BACTERIAL SEPSIS AND MENINGITIS - Nizet Laboratory at UCSD

cases of clostridial meningitis resulting from C. butyricum
and C. perfringens. Clostridial sepsis has a high mortality
rate [234].
NEONATAL TETANUS
Neonatal tetanus is caused by the gram-positive anaerobic
spore-forming bacillus C. tetani. The organism is present
in soil and can be present in human and animal feces.
Infection usually occurs after contamination of the umbilical
stump. Maternal and neonatal tetanus are important
causes of mortality in developing countries, resulting in
an estimated 180,000 deaths annually [237]. In the United
States, tetanus in the newborn is exceedingly rare [238].
Since 1984, only three cases of neonatal tetanus have been
reported [238–240]. The most recent case, reported from
Montana in 1998, was an infant born to an unimmunized
mother; the parents used a C. tetani–contaminated clay
powder to accelerate drying of the umbilical cord. The
use of this product had been promoted on an Internet site
on “cord care” for use by midwives [241].
In many developing countries, the incidence and
mortality of neonatal tetanus remain startlingly high
[242–245]. Mustafa and colleagues [246] conducted a retrospective
neonatal tetanus survey among rural and displaced
communities in the East Nile Province in the
Sudan and observed an incidence of neonatal tetanus of
7.1 cases per 1000 live births, more than double that
reported from the stable rural community (3.2 per
1000). In both communities, coverage with two doses of
tetanus toxoid was about 58%. Mortality attributable to
neonatal tetanus in Djakarta in 1982 was 6.9 deaths per
1000 live births, and in the island provinces of Indonesia,
it was 10.7 deaths per 1000 live births [247]. Among 62
cases of neonatal tetanus in Ethiopia, 90% were born at
home, and 70% lacked antenatal care [245]. Three quarters
of infants in this series died in the hospital, and risk
factors for fatal outcome included an incubation period
of less than 1 week, onset of symptoms less than 48 hours,
tachycardia, and fever [245]. The mortality rate for neonates
with tetanus in Lima, Peru, was 45% and was not
improved with use of intrathecal tetanus antitoxin [248].
A meta-analysis of intrathecal therapy in tetanus suggested
benefit in adults, but not in neonates [249].
Application of contaminated materials to the umbilical
cord is associated with deep-rooted customs and rituals
in developing countries. A case-control study to identify
risk factors for neonatal tetanus in rural Pakistan identified
application of ghee (i.e., clarified butter from the
milk of water buffaloes or cows) to the umbilical wound
as the most important risk factor [250]. Although commercial
ghee is available in Pakistan, the ghee used in
rural areas is made at home from unpasteurized milk.
Oudesluys-Murphy [251] observed that application of
some materials, including ghee and a stone wrapped in
wet cloth, increased the risk of neonatal tetanus among
Yoruba women, but that other practices of cord care
decreased the incidence, including searing of the cord
with heat in China during the Ming dynasty and use of
a candle flame to scar the cord in Guatemala. Neonatal
tetanus is a preventable disease; use of hygienic techniques
at delivery and a program of tetanus toxoid
CHAPTER 6 Bacterial Sepsis and Meningitis
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immunization of children and young adults, particularly
of pregnant women, are effective in eliminating this lethal
disease [251–254].
MIXED INFECTIONS
Multiple organisms frequently are present in brain, liver,
or lung abscesses; aspirates in the lung after pneumonia;
or pleural empyema. Such mixed infections infrequently
are found in cultures of the blood or CSF, however.
When several species are found, the significance of each
is uncertain because it is possible that one or more of
the organisms in a mixed culture is a contaminant.
Bacteremia with more than one organism occurs in
patients with immunodeficiency, major congenital
abnormalities, or contamination of a body fluid with multiple
organisms, as is present in peritonitis typically as a
sequela of severe necrotizing enterocolitis in a very low
birth weight infant. Neonatal meningitis caused by
S. pneumoniae and Acinetobacter calcoaceticus [255] and sepsis
caused by P. aeruginosa and Yersinia enterocolitica [256] have
been reported. Although included in a series of cases of
neonatal sepsis by some investigators, mixed cultures are
not identified by most. Mixed infections were reported by
Tessin and coworkers [257] in 5% of 231 Swedish
neonates, by Vesikari and associates [258] in 4% of 377
Finnish infants, and by Bruun and Paerregaard [259] in
7% of 81 Danish neonates. Faix and Kovarik [260] reviewed
the records of 385 specimens of blood or CSF submitted to
the microbiology laboratories at the University of Michigan
Medical Center for the period of September 1971 to June
1986. More than one organism was present in 38 specimens
from 385 infants in the NICU; 15 (3.9%) infants had multiple
pathogens associated with clinical signs of sepsis or
meningitis. The mortality rate was high (60%).
Factors predisposing to mixed infection included prolonged
rupture of membranes (>24 hours); total parenteral
nutrition; necrotizing enterocolitis; presence of an
intravascular catheter or ventriculostomy; and entities
associated with multiple pathogens, including peritonitis,
pseudomembranous colitis, and hepatic necrosis. Chow
and colleagues [217] reported polymicrobial bacteremia
in eight newborns with anaerobic coisolates or aerobic
and anaerobic organisms in combination. Jarvis and
associates [261] reported an outbreak of polymicrobial
bacteremia caused by K. pneumoniae and E. cloacae associated
with use of a contaminated lipid emulsion.
Mixed infections also can include bacteria and viruses
or bacteria and fungi, typically Candida, in the situation
of intravascular central catheter or peritoneal infections
associated with bowel perforation. Sferra and Pacini
[262] reported mixed viral-bacterial meningitis in five
patients, including neonates with CSF isolates of enterovirus
and GBS in a 10-day-old infant and enterovirus
and Salmonella in a 12-day-old infant.
UNCOMMON BACTERIAL PATHOGENS
Numerous additional bacterial pathogens have been
identified as rare or uncommon causes of neonatal sepsis
and meningitis. These are listed in Table 6–8 with their
references and were reviewed by Giacoia [263].