A sequential approach to young febrile infants on the basis of clinical and laboratory parameters, including procalcitonin, was recently described as an accurate tool in identifying patients at risk for invasive bacterial infection (IBI). Our aim was to prospectively validate the Step-by-Step approach and compare it with the Rochester criteria and the Lab-score.
Prospective study including infants ≤90 days with fever without source presenting in 11 European pediatric emergency departments between September 2012 and August 2014. The accuracy of the Step-by-Step approach, the Rochester criteria, and the Lab-score in identifying patients at low risk of IBI (isolation of a bacterial pathogen in a blood or cerebrospinal fluid culture) was compared.
Eighty-seven of 2185 infants (4.0%) were diagnosed with an IBI. The prevalence of IBI was significantly higher in infants classified as high risk or intermediate risk according to the Step by Step than in low risk patients. Sensitivity and negative predictive value for ruling out an IBI were 92.0% and 99.3% for the Step by Step, 81.6% and 98.3% for the Rochester criteria, and 59.8% and 98.1% for the Lab-score. Seven infants with an IBI were misclassified by the Step by Step, 16 by Rochester criteria, and 35 by the Lab-score.
We validated the Step by Step as a valuable tool for the management of infants with fever without source in the emergency department and confirmed its superior accuracy in identifying patients at low risk of IBI, compared with the Rochester criteria and the Lab-score.
Comments
In reply
We want to thank to Dr Howard for her interesting comment. The management of the young infant with fever without source has become a “hot topic” and several authors are proposing different approaches but with a common objective: performing a less invasive and more individualized management than those recommended by the classical guidelines. These new protocols and algorithms include not only the new blood biomarkers introduced in the last decades but also the use of rapid viral tests.
For instance, several studies conclude that the risk of bacteremia and meningitis is lower in infants with positive rapid influenza testing1-2, suggesting that those well-appearing infants attended during influenza season who test positive for influenza could be managed without performing blood tests. Since the rate of concomitant urinary tract infection is still high, collecting a urine sample is still recommended in these infants. However, most authors still exclude the neonates from this less invasive approach, recommending a full sepsis evaluation even if they have a positive rapid influenza test, since the evidence of a low rate of invasive bacterial infection in these youngest infants is very small.
In relation to the best management of those patients testing positive for Respiratory Syncytial Virus (RSV), most of the published studies refer to patients clinically diagnosed with bronchiolitis 3-4. All of them confirm a lower rate of concomitant bacterial infection when a positive RSV test is present, being mainly urinary tract infections. However, there is not enough evidence to confirm whether we can extrapolate these findings to infants with no respiratory findings when attended and so considered having fever without source. In the study by Levine et al, 91% of those infants testing positive for RSV presented respiratory symptoms and 37% were diagnosed with bronchiolitis. The only three patients with RSV infection and bacteremia were 9, 10 and 19 days5. Moreover, a more recent meta-analysis including this study concludes that rates of bacterial infection are not significantly different between febrile neonates 28 days or younger with and without a positive RSV test6. According to the current evidence, we consider that we should still be cautious when attending neonates with fever without source even if testing positive for RSV. On the other hand, these youngest patients are in a high risk of developing complications secondary to the RSV infection, even if they have not developed respiratory signs yet.
References:
1. Krief WI, Levine DA, Platt SL, et al. Influenza virus infection and the risk of serious bacterial infections in young febrile infants. Pediatrics. 2009;124(1):30.
2. Mintegi S, Garcia-Garcia JJ, Benito J, et al. Rapid influenza test in young febrile infants for the identification of low-risk patients. Pediatr Infect Dis J. 2009 Nov;28(11):1026-8.
3. Purcell K, Fergie J. Concurrent serious bacterial infections in 912 infants and children hospitalized for treatment of respiratory syncytial virus lower respiratory tract infection. Pediatr Infect Dis J. 2004;23(3):267.
4. Ralston S, Hill V, Waters A. Occult serious bacterial infection in infants younger than 60 to 90 days with bronchiolitis: a systematic review. Arch Pediatr Adolesc Med. 2011 Oct;165(10):951-6.
5. Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics. 2004;113(6):1728.
6. Bonadio W, Huang F, Nateson S, et al. Meta-analysis to Determine Risk for Serious Bacterial Infection in Febrile Outpatient Neonates With RSV Infection. Pediatr Emerg Care. 2016 May;32(5):286-9.
RE: Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants
We read with interest the “Validation of the ‘Step-by-Step’ Approach in the Management of Young Febrile Infants”. This study has re-started the discussion concerning work-up in febrile neonates. Formally, the Rochester (1), Philadelphia (2), and Boston Criteria (3) were the three guidelines for the basis of febrile infant management. According to the Rochester Criteria (1), low risk infants, 0-60 days of life without source of infection and absolute band count < 15,000 mm3, could be observed without undergoing lumbar puncture or administration of antibiotics. However, the Philadelphia (2) and Boston Criteria (3) exclude neonates less than 29 and 28 days of life, respectively. The “Validation of the ‘Step by Step’ Approach”, in contrast to the Rochester Criteria (1), immediately stratifies any infant less than 21 days old as high risk. Those over the age of 21 days are stratified as low risk by applying clinical and laboratory criteria in a sequential order using the Pediatric Assessment Triangle, lack of leukocyturia, procalcitonin ≤ 0.5 ng/mL, CRP < 20 mg/L, and absolute neutrophil count (ANC) < 10,000 mm3. The sensitivity and negative predictive value (NPV) for ruling out invasive bacterial infection for the “Validation of the ‘Step by Step’ Approach” was reported as 92.0% and 99.3% compared to 81.6% and 98.3% sensitivity and NPV for the Rochester Criteria (1). In the Gomez study there were 307 neonates ≤ 21 days old in whom 26 invasive bacterial infections were identified (8.5%). However, what is unclear from this study is if the authors excluded those neonates with evidence of viral infections such as Respiratory Syncytial Virus (RSV).
We believe this is important because of the low rate of invasive bacterial infections found in neonates with RSV demonstrated by Levine et al (4) who published results from a cohort of 269 infants ≤ 60 days of life who were RSV positive. Rate of systemic bacterial infection was 7.0%, which included UTI rate of 5.4%. There were no cases of positive CSF cultures. Initial published results from Purcell et al (5) from the Driscoll Children’s Hospital RSV database found that in 295 patients ≤ 6 weeks of age who were RSV positive, none had a positive CSF cultures and there were no significant positive blood cultures. Additional unpublished data from Driscoll Children’s Hospital extending the RSV database to 2005 confirms the absence of positive CSF cultures or significant positive blood cultures in 350 patients ≤ 30 days of life who were RSV positive. The rate of positive urine cultures was 4.28%, which is similar to Levine et al (4).
We conclude that the rate of invasive systemic bacterial infections in neonates with known RSV infection is low. Therefore we suggest that neonates less than 21 days of age with a positive RSV test be considered as low risk.
References
1. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile Infant Collaborative Study Group. Febrile infants at low risk for serious bacterial infection—an appraisal of the Rochester criteria and implications for management. Pediatrics. 1994; 94(3): 390-396.
2. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993;329 (20): 1437-1441.
3. Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr.1992;120(1): 22-27.
4. Levine D, Platt S, Dayan M. Risk of Serious Bacterial Infection in Young Febrile Infants With Respiratory Syncytial Virus Infections. Pediatrics. 2004;113 (6): 1728-1734.
5. Purcell K, Fergie J. Concurrent Serious Bacterial Infections in 2396 Infants and Children Hospitalized With Respiratory Syncytial Virus Lower Respiratory Tract infections. Arch Pediatr Adolesc Med. 2002; 156(10): 322-324.