All consensus papers agree that any child between the ages of 0-36 months who have a fever and is toxic looking should be admitted to hospital, have a septic work-up including CBC, blood cultures, LP, and urine cultures, and stared on parenetral antibiotics. Controversy arises when making decisions about a well looking febrile child: who are at risk for bacteremia and SBI, who should receive empiric antibiotic treatment, should the child be treated as an outpatient or inpatient, and what follow-up should be arranged. Two decision analysis reports published in 1991 that investigated the utility of diagnosis and treatment strategies of children at risk for bacteremia (temp greater than 39C, no significant source of infection, and clinically looks well) concluded that the strategy of combining routine blood cultures and empiric antibiotics treatment has the greatest clinical utility. The two reports came from Lieu et al and Down et al. Their decision strategies included any well looking child with a temp greater than 39 degrees C and a WBC greater than 15,000 received blood cultures and parentral or oral antibiotics. Since this time, several changes have occurred in the clinical assumptions made in these analyses. First, h. flu vaccine is now widespread reducing the probability of encountering this most virulent organism and reducing the prevalence of OB and SBI. Second, the emergence of Streptococcus pneumoniae as the number one organism to cause OB and the emerging resistant S. pneumococcus potentially affect the clinical decision to use empiric antibiotics. Third, the previous use of WBC of 15,000 as a cut point has not found to be highly sensitive or specific in detecting all OB. Finally, most child with S. pneumococal bacteremia will spontaneously resolve without antibiotic treatment.
Overall, S. pneumococcus comprised the majority of OB and there is approximately 90% spontaneous resolution of bacteremia when S. pneumococcus in the offending organism
Overall, in children under the age of 36 months each degree of temperature elevation above 39 degrees C increases the risk of bacteremia. However, the height of the temperature has a positive correlation with OB, reliance on this parameter alone will not detect all cases of OB. Bacteremia due to H. flu and S. pneumo still occurs at lower temperatures with up to 13% of bacteremic children being a febrile on presentation to the ED. EMR age of child: less than 7 months1%, 7-24 months 5.4%, 25-48 months 1.5%, and 48+ months 1.9%. The highest incidence of OB is in the 7-24 months age group. Alpern age group: 2-5 months 1%, 6-11 months 1.8%, 12-17 months 2,3%, 18-24 months 2%.
EMR WBC sen and spec: WBC 10,000 sensitivity is 92% specificity of 3%; WBC 15,000 sensitivity of 65% and specificity of 8%; WBC 20,000 sensitivity of 40% and specificity of 12%; WBC 25,000 sensitivity of 25% and specificity of 20%. Isaacman: fond that ANC cut-off 9.49 to have sen 76% and spec 76%, OR 8.7 for detecting OB; WBC 14.3 sen 76% and spec 75%, OR 6.24 for detecting OB; PMN% cut-off of 59% sen 64% and spec 65%, OR 1.89; temp 39.6 as cut-off sen 57% and spec 59%. Kupperman found that ANC, age , and temperature to be better predictors of OB. He found that ANC greater than 10,000 to have a higher sensitivity and specificity compared to WBC of 15,000 as a cut-off point. In his study 8.2% of well looking children with a fever greater than 39 degrees with ANC greater than 10,000 to have 8.2% incidence of OB compared with ANC less than 10,000 with an incidence of 0.8%.
Alpern found that 93.3% of repeated blood cultures were negative and only 4.8% had persistent bactereima which represents an overall 95.7% spontaneous resolution rate of OB without treatment with antibiotics. Debate exists as to whether children with a fever and OM, URTI, or diarrhea require evaluation for OB. It should be stressed that bacteremia can occur in a substantial number of children with these minor infections. In the large series by Fleisher of 6700 children with acute fever and no major infectious source, 12.8% of children with OM were bacteremic, although only one patient developed a serious bacterial infection.
Infants younger than 8 weeks old the retrospective studies did not use standardized objective score and only used ill looking as definition of clinical appearance. Overall results were mixed: infants with SBI had a percent ill appearance ranging from 37% to 100%. Those with UTI ill appearance ranged from 12% to 44%. He could only conclude that there was a trend towards most infants with SBI appeared ill and only a minority of infants with UTI appeared ill. Prospective studies examined the efficacy of the YOS and YIOS. Bacer et al Pediatrics 1990 showed limited efficacy of the YOS in distinguishing infectious outcome of febrile infants aged 4-8 weeks. Of those who appeared well (YOS score less than 10), 22% had serious illness; of those appeared to ill (YOS greater than 16), only 45% had serious illness.In a later study by the same group in the NEJM 1993, similar results were obtained assessing febrile infants aged 29-56 days: 66% with SBI appeared to be well (YOS less than 10). Bonadio et al Pediatric Infectious Disease 1993 assessed the utility of the Young Infant Observation Scale in correlating clinical appearance of infants younger than 8 weeks and infectious disease. They showed for a total YIOS score equal to or greater than 7 the sensitivity is 76% and specificity 75%, and negative predictive value 96% for outcome of SBI. Overall observational score are not highly sen or spec for SBI. Dr. Johnson? McCarthy et al Pediatrics 1985 devised and test the utility of the YOS in febrile children younger than 24 months and found a specificity of 88% and sensitivity of 77% for outcome of SBI. Teach et al J Pediatrics 1995 in a large prospective trial found that 71% of febrile children with OB had the lowest possible score of 6. He conclude that no YOS cut-off had a reliable sen or spec for detecting OB, limiting the utility of this single feature in accurately diagnosing OB.
Baker et al developed the Philadelphia protocol to evaluate the efficacy of managing fever in infants younger than three months of age without empirical antibiotics or routine hospitalization. They prospectively enrolled 287 well looking (i.e. non-toxic) infants under the age of three months and assigned them to either a low risk or high risk for OB group. According to the Philadelphia protocol, infants were identified as low risk if on presentation WBC was less than 15,000, BNR less than .2; less than 10 WBC/hpf on urinalysis, no bacteria on gram stain; LP showed less than 8 WBC/mm3, no bacteria on gram stain; CXR no evidence of infiltrate; stool smear negative for blood, less than 5 WBC on stool smear. Infants were allocated to the high risk group if any of these lab values were abnormal. The low risk group were observed as outpatients with no antibiotics and re-examined at 24 and 48 hrs. The high risk group were admitted and started on empiric antibiotics. Their initial screening protocol showed a sensitivity of 92% and negative predictive value of 98%. Their modified screening protocol which included BNR showed a 100% sensitivity and 100% negative predictive value for identifying serious bacterial infection. They conclude that it is possible to identify a group of febrile infants who are at low risk of SBI and who can be safely observed at home without antibiotics. In 1999 the same group validated their initial study in a group of infants age 29-60 days old using the Philadelphia protocol. Their result were the same as their 1993 study with 100% sensitivity and 100% negative predictive value for detecting infants at low risk for SBI.
Dagan et al in 1985 prospectively enrolled 233 febrile infants younger than 3 months into two groups, low risk vs non-low risk group according to their protocol which subsequently became known as the Rochester protocol. The purpose of their study was to identify febrile well looking infants that were at low risk for developing SBI. They defined SBI as either bacteremia, meningitis, cellulitis, osteomyeolitis, gastroenteritis, or UTI. Their protocol differed from the Philadelphia protocol in that they included more historical item as screening criteria for low risk infants. The Rochester protocol consists of: 1. Infant appears well 2. Infant has been previously healthy (read items) 3. No evidence of skin, soft tissue, bone, joint, or ear infection. 4. Laboratory values: WBC less than 15,000, ABC less than 1.5 x 10 to the 9 th , less than 10 WBC/hpf on microscopic urinalysis, less than 5 WBC on stool smear. The low risk group was hospitalized for observation while waiting for septic work-up results which included CBC, blood cultures, urine cultures, and LP. 82% of the low risk group received parenteral antibiotics. The non-low risk group were all hospitalized and started on parenteral antibiotics. Their results found that only 0.7% of the infants in the low risk group developed a SBI compared with 25% of the infants in the high risk group (p less than .0001). Problems with this study: Jaskiewizcz et al in 1994 attempted to validate the Rochester protocol. In their study they enrolled 1057 febrile infants less than 60 days old into either low risk treatment group or non-low risk treatment group according to the Rochester protocol. In their study all of the low risk group was hospitalized and 60% received antibiotics. The non-low risk group were all hospitalized and all received parenteral antibiotics. Based on their data, the negative predictive value of the Rochester protocol is 98% for SBI and 99.5% for bacteremia. Problems with this study: Avner et al attempted to validate the Rochester protocol and their data found that the accuracy for detecting SBI was only 66.6% and 64.1% for detecting bacteremia/meningitis. Their study could not validate the RP.
Several factor guide clinicians in this selective approach: 1. With each degree temp above 39 the incidence of OB increases so child with higher temp are at increased risk for OB. 2. In the post H. flu vaccine era over 90% of OB will be caused by S. pneumococcus which has a 90% spontaneous resolution rate. 3. There is increasing emergence of S. pneumococcus antibiotic resistance which may influence your decision to treat empirically. 4. With the new blood culture technique most blood cultures are positive in less than 24hr with some studies finding an average of 14.5 hrs so, follow up of patients treated without antibiotics can be done in less than 24hrs. 5. The highest incidence of OB is in the age group of 6-24 months so, this may represent a higher risk group. 6. Using a temp cut-off of 39 will miss up to 35% of OB children. 7. Recent studies suggest that ANC of greater than 10,000 is a better predictor of OB than WBC of 15,000.
Much controversy exist around the ideal treatment of children at risk fro OB. Children most susceptible to OB are between 3 and 36 months of age. The previous retrospective studies have indicated the incidence of OB to be between 3 and 11%. These studies have indicated that children in this age range with a fever greater than 39 degree and a WBC count greater than 15,00 have an increase incidence of having OB and developing SBI. Bulloch performed a meta-analysis of these studies to determine the effectiveness of antibiotics for reducing the probability of SBI in children at risk for OB. Their inclusion criteria included: children between the ages of 3 to 36 months, fever greater than 39 degree, no focal infection, and a blood culture on initial visit; the study had to be randomized, controlled trial; SBI defined as meningitis, pneumonia, periorbital cellulitis, septic arthritis, osteomyeolitis, or persistent bacteremia; intervention had to consist of either an antibiotic vs no antibiotic or an oral vs an IM antibiotic. Their results found that in their primary analysis, children at risk for OB, no significant effect of antibiotics vs placebo (OR=.60 CI .10-3.49) or the IM ceftriaxone vs oral antibiotics (OR=.38 95% CI .12-1.17). In the secondary analysis, children identified as bacteremic, there was a significant difference between the IM ceftriaxone group vs oral antibiotic in reducing the incidence of SBI. The analysis of the oral antibiotic vs no antibiotic did suggest a reduced OR of SBI with treatment but this did not reach statistical significance. Rothrock preformed a meta-analysis to determine the utility of oral antibiotics in preventing meningitis and SBI in children with S. pneumoniae OB. Their inclusion criteria included: non-toxic children between the ages of 3 to 36 months;no SBI present; children with S. pneumoniae bacteremia treated as outpatients; division of patients either retrospectively or prospectively into treatment with oral antibiotics or no treatment; and all patients had immediate f/u. They defined SBI as pneumonia, meningitis, soft tissue infection, and bone or joint infection. Persistent OB or persistent fever were not defined as SBI. Their results found of the 656 identified cases of S. pneumoniae there was a significant fewer SBI developed in treated children vs untreated children. However there was no significant difference in the development of meningitis in the treated vs no treatment children. In other words, oral antibiotic are not affective in preventing the development of meningitis. Dr. Johnson comment? Comments from paper H.flu incidence of OB, SBI and meningitis.
Acute febrile illness with a petechial rash in the pediatric patient may represent a benign, self-limiting viral illness or invasive bacterial infection. Some of the illnesses that can present with fever and petechial rash are: viral illness, OM, pneumonia, pharyngitis, meningitis, Henoch-Schoenlein purpura, Rocky Mountain spotted fever, and MMR vaccine reaction. The most concerning of these is meningitis because of serious sequelae associated with this illness. Baker et al performed a 1 year study to determine the incidence of meningococcal disease in children with fever and petechiae, the clinical predictors of meningococcal disease, and the appropriate initial treatment of children with these clinical findings. Their result were divided into two groups: group I had invasive bacterial disease which represented 8% of the study group and group II nonbacterial disease 92% of the study group. The incidence of meningococcal illness was 7%. The majority of nonbacteremic group had viral illness. The quality and location of petechiae were significantly different between the two groups. Group I invasive bacteremic group more commonly had a generalized rash compared to the nonbacteremic group. The anatomic location of petechiae was significantly different between the two groups. The patients with invasive bacterial infections tended to have more petechiae below the nipple line (trunk and extremities). No patient with petechiae only above the nipple line had serious illness. Their suggested management included CBC, throat culture, blood culture, and LP. Hospitalization and IV antibiotics in patients that appear ill, WBC above 15,000, peripheral ABC greater than 500 cell/ul, or CFS abnormalities. If CBC, ABC, LP are normal and petechiae below nipple line the risk of invasive bacterial infection is low and children can be treated less aggressively.
Well looking child: current recommendations, temp greater than 39 and WBC greater than 15,000 get blood culture, IM cetriaxone, and f/u 24hrs; urine culture boys less than 6 months and girls less than 2 years
Recent studies challenge these recommendations; selective approach
Repeated risk of infection with common bacterial pathogens, risk of Pneumocytsis carinii, mycobacterial infections (TB, AI), cryptococcosis, cytomegalovirus, Ebstein-Barr virus, lymphoma and other malignancies
Low CD4 similar approach to neutropenic cancer patient; septic work up and broad spectrum antibiotic
Children with valvular heart disease are at risk for endocarditis
Fever without obvious source with a new or changing murmur; hospitalization, serial blood cultures, echo, antibiotics against: S.viridans, S aureus, S. fecalis, S. pneumo, enterococci, H. flu, and other gram neg rods
Suggested antibiotics include Vancomycin and Gentamycin until cultures are positive