BACTERIAL SEPSIS AND MENINGITIS - Nizet Laboratory at UCSD

258 SECTION II Bacterial Infections
that an increase of 1 mg/dL in CSF protein occurs
for every 1000 red blood cells/mL. The concentration of
glucose does not seem to be altered by blood from a traumatic
lumbar puncture; a low CSF glucose concentration
should be considered an important finding even when
associated with a traumatic lumbar puncture.
Because a “bloody tap” is difficult to interpret, it can be
valuable to repeat the lumbar puncture 24 to 48 hours
later. If the results of the second lumbar puncture reveal
a normal white blood cell count, bacterial meningitis
can be excluded. Even if performed without trauma or
apparent bleeding, CSF occasionally can be ambiguous
because white blood cells can be elicited by the irritant
effect of blood in CSF.
Brain Abscess
Brain abscess is a rare entity in the neonate, usually complicating
meningitis caused by certain gram-negative
bacilli. CSF in an infant with a brain abscess can show a
pleocytosis of a few hundred cells with a mononuclear
predominance and an elevated protein level. Bacteria
may not be seen by Gram stain of CSF if meningitis is
not present. Sudden clinical deterioration and the appearance
of many cells (>1000/mm 3 ), with most polymorphonuclear
cells, suggest rupture of the abscess into CSF.
LABORATORY AIDS
Historically, aids in the diagnosis of systemic and focal
infection in the neonate include peripheral white blood
cell and differential counts, platelet counts, acute-phase
reactants, blood chemistries, histopathology of the placenta
and umbilical cord, smears of gastric or tracheal
aspirates, and diagnostic imaging studies. New assays
for diagnosis of early-onset sepsis, including serum concentrations
of neutrophil CD 11b [594], granulocyte
colony-stimulating factor [595], interleukin receptor
antagonist [596], interleukin-6 [597–599], procalcitonin
[600–602], serum amyloid A [603], and prohepcidin
[604], show promise for increased sensitivity and specificity
compared with other laboratory assessments,
such as white blood cell count, absolute neutrophil count,
and acute-phase reactants. Proinflammatory cytokines,
including interleukin-1, interleukin-6, and tumor necrosis
factor-a, have been identified in serum and CSF in infants
after perinatal asphyxia, raising doubts about the specificity
of some of these markers [581,582,605,606]. Mehr and
Doyle [607] reviewed the more recent literature on cytokines
as aids in the diagnosis of neonatal bacterial sepsis.
These assays and procedures are discussed in detail in
Chapter 36.
Attention has focused more recently on the use of realtime
polymerase chain reaction technologies, often based
on the 16S ribosomal RNA sequence of leading pathogens,
as a tool for the accelerated culture-independent
diagnosis of neonatal sepsis. Compared with the gold
standard of blood culture, the evaluation of sensitivity
and specificity of PCR technologies and their consequent
clinical utility has ranged from equivocal [608,609] to
highly promising [610,611]. Continued rapid advances in
nucleic acid–based diagnostics are certain to be explored
in this important clinical arena.
MANAGEMENT
If the maternal history or infant clinical signs suggest the
possibility of neonatal sepsis, blood and CSF (all infants)
and cultures of urine and other clinically evident focal sites
should be collected (all infants with suspected late-onset
infection). If respiratory abnormalities are apparent or
respiratory status has changed, a radiograph of the chest
should be performed. Because the clinical manifestations
of sepsis can be subtle, the progression of the disease can
be rapid, and the mortality rate remains high compared
with mortality for older infants with serious bacterial infection,
empirical treatment should be initiated promptly.
Many infants who have a clinical course typical of bacterial
sepsis are treated empirically because of the imperfect sensitivity
of a single blood culture in the diagnosis of sepsis.
CHOICE OF ANTIMICROBIAL AGENTS
Initial Therapy for Presumed Sepsis
The choice of antimicrobial agents for the treatment of
suspected sepsis is based on knowledge of the prevalent
organisms responsible for neonatal sepsis by age of onset
and hospital setting and on their patterns of antimicrobial
susceptibility. Initial therapy for the infant who develops
clinical signs of sepsis during the first few days of life
(early-onset disease) must include agents active against
gram-positive cocci, particularly GBS, other streptococci,
and L. monocytogenes, and gram-negative enteric bacilli.
Treatment of the infant who becomes septic while in
the nursery after age 6 days (late-onset disease) must
include therapy for hospital-acquired organisms, such as
S. aureus, gram-negative enteric bacilli, CoNS (in very
low birth weight infants), and occasionally P. aeruginosa,
and for maternally acquired etiologic agents.
GBS continue to exhibit significant in vitro susceptibility
to penicillins and cephalosporins. Of 3813 case isolates
in active population-based surveillance by the CDC from
1996-2003, all were sensitive to penicillin, ampicillin,
cefazolin, and vancomycin [612]. New reports in the
United States and Japan have identified GBS strains with
reduced b-lactam susceptibility, however, and first-step
mutations in the PBPx2 protein reminiscent of the emergence
of b-lactam resistance in pneumococci decades ago
[613,614]. In the CDC surveillance, GBS resistance to
clindamycin (15%) and erythromycin (30%) also was
noted to be increasing [612].
In vitro studies [615–617] and experimental animal
models of bacteremia [618,619] indicate that the bactericidal
activity of ampicillin and penicillin against GBS
and L. monocytogenes is enhanced by the addition of gentamicin
(synergy). Some physicians prefer to continue the
combination of ampicillin and gentamicin for 48 to 72
hours, but when GBS is identified as the etiologic agent,
the drug of choice for therapy is penicillin administered
intravenously for the remainder of the treatment regimen.
There are no clinical data to indicate that continuing an
aminoglycoside in combination with a penicillin results
in more rapid recovery or improved outcome for infected
neonates (see Chapter 13).
Most strains of S. aureus that cause disease in neonates
produce b-lactamase and are resistant to penicillin G and