Clinical Features of B. Cereus Sepsis in Premature Neonates

Background: To analyze the clinical characteristics and prognosis of bacillus cereus sepsis in premature neonates. Method: Retrospectively analyze the data of 8 premature neonates of bacillus cereus sepsis in Shanghai Children’s Hospital from January 2015 to December 2019, where clinical information is collected from patients’ medical records and charts, information of neurodevelopment is collected for patients from follow-up visits at corrected age of 6 months and 12 months. Results: 8 premature neonates of bacillus cereus sepsis were identied, among which 5 cases developed meningitis, abnormal Cerebral MRI images were seen in 5 cases. After empirical antibiotic treatment with Meropenem and Vancomycin, 1 patient died, 7 patients survived to discharge. Follow-up visits discovered that 1 patient developed hydrocephalus and showed severely delayed neurodevelopment, 2 patients had mild neurodevelopmental delay, and neurodevelopment was basically normal in other 4 patients. Conclusions: Bacillus cereus infection can cause severe nervous system complications, and affect neurodevelopmental outcome. Empirical antibiotic treatment with Meropenem and Vancomycin is proven effective.


Background
Neonatal sepsis is a serious disease which threatens life of neonates. Its incidence among survived neonates is 4.5‰~9.7‰ [1] .
It is a major risk factor in late-onset sepsis among term and/or premature neonates. Incidence rate increases as gestational age and body weight decreases [2] . Common pathogens for late-onset sepsis in China are Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, etc. The Bacillus cereus group is comprised of eight closely related species: B. cereus, B. cytotoxicus, B. mycoides, B. pseudomycoides, B. thuringiensis, B. weihenstephanensis, B. toyonensis, and B. anthracis [3][4][5] .
Bacillus Cereus is a type of gram positive, aerobic facultative bacillus which is widely distributed in the environment [6] . Besides food poisoning [7]  2.3 Treatment: Upon change in condition, 5 cases needed respiratory support; 2 cases were intubated and put on mechanical ventilation, 3 cases were on non-invasive ventilation; 2 cases developed septic shock, and received uid resuscitation and inotropes; 5 cases received immune support with IVIG. Based on blood culture results, we changed antibiotics to Vancomycin, 6 cases saw their condition improve after being administered with Vancomycin; 1 case was administered with Meropenem and Ampicilin to ght infection before its condition improved; 1 case was initially administered with Benzylpenicilin and Ceftazidime before the therapy was changed into Meropenem which showed no effect and neonate died. Among those whose condition improved, anti-infection treatment lasted 14-49 days. See Table 1. 2.4 Laboratory examination. Increased WBC and increased neutrophil ratio were seen in 2 cases; Leukocytopenia was seen in 5 cases; 2 cases developed thrombocytopenia; all the 8 cases had various degrees of increased CRP and increased PCT. All Bacillus cereus strains were resistant to penicillin and compound trimethoprim, sensitive to erythromycin, Clindamycin, Gentamicin, Vancomycin and Levo oxacin; All 8 cases received lumbar puncture; 5 cases had combined meningitis (

Discussion
Bacillus cereus is a spore forming and ubiquitous bacterium presents in soil, foods, insect larvae, almost all surfaces and human skin [8][9] . B. cereus has been found in environmental reservoirs such as ventilator equipment, intravascular catheters, and linen. In addition to food poisoning, B. cereus causes a number of systemic and focal infections in both immunologically compromised and immunocompetent individuals. Among those most commonly infected are neonates, especially with indwelling catheters.
The spectrum of infections includes fulminant bacteremia, central nervous system(CNS) involvement(meningitis and brain abscesses), to name a few [6] . Research found that a majority of strains(41%) were isolated in newborns, among which 3/4 were premature infants with low birth weight [10] . And, with virulence test of bacterial strain, it is found that the average production of bacterial strain toxin from newborns is low, this suggests that newborn may be particularly sensitive to B. cereus strains, even those with low toxin production, or that other unknown factors may be responsible for newborn infection. The pathogenicity of bacillus cereus is closely related to the production of tissue damaging/reactive exoenzymes. The secretin includes four kinds of hemolysins, three distinct phospholipases, an emesis-in-ducing toxin, and three pore-forming enterotoxin: hemolysin BL (HBL), nonhemolytic enterotoxins (NHE) and cytotoxin K.
Besides, B. cereus can cause severe late-onset hemorrhagic meningoencephalitis in preterm infants. In this study, 7/8 infants had signs and symptoms of meningitis (CSF showed leukocytosis, low glucose, and increased protein), among which 6 patients have shown abnormal expressions in cerebral MRIs. Early and continuous brain sonography is very important for neonates,especially for premature infants who are suspected of septicemia or having convulsions. Some research states [11] , Serial brain sonography showed that the hemorrhagic meningoencephalitis affects rst the white matter and later the basal ganglia and cortex.
According to past research, most bacillus cereus are resistant to penicillin and cephalosporin, but sensitive to aminoglycoside, carbapenem, vancomycin and chloramphenicol [12] . The cases in this research are all responsive to meropenem and vancomycin treatments.
In short, the clinical symptoms of bacillus cereus sepsis in preterm neonates are non-speci c, with increased CRP in lab tests, meningitis expressions in CSF examinations, and hemorrhagic meningoencephalitis in cerebral MRI. Meropenem and vancomycin are proven effective in treatment. The limit of the study is the small sample size, therefore more clinical and lab test features cannot be summarized.

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Positive blood culture of bacillus cereus in premature neonates should not be deemed as contamination. Bacillus cereus infection can cause severe nervous system complications. Lumbar puncture should be completed and anti-infection treatment should be given. Meropenem and vancomycin are effective in treatment.   A, B show hemorrhagic liquefactive necrosis of the left hemisphere. Figure A shows abnormal high signal at frontoparietal temporal lobes on both sides, T1WI sagittal view mixed low point high signal, T2WI shows high signal. Figure B shows the reexamination after two weeks of treatment: it shows multiple patchy abnormal high signal at frontoparietal temporal lobes on both sides, with similar range of that of Figure A, spotted signals of high signals of both T1WI, T2WI decrease; while there is no obvious change where T2WI has high signal, T1WI has low signal (softening lesions). C shows T2-air enhancement. Right temporal meningeal enhancement. Figure C: T2-air after enhanced, obvious enhancement of about 2.8 cm is seen on the right temporal meninx, right temporal meninx enhances. D encephalocele and parietal lobe on both sides show platy low T1 signal, high T2 signal, with ill-de ned borders, partially connected to the rear corners of encephalocele on both sides, encephalocele on both sides are enlarged, while diocoele and epicoele do not show obvious enlargement.