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EXPERIENCE AND REASON 463

Figure. Roentgenography of chest showing bilateral

hilar adenopathy and interstitial infiltration.

diagnosis of scrotal masses in adolescents and

chil-dren.

JANIS SCHAEFFER, MD

MICHAEL NUSSBAUM, MD

SANDY MEYERSFIELD, MD

Department of Pediatrics

Division of Adolescent Medicine

Long Island Jewish-Hifiside Medical Center

New Hyde Park, New York, and

Health Sciences Center

State University of New York at Stony Brook

Stony Brook, New York

REFERENCES

1. Kendig E: The clinical picture of sarcoidosis in children.

Pediatrics 54:289, 1974

2. Jasper P, Dennz F: Sarcoidosis in children. JPediatr 73:499, 1968

3. Gerstenhaber, B., Green, R., and Sachs, F.: Epididymal sarcoidosis: A report of two cases and a review of the litera-ture. Yale J Biol Med 50:669, 1977

4. Mikhail J, Mitchell D, Dyson J, et al: Sarcoidosis with genital involvement. Am Rev Respir Dis 106:465, 1972 5. Singer E, Hensler N, Flynn P: Sarcoidosis: Analysis of 45

cases in a large military hospital. Am J Med 26:364, 1959

6. Ricker W, Clarke M: Sarcoidosis. A clinico-pathologic review of 300 cases including 22 autopsies. Am J Clin Pathol 19:

725, 1949

7. Engle RL Jr: Sarcoid and sarcoid-like granulomas: A study of twenty-two autopsies. Am J Clin Pat/wI 29:53, 1953

8. Opal S, Pittman D, Hofeldt F: Testicular sarcoidosis. Am J Med 67:147, 1979

9. Rudin L, Megalli M, Messa-Tijader A: Genital sarcoidosis.

Urology 3:750, 1974

Excellent

Outcome

of

Bacteroides

Meningitis

in a

Newborn

Treated

with

Metron

idazole

Hydrocephalus has developed in all three

re-ported cases of Bacteroides fragilis meningitis in

newborns.’3 One author suggested this

complica-tion was related to the documented persistence of

Bacteroides in the CSF despite chioramphenicol

therapy.3 In two of the cases metronidazole was

tried late in the course, followed by prompt clinical

and bacteriologic resolution.”3 We report a newborn

Reprint requests to (M.I.M.) Department of Pediatric Infectious Diseases, University of Oklahoma Health Sciences Center, P0 Box 26901, Oklahoma City, OK 73190.

PEDIATRICS (ISSN 0031 4005). Copyright © 1980 by the

American Academy of Pediatrics.

with B fragilis meningitis in whom metronidazole

was used early, with rapid sterilization of the CSF, clinical cure, and no sequelae after 12 months of follow-up.

CASE REPORT

A 2,020-gm white male infant was delivered vaginally at 32 weeks gestation to a healthy primigravida, 52 hours after premature rupture of membranes. During labor, the

mother remained afebrile and received no antibiotics. A

scalp electrode was used to monitor fetal well-being.

Apgar scores were 4 and 8 at one and five minutes, respectively.

The baby was transferred to the Montreal Children’s Hospital because ofan imperforate anus. Additional prob-lems included moderate respiratory distress and a small

scalp laceration secondary to the electrode. Because of

prolonged rupture of membranes, cultures were obtained

and cloxacillin and gentamicin were prescribed.

(Antibi-otic dosages and laboratory data are shown in the Figure.)

Blood and urine cultures were sterile, whereas the gastric

aspirate and swabs of eye, ear, nose, and throat grew

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I f , I If f f t f f I 1

1195 209 663 118 22 0 41 11 10

(79) (13) (46) (41) (0) (44) (0) (0)

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25 24 23 71 30 41 35 38 38

(61 1 (79) [631 12291 1671 1941 (1 18) [56] 99

+ + + - - -

-intravenous

___(OOJ oral

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464

PEDIATRICS

Vol.66

No. 3 September

1980

LUMBAR csF WBC (% PMN) PROTEIN (mg/dO SUGAR (mg/d$) BLOOD SUGAR CULTURE ANTIBIOTIC THERAPY mg/Ig day CLOXACILLIN GENTAMICIN AMPICILUN CHLORAMPHENICOL ME TRONIDAZOL( INHIBITORY/KILLING POWER

reciprocal of t#{232}ter

SERUM

CSF

5 10 15 20 25 30 35 40 45 50 55

AGE (daysj

Figure. Sequential antibiotic therapy and laboratory

data in a newborn with B fragilis meningitis. Asterisk

indicates interval (hours) between receiving antibiotic

Escherichia coli. The imperforate anus was due to a thin

covering membrane which was perforated digitally,

fol-lowed by daily anal dilations. The scalp laceration was

washed daily with 3% hexachlorophene and covered with

sterile dressings. The respiratory distress resolved rapidly

and by day 7 antibiotics and supplemental oxygen were

discontinued and the patient was bottle-feeding. At this

time a scalp abscess was noted at the electrode site.

Cultures of the purulent exudate grew E coli, B fragilis,

and anaereobic streptococci. Local treatment with

de-bridement and repeated hexachlorophene washes was

prescribed.

On day 10 the baby suddenly developed periodic breathing and cyanotic spells. WBC was 33,000/cu mm

with 53% polymorphonuclear (PMN) cells, 8% band cells,

and 24% lymphocytes. CSF showed 266 red cells, 1,175

white cells (79% PMN), protein of 240 mg/100 ml, and

sugar of 25 mg/100 ml (blood sugar of 61 mg/100 ml);

Gram stain was negative. Therapy with Ampicillin and

gentamicin therapy was started. Over the next three days

the baby remained critically ill with recurrent seizures,

despite anticonvulsant therapy. On day 14, B fragilis was

isolated from the initial CSF while cultures of blood and

urine remained sterile. By tube dilution method, the

minimal inhibitory concentration (MIC)/minimal

bacte-ricidal concentration (MBC) was 32/64 units/nil for

pen-icillin and 2/128 .tg/m1 for chloramphenicol. Antibiotic

therapy was changed to intravenous chioramphenicol at

a dose of25 mg/kg every 12 hours. There was no

improve-ment over the next 36 hours, and in view of the reported

failure ofchloramphemcol to sterilize CSF despite in vitro

sensitivitofB fragilis,’3 the drug was discontinued and intravenous metromdazole was started (30 mg/kg/day in

two divided doses). The CSF culture obtained after three

doses of chloramphemcol grew B fragilis. After 48 hours

of metronidazole therapy the CSF was sterile and the baby, having shown marked clinical improvement, did

dose and sampling of blood or CSF. Inhibitory and killing

powers were determined by tube dilution method using

the patient’s serum and CSF isolate of B fragilis.

well for the remainder of his hospital stay. Computed

tomography showed normal sized ventricles with no

evi-dence of ventriculitis or focal abscess. Metronidazole was

discontinued after a three-week course; however a repeat

lumbar puncture three days later showed an increase in

PMNs and a low sugar leveL The Gram stain and culture

were negative. Although his clinical condition was good,

oral metromdazole (in the same dosage regimen as given

intravenously) was continued for one more week.

Subse-quently, the CSF improved except for a persistently low

sugar level. At the time of this report, the baby is 12

months old, in good health, and developing normally for

his age.

DISCUSSION

This report documents the development of local

and invasive Bacteroides fragilis infection

proba-bly due to the fetal monitoring scalp electrode.

Local abscesses have been reported to occur in 4.5%

of babies monitored with scalp electrodes; however,

B

fragilis infection has not been documented and

invasive disease is rare.4 This is also the first

re-ported case of Bacteroides meningitis in a newborn

with no sequelae. We feel the early use of

metroni-dazole with rapid sterilization of the cerebrospinal

fluid was critical in this patient’s remarkable

recov-ely.

Anaerobic infections, although uncommon in the

pediatric age group, are being recognized with

in-creased frequency. A recent prospective survey

found that 5.8% of clinically significant bacteremic

episodes in children were due to anaerobes.5 In the

neonatal age group the incidence was 8.7%; 43% of

these isolates were B fragilis which is notable

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EXPERIENCE AND REASON 465

among anaerobes for its frequent resistance to

pen-icillin. Although sensitive in vitro to

chioramphen-icol, clindamycin, and carbenidillin, only

chioram-phenicol reliably achieves CSF concentrations

ex-ceeding the MIC.6 Despite this, chloramphenicol

has not been very effective in sterilizing the CSF,’3

and has failed to cure septic anaerobic infection in

spite of documented sensitivity to the drug, the use

of recommended doses, and adequate surgical

drainage procedures.7 The bacteriostatic activity of

chloramphenicol against B fragilis may account for

some of the reported therapeutic failures.8

Although our patient had received only three

doses of chloramphenicol we considered the

ther-apy a failure in view of his clinical deterioration, an

increasing CSF polymorphonuclear response, and a

persistent low CSF sugar. This was confirmed by

the positive CSF culture, and low serum and CSF

killing powers obtained while the patient was being

treated with chloramphenicol. This was in contrast

to the rapid clinical and bacteriological response,

coupled with excellent serum and CSF killing

pow-ers shortly after starting metronidazole therapy.

Metronidazole has a rapid bactericidal action

against anaerobes9 and is known to achieve

excel-lent CSF concentrations even with oral

administra-3 An injectable form is now available,

al-though its use is stifi experimental. Several recent

reports confirm the remarkable efficacy and low

toxicity of this drug in treating anaerobic

infec-tions.’#{176}The major fear limiting its use comes from

reports of tumors occurring in mice who were fed

life-long diets of metronidazole in high doses.” The

clinical relevance of such data remains to be shown.

There are no pharmacokinetic data on the use of

metronidazole in infants. We chose a regimen based

on that used in two previous reports of neonatal B

fragilis Based on our experience we

recommend early consideration of metronidazole

therapy in similar cases.

ACKNOWLEDGMENTS

Thanks to Mr S. Sorger for technical assistance and to

Dr R. Fontaine of Poulenc Ltd for provision of injectable

metromdazole.

REFERENCES

BARBARA

J.

LAW,

MD

MELVIN

I.

MARKS,

MD

Montreal Children’s Hospital

Montreal

1. Feldman WE: BacterQides fragilis ventriculitis and menin-gitis. Am J Dis Child 130:880, 1976

2. Dysart NK Jr, Griswold WR, Schanberger JE, et al: Men-ingitis due to Bacteroides fragilis in a newborn infant. J Pediatr 89:509, 1976

3. Berman BW, King FH, Rubenstein DS, et al: Bacteroides

fragilis meningitis in a neonate successfully treated with metronidazole. J Pediatr 93:793, 1978

4. Okada DM, Chow AW, Bruce VT: Neonatal scalp abscess and fetal monitoring: Factors associated with infection, Am J Obstet Gynecol 129:185, 1977

5. Dunkle LM, Brotherton TJ, Feigin RD: Anaerobic infections in children: A prospective study. Pediatrics 57:311, 1976 6. Picardi JL, Lewis HP, Tan JS, et at: Clindamycin

concentra-tions in the central nervous system of primates before and after head trauma. J Neurosurg 43:717, 1975

7. Thadepalli H, Gorbach SL, Bartlett JG: Apparent failure of chloramphenicol in the treatment of anaerobic infections.

Curr Therap Res 22:421, 1977

8. Rahal JJ Jr, Simberkoff MS: Bactericidal and bacteriostatic action of chloramphemcol against meningeal pathogens.

Antimicrob Agents Chemother 16:13, 1979

9. Ralph ED, Kirby WMM: Unique bactericidal action of

met-romdazole against Bacteroides fragilis and Clostridium

per-fringens. Antimicrob Agents Chemother 8:409, 1975 10. Tally FP, Sutter VL, Finegold SM: Treatment of anaerobic

infections with metronidazole. Antimicrob Agents

Chemo-ther 7:672, 1975

11. Roe FJC: Metronidazole: Review of uses and toxicity, J

Antimicrob Chemother 3:205, 1977

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1980;66;463

Pediatrics

Barbara J. Law and Melvin I. Marks

Metronidazole

Meningitis in a Newborn Treated with

Bacteroides

Excellent Outcome of

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1980;66;463

Pediatrics

Barbara J. Law and Melvin I. Marks

Metronidazole

Meningitis in a Newborn Treated with

Bacteroides

Excellent Outcome of

http://pediatrics.aappublications.org/content/66/3/463

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American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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