EXPERIENCE AND REASON-BRIEFLY RECORDED 749
consist only of a milk substitute and a multiple
vitamin preparation not containing vitamin K.
Consideration should therefore be given to the
addition of small amounts of vitamin K to milk
substitutes lower in vitamin K activity than
skimmed cow’s milk. This has already been
done with the product Isomil.
SUMMARY
Sixty infants, 1 to 18 months of age, with
diarrhea, were treated with a skimmed milk
diet and succinylfathiazole. Thirty received supplemental vitamin K, and had oral vitamin
K intakes, expressed as K, activity, of 16.1 to
36.3 tg/kg/day. Hypoprothrombinemia was
riot observed. Thirty did not receive
supple-mentation and had intakes, similarly expressed,
of 9.2 to 29.5 jig/kg/day. A single episode
of hypoprothrombinemia was recorded on an
intake of 9.8 cg/kg/day.
In a group of 15 infants with clinical bleed-ing e1)isodes due to vitamin K deficiency, the oral vitamin K intakes, expressed as K, activity, were 0.0 to 8.4 sg/kg/day.
These data suggest that, in infants who have diarrhea and/or are receiving antimicrohials,
there exists a risk of vitamin K deficiency if the dietary intake contains less than the
ap-I)roximate equivalent of 10 tg/kg/day of vita-mm K1 activity.
HERBERT I. GOLDMAN, M.D.
64-01 Springfield Boulevard
Bayskie, New York 11364
PETER AMADIO, M.D.
Willingbctro, New Jersey
Supported by a grant from Merck, Sharpe, and Dohme Inc., West Point, Pennsylvania.
We are grateful to the following physicians who
were responsible for supplying clinical material:
Frederic Flynn, Newington, Connecticut, for Case 13; Audrey Reynolds, Stockton, California, for Case
14; and Leonard Vitale, Brooklyn, New York, for Case 15.
REFERENCES
I. Goldman, H. I., and Desposito, F.:
Hypopro-thrombinemic bleeding in young infants. Amer. J. Dis. Child., 111 :430, 1966.
2. Quick, A. J.: On quantitative estimation of
prothrombin. Amer. J. Clin. Path., 15:560, 1945.
:i. Food and Nutrition Board, National Research Council : Recommended Dietary Allowances,
ed. 6. Washington, D.C. : National Research
Council, 1964.
4. Ross Laboratories, Columbus, Ohio, based
upon assays performed by the Wisconsin
Alumni Research Foundation, Madison,
Wis-consin. Personal communication.
5. Almquist, H. J.: The assay of vitamin K. In
Cattell, J., Dann, W. J., and Satterfield, C. H., ed. : Biological Symposia, Vol. 12. San
Francisco: F. E. Booth Co., p. 517, 1947. 6. LeLong, M., Alagille, D., and Odievre, M. : La
forme neo-natale tardive de l’avitaminose K aigue idiopathique. Nouv. Rev. Franc.
Hemat., 4:173, 1964.
7. Vecchio, F., Schettini, F., and Pnionelli, S. : Su
una nuova sindnome emorragica in una neo-nate (deficit associate di PTC, fattore VII e prothrombina). Pediatria ( Napohi
),
64:188, 1956.8. Rapoport, S., and Dodd, K. :
Hypoprothrom-binemia in infants with diarrhea. Amer. J.
Dis. Child., 71:611, 1946.
9. Matoth, Y.: Plasma prothrombin in infantile
diarrhea. Amer. J. Dis. Child., 80:944, 1950.
10. Moss, M. : Hypoprothrombinemic bleeding in a
young infant. Amer. J. Dis. Child., 117:541,
1969.
11. Sutherland, J. M., Glueck, H. I., and Cleser, G. : Hemorrhagic disease of the newborn. Amer. J. Dis. Child., 113:524, 1967.
Cephalosporium
Meningitis
Numerous papers in the literature have
described the epidemiology, clinical findings,
and therapy of mycotic infections, with or
without involvement of the central nervous system.
Amphotericin B is currently a highly
effec-tive antimicrobial agent against most types of
disseminated or localized mycotic infections.”
Although the mucormycoses, cladosporium
localized lesions, and cephalosporium infections
belong among the extremely rare conditions
which can cause cerebral or pulmonary
involve-ment of variable severity under certain circum-stances, the establishment of an early
bacterio-logic diagnosis is essential in view of the
availability of amphotericin B, which may be expected to modify the course of the infection.
The following is the first case to be reported
of cephalosponium meningitis in a newborn
in-fant in which amphotenicin B has been
thera-peutically applied.
REPORT OF CASE
The patient, a white male infant, was born by cesarean section to a 30-year-old, gravida II,
healthy mother. Gestation was normal, and the
baby weighed 3,700 gm at birth. On admission to
750 CEPHALOSPORIUM MENINGITIS and physical examination was essentially negative.
He was discharged home at the age of 5 days, on
breast feeding with a weight of 3,500 gm. At the age of 10 days, he started to lose weight and was readmitted because of diarrhea, vomiting, and tern-peratures of 38#{176}to 39#{176}C.On that admission the
in-fant was pale, irritable, and dehydrated; he
weighed 3,200 gm. Fine nales were heard over the
left lung fields. A chest film showed accentuation of penihilar lung markings on the left without definite pulmonary infiltration. Hemoglobin was normal, and the leucocyte count was 7,500 with 49%
poly-morphonuclear cells and 43% lymphocytes. Blood
cultures were negative, but stool cultures revealed pathogenic E. coil (026:B6). The baby was started
on intravenous fluids, penicillin G (200,000 U),
and colistin (50,000 U) every 8 hours. His condi-tion improved markedly, although on the second hospital day he was still febnile. At the age of 12
days he was active and fully hydrated with normal electrolytes and a weight of 3,400 gm.
At the age of 15 days and still under antibiotic
therapy, the baby started refusing his feedings. He
became listless and irritable. He had to be fed by gavage. The anterior fontanelle was flat and there
was no nuchal rigidity. The liver was barely palpa-ble. Temperature was normal. The leucocyte count
was 9,500, with a normal differential.
A lumbar puncture revealed an opening pressure of 230 mm H20 and a slightly xanthochromatic fluid, with 12 polymorphonuclear, 8 mononuclear cells and normal chemical constituents. On a direct as well as on a Cram-stained smear of the cerebro-spinal fluid sediment, numerous yeast-like
orga-nisnis with long fine filaments were observed. These were initially thought to be of an obscure
and doubtful origin, and a second tap was done within 24 hours with all possible precautions taken to exclude accidental contamination. The same nu-merous yeast like organisms were again seen on a direct smear. Both cerebrospinal fluid specimens
were cultured in Sabouraud medium and
incu-bated at 37#{176}C,as well as at room temperatures. Growth was rapid and covered the surface of the medium in a few days. Direct smears showed fine septated filaments of organisms subsequently identi-fled on both cultures by one of us ( M.P. ) as well
as by Dr. E. Drouhet of the Pasteur Institute,
Paris, as cephalosporium.
The following day the baby was still listless, but some nuchal rigidity and hypertonia were now seen. Stool cultures and a nose and throat culture
Intrathecal administration of the drug was not con-sidered essential. The baby’s condition improved progressively over the weeks of hospitalization. A repeated lumbar puncture 40 days after initiation of therapy revealed a clear cerebrospinal fluid with a normal pressure, 52 cells (70% polymorphonu-clears and 30% lymphocytes
),
normal chemicalconstituents, and negative cultures.
The subsequent course of the patient was
nor-mal. A spinal tap before discharge was entirely
negative. At the most recent examination at the
age of 2 years, the child walks freely, talks fairly well, and seems to have a normal motor activity and adaptive behavior. Visual and auditory acuity appear grossly normal.
COMMENT
Saprophytes can rarely attain pathologic
properties and cause severe and even fatal
localized or generalized infections. Only one
case of a cerebral lesion due to cephalosponium has been published up to now in the literature,3
while candida infections, although unusual,
have nevertheless been reported to cause
dis-seminated or localized severe infections. In a
few instances, however, cephalosponia have
been isolated from mycetomas in the lower
extremities of African patients’ or from
ab-cesses and ulcerations in Europeans.#{176}
The evidence available at present indicates
that the intravenous use of amphotenicin B in
generalized mycotic infections frequently estab-lishes an impressive cultural negativity. Never-theless, the drug has not been detected in the spinal fluid during intravenous treatment of any patient whose spinal fluid protein has less than
75 mg/100 ml.2 Therefore, at the usual
intra-venous dosage, its effectiveness in patients with mycotic infections of the central nervous
sys-tern should be dubious. The causative agent in
our patient was identified by the morphological
characteristics of cephalosponium in two
sepa-rate cultures of cerebrospinal fluid obtained
within a period of 24 hours from each other.
As with candida meningitis, the cerebrospinal
fluid in cephalosporium meningitis may be
relatively free of cells, and glucose and protein
levels may be normal. Demonstration therefore
EXPERIENCE AND REASON-BRIEFLY RECORDED 751
sporium and that cephalosporiurn invaded the
cerebrospinal fluid, assumed pathogenic
prop-erties, and was eventually identified in two cerebrospinal fluid cultures, while Candida albicans was isolated from stool and nose and
throat cultures.
Although it has been well established that, with intravenous amphotericin B, low spinal fluid levels are attained, we selected this mode of therapy as we considered the possibility of the presence of cephalosporia in foci other than the cerebrospinal fluid in which fungistatic concentrations of the drug could be obtained.
It remains, however, quite possible that similar non-fatal infections of the central nervous
system remain undiagnosed and recover
spon-taneously.
SUMMARY
The first reported case of cephalosporium
meningitis in a newborn infant is presented.
The diagnosis was suspected by the
morpho-logical features of the yeast-like organisms on direct smears in two separate cerebrospinal fluid specimens and confirmed by two cerebro-spinal fluid cultures.
The outcome was entirely satisfactory. We consider it possible that recovery was
spon-taneous and that amphotericin B could be
in-strumental in the patient’s recovery only if cephalosporia were present in foci other than the cerebrospinal fluid.
CONSTANTINE PAPADATOS, M.D.
MARIA PAVLATOU, M.D.
DEMOSTHENES ALExI0U, M .D. Neonatal and Bacteriology Department
“Alexandra” Maternity Hospital
Athens (611)-Greece
We wish to acknowledge the generous donation of amphotericin B by Squibb Laboratories, 745 Fifth Avenue, New York.
REFERENCES
1. Utz, J. P., Treger, A., McCullough, N. B., and
Emmons, C. W.: Amphotericin B : Intrave-nous use in 21 patients with systemic fungal
diseases. In Welch, H., and Marti-Ibanez, F., ed. : Antibiotics annual: 1958-1959. Proceed-ings of the Sixth Annual Symposium on
Anti-biotics.
2. Seabury, J. H., and Dascomb, H. E. : Experience with Amphotericin B. Ann. N. P. Acad. Sci.,
89:202, 1960.
3. Drouhet, E., Martin, L., Segretain, C., and Destombes, P.: Mycose c#{233}r#{233}bromening#{233}e
a
cephalosporium. Presse Med., 73: 1809, 1965.4. Kozinn, P. J., Taschdjian, C. L., Pishvazadeh, P., Pourfar, M., and Neumann, E. : Candida
meningitis successfully treated with
Ampho-tericin B. New Eng.
J.
Med. 268:881, 1963. 5. Segretain, C. : Some new or infrequent fungouspathogens. In Fungi and Fungous Diseases.
Springfield, Illinois: Charles C Thomas, 1962. 6. Coutelen, F., Cochet, G., and Biguet,
