EBM Review: Ruling out bacteremia and bacterial meningitis in infants less than one month of age: is 48 hours of hospitalization necessary?

Fielding-Singh V, Hong DK, Harris SJ, Hamilton JR, Schroeder AR. Ruling out bacteremia and bacterial meningitis in infants less than one month of age: is 48 hours of hospitalization necessary? Hosp Pediatr. 2013 Oct;3(4):355-61.

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OBJECTIVE: The appropriate duration of hospitalization for infants ≤ 30 days admitted for fever or other concerns for a serious bacterial infection is an understudied area. We sought to determine the risk of a positive, pathogenic bacterial culture of blood or cerebrospinal fluid (CSF) in this population beyond 24 hours after collection.

METHODS: This study was a retrospective review of 1145 infants aged ≤30 days who had a blood or CSF culture from 1999 to 2010 at Santa Clara Valley Medical Center, a county health system in San Jose, California. Time to notification and the probability of a positive culture result after 24 hours were calculated. Infants were considered high risk if they had either a white blood cell count <5000 or >15 000 per µL, a band count >1500 per µL, or an abnormal urinalysis.

RESULTS: We identified 1876 cultures (1244 blood, 632 CSF) in 1145 infants aged ≤30 days; 901 (79%) of 1145 were hospitalized and 408 (45%) of 901 hospitalizations were for fever without source (FWS). Thirty-one (2.7%) of the 1145 infants had pathogenic cultures; 6 of 1145 infants (0.5% [95% confidence interval: 0.2-1.1]) had a time to notification >24 hours. All 6 patients had FWS (1.5% of hospitalized FWS sample) and met high-risk criteria on presentation. No low-risk patients had a time to notification >24 hours. Low-risk characteristics were found in 57% (232 of 408) of the entire hospitalized FWS population.

CONCLUSIONS: Low-risk infants hospitalized for FWS or other concerns for serious bacterial infection may not need hospitalization for a full 48 hours simply to rule out bacteremia and bacterial meningitis.

Reviewed by:

Deidra Ansah Deidra Ansah, MD

Bhavya Doshi Bhavya Doshi, MD

Study Aims:

  • Determine the probability of positive pathogenic blood and CSF culture after 24 hours in infants less than or equal to 30 days of age hospitalized outside of the ICU setting for suspected serious bacterial infection.
  • Assess whether stratifying infants into high and low risk categories based on presentation modifies the above probability.

Study Design:

  • Retrospective cohort from pediatric ward of community hospital from Jan 1999 – Dec 2010
  • All infants < 30 days of age who had blood and/or CSF cultures performed in clinics, ED or ward.
  • Excluded patients with cultures sent from NICU, PICU, those with indwelling central lines, lack of temperature > 38 by any method, or whose  initial evaluation was at an outside facility.
  • Narrowed to those admitted for fever without source
  • In the end, 1145 infants with 1876 cultures were studied (1244 blood, 632 CSF cultures).  408/1145 infants were admitted for fever without source.

Results:

  • Bacterial growth present in 196/1876 cultures from 189 infants
    • Contaminants comprised 135/1244 blood cultures and 28/632 CSF cultures
    • 74% of contaminants were coagulase-negative staphylococci
    • True pathogens for bacteremia included E. coli, S. aureus, Enterococcus, and Group B streptococcus.  True pathogens for bacterial meningitis included E. coli and Enterococcus.
  • Time to notification was greater for contaminants than pathogens (45.3 vs 24.5 hours, p < 0.001)
  • 25 of 31 infants had positive culture with time to notification < 24 hours, 6 of 31 grew after 24 hours
    • All 6 were classified as high risk (positive UA, elevated WBC, ill-appearing)
    • Of 6 with TTN > 24 hours, 3/6 had notification between 24-48 hours

Discussion:

  • The number needed to treat for all fever without source patients in this study was 17 (i.e. 17 infants would need to be hospitalized and treated with IV antibiotics to prevent one missed infant)
  • This number increased to 67 if narrowed to NNT for infants staying in the hospital beyond 24 hours.
  • Study is limited by classification of pathogens vs. contaminants by one Pediatric ID specialist looking only at microbiological diagnosis, lack of evaluation of nasopharyngeal viral testing, questionable overestimation of time to notification due to lack of reporting overnight, lack of evaluation of urine cultures, and overlap of the confidence intervals for high and low risk infants’ rates of positive cultures.

Take Away Points:

  • Bacteremia and bacterial meningitis are rare in well appearing infants
  • Absolute risk of a positive culture > 24 hours is 1.5% in infants with high risk attribute
  • Study cites a risk of positive culture > 24 hours in low risk infants is 0% but cannot trust zeros in statistics.
  • Decision eventually lies in clinical judgment and risk aversion.

Lemierre syndrome (Updated – Aug 2014.)

Righini CA, Karkas A, Tourniaire R, et al. Lemierre syndrome: A study of 11 cases and literature review. Head Neck. 2014 Jul;36(7):1044-51.

“Background: Lemierre syndrome is a rare but serious illness that associates throat infection and thrombosis of the internal jugular vein (IJV) or one of its tributaries with subsequent distant septic emboli. The aim of our study is to review the pathogenesis, clinical presentation, and treatment of this disease. Methods: Patients with confirmed Lemierre syndrome were included in our retrospective monocentric study. All patients had bacteriologic analyses as well as radiologic imaging. Results: There were 11 patients in our study (1998-2012). Fusobacterium necrophorum was responsible for the infection in 45% of cases. Surgical drainage of pharyngeal, cervical or mediastinal abscesses was carried out in 8 cases. All patients received broad-spectrum antibiotics. 6 patients were admitted to the intensive care unit (ICU). One patient (9%) died. Conclusion: Treatment with broad-spectrum antibiotics is the primary choice of treatment of Lemierre syndrome. Surgery is indicated in case of abscess formation.”

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Cardenas-Garcia J, Narasimhan M, Koenig SJ. A teenager with fever and sore throat. Diagnosis: Lemierre syndrome. Chest. 2014 Apr;145(4):e10-3.

Lemierre syndrome is a rare but serious illness that associates oropharyngeal infection involving the palatine tonsils or peritonsillar tissue and thrombosis of the internal jugular vein (IJV). There is a 1- to 3-week time interval [1] during which distant septic pulmonary and systemic emboli occur. Lemierre syndrome commonly occurs in young adults and is mainly caused by Fusobacterium necrophorum, [2,3] an anaerobic gram-negative bacillus that is part of the normal oral flora. However, other organisms, including Bacteroides, Eikenella, Streptococcus,Peptostreptococcus, Porphyromonas, Prevotella, Proteus, methicillin-resistant Staphylococcus aureus, and methicillin-sensitive S aureus may also cause Lemierre syndrome. [4,5]

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Young BJ, Steele RW. A teenager with sore throat and neck pain. Clin Pediatr (Phila). 2011 Apr;50(4):355-6.

“Characteristically a disease of previously healthy adolescents and young adults, the initial presentation of Lemierre’s syndrome is sore throat or neck pain. The primary pharyngitis is most often caused by a bacterium of the Streptococcus species, leading to formation of peritonsillar cellulitis or an abscess. Within the abscess, anaerobic species flourish,  penetrating into the closely neighboring internal or less commonly, external jugular vein. Usually within 1 to 2 weeks of the initial infection, a septic thrombus forms within the jugular vein. Ensuing bacteremia may lead to spiking fever, lethargy, or shock. Infected emboli may also disseminate from the clot. These often seed into the lungs, leading to cough, shortness of breath, pleurisy, hemoptysis, and respiratory failure. Septic emboli may also settle within the joints, leading to arthralgia or disseminate to the liver, kidneys, spleen, or meninges.”

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Weeks DF, Katz DS, Saxon P, Kubal WS. Lemierre syndrome: report of five new cases and literature review. Emerg Radiol. 2010 Jul;17(4):323-8.

“It is especially noteworthy that nearly half of patients in one review had a normal physical examination [6]. Clinical findings in the oropharynx, when present, may be deceptively mild, consisting of localized hyperemia or swelling with little to suggest more extensive disease [8, 9]. Cervical lymphadenopathy and tenderness may be present. Embolic disease to the lungs is most common and is associated with cough, dyspnea, and pleuritic pain. Emboli to numerous other sites, including muscle, bone, brain, and liver have been described, although nonpulmonary manifestations of LS most often affect large joints [5].”

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Ridgway JM, Parikh DA, Wright R, et al. Lemierre syndrome: a pediatric case series and review of literature. Am J Otolaryngol. 2010 Jan-Feb;31(1):38-45.

“Lemierre syndrome is a rare disease of the head and neck often affecting adolescents and young adults. Classically, infection begins in the oropharynx with thrombosis of the tonsillar veins followed by involvement of the parapharyngeal space and the internal jugular vein. Septicemia and pulmonary lesions develop as infection spreads via septic emboli. Although a rare entity in modern times, Lemierre syndrome remains a disease of considerable morbidity and potential mortality.”

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More PubMed results on Lemierre syndrome.

Created 09/24/13, updated 08/12/14.