CASE REPORT
Neonatal Listeriosis Shih-Yu Chen, Frank Leigh Lu, Ping-Ing Lee, Chun-Yi Lu, Chien-Yi Chen, Hung-Chieh Chou, Po-Nien Tsao, Wu-Shiun Hsieh* In Western developed countries, Listeria monocytogenes is not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks’ gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocytogenes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals. [J Formos Med Assoc 2007;106(2):161–164] Key Words: listeriosis, neonate, preterm infant
early-onset neonatal listeriosis who were born at National Taiwan University Hospital in 1990 and 2005, respectively.
Listeria monocytogenes is an uncommon pathogen of illness in the general population. However, it may cause severe infections among the elderly, patients with diabetes mellitus, immunosuppressed patients, pregnant women, and neonates.1,2 Neonatal listeriosis is not uncommon in Western developed countries and can result in significant mortality and morbidity. The case-fatality rate of perinatal infection was around 20–45%.3,4 Listeriosis is relatively rare in Eastern countries.5 The estimated incidence of listeriosis in Japan was 0.65 cases per million population, which is much lower than reported in Western countries.3,5,6 Perinatal infection accounts for 20% of listeriosis in Japan.5 Neonatal listeriosis has rarely been reported in Taiwan. We report two premature babies with
Case Reports Case 1 A male preterm baby weighing 1558 g was born via cesarean section due to fetal distress at a gestational age of 31 weeks. His mother had suffered from fever with chills 3 days prior to delivery. Preterm premature rupture of membranes before delivery and meconium-stained amniotic fluid were also noted. The 1- and 5-minute Apgar scores were 4 and 7, respectively.
©2007 Elsevier & Formosan Medical Association .
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Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Received: October 21, 2005 Revised: February 15, 2006 Accepted: June 6, 2006
*Correspondence to: Dr Wu-Shiun Hsieh, Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei 100, Taiwan. E-mail:
[email protected]
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Physical examination on admission revealed a tiny baby with poor activity and tachypnea. Erythematous maculopapular rashes were noted over the trunk and four limbs that had lasted for 2 days. Hemogram on the 1st day revealed leukocytosis of 42,970/mm3 leukocytes with left shift. C-reactive protein was 12.84 mg/dL. Lumbar puncture revealed turbid cerebrospinal fluid (CSF) with white blood cell count of 87/mm3 (mononuclear cell:polymorphonuclear cell, 20:67), red blood cell count of 8181/mm3, protein level of 693 mg/dL, and glucose level of 3 mg/dL. Empirical antibiotics with ampicillin (100 mg/kg/day q12h) and cefotaxime (100 mg/kg/day q12h) were used initially. Subtle seizure, bradycardia and desaturation were also noted on the same day. Anticonvulsant therapy was given and no further seizure occurred thereafter. Both blood and CSF culture collected on the 1st day yielded L. monocytogenes. In addition, his mother’s blood culture also yielded L. monocytogenes. The dosage of ampicillin was increased to 300 mg/kg/day and cefotaxime was switched to gentamicin (5 mg/kg/day q12h) after the culture result. By using standard disk diffusion methods, the L. monocytogenes isolated from the blood and CSF were both determined to be sensitive to ampicillin and intermediate sensitive to penicillin. Minimal inhibitory concentrations determined by E-tests were 0.38 μg/mL for penicillin, 2.0 μg/mL for ampicillin, and 24.0 μg/mL for cefotaxime. Serum bactericidal titers determined on the 10th day of antibiotics treatment were 1:256 for peak and 1:128 for trough. Pathologic examination of maternal placenta disclosed chorioamnionitis. Brain computed tomography revealed ventriculomegaly and irregular ventricular wall with septations over bilateral lateral ventricles. Auditory brain evoked potential examination showed normal findings and electroencephalography revealed focal seizure with diffuse cerebral dysfunction. The treatment course included 4 weeks of ampicillin and 10 days of gentamicin. Follow-up brain ultrasonography showed progressive ventriculomegaly. Ventriculoperitoneal shunt was performed on the 49th day of life. The symptoms were significantly improved 162
after operation. He was then discharged on the 58th day.
Case 2 A male newborn weighing 1180 g was born via vaginal delivery at a gestational age of 28 weeks. His mother had fever and a flu-like illness 3 days prior to the onset of labor. Chorioamnionitis and meconium-stained amniotic fluid were also noted. Apgar scores were both 4 at 1 and 5 minutes. Endotracheal intubation and ventilator support were provided due to respiratory distress and bradycardia. Chest X-ray examination showed bilateral reticulogranular infiltrations. Hemograms showed leukocytosis of 35,100/mm3 leukocytes with left shift. CSF had a turbid appearance, pleocytosis (1090/mm3; mononuclear cell:polymorphonuclear cell, 80:20), low glucose level (11 mg/dL), and elevated protein level (Pandy test: 3+). Initially, ampicillin and cefotaxime were administered on the 1st day, both at a dose of 100 mg/kg/day q12h; both were then increased to 200 mg/kg/day from the 2nd day. Brain ultrasonography on the 1st day showed multiple hypoechogenic cysts over bilateral enlarged ventricles, suggestive of ventriculitis. Blood culture on the 1st day yielded L. monocytogenes. Susceptibility to ampicillin and cefotaxime were both sensitive in the blood. CSF culture and urine culture were negative. Ventilator was weaned off and shifted to oxygen hood smoothly on the 6th day. Unfortunately, sudden deterioration with cyanosis and bradycardia developed on the 8th day, and the baby died on the same day.
Discussion Neonatal listeriosis is not uncommon in Western developed countries. Case-fatality rate of perinatal infection remains high.3,4 Listeriosis has rarely been reported in Eastern countries.5 Apart from group B streptococcus and Escherichia coli, L. monocytogenes is the third most common pathogen of neonatal meningitis in the West.7 There have been a few cases of neonatal listeriosis reported in Taiwan.8–10 The total number of J Formos Med Assoc | 2007 • Vol 106 • No 2
Neonatal listeriosis
cases including ours is only five. All five patients were born prematurely with low birth weights ranging from 1070 g to 2300 g. Their mothers manifested some of the illness including flu-like symptoms, malaise, headache, or lower abdominal pain. Also, preterm premature rupture of membranes, meconium-stained amniotic fluid, and chorioamnionitis were commonly found in the maternal history. Two of the mothers had positive L. monocytogenes cultures from the blood and amniotic fluid, respectively. The initial symptoms and signs of babies presented immediately after birth to within 2 days of age. Respiratory distress was the most common initial manifestation, followed by fever, seizure, apnea, and skin rash or mottling. Hemograms revealed leukocytosis in four cases, and leukopenia and thrombocytopenia in one case each. All of the blood cultures from these babies yielded L. monocytogenes. The CSF profiles of these patients were all abnormal, including pleocytosis in five and hypoglycorrhachia in three. However, positive CSF culture for L. monocytogenes could be documented in only two cases. The mortality rate was 40%. Among the three survivors, one developed hydrocephalus and received ventriculoperitoneal shunt operation. The neurologic development in this patient over 1 year of follow-up was normal. There was no associated morbidity in another survivor and the third survivor was lost to follow-up. The reason for the low incidence of neonatal listeriosis in Taiwan is not well established. The food habits of people in Taiwan are different from those of westerners. Incorrect determination of culture results due to the coccobacilli shape and changeable Gram-positive stain may be one of the impacting factors.9 Physicians seldom take cultures from aborted tissue or fetus, which may also result in missing the diagnosis of perinatal infection, and there are probably some cases of neonatal listeriosis not published. Thus, the incidence of perinatal infection may be underestimated. Similar to neonatal group B streptococcus sepsis, the clinical manifestations in the neonate after birth are classified into early and late onset forms J Formos Med Assoc | 2007 • Vol 106 • No 2
of the disease.11 Early-onset listeriosis is often associated with preterm delivery. It occurs in the first 7 days of life and is usually associated with maternal illness. Septic-like syndrome may predominate in these patients but other manifestations such as acute respiratory distress and pneumonia are common. Meningitis and myocarditis are relatively rare.1,11 The five patients reported in Taiwan had early-onset disease. Interestingly, in addition to the above described clinical manifestations, abnormal CSF findings were found in all five cases, and hydrocephalus developed in two. L. monocytogenes has a predilection for the central nervous system. It may directly invade cerebral parenchyma and the brain stem, causing meningoencephalitis and rhomboencephalitis. The ability of L. monocytogenes to cross the meninges and blood–brain barrier is likely to be the result of endothelial-cell or macrophage phagocytosis of the bacteria and their use of the host-cell contractile system to spread to and grow within the central nervous system in preterm infants.1,12 The reason for the high rate of meningitis is not clear, but may be due to the bias of the small case number in our series and the fact that all were preterm infants. Thorough evaluation of the central nervous system is recommended in preterm infants with listeria infection. The antibiotic therapy of choice for neonatal listeriosis is a high dose of intravenous ampicillin. Treatment should be extended to 3–4 weeks for neonatal listeriosis and up to 6 weeks for patients with brain abscess or endocarditis.11,13 Aminoglycoside is unlikely to be effective and the recommendations may differ.13 Cephalosporins should not be used due to reduced affinity of key penicillin-binding proteins and poor activity against L. monocytogenes.13 Although L. monocytogenes is reported to be susceptible to meropenem in vitro, treatment failure of meropenem in pediatric patients has been documented.14 In conclusion, L. monocytogenes may result in life threatening disease and cause significant morbidity in the fetus and neonate. Early diagnosis of perinatal infection relies on a high index of suspicion. Comprehensive evaluation and appropriate 163
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treatment are crucial in such neonates, especially when the central nervous system is involved.
Acknowledgments The authors wish to thank Professor Suh-Fang Jeng for her revision of the manuscript.
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