuroimaging findings without significant complications (Table, Supplemental Digital Content 2, https://links.lww.com/INF/E802 and Figure, Supplemental Digital Content 3, https://links.lww.com/INF/E803). Bilateral grade III IVH noted in 1 patient could have been related or due to underlying prematurity. There are several reports of infants with SGP meningitis with neurologic manifestations including infants with hydrocephalus requiring shunt placement, IVH, subdural effusion and ventriculitis.5,7,8 We report some variability in duration of treatment. Most patients with bacteremia received a 10-day course, those with meningitis received at least 14 days and an extended course was used for some patients.

Our study is subject to limitations including those inherent in a retrospective chart review. There may have been cases that were not captured through review of the TCH infectious disease consult database. Documentation in the electronic medical records was at times incomplete and follow-up information was not available for all patients.

S. gallolyticus is an infrequent cause of sepsis and meningitis among infants but can be associated with significant morbidity and should not be considered a contaminant. Due to the frequency of concomitant bacteremia and meningitis in young infants, we recommend that all infants with bacteremia undergo evaluation of CSF. For patients with meningitis, documenting penicillin susceptibility of the patient’s isolates is required before completing treatment with penicillin alone. As with bacterial meningitis due to any pathogen in the neonate, advanced head imaging for evaluation of neurologic complications is recommended for neonates with meningitis caused by S. gallolyticus.

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