Keywords
complication - hyperbilirubinemia - incidence -
Klebsiella pneumoniae
- neonate
Introduction
Bacteremia is a common problem in neonatal intensive care units (NICUs) even in developed
countries, and is associated with significant morbidity and mortality.[1] Prematurity and prolonged hospital stay are important predisposing factors for neonatal
bacteremia, which can be either early onset or late onset.[2]
[3]
[4]
[5] Klebsiella pneumoniae, a gram-negative bacterium that is a component of the normal gastrointestinal flora
of humans, is one important cause of neonatal bacteremia[6]
[7]
[8]; indeed in some centers, it is the most common cause of neonatal sepsis.[8]
[9]
[10]
[11]
[12]
We reviewed the incidence of, risks factors for, and complications of K. pneumoniae bacteremia in our NICU.
Patients and Methods
During the 1-year study period, 805 eligible neonates were admitted in NICU on the
first day of life and stayed for more than 7 days. Patients who were excluded were
those transferred from surgical wards or other hospitals, those admitted for a surgical
procedure, those with major congenital malformations, and those whose mothers had
prolonged rupture of membrane. A blood culture, collected on admission, and further
blood cultures were undertaken thereafter where there were new clinical or laboratory
findings suggestive of infection.
Clinical features of neonatal sepsis were as follows: (1) hypothermia or fever; (2)
lethargy, poor cry, and refusal to suck; (3) poor perfusion, prolonged capillary refill
time, hypotension, or shock; (4) hypotonia and absent neonatal reflexes; (5) bradycardia
or tachycardia; (6) respiratory distress, apnea, and gasping respiration; (7) signs
of meningitis (bulging anterior fontanelle, blank look, high-pitched cry, excess irritability,
not arousal, comatose, seizures, and neck retraction); (8) feed intolerance, vomiting,
diarrhea, abdominal distension, hepatomegaly, paralytic ileus, and suspicion of necrotizing
enterocolitis (NEC); (9) bleeding, petechiae, or purpura; and (10) skin changes, including
pustules, abscesses, sclerema, mottling, umbilical redness, and discharge.
Laboratory features of neonatal sepsis were as follows: hypoglycemia or hyperglycemia;
metabolic acidosis; hyperbilirubinemia; acute renal failure; elevated C-reactive protein
(CRP) concentration (> 1.5 mg/dL); leukopenia (< 5,000 cell/mm3); and thrombocytopenia (< 100,000 cell/mm3). All this information matched in patients with approved blood culture for Klebsiella.
Patients' survival followed and fatal cases recorded beside to complications which
occurred before leaving hospital.
Blood cultures were collected and processed, and isolates identified, using standard
techniques.[13] Empiric antibiotic treatment was with ampicillin plus either gentamicin or cefotaxime,
narrowed to organism-specific drugs as soon as possible.
For the study, clinical data were obtained by retrospective case note review. Nosocomial
infection was considered to be present if onset of infection was found after 72 hours
of birth. Statistical Package for Social Sciences (SPSS version 15), and T-independent
and chi-square tests; p values of less than 0.05 were considered to be significant.
Results
Of 805 neonates, 51 (6% of all admitted cases) had bacteremia with K. pneumonia presenting in the first week of life. Overall, 63% of those affected were in very
low-birth-weight (VLBW) group (< 1,500 g). The incidence of Klebsiella bacteremia
in neonate weighing 1,500 to 2,500 g was 33% (32/95), but only 2.7% in neonate weighing
over 2,500 g (p < 0.001). Klebsiella bacteremia was more frequent in males than females (32 vs. 19,
p = 0.04). Of 51, 22 cases (41%) of bacteremia were not seriously unwell at the time
of blood culture collection. The most common presentation among these cases was hyperbilirubinemia
(15/21; 71%). Indeed, hyperbilirubinemia was the single most common presenting feature
of Klebsiella bacteremia, occurring in 44 of 51 cases; 57% of all cases managed by
phototherapy and other 43% by exchange transfusion ([Fig. 1]).
Fig. 1 Complications and presentations of Klebsiella pneumoniae bacteremia in neonates (NEC; necrotizing enterocolitis).
Blood cultures collected before the 3rd day of life were positive in 10 of 51 cases
(19%); 25 cases presented between the 3rd and 5th days of life, whereas 16 cases presented
at between 5 and 7 days of age ([Fig. 2]). As well as hyperbilirubinemia, most patients (68%) had an elevated CRP concentration;
thrombocytopenia (62%), and leukopenia (20%) were the other common abnormal laboratory
investigations. Near half of patients had all three of the most common abnormal laboratory
tests (hyperbilirubinemia, elevated CRP concentration, and thrombocytopenia). Meningitis
was the most common serious complication, occurring in nine cases (18%); other complications
occurred in seven cases (NEC four cases, septic arthritis two cases, and hydrocephaly
one case).
Fig. 2 Time of diagnosis of Klebsiella pneumoniae bacteremia after birth.
Overall, 13 cases died, giving an overall mortality rate of 25%. Mortality was higher
in females and in the lower birth weight neonates; the mortality rate in VLBW neonates
(< 1,500 g) was 80%, compared with 23% in neonates weighing 1,500 to 2,500 g, and
0% in neonates weighing over 2,500 g group (p < 0.001) ([Fig. 3]).
Fig. 3 Mortality rate following Klebsiella pneumoniae bacteremia according to birth weight.
Discussion
Newborns, especially those born preterm, are prone to bacteremia.[2] Infections may be acquired around the time of birth (early onset), or be acquired
after admission to hospital (late onset).[3]
[4]
[5] Gram-negative bacteremia is a well-recognized cause of nosocomial infection in NICU[14]; Klebsiella spp. are one of the most common gram-negative bacteria isolated from neonates, causing
colonization as well as invasive infections.[7]
[8]
[15] Unsurprisingly, Klebsiella spp. have been reported to be as the most common cause of neonatal bacteremia in
some studies.[16] It may be due to a strong correlation between colonization of neonates at sites
such as the respiratory and gastrointestinal tracts and subsequent development of
infection.[17] The mortality rate in our study (25%) was lower than in reports of gram-negative
bacteremia (Escherichia coli or Klebsiella spp.) in developing countries where mortality rates of around 40% have been reported.[18]
[19] Male gender and prolonged hospital stay have been reported as risk factors for Klebsiella
infection,[2]
[20] and indeed we found that bacteremia were more common in males. We found that during
the first week of life, the risk of Klebsiella bacteremia increased by 15% per day
of hospital stay.
We found that thrombocytopenia was common in patients with Klebsiella bacteremia;
other investigators have reported this phenomenon.[20] In our study, we only included cases presenting in the first week of life, but previous
studies have shown that at least 50% of all cases occur within that time period.[8] Our finding of a strong correlation between bacteremia and low birth weight reflects
the results of previous studies.[21]
In our study, 51 of 805 (6% of all cases) neonates needed to advanced supportive care
get infected by Klebsiella. Although late-onset (nosocomially acquired) infection
is defined as infection which occurs at least 3 days after admission,[22] the time period between acquisition of gram-negative bacteria and onset of sepsis
can be as short as 1 day in neonates.[17] Given that all of our infants had a negative blood culture on admission, it is likely
that most of the 10 cases of bacteremia that presented within 3 days of birth would
have been acquired in the NICU.
However, our overall mortality rate of 25% masks the birth weight–related differences
in mortality; in neonates, weighing less than 1,500 g the mortality rate was 80%,
compared with 0% in those weighing over 2,500 g. Our findings show the clinical presentation
of neonatal Klebsiella bacteremia can be subtle mirrors, the findings of others who
have reported that a rising CRP concentration and/or hyperbilirubinemia are common
presenting features of neonatal Klebsiella bacteremia.[23]
[24] Interestingly, the same studies reported mortality rates of 21%, which is similar
to the mortality rate in our study.[23]
[24]
Conclusion
K. pneumoniae bacteremia during the first week of life affected 6% of neonates admitted to our
NICU. The mortality rate is high in the VLBW group. It is important to remember that
despite the potential lethality of this condition, neonatal Klebsiella bacteremia
may present with only nonspecific findings.
Ethical Aspects
This study was a retrospective review of routine clinical practices and, as such,
neither ethics committee approval nor consent was required.
