A 92-day-old male came to clinic with a fever to 101°F for 24 hours. He appeared well and had no localizing signs on physical examination. He returned to clinic 2 days later with continued fevers up to 102°F. His mother said he was also acting more tired and fussy but consolable. He was drinking and urinating well. His mother said that she had noticed strong smelling urine too. The past medical history showed an uneventful pregnancy and delivery. He had received appropriate health supervision and was current with his immunizations.
The family history was negative for any kidney diseases, hearing problems or genetic diseases. The pertinent physical exam showed an alert male who would get fussy during the examination but calm. His vital signs were normal including his blood pressure taken with an appropriately sized cuff. His temperature was 101.2°F in the office. HEENT was negative. He had no rashes. His abdominal examination was negative. His genitory examination showed a normal male who was uncircumcised. His diaper smelled strongly of urine. The laboratory evaluation showed an elevated white blood cell count of 18.2 x 1000/mm2 with a 32% left shift. His C-reactive protein was 4.8 mg/dl. The urinalyis could not be completed because of a problem in the laboratory but a catheter urine culture was sent. A blood culture was also sent.
The diagnosis of fever without localizing signs with possible febrile urinary tract infection/clinical pyelonephritis was made. The attending physician and the intern discussed potential options for treatment. The intern asked what ages was it appropriate to specifically treat for Listeria. “I know the highest risk is in the first month or so, but I know it certainly can occur after that time. By 90 days I think this infant is at low risk,” the attending answered. He was given intramuscular ceftriaxone and seen the next day. He had done well over the night but was still febrile. His blood culture was negative but the urine culture was growing gram-negative rods. He was given another dose of ceftriaxone. On the second day he returned and had been afebrile for 24 hours. His blood culture continued to be negative and his urine culture was growing E. coli that eventually was shown to be sensitive to cefoxitin. He was treated for 10 days and was awaiting evaluation for a possible urological anatomic abnormality.
Neonatal bacterial infections are commonly caused by Group B Streptococcus, enteric gram-negative organisms such as Escherichia coli, coagulase negative Staphylococcus, Listeria monocytogenes and Haemophilus influenza. Infections are usually because of transplacental infection or ascending infection from the mother’s genitourinary tract. Empiric treatment for suspected sepsis for neonates is usually combined IV aminoglycoside and expanded-spectrum penicillin antibiotic therapy in the US and Canada and this combination specifically covers for Listeria.
Listeria monocytogenes was first discovered in 1927 and named in honor of Joseph Lister. It is a ubiquitous, hardy organism that can withstand a wide range of temperatures (multiplying in temperatures from 4-45°C), dessication, low nutrient environments, acidity and salinity. Food borne transmission causes most initial cases as it is obviously difficult to eliminate from the food chain. Healthy individuals may not have symptoms or have mild flu-like or gastrointestinal illness, but can have sepsis or meningitis. The greatest risk is to the elderly, immunocompromised persons, pregnant women and fetuses and newborns of infected women. Listeria infections in these vulnerable populations can affect any organ system including arthritis, conjunctivitis, and endocarditis, but bacteremia/sepsis and central nervous system infections of meningitis and encephalitis and death may occur. For pregnant women, infection is associated with a 10-20% risk of fetal loss and increased risk of premature birth. For premature and term newborns, in addition to bacteremia/sepsis, meningitis, and encephalitis, they can also have pneumonia and granulomatosis infantiseptica. Precautions to potentially prevent Listeria infection are recommended for pregnant women and those considering pregnancy including avoidance of ready to eat deli and luncheon meats or hot dogs (unless reheated to steaming hot), soft cheeses, refrigerated pate or meat spread, refrigerated smoked seafood (such as lox), drinking unpasteurized milk or eating improperly stored food.
Recent data from the United Kingdom covering 1990-2013 found that most cases of Listeria in infants < 1 year were actually in those 1 month but did occur. Of the 5 cases that occurred in 31-90 day olds, these occurred at day 31, 33, 34, 56 and 62. The authors point out that 4 of the 5 had meningitis.
In another international review, 5 cases of Listeria were found in infants 1-3 months old of the total 524 cases of Listeria.
Empiric treatment for potential neonatal or early infant infection from Listeria with antibiotics such as ampicillin or amoxicillin or expanded-spectrum penicillin varies according to location with differing local practices. Some places recommend empiric antibiotic coverage for Listeria up to 3 months of age such as the United Kingdom and others such as in the United States, Listeria may not be empirically covered as early as 4 weeks depending on many clinical factors.
Questions for Further Discussion
1. What are the recommendations for treatment of pregnant women exposed to Listeria or suspected of having an infection?
2. What are the recommendations for treatment for urinary tract infections?
3. What are indications for evaluation of the genitourinary tract for infants and young children with urinary tract infections?
- Age: Infant
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Okike IO, Lamont RF, Heath PT. Do we really need to worry about Listeria in newborn infants? Pediatr Infect Dis J. 2013 Apr;32(4):405-6.
Arora R, Mahajan P. Evaluation of child with fever without source: review of literature and update. Pediatr Clin North Am. 2013 Oct;60(5):1049-62.
Maertens de Noordhout C, Devleesschauwer B, Angulo FJ, et.al.. The global burden of listeriosis: a systematic review and meta-analysis. Lancet Infect Dis. 2014 Nov;14(11):1073-82.
Anderson-Berry AL. Neonatal Sepsis. eMedicine.
Available from the Internet at http://emedicine.medscape.com/article/978352-overview (rev. 2/11/14, cited 10/26/15).
Okike IO, Awofisayo A, Adak B, Heath PT. Empirical antibiotic cover for Listeria monocytogenes infection beyond the neonatal period: a time for change? Arch Dis Child. 2015 May;100(5):423-5.
Koseki S, Nakamura N, Shiina T. Comparison of desiccation tolerance among Listeria monocytogenes, Escherichia coli O157:H7, Salmonella enterica, and Cronobacter sakazakii in powdered infant formula. J Food Prot. 2015 Jan;78(1):104-10.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital