Abstract
A newborn male infant was admitted to the neonatal unit with suspected early onset neonatal sepsis for monitoring and intravenous antibiotics. Despite his initial normal clinical and laboratory parameters, cerebrospinal fluid cultures done on day 4 of life confirmed Streptococcus oralis meningitis. His mother became unwell shortly after labour, and grew Streptococcus oralis in her blood cultures. Both were successfully treated with antibiotics and made a full recovery. Streptococcus oralis has been associated with meningitis in patients receiving spinal anaesthesia or following dental work, but is an uncommon cause of neonatal meningitis and maternal sepsis. We describe the first case in the literature where a mother-baby pair developed invasive non-pyogenic streptococcal disease with the same organism. There is a need for robust guidelines on antibiotic therapy in these cases.
Introduction
Neonatal sepsis is a systemic inflammatory response syndrome specifically presenting with abnormalities of temperature and/or leukocytosis in an infant from birth to 4 weeks of age as a result of proven infection [1]. The condition encompasses neonatal meningitis, septicaemia and a combination of both. Sepsis in the neonate can present with a variety of signs and symptoms including altered muscle tone, feed intolerances, jaundice in the first 24 hours of life, respiratory distress, and seizures [2]. The most common organisms associated with neonatal sepsis include Group B Streptococcus (GBS), Escherichia coli, other Enterobacteriaceae, Listeria monocytogenes and Staphylococcus aureus [3, 4].
Early onset neonatal sepsis presents in the first 6 days of life while late onset neonatal sepsis presents between 7 – 28 days [5]. Data from a prospective multicentre surveillance study involving 12 English neonatal units recorded an incidence of all (early and late onset) neonatal infections at 8/1000 live births; incidence of early onset sepsis (EOS) was 0.9/1000 live births [3]. Risk factors for early onset neonatal sepsis are highlighted in Table 1.
Risk factors for early onset neonatal sepsis [2]
Risk factors for early onset neonatal sepsis [2]
Streptococcal bacteria are a diverse genus of catalase negative, gram positive bacteria with two broad subgroups – pyogenic and non-pyogenic streptococci [6]. The mitis group consists of a number of closely related species of non-pyogenic or viridans-group streptococci. Non-pyogenic bacteria such as Streptococcus mitis are usually found as a commensal flora in the oral cavity, upper respiratory tract, gastrointestinal and female genital tracts [5]. This article describes a case of early onset neonatal meningitis and maternal sepsis caused by Streptococcus oralis, a member of the Streptococcus mitis group.
A male infant, born by normal vaginal delivery at term with a birth weight of 2.76 Kg was admitted to the neonatal unit immediately after delivery for assessment. Mother had prolonged rupture of membranes for 57 hours. Fever was not recorded in mother prior to delivery and she was not treated with antibiotics during labour. Mum had not received any dental treatment in the preceding 2 months prior to delivery. Clinical examination of the infant was normal and he was apyrexial. After a partial septic screen including blood cultures, intravenous benzyl penicillin and gentamicin were started. He continued to be clinically well and was establishing breast feeds. His initial C-reactive protein (CRP) was <1 mg/L, white cell count (WCC) was 25.2×109/L and neutrophil counts was 18.3×109/L.
His mother became unwell with fever (38°C) 2 hours post-delivery and was managed as puerperal sepsis with intravenous clindamycin and piperacillin with tazobactam. Her initial CRP was 40 mg/L which increased to 148 mg/L, along with rise in WCC from 13.8×109/L to 24.3×109/L and neutrophil counts from 10.9×109/L to 21.4×109/L. Maternal blood cultures grew an alpha haemolytic streptococci, later identified as Streptococcus oralis (phenotypic identification using the MALDI-TOF Mass spectrometry Identification system [Microflex, Bruker Daltonics]). An echocardiogram on day 4 postnatal showed no vegetations. The antibiotic regime was changed to oral amoxicillin on day 5 post-delivery for a further 10 days following advice from the microbiologist. Maternal CRP three days prior to discharge was 53 mg/L and she had clinically improved.
On day 4, a repeat CRP for the baby had increased from <1 mg/L to 20 mg/L. In view of a rise in neonatal CRP and maternal blood culture results, a lumbar puncture was performed. Cerebrospinal fluid (CSF) analysis showed WCC of 15×106/L (73% lymphocytes and 27% polymorphs) and red blood cells 1071×106/L, gram stain was negative. CSF glucose was 1.4 mmol/L (concurrent blood glucose – 3.0 mmol/L) and protein 0.63 g/L. In view of maternal positive blood culture results and the neonate’s initial CSF results suggestive of meningitis, antibiotics were changed to cefotaxime following advice from the microbiologist; this was as per recommendations made in the NICE guidelines [2]. Two days later, a scanty growth of alpha-haemolytic streptococci in the CSF was reported, which was later identified as Streptococcus oralis (Microflex, Bruker Daltonics). The isolate was sensitive to cefotaxime by disc diffusion testing. The infant’s blood culture had no growth reported after 5 days of incubation.
A diagnosis of early onset neonatal meningitis due to Streptococcus oralis was therefore made and cefotaxime was continued to complete a total course of 14 days of intravenous antibiotics. His CRP had decreased to 1 mg/L prior to discharge.
At discharge on day 14 of postnatal life, the infant had established well on breast feeding and weighed 3.096 Kg. Both the infant and mother were reported to be doing well when reviewed in the clinic six months later.
Discussion
This case of concurrent invasive Streptococcus oralis infection in both mother and baby is the first reported in the literature, although there are a number of published cases of neonatal Streptococcus mitis sepsis and/or meningitis [7–13]. The diagnosis of bacterial meningitis in a neonate is initially considered on the basis of the clinical presentation and the presence of pleocytosis in the CSF. In this case the CSF results were only marginally abnormal with a WCC of 15×106/L (normal range up to 20×106/L), with a low CSF glucose, however, a growth of Streptococcus oralis later confirmed the diagnosis. Cases of meningitis without a WCC response in the CSF are however well-recognised, and, in fact, may indicate a worse prognosis [17–19].
Non-pyogenic streptococci are not commonly found as a commensal skin flora in the new-borns and in the context of an unwell neonate with either a positive blood or CSF culture an invasive infection should be considered and treated with antibiotics [4, 10]. A single centre Polish study with 4000 live births, reported 11 cases of invasive neonatal infection over 6 months: 9/11 with positive blood cultures and 2/11 with positive CSF cultures [12]. Streptococcus mitis was the causative bacteria in 2/11 (18%) cases, 1 each in blood and CSF cultures [12]. In addition, the same study reported 2/11 babies with Streptococcus mitis/oralis detected in their eye secretions [12]. A single centre Brazilian study with 21219 live births, reported 36 cases of EOS (1.7 cases per 1000 live births) – non-pyogenic bacteria (Streptococcus mitis, Streptococcus salivarus [n = 2]) accounted for 5/36 (14%) cases [13].
Streptococcus oralis is a component of the normal human oral microbiota, and although viridans group streptococci are usually of low virulence, they can cause severe and life threatening infections in patients of all ages, in particular in immunosuppressed individuals with haematological malignancies [4]. They also classically cause infective endocarditis (often following recent dental work), and only rarely cause meningitis. Since 2010, there has been a 60% increase in cases of Streptococcus mitis bacteraemia in the UK, and the highest age-specific rate of Streptococcus mitis bacteraemia was found in children aged <1 year (18.7/100,000 population), albeit relatively low compared with other neonatal pathogens such as GBS (bacteraemia rates 70/100,000 population in <1 years) [6].
It is widely recognised that most cases of chorioamionitis and spontaneous septic abortions are as a result of ascending infection from the female genital tract [14, 15]. Similarly, neonatal infection often develops following rupture of the membranes and ascending infection; this is the most likely mechanism of infection in this case, although unfortunately we did not screen the maternal vaginal swab for Streptococcus oralis.
Prior to delivery, the foetus is in a largely sterile environment, and he/she becomes colonised with flora from their mother (and other carers) and the environment from birth – the importance of the development of a healthy diverse infant microbiota for future health is increasingly being recognised. However, colonisation can occasionally lead to invasion and infection, and this depends on factors including the virulence of the organism concerned and the host immune system. The relatively low virulence of the viridans group streptococci, when compared to Group B streptococci (GBS), is reflected in their differing carriage:infection rates. The carriage rates of viridans group streptococci, such as Streptococcus mitis/oralis, in the maternal cervix (and hence newborn gastric fluid and conjunctiva) are very high, but infection rates are low, whereas the converse is true for GBS [16]. The avirulent nature of the viridans group streptococci are poorly understood, particularly since they are 99% genetically identical to the pathogen Streptococcus pneumoniae.
Presence of pleocytosis in the CSF is considered to be the gold standard for a diagnosis of bacterial meningitis, a literature review revealed confirmed cases of meningitis without a WCC response in the CSF [17–19]. A case study from the USA reported 2 infants with bacterial meningitis, one of them being a 16 day old neonate with late onset GBS sepsis and meningitis whose CSF profile showed WCC of 0/mm3, protein of 0.41 g/L and glucose of 2.4 mmol/L [17]. A recent paediatric study from Taiwan with 175 children (aged 1 month – 18 years), with confirmed bacterial meningitis, CSF analysis revealed that 16.2% of patients had normal WCC [18]. The same study highlighted that atypical CSF findings in children, especially those with normal CSF WCC and increased protein level may indicate a worse prognosis [18]. A prospective Spanish study with 82 patients recruited between January 1987 and December 1990 with confirmed Neisseria meningitides meningitis, 8/82 patients (7 children, 1 adult) had no apparent CSF abnormalities in the initial lumbar puncture [19].
An unwell neonate with either a positive blood or CSF culture with Streptococcus mitis/oralis, should be carefully evaluated for an invasive infection, and be treated appropriately with antibiotics [4, 11]. Penicillin and gentamicin is suggested as the empirical antibiotic of choice pending septic screen where there is a suspicion of neonatal sepsis [2]. Antibiotics should be changed to a more appropriate agent dependant on identification, susceptibility testing and the site of infection in liaison with the local microbiology team. The viridans group streptococci are more likely to be penicillin resistant (18% of bacteraemia isolates) and/or erythromycin resistant (50%) compared with the pyogenic streptococci such as GBS (0% and 23% respectively) [6]. This potentially has implications for the selection of empirical antimicrobial agent to treat intra-partum fever, particularly in the penicillin allergic, and for the empirical choice of treatment for neonatal sepsis. Antibiotics duration is suggested between 2 to 3 weeks for the neonate and the mother.
Conclusions
Meningitis in neonates is a life threatening condition; prompt detection and suitable treatment is associated with a better outcome. Streptococcus oralis is an uncommon cause of neonatal meningitis and septicaemia in the UK, and enquiries into the maternal blood culture results should be made. Management of these cases of invasive non-pyogenic streptococcal infections will depend on specific susceptibility testing. A prolonged period of antibiotic therapy is suggested. We further suggest that cases where neonatal meningitis is strongly suspected, antibiotics should not be discontinued based on a finding of negative CSF pleocytosis pending CSF culture results. More evidence-based guidelines may become available in the future for management of invasive non-pyogenic streptococcal infection.
Conflicts of interests
Financial interests: None to declare for any of the authors
Contributor statement
All the authors have contributed equally to the manuscript
Footnotes
Acknowledgments
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