Fever without apparent source on clinical examination

Current Opinion in Pediatrics

Volumn 20, Issue 1, 2008, Pages 96-102

  Antonyrajah, Bernadette ^a   Mukundan, Deepa ^a  

^a MEDICAL COLLEGE OF OHIO   (United States)

Author keywords

Fever; Kawasaki disease; Serious bacterial infection

Indexed keywords

AMOXICILLIN PLUS CLAVULANIC ACID; CEFTRIAXONE; HEPTAVALENT PNEUMOCOCCAL CONJUGATE VACCINE; IBUPROFEN; IMMUNOGLOBULIN; LIGAND; MEPREDNISONE; NATURAL KILLER GROUP 2 MEMBER D; PARACETAMOL; UNCLASSIFIED DRUG; VACCINE;

BACTEREMIA; CLINICAL EXAMINATION; CLINICAL FEATURE; DIAGNOSTIC TEST; EARLY DIAGNOSIS; EPSTEIN BARR VIRUS; ESCHERICHIA COLI; GENETIC SUSCEPTIBILITY; HOST SUSCEPTIBILITY; HUMAN; IMMUNE RESPONSE; INCIDENCE; LABORATORY DIAGNOSIS; LOGISTIC REGRESSION ANALYSIS; MUCOCUTANEOUS LYMPH NODE SYNDROME; NEISSERIA MENINGITIDIS; NEUTROPHIL COUNT; PATHOPHYSIOLOGY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PYREXIA IDIOPATHICA; RESPIRATORY SYNCYTIAL PNEUMOVIRUS; REVIEW; SALMONELLA; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PYOGENES; URINARY TRACT INFECTION; VIRULENCE;

CHILD, PRESCHOOL; DISEASE SUSCEPTIBILITY; FEVER OF UNKNOWN ORIGIN; HUMANS; INFANT;

EID: 38149084260     PISSN: 10408703     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOP.0b013e3282f419fa     Document Type: Review

References (25)

1. Eagle RA, Trowsdale J. Promiscuity and the single receptor: NKG2D. Nat Rev Immunol 2007; 7:737-744.
2. Janssen R, Bont L, Siezen CL, Hodemaekers HM, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis 2007; 196:826-834.
3. Carstairs KL, Tanen DA, Johnson AS, et al. Pneumococcal bacteremia in febrile infants presenting to the emergency department before and after the introduction of the heptavalent pneumococcal vaccine. Ann Emerg Med 2007; 49:772-777. This retrospective study compares the rate of bacteremia between those who did and did not receive the PCV7 vaccine. They demonstrate that the rates of true bacteremia due to pneumococcus had decreased in the immunized and that UTI was the next most common cause of fever in children 3-36 months of age.
4. Herz AM, Greenhow TL, Alcantara J, et al. Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent conjugated pneumococcal vaccine. Pediatr Infect Dis J 2006; 25:293-300. The findings of this study support the idea that the routine practice of obtaining blood cultures and complete blood counts may no longer be indicated in the previously healthy, immunized, well-appearing febrile child.
5. Bergman DA, Mayer ML, Pantell RH, et al. Does clinical presentation explain practice variability in the treatment of febrile infants? Pediatrics 2006; 117:787-795. This is an interesting study that analysed variation in practices among physicians in the treatment of febrile infants using a statistical model. Based on the model they could explain about 50% of the variability and about 30% of the overall variability was dependent on clinical presentation.
6. Madsen KA, Bennett JE, Downs SM. The role of parental preferences in the management of fever without source among 3- to 36-month-old children: a decision analysis. Pediatrics 2006; 117:1067-1076. This is an elegantly conducted study which uses decision analysis to compare the benefits and outcomes of three management options (treat: blood culture and antibiotics, test: blood culture and complete blood count, and observe). The survival analysis model used is a must-read for all physicians taking care of febrile infants. Also, the exploration of parental preferences as the odds of SBI decrease in the post-PCV7 era is enlightening and probably needs consideration in the management of the immunized febrile infant in the future.
7. Stathakis T, Acworth JP, Barnett AG. Prediction tool for bacteraemia in children aged 3-36 months. Emerg Med Australas 2007; 19:353-358.
8. Andreola B, Bressan S, Callegaro S, et al. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. Pediatr Infect Dis J 2007; 26:672-677. In this study the value of procalcitonin and CRP levels was compared with total WBC and ANC in predicting SBI in febrile children in the emergency department. Although procalcitonin, CRP, WBC and ANC were significantly higher in patients with SBI, procalcitonin and CRP performed better than WBC and ANC in predicting SBI in children with fever without source.
9. Bleeker SE, Derksen-Lubsen G, Grobbee DE, et al. Validating and updating a prediction rule for serious bacterial infection in patients with fever without source. Acta Paediatr 2007; 96:100-104. The updated prediction tool did not have a perfect discrimination power and could be used as a screening tool to support decision-making in conjunction with clinical experience and should never be used as an independent diagnostic tool.
10. Peltola V, Mertsola J, Ruuskanen O. Comparison of total white blood cell count and serum C-reactive protein levels in confirmed bacterial and viral infections. J Pediatr 2006; 149:721-724.
11. Nuutila J, Hohenthal U, Laitinen I, et al. Quantitative analysis of complement receptors, CR1 (CD35) and CR3 (CD11b), on neutrophils improves distinction between bacterial and viral infections in febrile patients: comparison with standard clinical laboratory data. J Immunol Methods 2006; 315:191-201. A novel marker of bacterial infection designated CIS point, which incorporated standard clinical laboratory data and quantitative analysis of neutrophil complement receptors CR1 and CR3, was presented in this report. The storage time of samples was found to affect the levels of CR1 and CR3. Despite the shortcomings, this novel approach needs further study.
12. Hsiao AL, Chen L, Baker MD. Incidence and predictors of serious bacterial infections among 57- to 180-day-old infants. Pediatrics 2006; 117:1695-1701. This study investigated the epidemiology of febrile illness and evaluated the usefulness of screening tests in the post-PCV7 era. WBC and CRP are no longer useful screening tests but reliable tests for viruses have improved our knowledge of the epidemiology of fever without source and helped in the appropriate use of antibiotics.
13. Abanses JC, Dowd MD, Simon SD, Sharma V. Impact of rapid influenza testing at triage on management of febrile infants and young children. Pediatr Emerg Care 2006; 22:145-149. The authors found that those who test positive at triage for influenza have shorter time in the emergency department and less diagnostic testing, and cost of care is less. The children who test positive, however, also need to be clinically evaluated by the physician for concurrent bacterial infections before being discharged from the emergency department.
14. King RL, Lorch SA, Cohen DM, et al. Routine cerebrospinal fluid enterovirus polymerase chain reaction testing reduces hospitalization and antibiotic use for infants 90 days of age or younger. Pediatrics 2007; 120:489-496. The impact of rapid PCR testing of viruses is seen in the management of the febrile infant. This study reports that a positive cerebrospinal fluid enterovirus PCR test result was associated with a 1.54-day decrease in the length of stay and a shorter duration of antibiotic therapy in the febrile infant.
15. Sarrell EM, Wielunsky E, Cohen HA. Antipyretic treatment in young children with fever: acetaminophen, ibuprofen, or both alternating in a randomized, double-blind study. Arch Pediatr Adolesc Med 2006; 160:197-202. This study reports that the alternating regimen had lower mean temperature, more rapid reduction of fever and less absenteeism from day care (P<0.001). One concern with the alternating regimen is accidental overdosing with either drug. Drug-related adverse events need further evaluation.
16. Walsh A, Edwards H, Fraser J. Over-the-counter medication use for childhood fever: a cross-sectional study of Australian parents. J Paediatr Child Health 2007; 43:601-606. The authors surveyed 401 Australian parents with children aged between 6 months and 5 years about their medication practice and influences on medication use for childhood fever management. They conclude that the belief that these medications were harmful was overridden by fears of harmful outcomes from fever.
17. Doganis D, Siafas K, Mavrikou M, et al. Does early treatment of urinary tract infection prevent renal damage? Pediatrics 2007; 120:e922-e928.
18. Montini G, Toffolo A, Zucchetta P, et al. Antibiotic treatment for pyelonephritis in children: multicenter randomized controlled noninferiority trial. BMJ 2007; 335:386. This study is a noninferiority randomized controlled trial comparing the efficacy of oral antibiotic treatment alone with parenteral followed by oral therapy in children during the first episode of acute pyelonephritis. No significant difference was found between the groups for the time to defervesce or in the rate of renal scarring. Oral therapy is an option but should be used with caution in the appropriate patient.
19. Pasic S, Minic A, Djuric P, et al. Fever of unknown origin in 185 paediatric patients: a single-centre experience. Acta Paediatr 2006; 95:463-466.
20. Lee KY, Hong JH, Han JW, et al. Features of Kawasaki disease at the extremes of age. J Paediatr Child Health 2006; 42:423-427. A total of 136 children were studied and 10 (7.4%) patients were up to 6 months of age and 12 (8.8%) were at least 5 years of age. The clinical features outside the typical age range are described.
21. Chang FY, Hwang B, Chen SJ, et al. Characteristics of Kawasaki disease in infants younger than six months of age. Pediatr Infect Dis J 2006; 25:241-244. This study reports the clinical and laboratory characteristics of Kawasaki disease in infants less than 6 months of age. The infants less than 6 months were more likely to have incomplete presentation (35% versus 12%, P=0.025), coronary involvement (65% versus 19%, P<0.001), late IVIG therapy and relatively poor outcome.
22. Nigrovic LE, Nigrovic PA, Harper MB, Chiang VW. Extreme thrombocytosis predicts Kawasaki disease in infants. Clin Pediatr (Phila) 2006; 45:446-452. The authors investigated the value of an extremely elevated platelet count to help identify febrile infants with Kawasaki disease. Children less than 6 months of age with prolonged fever, extreme elevation of platelet count and no compelling alternative diagnosis should be evaluated for Kawasaki disease.
23. Newburger JW, Sleeper LA, McCrindle BW, et al. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med 2007; 356:663-675. The data from a well conducted multicenter, randomized, double-blind, placebo-controlled trial did not support the use of methylprednisone in addition to IVIG in Kawasaki disease.
24. Scagni P, Peisino MG, Bianchi M, et al. Kikuchi-Fujimoto disease is a rare cause of lymphadenopathy and fever of unknown origin in children: report of two cases and review of the literature. J Pediatr Hemotol Oncol 2005; 27:337-340.
25. Christie LJ, Honarmand S, Talkington DF, et al. Pediatric encephalitis: what is the role of Mycoplasma pneumonia? Pediatrics 2007; 120:305-313. The authors report the high prevalence (111 of 1988) of Mycoplasma pneumoniae-associated encephalitis in patients with unexplained encephalitis. Eighty-four (76%) were less than 18 years of age. Testing for M. pneumoniae should be considered in any child with unexplained encephalitis.