Group A Streptococcal Meningitis

(1)

Received for publication Dec 16, 1982; accepted April 13, 1982. Reprints not available.

VOLUME 71 . JANUARY 1983 #{149}NUMBER I

Pediatrics

Group

A Streptococcal

Meningitis

Daniel

J. Murphy,

Jr, MD

From the Children ‘s Hospital Medical Center, Cincinnati

ABSTRACT. A retrospective record study of six cases of

meningitis caused by group A /3-hemolytic Streptococcus

is presented. Associated findings included otitis media,

pharyngitis, and erysipelas. All patients survived their

infections despite major complications including seizures, shock, coma, renal failure, and hepatitis. Two patients

had neurologic sequelae. Group A Streptococcus causes

a severe form of bacterial meningitis in apparently healthy children. Pediatrics 1983;71:1-5; group A Strep-tococcus, streptococcal infections, meningitis.

patients given a discharge diagnosis of streptococcal

meningitis during the same period of time were

examined. Only cases of meningitis caused by a

hemolytic Streptococcus positively identified as

group A by bacitracin disk susceptibility testing are

presented. Although individual culture results were

not confirmed by an outside laboratory or by sero-logic testing, in all cases at least two separate

ciii-tures yielded identical organisms.

CASE REPORTS

Meningitis caused by group A fl-hemolytic Strep-tococcus

has

not been well described since the introduction of antibiotics. Discussions of bacterial meningitis in standard textbooks on pediatric and infectious disease either fail to mention group A

Streptococcus as a cause’ or list it with

infre-quently encountered organisms.5’6 A recent case of

this disease prompted a review of the literature and

an examination ofthe records ofpatients with group A streptococcal meningitis treated at Children’s Hospital Medical Center (CHMC) in Cincinnati during the past 15 years. Six case reports and a

review of the literature are presented.

SUBJECTS AND METHODS

The medical records of all patients with a CSJ’ culture positive for group A $-hemolytic Strepto-coccus between July 1, 1966 and June 30, 1981 were reviewed. In addition, the medical records of all

Case 1

A 4#{176}/12-year-old boy was admitted to CHMC in 1981.

He had been well until three days prior to admission at

which time he complained of a left-sided earache. The

following day he developed a frontal headache and was

warm to touch. The morning of admission he became

lethargic and appeared to be in a toxic condition. His past

history revealed three episodes of pneumonia for which

he had been treated as an outpatient. He had had only

one immunization. Upon admission he appeared

ma!-nourished and pale. He was lethargic and irritable when aroused. His temperature was 40#{176}C.His left tympanic

membrane was bulging and red and his neck was stiff. He

did not respond to verbal commands. Deep tendon

re-flexes were symmetrically decreased and plantar

re-sponses were downgomg.

Laboratory results included: WBC count 37,lOO4uL

with 82% polymorphonuclear leukocytes and 5% band

forms; hemoglobin 9.9 g/dL; serum glucose 162 mg/dL;

and normal electrolytes. Lumbar puncture yielded cloudy

CSF with 1,400 WBC/jzL. Gram stain revealed many

Gram-positive cocci in pairs and chains. Two CSF

cul-tures grew group A 1G-hemolytic Streptococcus.

The patient was initially treated with ampicillin and

chloramphenicol. After 24 hours chloramphenico!

(2)

U/kg/d) was begun. He was treated with antibiotics for ten days. He developed signs of inappropriate secretion of antidiuretic hormone on day 2. Recovery was otherwise

uneventful and there were no apparent sequelae of the

infection.

Case 2

An 85/12.year-old girl was admitted to CHMC in 1978.

She had been in good health until five days prior to

admission, at which time she developed a fever of 38.3#{176}C

and complained of headache, sore throat, and malaise.

Two days later she began vomiting and her headaches

became more severe. On the morning of admission she

experienced photophobia and blurred vision. She rapidly

became lethargic and disoriented. Upon admission she

was comatose with no response to pain. Her temperature was 39.9#{176}C.Her neck was stiff and Kernig’s and Brudzin-ski’s signs were elicited. Deep tendon reflexes were de-creased and plantar responses were upgoing.

Laboratory results included: WBC count 8,800/cL with

71% polymorphonuclear leukocytes and 5% band forms;

hemoglobin 11.7 g/dL; normal serum electrolytes; serum

glucose 127 mg/dL; SGOT 186 U/dL; SGPT 178 U/dL;

total biirubin 0.5 mg/dL; and ammonia 70 ug/dL. Lum-bar puncture yielded clear CSF with opening and closing

pressures greater than 50 cm H20. CSF contained WBC,

2204uL and RBC, 20 jL. Gram stain revealed a few

Gram-positive cocci. CSF protein was 49 mg/dL; glucose was 44

mg/dL. Roentgenograms of the chest and sinuses were

normal. A liver biopsy revealed portal and periportal

inflammation consistent with mild acute hepatitis. Two

CSF cultures, three blood cultures, and a nasopharyngeal culture grew group A /9-hemolytic Streptococcus.

The patient was treated with fluid restriction and

intravenous penicillin G (250,000 U/kg/d). She showed

gradual neurologic improvement during the first week of

hospitalization and her liver enzymes returned to normal. She received penicillin for 14 days and was discharged in good condition. She has had no apparent sequelae.

Case 3

A 7’#{176}/12-year-old boy was admitted to CHMC in 1977.

He was well until three days prior to admission when he

complained of a sore throat. Headache, fever, and

vom-iting developed two days later. On the morning of admis-sion he became lethargic and was admitted to an outlying

hospital. Upon admission he was responsive and

corn-municative. His temperature was 41.1#{176}C. His pharynx was injected and his neck was stiff. Kernig’s and Brudzin-ski’s signs were positive.

Laboratory results included: WBC count 15,900/jsL

forms; hemoglobin 12.7 g/dL; and normal serum

electro-lytes. CSF was cloudy with WBC, 2,900/giL. CSF protein

was 184 mg/dL and glucose was 87 mg/dL. CSF and

blood cultures grew group A f3-hernolytic Streptococcus. Throat culture was negative.

The patient was treated initially with intravenous am-picilhin and chioramphenicol. Penicillin G (200,000 U/kg! d) was substituted after three days. Shortly after

adrnis-sion he began to have generalized seizure activity. The

patient was treated with dexamethasone, phenobarbital,

phenytoin, and amobarbital with poor control of his

sei-zures. By the fifth hospital day he was experiencing renal

failure with serum potassium 7.0 mEq/L, BUN 113 rng/

dL, and creatinine 4.7 mg/dL. He was transferred to

CHMC.

Upon arrival the patient was unresponsive and hyper-reflexic. Temperature was 40#{176}C,pulse 140 beats per

mm-ute, and blood pressure 50/30. Laboratory results

in-cluded elevated liver enzymes and depressed serum

corn-plement levels. Supportive measures included

intrave-nous epinephrine therapy, mechanical ventilation, and

peritoneal dialysis. Seizure activity continued until the ninth hospital day. The patient received penicillin for 14

days. There was gradual improvement and at the time of

discharge he had some muscle weakness and was taking

phenobarbital. Four years later, he was free of sequelae and taking no medications.

Case 4

A 10-week-old male infant was admitted to CHMC in

1977. He had been well until two days prior to admission

at which time he became irritable and febrile to 39.9#{176}C. He became progressively lethargic and refused fluids.

Upon admission he was irritable but vigorous. He was

afebrile. His anterior fontanel was flat and his neck was

supple. His hands were held fisted and there were

epi-sodes ofmottling with increased tone and deviation of the eyes to the right.

Laboratory results included: WBC count, 20,8004tL

forms; hemoglobin 9.7 g/dL; and normal serum

electro-lytes. CSF was cloudy with WBC, 25,000/jL. Gram stain

revealed Gram-positive cocci in pairs and chains. Two

CSF and two blood cultures were positive for group A

/9-hemolytic Streptococcus. Nasopharyngeal culture was

negative.

Initial management consisted of fluid restriction,

phenobarbital, and intravenous penicfflin G therapy

(200,000 U/kg/d). His course was complicated by

evi-dence of inappropriate secretion of antidiuretic hormone and recurrent seizures. He received penicfflin for 14 days.

At discharge the infant had obvious neurologic deficits,

including hypertoma, hyperreflexia, and poor response to

visual stimuli. Follow-up revealed that at age 2 years he was functioning at a 3-month-old level with psychomotor

retardation, seizure disorder; microcephaly, and optic

atrophy.

Case 5

A 124/12-year-old girl was admitted to CHMC in 1974.

She had been in good health until one week prior to

admission at which time she developed a sore throat and

rhinorrhea. Three days later she complained of headache, fever, and malaise. On the day of admission she became

disoriented and began to speak incoherently. Her past

history was positive for two episodes of pneumonia for

which she had been treated as an outpatient. Upon

ad-mission she was comatose with occasional purposeless

movements. Her temperature was 38.9#{176}C. Her pupils

were unreactive and her neck was stiff.

Laboratory results included: WBC count 42,700/juL

(3)

g/dL; serum bicarbonate 14.4 mEq/L; and serum glucose 142 mg/dL. CSF was cloudy with WBC, 2,750/juL; glucose

was 4 mg/dL; and protein was 800 mg/dL. CSF and

nasopharyngeal cultures were positive for group A

f3-hemolytic Streptococcus.

Initial management consisted of ampidillin,

dexameth-asone, and mannitol. Penicfflin G (200,000 U/kg/d) was

substituted for ampidillin and given for 14 days. There

was gradual neurologic improvement. Ophthalmologic

evaluation on the 19th hospital day revealed a bilateral hemianopsia. The patient was discharged with a persist-ent hemianopsia.

Case 6

A 2-week-old female infant was admitted to CHMC in

1973. Several days prior to admission she had become

irritable and fed poorly. A cystic gingival lesion was

drained of purulent material the day prior to admission.

On the evening of admission she was limp and gray and

had a weak cry. Upon admission she was unresponsive

and had continuous seizure activity. Her temperature was 37.8#{176}C.Her anterior fontanel was flat. There was a small

gingival lesion without erytherna or drainage. Her neck

was supple. There were raised areas of violaceous disco!-oration overlying the right distal radius and the dorsum of the left foot.

Laboratory results included: WBC count, 44,200/juL

with 42% polymorphonuclear leukocytes, normal serum

electrolytes; and serum glucose 16 mg/dL. CSF was

cloudy and Gram stain revealed Gram positive cocci in

pairs and chains. Cultures from CSF, blood, and an as-pirate from the lesion on her left foot were positive for group A -hemolytic Streptococcus.

Initial management included intravenous penicfflin,

gentamicin, phenobarbital, and phenytoin. She was

treated with heparmn for disseminated intravascular

co-agulation. Because of possible osteomyelitis of the hip, penicillin was given for 7 weeks. Seizures abated after the first week. At age 8 years, she was normally developed and was free of sequelae.

DISCUSSION

Incidence

Prior to the introduction of antibiotics, the strep-tococci were among the four most frequent

causa-tive organisms in nontuberculous pyogenic

menin-gitis accounting for 10% to 20% of cases.79 Some

reports specify the hemolytic reaction, but

Lance-field grouping was not reported. Therefore, the true incidence of group A streptococcal meningitis is unknown. Before antibiotics became available,

streptococcal meningitis had a case fatality ratio of

95%#{149}950

Many large series and reviews of bacterial

men-ingitis

have been published since the advent of

specific antimicrobial therapy. The frequency of group A f3-hemolytic Streptococcus as an etiologic agent is 0.5% to 4.0% in unselected populations#{176}”’4

and in children beyond the neonatal period.’3

Dur-ing the past 15 years at CHMC, 1,100 patients have

been admitted for the treatment of pyogenic

men-ingitis. Six cases of group A streptococcal disease

represent an incidence of 0.5%. During the neonatal period /3-hemolytic streptococci accounted for 10% to 20% of the organisms isolated prior to 1967.1518

With the emergence of the group B Streptococcus

as a significant neonatal pathogen,’#{176} the incidence

of streptococcal meningitis has risen but group A

Streptococcus is only rarely reported.

A review of the literature revealed detailed case

reports describing two

adults,20’2’

one child,22 and

five infants.2326 There is also a report of a nursery epidemic of group A streptococcal disease including

seven infants with meningitis.27 Reviews of serious

streptococcal infections have included an additional

three children28’ and three newborn infants#{176}’3’

with group A streptococcal meningitis, but the cases were not described. At least one large review

in-cluded no cases of meningitis.32

Pathogenesis

It has been stated that streptococcal meningitis is usually associated with otitis media, sinusitis, infection of the respiratory tract, or head injury.8’33

In one study 25% of the patients with streptococcal

meningitis had nose and throat cultures that were

positive for group A Streptococcus?A Of the patients

in the current series, two had positive

nasopharyn-geal cultures and one had otitis media (Table 1). Of the eight cases reported in the literature one case

occurred following head trauma2’ and another

oc-curred in a patient with a congenital dermal sinus

of the nose.22 Other associated findings are listed in Table 2. The infants reported to have necrotizing

fasciitis25 and erysipelas23 bear a striking

resem-blance to case 6 in the current series. In fact it is

likely that the infant reported to have erysipelas

may have had fasciitis, which is characterized by

erythema, induration, warmth, and local

tender-ness. In contrast to erysipelas the borders of the

lesion are not raised and lymphangitis is

uncom-mon. The overlying skin generally develops a dusky color. There has recently been a report of a pyogenic

gingival cyst caused by group A Streptococcus in a

6-month-old infant.35 Case 6 had a pyogenic gingival lesion which preceded the onset of her streptococcal

meningitis. Puerperal transmission is suggested by

positive maternal cervical cultures in the case of an

infant

who developed streptococcal meningitis.2#{176} All of the current cases occurred in apparently healthy, previously well children.

Course and Outcome

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TABLE 1. Clinical Characteristics of Patients Seen at Children’s Hospital Medical Center (CHMC), 19661981*

Patient Age Sex Cultures Positive for

Group A Streptococcus

Complications Sequelae

1 4/12 311 M CSF (2) SIADH None

2 88/12 )T F CSF (2), blood (3), NP Acute hepatitis, coma None

3 7’#{176}/123TI M CSF, blood Seizures, shock,

glomeru-lonephritis, renal failure

None

4 10 wk M CSF (2), blood (2) Seizures, SIADH Seizure disorder, optic atrophy,

microcephaly, psychomotor

re-tardation

5 12/12 F CSF, NP Coma, hemianopsia Hemianopsia

6 14 d F CSF, blood, aspirate

from left foot

Seizures, erysipelas, DIC None

aAbbreviations used are: SIADH, inappropriate secretion of antidiuretic hormone; NP, nasopharyngeal; DIC,

dissem-mated intravascular coagulation.

TABLE 2. Clinical Characteristics of E ight Patients Reporte d in Literature*

Age Sex Cultures Positive for

Group A Streptococcus

Associated Findings Complications Outcome

Refer-ence No.

31 yr F CSF, blood Coryza, cough Coma Died 20

24 yr M CSF Head trauma Recovered 21

18 mo M CSF Dermal sinus of

nose

Recovered 22

6 d M CSF, blood, umbilicus Erysipelas Recovered 23

1 mo F CSF Seizures Died 24

8 d M CSF Seizures Died 24

3 d F CSF, blood, NP, skin,

maternal cervix

Fasciitis Recovered 25

6 wk M CSF, blood, ear exu-date

Otitis, pneumonia Seizures, coma Psychomotor retardation, blindness

26

aAbbreviation used is: NP, nasopharyngeal.

that group A Streptococcus causes a severe form of bacterial meningitis. All of our patients required intensive care. In most of the cases major

compli-cations arose, including shock, seizures,

inappro-priate secretion of antidiuretic hormone, acute gb-merulonephritis, osteomyelitis, disseminated

intra-vascular coagulation, and hepatitis. Literature

re-view reveals that one of two

adults

and

seven of 12 neonates died as a result of the disease. Two of the children reported had prolonged illnesses.#{176} Two of our patients had sequelae. One infant reported had

severe neurologic damage2#{176} and an older child was left with a resistant fourth nerve

palsy.29

SUMMARY

Group A $-hemolytic Streptococcus is an uncom-mon cause of bacterial meningitis. It may occur in

all age groups with approximately half of the cases reported during the neonatal period. It may be

associated with a primary focus of infection in the

middle ear or nasopharynx, but often there is no apparent source. It seems to affect previously well individuals. Fatalities may occur, particularly in the

neonatal period. Patients who survive often have

complicated illnesses. Neurologic sequebae may

fol-bow this infection, although many cases resolve

without any residua, despite major clinical

compli-cations. This organism should be considered in the

patient who is severely ifi with meningitis due to Gram-positive cocci.

REFERENCES

1. Feigin RD: Acute bacterial meningitis beyond the neonatal period, in Vaughan VC Ill, Mckay RJ Jr, Behrman RE (eds): Nelson Textbook of Pediatrics, ed 11. Philadelphia, WB Saunders Co, 1979, pp 720-726

2. Feigiri RD: Bacterial meningitis beyond the neonatal period, in Feigin RD, Cherry JR (eds): Textbook ofPediatric Infec-tious Diseases. Philadelphia, WB Saunders Co, 1981, pp 293-308

3. Moffet HL: Pediatric Infectious Diseases. Philadelphia, JB Lippmcott Co. 1975, pp 143-153

4. Einhorn AH: Bacteria! meningitis, in Rudolph AM (ed):

Pediatrics, ed 16. New York, Appleton-Century-Crofts, 1977, p 19

5. Knugman S, Katz SL: Infectious Diseases ofChildren, ed 7. St Louis, CV Mosby Co, 1981, pp 168-183

6. Bell WE, McCormick WF: Neurologic Infections in Chil-dren, ed 2. Philadelphia, WB Saunders Co, 1981, p4 7. Holt LE: Observations on three hundred cases of acute

meningitis in infants and young children. Am J Dis Child 1911;1:26

8. Appelbaum E, Abler C: Advances in the diagnosis and

treat-ment of acute pyogenic meningitis. NY State J Med

1958;58:204

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10. Berk M: Traumatic streptococcic meningitis. Am JMed Sci 1946;212:18

11. Eigler JOC, Wellman WE, Rooke ED, et a!: Bacteria! men-ingitis. Mayo Clin Proc 1961;36:357

12. Fraser DW, Henke CE, Feldman RA: Changing patterns of bacterial meningitis in Olmsted County, Minnesota, 1935-1970. J Infect Dir 1973;128:300

13. Qadri SMH, Berotte JM, Wende RD: Incidence and etiology of septic meningitis in ametropolitan county hospital. Am J Clin Pathol 1976;65:550

14. Keys TF, Weilman WE, Needham GM, et al: Bacteria!

meningitis: IV. Infections caused by multiple organisms. Mayo Clin Proc 1966;41:179

15. Watson DG: Purulent neonatal meningitis. J Pediatr

1957;50:352

16. Ziai M, Haggerty PA: Neonatal meningitis. N Engl J Med 1958;259:314

17. Groover RV, Sutherland JM, Landing BH: Purulent men-ingitis of newborn infants. N Engl JMed 1961;264:1115 18. Berman PH, Banker BQ: Neonatal meningitis. Pediatrics

1966;38:6

19. Baker CJ, Barrett FF, Gordon RD, et a!: Suppurative men-ingitis due to streptococci of Lancefield group B: A study of 33 infants. J Pediatr 1973;82:724

20. Hempling SM, Coutinho MLP: Streptococcal meningitis. Br Med J 1971;2:166

21. Jones SR, Luby JP, Sanford JP: Bacteria! meningitis com-plicating cranial-spinal trauma. J Trauma 1973;13:895 22. Shadravan I, Fishbein J, Hebert U: Streptococca!

menin-gitis with an unusual port of entry. Am J Dis Child 1976;130:214

23. Dillon HC: Group A type 12 streptococcal infection in a newborn nursery. Am J Dir Child 1966;112:177

24. Rannanathan K, Grossman A: Neonatal streptococcal men-ingitis. Ill Med J 1967;130:705

25. Nutman J, Henig E, Wilunsky E, et a!: Acute necrotising fasciitis due to streptococcal infection in a newborn infant. Arch Dis Child 1979;54:637

26. McMahon BJ, Barrett DH, Bender TR, et al: Group A

streptococcal meningitis in an infant: Report of a case asso-ciated with a community outbreak due to m-type 4 orga-nisms. Alaska Med 1979;21:57

27. Nicol CGM: Neonatal streptococcal meningitis in a

mater-nity unit. Monthly Bull Mm Health Pub Lab Service

1961;20:68

28. Black PH, Swartz MN, Sharp JT, et a!: Severe streptococcal disease. N Engl JMed 1961;264:898

29. Burech DL, Koranyi KI, Haynes RE: Serious group A strep-tocococca! diseases in children. J Pediatr 1976;88:972 30. Beveridge J: Puru!ent meningitis in infancy and childhood.

Med JAust 1954;1:932

31. Peter G, Hazard J: Neonatal group A streptococcal disease. J Pediatr 1975;87:454

32. Duma Ri, Weinberg AN, Medrek TF, et al: Streptococcal infections. Medicine 1969;48:87

33. Breese BB: Beta hemolytic streptococcal infections in chil-then. Pediatr Clin North Am 1960;7:843

34. Swartz MN, Dodge PR: Bacterial meningitis: A review of selected aspects. N Engl J Med 1965;272:725

35. Patamasucon P, Wientzen RL, Schwartz RH: Group A /3-hemolytic streptococci causing pyogenic gingival cyst in in-fancy. Am J Dis Child 1980;134:617

HOW’S THAT AGAIN???

I can say again that those who teach have done something without which

most people could not do for themselves whatever it is they do; that the act of

teaching is an exemplary act, of self-fashioning on behalf of knowledge that

teaches others how to fashion the sebf that no teacher is due more respect or

affection than he or she has earned, but that the drive behind the teaching effort is a positive one. . . . That moment of poise when what is known becomes

accessible and must then become what is to be found, is the act of teaching, and

those acts in sequence are a life, in which, once we learn how, we are all teachers

and students of ourselves.

Submitted by Student

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1983;71;1

Pediatrics

Daniel J. Murphy, Jr