Originalia C. Th. K o o r e v a a r , P. G. N. S c h e r p e n z e e l , H. J. N e i j e n s , G. D e r k s e n - L u b s e n , G. D z o l j i c - D a n i l o v i c , R. d e G r o o t

Childhood Meningitis Caused by Enterococci and Viridans Streptococci Summary: Selected clinical and laboratory parameters were studied respectively in patients with meningitis caused by enterococci and viridans streptococci in an academic children's hospital. During a nine-year period (1981-1989), enterococci or viridans streptococci were isolated from the cerobrospinal fluid (CSF) of 48 patients. In nine of these 48 patients, enterococci or viridans streptococci were the causative agents of meningitis. These nine children constituted 2.0% of 450 patients with bacterial meningitis in this period. All nine children suffered from underlying diseases; neurosurgical procedures were performed in six of these patients, of whom four had ventricular drains. A

head trauma preceded the development of meningitis in another patient. Drainage of the lacrimal duct was associated with the development of meningitis in another patient. One child concurrently suffered from severe gastroenteritis. CSF leukocyte count and CSF protein levels were moderately elevated, whereas CSF glucose levels were either slightly decreased or within the normal range. Meningitis due to enterococci or viridans streptococci is seen predominantly in children under the age of one year. Predisposing factors, including neurosurgical procedures, head trauma and severe gastroenteritis, are usually present in these patients. The prognosis for recovery is generally good.

Zusammenfassung: Meningitis im K~ndesalter durch Enterokokken und viridans-Streptokokken. In einer

neurochirurgische Eingriffe, vier davon Ventrikelshunts, behandelt wurde. Bei einem Kind war ein Sch/ideltrauma vorausgegangen, ein Kind hatte nach Tr~inengangsdrainage eine Meningitis entwickelt. Bei einem Kind lag eine schwere Gastroenteritis vor. Im Liquor fanden sich nur m~iBig erh6hte EiweiB- und leicht erniedrigte oder normale Glukosespiegel. Eine Meningitis durch Enterokokken oder viridansStreptokokken wird vor atlem im ersten Lebensjahr beobachtet, wobei meistens eine Pr/idisposition durch neurochirurgische Eingriffe, Sch~ideltrauma oder schwere Gastroenteritis besteht. Die Heilungsaussicht ist im allgemeinen gut.

Universit/itskinderklinik wurde eine retrospektive Analyse klinischer und Laborparameter bei Patienten mit Meningitis durch Enterokokken und viridansStreptokkoken durchgefiihrt. In einem Zeitraum von neun Jahren (1981-1989) wurden aus dem Liquor von 48 Patienten Enterokokken oder viridans-Streptokokken isoliert und bei neun dieser Fglle als kausale Erreger einer Meningitis gesichert. Diese neun Kinder stellten einen Anteil von 2% der 450 Patienten mit Meningitis im Untersuchungszeitraum dar. Bei allen bestand eine Grundkrankheit, die in sechs Fallen durch

Introduction Viridans streptococci and enterococci are occasionally isolated from the cerebrospinal fluid (CSF) in children. The pathogenicity of these microorganisms as causative agents in meningitis is poorly understood. Enterococci, members of Lancefield group D streptococci and viridans streptococci are usually saprophytic inhabitants of the gastrointestinal and upper respiratory tracts. These microorganisms may be causative agents in several diseases such as endocarditis, intestinal infections, wound infections and infections of the urinary tract [1]. A literature study revealed three publications describing small numbers of patients with meningitis caused by enterococci and viridans streptococci [2--4]. In addition, several case reports have been published [1, 5-14]. The majority of patients with meningitis due to enterococci or viridans streptococci suffer from underlying diseases, including anatomic defects of the central nervous system, prior neurologic or neurosurgical interventions, endocarditis or urinary tract infections. The mortality of 8 / 118

meningitis caused by enterococci is high and is probably determined by the underlying disorder as well as by the infection itself [6]. We retrospectively studied all patients admitted to our hospital with bacterial meningitis during a nine-year period. We report here the clinical and laboratory parameters, including the presence of underlying diseases, of the patients with enterococcal and viridans streptococcal meningitis. We also studied the portal of entry of these microorganisms in the CSF. In addition, we compared our findings with three previous publications on meningitis caused by enterococci and viridans streptococci [2-4]. Received: 21 January 1991/Revision accepted: 20 January 1992 C. Th. Koorevaar, B. Sc., Petra G. N. Scherpenzeel, B. Sc., H. J. Neijens, M.D., Gerarda Derksen-Lubsen, M.D., P~ de Groot, M. D., Dept. of Pediatrics, Gordena Dzoljic-Danilovic, M.D., Dept. of Clinical Microbiology, Sophia Children's Hospital and University Hospital Rotterdam, Gordelweg 160, NL-3038 GE Rotterdam, The Netherlands.

Correspondence to: R. de Groot.

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C. Th. Keorevaar: Meningitis Caused by Enterococci and Viridans Streptococci

Table 1 : Clinical characteristics of nine patients with meningitis caused by enterococci and viridans streptococci. ?i.~;'~)~i~i~,i~!~~ ' (~i~.'~.'~i~ ' i'~ ' ;~ ?;!:.~.:~:::~'J;::.:.~':'.~:'::.i~:;'~:~. ;:: ~.~.?~.~.~.~.~.~:.~.~:.~.~.~.~.~.~.~:.~.~.:.~.~.~.~.~.~.~.~.~.~.~.~.~.~.~.~.~:~.~.~.~.~.~.~.~.~.:.~.~.~.~..~:~.`;~.~.~.~::.~.~.~.~.~:.:~.::~ ~.~:.~.~.:~' ..~.'::~.~..h:.. .~.~.~:,:.:.~~.~.::..~::.~..~~.~::.~~.,::.~:;.~.~.~.:,.~.~.::~:.:.:V .'~:.~ .:.':.~ : .~:.~?:.~.~.:.'~.~i:::~.%;,: .:.:;:.'; :.;:;:~,~:;,.~;'::.i:;:~i~i(.i(~i((:.~:. A B C D E F G H I

1.5 months 14 days 9 days 10 months 3 years 3 years 1 month 4 months 10 months

Male Male Female Male Male Male Female Male Male

Enterococci Enterococci Enterococci Enterococci Enterococci Viridans streptococci Viridans streptococci Viridans streptococci Viridans streptococci

Meningomyelocele Meningomyelocele Meningomyelocele Congenital hydrocephalus Hydrocephalus Astrocytoma Battered child syndrome Drainage of lacrimal duct Gastroenteritis

Rickham and external None External Ventricuto-peritoneal External None None None None

Table 2: Selected laboratory parameters in nine patients with meningitis caused by enterococci and viridans streptococci. ~`%!~!:~i!~:i:~:`:i:`~`~:!;~?~:~:i:i:~`~`i~:i:~:`~;i!~`~:``~;:~:`:`~:~;~i`~iii~iii:i:~::!~:i~:;~:i~:~::~```~;.::~?i~:.:::~+;.~°::~:i~i:~:~;.:~:~;::~;.:`~i~:;::~:::~:::~:+`::~:~::`~?~:::~i:~::~`:`~;~!~`~:~:`~:~::~:`~=:;: ~+~:I::~:

A B C D E F G H I

533 1,000 11 333 533 1,067 2,433 2,133 220

50 90 10 95 80 90 99 60 10

234 398 485 231 97 611 316 160 51

Patients and Methods The records of all patients with CSF cultures positive for enterococci or viridans streptococci admitted to Sophia Children's Hospital in the period 1981-1989 were reviewed using a standard format for collecting information. Criteria for establishing the diagnosis of enterococcal or viridans streptococcal meningitis included the following: clinical findings consistent with bacterial meningitis such as fever, altered mental status, meningeal irritability, bulging fontanel, vomiting and convulsions; and isolation of enterococci or viridans streptococci from the CSF. Exclusion criteria included the growth of microorganisms in post mortem cultures and the additional presence of microorganisms other than enterococci or viridans streptococci in the same CSF sample. In addition, we analysed Gram stain findings, CSF glucose levels and CSF protein levels. CSF specimens were centrifuged at 3,000 x g for 5 min. The sediment was Gram stained and cultured on Columbia blood agar, Columbia Leventhal agar, thioglycollate broth and serum broth. All bacteria were identified using standard biochemical and serological methods. Streptococci were identified using the typing scheme described by F a c k l a m [15].

0.7 0.3 0.4 2.1 5.7 1.5 3.1 3.2 3.2

positive positive negative negative negative positive negative positive negative

20.0 26.0 15.8 28.6 10.4 15.3 21.4 14.6 20.4

not done negative not done not done not done negative not done negative negative

aureus and E s c h e r i c h i a coli. O f the remaining 33 patients, 24 were excluded because clinical findings were inconsistent with the presence of bacterial meningitis. None of these 24 patients had CSF cell counts above 15/mm 3. Nine patients were diagnosed as having meningitis caused by enterococci or viridans streptococci based on the criteria mentioned above. Four children had meningeal irritability. Six children were lethargic or somnolent, one was comatose. Five patients vomited and three patients had convulsions as initial sign of meningitis.

Staphylococcus

Results

The relevant clinical parameters are presented in Table 1. All children with meningitis caused by enterococci and viridans streptococci were under the age of 3 years; four of the nine children were neonates ( < 3 months). Five children had enterococci cultured from the CSF and four viridans streptococci. Neurosurgical procedures were performed in six patients. Three of these children had a meningomyelocele, two hydrocephalus and one an astrocytoma. Four of the patients had a ventricular drain. One child developed meningitis after drainage of the lacrimal duct and one after battering. In one patient meningitis was associated with severe gastroenteritis.

Enterococci or viridans streptococci were isolated from the CSF of 48 patients over a nine-year period. Viridans streptococci were cultured in 30 patients and enterococci in 18. Two patients were excluded from the study because cultures were taken post mortem. Thirteen patients were excluded because additional bacteria other than enterococci or viridans streptococci were present in the same CSF sample: S t a p h y l o c o c c u s epidermidis,

The results of CSF and blood parameters are presented in Table 2. All meningitis patients had elevated CSF protein levels ( > 45 mg/dl). We found no decrease in CSF glucose levels in our patients. Four children had CSF glucose levels above 2.2 mmol/dl and five were within the normal range. Four of the nine G r a m stains were positive. Blood cultures were performed in four of nine patients. All of these cultures remained negative.

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C. Th. Koorevaar: Meningitis Caused by Enterococci and Viridans Streptococci Discussion

Meningitis caused by enterococci and viridans streptococci is uncommon and not well documented, although meningitis caused by enterococci is occasionally diagnosed in neonates. Enterococci and viridans streptococci are saprophytic inhibitants of the gastrointestinal and upper respiratory tracts. They are well known as causative agents of endocarditis: 30-40% of all cases of endocarditis are caused by viridans streptococci and 5-18% by enterococci [16]. We retrospectively detected nine patients with meningitis caused by enterococci or viridans streptococci in nine years (1981-1989). In this period 450 patients with bacterial meningitis were diagnosed and treated in our institution. Thus, meningitis due to enterococci and viridans streptococci accounts for 2.0% of all cases with bacterial meningitis in our hospital. Hoyne and Herzon [2] reported that viridans streptococci are cultured in 0.3% to 2.4% of all cases of purulent meningitis. Quaade et al. [17] and Eigler et al. [18] reported that enterococci are cultured in 0.3% and 4%, respectively, of all patients with bacterial meningitis. Enterococci and viridans streptococci usually do not cause meningitis in healthy children but are occasionally responsible for meningitis in patients with underlying diseases. Neurosurgical procedures were performed in six of our patients, four of whom had a ventricular drain. Enterococci and viridans streptococci may have been introduced to the meninges by CSF leakage during the neurosurgical procedure (including insertion of a drain) or by secondary infection of a ventricular drain. In four of the six meningitis patients with neurosurgical procedures, a CSF leakage was present: two through the operation scar and two through an external drain. Organisms involved in meningitis in neurosurgical patients are frequently part of the normal skin flora. Nachamkin and Dalton [4] examined the lumbar puncture skin site of 35 patients for the presence of bacteria. Staphylococcus epidermidis accounted for the majority of bacterial species isolated, and enterococci were isolated as well. Although viridans streptococci are usually associated with the normal flora of the mouth, they were not found on the skin [4]. In one patient who developed meningitis after insertion of a ventriculo-peritoneal drain, a local peritoneal abscess was found; culture of the abscess showed enterococci. The association of enterococci with ventriculo-peritoneal shunts has been suggested in a previous report [19]. One patient with a meningomyelocele had suffered from meningitis caused by Staphylococcus aureus. Lumbar punctures were performed and an external drain installed. The patient subsequently developed meningitis caused by enterococci. Hoyne and Herzon [2] reported that head trauma can be responsible for meningitis. A fracture offers microorganisms an entrance to the CSF. The presence of a head trauma in patient G was very likely, although X-rays of the skull showed no fracture. The child with meningitis due to 10 / 120

viridans streptococci after drainage of the lacrimal duct is remarkable. Plotkin [13] reported that intracranial infections usually arise in structures contiguous to the cranial cavity, such as the paranasal sinuses. The infection could have been propagated from the lacrimal duct to the meninges, but a traumatic drainage leading to bacteraemia should also be considered as a portal of entry. A culture of a swab was taken from the lacrimal duct and showed no viridans streptococci. In contrast to those circumstances in which organisms infect the central nervous system directly, secondary invasion of the meninges may occur during bacteraemia. Meningitis after bacteraemia due to a genitourinary infection and group D enterococcal endocarditis was reported by Bayer et al. [6]. Nagel and Ritter [20] isolated enterococci from the CSF of 33 of 56 patients with "severe" urinary tract infections, but only four of these patients fulfilled criteria of meningitis. Kuipers and De Jong [21] discussed the association between Streptococcus bovis bacteraemia and gastrointestinal disease. In patients with colon or rectum carcinoma, they found a higher prevalence of S. bovis in the faeces and in association with this more frequent S. bovis bacteraemia than in a control group. Overgrowth of bacteria in the gastrointestinal tract may cause bacteraemia. The patient with severe gastroenteritis in this study may have developed bacteraemia in the same way and subsequently developed meningitis. The clinical presentation of the nine patients in our study was variable. Eight patients had two or more of the following symptoms: altered mental state, meningeal irritability, bulging fontanel, vomiting and convulsions. Patient F had only minimal symptoms. The majority of patients with meningitis in this study had moderately elevated cell counts in the CSF of between 500 and 2,500 leukocytes/mm3. Although patient C had only 11 leukocytes in the CSF, he undoubtedly had clinical symptoms of meningitis: fever, meningeal irritability, lethargy, convulsions and a bulging fontanel. In contrast, Bayer et al. [6] reported a frequent lack of cellular response in the CSF of patients with group D streptococcal meningitis. In their review, all but two patients had leukocyte counts in the CSF below 200/mm 3, which they considered as a lack of cellular response. However, only one patient in our study had leukocyte counts below 200/mm3. We compared CSF findings of meningitis patients in this and three other studies on meningitis caused by enterococci and viridans streptococci [2-4]. All studies confirmed the presence of moderately elevated CSF leukocyte count and elevated CSF protein. The CSF glucose level was occasionally decreased. It is important to perform in vitro sensitivity testing with the clinical isolates of enterococci a n d viridans streptococci to determine appropriate therapy. Viridans streptococci are usually susceptible to a wide variety of antibiotics, although penicillin-resistant strains have been described [7,11]. In contrast, enterococci are generally

Infection 20 (1992) No. 3 © MMV Medizin Verlag GmbH Miinchen, Miinchen 1992

C. Th. Koorevaar: Meningitis Caused by Enterococci and Viridans Streptococci

difficult to eradicate with a single antimicrobial agent. Enterococci are known to be resistant to penicillin [6]. An appropriate treatment for enterococcal meningitis is the combination of a IMactam (penicillin G or ampicillin) and an aminoglycoside [6]. When penicillin-resistant microorganisms are present, or, in patients with penicillin allergy, vancomycin (in combination with an aminoglycoside in case of an enterococcal meningitis) can be used. Bayer et al. [6] reported a mortality of 33% in

patients with enterococcal meningitis. All patients in our study recovered. In summary, we found that underlying diseases were present in all children with meningitis due to enterococci or viridans streptococci. Most children were under the age of one year and recovered completely. Children with neurosurgical procedures, head trauma and severe gastroenteritis belong to risk groups for the development of meningitis due tO enterococci and viridans streptococci.

References

11. Goldfarb, J., Wormser, G. P., Glaser, J. H.: Meningitis caused by multiply antibiotic-resistant viridans streptococci. J. Pediatr. 105 (1984) 891--895. 12. Nathavitharana, K. A., Arseculeratne, S. N., Aponso, H. A., VUeratnam, R., Jayasena, L., Navaratnam, C.: Acute meningitis in early childhood caused byAerococcus viridans. Br. Med. J. 286 (t983) 1248. 13. Plotkin, G. R.: Streptococcus anginosus-constellatus infections of the nervous system. South. Med. J. 75 (1982) 608-610. 14. Skeel, R. T., Wright, L. J., Leventhal, C. M., Henderson, E. S.: Group D streptococcal meningitis masked by meningeal leukemia. Am. J. Dis. Child 117 (1969) 334-337. 15. Facldam, R. R.: Comparison of several laboratory media for presumptive identification of enterococci and group D streptococci. Appl. Environ. Microhiol. 26 (1973) 138-145. 16. Schdd, W. M., Sande, M. A.: Endocarditis and intravascular infections. In: Mandell, G. L., Douglas, R. G., Bennett, Z E. (eds.): Principles and practice of infectious diseases. 3rd edition. Churchill Livingstone, New York 1990, pp. 681-682. 17. Qnaade, F., Kristensen, K. P.: Purulent meningitis. A review of 685 cases. Acta Med. Scand. 171 (1962) 543-550. 18. Eigler, J. O., Wellman, W. E., Rooke, E., Keith, H. M., Svien, H. J.: Bacterial meningitis: general review (294 cases). Mayo Clin. Proc. 36 (1961) 357-364. 19. Schoenbaum, S. C., Gardner, P., Shillitio, J.: Infections of cerebrospinal fluid shunts: epidemiology, clinical manifestations and therapy. J. Infect. Dis. 131 (1975) 543-552. 20. Nagel, A., Ritter, G.: Enterococcal meningitis associated with urinary tract infection. Axz. Wochenschr. 3 (1948) 303-306. 21. Kuipers, E. J., De Jong, A.: Gastrointestinal disorders and Streptococcus bovis bacteremia. Ned. Tijdschr. Geneeskd. 134 (1990) 1337-1339.

1. Goldbloom, A. A~, Goldfarb, M. L , Schlachman, M.: Primary enterococci (Streptococcus faecalis) meningitis. JAMA 148 (1952) 1026-1027. 2. Hoyne, A. L., Herzon, H.: Streptococcic viridans meningitis: a review of the literature and report of nine recoveries. Ann. Intern. Med. 33 (1950) 879-902. 3. Lenaer, P. I.: i~,leningitis caused by Streptococcus in adults. J. Infect. Dis. 131 (Suppl.) (1975) $9-S16. 4. Nachamldn, I., Dalton, H. P.: The clinical significance of streptococcal species isolated from cerebrospinal fluid. Am. J. Clin. Pathol. 79 (1983) 195-199. 5. Brown, D. R., Reichman, 1~ C.: Enterococcal meningitis: a subacute presentation. NY State J. Med. 89 (1989) 92-93. 6. Bayer, A. S., Seldel, J. S, Yoshikawa, T. T., Anthony, B. F., Guze, L B.: Group D enterococcal meningitis. Clinical and therapeutic considerations with report of three cases and review of the literature. Arch. Intern. Med. 136 (1976) 883-886. 7. Quinn, J. P., DiVincenzo, C. A., Lucks, D. A., Luskin, R. L., Shatzer, K. L., Lerner, S. A.: Serious infections due to penicillin-resistant strains of viridans streptococci with altered penicillin-binding proteins. J. Infect. Dis. 157 (1988) 764-769. 8. Barriere, S. L, Lutwiek, L I., Jacobs, R. A, Conte, J. E.: Vancomycin treatment for enterococcal meningitis. Arch. Neurol. 42 (1985) 686--688. 9. Ram, W., Hellwege, H. H.: Neonatal meningitis caused by Streptococcus miffs. Monatsschr. Kinderheilk. 133 (1985) 843-844. 10. Venezio, F. R., Masters, D., O'Keefe, P.: Enterococcal meningitis: failure of treatment with ampicillin and chloramphenicol. J. Infect. Dis. 150 (1984) 305.

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Childhood meningitis caused by enterococci and viridans streptococci.

Selected clinical and laboratory parameters were studied respectively in patients with meningitis caused by enterococci and viridans streptococci in a...
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