The goal was to determine the performance of low-risk criteria for serious bacterial illnesses (SBIs) in febrile infants in prospective studies in which empiric antibiotic treatment was withheld, compared with studies (prospective and retrospective) in which empiric antibiotic treatment was administered.
A search of the English-language literature was undertaken by using a PubMed database and reference lists of relevant studies of fever, low-risk criteria, and SBIs. Studies of infants >90 days of age, infants with specific infections, or infants with additional risk factors for infection were excluded. Publications were categorized as retrospective, prospective with empiric antibiotic treatment for all patients, or prospective with antibiotics withheld. The relative risk of SBI in high-risk versus low-risk patients was determined for pooled data in each category. The rates of SBIs in low-risk patients in each category were compared.
Twenty-one studies met the inclusion criteria. In prospective studies in which patients were cared for without empiric antibiotic treatment, 6 patients assigned to the low-risk category had SBIs; all recovered uneventfully. The rate of SBIs in these low-risk patients was 0.67%. The relative risk of SBIs in high-risk versus low-risk patients in these studies was 30.56 (95% confidence interval: 7.0–68.13). The rate of SBIs in low-risk patients in all studies was 2.23%. The rate of SBIs in low-risk patients in the prospective studies without empiric antibiotic treatment was significantly different from the rate in all other studies (0.67% vs 2.71%; P = .01).
Low-risk criteria perform well in prospective studies in which empiric antibiotic treatment is withheld. These criteria allow ∼30% of young febrile infants to be observed without antibiotic treatment, thus avoiding unnecessary hospitalization, nosocomial infection, injudicious use of antibiotics, and adverse effects of antibiotics.
Departments of Pediatrics C and A
January 28, 2010 The Editors Pediatrics Dear Editor,
We have read with great interest the article by Huppler et al regarding the performance of the low-risk criteria in the evaluation of febrile infants aged ¡Ü3 months [1]. We think this issue is one of the cornerstones of every pediatrician and every new manuscript on this subject is blessed. However, we believe the conclusions of the authors should be addressed with cautions due to fundamental bias in the method section of their article.
The authors pooled together infants aged ¡Ü3 months while infants in this age group truly represent 3 different age groups. In most of the institutes, infant older than 2 months are subjects to regular evaluation of fever as older infants aged ¡Ý3 months and ¡Ü3 years are. Another group is those of infants aged ¡Ü2 months and ¡Ý1 months, which is managed in most institutes using a local modification of the low and high risk criteria, and infants in this age group are subjects for discharge without antibiotic treatment based on the risk status. Thus, there is no argument that infants older than 1 months can be managed using the low-risk criteria in outpatients setting without empirical antibiotic treatment.
However, we believe neonates aged ¡Ü1 months should be addressed differentially and data regarding this age group should be interpreted separately. The management of this age group is most challenging because of the relatively high prevalence of serious bacterial infection (SBI) concomitant with the lack of specific signs and symptoms to discriminate SBI from simple viral infection. Huppler et al state that there are 5 prospective studies in which patients in the low risk group underwent observation alone [2-6]. Two of these articles deal only with infant older than 29 days [5, 6], two with infants ¡Ü60 days [2, 3] and only one focused on infants ¡Ü28 days only [4]. Dagan et al found a total of 93 infants aged ¡Ü1 months but does not report how many of them were in the high and low risk group [2]. Pooling together the data from the other 2 articles regarding infants younger than one month show that of a total of 358 low risk neonates, 3 had SBI including one case of Neisseria meningitidis bacteremia in a child who were treated empirically with intramuscular ceftriaxone at the time of the first evaluation. Thus, the low-risk criteria will miss about one child with SBI on every 118 infant that would discharge in the group of infants aged ¡Ü1 months. Thus, every clinician that work in the setting of emergency-room in which infants in this age group are discharged without empirical antibiotic treatment should be aware of that number and remember that here and there the "missing" infant will have more invasive SBI than UTI, bacteremia for instance. We believe that in the setting of neonate with fever, zero tolerance to missing children should be the goal.
Recently, a retrospective study that was not included in the above analysis reported that 6.2% of the neonates who met the low-risk criteria had SBI, including one with bacteremia and meningitis [7].
Our institute protocol for evaluation of young febrile infants distinguished between infants aged more or less than 28 days, and hospitalized all of those younger than 28 days regardless of their risk status. Whether empirical antibiotic treatment should be initiated in all of these neonates, or maybe a more conservative approach of monitoring should be undertaken, that is another question. However, pediatrician should be aware of the practice that was adopted by the 1993 practice guidelines for management of febrile infants which recommend empirical antibiotic treatment even for low-risk neonates aged ¡Ü28 days [8]. Moreover, clinicians should bear in mind that the low and high risk criteria indicates only the probability, but never the certainty, of the presence or absence of SBI, and as such, cannot be relied completely as the sole basis for diagnosing SBI, including invasive SBI, in this more challenging age group of neonates aged ¡Ü1 month. We therefore suggest that all febrile neonates in this age group should undergo complete fever evaluation including blood, urine and CSF cultures, and be hospitalized for consideration of empirical intravenous antibiotic treatment.
References: 1. Huppler AR, Eickhoff JC, Wald ER. Performance of Low-Risk Criteria in the Evaluation of Young Infants With Fever: Review of the Literature. Pediatrics. 2010 Feb; 125(2):228-33. 2. Dagan R, Sofer S, Phillip M, Shachak E. Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serious bacterial infections. J Pediatr. 1988; 112(3):355-60. 3. Jaskiewicz JA, McCarthy CA, Richardson AC, White KC, Fisher DJ, Dagan R, Powell KR. Febrile infants at low risk for serious bacterial infection- -an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics. 1994; 94(3):390-6. 4. Chiu CH, Lin TY, Bullard MJ. Application of criteria identifying febrile outpatient neonates at low risk for bacterial infections. Pediatr Infect Dis J. 1994 Nov; 13(11):946-9. 5. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993 Nov 11; 329(20): 1437-41. 6. Baker MD, Bell LM, Avner JR. The efficacy of routine outpatient management without antibiotics of fever in selected infants. Pediatrics. 1999 Mar; 103(3):627-31. 7. Schwartz S, Raveh D, Toker O, Segal G, Godovitch N, Schlesinger Y. A week-by-week analysis of the low-risk criteria for serious bacterial infection in febrile neonates. Arch Dis Child. 2009 Apr; 94(4):287-92. 8. Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH Jr, Powell KR, Schriger DL. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Ann Emerg Med. 1993 Jul; 22(7):1198-210.
Yours sincerely,
Efraim Bilavsky, MD Department of Pediatrics C Schneider Children's Medical Center of Israel 14 Kaplan Street Petah Tiqva 49202 Israel Tel: +972-3-925 3775 Fax: +972-3-925 3801 E-mail: yoji@netvision.net.il
Conflict of Interest:
None declared