A 9-day-old, 34-week premature male, who had good prenatal care and
cesarean section delivery caused by severe preeclampsia, developed fever and
irritability and had a sepsis workup that showed a complete blood count with
23,700 white blood cells/mm3 with 69% granulocytes; cerebrospinal
fluid with more than 9,000 white blood cells and 180,000 red blood cells;
glucose of zero with an increased protein; and negative Gram’s stain.
Serum chemistries revealed an anion gap of 18 mmol/L.
James H. Brien
The baby had an MRI done revealing subgaleal, subdural and subarachnoid
blood with multiple, scattered deep white matter infarcts (Figures 1-4).
Empiric treatment was started with ampicillin, gentamicin and acyclovir,
pending cerebrospinal fluid (CSF) cultures and herpes polymerase chain reaction
(PCR) and blood cultures, which all turned out to be negative. Other pertinent
negatives obtained during the next week included a respiratory virus panel
(PCRs for influenza, parainfluenza, adenovirus, enterovirus and respiratory
syncytial virus) and CSF enterovirus PCR, cytomegalovirus urine screen and
Toxoplasma serologies. The empiric antibiotics were continued, despite the lack
of an organism being identified because of the baby’s overall condition.
Because of technical difficulties, the lumbar puncture was not repeated until
the baby began having seizure-like activity about 10 days after the onset of
fever (which never re-occurred but developed temperature control problems). At
that time, the CSF revealed a white blood cell count of 2,015 and zero red
blood cells, a protein of 590 mg/dL and glucose of zero. CSF cultures were
again sent for routine stains and cultures plus herpes simplex virus PCR,
acid-fast bacterial and fungal stains and cultures, as well as culture in
urea-containing broth and special Mycoplasma hominis media. A repeat MRI
is shown in Figures 5 and 6.
Figure 1. The baby had an MRI done revealing subgaleal, subdural and subarachnoid
blood with multiple, scattered deep white matter infarcts (Figures 1-4)
Images: Brien JH
Figure 5. A repeat MRI
is shown in Figures 5 and 6.
What’s Your Diagnosis?
B.Group B streptococcus meningitis
C.Ureaplasma urealyticum meningitis
D.Listeria monocytogenes meningitis
The hydrocephalus and other damage to the baby’s brain shown in the
MRI figures could be caused by any of the choices. There was no way to know the
cause of this baby’s meningitis with certainty until the Ureaplasma
culture came back positive for (C) Ureaplasma urealyticum. However,
using good test-taking skills, there are some hints that should lead one to
suspect something a bit unusual. Certainly, there’s nothing too unusual
about a premature newborn with herpes or group B strep, plus the baby was on
appropriate empiric therapy for neonatal sepsis with meningitis with the use of
ampicillin, gentamicin and acyclovir, which should have been helpful against
these possibilities. Despite this, his CSF continued to remain abnormal with
marked pleocytosis and severe hypoglycorrhachia. All the routine cultures
remained negative and the herpes PCR was negative again on the second CSF
sample. As soon as the Ureaplasma culture result was known, he was
started on a 21-day course of IV azithromycin plus doxycycline. About a week
into the treatment, another CSF sample was obtained revealing significant
improvement in its parameters and was culture-negative for Ureaplasma.
The baby received a ventriculoperitoneal shunt soon after the second MRI
(Figure 7) and was discharged at 2 months of age, significantly improved and
continuing to do well.
Figure 7. The baby received a
ventriculoperitoneal shunt soon after the second MRI above.
When I was a fellow in 1982, Jim Bass (my fellowship director) taught us
about U. urealyticum and M. hominis and their capability for
causing a variety of infectious problems in newborns (especially U.
urealyticum and especially in premature neonates), from pneumonia to sepsis
and meningitis to stillbirths. However, this is only the second case I can
recall seeing since then. I suspect there have been others that went
unrecognized because I either did not think about it or our cultures missed it.
As noted in the question section, these organisms require special culture
media, but can be recovered within a few days if properly handled. As pointed
out in the Red Book, sometimes it’s hard to tell what is caused by
the Ureaplasma and what is part of the baby’s underlying problems
related to prematurity. However, in a case like this, with the positive CSF
culture and the temporal improvement with appropriate anti-Ureaplasma
therapy, it would seem to leave little doubt as to the role of
Ureaplasma in the baby’s meningitis. These organisms lack cell
walls, therefore, penicillins and cephalosporins will not work. Macrolides work
by binding to the 50S subunit of the ribosome, inhibiting protein synthesis,
resulting in a bacteriostatic effect.
Tetracyclines also inhibit protein synthesis by binding to the 30S
subunit. Ureaplasma is a prokaryote, having both subunits. Therefore,
either should be effective if able to reach the organism; however, there are no
clear guidelines, only advice from recognized experts and case reports. The
treatment given to this baby was based on similar reports. Since this case
occurred, an excellent review was published in The Pediatric Infectious
Diseases Journal by Clifford and colleagues of Australia. If you are faced
with a similar case, I would review this paper before making any therapy
I know that a rare case with nothing but images to show is probably not
of much interest to those of you not involved in the care of premature
neonates, but we should all be aware of this possibility and understand the
potential devastating consequences of a central nervous system infection caused
by one of these peculiar organisms in these fragile neonates. Even if you
don’t see newborns at all, you may be taking care of one of these babies
when they seek a primary provider, and the above paper will give you good
information on that baby’s infectious disease background. Also, the
parents may come, already well-read on this subject.
James H. Brien, DO, is a member of the Infectious Diseases in
Children Editorial Board as well as Vice Chair for Education at The
Childrens Hospital at Scott and White and is the Associate Professor of
Pediatrics at Texas A&M University, College of Medicine, Temple, Texas.
email: email@example.com. Disclosure: Dr. Brien reports no
relevant financial disclosures.